2014
|
Paton, Nicholas I.; Kityo, Cissy; Hoppe, Anne; Reid, Andrew; Kambugu, Andrew; Lugemwa, Abbas; van Oosterhout, Joep J.; Kiconco, Mary; Siika, Abraham; Mwebaze, Raymond; Abwola, Mary; Abongomera, George; M.Med. Aggrey Mweemba, Hillary Alima; Atwongyeire, Dickens; Nyirenda, Rose; Boles, Justine; Thompson, Jennifer; Tumukunde, Dinah; Ennie Chidziva, Dipl. G. N.; Arribas, Ivan Mambule Jose R.; Easterbrook, Philippa J.; Hakim, James; Walker, A. Sarah; Mugyenyi, Peter Assessment of Second-Line Antiretroviral Regimens for HIV Therapy in Africa Journal Article In: The New England Journal of Medicine, vol. 37, no. 1, pp. 234-47, 2014. @article{Paton2014,
title = {Assessment of Second-Line Antiretroviral Regimens for HIV Therapy in Africa},
author = {Nicholas I. Paton and Cissy Kityo and Anne Hoppe and Andrew Reid and Andrew Kambugu and Abbas Lugemwa and
Joep J. van Oosterhout and Mary Kiconco and Abraham Siika and Raymond Mwebaze and Mary Abwola and George Abongomera and
Aggrey Mweemba, M.Med., Hillary Alima and Dickens Atwongyeire and Rose Nyirenda and Justine Boles and Jennifer Thompson and Dinah Tumukunde and Ennie Chidziva, Dipl.G.N. and Ivan Mambule
Jose R. Arribas and Philippa J. Easterbrook and James Hakim and A. Sarah Walker and Peter Mugyenyi},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Assessment-of-Second-Line-Antiretroviral-Regimens-for-HIV-Therapy-in-Africa.pdf},
doi = {10.1056/NEJMoa1311274},
year = {2014},
date = {2014-07-17},
journal = {The New England Journal of Medicine},
volume = {37},
number = {1},
pages = {234-47},
abstract = {Background
The efficacy and toxic effects of nucleoside reverse-transcriptase inhibitors (NRTIs)
are uncertain when these agents are used with a protease inhibitor in second-line
therapy for human immunodeficiency virus (HIV) infection in resource-limited set
-
tings. Removing the NRTIs or replacing them with raltegravir may provide a benefit.
Methods
In this open-label trial in sub-Saharan Africa, we randomly assigned 1277 adults and
adolescents with HIV infection and first-line treatment failure to receive a ritonavir-
boosted protease inhibitor (lopinavir–ritonavir) plus clinician-selected NRTIs (NRTI
group, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison
(raltegravir group, 433 patients), or protease-inhibitor monotherapy after 12 weeks of
induction therapy with raltegravir in a noninferiority comparison (monotherapy group,
418 patients). The primary composite end point, good HIV disease control, was
defined as survival with no new World Health Organization stage 4 events, a CD4+
count of more than 250 cells per cubic millimeter, and a viral load of less than
10,000 copies per milliliter or 10,000 copies or more with no protease resistance
mutations at week 96 and was analyzed with the use of imputation of data (≤4%).
Results
Good HIV disease control was achieved in 60% of the patients (mean, 255 patients) in
the NRTI group, 64% of the patients (mean, 277) in the raltegravir group (P
= 0.21 for
the comparison with the NRTI group; superiority of raltegravir not shown), and 55%
of the patients (mean, 232) in the monotherapy group (noninferiority of monotherapy
not shown, based on a 10-percentage-point margin). There was no significant differ
-
ence in rates of grade 3 or 4 adverse events among the three groups (P
= 0.82). The viral
load was less than 400 copies per milliliter in 86% of patients in the NRTI group, 86%
in the raltegravir group (P
= 0.97), and 61% in the monotherapy group (P<0.001).
Conclusions
When given with a protease inhibitor in second-line therapy, NRTIs retained sub
-
stantial virologic activity without evidence of increased toxicity, and there was no
advantage to replacing them with raltegravir. Virologic control was inferior with
protease-inhibitor monotherapy. (Funded by European and Developing Countries
Clinical Trials Partnership and others; EARNEST Current Controlled Trials number,
ISRCTN 37737787, and ClinicalTrials.gov number, NCT00988039.)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
The efficacy and toxic effects of nucleoside reverse-transcriptase inhibitors (NRTIs)
are uncertain when these agents are used with a protease inhibitor in second-line
therapy for human immunodeficiency virus (HIV) infection in resource-limited set
-
tings. Removing the NRTIs or replacing them with raltegravir may provide a benefit.
Methods
In this open-label trial in sub-Saharan Africa, we randomly assigned 1277 adults and
adolescents with HIV infection and first-line treatment failure to receive a ritonavir-
boosted protease inhibitor (lopinavir–ritonavir) plus clinician-selected NRTIs (NRTI
group, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison
(raltegravir group, 433 patients), or protease-inhibitor monotherapy after 12 weeks of
induction therapy with raltegravir in a noninferiority comparison (monotherapy group,
418 patients). The primary composite end point, good HIV disease control, was
defined as survival with no new World Health Organization stage 4 events, a CD4+
count of more than 250 cells per cubic millimeter, and a viral load of less than
10,000 copies per milliliter or 10,000 copies or more with no protease resistance
mutations at week 96 and was analyzed with the use of imputation of data (≤4%).
Results
Good HIV disease control was achieved in 60% of the patients (mean, 255 patients) in
the NRTI group, 64% of the patients (mean, 277) in the raltegravir group (P
= 0.21 for
the comparison with the NRTI group; superiority of raltegravir not shown), and 55%
of the patients (mean, 232) in the monotherapy group (noninferiority of monotherapy
not shown, based on a 10-percentage-point margin). There was no significant differ
-
ence in rates of grade 3 or 4 adverse events among the three groups (P
= 0.82). The viral
load was less than 400 copies per milliliter in 86% of patients in the NRTI group, 86%
in the raltegravir group (P
= 0.97), and 61% in the monotherapy group (P<0.001).
