Peer Reviewed Publications
2022 |
Martha Namusobya Felix Bongomin, John Mukisa William Kane Olwit Charles Batte Claudine Mukashyaka Emmanuel Mande Richard Kwizera David Denning Joshua Rhein Shailendra Prasad Christine Sekaggya-Wiltshire W Chronic pulmonary aspergillosis in patients with active pulmonary tuberculosis with persisting symptoms in Uganda Journal Article Mycoses, 65 (6), pp. 625-634, 2022. @article{Namusobya2022, title = {Chronic pulmonary aspergillosis in patients with active pulmonary tuberculosis with persisting symptoms in Uganda}, author = {Martha Namusobya, Felix Bongomin, John Mukisa, William Kane Olwit, Charles Batte, Claudine Mukashyaka, Emmanuel Mande, Richard Kwizera, David W. Denning, Joshua Rhein, Shailendra Prasad, Christine Sekaggya-Wiltshire }, year = {2022}, date = {2022-06-01}, journal = {Mycoses}, volume = {65}, number = {6}, pages = {625-634}, abstract = {Background The occurrence of chronic pulmonary aspergillosis (CPA) among drug sensitive pulmonary tuberculosis (PTB) patients on optimal therapy with persistent symptoms was investigated. Methods We consecutively enrolled participants with PTB with persistent pulmonary symptoms after 2 months of anti-TB treatment at Mulago Hospital, Kampala, Uganda, between July 2020 and June 2021. CPA was defined as a positive Aspergillus-specific IgG/IgM immunochromatographic test (ICT), a cavity with or without a fungal ball on chest X-ray (CXR), and compatible symptoms >3 months. Results We enrolled 162 participants (median age 30 years; IQR: 25–40), 97 (59.9%) were male, 48 (29.6%) were HIV-infected and 15 (9.3%) had prior PTB. Thirty-eight (23.4%) sputum samples grew A. niger and 13 (8.0%) A. fumigatus species complexes. Six (3.7%) participants had intracavitary fungal balls and 52 (32.1%) had cavities. Overall, 32 (19.8%) participants had CPA. CPA was associated with prior PTB (adjusted odds ratio [aOR]: 6.61, 95% CI: 1.85–23.9, p = .004), and far advanced CXR changes (aOR: 4.26, 95% CI: 1.72–10.52, p = .002). The Aspergillus IgG/IgM ICT was positive in 10 (31.3%) participants with CPA. Conclusions Chronic pulmonary aspergillosis may cause persistent respiratory symptoms in up to one-fifth of patients after intensive treatment for PTB. The Aspergillus IgG/IgM ICT positivity rate was very low and may not be used alone for the diagnosis of CPA in Uganda.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background The occurrence of chronic pulmonary aspergillosis (CPA) among drug sensitive pulmonary tuberculosis (PTB) patients on optimal therapy with persistent symptoms was investigated. Methods We consecutively enrolled participants with PTB with persistent pulmonary symptoms after 2 months of anti-TB treatment at Mulago Hospital, Kampala, Uganda, between July 2020 and June 2021. CPA was defined as a positive Aspergillus-specific IgG/IgM immunochromatographic test (ICT), a cavity with or without a fungal ball on chest X-ray (CXR), and compatible symptoms >3 months. Results We enrolled 162 participants (median age 30 years; IQR: 25–40), 97 (59.9%) were male, 48 (29.6%) were HIV-infected and 15 (9.3%) had prior PTB. Thirty-eight (23.4%) sputum samples grew A. niger and 13 (8.0%) A. fumigatus species complexes. Six (3.7%) participants had intracavitary fungal balls and 52 (32.1%) had cavities. Overall, 32 (19.8%) participants had CPA. CPA was associated with prior PTB (adjusted odds ratio [aOR]: 6.61, 95% CI: 1.85–23.9, p = .004), and far advanced CXR changes (aOR: 4.26, 95% CI: 1.72–10.52, p = .002). The Aspergillus IgG/IgM ICT was positive in 10 (31.3%) participants with CPA. Conclusions Chronic pulmonary aspergillosis may cause persistent respiratory symptoms in up to one-fifth of patients after intensive treatment for PTB. The Aspergillus IgG/IgM ICT positivity rate was very low and may not be used alone for the diagnosis of CPA in Uganda. |
Sarah M Lofgren Joanita Kigozi, Nakita Natala Sharon Tsui Anita Arinda Vanessa Akinyange Raymond Sebuliba David Boulware Barbara Castelnuovo G R Can COVID-19 changes reduce stigma in African HIV clinics? Journal Article The Lancet HIV, 9 (5), pp. e304-e305, 2022. @article{Lofgren2022, title = {Can COVID-19 changes reduce stigma in African HIV clinics?}, author = {Sarah M Lofgren, Joanita Kigozi, Nakita G Natala, Sharon Tsui, Anita Arinda, Vanessa Akinyange, Raymond Sebuliba, David R Boulware, Barbara Castelnuovo}, doi = {https://doi.org/10.1016/S2352-3018(22)00045-5}, year = {2022}, date = {2022-05-01}, journal = {The Lancet HIV}, volume = {9}, number = {5}, pages = {e304-e305}, abstract = {There is an extensive body of literature showing that HIV stigma is a barrier to HIV care at every level of the care cascade.1 HIV stigma reduces HIV testing, disclosure, engagement in treatment, adherence to medication, and retention in care.2 Stigma is also related to poor social support and increased depression, both of which worsen health outcomes.1 HIV stigma interventions that have been proposed and completed globally show small, targeted changes in stigma; however, overall, the efficacy of stigma interventions is disappointing,3, 4 perhaps because interventions are often designed by those outside the communities served. Thus, although further work on stigma interventions is vital, particularly those that have been initiated locally with the involvement of community members, perhaps in order to improve HIV care the focus should be shifted to clinic systems.}, keywords = {}, pubstate = {published}, tppubtype = {article} } There is an extensive body of literature showing that HIV stigma is a barrier to HIV care at every level of the care cascade.1 HIV stigma reduces HIV testing, disclosure, engagement in treatment, adherence to medication, and retention in care.2 Stigma is also related to poor social support and increased depression, both of which worsen health outcomes.1 HIV stigma interventions that have been proposed and completed globally show small, targeted changes in stigma; however, overall, the efficacy of stigma interventions is disappointing,3, 4 perhaps because interventions are often designed by those outside the communities served. Thus, although further work on stigma interventions is vital, particularly those that have been initiated locally with the involvement of community members, perhaps in order to improve HIV care the focus should be shifted to clinic systems. |
Cresswell Fiona V. ; Lamorde, Mohammed Implementation of long-acting antiretroviral therapy in low-income and middle-income countries. Journal Article Current Opinion in HIV and AIDS, 17 (3), pp. 127-134(8), 2022. @article{Cresswell2022, title = {Implementation of long-acting antiretroviral therapy in low-income and middle-income countries. }, author = {Cresswell, Fiona V. ; Lamorde, Mohammed }, doi = {https://doi.org/10.1097/COH.0000000000000732}, year = {2022}, date = {2022-05-01}, journal = {Current Opinion in HIV and AIDS}, volume = {17}, number = {3}, pages = {127-134(8)}, abstract = { Purpose of review With oral antiretroviral therapy, HIV has become a manageable chronic illness. However, UNAIDS targets for virologic suppression have not yet been attained in many low-income and middle-income countries (LMICs). Long-acting drug formulations hold promise to improve treatment outcomes. In this rapidly evolving area of research, we aim to review recent literature on the treatment of HIV with long-acting agents and identify implementation considerations for LMICs. Recent findings Randomized controlled trials have shown that monthly long-acting injectable cabotegravir (CAB) and rilpivirine (RPV) is noninferior to oral ART, and 2-monthly CAB/RPV is noninferior to monthly injections. However, few people from LMICs were included. A modelling study predicts that in sub-Saharan Africa, injectable CAB/RPV is best targeted to those with poor adherence (HIV viral load >1000 copies/ml) in whom cost-effectiveness is greatest and risk of contributing to further resistance is no greater than continuation of oral ART. Other promising agents, such as lenacapavir are under investigation and may prove particularly useful in heavily treatment-experienced adults. Summary Long-acting regimens are a promising advance in HIV treatment. By extending the dosing interval, increasing convenience and being discreet these regimens may reduce HIV treatment challenges. However, there are multiple implementation considerations in LMICs including the need for exclusion of hepatitis B, cold chain, oral bridging in case of missed dosing and switching during tuberculosis therapy. Efficacy and safety data are also awaited for settings without routine access to baseline resistance testing or regular viral load monitoring and for special populations, such as pregnancy, children and the elderly. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Purpose of review With oral antiretroviral therapy, HIV has become a manageable chronic illness. However, UNAIDS targets for virologic suppression have not yet been attained in many low-income and middle-income countries (LMICs). Long-acting drug formulations hold promise to improve treatment outcomes. In this rapidly evolving area of research, we aim to review recent literature on the treatment of HIV with long-acting agents and identify implementation considerations for LMICs. Recent findings Randomized controlled trials have shown that monthly long-acting injectable cabotegravir (CAB) and rilpivirine (RPV) is noninferior to oral ART, and 2-monthly CAB/RPV is noninferior to monthly injections. However, few people from LMICs were included. A modelling study predicts that in sub-Saharan Africa, injectable CAB/RPV is best targeted to those with poor adherence (HIV viral load >1000 copies/ml) in whom cost-effectiveness is greatest and risk of contributing to further resistance is no greater than continuation of oral ART. Other promising agents, such as lenacapavir are under investigation and may prove particularly useful in heavily treatment-experienced adults. Summary Long-acting regimens are a promising advance in HIV treatment. By extending the dosing interval, increasing convenience and being discreet these regimens may reduce HIV treatment challenges. However, there are multiple implementation considerations in LMICs including the need for exclusion of hepatitis B, cold chain, oral bridging in case of missed dosing and switching during tuberculosis therapy. Efficacy and safety data are also awaited for settings without routine access to baseline resistance testing or regular viral load monitoring and for special populations, such as pregnancy, children and the elderly. |
Nahum Méndez-Sánchez Elisabetta Bugianesi, Robert Gish Frank Lammert Herbert Tilg Mindie Nguyen Shiv Sarin Núria Fabrellas Shira Zelber-Sagi Jian-Gao Fan Gamal Shiha Giovanni Targher Ming-Hua Zheng Wah-Kheong Chan Shlomo Vinker Kakumi Kawaguchi Laurent Castera Yusuf Yilmaz Marko Korenjak Wendy Spearman Mehmet Ungan Melissa Palmer Mortada El-Shabrawi Hans-Juergen Gruss Jean-François Dufour Anil Dhawan Heiner Wedemeyer Jacob George Luca Valenti Yasser Fouad Manuel Romero‐Gomez Mohammed Eslam G H K C; in alcohol-related harm in the March 03, 2022DOI: PlumX Metrics Previous ArticleInequities Philippines Global multi-stakeholder endorsement of the MAFLD definition Journal Article The Lancet; Gastroentology & Hepatology, 7 (5), pp. 388-390, 2022. @article{Méndez-Sánchez2022, title = {Global multi-stakeholder endorsement of the MAFLD definition}, author = {Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Kakumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam and theGlobal multi-stakeholder consensus on the redefinition of fatty liver disease March 03, 2022DOI: PlumX Metrics Previous ArticleInequities in alcohol-related harm in the Philippines}, doi = {https://doi.org/10.1016/S2468-1253(22)00062-0}, year = {2022}, date = {2022-05-01}, journal = {The Lancet; Gastroentology & Hepatology}, volume = {7}, number = {5}, pages = {388-390}, abstract = {Comprising over 1000 signatories representative of multiple stakeholders, including hepatologists, internists, diabetologists, endocrinologists, paediatricians, primary-care providers, nephrologists, cardiologists, pathologists, patient advocates, nurses, nutritionists, and pharmaceutical experts from over 134 countries, we—the undersigned—endorse both the name metabolic (dysfunction)-associated fatty liver disease (MAFLD) as an overarching term and its definition for fatty liver diseases associated with metabolic dysregulation. 1, 2, 3 We advocate for this change because it more accurately reflects the underlying pathogenesis of the disease than does the previously used term, non-alcoholic fatty liver disease (NAFLD). Furthermore, we believe that this designation will enhance our ability to advance the science of fatty liver disease and to improve patient care. 4, 5 This open letter represents the voices of individuals and multiple stakeholders across the global liver health community; it is not intended to devalue any other initiative, but to complement and inform them.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Comprising over 1000 signatories representative of multiple stakeholders, including hepatologists, internists, diabetologists, endocrinologists, paediatricians, primary-care providers, nephrologists, cardiologists, pathologists, patient advocates, nurses, nutritionists, and pharmaceutical experts from over 134 countries, we—the undersigned—endorse both the name metabolic (dysfunction)-associated fatty liver disease (MAFLD) as an overarching term and its definition for fatty liver diseases associated with metabolic dysregulation. 1, 2, 3 We advocate for this change because it more accurately reflects the underlying pathogenesis of the disease than does the previously used term, non-alcoholic fatty liver disease (NAFLD). Furthermore, we believe that this designation will enhance our ability to advance the science of fatty liver disease and to improve patient care. 4, 5 This open letter represents the voices of individuals and multiple stakeholders across the global liver health community; it is not intended to devalue any other initiative, but to complement and inform them. |
Johan H. Melendez Justin Hardick, Annet Onzia Tong Yu Peter Kyambadde Rosalind Parkes-Ratanshi Edith Nakku-Joloba Agnes Kiragga Yukari Manabe Matthew Hamill C M Retrospective Analysis of Ugandan Men with Urethritis Reveals Mycoplasma genitalium and Associated Macrolide Resistance Journal Article Microbiology Spectrum, 10 (2), pp. e0230421, 2022. @article{Melendez2022, title = {Retrospective Analysis of Ugandan Men with Urethritis Reveals Mycoplasma genitalium and Associated Macrolide Resistance}, author = {Johan H. Melendez, Justin Hardick, Annet Onzia, Tong Yu, Peter Kyambadde, Rosalind Parkes-Ratanshi, Edith Nakku-Joloba, Agnes Kiragga, Yukari C. Manabe, Matthew M. Hamill}, doi = {https://doi.org/10.1128/spectrum.02304-21}, year = {2022}, date = {2022-04-27}, journal = {Microbiology Spectrum}, volume = {10}, number = {2}, pages = {e0230421}, abstract = {The rising rates of antimicrobial resistance (AMR) in Mycoplasma genitalium globally and the association of this sexually transmitted infection (STI) with cervicitis, urethritis, and HIV are potentially of great public health concern. Data on the epidemiology of M. genitalium in men in sub-Saharan Africa are limited. We sought to determine the prevalence of M. genitalium and macrolide resistance in men with urethritis in Kampala, Uganda. Self-collected penile-meatal swabs and/or urine samples from men with symptomatic urethritis (n = 250) were retrospectively analyzed for the presence of M. genitalium and macrolide resistance markers with the Aptima M. genitalium and ResistancePlus M. genitalium assays. Additionally, demographic and STI coinfection data were used to investigate associations with M. genitalium infection. M. genitalium was detected in 12.8% (32/250) of individuals; 40.6% (n = 13) had M. genitalium monoinfection. Mutations associated with macrolide resistance were detected in 10.7% (3/28) of participants. Coinfection with Neisseria gonorrhoeae was common (41.0%), but M. genitalium was more prevalent in participants without N. gonorrhoeae coinfection (P = 0.001). M. genitalium is common in Ugandan men with urethritis both as a monoinfection and as a coinfection with other curable STIs. Macrolide resistance was present and warrants further research on treatment outcomes and the association between untreated M. genitalium and subsequent morbidity. IMPORTANCE Mycoplasma genitalium is a common sexually transmitted infection associated with urethritis in men. Little is known about M. genitalium infection in men with urethritis in Uganda. We report that 12% of participants in this study were positive for M. genitalium and that resistance to azithromycin, a macrolide antibiotic, is present. Furthermore, we show that either self-collected penile-meatal swabs or urine can be used for detection of M. genitalium.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The rising rates of antimicrobial resistance (AMR) in Mycoplasma genitalium globally and the association of this sexually transmitted infection (STI) with cervicitis, urethritis, and HIV are potentially of great public health concern. Data on the epidemiology of M. genitalium in men in sub-Saharan Africa are limited. We sought to determine the prevalence of M. genitalium and macrolide resistance in men with urethritis in Kampala, Uganda. Self-collected penile-meatal swabs and/or urine samples from men with symptomatic urethritis (n = 250) were retrospectively analyzed for the presence of M. genitalium and macrolide resistance markers with the Aptima M. genitalium and ResistancePlus M. genitalium assays. Additionally, demographic and STI coinfection data were used to investigate associations with M. genitalium infection. M. genitalium was detected in 12.8% (32/250) of individuals; 40.6% (n = 13) had M. genitalium monoinfection. Mutations associated with macrolide resistance were detected in 10.7% (3/28) of participants. Coinfection with Neisseria gonorrhoeae was common (41.0%), but M. genitalium was more prevalent in participants without N. gonorrhoeae coinfection (P = 0.001). M. genitalium is common in Ugandan men with urethritis both as a monoinfection and as a coinfection with other curable STIs. Macrolide resistance was present and warrants further research on treatment outcomes and the association between untreated M. genitalium and subsequent morbidity. IMPORTANCE Mycoplasma genitalium is a common sexually transmitted infection associated with urethritis in men. Little is known about M. genitalium infection in men with urethritis in Uganda. We report that 12% of participants in this study were positive for M. genitalium and that resistance to azithromycin, a macrolide antibiotic, is present. Furthermore, we show that either self-collected penile-meatal swabs or urine can be used for detection of M. genitalium. |
for the Nicholas I Paton Joseph Musaazi, Cissy Kityo Stephen Walimbwa Anne Hoppe Apolo Balyegisawa Jesca Asienzo Arvind Kaimal Grace Mirembe Abbas Lugemwa Gilbert Ategeka Margaret Borok Henry Mugerwa Abraham Siika Eva Laker Odongpiny Barbara Castelnuovo Agnes Kiragga Andrew Kambugu NADIA Trial Team† A The Lancet HIV, 9 (6), pp. e381-e393, 2022. @article{Paton2022, title = {Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial}, author = {Nicholas I Paton, Joseph Musaazi, Cissy Kityo, Stephen Walimbwa, Anne Hoppe, Apolo Balyegisawa, Jesca Asienzo, Arvind Kaimal, Grace Mirembe, Abbas Lugemwa, Gilbert Ategeka, Margaret Borok, Henry Mugerwa, Abraham Siika, Eva Laker A Odongpiny, Barbara Castelnuovo, Agnes Kiragga, Andrew Kambugu for the NADIA Trial Team†}, doi = {https://doi.org/10.1016/S2352-3018(22)00092-3}, year = {2022}, date = {2022-04-22}, journal = {The Lancet HIV}, volume = {9}, number = {6}, pages = {e381-e393}, abstract = {Background WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine. Methods In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete. Findings Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI −3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3–4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication. Interpretation Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine. Methods In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete. Findings Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI −3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3–4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication. Interpretation Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine. |
Joan Nankya-Mutyoba David Ejalu, Claude Wandera Rachel Beyagira Jacinto Amandua Emmanuel Seremba Kaggwa Mugagga Andrew Kambugu Alex Muganzi Philippa Easterbrook & Ponsiano Ocama BMC Medical Education volume, 22 (297), 2022. @article{Nankya-Mutyoba2022, title = {A training for health care workers to integrate hepatitis B care and treatment into routine HIV care in a high HBV burden, poorly resourced region of Uganda: the ‘2for1’ project}, author = {Joan Nankya-Mutyoba, David Ejalu, Claude Wandera, Rachel Beyagira, Jacinto Amandua, Emmanuel Seremba, Kaggwa Mugagga, Andrew Kambugu, Alex Muganzi, Philippa Easterbrook & Ponsiano Ocama }, doi = {https://doi.org/10.1186/s12909-022-03329-3}, year = {2022}, date = {2022-04-20}, journal = {BMC Medical Education volume}, volume = {22}, number = {297}, abstract = {Introduction The “2for1” project is a demonstration project to examine the feasibility and effectiveness of HBV care integrated into an HIV clinic and service. An initial phase in implementation of this project was the development of a specific training program. Our objective was to describe key features of this integrated training curriculum and evaluation of its impact in the initial cohort of health care workers (HCWs). Methods A training curriculum was designed by experts through literature review and expert opinion. Key distinctive features of this training program (compared to standard HBV training provided in the Government program) were; (i) Comparison of commonalities between HIV and HBV (ii) Available clinic- and community-level infrastructure, and the need to strengthen HBV care through integration (iii) Planning and coordination of sustained service integration. The training was aided by a power-point guided presentation, question and answer session and discussion, facilitated by physicians and hepatologists with expertise in viral hepatitis. Assessment approach used a self-administered questionnaire among a cohort of HCWs from 2 health facilities to answer questions on demographic information, knowledge and attitudes related to HBV and its prevention, before and after the training. Knowledge scores were generated and compared using paired t- tests. Results A training curriculum was developed and delivered to a cohort of 44 HCWs including medical and nursing staff from the two project sites. Of the 44 participants, 20 (45.5%) were male, average age (SD) was 34.3 (8.3) with an age range of 22–58 years. More than half (24, 54.5%) had been in service for fewer than 5 years. Mean correct knowledge scores increased across three knowledge domains (HBV epidemiology and transmission, natural history and treatment) post-intervention. However, knowledge related to diagnosis and prevention of HBV did not change. Conclusion A structured HBV education intervention conducted as part of an HIV/HBV care integration training for health care workers yielded improved knowledge on HBV and identified aspects that require further training. This approach may be replicated in other settings, as a public health strategy to heighten HBV elimination efforts.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Introduction The “2for1” project is a demonstration project to examine the feasibility and effectiveness of HBV care integrated into an HIV clinic and service. An initial phase in implementation of this project was the development of a specific training program. Our objective was to describe key features of this integrated training curriculum and evaluation of its impact in the initial cohort of health care workers (HCWs). Methods A training curriculum was designed by experts through literature review and expert opinion. Key distinctive features of this training program (compared to standard HBV training provided in the Government program) were; (i) Comparison of commonalities between HIV and HBV (ii) Available clinic- and community-level infrastructure, and the need to strengthen HBV care through integration (iii) Planning and coordination of sustained service integration. The training was aided by a power-point guided presentation, question and answer session and discussion, facilitated by physicians and hepatologists with expertise in viral hepatitis. Assessment approach used a self-administered questionnaire among a cohort of HCWs from 2 health facilities to answer questions on demographic information, knowledge and attitudes related to HBV and its prevention, before and after the training. Knowledge scores were generated and compared using paired t- tests. Results A training curriculum was developed and delivered to a cohort of 44 HCWs including medical and nursing staff from the two project sites. Of the 44 participants, 20 (45.5%) were male, average age (SD) was 34.3 (8.3) with an age range of 22–58 years. More than half (24, 54.5%) had been in service for fewer than 5 years. Mean correct knowledge scores increased across three knowledge domains (HBV epidemiology and transmission, natural history and treatment) post-intervention. However, knowledge related to diagnosis and prevention of HBV did not change. Conclusion A structured HBV education intervention conducted as part of an HIV/HBV care integration training for health care workers yielded improved knowledge on HBV and identified aspects that require further training. This approach may be replicated in other settings, as a public health strategy to heighten HBV elimination efforts. |