Conclusions
When given with a protease inhibitor in second-line therapy, NRTIs retained sub
-
stantial virologic activity without evidence of increased toxicity, and there was no
advantage to replacing them with raltegravir. Virologic control was inferior with
protease-inhibitor monotherapy. (Funded by European and Developing Countries
Clinical Trials Partnership and others; EARNEST Current Controlled Trials number,
ISRCTN 37737787, and ClinicalTrials.gov number, NCT00988039.) |
Manabe, Yukari C.; Nonyane, Bareng A. S.; Nakiyingia, Lydia; Mbabazi, Olive; Lubega, Gloria; Shah, Maunank; Moulton, Lawrence H.; Joloba, Moses; Ellner, Jerrold; Dorman, Susan E. Point-of-Care Lateral Flow Assays for Tuberculosis and Cryptococcal Antigenuria Predict Death in HIV Infected Adults in Uganda Journal Article In: PloS One, vol. 9, no. 7, 2014. @article{Manabe2014,
title = {Point-of-Care Lateral Flow Assays for Tuberculosis and Cryptococcal Antigenuria Predict Death in HIV Infected Adults in Uganda},
author = {Yukari C. Manabe and Bareng A. S. Nonyane and Lydia Nakiyingia and Olive Mbabazi and Gloria Lubega and Maunank Shah and Lawrence H. Moulton and Moses Joloba and Jerrold Ellner and Susan E. Dorman
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Point-of-Care-Lateral-Flow-Assays-for-Tuberculosis-and....pdf},
doi = { 10.1371/journal.pone.0101459},
year = {2014},
date = {2014-07-07},
journal = {PloS One},
volume = {9},
number = {7},
abstract = {BACKGROUND:
Mortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, particularly disseminated tuberculosis (TB) and cryptococcal disease. We sought to determine if a positive lateral flow assay (LFA) result for urine lipoarabinomannan (LAM) and cryptococcal antigenuria was associated with mortality.
METHODS:
351 hospitalized, HIV-positive adults with symptoms consistent with TB and who were able to provide both urine and sputum specimens were prospectively enrolled at Mulago National Referral Hospital in Uganda as part of a prospective accuracy evaluation of the lateral flow Determine TB LAM test. Stored frozen urine was retrospectively tested for cryptococcal antigen (CRAG) using the LFA. We fitted a multinomial logistic regression model to analyze factors associated with death within 2 months after initial presentation.
RESULTS:
The median CD4 of the participants was 57 (IQR: 14-179) cells/µl and 41% (145) were microbiologically confirmed TB cases. LAM LFA was positive in 38% (134), 7% (25) were CRAG positive, and 43% (151) were positive for either test in urine. Overall, 21% (75) died within the first 2 months, and a total of 32% (114) were confirmed dead by 6 months. At 2 months, 30% of LAM or CRAG positive patients were confirmed dead compared to 15.0% of those who were negative. In an adjusted model, LAM or CRAG positive results were associated with an increased risk of death (RRR 2.29, 95% CI: 1.29, 4.05; P = 0.005).
CONCLUSIONS:
In hospitalized HIV-infected patients, LAM or CRAG LFA positivity was associated with subsequent death within 2 months. Further studies are warranted to examine the impact of POC diagnostic 'test and treat' approach on patient-centered outcomes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Mortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, particularly disseminated tuberculosis (TB) and cryptococcal disease. We sought to determine if a positive lateral flow assay (LFA) result for urine lipoarabinomannan (LAM) and cryptococcal antigenuria was associated with mortality.
METHODS:
351 hospitalized, HIV-positive adults with symptoms consistent with TB and who were able to provide both urine and sputum specimens were prospectively enrolled at Mulago National Referral Hospital in Uganda as part of a prospective accuracy evaluation of the lateral flow Determine TB LAM test. Stored frozen urine was retrospectively tested for cryptococcal antigen (CRAG) using the LFA. We fitted a multinomial logistic regression model to analyze factors associated with death within 2 months after initial presentation.
RESULTS:
The median CD4 of the participants was 57 (IQR: 14-179) cells/µl and 41% (145) were microbiologically confirmed TB cases. LAM LFA was positive in 38% (134), 7% (25) were CRAG positive, and 43% (151) were positive for either test in urine. Overall, 21% (75) died within the first 2 months, and a total of 32% (114) were confirmed dead by 6 months. At 2 months, 30% of LAM or CRAG positive patients were confirmed dead compared to 15.0% of those who were negative. In an adjusted model, LAM or CRAG positive results were associated with an increased risk of death (RRR 2.29, 95% CI: 1.29, 4.05; P = 0.005).
CONCLUSIONS:
In hospitalized HIV-infected patients, LAM or CRAG LFA positivity was associated with subsequent death within 2 months. Further studies are warranted to examine the impact of POC diagnostic 'test and treat' approach on patient-centered outcomes. |
Nakiyingi, Lydia; Moodley, Mischka; Manabe, Yukari C.; Nicol, Mark P.; Holshouser, Molly; Armstrong, Derek T.; Zemana, Widaad; Sikhondze, Welile; Mbabazi, Olive; Nonyane, Bareng A. S.; Shah, Maunank; Joloba, Moses L.; Alland, David; Ellne, Jerrold J.; Susan E. Dorman, MD Diagnostic accuracy of a rapid urine lipoarabinomannan test for tuberculosis in HIV-infected adults Journal Article In: Journal of Acquired Imune Dificiency syndrome, vol. 66, no. 3, pp. 270-9, 2014. @article{Nakiyingi2014,
title = {Diagnostic accuracy of a rapid urine lipoarabinomannan test for tuberculosis in HIV-infected adults},
author = {Lydia Nakiyingi and Mischka Moodley and Yukari C. Manabe and Mark P. Nicol and Molly Holshouser and Derek T. Armstrong and Widaad Zemana and Welile Sikhondze and Olive Mbabazi and Bareng A.S. Nonyane and Maunank Shah and Moses L. Joloba and David Alland and Jerrold J. Ellne and Susan E. Dorman, MD
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Diagnostic-accuracy-of-a-rapid-urine-lipoarabinomannan-test-for....pdf},
doi = { 10.1097/QAI.0000000000000151},
year = {2014},
date = {2014-07-01},
journal = {Journal of Acquired Imune Dificiency syndrome},
volume = {66},
number = {3},
pages = {270-9},
abstract = {OBJECTIVE:
In settings of high HIV prevalence, tuberculosis control and patient management are hindered by lack of accurate, rapid tuberculosis diagnostic tests that can be performed at point-of-care. The Determine TB LAM Ag (TB LAM) test is a lateral flow immunochromatographic test for detection of mycobacterial lipoarabinomannan (LAM) in urine. Our objective was to determine sensitivity and specificity of the TB LAM test for tuberculosis diagnosis.
DESIGN:
Prospective diagnostic accuracy study.
SETTING:
Hospital and outpatient settings in Uganda and South Africa.
PARTICIPANTS:
HIV-infected adults with tuberculosis symptoms and/or signs.
METHODS:
Participants provided a fresh urine specimen for TB LAM testing, blood for mycobacterial culture, and 2 respiratory specimens for smear microscopy and mycobacterial culture.
MAIN OUTCOME MEASURES:
For the TB LAM test, sensitivity in participants with culture-positive tuberculosis and specificity in participants without tuberculosis.
RESULTS:
A total of 1013 participants were enrolled. Among culture-positive tuberculosis patients, the TB LAM test identified 136/367 (37.1%) overall and 116/196 (59.2%) in the group with CD4 ≤100 cells per cubic millimeter. The test was specific in 559/573 (97.6%) patients without tuberculosis. Sensitivity of the urine TB LAM test plus sputum smear microscopy was 197/367 (53.7%) overall and 133/196 (67.9%) among those with CD4 ≤100. CD4 ≤50 [adjusted odds ratio (AOR), 6.2; P < 0.001] or 51-100 (AOR, 7.1; P < 0.001), mycobacteremia (AOR, 6.1; P < 0.01) and hospitalization (AOR, 2.6; P = 0.03) were independently associated with a positive TB LAM test.
CONCLUSIONS:
In HIV-positive adults with CD4 ≤100, the TB LAM urine test detected over half of culture-positive tuberculosis patients, in <30 minutes and without the need for equipment or reagents.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE:
In settings of high HIV prevalence, tuberculosis control and patient management are hindered by lack of accurate, rapid tuberculosis diagnostic tests that can be performed at point-of-care. The Determine TB LAM Ag (TB LAM) test is a lateral flow immunochromatographic test for detection of mycobacterial lipoarabinomannan (LAM) in urine. Our objective was to determine sensitivity and specificity of the TB LAM test for tuberculosis diagnosis.
DESIGN:
Prospective diagnostic accuracy study.
SETTING:
Hospital and outpatient settings in Uganda and South Africa.
PARTICIPANTS:
HIV-infected adults with tuberculosis symptoms and/or signs.
METHODS:
Participants provided a fresh urine specimen for TB LAM testing, blood for mycobacterial culture, and 2 respiratory specimens for smear microscopy and mycobacterial culture.
MAIN OUTCOME MEASURES:
For the TB LAM test, sensitivity in participants with culture-positive tuberculosis and specificity in participants without tuberculosis.
RESULTS:
A total of 1013 participants were enrolled. Among culture-positive tuberculosis patients, the TB LAM test identified 136/367 (37.1%) overall and 116/196 (59.2%) in the group with CD4 ≤100 cells per cubic millimeter. The test was specific in 559/573 (97.6%) patients without tuberculosis. Sensitivity of the urine TB LAM test plus sputum smear microscopy was 197/367 (53.7%) overall and 133/196 (67.9%) among those with CD4 ≤100. CD4 ≤50 [adjusted odds ratio (AOR), 6.2; P < 0.001] or 51-100 (AOR, 7.1; P < 0.001), mycobacteremia (AOR, 6.1; P < 0.01) and hospitalization (AOR, 2.6; P = 0.03) were independently associated with a positive TB LAM test.