Buyego, Paul; Elizabeth Katwesigye Grace Kebirungi, Mike Nsubuga ; Shirley Nakyejwe Phillip Cruz, Meghan McCarthy ; Darrell Hurt Andrew Kambugu, Joseph Walter Arinaitwe ; Umaru Ssekabira Daudi Jjingo, Daudi Jjingo Feasibility of Virtual Reality based Training for Optimising COVID-19 Case Handling in Uganda Journal Article Research Square, 22 (1:274), pp. 21, 2022. @article{Buyego2022, title = {Feasibility of Virtual Reality based Training for Optimising COVID-19 Case Handling in Uganda}, author = {Paul Buyego and Elizabeth Katwesigye, Grace Kebirungi, Mike Nsubuga, and Shirley Nakyejwe, Phillip Cruz, Meghan McCarthy, and Darrell Hurt, Andrew Kambugu, Joseph Walter Arinaitwe, and Umaru Ssekabira, Daudi Jjingo, Daudi Jjingo}, doi = { doi: 10.21203/rs.3.rs-882147/v1}, year = {2022}, date = {2022-04-13}, journal = {Research Square}, volume = {22}, number = {1:274}, pages = {21}, abstract = {Background Epidemics and pandemics are causing high morbidity and mortality on a still-evolving scale exemplified by the COVID-19 pandemic. Infection prevention and control (IPC) training for frontline health workers is thus essential. However, classroom or hospital ward based training portends an infection risk due to the in-person interaction of participants. We explored the use of Virtual Reality (VR) simulations for frontline health worker training since it trains participants without exposing them to infections that would arise from in-person training. It does away with the requirement for expensive Personal Protective Equipment (PPE) that has been in acute shortage and improves learning, retention and recall. This represents the first attempt in deploying VR-based pedagogy in a Ugandan medical education context. Methods We used animated VR-based simulations of bedside and ward-based training scenarios for frontline health workers. The training covered the wearing and stripping of PPE, case management of COVID-19 infected individuals and hand hygiene. It used VR headsets and Graphics Processing Units (GPUs) to actualize an immersive experience, via a hybrid of VR renditions and 360degrees videos. We then compared the level of knowledge acquisition between individuals trained using this method to comparable cohorts previously trained in a classroom setting. That evaluation was supplemented by a qualitative assessment based on feedback from participants about their experience. Results The effort resulted into a well-designed COVID-19 IPC VR curriculum, equivalent VR content and a pioneer cohort of trained frontline health workers. The formalized comparison with classroom-trained cohorts showed relatively better outcomes by way of skills acquired, speed of learning and rates of information retention (P-value =4.0e-09) - suggesting the effectiveness and feasibility of VR as a medium of medical training. Additionally, in the qualitative assessment 90% of the participants rated the method as very good, 58.1% strongly agreed that the activities met the course objectives, and 97.7 % strongly indicated willingness to refer the course to colleagues. Conclusion VR-based COVID-19 IPC training is feasible, effective and achieves enhanced learning while protecting participants from infections within a pandemic context in Uganda. It is a delivery medium transferable to the contexts of other highly infectious diseases. Keywords: Virtual Reality, COVID-19, Personal Protective Equipment, Medical Education, Pandemics}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Epidemics and pandemics are causing high morbidity and mortality on a still-evolving scale exemplified by the COVID-19 pandemic. Infection prevention and control (IPC) training for frontline health workers is thus essential. However, classroom or hospital ward based training portends an infection risk due to the in-person interaction of participants. We explored the use of Virtual Reality (VR) simulations for frontline health worker training since it trains participants without exposing them to infections that would arise from in-person training. It does away with the requirement for expensive Personal Protective Equipment (PPE) that has been in acute shortage and improves learning, retention and recall. This represents the first attempt in deploying VR-based pedagogy in a Ugandan medical education context. Methods We used animated VR-based simulations of bedside and ward-based training scenarios for frontline health workers. The training covered the wearing and stripping of PPE, case management of COVID-19 infected individuals and hand hygiene. It used VR headsets and Graphics Processing Units (GPUs) to actualize an immersive experience, via a hybrid of VR renditions and 360degrees videos. We then compared the level of knowledge acquisition between individuals trained using this method to comparable cohorts previously trained in a classroom setting. That evaluation was supplemented by a qualitative assessment based on feedback from participants about their experience. Results The effort resulted into a well-designed COVID-19 IPC VR curriculum, equivalent VR content and a pioneer cohort of trained frontline health workers. The formalized comparison with classroom-trained cohorts showed relatively better outcomes by way of skills acquired, speed of learning and rates of information retention (P-value =4.0e-09) - suggesting the effectiveness and feasibility of VR as a medium of medical training. Additionally, in the qualitative assessment 90% of the participants rated the method as very good, 58.1% strongly agreed that the activities met the course objectives, and 97.7 % strongly indicated willingness to refer the course to colleagues. Conclusion VR-based COVID-19 IPC training is feasible, effective and achieves enhanced learning while protecting participants from infections within a pandemic context in Uganda. It is a delivery medium transferable to the contexts of other highly infectious diseases. Keywords: Virtual Reality, COVID-19, Personal Protective Equipment, Medical Education, Pandemics |
Eva Laker Agnes Odongpiny Fiona Cresswell, Arnold Arinaitwe Vivian Nakate Joshua Kyenkya Mohammed Lamorde Catriona Waitt David Meya Agnes Kiragga HIV Medicine, 23 (4), pp. 319-323, 2022. @article{Odongpiny2022, title = {High willingness to use injectable antiretroviral therapy among women who have been lost to follow-up from HIV programmes: A nested cross-sectional study.}, author = {Eva Laker Agnes Odongpiny, Fiona Cresswell, Arnold Arinaitwe, Vivian Nakate, Joshua Kyenkya, Mohammed Lamorde, Catriona Waitt, David Meya, Agnes Kiragga}, doi = {https://doi.org/10.1111/hiv.13260}, year = {2022}, date = {2022-04-01}, journal = {HIV Medicine}, volume = {23}, number = {4}, pages = {319-323}, abstract = {Objectives Efforts to achieve zero transmission of HIV to infants born to women living with HIV in sub-Saharan African are undermined by high rates of loss to follow-up in prevention of vertical transmission (PVT) programmes. The fear of HIV status disclosure through the discovery of pill bottles at home is a major contributor. Injectable antiretroviral therapy (ART) has proved to be efficacious in clinical trials and is discreet, offering a potential solution. We investigated the knowledge and willingness to use injectable ART among women who were lost to follow-up from the PVT programme in Uganda. Methods Women were traced by nurse counsellors and knowledge and opinions relating to injectable ART, including willingness to use it when it becomes available, were collected. Generalized linear models were used to determine predictors of willingness to use injectable ART. Conclusions Among 1023 women registered between 2017 and 2019 under the PVT programmes in Kampala and Wakiso districts, Uganda, 385 (38%) were lost to follow-up from care and 22% of these (83/385) were successfully traced and interviewed. Only 25% (21/83) had heard of injectable ART. Over half (55%, 46/83) were very willing to use injectable ART, 40% (33/83) were somewhat willing and four (5%) were not willing. Those who associated ART tablets with disclosure risk were more willing to consider injectable ART (adjusted odds ratio = 4.21; 95% confidence interval: 1.45–12.19; p = 0.008). We report high willingness to use injectable ART associated with fears that ART tablets were a potential source of HIV status disclosure. Injectable ART could be a solution for women who have challenges with disclosure. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Objectives Efforts to achieve zero transmission of HIV to infants born to women living with HIV in sub-Saharan African are undermined by high rates of loss to follow-up in prevention of vertical transmission (PVT) programmes. The fear of HIV status disclosure through the discovery of pill bottles at home is a major contributor. Injectable antiretroviral therapy (ART) has proved to be efficacious in clinical trials and is discreet, offering a potential solution. We investigated the knowledge and willingness to use injectable ART among women who were lost to follow-up from the PVT programme in Uganda. Methods Women were traced by nurse counsellors and knowledge and opinions relating to injectable ART, including willingness to use it when it becomes available, were collected. Generalized linear models were used to determine predictors of willingness to use injectable ART. Conclusions Among 1023 women registered between 2017 and 2019 under the PVT programmes in Kampala and Wakiso districts, Uganda, 385 (38%) were lost to follow-up from care and 22% of these (83/385) were successfully traced and interviewed. Only 25% (21/83) had heard of injectable ART. Over half (55%, 46/83) were very willing to use injectable ART, 40% (33/83) were somewhat willing and four (5%) were not willing. Those who associated ART tablets with disclosure risk were more willing to consider injectable ART (adjusted odds ratio = 4.21; 95% confidence interval: 1.45–12.19; p = 0.008). We report high willingness to use injectable ART associated with fears that ART tablets were a potential source of HIV status disclosure. Injectable ART could be a solution for women who have challenges with disclosure. |
Diksha Srishyla Gabriel Saemisch, Fred Turya Elizabeth Nalintya Samuel Jjunju Enock Kagimu Morris Rutakingirwa Caleb Skipper David Boulware David Meya Radha Rajasingham K P R B Determinants of cryptococcal antigen (CrAg) screening uptake in Kampala, Uganda: An assessment of health center characteristics Journal Article Medical Mycology, 60 (4), pp. myac013, 2022. @article{Srishyla2022, title = {Determinants of cryptococcal antigen (CrAg) screening uptake in Kampala, Uganda: An assessment of health center characteristics}, author = {Diksha Srishyla, Gabriel Saemisch, Fred Turya, Elizabeth Nalintya, Samuel Jjunju, Enock Kagimu, Morris K Rutakingirwa, Caleb P Skipper, David R Boulware, David B Meya, Radha Rajasingham}, doi = {https://doi.org/10.1093/mmy/myac013}, year = {2022}, date = {2022-04-01}, journal = {Medical Mycology}, volume = {60}, number = {4}, pages = {myac013}, abstract = {Abstract Cryptococcal antigen (CrAg) screening and pre-emptive antifungal therapy for people with CD4 cell counts <100 cells/μl are recommended by the World Health Organization and several national HIV guidelines. We sought to evaluate CrAg screening program implementation across Uganda, in relation to health center level and distance from the capital. We conducted a cross-sectional study of 22 health centers across southern Uganda from April to June 2019. We reviewed laboratory records regarding number of CD4 cell count tests performed, proportion of outpatients with CD4 counts <200 cells/μl, and number of CrAg screening tests performed. We administered surveys to health center staff to understand barriers to advanced HIV care. We observed no significant difference in health center level and performance of CrAg screening; with each subsequent health center level, there was 1.17-fold (95% CI: 0.92–1.41) higher odds of CrAg screening performed per level. CrAg screening uptake was not associated with distance from the capital city (odds ratio = 0.96, 95% CI: 0.89–1.04). Qualitative data from surveys indicated that limitations to uptake of CrAg screening were secondary to dysfunctional CD4 machines, lack of provider awareness of CrAg screening guidelines, and inadequate/intermittent supply of CrAg tests. There were no significant associations between CrAg screening uptake and level of health center or distance of health center from the capital city. We identified systemic barriers to CrAg screening related to inadequate CD4 testing, insufficient knowledge regarding national screening guidelines, and irregular laboratory testing supplies. Lay summary The objective of this study was to evaluate cryptococcal antigen (CrAg) screening program implementation in Uganda, by type of healthcare center and by distance from the capital city. CrAg screening uptake was not associated with distance from the capital city, or the type of healthcare center. Key Terms Cryptococcal screening, advanced HIV disease, cryptococcal meningitis, implementation science Topic: hiv antifungal agents cryptococcal meningitis cd4 count determination procedure health status laboratory techniques and procedures outpatients uganda world health organization cryptococcus guidelines hiv infections cryptococcal polysaccharide test screening test hiv guidelines implementation }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Cryptococcal antigen (CrAg) screening and pre-emptive antifungal therapy for people with CD4 cell counts <100 cells/μl are recommended by the World Health Organization and several national HIV guidelines. We sought to evaluate CrAg screening program implementation across Uganda, in relation to health center level and distance from the capital. We conducted a cross-sectional study of 22 health centers across southern Uganda from April to June 2019. We reviewed laboratory records regarding number of CD4 cell count tests performed, proportion of outpatients with CD4 counts <200 cells/μl, and number of CrAg screening tests performed. We administered surveys to health center staff to understand barriers to advanced HIV care. We observed no significant difference in health center level and performance of CrAg screening; with each subsequent health center level, there was 1.17-fold (95% CI: 0.92–1.41) higher odds of CrAg screening performed per level. CrAg screening uptake was not associated with distance from the capital city (odds ratio = 0.96, 95% CI: 0.89–1.04). Qualitative data from surveys indicated that limitations to uptake of CrAg screening were secondary to dysfunctional CD4 machines, lack of provider awareness of CrAg screening guidelines, and inadequate/intermittent supply of CrAg tests. There were no significant associations between CrAg screening uptake and level of health center or distance of health center from the capital city. We identified systemic barriers to CrAg screening related to inadequate CD4 testing, insufficient knowledge regarding national screening guidelines, and irregular laboratory testing supplies. Lay summary The objective of this study was to evaluate cryptococcal antigen (CrAg) screening program implementation in Uganda, by type of healthcare center and by distance from the capital city. CrAg screening uptake was not associated with distance from the capital city, or the type of healthcare center. Key Terms Cryptococcal screening, advanced HIV disease, cryptococcal meningitis, implementation science Topic: hiv antifungal agents cryptococcal meningitis cd4 count determination procedure health status laboratory techniques and procedures outpatients uganda world health organization cryptococcus guidelines hiv infections cryptococcal polysaccharide test screening test hiv guidelines implementation |
Sally H. Mohamed Tinashe K. Nyazika, Kenneth Ssebambulidde Michail Lionakis David Meya S B; author, Rebecca Drummondcorresponding A Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis Journal Article Front Immunol, 13 , pp. 804674. , 2022. @article{Mohamed2022, title = {Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis}, author = {Sally H. Mohamed, Tinashe K. Nyazika, Kenneth Ssebambulidde, Michail S. Lionakis, David B. Meya and Rebecca A. Drummondcorresponding author }, doi = {doi: 10.3389/fimmu.2022.804674}, year = {2022}, date = {2022-04-01}, journal = {Front Immunol}, volume = {13}, pages = {804674. }, abstract = {Cryptococcal meningitis (CM) is the leading cause of central nervous system (CNS) fungal infections in humans, with the majority of cases reported from the African continent. This is partly due to the high burden of HIV infection in the region and reduced access to standard-of-care including optimal sterilising antifungal drug treatments. As such, CM is responsible for 10-15% of all HIV-related mortality, with a large proportion being preventable. Immunity to the causative agent of CM, Cryptococcus neoformans, is only partially understood. IFNγ producing CD4+ T-cells are required for the activation of myeloid cells, especially macrophages, to enable fungal killing and clearance. However, macrophages may also act as a reservoir of the fungal yeast cells, shielding them from host immune detection thus promoting latent infection or persistent chronic inflammation. In this chapter, we review the epidemiology and pathogenesis of CNS fungal infections in Africa, with a major focus on CM, and the antifungal immune pathways operating to protect against C. neoformans infection. We also highlight the areas of research and policy that require prioritisation to help reduce the burden of CNS fungal diseases in Africa. Keywords: microglia, cryptococcal meningitis, fungal infection, astrocyte, HAART}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cryptococcal meningitis (CM) is the leading cause of central nervous system (CNS) fungal infections in humans, with the majority of cases reported from the African continent. This is partly due to the high burden of HIV infection in the region and reduced access to standard-of-care including optimal sterilising antifungal drug treatments. As such, CM is responsible for 10-15% of all HIV-related mortality, with a large proportion being preventable. Immunity to the causative agent of CM, Cryptococcus neoformans, is only partially understood. IFNγ producing CD4+ T-cells are required for the activation of myeloid cells, especially macrophages, to enable fungal killing and clearance. However, macrophages may also act as a reservoir of the fungal yeast cells, shielding them from host immune detection thus promoting latent infection or persistent chronic inflammation. In this chapter, we review the epidemiology and pathogenesis of CNS fungal infections in Africa, with a major focus on CM, and the antifungal immune pathways operating to protect against C. neoformans infection. We also highlight the areas of research and policy that require prioritisation to help reduce the burden of CNS fungal diseases in Africa. Keywords: microglia, cryptococcal meningitis, fungal infection, astrocyte, HAART |
Jeffrey V. Lazarus Henry E. Mark, Marcela Villota-Rivas Adam Palayew Patrizia Carrieri Massimo Colombo Mattias Ekstedt Gamal Esmat Jacob George Giulio Marchesini Katja Novak Ponsiano Ocama Vlad Ratziu Homie Razavi Manuel Romero-Gómez Marcelo Silva Wendy Spearman Frank Tacke Edford Sinkala C The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge? Journal Article International Journal of Hepatology, 76 (4), pp. 771-780, 2022. @article{Lazarus2022, title = {The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge?}, author = {Jeffrey V. Lazarus, Henry E. Mark, Marcela Villota-Rivas, Adam Palayew, Patrizia Carrieri, Massimo Colombo, Mattias Ekstedt, Gamal Esmat, Jacob George,Giulio Marchesini, Katja Novak, Ponsiano Ocama, Vlad Ratziu,Homie Razavi, Manuel Romero-Gómez, Marcelo Silva, C. Wendy Spearman, Frank Tacke, Edford Sinkala }, doi = {https://doi.org/10.1016/j.jhep.2021.10.025}, year = {2022}, date = {2022-04-01}, journal = {International Journal of Hepatology}, volume = {76}, number = {4}, pages = {771-780}, abstract = {Background & Aims Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, yet largely underappreciated liver condition which is closely associated with obesity and metabolic disease. Despite affecting an estimated 1 in 4 adults globally, NAFLD is largely absent on national and global health agendas. Methods We collected data from 102 countries, accounting for 86% of the world population, on NAFLD policies, guidelines, civil society engagement, clinical management, and epidemiologic data. A preparedness index was developed by coding questions into 6 domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) and categorising the responses as high, medium, and low; a multiple correspondence analysis was then applied. Results The highest scoring countries were India (42.7) and the United Kingdom (40.0), with 32 countries (31%) scoring zero out of 100. For 5 of the domains a minority of countries were categorised as high-level while the majority were categorised as low-level. No country had a national or sub-national strategy for NAFLD and <2% of the different strategies for related conditions included any mention of NAFLD. National NAFLD clinical guidelines were present in only 32 countries. Conclusions Although NAFLD is a pressing public health problem, no country was found to be well prepared to address it. There is a pressing need for strategies to address NAFLD at national and global levels. Lay summary Around a third of the countries scored a zero on the NAFLD policy preparedness index, with no country scoring over 50/100. Although NAFLD is a pressing public health problem, a comprehensive public health response is lacking in all 102 countries. Policies and strategies to address NAFLD at the national and global levels are urgently needed.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background & Aims Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, yet largely underappreciated liver condition which is closely associated with obesity and metabolic disease. Despite affecting an estimated 1 in 4 adults globally, NAFLD is largely absent on national and global health agendas. Methods We collected data from 102 countries, accounting for 86% of the world population, on NAFLD policies, guidelines, civil society engagement, clinical management, and epidemiologic data. A preparedness index was developed by coding questions into 6 domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) and categorising the responses as high, medium, and low; a multiple correspondence analysis was then applied. Results The highest scoring countries were India (42.7) and the United Kingdom (40.0), with 32 countries (31%) scoring zero out of 100. For 5 of the domains a minority of countries were categorised as high-level while the majority were categorised as low-level. No country had a national or sub-national strategy for NAFLD and <2% of the different strategies for related conditions included any mention of NAFLD. National NAFLD clinical guidelines were present in only 32 countries. Conclusions Although NAFLD is a pressing public health problem, no country was found to be well prepared to address it. There is a pressing need for strategies to address NAFLD at national and global levels. Lay summary Around a third of the countries scored a zero on the NAFLD policy preparedness index, with no country scoring over 50/100. Although NAFLD is a pressing public health problem, a comprehensive public health response is lacking in all 102 countries. Policies and strategies to address NAFLD at the national and global levels are urgently needed. |
Miranda Ravicz Bernadette Muhongayire, Stella Kamagaju Robin Klabbers Zikama Faustin Andrew Kambugu Ingrid Bassett & Kelli O’Laughlin E Using Intervention Mapping methodology to design an HIV linkage intervention in a refugee settlement in rural Uganda Journal Article AIDS, Care, 34 (4), pp. 446-458, 2022. @article{Ravicz2022, title = {Using Intervention Mapping methodology to design an HIV linkage intervention in a refugee settlement in rural Uganda}, author = {Miranda Ravicz, Bernadette Muhongayire, Stella Kamagaju, Robin E. Klabbers, Zikama Faustin, Andrew Kambugu, Ingrid Bassett & Kelli O’Laughlin}, doi = {https://doi.org/10.1080/09540121.2021.1900532}, year = {2022}, date = {2022-04-01}, journal = {AIDS, Care}, volume = {34}, number = {4}, pages = {446-458}, abstract = {Nearly 80 million people have been forcibly displaced by persecution, violence, and disaster. Displaced populations, including refugees, face health challenges such as resource shortages, food and housing insecurity, violence, and disrupted social support. People living with HIV in refugee settings have decreased engagement with HIV services compared to non-refugee populations, and interventions are needed to enhance linkage to care. However, designing health interventions in humanitarian settings is challenging. We used Intervention Mapping (IM), a six-step method for developing theory- and evidence-based health interventions, to design a program to increase linkage to HIV care for refugees and Ugandan nationals in Nakivale Refugee Settlement in Uganda. We engaged a diverse group of stakeholders (N = 14) in Nakivale, including community members and humanitarian actors, in an interactive workshop focusing on IM steps 1–4. We developed a chronic care program that would integrate HIV care with services for hypertension and diabetes at accessible community sites, thereby decreasing stigma around HIV treatment and improving access to care. IM provided an inclusive, efficient method for integrating community members and program implementers in the intervention planning process, and can be used as a method-driven approach to intervention design in humanitarian settings.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Nearly 80 million people have been forcibly displaced by persecution, violence, and disaster. Displaced populations, including refugees, face health challenges such as resource shortages, food and housing insecurity, violence, and disrupted social support. People living with HIV in refugee settings have decreased engagement with HIV services compared to non-refugee populations, and interventions are needed to enhance linkage to care. However, designing health interventions in humanitarian settings is challenging. We used Intervention Mapping (IM), a six-step method for developing theory- and evidence-based health interventions, to design a program to increase linkage to HIV care for refugees and Ugandan nationals in Nakivale Refugee Settlement in Uganda. We engaged a diverse group of stakeholders (N = 14) in Nakivale, including community members and humanitarian actors, in an interactive workshop focusing on IM steps 1–4. We developed a chronic care program that would integrate HIV care with services for hypertension and diabetes at accessible community sites, thereby decreasing stigma around HIV treatment and improving access to care. IM provided an inclusive, efficient method for integrating community members and program implementers in the intervention planning process, and can be used as a method-driven approach to intervention design in humanitarian settings. |