CONCLUSIONS:
In HIV-positive adults with CD4 ≤100, the TB LAM urine test detected over half of culture-positive tuberculosis patients, in <30 minutes and without the need for equipment or reagents. |
Lowenthal, Elizabeth D; Bakeera-Kitaka, Sabrina; Marukutira, Tafireyi; Chapman, Jennifer; Goldrath, Kathryn; Ferran, Rashida A Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges Journal Article In: Lancent Infectious Diseases, vol. 14, no. 7, pp. 627-39, 2014. @article{Lowenthal2014,
title = {Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges},
author = {Elizabeth D Lowenthal and Sabrina Bakeera-Kitaka and Tafireyi Marukutira and Jennifer Chapman and Kathryn Goldrath and
Rashida A Ferran},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Perinatally-acquired-HIV-infection-in-adolescents-from-subSaharan-Africa...pdf},
doi = { 10.1016/S1473-3099(13)70363-3},
year = {2014},
date = {2014-07-01},
journal = {Lancent Infectious Diseases},
volume = {14},
number = {7},
pages = {627-39},
abstract = {Worldwide, more than three million children are infected with HIV, 90% of whom live in sub-
Saharan Africa. As the HIV epidemic matures and antiretroviral treatment is scaled up, children
with HIV are reaching adolescence in large numbers. The growing population of adolescents with
perinatally acquired HIV infection living within this region presents not only unprecedented
challenges but also opportunities to learn about the pathogenesis of HIV infection. In this Review,
we discuss the changing epidemiology of paediatric HIV and the particular features of HIV
infection in adolescents in sub-Saharan Africa. Longstanding HIV infection acquired when the
immune system is not developed results in distinctive chronic clinical complications that cause
severe morbidity. As well as dealing with chronic illness, HIV-infected adolescents have to
confront psychosocial issues, maintain adherence to drugs, and learn to negotiate sexual
relationships, while undergoing rapid physical and psychological development. Context-specific
strategies for early identification of HIV infection in children and prompt linkage to care need to
be developed. Clinical HIV care should integrate age-appropriate sexual and reproductive health
and psychological, educational, and social services. Health-care workers will need to be trained to
recognise and manage the needs of these young people so that the increasing numbers of children
surviving to adolescence can access quality care beyond specialist services at low-level health-care
facilities},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Worldwide, more than three million children are infected with HIV, 90% of whom live in sub-
Saharan Africa. As the HIV epidemic matures and antiretroviral treatment is scaled up, children
with HIV are reaching adolescence in large numbers. The growing population of adolescents with
perinatally acquired HIV infection living within this region presents not only unprecedented
challenges but also opportunities to learn about the pathogenesis of HIV infection. In this Review,
we discuss the changing epidemiology of paediatric HIV and the particular features of HIV
infection in adolescents in sub-Saharan Africa. Longstanding HIV infection acquired when the
immune system is not developed results in distinctive chronic clinical complications that cause
severe morbidity. As well as dealing with chronic illness, HIV-infected adolescents have to
confront psychosocial issues, maintain adherence to drugs, and learn to negotiate sexual
relationships, while undergoing rapid physical and psychological development. Context-specific
strategies for early identification of HIV infection in children and prompt linkage to care need to
be developed. Clinical HIV care should integrate age-appropriate sexual and reproductive health
and psychological, educational, and social services. Health-care workers will need to be trained to
recognise and manage the needs of these young people so that the increasing numbers of children
surviving to adolescence can access quality care beyond specialist services at low-level health-care
facilities |
Yukari C. Manabe Edward Jones-López, Moises Palaci Prospective Cross-Sectional Evaluation of the Small Membrane Filtration Method for Diagnosis of Pulmonary Tuberculosis Journal Article In: Journal of Clinical Microbiology, vol. 52, no. 7, 2014. @article{Jones-López2014,
title = {Prospective Cross-Sectional Evaluation of the Small Membrane Filtration Method for Diagnosis of Pulmonary Tuberculosis},
author = {Edward Jones-López, Yukari C. Manabe, Moises Palaci, Carol Kayiza, Derek Armstrong, Lydia Nakiyingi, Willy Ssengooba, Mary Gaeddert, Rachel Kubiak, Pedro Almeida Júnior, David Alland, Reynaldo Dietze, Moses Joloba, Jerrold J. Ellner, Susan E. Dorman },
doi = {https://doi.org/10.1128/JCM.00642-14},
year = {2014},
date = {2014-06-26},
journal = {Journal of Clinical Microbiology},
volume = {52},
number = {7},
abstract = {Smear microscopy has suboptimal sensitivity, and there is a need to improve its performance since it is commonly used to diagnose tuberculosis (TB). We prospectively evaluated the diagnostic accuracy of the small membrane filtration (SMF) method, an approach that uses a vacuum manifold and is designed to concentrate bacilli onto a filter that can be examined microscopically. We enrolled hospitalized adults suspected to have pulmonary TB in Kampala, Uganda. We obtained a clinical history and three spontaneously expectorated sputum specimens for smear microscopy (direct, concentrated, and SMF), MGIT (mycobacterial growth indicator tube) 960 and Lowenstein-Jensen (LJ) cultures, and Xpert MTB/RIF testing. We performed per-specimen (primary) and per-patient analyses. From October 2012 to June 2013, we enrolled 212 patients (579 sputum specimens). The participants were mostly female (63.2%), and 81.6% were HIV infected; their median CD4 cell count was 47 cells/μl. Overall, 19.0%, 20.4%, 27.1%, 25.2%, and 25.9% of specimens tested positive by direct smear, concentrated smear, MGIT culture, LJ culture, and Xpert test, respectively. In the per-specimen analysis, the sensitivity of the SMF method (48.5%; 95% confidence interval [CI], 37.4 to 59.6) was lower than those of direct smear (60.9%; 51.4 to 70.5 [P = 0.0001]) and concentrated smear (63.3%; 53.6 to 73.1 [P < 0.0001]). Subgroup analyses showed that SMF performed poorly in specimens having a low volume or low bacterial load. The SMF method performed poorly compared to standard smear techniques and was sensitive to sample preparation techniques. The optimal laboratory SMF protocol may require striking a fine balance between sample dilution and filtration failure rate.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Smear microscopy has suboptimal sensitivity, and there is a need to improve its performance since it is commonly used to diagnose tuberculosis (TB). We prospectively evaluated the diagnostic accuracy of the small membrane filtration (SMF) method, an approach that uses a vacuum manifold and is designed to concentrate bacilli onto a filter that can be examined microscopically. We enrolled hospitalized adults suspected to have pulmonary TB in Kampala, Uganda. We obtained a clinical history and three spontaneously expectorated sputum specimens for smear microscopy (direct, concentrated, and SMF), MGIT (mycobacterial growth indicator tube) 960 and Lowenstein-Jensen (LJ) cultures, and Xpert MTB/RIF testing. We performed per-specimen (primary) and per-patient analyses. From October 2012 to June 2013, we enrolled 212 patients (579 sputum specimens). The participants were mostly female (63.2%), and 81.6% were HIV infected; their median CD4 cell count was 47 cells/μl. Overall, 19.0%, 20.4%, 27.1%, 25.2%, and 25.9% of specimens tested positive by direct smear, concentrated smear, MGIT culture, LJ culture, and Xpert test, respectively. In the per-specimen analysis, the sensitivity of the SMF method (48.5%; 95% confidence interval [CI], 37.4 to 59.6) was lower than those of direct smear (60.9%; 51.4 to 70.5 [P = 0.0001]) and concentrated smear (63.3%; 53.6 to 73.1 [P < 0.0001]). Subgroup analyses showed that SMF performed poorly in specimens having a low volume or low bacterial load. The SMF method performed poorly compared to standard smear techniques and was sensitive to sample preparation techniques. The optimal laboratory SMF protocol may require striking a fine balance between sample dilution and filtration failure rate. |
David B. Meya David R. Boulware, Conrad Muzoora; Graeme Meintjes, for the COAT Trial Team Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis Journal Article In: The New England Journal of Medicine, vol. 370, no. 26, pp. 2487-2498, 2014. @article{Boulware2014c,
title = {Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis},
author = {David R. Boulware, David B. Meya, Conrad Muzoora, M.Med., Melissa A. Rolfes, Katherine Huppler Hullsiek, Abdu Musubire, Kabanda Taseera, Henry W. Nabeta, Charlotte Schutz, Darlisha A. Williams, Radha Rajasingham, Joshua Rhein, Friedrich Thienemann, Melanie W. Lo, Kirsten Nielsen, Tracy L. Bergemann, Andrew Kambugu, M.Med., Yukari C. Manabe, Edward N. Janoff, Paul R. Bohjanen, and Graeme Meintjes, for the COAT Trial Team},
doi = {DOI: 10.1056/NEJMoa1312884},
year = {2014},
date = {2014-06-26},
journal = {The New England Journal of Medicine},
volume = {370},
number = {26},
pages = {2487-2498},
abstract = {Background
Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome–related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered.
Methods
We assessed survival at 26 weeks among 177 human immunodeficiency virus–infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole.
Results
The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P=0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P=0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P=0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P=0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups.
Conclusions
Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. (Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152. opens in new tab.)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome–related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered.
Methods
We assessed survival at 26 weeks among 177 human immunodeficiency virus–infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole.
Results
The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P=0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P=0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P=0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P=0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups.
Conclusions
Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. (Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152. opens in new tab.) |
Mbonye, Martin; Rutakumwa, Rwamahe; Weiss, Helen; Seeley, Janat Alcohol consumption and high risk sexual behaviour among female sex workers in Uganda Journal Article In: African Journal of AIDS Research, vol. 13, no. 2, pp. 145-51, 2014. @article{Mbonye2014b,
title = {Alcohol consumption and high risk sexual behaviour among female sex workers in Uganda},
author = { Martin Mbonye and Rwamahe Rutakumwa and Helen Weiss and Janat Seeley },
url = {https://www.tandfonline.com/doi/abs/10.2989/16085906.2014.927779},
doi = {10.2989/16085906.2014.927779},
year = {2014},
date = {2014-06-21},
journal = {African Journal of AIDS Research},
volume = {13},
number = {2},
pages = {145-51},
abstract = {Alcohol consumption has been associated with high risk sexual behaviour among key populations such as female sex workers. We explored the drivers of alcohol consumption and its relationship to high risk sexual behaviour. Participants were drawn from a cohort of 1 027 women selected from ‘hot spots’ in the suburbs of Kampala city. We conducted 3 in-depth interviews with 40 female sex workers between 2010 and 2011. Data were analysed thematically, focusing on alcohol use within the context of sex work. Alcohol consumption was very high with only seven women reporting that they did not drink. Alcohol consumption was driven by the emotional and economic needs of the participants, but also promoted by clients who encouraged consumption. Many sex workers only started drinking alcohol when they joined sex work on the advice of more experienced peers, as a way to cope with the job. Alcohol was blamed for unsafe sex, acts of violence and poor decision making which increased sexual and physical violence. Alcohol was reported to affect medication adherence for HIV-positive women who forgot to take medicine. The findings suggest that the drivers of alcohol consumption are multifaceted in this group and require both individual and structural interventions. Alcohol reduction counselling can be supportive at the individual level and should be an integral part of HIV prevention programmes for female sex workers and others such as patrons in bars. The counselling should be addressed in a sensitive manner to bar owners and managers.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alcohol consumption has been associated with high risk sexual behaviour among key populations such as female sex workers. We explored the drivers of alcohol consumption and its relationship to high risk sexual behaviour. Participants were drawn from a cohort of 1 027 women selected from ‘hot spots’ in the suburbs of Kampala city. We conducted 3 in-depth interviews with 40 female sex workers between 2010 and 2011. Data were analysed thematically, focusing on alcohol use within the context of sex work. Alcohol consumption was very high with only seven women reporting that they did not drink. Alcohol consumption was driven by the emotional and economic needs of the participants, but also promoted by clients who encouraged consumption. Many sex workers only started drinking alcohol when they joined sex work on the advice of more experienced peers, as a way to cope with the job. Alcohol was blamed for unsafe sex, acts of violence and poor decision making which increased sexual and physical violence. Alcohol was reported to affect medication adherence for HIV-positive women who forgot to take medicine. The findings suggest that the drivers of alcohol consumption are multifaceted in this group and require both individual and structural interventions. Alcohol reduction counselling can be supportive at the individual level and should be an integral part of HIV prevention programmes for female sex workers and others such as patrons in bars. The counselling should be addressed in a sensitive manner to bar owners and managers. |
Carlson, Renee Donahue; Rolfes, Melissa A; Birkenkamp, Kate E; Nakasujja, Noeline; Rajasingham, Radha; Meya, David B; David R Boulware, Predictors of Neurocognitive Outcomes on Antiretroviral Therapy after Cryptococcal Meningitis: A prospective cohort study Journal Article In: Metabolic Brain Disease, vol. 29, no. 2, pp. 269-279, 2014. @article{Carlson2014,
title = {Predictors of Neurocognitive Outcomes on Antiretroviral Therapy after Cryptococcal Meningitis: A prospective cohort study},
author = {Renee Donahue Carlson and Melissa A Rolfes and Kate E Birkenkamp and Noeline Nakasujja and Radha Rajasingham and David B Meya and David R Boulware,
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Predictors-of-Neurocognitive-Outcomes-on-Antiretroviral.pdf},
doi = {10.1007/s11011-013-9476-1},
year = {2014},
date = {2014-06-01},
journal = {Metabolic Brain Disease},
volume = {29},
number = {2},
pages = {269-279},