Glenn J. Wagner Laura M. Bogart, Harold Green Erik Storholm David Klein Ryan McBain Richard Serunkuuma Kuraish Mubiru Joseph Matovu & Stephen Okoboi D D J K K B Trials, 23 (233), 2022. @article{Wagner2022, title = {Social network-based group intervention to promote HIV prevention in Uganda: study protocol for a cluster randomized controlled trial of Game Changers}, author = {Glenn J. Wagner, Laura M. Bogart, Harold D. Green, Erik D. Storholm, David J. Klein, Ryan K. McBain, Richard Serunkuuma, Kuraish Mubiru, Joseph K. B. Matovu & Stephen Okoboi }, doi = {https://doi.org/10.1186/s13063-022-06186-z}, year = {2022}, date = {2022-03-28}, journal = {Trials}, volume = {23}, number = {233}, abstract = {Introduction Innovative strategies are needed to disseminate HIV prevention messages across communities efficiently, as well as reduce HIV stigma while promoting HIV prevention. This randomized controlled trial will evaluate the efficacy of a social network-based group intervention, Game Changers, which trains persons living with HIV (PLWH) to encourage members of their social network to use HIV protective behaviors Methods PLWH in HIV care for at least 1 year will be randomly assigned to receive the 8-session group advocacy training intervention or no-intervention control group. Each enrolled PLWH (index participant) will be asked to recruit up to four social network members (alter participant). Assessments will be administered at baseline and months 6, 12, and 18 to both index and alter participants. The primary outcomes are HIV testing and condom use among alter participants; secondary outcomes are engagement in HIV prevention advocacy and internalized HIV stigma among index participants. Repeated-measures multivariable regression analyses will be conducted to compare outcomes between the intervention and control arms, in addition to a cost-effectiveness evaluation. Discussion This social network-based approach to HIV prevention is particularly timely in the era of biomedical interventions, which require widespread penetration of effective HIV prevention and care messaging into communities. Positioning PLWH as central to the solution for controlling (vs. causing) the HIV epidemic has the potential to reduce HIV stigma and improve prevention outcomes at the individual and network levels.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Introduction Innovative strategies are needed to disseminate HIV prevention messages across communities efficiently, as well as reduce HIV stigma while promoting HIV prevention. This randomized controlled trial will evaluate the efficacy of a social network-based group intervention, Game Changers, which trains persons living with HIV (PLWH) to encourage members of their social network to use HIV protective behaviors Methods PLWH in HIV care for at least 1 year will be randomly assigned to receive the 8-session group advocacy training intervention or no-intervention control group. Each enrolled PLWH (index participant) will be asked to recruit up to four social network members (alter participant). Assessments will be administered at baseline and months 6, 12, and 18 to both index and alter participants. The primary outcomes are HIV testing and condom use among alter participants; secondary outcomes are engagement in HIV prevention advocacy and internalized HIV stigma among index participants. Repeated-measures multivariable regression analyses will be conducted to compare outcomes between the intervention and control arms, in addition to a cost-effectiveness evaluation. Discussion This social network-based approach to HIV prevention is particularly timely in the era of biomedical interventions, which require widespread penetration of effective HIV prevention and care messaging into communities. Positioning PLWH as central to the solution for controlling (vs. causing) the HIV epidemic has the potential to reduce HIV stigma and improve prevention outcomes at the individual and network levels. |
van Joseph N. Jarvis David S. Lawrence, David Meya Enock Kagimu John Kasibante Edward Mpoza Morris Rutakingirwa Kenneth Ssebambulidde Lillian Tugume Joshua Rhein David Boulware Henry Mwandumba Melanie Moyo Henry Mzinganjira Cecilia Kanyama Mina Hosseinipour Chimwemwe Chawinga Graeme Meintjes Charlotte Schutz Kyla Comins Achita Singh Conrad Muzoora Samuel Jjunju Edwin Nuwagira Mosepele Mosepele Tshepo Leeme Keatlaretse Siamisang Chiratidzo Ndhlovu Admire Hlupeni Constantine Mutata Erik Widenfelt Tao Chen Duolao Wang William Hope Timothée Boyer-Chammard Angela Loyse Síle Molloy Nabila Youssouf Olivier Lortholary David Lalloo Shabbar Jaffar B K R C C E F G; for the Thomas S. Harrison, Ambition Study Group M D Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. Journal Article The New England Journal of Medicine, 386 (12), pp. 1109-1120, 2022. @article{Jarvis2022, title = {Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.}, author = {Joseph N. Jarvis, David S. Lawrence, David B. Meya, Enock Kagimu, John Kasibante, Edward Mpoza, Morris K. Rutakingirwa, Kenneth Ssebambulidde, Lillian Tugume, Joshua Rhein, David R. Boulware, Henry C. Mwandumba, Melanie Moyo, Henry Mzinganjira, Cecilia Kanyama, Mina C. Hosseinipour, Chimwemwe Chawinga, Graeme Meintjes, Charlotte Schutz, Kyla Comins, Achita Singh, Conrad Muzoora, Samuel Jjunju, Edwin Nuwagira, Mosepele Mosepele, Tshepo Leeme, Keatlaretse Siamisang, Chiratidzo E. Ndhlovu, Admire Hlupeni, Constantine Mutata, Erik van Widenfelt, Tao Chen, Duolao Wang, William Hope, Timothée Boyer-Chammard, Angela Loyse, Síle F. Molloy, Nabila Youssouf, Olivier Lortholary, David G. Lalloo, Shabbar Jaffar and Thomas S. Harrison, M.D. for the Ambition Study Group}, doi = {DOI: 10.1056/NEJMoa2111904}, year = {2022}, date = {2022-03-24}, journal = {The New England Journal of Medicine}, volume = {386}, number = {12}, pages = {1109-1120}, abstract = {Background Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)–related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. Methods In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization–recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. Results A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, −3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was −0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and −0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). Conclusions Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687. opens in new tab.)}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)–related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. Methods In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization–recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. Results A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, −3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was −0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and −0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). Conclusions Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687. opens in new tab.) |
Abigail Link Mark Okwir, Betty Nabongo David Meya Sarah Iribarren Paul Bohjanen ; Kasprzyk, Danuta Delays in Cryptococcal Meningitis Diagnosis and Care: A Mixed Methods Study in Rural Uganda Journal Article Annals of Global Health., 88 (1), pp. 22, 2022. @article{Link2022, title = {Delays in Cryptococcal Meningitis Diagnosis and Care: A Mixed Methods Study in Rural Uganda}, author = {Abigail Link, Mark Okwir, Betty Nabongo, David Meya, Sarah Iribarren, Paul Bohjanen and Danuta Kasprzyk}, doi = {doi: 10.5334/aogh.3524}, year = {2022}, date = {2022-03-18}, journal = {Annals of Global Health.}, volume = {88}, number = {1}, pages = {22}, abstract = {Background: Cryptococcal meningitis (CM) remains a major cause of mortality for HIV-infected persons in sub-Saharan Africa, despite widespread access to antiretroviral therapy. Delays in CM diagnosis and treatment contribute to high mortality, with patients often arriving “too late” for treatment to be effective. Little is known about patient-related delays and their experiences with CM. Objectives: This study seeks to identify the factors related to delays in diagnosis and care among patients with cryptococcal meningitis. Methods: A convergent mixed-methods approach was used to understand delays related to diagnosis and treatment of CM among patients admitted to Lira Regional Referral Hospital in rural northern Uganda. We collected data from February to March 2020 using surveys followed by semi-structured interviews from 20 CM patients who survived hospitalization and 20 family members of deceased patients during February 2017–November 2019. Interviews were audio-recorded, transcribed, and thematically coded for analysis. Findings: Delays to CM care were related to 1) self-medication, 2) lack of CM education, 3) seeking treatment multiple times at health centers with 4) missed/misdiagnosis, and 5) cultural factors. Among patients who died, 70% sought care ≥3 times, while those who survived, 35% of sought care ≥3 times before CM diagnosis. Only 10% of patients and 40% of family members knew what caused CM, indicating a lack of knowledge. Conclusions: Patients sought medical care for CM symptoms, but several factors contributed to CM diagnosis and care delays. Many of these factors relate to a lack of CM education and knowledge among patients and providers. A CM awareness campaign for the general public, targeted education for HIV patients, and continuing medical education for healthcare providers can decrease delays and improve outcomes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Cryptococcal meningitis (CM) remains a major cause of mortality for HIV-infected persons in sub-Saharan Africa, despite widespread access to antiretroviral therapy. Delays in CM diagnosis and treatment contribute to high mortality, with patients often arriving “too late” for treatment to be effective. Little is known about patient-related delays and their experiences with CM. Objectives: This study seeks to identify the factors related to delays in diagnosis and care among patients with cryptococcal meningitis. Methods: A convergent mixed-methods approach was used to understand delays related to diagnosis and treatment of CM among patients admitted to Lira Regional Referral Hospital in rural northern Uganda. We collected data from February to March 2020 using surveys followed by semi-structured interviews from 20 CM patients who survived hospitalization and 20 family members of deceased patients during February 2017–November 2019. Interviews were audio-recorded, transcribed, and thematically coded for analysis. Findings: Delays to CM care were related to 1) self-medication, 2) lack of CM education, 3) seeking treatment multiple times at health centers with 4) missed/misdiagnosis, and 5) cultural factors. Among patients who died, 70% sought care ≥3 times, while those who survived, 35% of sought care ≥3 times before CM diagnosis. Only 10% of patients and 40% of family members knew what caused CM, indicating a lack of knowledge. Conclusions: Patients sought medical care for CM symptoms, but several factors contributed to CM diagnosis and care delays. Many of these factors relate to a lack of CM education and knowledge among patients and providers. A CM awareness campaign for the general public, targeted education for HIV patients, and continuing medical education for healthcare providers can decrease delays and improve outcomes. |
Kagimu Enock Kiwanuka Julius, Bridget Griffith Derrick Bary Abila Morris Rutakingirwa John Kasibante Kiiza Tadeo Kandole Richard Kwizera Aggrey Semeere & David Meya C K B BMC Health Services Research, 22 , pp. 301, 2022. @article{Enock2022, title = {Evaluation of the initial 12 months of a routine cryptococcal antigen screening program in reduction of HIV-associated cryptococcal meningitis in Uganda}, author = {Kagimu Enock, Kiwanuka Julius, Bridget C. Griffith, Derrick Bary Abila, Morris K. Rutakingirwa, John Kasibante, Kiiza Tadeo Kandole, Richard Kwizera, Aggrey Semeere & David B. Meya }, doi = {https://doi.org/10.1186/s12913-022-07624-z}, year = {2022}, date = {2022-03-04}, journal = {BMC Health Services Research}, volume = {22}, pages = {301}, abstract = {Background Asymptomatic Cryptococcal Antigenemia (CrAg) patients develop meningitis within a month of testing positive. Pre-emptive antifungal therapy can prevent progression to Cryptococcal meningitis (CM). In April 2016, a national CrAg screening program was initiated in 206 high-volume health facilities that provide antiretroviral therapy in Uganda. We report the evaluation of the CrAg screening cascade focusing on linkage to care, fluconazole therapy for 10 weeks and 6 months follow up, and ART initiation in a subset of facilities. Methods We conducted a retrospective, cross-sectional survey of patients with CD4 < 100 at seven urban and seven rural facilities after 1 year of program implementation. We quantified the number of patients who transitioned through the steps of the CrAg screening cascade over six-months follow-up. We defined cascade completion as a pre-emptive fluconazole prescription for the first 10 weeks. We conducted semi-structured interviews with lab personnel and clinic staff to assess functionality of the CrAg screening program. Data was collected using REDCap. Results We evaluated 359 patient records between April 2016 to March 2017; the majority (358/359, 99.7%) were from government owned health facilities and just over half (193/359, 53.8%) had a median baseline CD4 cell count of < 50 cell/μL. Overall, CrAg screening had been performed in 255/359 (71.0, 95% CI, 66.0–75.7) of patients’ records reviewed, with a higher proportion among urban facilities (170/209 (81.3, 95% CI, 75.4–86.4)) than rural facilities (85/150 (56.7, 95% CI, 48.3–64.7)). Among those who were CrAg screened, 56/255 (22.0, 95% CI, 17.0–27.5%) had cryptococcal antigenemia, of whom 47/56 (83.9, 95% CI, 71.7–92.4%) were initiated on pre-emptive therapy with fluconazole and 8/47 (17.0, 95% CI, 7.6–30.8%) of these were still receiving antifungal therapy at 6 months follow up. At least one CNS symptom was present in 70% (39/56) of those with antigenemia. In patients who had started ART, almost 40% initiated ART prior to CrAg screening. Inadequacy of equipment/supplies was reported by 15/26 (58%) of personnel as a program barrier, while 13/26 (50%) reported a need for training about CM and CrAg screening. Conclusion There was a critical gap in the follow-up of patients after initiation on fluconazole therapy. ART had been initiated in almost 40% of patients prior to CrAg screening.. Higher antigenemia patients presenting with CNS symptoms could be related to late presentation. There is need to address these gaps after a more thorough evaluation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Asymptomatic Cryptococcal Antigenemia (CrAg) patients develop meningitis within a month of testing positive. Pre-emptive antifungal therapy can prevent progression to Cryptococcal meningitis (CM). In April 2016, a national CrAg screening program was initiated in 206 high-volume health facilities that provide antiretroviral therapy in Uganda. We report the evaluation of the CrAg screening cascade focusing on linkage to care, fluconazole therapy for 10 weeks and 6 months follow up, and ART initiation in a subset of facilities. Methods We conducted a retrospective, cross-sectional survey of patients with CD4 < 100 at seven urban and seven rural facilities after 1 year of program implementation. We quantified the number of patients who transitioned through the steps of the CrAg screening cascade over six-months follow-up. We defined cascade completion as a pre-emptive fluconazole prescription for the first 10 weeks. We conducted semi-structured interviews with lab personnel and clinic staff to assess functionality of the CrAg screening program. Data was collected using REDCap. Results We evaluated 359 patient records between April 2016 to March 2017; the majority (358/359, 99.7%) were from government owned health facilities and just over half (193/359, 53.8%) had a median baseline CD4 cell count of < 50 cell/μL. Overall, CrAg screening had been performed in 255/359 (71.0, 95% CI, 66.0–75.7) of patients’ records reviewed, with a higher proportion among urban facilities (170/209 (81.3, 95% CI, 75.4–86.4)) than rural facilities (85/150 (56.7, 95% CI, 48.3–64.7)). Among those who were CrAg screened, 56/255 (22.0, 95% CI, 17.0–27.5%) had cryptococcal antigenemia, of whom 47/56 (83.9, 95% CI, 71.7–92.4%) were initiated on pre-emptive therapy with fluconazole and 8/47 (17.0, 95% CI, 7.6–30.8%) of these were still receiving antifungal therapy at 6 months follow up. At least one CNS symptom was present in 70% (39/56) of those with antigenemia. In patients who had started ART, almost 40% initiated ART prior to CrAg screening. Inadequacy of equipment/supplies was reported by 15/26 (58%) of personnel as a program barrier, while 13/26 (50%) reported a need for training about CM and CrAg screening. Conclusion There was a critical gap in the follow-up of patients after initiation on fluconazole therapy. ART had been initiated in almost 40% of patients prior to CrAg screening.. Higher antigenemia patients presenting with CNS symptoms could be related to late presentation. There is need to address these gaps after a more thorough evaluation. |
Frank Mulindwa Habiba Kamal, Barbara Castelnuovo Robert Bollinger Jean-Marc Schwarz Nele Brussealers C PLOS ONE, 17 (3), 2022. @article{Mulindwa2022, title = {Association between integrase strand transfer inhibitor (INSTIs) use with insulin resistance and incident diabetes mellitus in persons living with HIV: A systematic review and meta-analysis protocol}, author = {Frank Mulindwa, Habiba Kamal, Barbara Castelnuovo, Robert C. Bollinger, Jean-Marc Schwarz, Nele Brussealers}, doi = {https://doi.org/10.1371/journal.pone.0264792}, year = {2022}, date = {2022-03-02}, journal = {PLOS ONE}, volume = {17}, number = {3}, abstract = {Introduction Poeple living with HIV have higher prevalence of diabetes mellitus and metabolic perturbations compared to non-HIV populations. Diabetes and metabolic syndrome co-morbidities add significant burden to HIV care. Currently, WHO recommends integrase strand transfer inhibitors (INSTIs) as the first or second line therapy in people with HIV due to overall good tolerability and safety profile. However, whether INSTI use increases the risk of incident diabetes (with or without metabolic syndrome) compared to other anti-retroviral therapies (ART) is controversial. In this systematic review and meta-analysis, we aim to examine this risk in HIV-positive populations receiving INSTIs compared to other ART regimens (not containing INSTIs). Methods and analysis The study will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. This protocol adheres to the Standard Protocol Items for reporting systematic reviews and meta-analyses checklist. Eligibility criteria will be original peer-reviewed published articles and conference abstracts with no language or geographical restriction; that report the ocurrence of diabetes mellitus as a discrete outcome or part of metabolic syndrome, in adult PLWHIV receiving INSTIs compared to other ART regimens. PubMed/ Medline, Web of Science, Embase and Cochrane Database of Systematic Reviews will be searched from 1st- January-2000 to 31st—January-2022. Per our a priori, screening, inclusion and data extraction will be conducted separately by two investigators, and a senior researcher will be consulted in case of disagreement. The quality of included studies will be assessed by the Newcastle-Ottawa Scale (NOS) for cohort and case-control studies and the revised Cochrane risk-of-bias tool (ROB2) for randomized controlled trials. The quantitative synthesis of the study outcomes will be explored in different subgroups and sensitivity analyses. Meta regression will also be performed to further test the predictors of the outcome. Ethics and dissemination Ethical approval is waived as the study is a review of published litterature. The analyses will be presented in conferences and published as a scientific article.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Introduction Poeple living with HIV have higher prevalence of diabetes mellitus and metabolic perturbations compared to non-HIV populations. Diabetes and metabolic syndrome co-morbidities add significant burden to HIV care. Currently, WHO recommends integrase strand transfer inhibitors (INSTIs) as the first or second line therapy in people with HIV due to overall good tolerability and safety profile. However, whether INSTI use increases the risk of incident diabetes (with or without metabolic syndrome) compared to other anti-retroviral therapies (ART) is controversial. In this systematic review and meta-analysis, we aim to examine this risk in HIV-positive populations receiving INSTIs compared to other ART regimens (not containing INSTIs). Methods and analysis The study will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. This protocol adheres to the Standard Protocol Items for reporting systematic reviews and meta-analyses checklist. Eligibility criteria will be original peer-reviewed published articles and conference abstracts with no language or geographical restriction; that report the ocurrence of diabetes mellitus as a discrete outcome or part of metabolic syndrome, in adult PLWHIV receiving INSTIs compared to other ART regimens. PubMed/ Medline, Web of Science, Embase and Cochrane Database of Systematic Reviews will be searched from 1st- January-2000 to 31st—January-2022. Per our a priori, screening, inclusion and data extraction will be conducted separately by two investigators, and a senior researcher will be consulted in case of disagreement. The quality of included studies will be assessed by the Newcastle-Ottawa Scale (NOS) for cohort and case-control studies and the revised Cochrane risk-of-bias tool (ROB2) for randomized controlled trials. The quantitative synthesis of the study outcomes will be explored in different subgroups and sensitivity analyses. Meta regression will also be performed to further test the predictors of the outcome. Ethics and dissemination Ethical approval is waived as the study is a review of published litterature. The analyses will be presented in conferences and published as a scientific article. |
Fan Yang Kenneth R. Katumba, Bram Roudijk Zhihao Yang Paul Revill Susan Griffin Perez Ochanda Mohammed Lamorde Giulia Greco Janet Seeley & Mark Sculpher N Developing the EQ-5D-5L Value Set for Uganda Using the ‘Lite’ Protocol Journal Article PharmacoEconomics, 40 (3), pp. 309–321, 2022. @article{Yang2022, title = {Developing the EQ-5D-5L Value Set for Uganda Using the ‘Lite’ Protocol}, author = {Fan Yang, Kenneth R. Katumba, Bram Roudijk, Zhihao Yang, Paul Revill, Susan Griffin, Perez N. Ochanda, Mohammed Lamorde, Giulia Greco, Janet Seeley & Mark Sculpher }, doi = {https://doi.org/10.1007/s40273-021-01101-x}, year = {2022}, date = {2022-03-01}, journal = {PharmacoEconomics}, volume = {40}, number = {3}, pages = {309–321}, abstract = {Objective A ‘lite’ version of the EQ-5D-5L valuation protocol, which requires a smaller sample by collecting more data from each participant, was proposed and used to develop an EQ-5D-5L value set for Uganda. Methods Adult respondents from the general Ugandan population were quota sampled based on age and sex. Eligible participants were asked to complete 20 composite time trade-off tasks in the tablet-assisted personal interviews using the offline EuroQol Portable Valuation Technology software under routine quality control. No discrete choice experiment task was administered. The composite time trade-off data were modelled using four additive and two multiplicative regression models. Model performance was evaluated based on face validity, prediction accuracy in cross-validation and in predicting mild health states. The final value set was generated using the best-performing model. Results A representative sample (N = 545) participated in this study. Responses to composite time trade-off tasks from 492 participants were included in the primary analysis. All models showed face validity and generated comparable prediction accuracy. The Tobit model with constrained intercepts and corrected for heteroscedasticity was considered the preferred model for the value set on the basis of better performance. The value set ranges from − 1.116 (state 55555) to 1 (state 11111) with ‘pain/discomfort’ as the most important dimension. Conclusions This is the first EQ-5D-5L valuation study using a ‘lite’ protocol involving composite time trade-off data only. Our results suggest its feasibility in resource-constrained settings. The established EQ-5D-5L value set for Uganda is expected to be used for economic evaluations and decision making in Uganda and the East Africa region.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Objective A ‘lite’ version of the EQ-5D-5L valuation protocol, which requires a smaller sample by collecting more data from each participant, was proposed and used to develop an EQ-5D-5L value set for Uganda. Methods Adult respondents from the general Ugandan population were quota sampled based on age and sex. Eligible participants were asked to complete 20 composite time trade-off tasks in the tablet-assisted personal interviews using the offline EuroQol Portable Valuation Technology software under routine quality control. No discrete choice experiment task was administered. The composite time trade-off data were modelled using four additive and two multiplicative regression models. Model performance was evaluated based on face validity, prediction accuracy in cross-validation and in predicting mild health states. The final value set was generated using the best-performing model. Results A representative sample (N = 545) participated in this study. Responses to composite time trade-off tasks from 492 participants were included in the primary analysis. All models showed face validity and generated comparable prediction accuracy. The Tobit model with constrained intercepts and corrected for heteroscedasticity was considered the preferred model for the value set on the basis of better performance. The value set ranges from − 1.116 (state 55555) to 1 (state 11111) with ‘pain/discomfort’ as the most important dimension. Conclusions This is the first EQ-5D-5L valuation study using a ‘lite’ protocol involving composite time trade-off data only. Our results suggest its feasibility in resource-constrained settings. The established EQ-5D-5L value set for Uganda is expected to be used for economic evaluations and decision making in Uganda and the East Africa region. |