abstract = {Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n = 100). Comparison was made with an HIV-infected, non-meningitis cohort (n = 110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P = 0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores < -1), only in domains of motor speed, gross motor and executive function at 12 months. There was no evidence that neurocognitive outcome was associated with initial demographics, HIV parameters, or meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P = 0.002). Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n = 100). Comparison was made with an HIV-infected, non-meningitis cohort (n = 110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P = 0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores < -1), only in domains of motor speed, gross motor and executive function at 12 months. There was no evidence that neurocognitive outcome was associated with initial demographics, HIV parameters, or meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P = 0.002). Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome. |
Jaganath, Devan; Ssali, A. Sarah Walker Francis; Musiime, Victor; Kiweewa, Francis; Kityo, Cissy; Salata, Robert; for the DART, Peter Mugyenyi; Trials, ARROW HIV-Associated Anemia After 96 Weeks on Therapy: Determinants Across Age Ranges in Uganda and Zimbabwe Journal Article In: AIDS Resaerch and Human Retroviruses, vol. 30, no. 6, pp. 523-30, 2014. @article{Jaganath2014,
title = {HIV-Associated Anemia After 96 Weeks on Therapy: Determinants Across Age Ranges in Uganda and Zimbabwe},
author = {Devan Jaganath and A. Sarah Walker Francis Ssali and Victor Musiime and Francis Kiweewa and Cissy Kityo and Robert Salata and Peter Mugyenyi for the DART and ARROW Trials},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/HIV-Associated-Anemia-After-96-Weeks-on-Therapy....pdf},
doi = {10.1089/aid.2013.0255},
year = {2014},
date = {2014-06-01},
journal = {AIDS Resaerch and Human Retroviruses},
volume = {30},
number = {6},
pages = {523-30},
abstract = {Given the detrimental effects of HIV-associated anemia on morbidity, we determined factors associated with anemia after 96 weeks of antiretroviral therapy (ART) across age groups. An HIV-positive cohort (n=3,580) of children age 5-14, reproductive age adults 18-49, and older adults ≥50 from two randomized trials in Uganda and Zimbabwe were evaluated from initiation of therapy through 96 weeks. We conducted logistic and multinomial regression to evaluate common and differential determinants for anemia at 96 weeks on therapy. Prior to initiation of ART, the prevalence of anemia (age 5-11 <10.5 g/dl, 12-14 <11 g/dl, adult females <11 g/dl, adult males <12 g/dl) was 43%, which decreased to 13% at week 96 (p<0.001). Older adults had a significantly higher likelihood of anemia compared to reproductive age adults (OR 2.60, 95% CI 1.44-4.70, p=0.002). Reproductive age females had a significantly higher odds of anemia compared to men at week 96 (OR 2.56, 95% CI 1.92-3.40, p<0.001), and particularly a greater odds for microcytic anemia compared to males in the same age group (p=0.001). Other common factors associated with anemia included low body mass index (BMI) and microcytosis; greater increases in CD4 count to week 96 were protective. Thus, while ART significantly reduced the prevalence of anemia at 96 weeks, 13% of the population continued to be anemic. Specific groups, such as reproductive age females and older adults, have a greater odds of anemia and may guide clinicians to pursue further evaluation and management},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Given the detrimental effects of HIV-associated anemia on morbidity, we determined factors associated with anemia after 96 weeks of antiretroviral therapy (ART) across age groups. An HIV-positive cohort (n=3,580) of children age 5-14, reproductive age adults 18-49, and older adults ≥50 from two randomized trials in Uganda and Zimbabwe were evaluated from initiation of therapy through 96 weeks. We conducted logistic and multinomial regression to evaluate common and differential determinants for anemia at 96 weeks on therapy. Prior to initiation of ART, the prevalence of anemia (age 5-11 <10.5 g/dl, 12-14 <11 g/dl, adult females <11 g/dl, adult males <12 g/dl) was 43%, which decreased to 13% at week 96 (p<0.001). Older adults had a significantly higher likelihood of anemia compared to reproductive age adults (OR 2.60, 95% CI 1.44-4.70, p=0.002). Reproductive age females had a significantly higher odds of anemia compared to men at week 96 (OR 2.56, 95% CI 1.92-3.40, p<0.001), and particularly a greater odds for microcytic anemia compared to males in the same age group (p=0.001). Other common factors associated with anemia included low body mass index (BMI) and microcytosis; greater increases in CD4 count to week 96 were protective. Thus, while ART significantly reduced the prevalence of anemia at 96 weeks, 13% of the population continued to be anemic. Specific groups, such as reproductive age females and older adults, have a greater odds of anemia and may guide clinicians to pursue further evaluation and management |
Nansunga, Miriam; Manabe, Yukari C.; Alele, Paul E.; Kasolo, Josephine Association of testosterone levels with socio-demographic characteristics in a sample of Ugandan men Journal Article In: African Health Sciences, vol. 14, no. 2, pp. 348-55, 2014. @article{Nansunga2014,
title = {Association of testosterone levels with socio-demographic characteristics in a sample of Ugandan men},
author = {Miriam Nansunga and Yukari C. Manabe and Paul E. Alele and Josephine Kasolo},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Association-of-testosterone-levels-with-socio-demographic-characteristics-in-a-sample-of-Ugandan-Men.pdf},
doi = {10.4314/ahs.v14i2.9},
year = {2014},
date = {2014-06-01},
journal = {African Health Sciences},
volume = {14},
number = {2},
pages = {348-55},
abstract = {BACKGROUND:
Testosterone, a male reproductive hormone, affects several physiological processes, such as sperm production, energy, strength, sexual behavior, sleep and the general well being of men. Normal levels of testosterone are necessary to effect these physiological processes. The objective of this study was to study the association between testosterone levels in a sample of Ugandan men with socio-demographic characteristics, and compare the testosterone levels of Ugandan men with that of men in other countries.
METHODS:
Eighty men were enrolled from the medical campus at Makerere University. Blood samples were drawn from 7.00 - 8.00 a.m. and total testosterone was measured using radioimmunoassay. The free and bioavailable testosterone was calculated after measuring sex hormone binding globulin (SHBG) and albumin in the blood samples. Self-administered questionnaires were used to obtain socio-demographic characteristics of the subjects. Biometric measurements including weight, height and waist circumference were also recorded.
RESULTS:
Serum testosterone levels of Ugandan men were within the normal physiological ranges. Married participants and those with dependents had lower testosterone than unmarried participants and those without dependents respectively. Sexually active participants had lower testosterone levels than those who were not sexually active.
CONCLUSION:
Testosterone levels were lower in association with several socio-demographic characteristics including being married, having dependents, and daily coital frequency. Further research is warranted into the relationship between testosterone levels and contributory sexual behavior that may be important in understanding the spread of HIV/AIDS, given its high prevalence in sub-Saharan Africa.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Testosterone, a male reproductive hormone, affects several physiological processes, such as sperm production, energy, strength, sexual behavior, sleep and the general well being of men. Normal levels of testosterone are necessary to effect these physiological processes. The objective of this study was to study the association between testosterone levels in a sample of Ugandan men with socio-demographic characteristics, and compare the testosterone levels of Ugandan men with that of men in other countries.
METHODS:
Eighty men were enrolled from the medical campus at Makerere University. Blood samples were drawn from 7.00 - 8.00 a.m. and total testosterone was measured using radioimmunoassay. The free and bioavailable testosterone was calculated after measuring sex hormone binding globulin (SHBG) and albumin in the blood samples. Self-administered questionnaires were used to obtain socio-demographic characteristics of the subjects. Biometric measurements including weight, height and waist circumference were also recorded.
RESULTS:
Serum testosterone levels of Ugandan men were within the normal physiological ranges. Married participants and those with dependents had lower testosterone than unmarried participants and those without dependents respectively. Sexually active participants had lower testosterone levels than those who were not sexually active.
CONCLUSION:
Testosterone levels were lower in association with several socio-demographic characteristics including being married, having dependents, and daily coital frequency. Further research is warranted into the relationship between testosterone levels and contributory sexual behavior that may be important in understanding the spread of HIV/AIDS, given its high prevalence in sub-Saharan Africa. |
Nyabigambo, Agnes; Muliira, Joshua Kanaabi; Babikako, Harriet M; Kambugu, Andrew; Ndoleriire, Christopher Determinants of utilization of a no-cost HIV transition clinic: a cross-sectional study of young adults living with HIV/AIDS Journal Article In: Adolescents Health, Medicine and Therapeutics, vol. 5, pp. 89-99, 2014. @article{Nyabigambo2014,
title = {Determinants of utilization of a no-cost HIV transition clinic: a cross-sectional study of young adults living with HIV/AIDS},
author = {Agnes Nyabigambo and Joshua Kanaabi Muliira and Harriet M Babikako and Andrew Kambugu and Christopher Ndoleriire
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Determinants-of-utilization-of-a-no-cost-HiV-transition-clinic...pdf},
doi = {10.2147/AHMT.S57950},
year = {2014},
date = {2014-05-29},
journal = {Adolescents Health, Medicine and Therapeutics},
volume = {5},
pages = {89-99},
abstract = { There is minimal research that has been conducted among young adults to understand
the determinants of the utilization of human immunodeficiency virus (HIV) health services in this
population. The purpose of this study was to explore the levels and determinants of HIV transition
clinic (HTC) services utilization by young adults living with HIV/acquired immunodeficiency
syndrome (YALHA). The study used a cross-sectional design and quantitative methods to col
-
lect data from a sample of 379 YALHA between the ages of 15–24 years who were registered
clients of an HTC in Uganda. During data analysis, utilization was categorized into two levels:
regular (kept all appointment visits) and irregular (missed one or more appointment visits)
utilization. Univariable, bivariable, and multivariable logistic regression analyses were used to
examine the determinants associated with HTC utilization. The HTC services that were most
utilized by the YALHA were those based at the clinic and provided by professional health care
providers and these were: clinical examination (96%); laboratory services (87.1%); and counsel
-
ing (69.7%). The services that were least utilized were home visiting (5.8%) and peer support
services (19.8%). Of the 379 YALHA, only 32.4% regularly utilized the HTC. Multivariable
analysis showed that the main determinants of HTC utilization were CD4 count category of
251/
μ
L (adjusted odds ratio [AOR]
=
0.58, 95% confidence interval [CI]
=
0.36–0.95); not
being on antiretroviral therapy (AOR
=
0.27, 95% CI
=
0.15–0.47); and not receiving counseling
services (AOR
=
0.47, 95% CI
=
0.27–0.83). Regular utilization of the HTC by YALHA was low
and utilization seems to be influenced by HIV infection stage and HIV counseling services, but
not sociodemographic factors or community factors.