Ronald Nsubuga Norbert Adrawa, Stephen Okoboi Alimah Komuhangi & Jonathan Izudi Complete sputum smear monitoring among adults with pulmonary tuberculosis in central Uganda: evidence from a retrospective cohort study Journal Article BMC Infectious Diseases , 22 (1), pp. 191, 2022. @article{Nsubuga2022, title = {Complete sputum smear monitoring among adults with pulmonary tuberculosis in central Uganda: evidence from a retrospective cohort study}, author = {Ronald Nsubuga, Norbert Adrawa, Stephen Okoboi, Alimah Komuhangi & Jonathan Izudi}, doi = {https://doi.org/10.1186/s12879-022-07178-9}, year = {2022}, date = {2022-02-25}, journal = {BMC Infectious Diseases }, volume = {22}, number = {1}, pages = {191}, abstract = {Background People with bacteriologically confirmed pulmonary tuberculosis require sputum smear monitoring at 2, 5, and 6 months to establish treatment outcomes. However, there is limited information about sputum smear monitoring in Uganda, similar to other developing countries. We examined factors associated with complete sputum smear monitoring among persons with bacteriologically confirmed pulmonary TB aged ≥ 15 years in central Uganda. Methods We retrospectively reviewed and abstracted data for persons with bacteriologically confirmed pulmonary TB initiated on treatment between January 2017 and December 2019 across 11 large TB units in Masaka district in central Uganda. Complete sputum smear monitoring was measured as the receipt of three sputum smear microscopy tests at 2, 5, and 6 months of TB treatment. The data were summarized descriptively and the differences in the outcome with independent variables were examined using tests of statistical significance, namely the Chi-square or Fisher’s exact test and the student’s t-test. The factors independently associated with the outcome were established using the modified Poisson regression analysis with robust standard errors, reported as adjusted risk ratio (aRR) along with the 95% confidence interval (CI). Results A total of 416 participants were enrolled, with a mean age of 37.3 ± 12.9 years. Of the participants, 290 (69.7) were males, 269 (64.7) were rural residents, and 128 (30.8%) had complete sputum smear monitoring. Urban residence (aRR, 1.45; 95% CI 1.12–1.90) and treatment under the community-based directly observed therapy short-course strategy (DOTS) (aRR, 1.91; 95% CI 1.25–2.92) were associated with a higher likelihood of complete sputum smear monitoring while TB and human immunodeficiency virus (TB/HIV) comorbidity (aRR 0.45, 95% CI 0.30–0.68) was associated with a lower likelihood of complete sputum smear monitoring. Conclusions We found a low magnitude of complete sputum smear monitoring among persons with bacteriologically confirmed pulmonary TB aged ≥ 15 years in central Uganda. Strategies to enhance the performance of sputum smear monitoring should target rural health facilities, strengthen TB/HIV collaboration and the implementation of community-based DOTS.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background People with bacteriologically confirmed pulmonary tuberculosis require sputum smear monitoring at 2, 5, and 6 months to establish treatment outcomes. However, there is limited information about sputum smear monitoring in Uganda, similar to other developing countries. We examined factors associated with complete sputum smear monitoring among persons with bacteriologically confirmed pulmonary TB aged ≥ 15 years in central Uganda. Methods We retrospectively reviewed and abstracted data for persons with bacteriologically confirmed pulmonary TB initiated on treatment between January 2017 and December 2019 across 11 large TB units in Masaka district in central Uganda. Complete sputum smear monitoring was measured as the receipt of three sputum smear microscopy tests at 2, 5, and 6 months of TB treatment. The data were summarized descriptively and the differences in the outcome with independent variables were examined using tests of statistical significance, namely the Chi-square or Fisher’s exact test and the student’s t-test. The factors independently associated with the outcome were established using the modified Poisson regression analysis with robust standard errors, reported as adjusted risk ratio (aRR) along with the 95% confidence interval (CI). Results A total of 416 participants were enrolled, with a mean age of 37.3 ± 12.9 years. Of the participants, 290 (69.7) were males, 269 (64.7) were rural residents, and 128 (30.8%) had complete sputum smear monitoring. Urban residence (aRR, 1.45; 95% CI 1.12–1.90) and treatment under the community-based directly observed therapy short-course strategy (DOTS) (aRR, 1.91; 95% CI 1.25–2.92) were associated with a higher likelihood of complete sputum smear monitoring while TB and human immunodeficiency virus (TB/HIV) comorbidity (aRR 0.45, 95% CI 0.30–0.68) was associated with a lower likelihood of complete sputum smear monitoring. Conclusions We found a low magnitude of complete sputum smear monitoring among persons with bacteriologically confirmed pulmonary TB aged ≥ 15 years in central Uganda. Strategies to enhance the performance of sputum smear monitoring should target rural health facilities, strengthen TB/HIV collaboration and the implementation of community-based DOTS. |
Mark Okwir Abigail Link, Joshua Rhein John Stephen Obbo James Okello Betty Nabongo Jimmy Alal David Meya Paul Bohjanen R Open Forum Infectious Diseases, 9 (2), pp. ofac004, 2022. @article{Okwir2022, title = {High Burden of Cryptococcal Meningitis Among Antiretroviral Therapy–Experienced Human Immunodeficiency Virus–Infected Patients in Northern Uganda in the Era of “Test and Treat”: Implications for Cryptococcal Screening Programs }, author = {Mark Okwir, Abigail Link, Joshua Rhein, John Stephen Obbo, James Okello, Betty Nabongo, Jimmy Alal, David Meya, Paul R Bohjanen}, doi = {https://doi.org/10.1093/ofid/ofac004}, year = {2022}, date = {2022-02-01}, journal = {Open Forum Infectious Diseases}, volume = {9}, number = {2}, pages = {ofac004}, abstract = {Background The impact of the “test and treat” program for human immunodeficiency virus (HIV) treatment in rural areas of Uganda on cryptococcal antigen (CrAg) screening or cryptococcal meningitis (CM) is poorly understood. Methods We retrospectively evaluated clinical factors in 212 HIV-infected patients diagnosed with CM from February of 2017 to November of 2019 at Lira Regional Referral Hospital in northern Uganda. Results Among 212 patients diagnosed with CM, 58.5% were male. Median age was 35 years; CD4 count and HIV viral load (VL) were 86 cells/μL and 9463 copies/mL, respectively. Only 10% of patients had a previous history of CM. We found that 190 of 209 (90.9%) patients were ART experienced and 19 (9.1%) were ART naive. Overall, 90 of 212 (42.5%) patients died while hospitalized (median time to death, 14 days). Increased risk of death was associated with altered mental status (hazard ratio [HR], 6.6 [95% confidence interval {CI}, 2.411–18.219]; P ≤ .0001) and seizures (HR, 5.23 [95% CI, 1.245–21.991]; P = .024). Conclusions Current guidelines recommend CrAg screening based on low CD4 counts for ART-naive patients and VL or clinical failure for ART-experienced patients. Using current guidelines for CrAg screening, some ART-experienced patients miss CrAg screening in resource-limited settings, when CD4 or VL tests are unavailable. We found that the majority of HIV-infected patients with CM were ART experienced (90.9%) at presentation. The high burden of CM in ART-experienced patients supports a need for improved CrAg screening of ART-exposed patients. Key Terms antiretroviral therapy, cryptococcal meningitis outcomes, screening Topic: hiv seizures cryptococcal meningitis cd4 count determination procedure uganda cryptococcus guidelines mortality hiv infections anti-retroviral agents }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background The impact of the “test and treat” program for human immunodeficiency virus (HIV) treatment in rural areas of Uganda on cryptococcal antigen (CrAg) screening or cryptococcal meningitis (CM) is poorly understood. Methods We retrospectively evaluated clinical factors in 212 HIV-infected patients diagnosed with CM from February of 2017 to November of 2019 at Lira Regional Referral Hospital in northern Uganda. Results Among 212 patients diagnosed with CM, 58.5% were male. Median age was 35 years; CD4 count and HIV viral load (VL) were 86 cells/μL and 9463 copies/mL, respectively. Only 10% of patients had a previous history of CM. We found that 190 of 209 (90.9%) patients were ART experienced and 19 (9.1%) were ART naive. Overall, 90 of 212 (42.5%) patients died while hospitalized (median time to death, 14 days). Increased risk of death was associated with altered mental status (hazard ratio [HR], 6.6 [95% confidence interval {CI}, 2.411–18.219]; P ≤ .0001) and seizures (HR, 5.23 [95% CI, 1.245–21.991]; P = .024). Conclusions Current guidelines recommend CrAg screening based on low CD4 counts for ART-naive patients and VL or clinical failure for ART-experienced patients. Using current guidelines for CrAg screening, some ART-experienced patients miss CrAg screening in resource-limited settings, when CD4 or VL tests are unavailable. We found that the majority of HIV-infected patients with CM were ART experienced (90.9%) at presentation. The high burden of CM in ART-experienced patients supports a need for improved CrAg screening of ART-exposed patients. Key Terms antiretroviral therapy, cryptococcal meningitis outcomes, screening Topic: hiv seizures cryptococcal meningitis cd4 count determination procedure uganda cryptococcus guidelines mortality hiv infections anti-retroviral agents |
Radha Rajasingham Elizabeth Nalintya, Dennis Israelski David Meya Bruce Larson David Boulware M B A R Medical Mycology, 60 (2), pp. myab078, 2022. @article{Rajasingham2022, title = {Cost-effectiveness of single-dose AmBisome pre-emptive treatment for the prevention of cryptococcal meningitis in African low and middle-income countries}, author = {Radha Rajasingham, Elizabeth Nalintya, Dennis M Israelski, David B Meya, Bruce A Larson, David R Boulware}, doi = { https://doi.org/10.1093/mmy/myab078}, year = {2022}, date = {2022-02-01}, journal = {Medical Mycology}, volume = {60}, number = {2}, pages = {myab078}, abstract = {Abstract Cryptococcal antigen (CrAg) screening is recommended for patients with advanced HIV to reduce AIDS-related mortality. For asymptomatic CrAg-positive persons, fluconazole pre-emptive therapy is standard, despite a ∼25% failure rate. Single-dose liposomal amphotericin B (AmBisome) is non-inferior to standard treatment for cryptococcal meningitis. We evaluate the threshold of efficacy necessary for AmBisome + fluconazole to be cost-effective as pre-emptive therapy for CrAg-positive persons. We created a decision analytic model to evaluate CrAg screening and treatment in HIV-infected persons with CD4 < 100 cells/μL. Costs were estimated for screening, pre-emptive therapy, and hospitalization for an example low-income country (Uganda) and middle-income country (South Africa). We used a discounted price range of AmBisome® at $16.25 to $40 per 50 mg vial for both Uganda and South Africa. We estimated AmBisome efficacy from 75 to 95%. Parameter assumptions were based on prospective CrAg screening studies and clinical trials in Africa. Disability adjusted life years (DALYs) were calculated using the age-specific life expectancy in Uganda, per WHO Global Health Observatory data. We modeled the theoretical efficacy of adjunctive AmBisome to determine cost per DALY averted. In South Africa, at $16.25 per vial cost and a minimum efficacy of 85%, adjunctive AmBisome is cost-saving compared to fluconazole monotherapy. Compared to fluconazole pre-emptive therapy in Uganda, AmBisome + fluconazole would cost $475, $220, or $136 per DALY averted if meningitis-free survival efficacy was 80, 85, or 90% at $24 per vial cost. Investing in AmBisome may be cost-effective in low-income settings compared to using fluconazole pre-emptive therapy alone, if efficacy is 85% or greater. AmBisome pre-emptive therapy appears more cost-efficient in middle-income settings where hospitalization costs for meningitis, and GDP per capita are higher. Lay Summary We evaluate the efficacy necessary for AmBisome + fluconazole to be cost-effective to prevent cryptococcal meningitis. We found that if AmBisome pre-emptive therapy has an efficacy of 85% or greater, it is likely to be cost-effective in low-income settings. Topic: meningitis amphotericin b cryptococcal meningitis cost effectiveness fluconazole income south africa uganda disability-adjusted life years vial single-dose regimen prevention }, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Cryptococcal antigen (CrAg) screening is recommended for patients with advanced HIV to reduce AIDS-related mortality. For asymptomatic CrAg-positive persons, fluconazole pre-emptive therapy is standard, despite a ∼25% failure rate. Single-dose liposomal amphotericin B (AmBisome) is non-inferior to standard treatment for cryptococcal meningitis. We evaluate the threshold of efficacy necessary for AmBisome + fluconazole to be cost-effective as pre-emptive therapy for CrAg-positive persons. We created a decision analytic model to evaluate CrAg screening and treatment in HIV-infected persons with CD4 < 100 cells/μL. Costs were estimated for screening, pre-emptive therapy, and hospitalization for an example low-income country (Uganda) and middle-income country (South Africa). We used a discounted price range of AmBisome® at $16.25 to $40 per 50 mg vial for both Uganda and South Africa. We estimated AmBisome efficacy from 75 to 95%. Parameter assumptions were based on prospective CrAg screening studies and clinical trials in Africa. Disability adjusted life years (DALYs) were calculated using the age-specific life expectancy in Uganda, per WHO Global Health Observatory data. We modeled the theoretical efficacy of adjunctive AmBisome to determine cost per DALY averted. In South Africa, at $16.25 per vial cost and a minimum efficacy of 85%, adjunctive AmBisome is cost-saving compared to fluconazole monotherapy. Compared to fluconazole pre-emptive therapy in Uganda, AmBisome + fluconazole would cost $475, $220, or $136 per DALY averted if meningitis-free survival efficacy was 80, 85, or 90% at $24 per vial cost. Investing in AmBisome may be cost-effective in low-income settings compared to using fluconazole pre-emptive therapy alone, if efficacy is 85% or greater. AmBisome pre-emptive therapy appears more cost-efficient in middle-income settings where hospitalization costs for meningitis, and GDP per capita are higher. Lay Summary We evaluate the efficacy necessary for AmBisome + fluconazole to be cost-effective to prevent cryptococcal meningitis. We found that if AmBisome pre-emptive therapy has an efficacy of 85% or greater, it is likely to be cost-effective in low-income settings. Topic: meningitis amphotericin b cryptococcal meningitis cost effectiveness fluconazole income south africa uganda disability-adjusted life years vial single-dose regimen prevention |
Glenn J. Wagner Laura M. Bogart, David Klein Harold Green Joan Nampiima Andrew Kambugu & Joseph Matovu J D K B AIDS and Behavior, 26 , pp. 2485–2493, 2022. @article{Wagner2022b, title = {Association of Condom Use Advocacy with Perceived Condom Use Among Social Network Members: The Mediating Role of Advocates’ Internalized HIV Stigma and Own Condom Use}, author = {Glenn J. Wagner, Laura M. Bogart, David J. Klein, Harold D. Green, Joan Nampiima, Andrew Kambugu & Joseph K. B. Matovu }, doi = {https://doi.org/10.1007/s10461-022-03601-z}, year = {2022}, date = {2022-01-29}, journal = {AIDS and Behavior}, volume = {26}, pages = {2485–2493}, abstract = {We examined the association of HIV prevention advocacy with social network members (alters) on alter condom use behavior, and factors that may mediate and moderate this relationship, among people living with HIV (PLWH) in Uganda. Ninety PLWH completed all assessments (baseline and 5- and 8-month follow-ups). Internalized HIV stigma, HIV disclosure self-efficacy, positive living behavior (i.e., condom use), and advocacy self-efficacy were examined as mediators (at 5-month follow-up) of the association between condom use advocacy and perceived alter condom use. Individual socio-demographic and social network characteristics at baseline were examined as moderators. Among alters who received condom use advocacy in the months prior to both baseline and 5-month follow-up, 69.9% (51/73) were perceived to mostly/always use condoms at either the 5- or 8-month follow-up, which was significantly higher than the 36.4% (235/645) of alters who received none or less advocacy. Participants’ internalized HIV stigma and consistent condom use mediated the association of advocacy and perceived consistent condom use among alters; the participant having any secondary education and the alter being male were associated with increased magnitude of the associations between advocacy and alter condom use. These findings highlight the importance of sustained advocacy to promote consistent condom use, and the value of anti-stigma and positive living interventions as mechanisms for enhancing effective advocacy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We examined the association of HIV prevention advocacy with social network members (alters) on alter condom use behavior, and factors that may mediate and moderate this relationship, among people living with HIV (PLWH) in Uganda. Ninety PLWH completed all assessments (baseline and 5- and 8-month follow-ups). Internalized HIV stigma, HIV disclosure self-efficacy, positive living behavior (i.e., condom use), and advocacy self-efficacy were examined as mediators (at 5-month follow-up) of the association between condom use advocacy and perceived alter condom use. Individual socio-demographic and social network characteristics at baseline were examined as moderators. Among alters who received condom use advocacy in the months prior to both baseline and 5-month follow-up, 69.9% (51/73) were perceived to mostly/always use condoms at either the 5- or 8-month follow-up, which was significantly higher than the 36.4% (235/645) of alters who received none or less advocacy. Participants’ internalized HIV stigma and consistent condom use mediated the association of advocacy and perceived consistent condom use among alters; the participant having any secondary education and the alter being male were associated with increased magnitude of the associations between advocacy and alter condom use. These findings highlight the importance of sustained advocacy to promote consistent condom use, and the value of anti-stigma and positive living interventions as mechanisms for enhancing effective advocacy. |
Hussein Mukasa Kafeero Dorothy Ndagire, Ponsiano Ocama Charles Drago Kato Eddie Wampande Henry Kajumbula David Kateete Abdul Walusansa Ali Kudamba Kigozi Edgar Fred Ashaba Katabazi Maria Magdalene Namaganda Jamilu Ssenku E; Sendagire, Hakim International Journal of Hepatology, 2022 (688547,), pp. 15 Pages, 2022. @article{Kafeero2022, title = {Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management}, author = {Hussein Mukasa Kafeero, Dorothy Ndagire, Ponsiano Ocama, Charles Drago Kato, Eddie Wampande, Henry Kajumbula, David Kateete, Abdul Walusansa, Ali Kudamba, Kigozi Edgar, Fred Ashaba Katabazi, Maria Magdalene Namaganda, Jamilu E. Ssenku and Hakim Sendagire}, doi = {https://doi.org/10.1155/2022/3688547}, year = {2022}, date = {2022-01-11}, journal = {International Journal of Hepatology}, volume = {2022}, number = {688547,}, pages = {15 Pages}, abstract = {Abstract Background. Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease. Methods. A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson’s chi-square, multinomial logistic regression, and Mann–Whitney tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A was considered statistically significant. Results. Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly (). Genotype D was significantly associated with elevated viral load and direct bilirubin (). The recombinant genotype D/E was significantly associated with elevated viral load (). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels (). Conclusion. There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Background. Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease. Methods. A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson’s chi-square, multinomial logistic regression, and Mann–Whitney tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A was considered statistically significant. Results. Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly (). Genotype D was significantly associated with elevated viral load and direct bilirubin (). The recombinant genotype D/E was significantly associated with elevated viral load (). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels (). Conclusion. There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies. |
Matthew L. Romo Rena C. Patel, Jessie Edwards John Humphrey Beverly Musick Caitlin Bernard Mercy Maina Ellen Brazier Barbara Castelnuovo Jeremy Penner Katarzyna Wyka Sandra Wagner Cardoso Penh Sun Ly Cordelia Kunzekwenyika Claudia Cortés Radoslaw Panczak Elizabeth Kelvin Kara Wools-Kaloustian K M S W P A K; on behalf of epidemiology to Denis Nash, International Databases Evaluate AIDS (IeDEA) Annals of Internal Medicine, 175 (1), pp. 84-94, 2022. @article{Romo2022, title = {Disparities in Dolutegravir Uptake Affecting Females of Reproductive Age With HIV in Low- and Middle-Income Countries After Initial Concerns About Teratogenicity}, author = {Matthew L. Romo, Rena C. Patel, Jessie K. Edwards, John M. Humphrey, Beverly S. Musick, Caitlin Bernard, Mercy W. Maina, Ellen Brazier, Barbara Castelnuovo,Jeremy Penner, Katarzyna Wyka, Sandra Wagner Cardoso, Penh Sun Ly, Cordelia Kunzekwenyika, Claudia P. Cortés, Radoslaw Panczak, Elizabeth A. Kelvin, Kara K. Wools-Kaloustian and Denis Nash, on behalf of International epidemiology Databases to Evaluate AIDS (IeDEA)}, doi = {https://doi.org/10.7326/M21-3037}, year = {2022}, date = {2022-01-03}, journal = {Annals of Internal Medicine}, volume = {175}, number = {1}, pages = {84-94}, abstract = {Background: The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. Objective: To describe dolutegravir uptake and disparities by sex and age group in LMICs. Design: Observational cohort study. Setting: 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Patients: 134 672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. Measurements: Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). Results: Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. Limitation: Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. Conclusion: Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. Objective: To describe dolutegravir uptake and disparities by sex and age group in LMICs. Design: Observational cohort study. Setting: 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Patients: 134 672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. Measurements: Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). Results: Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. Limitation: Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. Conclusion: Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. |
Innocent G. Asiimwe Marc Blockman, Karen Cohen Clint Cupido Claire Hutchinson Barry Jacobson Mohammed Lamorde Jennie Morgan Johannes Mouton Doreen Nakagaayi Emmy Okello Elise Schapkaitz Christine Sekaggya-Wiltshire Jerome Semakula Catriona Waitt Eunice Zhang Andrea Jorgensen Munir Pirmohamed P R J L CPT: Pharmacometrics & System Pharmacology, 11 (1), pp. 20-29, 2022. @article{Asiimwe2022, title = {Stable warfarin dose prediction in sub-Saharan African patients: A machine-learning approach and external validation of a clinical dose–initiation algorithm}, author = {Innocent G. Asiimwe, Marc Blockman, Karen Cohen, Clint Cupido, Claire Hutchinson, Barry Jacobson, Mohammed Lamorde, Jennie Morgan, Johannes P. Mouton, Doreen Nakagaayi, Emmy Okello, Elise Schapkaitz, Christine Sekaggya-Wiltshire, Jerome R. Semakula, Catriona Waitt, Eunice J. Zhang, Andrea L. Jorgensen, Munir Pirmohamed}, doi = { https://doi.org/10.1002/psp4.12740}, year = {2022}, date = {2022-01-02}, journal = {CPT: Pharmacometrics & System Pharmacology}, volume = {11}, number = {1}, pages = {20-29}, abstract = {Warfarin remains the most widely prescribed oral anticoagulant in sub-Saharan Africa. However, because of its narrow therapeutic index, dosing can be challenging. We have therefore (a) evaluated and compared the performance of 21 machine-learning techniques in predicting stable warfarin dose in sub-Saharan Black-African patients and (b) externally validated a previously developed Warfarin Anticoagulation in Patients in Sub-Saharan Africa (War-PATH) clinical dose–initiation algorithm. The development cohort included 364 patients recruited from eight outpatient clinics and hospital departments in Uganda and South Africa (June 2018–July 2019). Validation was conducted using an external validation cohort (270 patients recruited from August 2019 to March 2020 in 12 outpatient clinics and hospital departments). Based on the mean absolute error (MAE; mean of absolute differences between the actual and predicted doses), random forest regression (12.07 mg/week; 95% confidence interval [CI], 10.39–13.76) was the best performing machine-learning technique in the external validation cohort, whereas the worst performing technique was model trees (17.59 mg/week; 95% CI, 15.75–19.43). By comparison, the simple, commonly used regression technique (ordinary least squares) performed similarly to more complex supervised machine-learning techniques and achieved an MAE of 13.01 mg/week (95% CI, 11.45–14.58). In summary, we have demonstrated that simpler regression techniques perform similarly to more complex supervised machine-learning techniques. We have also externally validated our previously developed clinical dose–initiation algorithm, which is being prospectively tested for clinical utility.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Warfarin remains the most widely prescribed oral anticoagulant in sub-Saharan Africa. However, because of its narrow therapeutic index, dosing can be challenging. We have therefore (a) evaluated and compared the performance of 21 machine-learning techniques in predicting stable warfarin dose in sub-Saharan Black-African patients and (b) externally validated a previously developed Warfarin Anticoagulation in Patients in Sub-Saharan Africa (War-PATH) clinical dose–initiation algorithm. The development cohort included 364 patients recruited from eight outpatient clinics and hospital departments in Uganda and South Africa (June 2018–July 2019). Validation was conducted using an external validation cohort (270 patients recruited from August 2019 to March 2020 in 12 outpatient clinics and hospital departments). Based on the mean absolute error (MAE; mean of absolute differences between the actual and predicted doses), random forest regression (12.07 mg/week; 95% confidence interval [CI], 10.39–13.76) was the best performing machine-learning technique in the external validation cohort, whereas the worst performing technique was model trees (17.59 mg/week; 95% CI, 15.75–19.43). By comparison, the simple, commonly used regression technique (ordinary least squares) performed similarly to more complex supervised machine-learning techniques and achieved an MAE of 13.01 mg/week (95% CI, 11.45–14.58). In summary, we have demonstrated that simpler regression techniques perform similarly to more complex supervised machine-learning techniques. We have also externally validated our previously developed clinical dose–initiation algorithm, which is being prospectively tested for clinical utility. |
2021 |
Paul W. Blair, Mohammed Lamorde ; Dumler, Stephen J Rickettsioses and Q Fever in Tanzania: Estimating the Burden of Pervasive and Neglected Causes of Severe Febrile Illness in Sub-Saharan Africa Journal Article The American Journal of Tropical Medicine and Hygiene, 106 (2), pp. 371–372, 2021. @article{Blair2021, title = {Rickettsioses and Q Fever in Tanzania: Estimating the Burden of Pervasive and Neglected Causes of Severe Febrile Illness in Sub-Saharan Africa}, author = {Paul W. Blair, Mohammed Lamorde and J. Stephen Dumler}, doi = {doi: 10.4269/ajtmh.21-0963}, year = {2021}, date = {2021-12-20}, journal = {The American Journal of Tropical Medicine and Hygiene}, volume = {106}, number = {2}, pages = {371–372}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Pauline Byakika-Kibwika Christine Sekaggya-Wiltshire, Jerome Roy Semakula Jane Nakibuuka Joseph Musaazi James Kayima Cornelius Sendagire David Meya Bruce Kirenga Sarah Nanzigu Arthur Kwizera Fred Nakwagala Ivan Kisuule Misaki Wayengera Henry Mwebesa Moses Kamya & William Bazeyo G R BMC Infectious Diseases, 21 (1218), 2021. @article{Byakika-Kibwika2021, title = {Safety and efficacy of hydroxychloroquine for treatment of non-severe COVID-19 among adults in Uganda: a randomized open label phase II clinical trial.}, author = {Pauline Byakika-Kibwika, Christine Sekaggya-Wiltshire, Jerome Roy Semakula, Jane Nakibuuka, Joseph Musaazi, James Kayima, Cornelius Sendagire, David Meya, Bruce Kirenga, Sarah Nanzigu, Arthur Kwizera, Fred Nakwagala, Ivan Kisuule, Misaki Wayengera, Henry G. Mwebesa, Moses R. Kamya & William Bazeyo}, doi = {https://doi.org/10.1186/s12879-021-06897-9}, year = {2021}, date = {2021-12-06}, journal = {BMC Infectious Diseases}, volume = {21}, number = {1218}, abstract = {Background Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. Design We conducted a randomized open label Phase II clinical trial from October–December 2020. Methods Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. Results Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3–4) vs 4(2–4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. Conclusion Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. Design We conducted a randomized open label Phase II clinical trial from October–December 2020. Methods Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. Results Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3–4) vs 4(2–4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. Conclusion Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda. |
Kenneth Mulungu Proscovia Katumba, Rosalind Parkes Ratanshi Adelline Twimukye Barbara Castelnuovo Aidah Nanvuma & Godfrey Akileng Intrapreneurship and technological innovation in optimizing qualitative research as evidenced at Infectious Diseases Institute, Uganda Journal Article Journal of Innovation and Entrepreneurship, 10 (47), 2021. @article{Mulungu2021, title = {Intrapreneurship and technological innovation in optimizing qualitative research as evidenced at Infectious Diseases Institute, Uganda}, author = {Kenneth Mulungu, Proscovia Katumba, Rosalind Parkes Ratanshi, Adelline Twimukye, Barbara Castelnuovo, Aidah Nanvuma & Godfrey Akileng }, doi = {https://doi.org/10.1186/s13731-021-00188-y}, year = {2021}, date = {2021-12-05}, journal = {Journal of Innovation and Entrepreneurship}, volume = {10}, number = {47}, abstract = {Background Discrepancies between what is transcribed and the actual interview recordings were noticed in qualitative research reports. This study aimed at the development of a new transcription software (Jiegnote), and the evaluation of its effectiveness in the optimization of the transcription process, to minimize transcription completion time, and errors in qualitative research. Methods The study was a mixed methods project implemented from September to November 2020. The qualitative aspect of the study was phenomenological in perspective whereas the quantitative consisted of a randomized controlled trial (RCT) with a parallel design. Results At the time of the study, the Jiegnote software was a working prototype. We enrolled a total of 26 participants; 14 participants had their data analyzed in the RCT part of the study, 13 participated in the in-depth interviews, and 22 in the answering of Semi Structured Questionnaires. Upon the execution of an independent t test, results showed that, there was no statistical significance between the intervention and control means. On considering the total average transcription completion time and the type of language in which an audio case was recorded, the effect size evaluation implied that the Jiegnote software had a small impact (Hedges' g = 0.413438) in reducing the total average time taken to translate and transcribe audio cases that were recorded in a local language (Luganda), and a large impact (Hedges' g = 1.190919) in reducing the total average time taken to transcribe audio cases that were recorded in a foreign language (English). On considering the total average number of transcription errors and the type of language in which an audio case is recorded, the effect size evaluation implied that the Jiegnote software had a small impact (Hedges' g = 0.213258) in reducing the total average time taken to translate and transcribe audio cases that were recorded in a local language (Luganda). This was further observed (Hedges' g = 0.039928) in the transcription of cases that were recorded in a foreign language (English). On considering the in-depth interview data outcomes, participants responded that the Jiegnote software media looping functions (algorithm) enabled them to accomplish their transcription tasks in a shorter time and with fewer errors compared to the traditional methods. Conclusion The study demonstrates utilities associated with intrapreneurship and technological innovation in an organization setting whereby, the Jiegnote technology that was developed by the researchers, had some impact on the optimization of the qualitative research value chain. This was observed through the effect size (impact) evaluations that were conducted to investigate the superiority of the Jiegnote software against the traditional transcription methods, in minimizing the average number of errors committed, and time taken to complete a transcription process.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Discrepancies between what is transcribed and the actual interview recordings were noticed in qualitative research reports. This study aimed at the development of a new transcription software (Jiegnote), and the evaluation of its effectiveness in the optimization of the transcription process, to minimize transcription completion time, and errors in qualitative research. Methods The study was a mixed methods project implemented from September to November 2020. The qualitative aspect of the study was phenomenological in perspective whereas the quantitative consisted of a randomized controlled trial (RCT) with a parallel design. Results At the time of the study, the Jiegnote software was a working prototype. We enrolled a total of 26 participants; 14 participants had their data analyzed in the RCT part of the study, 13 participated in the in-depth interviews, and 22 in the answering of Semi Structured Questionnaires. Upon the execution of an independent t test, results showed that, there was no statistical significance between the intervention and control means. On considering the total average transcription completion time and the type of language in which an audio case was recorded, the effect size evaluation implied that the Jiegnote software had a small impact (Hedges' g = 0.413438) in reducing the total average time taken to translate and transcribe audio cases that were recorded in a local language (Luganda), and a large impact (Hedges' g = 1.190919) in reducing the total average time taken to transcribe audio cases that were recorded in a foreign language (English). On considering the total average number of transcription errors and the type of language in which an audio case is recorded, the effect size evaluation implied that the Jiegnote software had a small impact (Hedges' g = 0.213258) in reducing the total average time taken to translate and transcribe audio cases that were recorded in a local language (Luganda). This was further observed (Hedges' g = 0.039928) in the transcription of cases that were recorded in a foreign language (English). On considering the in-depth interview data outcomes, participants responded that the Jiegnote software media looping functions (algorithm) enabled them to accomplish their transcription tasks in a shorter time and with fewer errors compared to the traditional methods. Conclusion The study demonstrates utilities associated with intrapreneurship and technological innovation in an organization setting whereby, the Jiegnote technology that was developed by the researchers, had some impact on the optimization of the qualitative research value chain. This was observed through the effect size (impact) evaluations that were conducted to investigate the superiority of the Jiegnote software against the traditional transcription methods, in minimizing the average number of errors committed, and time taken to complete a transcription process. |
on behalf of the collaboration Win Min Han Matthew G Law, Matthias Egger Kara Wools-Kaloustian Richard Moore Catherine McGowan Nagalingesawaran Kumarasamy Sophie Desmonde Andrew Edmonds Mary-Ann Davies Constantin Yiannoutsos Keri Althoff Claudia Cortes Thahira Jamal Mohamed Antoine Jaquet Kathryn Anastos Jonathan Euvrard Barbara Castelnuovo Kate Salters Lara Esteves Coelho Didier Ekouevi Brian Eley Lameck Diero Elizabeth Zaniewski Nathan Ford Annette Sohn Azar Kariminia IeDEA N P K H The Lancet HIV, 8 (12), pp. e766-e775, 2021. @article{Han2021, title = {Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries}, author = {Win Min Han, Matthew G Law, Matthias Egger, Kara Wools-Kaloustian, Richard Moore, Catherine McGowan, Nagalingesawaran Kumarasamy, Sophie Desmonde, Andrew Edmonds, Mary-Ann Davies, Constantin Yiannoutsos, Keri N Althoff, Claudia P Cortes, Thahira Jamal Mohamed, Antoine Jaquet, Kathryn Anastos, Jonathan Euvrard, Barbara Castelnuovo, Kate Salters, Lara Esteves Coelho, Didier K Ekouevi, Brian Eley, Lameck Diero, Elizabeth Zaniewski, Nathan Ford, Annette H Sohn, Azar Kariminia, on behalf of the IeDEA collaboration}, doi = {https://doi.org/10.1016/S2352-3018(21)00265-4}, year = {2021}, date = {2021-12-01}, journal = {The Lancet HIV}, volume = {8}, number = {12}, pages = {e766-e775}, abstract = {Background As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. Methods In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. Findings 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43–81]) of 18 835 at 1 year, 10 796 (62% [41–77]) of 17 553 at 2 years, and 9177 (59% [38–91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53–80]) of 225 418 at 1 year, 145 552 (72% [48–79]) of 201 238 at 2 years, and 115 260 (65% [43–69]) of 178 458 at 3 years after ART initiation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. Methods In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. Findings 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43–81]) of 18 835 at 1 year, 10 796 (62% [41–77]) of 17 553 at 2 years, and 9177 (59% [38–91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53–80]) of 225 418 at 1 year, 145 552 (72% [48–79]) of 201 238 at 2 years, and 115 260 (65% [43–69]) of 178 458 at 3 years after ART initiation. |
Okello Michael, Kayondo Derick ; Ponsiano, Ocama Gastroduodenal intussusception as a rare cause of pancreatitis in a young female Ugandan: A case report Journal Article International Journal of Surgery Case Reports, 89 , pp. 106632, 2021. @article{Michael2021, title = {Gastroduodenal intussusception as a rare cause of pancreatitis in a young female Ugandan: A case report}, author = {Okello Michael, Kayondo Derick and Ocama Ponsiano}, doi = {https://doi.org/10.1016/j.ijscr.2021.106632}, year = {2021}, date = {2021-12-01}, journal = {International Journal of Surgery Case Reports}, volume = {89}, pages = {106632}, abstract = {Introduction and importance Gastroduodenal intussusceptions are rare and usually secondary to gastric lesions acting as the lead point. Gastrointestinal stromal tumors (GISTs) commonly occur in the stomach (40–60%). Other gastric tumors include; adenocarcinomas, leiomyomas, lymphomas among others. When gastric tumors act as lead points in gastroduodenal intussusception, pancreatitis may arise due to compression of the ampulla of Vater or pancreatic head. Gastroduodenal intussusception may mimic other inflammatory upper gastrointestinal conditions leading to delays in early diagnosis and timely intervention. Case presentation A twenty three year old female with gastroduodenal intussusception secondary to a gastric body GIST with associated pancreatitis. This gastroduodenal mass was initially diagnosed as a pancreatic head echo-complex mass by ultrasound. Confirmatory preoperative diagnosis was made after doing contrasted abdominal computed tomography (CT) scan and upper gastrointestinal endoscopy. Open gastric wedge resection was done. Patient had uneventful recovery and was discharged on the fifth postoperative day. Clinical discussion Gastroduodenal intussusceptions have non-specific clinical features that may lead to delays in making the correct diagnosis. CT scan is a good imaging modality for diagnosing this condition but access is limited in low resource settings. Resection of the organic cause after reducing the intussusception leads to resolution of the symptoms caused by the intussusception, the GIST and the resultant pancreatitis. Conclusion Gastroduodenal intussusception is rare and may present with nonspecific clinical features. Pancreatitis may arise due to the compression effects on the ampulla of Vater or pancreatic head. A high index of suspicion is key in making a timely diagnosis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Introduction and importance Gastroduodenal intussusceptions are rare and usually secondary to gastric lesions acting as the lead point. Gastrointestinal stromal tumors (GISTs) commonly occur in the stomach (40–60%). Other gastric tumors include; adenocarcinomas, leiomyomas, lymphomas among others. When gastric tumors act as lead points in gastroduodenal intussusception, pancreatitis may arise due to compression of the ampulla of Vater or pancreatic head. Gastroduodenal intussusception may mimic other inflammatory upper gastrointestinal conditions leading to delays in early diagnosis and timely intervention. Case presentation A twenty three year old female with gastroduodenal intussusception secondary to a gastric body GIST with associated pancreatitis. This gastroduodenal mass was initially diagnosed as a pancreatic head echo-complex mass by ultrasound. Confirmatory preoperative diagnosis was made after doing contrasted abdominal computed tomography (CT) scan and upper gastrointestinal endoscopy. Open gastric wedge resection was done. Patient had uneventful recovery and was discharged on the fifth postoperative day. Clinical discussion Gastroduodenal intussusceptions have non-specific clinical features that may lead to delays in making the correct diagnosis. CT scan is a good imaging modality for diagnosing this condition but access is limited in low resource settings. Resection of the organic cause after reducing the intussusception leads to resolution of the symptoms caused by the intussusception, the GIST and the resultant pancreatitis. Conclusion Gastroduodenal intussusception is rare and may present with nonspecific clinical features. Pancreatitis may arise due to the compression effects on the ampulla of Vater or pancreatic head. A high index of suspicion is key in making a timely diagnosis. |
Wendy Spearman Mary Afihene, Omolade Betiku Bilal Bobat Lina Cunha Chris Kassianides Leolin Katsidzira DPhil Hailemichael Mekonnen Ponsiano Ocama Olusegun Ojo Imran Paruk Cert Endo Metab Christian Tzeuton Mark Sonderup Gastroenterology D W; of sub-Saharan (GHASSA), Hepatology Association Africa Epidemiology, risk factors, social determinants of health, and current management for non-alcoholic fatty liver disease in sub-Saharan Africa Journal Article The Lancet; Gastroentology & Hepatology, 6 (12), pp. 1036-1046, 2021. @article{Spearman2021, title = {Epidemiology, risk factors, social determinants of health, and current management for non-alcoholic fatty liver disease in sub-Saharan Africa}, author = {Wendy Spearman, Mary Afihene, Omolade Betiku, Bilal Bobat, Lina Cunha, Chris Kassianides, Leolin Katsidzira, DPhil, Hailemichael D Mekonnen, Ponsiano Ocama, Olusegun Ojo, Imran Paruk Cert Endo Metab, Christian Tzeuton, Mark W Sonderup, Gastroenterology and Hepatology Association of sub-Saharan Africa (GHASSA)}, doi = {https://doi.org/10.1016/S2468-1253(21)00275-2}, year = {2021}, date = {2021-12-01}, journal = {The Lancet; Gastroentology & Hepatology}, volume = {6}, number = {12}, pages = {1036-1046}, abstract = {Summary Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally and is estimated to affect approximately 25% of the world's population. Data about the prevalence and incidence of NAFLD in Africa are scarce, but the prevalence is estimated to be 13·5% for the general population. This is likely to be an underestimate considering the increasing burden of non-communicable diseases, particularly the rising prevalence of obesity and type 2 diabetes, driven by the overlapping challenges of food insecurity, nutritional transition, and associated increased consumption of calorie-dense foods. Establishing the true prevalence of NAFLD, raising public awareness around the risk factors behind the increase in NAFLD, and proactively addressing all components of metabolic syndrome will be important to combat this silent epidemic, which will have long-term health-care costs and economic consequences for the region.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Summary Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally and is estimated to affect approximately 25% of the world's population. Data about the prevalence and incidence of NAFLD in Africa are scarce, but the prevalence is estimated to be 13·5% for the general population. This is likely to be an underestimate considering the increasing burden of non-communicable diseases, particularly the rising prevalence of obesity and type 2 diabetes, driven by the overlapping challenges of food insecurity, nutritional transition, and associated increased consumption of calorie-dense foods. Establishing the true prevalence of NAFLD, raising public awareness around the risk factors behind the increase in NAFLD, and proactively addressing all components of metabolic syndrome will be important to combat this silent epidemic, which will have long-term health-care costs and economic consequences for the region. |
Glenn J. Wagner Laura M. Bogart, David Klein Harold Green Andrew Kambugu Joan Nampiima & Joseph Matovu J D K B International Journal of Behavioral Medicine volume, 28 (6), pp. 737–745, 2021. @article{Wagner2021, title = {Examination of Mediators and Moderators to Understand How and in What Context Game Changers Increases HIV Prevention Advocacy Among Persons Living With HIV in Uganda}, author = {Glenn J. Wagner, Laura M. Bogart, David J. Klein, Harold D. Green, Andrew Kambugu, Joan Nampiima & Joseph K. B. Matovu }, doi = {https://doi.org/10.1007/s12529-021-09983-z}, year = {2021}, date = {2021-12-01}, journal = {International Journal of Behavioral Medicine volume}, volume = {28}, number = {6}, pages = {737–745}, abstract = {Background Our randomized controlled trial (RCT) of the group-based Game Changers intervention demonstrated effects on the primary goal of increased HIV-protective behaviors among social network members (alters), via the mechanism of increased participant engagement in HIV prevention advocacy with alters. We sought to understand how and in what context the intervention has its effects by examining specific mediators and moderators of the intervention’s effect on increased prevention advocacy. Methods The RCT was conducted with 98 adult PLWH in Uganda. Intervention content targeted internalized HIV stigma, HIV disclosure, positive living behaviors, and self-efficacy for advocacy; these constructs were examined as intervention mediators (at the 5-month follow-up) of advocacy effects reported at the 8-month follow-up. Baseline sample characteristics were explored as moderators. Results Internalized HIV stigma and HIV disclosure mediated intervention effects on prevention advocacy, but not antiretroviral adherence or self-efficacy for advocacy. Moderators of the intervention effect included several network characteristics (trust in, support from, stigma from, and connectedness among network members), but not respondent socio-demographics or HIV disease characteristics. The intervention was associated with greater prevention advocacy when trust in, support from, and connectedness among alters were high, and stigma from alters was low. Conclusions These findings highlight the importance of helping PLWH cope with self-stigma and gain comfort with disclosure, as well as the potential influence of network support, trustworthiness, connectedness, and stigmatization on engagement in prevention advocacy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Our randomized controlled trial (RCT) of the group-based Game Changers intervention demonstrated effects on the primary goal of increased HIV-protective behaviors among social network members (alters), via the mechanism of increased participant engagement in HIV prevention advocacy with alters. We sought to understand how and in what context the intervention has its effects by examining specific mediators and moderators of the intervention’s effect on increased prevention advocacy. Methods The RCT was conducted with 98 adult PLWH in Uganda. Intervention content targeted internalized HIV stigma, HIV disclosure, positive living behaviors, and self-efficacy for advocacy; these constructs were examined as intervention mediators (at the 5-month follow-up) of advocacy effects reported at the 8-month follow-up. Baseline sample characteristics were explored as moderators. Results Internalized HIV stigma and HIV disclosure mediated intervention effects on prevention advocacy, but not antiretroviral adherence or self-efficacy for advocacy. Moderators of the intervention effect included several network characteristics (trust in, support from, stigma from, and connectedness among network members), but not respondent socio-demographics or HIV disease characteristics. The intervention was associated with greater prevention advocacy when trust in, support from, and connectedness among alters were high, and stigma from alters was low. Conclusions These findings highlight the importance of helping PLWH cope with self-stigma and gain comfort with disclosure, as well as the potential influence of network support, trustworthiness, connectedness, and stigmatization on engagement in prevention advocacy. |
Timothy M. Rawson Richard C. Wilson, Danny O’Hare Pau Herrero Andrew Kambugu Mohammed Lamorde Matthew Ellington Pantelis Georgiou Anthony Cass William Hope & Alison Holmes W H Optimizing antimicrobial use: challenges, advances and opportunities Journal Article Nature Reviews Microbiology, 19 (12), pp. 747–758, 2021. @article{Rawson2021, title = {Optimizing antimicrobial use: challenges, advances and opportunities}, author = {Timothy M. Rawson, Richard C. Wilson, Danny O’Hare, Pau Herrero, Andrew Kambugu, Mohammed Lamorde, Matthew Ellington, Pantelis Georgiou, Anthony Cass, William W. Hope & Alison H. Holmes }, doi = {https://doi.org/10.1038/s41579-021-00578-9}, year = {2021}, date = {2021-12-01}, journal = {Nature Reviews Microbiology}, volume = {19}, number = {12}, pages = {747–758}, abstract = {An optimal antimicrobial dose provides enough drug to achieve a clinical response while minimizing toxicity and development of drug resistance. There can be considerable variability in pharmacokinetics, for example, owing to comorbidities or other medications, which affects antimicrobial pharmacodynamics and, thus, treatment success. Although current approaches to antimicrobial dose optimization address fixed variability, better methods to monitor and rapidly adjust antimicrobial dosing are required to understand and react to residual variability that occurs within and between individuals. We review current challenges to the wider implementation of antimicrobial dose optimization and highlight novel solutions, including biosensor-based, real-time therapeutic drug monitoring and computer-controlled, closed-loop control systems. Precision antimicrobial dosing promises to improve patient outcome and is important for antimicrobial stewardship and the prevention of antimicrobial resistance.}, keywords = {}, pubstate = {published}, tppubtype = {article} } An optimal antimicrobial dose provides enough drug to achieve a clinical response while minimizing toxicity and development of drug resistance. There can be considerable variability in pharmacokinetics, for example, owing to comorbidities or other medications, which affects antimicrobial pharmacodynamics and, thus, treatment success. Although current approaches to antimicrobial dose optimization address fixed variability, better methods to monitor and rapidly adjust antimicrobial dosing are required to understand and react to residual variability that occurs within and between individuals. We review current challenges to the wider implementation of antimicrobial dose optimization and highlight novel solutions, including biosensor-based, real-time therapeutic drug monitoring and computer-controlled, closed-loop control systems. Precision antimicrobial dosing promises to improve patient outcome and is important for antimicrobial stewardship and the prevention of antimicrobial resistance. |
Nicholaus P. Mnyambwa Doreen Philbert, Godfather Kimaro Steve Wandiga Bruce Kirenga Blandina Theophil Mmbaga Winters Muttamba Irene Najjingo Simon Walusimbi Roseline Nuwarinda Douglas Okello Hadja Semvua James Ngocho Mbazi Senkoro Okoboi Stephen Barbara Castelnuovo Aman Wilfred Erick Mgina EstherNgadayaa Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 25 , pp. 100278, 2021. @article{Mnyambwa2021, title = {Gaps related to screening and diagnosis of tuberculosis in care cascade in selected health facilities in East Africa countries: A retrospective study}, author = {Nicholaus P. Mnyambwa, Doreen Philbert, Godfather Kimaro, Steve Wandiga, Bruce Kirenga, Blandina Theophil Mmbaga, Winters Muttamba, Irene Najjingo, Simon Walusimbi, Roseline Nuwarinda, Douglas Okello, Hadja Semvua, James Ngocho, Mbazi Senkoro, Okoboi Stephen, Barbara Castelnuovo, Aman Wilfred, Erick Mgina, EstherNgadayaa}, doi = {https://doi.org/10.1016/j.jctube.2021.100278}, year = {2021}, date = {2021-12-01}, journal = {Journal of Clinical Tuberculosis and Other Mycobacterial Diseases}, volume = {25}, pages = {100278}, abstract = {Introduction East Africa countries (Tanzania, Kenya, and Uganda) are among tuberculosis high burdened countries globally. As we race to accelerate progress towards a world free of tuberculosis by 2035, gaps related to screening and diagnosis in the cascade care need to be addressed. Methods We conducted a three-year (2015–2017) retrospective study using routine program data in 21 health facilities from East Africa. Data abstraction were done at tuberculosis clinics, outpatient departments (OPD), human immunodeficiency virus (HIV) and diabetic clinics, and then complemented with structured interviews with healthcare providers to identify possible gaps related to integration, screening, and diagnosis of tuberculosis. Data were analyzed using STATA™ Version 14.1. Results We extracted information from 49,454 presumptive TB patients who were registered in the 21 facilities between January 2015 and December 2017. A total of 9,565 tuberculosis cases were notified; 46.5% (4,450) were bacteriologically confirmed and 31.5% (3,013) were HIV-infected. Prevalence of tuberculosis among presumptive pulmonary tuberculosis cases was 17.4%. The outcomes observed were as follows: 79.8% (7,646) cured or completed treatment, 6.6% (634) died, 13.3% (1,270) lost to follow-up or undocumented and 0.4% (34) treatment failure. In all countries, tuberculosis screening was largely integrated at OPD and HIV clinics. High patient load, weak laboratory specimen referral system, shortage of trained personnel, and frequent interruption of laboratory supplies were the major cited challenges in screening and diagnosis of tuberculosis. Conclusion Screening and diagnostic activities were frequently affected by scarcity of human and financial resources. Tuberculosis screening was mainly integrated at OPD and HIV clinics, with less emphasis on the other health facility clinics. Closing gaps related to TB case finding and diagnosis in developing countries requires sustainable investment for both human and financial resources and strengthen the integration of TB activities within the health system.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Introduction East Africa countries (Tanzania, Kenya, and Uganda) are among tuberculosis high burdened countries globally. As we race to accelerate progress towards a world free of tuberculosis by 2035, gaps related to screening and diagnosis in the cascade care need to be addressed. Methods We conducted a three-year (2015–2017) retrospective study using routine program data in 21 health facilities from East Africa. Data abstraction were done at tuberculosis clinics, outpatient departments (OPD), human immunodeficiency virus (HIV) and diabetic clinics, and then complemented with structured interviews with healthcare providers to identify possible gaps related to integration, screening, and diagnosis of tuberculosis. Data were analyzed using STATA™ Version 14.1. Results We extracted information from 49,454 presumptive TB patients who were registered in the 21 facilities between January 2015 and December 2017. A total of 9,565 tuberculosis cases were notified; 46.5% (4,450) were bacteriologically confirmed and 31.5% (3,013) were HIV-infected. Prevalence of tuberculosis among presumptive pulmonary tuberculosis cases was 17.4%. The outcomes observed were as follows: 79.8% (7,646) cured or completed treatment, 6.6% (634) died, 13.3% (1,270) lost to follow-up or undocumented and 0.4% (34) treatment failure. In all countries, tuberculosis screening was largely integrated at OPD and HIV clinics. High patient load, weak laboratory specimen referral system, shortage of trained personnel, and frequent interruption of laboratory supplies were the major cited challenges in screening and diagnosis of tuberculosis. Conclusion Screening and diagnostic activities were frequently affected by scarcity of human and financial resources. Tuberculosis screening was mainly integrated at OPD and HIV clinics, with less emphasis on the other health facility clinics. Closing gaps related to TB case finding and diagnosis in developing countries requires sustainable investment for both human and financial resources and strengthen the integration of TB activities within the health system. |
Susan Alum Moses Asiimwe, Gerald Kanyomozi Jacqueline Nalikka Peace Okwaro Isabella Migisha Brenda Muhindo Abdullah Wailagala Stephen Okello Paul Blair Peter Waitt Nahid Bhadelia Rodgers Ayebare Antonia Kwiecien David Saunders Mohammed Lamorde Hannah Kibuuka ; Clark, Danielle Optimizing Highly Infectious Disease Isolation Unit Management: Experiences From the Infectious Diseases Isolation and Research Unit, Fort Portal, Uganda Journal Article DOI: https://doi.org/10.1017/dmp.2021.339, pp. 1-5, 2021. @article{Alum2021, title = {Optimizing Highly Infectious Disease Isolation Unit Management: Experiences From the Infectious Diseases Isolation and Research Unit, Fort Portal, Uganda}, author = {Susan Alum, Moses Asiimwe, Gerald Kanyomozi, Jacqueline Nalikka, Peace Okwaro, Isabella Migisha, Brenda Muhindo, Abdullah Wailagala, Stephen Okello, Paul Blair, Peter Waitt, Nahid Bhadelia, Rodgers Ayebare, Antonia Kwiecien, David Saunders, Mohammed Lamorde, Hannah Kibuuka and Danielle Clark}, year = {2021}, date = {2021-11-25}, journal = {DOI: https://doi.org/10.1017/dmp.2021.339}, pages = {1-5}, abstract = {Infectious disease outbreaks on the scale of the current coronavirus disease 2019 (COVID-19) pandemic are a new phenomenon in many parts of the world. Many isolation unit designs with corresponding workflow dynamics and personal protective equipment postures have been proposed for each emerging disease at the health facility level, depending on the mode of transmission. However, personnel and resource management at the isolation units for a resilient response will vary by human resource capacity, reporting requirements, and practice setting. This study describes an approach to isolation unit management at a rural Uganda Hospital and shares lessons from the Uganda experience for isolation unit managers in low- and middle-income settings. Keywords Patient Isolation, Public Health Practice, COVID-19, Nurse’s Role}, keywords = {}, pubstate = {published}, tppubtype = {article} } Infectious disease outbreaks on the scale of the current coronavirus disease 2019 (COVID-19) pandemic are a new phenomenon in many parts of the world. Many isolation unit designs with corresponding workflow dynamics and personal protective equipment postures have been proposed for each emerging disease at the health facility level, depending on the mode of transmission. However, personnel and resource management at the isolation units for a resilient response will vary by human resource capacity, reporting requirements, and practice setting. This study describes an approach to isolation unit management at a rural Uganda Hospital and shares lessons from the Uganda experience for isolation unit managers in low- and middle-income settings. Keywords Patient Isolation, Public Health Practice, COVID-19, Nurse’s Role |
Stephen I. Walimbwa Julian P. Kaboggoza, Catriona Waitt Pauline Byakika-Kibwika Antonio D’Avolio & Mohammed Lamorde Trials, 22 (1), pp. 831, 2021. @article{Walimbwa2021, title = {An open-label, randomized, single intravenous dosing study to investigate the effect of fixed-dose combinations of tenofovir/lamivudine or atazanavir/ritonavir on the pharmacokinetics of remdesivir in Ugandan healthy volunteers (RemTLAR)}, author = {Stephen I. Walimbwa, Julian P. Kaboggoza, Catriona Waitt, Pauline Byakika-Kibwika, Antonio D’Avolio & Mohammed Lamorde }, doi = {https://doi.org/10.1186/s13063-021-05752-1}, year = {2021}, date = {2021-11-23}, journal = {Trials}, volume = {22}, number = {1}, pages = {831}, abstract = {Background Remdesivir is a novel broad-spectrum antiviral therapeutic with activity against several viruses that cause emerging infectious diseases. The purpose of this study is to explore how commonly utilized antiretroviral therapy (tenofovir disoproxil fumarate/lamivudine [TDF/3TC] and atazanavir/ritonavir [ATV/r]) influence plasma and intracellular concentrations of remdesivir. Methods This is an open-label, randomized, fixed sequence single intravenous dosing study to assess pharmacokinetic interactions between remdesivir and TDF/3TC (Study A, crossover design) or TDF/3TC plus ATV/r (Study B). Healthy volunteers satisfying study entry criteria will be enrolled in the study and randomized to either Study A; N=16 (Sequence 1 or Sequence 2) or Study B; N=8. Participants will receive standard adult doses of antiretroviral therapy for 7 days and a single 200mg remdesivir infusion administered over 60 min. Pharmacokinetic blood sampling will be performed relative to the start of remdesivir infusion; predose (before the start of remdesivir infusion) and 30 min after the start of remdesivir infusion. Additional blood samples will be taken at 2, 4, 6, 12, and 24 h after the end of remdesivir infusion. Discussion This study will characterize the pharmacokinetics of remdesivir from a typical African population in whom clinical use is anticipated. Furthermore, this study will deliver pharmacokinetic datasets for remdesivir drug concentrations and demographic characteristics which could support pharmacometric approaches for simulation of remdesivir treatment regimens in patients concurrently using tenofovir/lamivudine and/or atazanavir/ritonavir.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Remdesivir is a novel broad-spectrum antiviral therapeutic with activity against several viruses that cause emerging infectious diseases. The purpose of this study is to explore how commonly utilized antiretroviral therapy (tenofovir disoproxil fumarate/lamivudine [TDF/3TC] and atazanavir/ritonavir [ATV/r]) influence plasma and intracellular concentrations of remdesivir. Methods This is an open-label, randomized, fixed sequence single intravenous dosing study to assess pharmacokinetic interactions between remdesivir and TDF/3TC (Study A, crossover design) or TDF/3TC plus ATV/r (Study B). Healthy volunteers satisfying study entry criteria will be enrolled in the study and randomized to either Study A; N=16 (Sequence 1 or Sequence 2) or Study B; N=8. Participants will receive standard adult doses of antiretroviral therapy for 7 days and a single 200mg remdesivir infusion administered over 60 min. Pharmacokinetic blood sampling will be performed relative to the start of remdesivir infusion; predose (before the start of remdesivir infusion) and 30 min after the start of remdesivir infusion. Additional blood samples will be taken at 2, 4, 6, 12, and 24 h after the end of remdesivir infusion. Discussion This study will characterize the pharmacokinetics of remdesivir from a typical African population in whom clinical use is anticipated. Furthermore, this study will deliver pharmacokinetic datasets for remdesivir drug concentrations and demographic characteristics which could support pharmacometric approaches for simulation of remdesivir treatment regimens in patients concurrently using tenofovir/lamivudine and/or atazanavir/ritonavir. |
George Abongomera Maurice Koller, Joseph Musaazi Mohammed Lamorde Marisa Kaelin Hannington Tasimwa Nadia Eberhard Jan Hongler Sabine Haller Andrew Kambugu Barbara Castelnuovo & Jan Fehr B Spectrum of antibiotic resistance in UTI caused by Escherichia coli among HIV-infected patients in Uganda: a cross-sectional study Journal Article BMC Infectious Diseases , 29 (1179), 2021. @article{Abongomera2021, title = {Spectrum of antibiotic resistance in UTI caused by Escherichia coli among HIV-infected patients in Uganda: a cross-sectional study}, author = { George Abongomera, Maurice Koller, Joseph Musaazi, Mohammed Lamorde, Marisa Kaelin, Hannington B. Tasimwa, Nadia Eberhard, Jan Hongler, Sabine Haller, Andrew Kambugu, Barbara Castelnuovo & Jan Fehr }, doi = {https://doi.org/10.1186/s12879-021-06865-3}, year = {2021}, date = {2021-11-23}, journal = {BMC Infectious Diseases }, volume = {29}, number = {1179}, abstract = {Background Antimicrobial drug resistance is one of the top ten threats to global health according to the World Health Organization. Urinary tract infections (UTIs) are among the most common bacterial infections and main reason for antibiotic prescription. The incidence of UTIs appears to be high among people living with HIV. We sought to determine the most common UTI pathogens among HIV infected patients and evaluate their susceptibility towards antibiotics. Methods We performed a cross-sectional study among HIV-infected patients aged ≥ 18 years presenting at an HIV care specialized clinic with symptoms suggestive of a urethritis. Urine cultures were subjected to antibiotic susceptibility testing according to Clinical Laboratory Standards Institute. The data was analyzed using STATA, we performed Pearson’s Chi-square and Fisher’s exact tests to compare differences between proportions. Results Out of the 200 patients, 123 (62%) were female. The median age was 41.9 years (IQR 34.7–49.3). Only 32 (16%) urine cultures showed bacterial growth. Escherichia coli was the most commonly isolated uropathogen (72%), followed by Klebsiella pneumoniae (9%). E. coli was completely resistant to cotrimoxazole and ampicillin; resistance to ciprofloxacin and ceftriaxone was 44% and 35% respectively; 9% to gentamicin; no resistance detected to nitrofurantoin and imipenem. Conclusions Our findings are congruent with the Uganda national clinical guidelines which recommends nitrofurantoin as the first line antibiotic for uncomplicated UTI. Significant ciprofloxacin and ceftriaxone resistance was detected. In the era of emerging antibiotic resistance, understanding the local susceptibilities among sub-populations such as HIV infected patients is crucial. Further investigation is needed to address reasons for the low bacterial growth rate observed in the urine cultures.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Antimicrobial drug resistance is one of the top ten threats to global health according to the World Health Organization. Urinary tract infections (UTIs) are among the most common bacterial infections and main reason for antibiotic prescription. The incidence of UTIs appears to be high among people living with HIV. We sought to determine the most common UTI pathogens among HIV infected patients and evaluate their susceptibility towards antibiotics. Methods We performed a cross-sectional study among HIV-infected patients aged ≥ 18 years presenting at an HIV care specialized clinic with symptoms suggestive of a urethritis. Urine cultures were subjected to antibiotic susceptibility testing according to Clinical Laboratory Standards Institute. The data was analyzed using STATA, we performed Pearson’s Chi-square and Fisher’s exact tests to compare differences between proportions. Results Out of the 200 patients, 123 (62%) were female. The median age was 41.9 years (IQR 34.7–49.3). Only 32 (16%) urine cultures showed bacterial growth. Escherichia coli was the most commonly isolated uropathogen (72%), followed by Klebsiella pneumoniae (9%). E. coli was completely resistant to cotrimoxazole and ampicillin; resistance to ciprofloxacin and ceftriaxone was 44% and 35% respectively; 9% to gentamicin; no resistance detected to nitrofurantoin and imipenem. Conclusions Our findings are congruent with the Uganda national clinical guidelines which recommends nitrofurantoin as the first line antibiotic for uncomplicated UTI. Significant ciprofloxacin and ceftriaxone resistance was detected. In the era of emerging antibiotic resistance, understanding the local susceptibilities among sub-populations such as HIV infected patients is crucial. Further investigation is needed to address reasons for the low bacterial growth rate observed in the urine cultures. |
Felix Bongomin Brian Fleischer, Ronald Olum Barbra Natukunda Sarah Kiguli Pauline Byakika-Kibwika Joseph Baruch Baluku Frederick Nelson Nakwagala Open Forum Infectious Diseases, 8 (11), pp. ofab530, 2021. @article{Bongomin2021d, title = {High Mortality During the Second Wave of the Coronavirus Disease 2019 (COVID-19) Pandemic in Uganda: Experience From a National Referral COVID-19 Treatment Unit}, author = {Felix Bongomin, Brian Fleischer, Ronald Olum, Barbra Natukunda, Sarah Kiguli, Pauline Byakika-Kibwika, Joseph Baruch Baluku, Frederick Nelson Nakwagala}, doi = {https://doi.org/10.1093/ofid/ofab530}, year = {2021}, date = {2021-11-18}, journal = {Open Forum Infectious Diseases}, volume = {8}, number = {11}, pages = {ofab530}, abstract = {Background We evaluated clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in the second wave of the pandemic in a national COVID-19 treatment unit (CTU) in Uganda. Methods We conducted a retrospective cohort study of COVID-19 patients hospitalized at the Mulago National Referral Hospital CTU between May 1 and July 11, 2021. We performed Kaplan-Meier analysis to evaluate all-cause in-hospital mortality. Results Of the 477 participants, 247 (52%) were female, 15 (3%) had received at least 1 dose of the COVID-19 vaccine, and 223 (46%) had at least 1 comorbidity. The median age was 52 (interquartile range, 41–65) years. More than 80% of the patients presented with severe (19%, n=91) or critical (66%, n=315) COVID-19 illness. Overall, 174 (37%) patients died. Predictors of all-cause in-hospital mortality were as follows; age ≥50 years (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2–3.2; P=.011), oxygen saturation at admission of ≥92% (aOR, 0.97; 95% CI, 0.91–0.95; P<.001), and admission pulse rate of ≥100 beats per minute (aOR, 1.01; 95% CI, 1.00–1.02; P=.042). The risk of death was 1.4-fold higher in female participants compared with their male counterparts (hazards ratio, 1.4; 95% CI, 1.0–2.0; P=.025). Conclusions In this cohort, where the majority of the patients presented with severe or critical illness, more than one third of the patients hospitalized with COVID-19 at a national CTU died of the illness. COVID-19, mortality, high-dependency unit, second wave, Uganda Topic: patient referral comorbidity uganda mortality pandemics covid-19 }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background We evaluated clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in the second wave of the pandemic in a national COVID-19 treatment unit (CTU) in Uganda. Methods We conducted a retrospective cohort study of COVID-19 patients hospitalized at the Mulago National Referral Hospital CTU between May 1 and July 11, 2021. We performed Kaplan-Meier analysis to evaluate all-cause in-hospital mortality. Results Of the 477 participants, 247 (52%) were female, 15 (3%) had received at least 1 dose of the COVID-19 vaccine, and 223 (46%) had at least 1 comorbidity. The median age was 52 (interquartile range, 41–65) years. More than 80% of the patients presented with severe (19%, n=91) or critical (66%, n=315) COVID-19 illness. Overall, 174 (37%) patients died. Predictors of all-cause in-hospital mortality were as follows; age ≥50 years (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2–3.2; P=.011), oxygen saturation at admission of ≥92% (aOR, 0.97; 95% CI, 0.91–0.95; P<.001), and admission pulse rate of ≥100 beats per minute (aOR, 1.01; 95% CI, 1.00–1.02; P=.042). The risk of death was 1.4-fold higher in female participants compared with their male counterparts (hazards ratio, 1.4; 95% CI, 1.0–2.0; P=.025). Conclusions In this cohort, where the majority of the patients presented with severe or critical illness, more than one third of the patients hospitalized with COVID-19 at a national CTU died of the illness. COVID-19, mortality, high-dependency unit, second wave, Uganda Topic: patient referral comorbidity uganda mortality pandemics covid-19 |
Adelline Twimukye Miriam Laker, Eva Agnes Laker Odongpiny Florence Ajok Henry Onen Ivan Kalule Phoebe Kajubi Kay Seden Noela Owarwo Agnes Kiragga Mari Armstrong-Hough Anne Katahoire Andrew Mujugira Mohammed Lamorde & Barbara Castelnuovo Patient experiences of switching from Efavirenz- to Dolutegravir-based antiretroviral therapy: a qualitative study in Uganda Journal Article BMC Infectious Diseases, 21 (1154), 2021. @article{Twimukye2021b, title = {Patient experiences of switching from Efavirenz- to Dolutegravir-based antiretroviral therapy: a qualitative study in Uganda}, author = {Adelline Twimukye, Miriam Laker, Eva Agnes Laker Odongpiny, Florence Ajok, Henry Onen, Ivan Kalule, Phoebe Kajubi, Kay Seden, Noela Owarwo, Agnes Kiragga, Mari Armstrong-Hough, Anne Katahoire, Andrew Mujugira, Mohammed Lamorde & Barbara Castelnuovo }, doi = {https://doi.org/10.1186/s12879-021-06851-9}, year = {2021}, date = {2021-11-13}, journal = {BMC Infectious Diseases}, volume = {21}, number = {1154}, abstract = {Background In 2019, the World Health Organisation (WHO) recommended Dolutegravir (DTG) as the preferred first-line antiretroviral treatment (ART) for all persons with HIV. ART regimen switches may affect HIV treatment adherence. We sought to describe patient experiences switching from EFV to DTG-based ART in Kampala, Uganda. Methods Between July and September 2019, we purposively sampled adults living with HIV who had switched to DTG at the Infectious Diseases Institute HIV clinic. We conducted in-depth interviews with adults who switched to DTG, to explore their preparation to switch and experiences on DTG. Interviews were audio-recorded, transcribed and analysed thematically using Atlas ti version 8 software. Results We interviewed 25 adults: 18 (72%) were women, and the median age was 35 years (interquartile range [IQR] 30–40). Median length on ART before switching to DTG was 67 months (IQR 51–125). Duration on DTG after switching was 16 months (IQR 10–18). Participants reported accepting provider recommendations to switch to DTG mainly because they anticipated that swallowing a smaller pill once a day would be more convenient. While most participants initially felt uncertain about drug switching, their providers offer of frequent appointments and a toll-free number to call in the event of side effects allayed their anxiety. At the same time, participants said they felt rushed to switch to the new ART regimen considering that they had been on their previous regimen(s) for several years and the switch to DTG happened during a routine visit when they had expected their regular prescription. Some participants felt unprepared for new adverse events associated with DTG and for the abrupt change in treatment schedule. Most participants said they needed additional support from their health providers before and after switching to DTG. Conclusion and recommendations Adults living with HIV stable on an EFV-based regimen but were switched to DTG in a program-wide policy change found the duration between counselling and drug switching inadequate. DTG was nonetheless largely preferred because of the small pill size, once daily dosing, and absence of EFV-like side effects. Community-engaged research is needed to devise acceptable ways to prepare participants for switching ART at scale.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background In 2019, the World Health Organisation (WHO) recommended Dolutegravir (DTG) as the preferred first-line antiretroviral treatment (ART) for all persons with HIV. ART regimen switches may affect HIV treatment adherence. We sought to describe patient experiences switching from EFV to DTG-based ART in Kampala, Uganda. Methods Between July and September 2019, we purposively sampled adults living with HIV who had switched to DTG at the Infectious Diseases Institute HIV clinic. We conducted in-depth interviews with adults who switched to DTG, to explore their preparation to switch and experiences on DTG. Interviews were audio-recorded, transcribed and analysed thematically using Atlas ti version 8 software. Results We interviewed 25 adults: 18 (72%) were women, and the median age was 35 years (interquartile range [IQR] 30–40). Median length on ART before switching to DTG was 67 months (IQR 51–125). Duration on DTG after switching was 16 months (IQR 10–18). Participants reported accepting provider recommendations to switch to DTG mainly because they anticipated that swallowing a smaller pill once a day would be more convenient. While most participants initially felt uncertain about drug switching, their providers offer of frequent appointments and a toll-free number to call in the event of side effects allayed their anxiety. At the same time, participants said they felt rushed to switch to the new ART regimen considering that they had been on their previous regimen(s) for several years and the switch to DTG happened during a routine visit when they had expected their regular prescription. Some participants felt unprepared for new adverse events associated with DTG and for the abrupt change in treatment schedule. Most participants said they needed additional support from their health providers before and after switching to DTG. Conclusion and recommendations Adults living with HIV stable on an EFV-based regimen but were switched to DTG in a program-wide policy change found the duration between counselling and drug switching inadequate. DTG was nonetheless largely preferred because of the small pill size, once daily dosing, and absence of EFV-like side effects. Community-engaged research is needed to devise acceptable ways to prepare participants for switching ART at scale. |
Hussein Mukasa Kafeero Dorothy Ndagire, Ponsiano Ocama Abdul Walusansa & Hakim Sendagire Sero-prevalence of human immunodeficiency virus–hepatitis B virus (HIV–HBV) co-infection among pregnant women attending antenatal care (ANC) in sub-Saharan Africa (SSA) and the associated risk factors: a systematic review and meta-analysis Journal Article Forthcoming Virology Journal, 17 (170), Forthcoming. @article{Kafeero2021, title = {Sero-prevalence of human immunodeficiency virus–hepatitis B virus (HIV–HBV) co-infection among pregnant women attending antenatal care (ANC) in sub-Saharan Africa (SSA) and the associated risk factors: a systematic review and meta-analysis}, author = {Hussein Mukasa Kafeero, Dorothy Ndagire, Ponsiano Ocama, Abdul Walusansa & Hakim Sendagire }, doi = {https://doi.org/10.1186/s12985-020-01443-6}, year = {2021}, date = {2021-11-07}, journal = {Virology Journal}, volume = {17}, number = {170}, abstract = {Background There is plenitude of information on HIV infection among pregnant mothers attending antenatal care (ANC) in sub-Saharan Africa. However, the epidemiology of HBV–HIV co-infections in the same cohort is not clear despite the common route of transmission of both viruses. The aim of our study was to synthesize data on the prevalence of HBV–HIV co-infection among pregnant women attending ANC in Sub-Saharan Africa to assist in the design of public health interventions to mitigate the challenge. Methods The study was done in tandem with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards and the Cochran’s Q test, I2 statistics for heterogeneity and the prevalence were calculated using commercially available software called MedCalcs (https://www.medcalc.org). A random effect model was used to pool the prevalence since all the heterogeneities were high (≥ 78%) and Phet < 0.05 indicated significant heterogeneities. The risk factors and risk differences for HBV–HIV co-infection were analyzed. Any likely sources of heterogeneity were analyzed through sensitivity analysis, meta-regression and sub-group analysis. All analyses were done at 95% level of significance and a P < 0.05 was considered significant. Results The overall pooled prevalence of HBV–HIV co-infection among pregnant mothers in sub-Saharan Africa was low 3.302% (95%CI = 2.285 to 4.4498%) with heterogeneities (I2) of 97.59% (P > 0.0001). Within regional sub group meta-analyses, West Africa had significantly higher prevalence of 5.155% (95% = 2.671 to 8.392%) with heterogeneity (I2) of 92.25% (P < 0.0001) than any other region (P < 0.001). Articles published from 2004–2010 had significantly higher prevalence of 6.356% (95% = 3.611 to 9.811%) with heterogeneity (I2) 91.15% (P < 0.0001) compared to those published from 2011 to 2019 (P < 0.001). The HIV positive cohort had significantly higher prevalence of HBV–HIV co-infection of 8.312% (95% CI = 5.806 to 11.22%) with heterogeneity (I2)94.90% (P < 0.0001) than the mothers sampled from the general population with a prevalence of 2.152% (95% CI = 1.358 to 3.125%) (P < 0.001). The overall and sub group analyses had high heterogeneities (I2 > 89%, P < 0.0001) but was reduced for South Africa (I2) = 78.4% (P = 0.0314). Age, marital status and employment were independent factors significantly associated with risk of HBV–HIV co-infection (P < 0.001) but not extent of gravidity and education level (P > 0.05). After meta-regression for year of publication and sample size for HBsAg positivity, the results were not significantly associated with HBV pooled prevalence for sample size (P = 0.146) and year of publication (P = 0.560). Following sensitivity analysis, the HBsAg pooled prevalence slightly increased to 3.429% (95% CI = 2.459 to 4.554%) with heterogeneity I2 = 96.59% (95% CI = 95.93 to 97.14%), P < 0.0001 Conclusion There is an urgent need for routine HBV screening among HIV positive pregnant mothers attending antenatal care in sub-Saharan Africa to establish the extent of HBV–HIV co-infection in this cohort. Future studies need to investigate the putative risk factors for HBV–HIV co-infection and prioritize plausible control strategies.}, keywords = {}, pubstate = {forthcoming}, tppubtype = {article} } Background There is plenitude of information on HIV infection among pregnant mothers attending antenatal care (ANC) in sub-Saharan Africa. However, the epidemiology of HBV–HIV co-infections in the same cohort is not clear despite the common route of transmission of both viruses. The aim of our study was to synthesize data on the prevalence of HBV–HIV co-infection among pregnant women attending ANC in Sub-Saharan Africa to assist in the design of public health interventions to mitigate the challenge. Methods The study was done in tandem with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards and the Cochran’s Q test, I2 statistics for heterogeneity and the prevalence were calculated using commercially available software called MedCalcs (https://www.medcalc.org). A random effect model was used to pool the prevalence since all the heterogeneities were high (≥ 78%) and Phet < 0.05 indicated significant heterogeneities. The risk factors and risk differences for HBV–HIV co-infection were analyzed. Any likely sources of heterogeneity were analyzed through sensitivity analysis, meta-regression and sub-group analysis. All analyses were done at 95% level of significance and a P < 0.05 was considered significant. Results The overall pooled prevalence of HBV–HIV co-infection among pregnant mothers in sub-Saharan Africa was low 3.302% (95%CI = 2.285 to 4.4498%) with heterogeneities (I2) of 97.59% (P > 0.0001). Within regional sub group meta-analyses, West Africa had significantly higher prevalence of 5.155% (95% = 2.671 to 8.392%) with heterogeneity (I2) of 92.25% (P < 0.0001) than any other region (P < 0.001). Articles published from 2004–2010 had significantly higher prevalence of 6.356% (95% = 3.611 to 9.811%) with heterogeneity (I2) 91.15% (P < 0.0001) compared to those published from 2011 to 2019 (P < 0.001). The HIV positive cohort had significantly higher prevalence of HBV–HIV co-infection of 8.312% (95% CI = 5.806 to 11.22%) with heterogeneity (I2)94.90% (P < 0.0001) than the mothers sampled from the general population with a prevalence of 2.152% (95% CI = 1.358 to 3.125%) (P < 0.001). The overall and sub group analyses had high heterogeneities (I2 > 89%, P < 0.0001) but was reduced for South Africa (I2) = 78.4% (P = 0.0314). Age, marital status and employment were independent factors significantly associated with risk of HBV–HIV co-infection (P < 0.001) but not extent of gravidity and education level (P > 0.05). After meta-regression for year of publication and sample size for HBsAg positivity, the results were not significantly associated with HBV pooled prevalence for sample size (P = 0.146) and year of publication (P = 0.560). Following sensitivity analysis, the HBsAg pooled prevalence slightly increased to 3.429% (95% CI = 2.459 to 4.554%) with heterogeneity I2 = 96.59% (95% CI = 95.93 to 97.14%), P < 0.0001 Conclusion There is an urgent need for routine HBV screening among HIV positive pregnant mothers attending antenatal care in sub-Saharan Africa to establish the extent of HBV–HIV co-infection in this cohort. Future studies need to investigate the putative risk factors for HBV–HIV co-infection and prioritize plausible control strategies. |
Richard Muhindo Andrew Mujugira, Barbara Castelnuovo Nelson Sewankambo Rosalind Parkes-Ratanshi Nazarius Mbona Tumwesigye Edith Nakku-Joloba & Juliet Kiguli K BMC Public Health, 21 (1982), 2021. @article{Muhindo2021b, title = {“I felt very small and embarrassed by the health care provider when I requested to be tested for syphilis”: barriers and facilitators of regular syphilis and HIV testing among female sex workers in Uganda}, author = {Richard Muhindo, Andrew Mujugira, Barbara Castelnuovo, Nelson K. Sewankambo, Rosalind Parkes-Ratanshi, Nazarius Mbona Tumwesigye, Edith Nakku-Joloba & Juliet Kiguli }, doi = {https://doi.org/10.1186/s12889-021-12095-8}, year = {2021}, date = {2021-11-02}, journal = {BMC Public Health}, volume = {21}, number = {1982}, abstract = {Background Periodic testing of female sex workers (FSW) for sexually transmitted infections (STIs) is a core component of global and national responses to achieve population-level STI elimination. We conducted a qualitative study to explore barriers and facilitators of regular syphilis and HIV testing among FSW in Uganda. Methods Within a quasi-experimental study among 436 FSW to assess the effect of peer education and text message reminders on uptake of regular STI and HIV testing among FSW, we conducted 48 qualitative interviews in four cities in Uganda from August–December 2018. We purposively selected FSW who tested for syphilis and HIV every 3–6 months; 12 FSW were interviewed in each city. Sex worker interviews explored: 1) reasons for periodic syphilis and HIV testing; 2) barriers and facilitators of testing; 3) experiences of testing; and 4) challenges faced while seeking testing services. Data were analyzed using thematic content analysis. Results Thematic analysis revealed individual- and health system-level barriers and facilitators of testing. For syphilis, barriers were a) interpersonal stigma, low perceived severity of syphilis and testing misconceptions (individual); and b) judgmental provider attitudes, paucity of facilities offering syphilis testing, stockouts of test kits and high cost (health system). Facilitators were c) desire to remain healthy, get married and have children, knowing the benefits of early treatment, influence of male partners/clients and normative testing behaviors (individual); and d) sex worker clinics offering dual syphilis/HIV testing (health system). For HIV, barriers included: a) internalized stigma (individual); and b) unfavorable clinic hours, stigma, discrimination, and unfriendly provider (health system). Facilitators were a) motivations to stay healthy and attract clients, habitual testing, self-efficacy, doubts about accuracy of negative test results, and use of post-exposure prophylaxis (individual); and d) availability of testing facilities (health system). Syphilis and HIV had similar testing barriers and facilitators. Conclusions HIV programs are likely to be important entry points for syphilis testing among FSW. Multi-level interventions to address testing barriers should consider focusing on these service delivery points. Extending the dual syphilis and HIV testing approach to FSW may improve testing uptake for both infections at public health facilities and decrease population-level incidence.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Periodic testing of female sex workers (FSW) for sexually transmitted infections (STIs) is a core component of global and national responses to achieve population-level STI elimination. We conducted a qualitative study to explore barriers and facilitators of regular syphilis and HIV testing among FSW in Uganda. Methods Within a quasi-experimental study among 436 FSW to assess the effect of peer education and text message reminders on uptake of regular STI and HIV testing among FSW, we conducted 48 qualitative interviews in four cities in Uganda from August–December 2018. We purposively selected FSW who tested for syphilis and HIV every 3–6 months; 12 FSW were interviewed in each city. Sex worker interviews explored: 1) reasons for periodic syphilis and HIV testing; 2) barriers and facilitators of testing; 3) experiences of testing; and 4) challenges faced while seeking testing services. Data were analyzed using thematic content analysis. Results Thematic analysis revealed individual- and health system-level barriers and facilitators of testing. For syphilis, barriers were a) interpersonal stigma, low perceived severity of syphilis and testing misconceptions (individual); and b) judgmental provider attitudes, paucity of facilities offering syphilis testing, stockouts of test kits and high cost (health system). Facilitators were c) desire to remain healthy, get married and have children, knowing the benefits of early treatment, influence of male partners/clients and normative testing behaviors (individual); and d) sex worker clinics offering dual syphilis/HIV testing (health system). For HIV, barriers included: a) internalized stigma (individual); and b) unfavorable clinic hours, stigma, discrimination, and unfriendly provider (health system). Facilitators were a) motivations to stay healthy and attract clients, habitual testing, self-efficacy, doubts about accuracy of negative test results, and use of post-exposure prophylaxis (individual); and d) availability of testing facilities (health system). Syphilis and HIV had similar testing barriers and facilitators. Conclusions HIV programs are likely to be important entry points for syphilis testing among FSW. Multi-level interventions to address testing barriers should consider focusing on these service delivery points. Extending the dual syphilis and HIV testing approach to FSW may improve testing uptake for both infections at public health facilities and decrease population-level incidence. |
Patience A Muwanguzi Tom Denis Ngabirano, Noah Kiwanuka LaRon Nelson Esther Nasuuna Charles Peter Osingada Racheal Nabunya Damalie Nakanjako Nelson Sewankambo E M K JMIR Research Protocols, 10 (11), pp. e25099, 2021. @article{Muwanguzi2021, title = {The Effects of Workplace-Based HIV Self-testing on Uptake of Testing and Linkage to HIV Care or Prevention by Men in Uganda (WISe-Men): Protocol for a Cluster Randomized Trial }, author = {Patience A Muwanguzi, Tom Denis Ngabirano, Noah Kiwanuka, LaRon E Nelson, Esther M Nasuuna, Charles Peter Osingada, Racheal Nabunya, Damalie Nakanjako, Nelson K Sewankambo}, doi = {doi:10.2196/25099}, year = {2021}, date = {2021-11-01}, journal = {JMIR Research Protocols}, volume = {10}, number = {11}, pages = {e25099}, abstract = {Background: HIV testing uptake remains low among men in sub-Saharan Africa. HIV self-testing (HIVST) at the workplace is a novel approach to increase the availability of, and access to, testing among men. However, both access and linkage to posttest services remain a challenge. Objective: The aim of this protocol is to describe a cluster randomized trial (CRT)—Workplace-Based HIV Self-testing Among Men (WISe-Men)—to evaluate the effect of HIVST in workplace settings on the uptake of HIV testing services (HTS) and linkage to treatment and prevention services among men employed in private security services in Uganda. Methods: This is a two-arm CRT involving men employed in private security services in two Ugandan districts. The participants in the intervention clusters will undergo workplace-based HIVST using OraQuick test kits. Those in the control clusters will receive routine HTS at their work premises. In addition to HTS, participants in both the intervention and control arms will undergo other tests and assessments, which include blood pressure assessment, blood glucose and BMI measurement, and rapid diagnostic testing for syphilis. The primary outcome is the uptake of HIV testing. The secondary outcomes include HIV status reporting, linkage into HIV care and confirmatory testing following HIVST, initiation of antiretroviral therapy following a confirmatory HIV test, the uptake of voluntary medical male circumcision, consistent condom use, and the uptake of pre-exposure prophylaxis by the most at-risk populations. Results: Participant enrollment commenced in February 2020, and the trial is still recruiting study participants. Follow-up for currently enrolled participants is ongoing. Data collection and analysis is expected to be completed in December 2021. Conclusions: The WISe-Men trial will provide information regarding whether self-testing at worksites increases the uptake of HIV testing as well as the linkage to care and prevention services at male-dominated workplaces in Uganda. Additionally, the findings will help us propose strategies for improving men’s engagement in HTS and ways to improve linkage to further care following a reactive or nonreactive HIVST result. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: HIV testing uptake remains low among men in sub-Saharan Africa. HIV self-testing (HIVST) at the workplace is a novel approach to increase the availability of, and access to, testing among men. However, both access and linkage to posttest services remain a challenge. Objective: The aim of this protocol is to describe a cluster randomized trial (CRT)—Workplace-Based HIV Self-testing Among Men (WISe-Men)—to evaluate the effect of HIVST in workplace settings on the uptake of HIV testing services (HTS) and linkage to treatment and prevention services among men employed in private security services in Uganda. Methods: This is a two-arm CRT involving men employed in private security services in two Ugandan districts. The participants in the intervention clusters will undergo workplace-based HIVST using OraQuick test kits. Those in the control clusters will receive routine HTS at their work premises. In addition to HTS, participants in both the intervention and control arms will undergo other tests and assessments, which include blood pressure assessment, blood glucose and BMI measurement, and rapid diagnostic testing for syphilis. The primary outcome is the uptake of HIV testing. The secondary outcomes include HIV status reporting, linkage into HIV care and confirmatory testing following HIVST, initiation of antiretroviral therapy following a confirmatory HIV test, the uptake of voluntary medical male circumcision, consistent condom use, and the uptake of pre-exposure prophylaxis by the most at-risk populations. Results: Participant enrollment commenced in February 2020, and the trial is still recruiting study participants. Follow-up for currently enrolled participants is ongoing. Data collection and analysis is expected to be completed in December 2021. Conclusions: The WISe-Men trial will provide information regarding whether self-testing at worksites increases the uptake of HIV testing as well as the linkage to care and prevention services at male-dominated workplaces in Uganda. Additionally, the findings will help us propose strategies for improving men’s engagement in HTS and ways to improve linkage to further care following a reactive or nonreactive HIVST result. |
Carson M Quinn Enock Kagimu, Michael Okirworth Ananta Bangdiwala Gerald Mugumya Prashanth Ramachandran Michael Wilson David Meya Fiona Cresswell Nathan Bahr David Boulware S S R B V C R Fujifilm SILVAMP TB LAM Assay on Cerebrospinal Fluid for the Detection of Tuberculous Meningitis in Adults With Human Immunodeficiency Virus Journal Article Clinical Infectious Diseases, 73 (9), pp. e3428–e3434,, 2021. @article{Quinn2021, title = {Fujifilm SILVAMP TB LAM Assay on Cerebrospinal Fluid for the Detection of Tuberculous Meningitis in Adults With Human Immunodeficiency Virus }, author = {Carson M Quinn, Enock Kagimu, Michael Okirworth, Ananta S Bangdiwala, Gerald Mugumya, Prashanth S Ramachandran, Michael R Wilson, David B Meya, Fiona V Cresswell, Nathan C Bahr, David R Boulware}, doi = {https://doi.org/10.1093/cid/ciaa1910}, year = {2021}, date = {2021-11-01}, journal = {Clinical Infectious Diseases}, volume = {73}, number = {9}, pages = {e3428–e3434,}, abstract = {Background Tuberculous meningitis (TBM) has a high fatality rate, with inadequate diagnostic tests being a major contributor. The rollout of Xpert MTB/Rif and Xpert MTB/RIF Ultra (Xpert Ultra) have improved time-to-diagnosis with sensitivities similar to culture, yet test availability and sensitivity are inadequate. The TB lipoarabinomannan lateral flow assay (AlereLAM) offers ease of use, but its low sensitivity in cerebrospinal fluid (CSF) limits clinical utility for TBM. The Fujifilm SILVAMP TB LAM (FujiLAM) assay has excellent sensitivity in urine, but performance on cerebrospinal fluid is uncertain. Methods We conducted a prospective cohort study at Kiruddu National Referral Hospital in Kampala, Uganda, enrolling patients suspected to have TBM. CSF was tested using AlereLAM, Xpert Ultra, culture, and FujiLAM. Results were compared with 2 reference standards: probable and definite TBM or definite TBM alone by the uniform TBM case definition. Results Of 101 patients enrolled (95/101 HIV-positive), 34 had definite TBM and 24 had probable TBM. FujiLAM sensitivity on CSF was 52% (30/58) for definite or probable TBM compared with 55% (32/58) for Xpert Ultra. AlereLAM had lower sensitivity than FujiLAM in the subgroup of patients tested with both assays (14% [4/28] vs 50% [14/28]; P < .01). FujiLAM specificity was 98% (42/43) for patients without probable or definite TBM. Conclusions FujiLAM showed higher sensitivity than AlereLAM, with sensitivity potentially approaching that of Xpert Ultra. FujiLAM could improve time-to-treatment-initiation, especially in settings where the more technical Xpert Ultra system might not be feasible. Large confirmatory studies are needed. Key Terms Mycobacterium tuberculosis, tuberculous meningitis, lipoarabinomannan, diagnostic accuracy, Fujifilm SILVAMP TB LAM Topic: hiv adult hiv seropositivity reference standards tuberculosis tuberculous meningitis cerebrospinal fluid diagnosis lipoarabinomanna}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Tuberculous meningitis (TBM) has a high fatality rate, with inadequate diagnostic tests being a major contributor. The rollout of Xpert MTB/Rif and Xpert MTB/RIF Ultra (Xpert Ultra) have improved time-to-diagnosis with sensitivities similar to culture, yet test availability and sensitivity are inadequate. The TB lipoarabinomannan lateral flow assay (AlereLAM) offers ease of use, but its low sensitivity in cerebrospinal fluid (CSF) limits clinical utility for TBM. The Fujifilm SILVAMP TB LAM (FujiLAM) assay has excellent sensitivity in urine, but performance on cerebrospinal fluid is uncertain. Methods We conducted a prospective cohort study at Kiruddu National Referral Hospital in Kampala, Uganda, enrolling patients suspected to have TBM. CSF was tested using AlereLAM, Xpert Ultra, culture, and FujiLAM. Results were compared with 2 reference standards: probable and definite TBM or definite TBM alone by the uniform TBM case definition. Results Of 101 patients enrolled (95/101 HIV-positive), 34 had definite TBM and 24 had probable TBM. FujiLAM sensitivity on CSF was 52% (30/58) for definite or probable TBM compared with 55% (32/58) for Xpert Ultra. AlereLAM had lower sensitivity than FujiLAM in the subgroup of patients tested with both assays (14% [4/28] vs 50% [14/28]; P < .01). FujiLAM specificity was 98% (42/43) for patients without probable or definite TBM. Conclusions FujiLAM showed higher sensitivity than AlereLAM, with sensitivity potentially approaching that of Xpert Ultra. FujiLAM could improve time-to-treatment-initiation, especially in settings where the more technical Xpert Ultra system might not be feasible. Large confirmatory studies are needed. Key Terms Mycobacterium tuberculosis, tuberculous meningitis, lipoarabinomannan, diagnostic accuracy, Fujifilm SILVAMP TB LAM Topic: hiv adult hiv seropositivity reference standards tuberculosis tuberculous meningitis cerebrospinal fluid diagnosis lipoarabinomanna |
Mahsa Abassi Ananta S Bangdiwala, Edwin Nuwagira Kiiza Kandole Tadeo Michael Okirwoth Darlisha Williams Edward Mpoza Lillian Tugume Kenneth Ssebambulidde Kathy Huppler Hullsiek Abdu Musubire Conrad Muzoora Joshua Rhein David Meya David Boulware A K B R Cerebrospinal Fluid Lactate as a Prognostic Marker of Disease Severity and Mortality in Cryptococcal Meningitis Journal Article Clinical Infectious Diseases, 73 (9), pp. e3077–e3082, 2021. @article{Abassi2021, title = {Cerebrospinal Fluid Lactate as a Prognostic Marker of Disease Severity and Mortality in Cryptococcal Meningitis }, author = {Mahsa Abassi, Ananta S Bangdiwala, Edwin Nuwagira, Kiiza Kandole Tadeo, Michael Okirwoth, Darlisha A Williams, Edward Mpoza, Lillian Tugume, Kenneth Ssebambulidde, Kathy Huppler Hullsiek, Abdu K Musubire, Conrad Muzoora, Joshua Rhein, David B Meya, David R Boulware}, doi = {https://doi.org/10.1093/cid/ciaa1749}, year = {2021}, date = {2021-11-01}, journal = {Clinical Infectious Diseases}, volume = {73}, number = {9}, pages = {e3077–e3082}, abstract = {Background Cerebrospinal fluid (CSF) lactate levels can be used to differentiate between bacterial and viral meningitis. We measured CSF lactate in individuals with cryptococcal meningitis to determine its clinical significance. Methods We measured point-of-care CSF lactate at the bedside of 319 Ugandan adults living with human immunodeficiency virus at diagnosis of cryptococcal meningitis. We summarized demographic variables and clinical characteristics by CSF lactate tertiles. We evaluated the association of CSF lactate with clinical characteristics and survival. Results Individuals with high CSF lactate >5 mmol/L at cryptococcal diagnosis more likely presented with altered mental status (P < .0001), seizures (P = .0005), elevated intracranial opening pressure (P = .03), higher CSF white cells (P = .007), and lower CSF glucose (P = .0003) compared with those with mid-range (3.1 to 5 mmol/L) or low (≤3 mmol/L) CSF lactate levels. Two-week mortality was higher among individuals with high baseline CSF lactate >5 mmol/L (35%; 38 of 109) compared with individuals with mid-range (22%; 25 of 112) or low CSF lactate (9%; 9 of 97; P =<.0001). After multivariate adjustment, CSF lactate >5 mmol/L remained independently associated with excess mortality (adjusted hazard ratio = 3.41; 95% confidence interval, 1.55–7.51; P = .002). We found no correlation between baseline CSF lactate levels and blood capillary lactate levels. Conclusions Baseline point-of-care CSF lactate levels are a prognostic marker of disease severity and mortality in cryptococcal meningitis. Individuals with an elevated baseline CSF lactate level are more likely to present with altered mental status, seizures, and elevated CSF opening pressure and are at a greater risk of death. Future studies are needed to determine targeted therapeutic management strategies in persons with high CSF lactate. Key Terms cryptococcal meningitis, cerebrospinal fluid, lactic acid, prognostic marker, mortality Topic: hiv seizures cryptococcal meningitis lactates cerebrospinal fluid mortality mental state abnormal prognostic marker severity of illness }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Cerebrospinal fluid (CSF) lactate levels can be used to differentiate between bacterial and viral meningitis. We measured CSF lactate in individuals with cryptococcal meningitis to determine its clinical significance. Methods We measured point-of-care CSF lactate at the bedside of 319 Ugandan adults living with human immunodeficiency virus at diagnosis of cryptococcal meningitis. We summarized demographic variables and clinical characteristics by CSF lactate tertiles. We evaluated the association of CSF lactate with clinical characteristics and survival. Results Individuals with high CSF lactate >5 mmol/L at cryptococcal diagnosis more likely presented with altered mental status (P < .0001), seizures (P = .0005), elevated intracranial opening pressure (P = .03), higher CSF white cells (P = .007), and lower CSF glucose (P = .0003) compared with those with mid-range (3.1 to 5 mmol/L) or low (≤3 mmol/L) CSF lactate levels. Two-week mortality was higher among individuals with high baseline CSF lactate >5 mmol/L (35%; 38 of 109) compared with individuals with mid-range (22%; 25 of 112) or low CSF lactate (9%; 9 of 97; P =<.0001). After multivariate adjustment, CSF lactate >5 mmol/L remained independently associated with excess mortality (adjusted hazard ratio = 3.41; 95% confidence interval, 1.55–7.51; P = .002). We found no correlation between baseline CSF lactate levels and blood capillary lactate levels. Conclusions Baseline point-of-care CSF lactate levels are a prognostic marker of disease severity and mortality in cryptococcal meningitis. Individuals with an elevated baseline CSF lactate level are more likely to present with altered mental status, seizures, and elevated CSF opening pressure and are at a greater risk of death. Future studies are needed to determine targeted therapeutic management strategies in persons with high CSF lactate. Key Terms cryptococcal meningitis, cerebrospinal fluid, lactic acid, prognostic marker, mortality Topic: hiv seizures cryptococcal meningitis lactates cerebrospinal fluid mortality mental state abnormal prognostic marker severity of illness |
Owain Roberts Hannah Kinvig, Andrew Owen Mohammed Lamorde Marco Siccardi Kimberly Scarsi K In vitro assessment of the potential for dolutegravir to affect hepatic clearance of levonorgestrel Journal Article HIV Medicine, 22 (10), pp. 898-906, 2021. @article{Roberts2021, title = {In vitro assessment of the potential for dolutegravir to affect hepatic clearance of levonorgestrel}, author = {Owain Roberts, Hannah Kinvig, Andrew Owen, Mohammed Lamorde, Marco Siccardi, Kimberly K. Scarsi}, doi = {https://doi.org/10.1111/hiv.13136}, year = {2021}, date = {2021-11-01}, journal = {HIV Medicine}, volume = {22}, number = {10}, pages = {898-906}, abstract = {Objectives The World Health Organization recommends that all countries adopt dolutegravir-based antiretroviral therapy as the preferred regimen for all individuals living with HIV. Levonorgestrel is a commonly used hormonal contraceptive, which undergoes drug–drug interactions with some antiretrovirals, but the potential interaction between dolutegravir and levonorgestrel has not been examined. We aimed to evaluate cytochrome P450 (CYP)-mediated levonorgestrel metabolism and quantify the effects of dolutegravir on levonorgestrel apparent intrinsic clearance (CLint.app.) and CYP gene expression. Methods In vitro CYP-mediated CLint.app. of levonorgestrel was quantified using a recombinant human CYP (rhCYP) enzyme system. A primary human hepatocyte model of drug metabolism was used to assess the effects of dolutegravir on (1) levonorgestrel CLint.app., using liquid chromatography-tandem mass spectrometry, and (2) the expression of specific CYP enzymes, using quantitative real-time polymerase chain reaction. Results Levonorgestrel clearance was mediated by multiple rhCYPs, including rhCYP3A4. Under control conditions, levonorgestrel CLint.app. was 22.4 ± 5.0 μL/min/106 hepatocytes. Incubation with 43.1 nM of unbound dolutegravir elevated levonorgestrel CLint.app. to 31.4 ± 7.8 µL/min/106 hepatocytes (P = 0.168), while 142.23 nM increased levonorgestrel CLint.app. to 37.0 ± 2.9 µL/min/106 hepatocytes (P = 0.012). Unbound dolutegravir ≥ 431 nM induced expression of CYP3A4 (≥ two-fold) in a dose-dependent manner, while 1.44 μM of unbound dolutegravir induced CYP2B6 expression 2.2 ± 0.3-fold (P = 0.0004). Conclusions In summary, this in vitro study suggests that dolutegravir has the potential to increase hepatic clearance of levonorgestrel by inducing both CYP3A and non-CYP3A enzymes. The observed in vitro dolutegravir–levonorgestrel drug–drug interaction should be further examined in clinical studies. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Objectives The World Health Organization recommends that all countries adopt dolutegravir-based antiretroviral therapy as the preferred regimen for all individuals living with HIV. Levonorgestrel is a commonly used hormonal contraceptive, which undergoes drug–drug interactions with some antiretrovirals, but the potential interaction between dolutegravir and levonorgestrel has not been examined. We aimed to evaluate cytochrome P450 (CYP)-mediated levonorgestrel metabolism and quantify the effects of dolutegravir on levonorgestrel apparent intrinsic clearance (CLint.app.) and CYP gene expression. Methods In vitro CYP-mediated CLint.app. of levonorgestrel was quantified using a recombinant human CYP (rhCYP) enzyme system. A primary human hepatocyte model of drug metabolism was used to assess the effects of dolutegravir on (1) levonorgestrel CLint.app., using liquid chromatography-tandem mass spectrometry, and (2) the expression of specific CYP enzymes, using quantitative real-time polymerase chain reaction. Results Levonorgestrel clearance was mediated by multiple rhCYPs, including rhCYP3A4. Under control conditions, levonorgestrel CLint.app. was 22.4 ± 5.0 μL/min/106 hepatocytes. Incubation with 43.1 nM of unbound dolutegravir elevated levonorgestrel CLint.app. to 31.4 ± 7.8 µL/min/106 hepatocytes (P = 0.168), while 142.23 nM increased levonorgestrel CLint.app. to 37.0 ± 2.9 µL/min/106 hepatocytes (P = 0.012). Unbound dolutegravir ≥ 431 nM induced expression of CYP3A4 (≥ two-fold) in a dose-dependent manner, while 1.44 μM of unbound dolutegravir induced CYP2B6 expression 2.2 ± 0.3-fold (P = 0.0004). Conclusions In summary, this in vitro study suggests that dolutegravir has the potential to increase hepatic clearance of levonorgestrel by inducing both CYP3A and non-CYP3A enzymes. The observed in vitro dolutegravir–levonorgestrel drug–drug interaction should be further examined in clinical studies. |
Alexandra Marie Medley Jonan Gasanani, Ceaser Adibaku Nyolimati Elvira McIntyre Sarah Ward Bosco Okuyo Duncan Kabiito Cristel Bender Zainab Jafari Mohammed LaMorde Peter Ahabwe Babigumira Lydia Nakiire Constance Agwang Rebecca Merrill Deo Ndumu Kiconco Doris Preventing the cross-border spread of zoonotic diseases: Multisectoral community engagement to characterize animal mobility—Uganda, 2020 Journal Article Zooneses and Public Health, 68 (7), pp. 747-759, 2021. @article{Medley2021, title = {Preventing the cross-border spread of zoonotic diseases: Multisectoral community engagement to characterize animal mobility—Uganda, 2020}, author = {Alexandra Marie Medley, Jonan Gasanani, Ceaser Adibaku Nyolimati, Elvira McIntyre, Sarah Ward, Bosco Okuyo, Duncan Kabiito, Cristel Bender, Zainab Jafari, Mohammed LaMorde, Peter Ahabwe Babigumira, Lydia Nakiire, Constance Agwang, Rebecca Merrill, Deo Ndumu, Kiconco Doris}, doi = { https://doi.org/10.1111/zph.12823}, year = {2021}, date = {2021-11-01}, journal = {Zooneses and Public Health}, volume = {68}, number = {7}, pages = {747-759}, abstract = {In Uganda, the borders are highly porous to animal movement, which may contribute to zoonotic disease spread. We piloted an animal adaptation of an existing human-focused toolkit to collect data on animal movement patterns and interactions to inform One Health programs. During January 2020, we conducted focus group discussions and key informant interviews with participatory mapping of 2 national-level One Health stakeholders and 2 local-level abattoir representatives from Kampala. Zoonotic disease hotspots changed in 2020 compared with reports from 2017–2019. In contrast to local-level participants, national-level participants highlighted districts rather than specific locations. Everyone discussed livestock species; only national-level participants mentioned wildlife. Participants described seasonality differently. Stakeholders used the results to identify locations for zoonotic disease interventions and sites for future data collection. This implementation of an animal-adapted population mobility mapping exercise highlights the importance of multisectoral initiatives to promote One Health border health approaches.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In Uganda, the borders are highly porous to animal movement, which may contribute to zoonotic disease spread. We piloted an animal adaptation of an existing human-focused toolkit to collect data on animal movement patterns and interactions to inform One Health programs. During January 2020, we conducted focus group discussions and key informant interviews with participatory mapping of 2 national-level One Health stakeholders and 2 local-level abattoir representatives from Kampala. Zoonotic disease hotspots changed in 2020 compared with reports from 2017–2019. In contrast to local-level participants, national-level participants highlighted districts rather than specific locations. Everyone discussed livestock species; only national-level participants mentioned wildlife. Participants described seasonality differently. Stakeholders used the results to identify locations for zoonotic disease interventions and sites for future data collection. This implementation of an animal-adapted population mobility mapping exercise highlights the importance of multisectoral initiatives to promote One Health border health approaches. |
Christopher K. Opio Francis Kazibwe, Lalitha Rejani Narcis Kabatereine & Ponsiano Ocama B Hepatic schistosomiasis, upper gastrointestinal bleeding, and health related quality of life measurements from the Albert Nile Basin Journal Article Journal of Patient-Reported Outcomes, 5 (112), 2021. @article{Opio2021, title = {Hepatic schistosomiasis, upper gastrointestinal bleeding, and health related quality of life measurements from the Albert Nile Basin}, author = {Christopher K. Opio, Francis Kazibwe, Lalitha Rejani, Narcis B. Kabatereine & Ponsiano Ocama }, doi = {https://doi.org/10.1186/s41687-021-00389-9}, year = {2021}, date = {2021-10-30}, journal = {Journal of Patient-Reported Outcomes}, volume = {5}, number = {112}, abstract = {Background Health related quality of life measurements are vital elements of public health surveillance that uncover unmet health needs and predict the success of health interventions. We described health related quality of life measurements using the EuroQoL 5-dimension (EQ-VAS/EQ-5D) instrument and associated factors among patients with upper gastrointestinal bleeding (UGIB) and hepatic schistosomiasis at a rural health facility in the Albert Nile Basin, Uganda. Methods and materials This was a cross-sectional study at Pakwach Health Centre IV. Participants included adult inpatients and outpatients with a history of UGIB and ultrasound evidence of hepatic schistosomiasis. We evaluated and recorded each participant’s medical history, physical examination, laboratory tests results, ultrasound results, and endoscopy findings. We also recorded health related quality of life measurements using the EuroQoL 5-dimension instrument and derived disability weights from EQ-VAS and EQ-5D measurements. These were our dependent variables. Descriptive and inferential statistics were generated summarizing our findings. Results We found 103 participants had a history of upper gastrointestinal bleeding and hepatosplenic schistosomiasis. Sixty percent were between the ages of 30–49 years, 59% were females, 74% were farmers, 92% had splenomegaly, 88% had varices at endoscopy, 22% were medical emergencies with acute variceal upper gastrointestinal bleeding, and 62% had anemia. Measures of the different dimensions of health from 101 participants with patient reported outcomes revealed 77 (76%) participants experienced problems in self-care, 89 (88%) participants reported anxiety or depression, and 89 (88%) participants experienced pain or discomfort. The median EQ-VAS derived disability weights and median EQ-5D index-derived disability weights were 0.3 and 0.34, respectively. Acute upper gastrointestinal bleeding, praziquantel drug treatment, and age by decade predicted higher EQ-VAS derived disability weights (p value < 0.05). Under weight (Body mass index ≤ 18.5), acute upper gastrointestinal bleeding, ascites, age by decade, female gender, and praziquantel drug treatment predicted higher EQ-5D index- derived disability weights (p value < 0.05). Conclusion Adult patients with upper gastrointestinal bleeding and hepatic schistosomiasis from this primary health facility experience poor health and considerable health loss. Several factors predicted increased health loss. These factors probably represent key areas of health intervention towards mitigating increased health loss in this population.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Health related quality of life measurements are vital elements of public health surveillance that uncover unmet health needs and predict the success of health interventions. We described health related quality of life measurements using the EuroQoL 5-dimension (EQ-VAS/EQ-5D) instrument and associated factors among patients with upper gastrointestinal bleeding (UGIB) and hepatic schistosomiasis at a rural health facility in the Albert Nile Basin, Uganda. Methods and materials This was a cross-sectional study at Pakwach Health Centre IV. Participants included adult inpatients and outpatients with a history of UGIB and ultrasound evidence of hepatic schistosomiasis. We evaluated and recorded each participant’s medical history, physical examination, laboratory tests results, ultrasound results, and endoscopy findings. We also recorded health related quality of life measurements using the EuroQoL 5-dimension instrument and derived disability weights from EQ-VAS and EQ-5D measurements. These were our dependent variables. Descriptive and inferential statistics were generated summarizing our findings. Results We found 103 participants had a history of upper gastrointestinal bleeding and hepatosplenic schistosomiasis. Sixty percent were between the ages of 30–49 years, 59% were females, 74% were farmers, 92% had splenomegaly, 88% had varices at endoscopy, 22% were medical emergencies with acute variceal upper gastrointestinal bleeding, and 62% had anemia. Measures of the different dimensions of health from 101 participants with patient reported outcomes revealed 77 (76%) participants experienced problems in self-care, 89 (88%) participants reported anxiety or depression, and 89 (88%) participants experienced pain or discomfort. The median EQ-VAS derived disability weights and median EQ-5D index-derived disability weights were 0.3 and 0.34, respectively. Acute upper gastrointestinal bleeding, praziquantel drug treatment, and age by decade predicted higher EQ-VAS derived disability weights (p value < 0.05). Under weight (Body mass index ≤ 18.5), acute upper gastrointestinal bleeding, ascites, age by decade, female gender, and praziquantel drug treatment predicted higher EQ-5D index- derived disability weights (p value < 0.05). Conclusion Adult patients with upper gastrointestinal bleeding and hepatic schistosomiasis from this primary health facility experience poor health and considerable health loss. Several factors predicted increased health loss. These factors probably represent key areas of health intervention towards mitigating increased health loss in this population. |
the Jeffrey V. Lazarus Henry E. Mark, Quentin Anstee Juan Pablo Arab Rachel Batterham Laurent Castera Helena Cortez-Pinto Javier Crespo Kenneth Cusi Ashworth Dirac Sven Francque Jacob George Hannes Hagström Terry Huang Mona Ismail Achim Kautz Shiv Kumar Sarin Rohit Loomba Veronica Miller Philip Newsome Michael Ninburg Ponsiano Ocama Vlad Ratziu Mary Rinella Diana Romero Manuel Romero-Gómez Jörn Schattenberg Emmanuel Tsochatzis Luca Valenti Vincent Wai-Sun Wong Yusuf Yilmaz Zobair Younossi Shira Zelber-Sagi & NAFLD Consensus Consortium M L M T -K H N M A M Advancing the global public health agenda for NAFLD: a consensus statement Journal Article Nature Reviews Gastroenterology & Hepatology, 19 , pp. 60-78, 2021. @article{Lazarus2021, title = {Advancing the global public health agenda for NAFLD: a consensus statement}, author = {Jeffrey V. Lazarus, Henry E. Mark, Quentin M. Anstee, Juan Pablo Arab, Rachel L. Batterham, Laurent Castera, Helena Cortez-Pinto, Javier Crespo, Kenneth Cusi, M. Ashworth Dirac, Sven Francque, Jacob George, Hannes Hagström, Terry T.-K. Huang, Mona H. Ismail, Achim Kautz, Shiv Kumar Sarin, Rohit Loomba, Veronica Miller, Philip N. Newsome, Michael Ninburg, Ponsiano Ocama, Vlad Ratziu, Mary Rinella, Diana Romero, Manuel Romero-Gómez, Jörn M. Schattenberg, Emmanuel A. Tsochatzis, Luca Valenti, Vincent Wai-Sun Wong, Yusuf Yilmaz, Zobair M. Younossi, Shira Zelber-Sagi & the NAFLD Consensus Consortium}, doi = {https://doi.org/10.1038/s41575-021-00523-4}, year = {2021}, date = {2021-10-27}, journal = {Nature Reviews Gastroenterology & Hepatology}, volume = {19}, pages = {60-78}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics — from epidemiology, awareness, care and treatment to public health policies and leadership — that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics — from epidemiology, awareness, care and treatment to public health policies and leadership — that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD. |
Susan Nabadda Francis Kakooza, Reuben Kiggundu Richard Walwema Joel Bazira Jonathan Mayito Ibrahimm Mugerwa Musa Sekamatte Andrew Kambugu Mohammed Lamorde Henry Kajumbula ; Mwebasa, Henry JMIR Public Health and Surveillance , 7 (10), 2021. @article{Nabadda2021, title = {Implementation of the World Health Organization Global Antimicrobial Resistance Surveillance System in Uganda, 2015-2020: Mixed-Methods Study Using National Surveillance Data }, author = {Susan Nabadda, Francis Kakooza, Reuben Kiggundu, Richard Walwema, Joel Bazira, Jonathan Mayito, Ibrahimm Mugerwa, Musa Sekamatte, Andrew Kambugu, Mohammed Lamorde, Henry Kajumbula and Henry Mwebasa }, doi = {doi: 10.2196/29954 }, year = {2021}, date = {2021-10-21}, journal = {JMIR Public Health and Surveillance }, volume = {7}, number = {10}, abstract = {Background: Antimicrobial resistance (AMR) is an emerging public health crisis in Uganda. The World Health Organization (WHO) Global Action Plan recommends that countries should develop and implement National Action Plans for AMR. We describe the establishment of the national AMR program in Uganda and present the early microbial sensitivity results from the program. Objective: The aim of this study is to describe a national surveillance program that was developed to perform the systematic and continuous collection, analysis, and interpretation of AMR data. Methods: A systematic qualitative description of the process and progress made in the establishment of the national AMR program is provided, detailing the progress made from 2015 to 2020. This is followed by a report of the findings of the isolates that were collected from AMR surveillance sites. Identification and antimicrobial susceptibility testing (AST) of the bacterial isolates were performed using standard methods at both the surveillance sites and the reference laboratory. Results: Remarkable progress has been achieved in the establishment of the national AMR program, which is guided by the WHO Global Laboratory AMR Surveillance System (GLASS) in Uganda. A functional national coordinating center for AMR has been established with a supporting designated reference laboratory. WHONET software for AMR data management has been installed in the surveillance sites and laboratory staff trained on data quality assurance. Uganda has progressively submitted data to the WHO GLASS reporting system. Of the 19,216 isolates from WHO GLASS priority specimens collected from October 2015 to June 2020, 22.95% (n=4411) had community-acquired infections, 9.46% (n=1818) had hospital-acquired infections, and 68.57% (n=12,987) had infections of unknown origin. The highest proportion of the specimens was blood (12,398/19,216, 64.52%), followed by urine (5278/19,216, 27.47%) and stool (1266/19,216, 6.59%), whereas the lowest proportion was urogenital swabs (274/19,216, 1.4%). The mean age was 19.1 (SD 19.8 years), whereas the median age was 13 years (IQR 28). Approximately 49.13% (9440/19,216) of the participants were female and 50.51% (9706/19,216) were male. Participants with community-acquired infections were older (mean age 28, SD 18.6 years; median age 26, IQR 20.5 years) than those with hospital-acquired infections (mean age 17.3, SD 20.9 years; median age 8, IQR 26 years). All gram-negative (Escherichia coli, Klebsiella pneumoniae, and Neisseria gonorrhoeae) and gram-positive (Staphylococcus aureus and Enterococcus sp) bacteria with AST showed resistance to each of the tested antibiotics. Conclusions: Uganda is the first African country to implement a structured national AMR surveillance program in alignment with the WHO GLASS. The reported AST data indicate very high resistance to the recommended and prescribed antibiotics for treatment of infections. More effort is required regarding quality assurance of laboratory testing methodologies to ensure optimal adherence to WHO GLASS–recommended pathogen-antimicrobial combinations. The current AMR data will inform the development of treatment algorithms and clinical guidelines.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Antimicrobial resistance (AMR) is an emerging public health crisis in Uganda. The World Health Organization (WHO) Global Action Plan recommends that countries should develop and implement National Action Plans for AMR. We describe the establishment of the national AMR program in Uganda and present the early microbial sensitivity results from the program. Objective: The aim of this study is to describe a national surveillance program that was developed to perform the systematic and continuous collection, analysis, and interpretation of AMR data. Methods: A systematic qualitative description of the process and progress made in the establishment of the national AMR program is provided, detailing the progress made from 2015 to 2020. This is followed by a report of the findings of the isolates that were collected from AMR surveillance sites. Identification and antimicrobial susceptibility testing (AST) of the bacterial isolates were performed using standard methods at both the surveillance sites and the reference laboratory. Results: Remarkable progress has been achieved in the establishment of the national AMR program, which is guided by the WHO Global Laboratory AMR Surveillance System (GLASS) in Uganda. A functional national coordinating center for AMR has been established with a supporting designated reference laboratory. WHONET software for AMR data management has been installed in the surveillance sites and laboratory staff trained on data quality assurance. Uganda has progressively submitted data to the WHO GLASS reporting system. Of the 19,216 isolates from WHO GLASS priority specimens collected from October 2015 to June 2020, 22.95% (n=4411) had community-acquired infections, 9.46% (n=1818) had hospital-acquired infections, and 68.57% (n=12,987) had infections of unknown origin. The highest proportion of the specimens was blood (12,398/19,216, 64.52%), followed by urine (5278/19,216, 27.47%) and stool (1266/19,216, 6.59%), whereas the lowest proportion was urogenital swabs (274/19,216, 1.4%). The mean age was 19.1 (SD 19.8 years), whereas the median age was 13 years (IQR 28). Approximately 49.13% (9440/19,216) of the participants were female and 50.51% (9706/19,216) were male. Participants with community-acquired infections were older (mean age 28, SD 18.6 years; median age 26, IQR 20.5 years) than those with hospital-acquired infections (mean age 17.3, SD 20.9 years; median age 8, IQR 26 years). All gram-negative (Escherichia coli, Klebsiella pneumoniae, and Neisseria gonorrhoeae) and gram-positive (Staphylococcus aureus and Enterococcus sp) bacteria with AST showed resistance to each of the tested antibiotics. Conclusions: Uganda is the first African country to implement a structured national AMR surveillance program in alignment with the WHO GLASS. The reported AST data indicate very high resistance to the recommended and prescribed antibiotics for treatment of infections. More effort is required regarding quality assurance of laboratory testing methodologies to ensure optimal adherence to WHO GLASS–recommended pathogen-antimicrobial combinations. The current AMR data will inform the development of treatment algorithms and clinical guidelines. |