Keywords:
transition clinic, HIV/AIDS, young adults, service utilization, Uganda},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
There is minimal research that has been conducted among young adults to understand
the determinants of the utilization of human immunodeficiency virus (HIV) health services in this
population. The purpose of this study was to explore the levels and determinants of HIV transition
clinic (HTC) services utilization by young adults living with HIV/acquired immunodeficiency
syndrome (YALHA). The study used a cross-sectional design and quantitative methods to col
-
lect data from a sample of 379 YALHA between the ages of 15–24 years who were registered
clients of an HTC in Uganda. During data analysis, utilization was categorized into two levels:
regular (kept all appointment visits) and irregular (missed one or more appointment visits)
utilization. Univariable, bivariable, and multivariable logistic regression analyses were used to
examine the determinants associated with HTC utilization. The HTC services that were most
utilized by the YALHA were those based at the clinic and provided by professional health care
providers and these were: clinical examination (96%); laboratory services (87.1%); and counsel
-
ing (69.7%). The services that were least utilized were home visiting (5.8%) and peer support
services (19.8%). Of the 379 YALHA, only 32.4% regularly utilized the HTC. Multivariable
analysis showed that the main determinants of HTC utilization were CD4 count category of
251/
μ
L (adjusted odds ratio [AOR]
=
0.58, 95% confidence interval [CI]
=
0.36–0.95); not
being on antiretroviral therapy (AOR
=
0.27, 95% CI
=
0.15–0.47); and not receiving counseling
services (AOR
=
0.47, 95% CI
=
0.27–0.83). Regular utilization of the HTC by YALHA was low
and utilization seems to be influenced by HIV infection stage and HIV counseling services, but
not sociodemographic factors or community factors.
Keywords:
transition clinic, HIV/AIDS, young adults, service utilization, Uganda |
Kiggundu, Reuben; Rhein, Joshua; Meya, David B.; Boulware, David R.; Bahr, Nathan C. Unmasking cryptococcal meningitis immune reconstitution inflammatory syndrome in pregnancy induced by HIV antiretroviral therapy with postpartum paradoxical exacerbation Journal Article In: Medical Mycology Case Reports, vol. 5, pp. 16-9, 2014. @article{Kiggundu2014,
title = {Unmasking cryptococcal meningitis immune reconstitution inflammatory syndrome in pregnancy induced by HIV antiretroviral therapy with postpartum paradoxical exacerbation},
author = {Reuben Kiggundu and Joshua Rhein and David B. Meya and David R. Boulware and Nathan C. Bahr},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Unmasking-cryptococcal-meningitis-immune-reconstitution....pdf},
doi = { 10.1016/j.mmcr.2014.05.001},
year = {2014},
date = {2014-05-29},
journal = {Medical Mycology Case Reports},
volume = {5},
pages = {16-9},
abstract = {Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune reconstitution inflammatory syndrome (IRIS) is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS) and markedly worsened postpartum after delivery (paradoxical IRIS).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune reconstitution inflammatory syndrome (IRIS) is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS) and markedly worsened postpartum after delivery (paradoxical IRIS). |
Psaros, Christina; Haberer, Jessica E.; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Campbell, James D.; Wangisi, Jonathan; Mugwanya, Kenneth; Kintu, Alex; Enyakoit, Michael; Thomas, Katherine K.; Donnell, Deborah; Krows, Meighan; Kidoguchi, Lara; Ware, Norma; Baeten, Jared M.; Celum, Connie; Bangsber, David R.; Safren, Steve A. An intervention to support HIV pre-exposure prophylaxis (PrEP) adherence in HIV serodiscordant couples in Uganda Journal Article In: Journal of Acquired Imune Dificiency syndrome, vol. 66, no. 5, pp. 522–529, 2014. @article{Psaros2014,
title = {An intervention to support HIV pre-exposure prophylaxis (PrEP) adherence in HIV serodiscordant couples in Uganda},
author = {Christina Psaros and Jessica E. Haberer and Elly Katabira and Allan Ronald and Elioda Tumwesigye and James D. Campbell and Jonathan Wangisi and Kenneth Mugwanya and Alex Kintu and Michael Enyakoit and Katherine K. Thomas and Deborah Donnell and Meighan Krows and Lara Kidoguchi and Norma Ware and Jared M. Baeten and Connie Celum and David R. Bangsber and Steve A. Safren},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/An-intervention-to-support-HIV-pre-exposure-prophylaxis-PrEP-adherence-in-HIV-serodiscordant-couples-in-Uganda-1.pdf},
doi = {10.1097/QAI.0000000000000212},
year = {2014},
date = {2014-05-21},
journal = {Journal of Acquired Imune Dificiency syndrome},
volume = {66},
number = {5},
pages = {522–529},
abstract = {BACKGROUND:
Daily preexposure prophylaxis (PrEP) is an effective HIV prevention strategy, but adherence is required for maximum benefit. To date, there are no empirically supported PrEP adherence interventions. This article describes the process of developing a PrEP adherence intervention and presents results on its impact on adherence.
METHODS:
The Partners PrEP Study was a placebo-controlled efficacy trial of daily oral tenofovir and emtricitabine/tenofovir PrEP among uninfected members of HIV-serodiscordant couples. An ancillary adherence study was conducted at 3 study sites in Uganda. Participants with <80% adherence as measured by unannounced pill count received an additional adherence counseling intervention based on Lifesteps, an evidence-based HIV treatment adherence intervention, based on principles of cognitive-behavioral theory.
FINDINGS:
Of the 1147 HIV-seronegative participants enrolled in the ancillary adherence study, 168 (14.6%) triggered the adherence intervention. Of participants triggering the intervention, 62% were men; median age was 32.5 years. The median number of adherence counseling sessions was 10. Mean adherence during the month before the intervention was 75.7% and increased significantly to 84.1% in the month after the first intervention session (P < 0.001). The most frequently endorsed adherence barriers at session 1 were travel and forgetting.
INTERPRETATION:
A PrEP adherence intervention was feasible in a clinical trial of PrEP in Uganda and PrEP adherence increased after the intervention. Future research should identify PrEP users with low adherence for enhanced adherence counseling and determine optimal implementation strategies for interventions to maximize PrEP effectiveness.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Daily preexposure prophylaxis (PrEP) is an effective HIV prevention strategy, but adherence is required for maximum benefit. To date, there are no empirically supported PrEP adherence interventions. This article describes the process of developing a PrEP adherence intervention and presents results on its impact on adherence.
METHODS:
The Partners PrEP Study was a placebo-controlled efficacy trial of daily oral tenofovir and emtricitabine/tenofovir PrEP among uninfected members of HIV-serodiscordant couples. An ancillary adherence study was conducted at 3 study sites in Uganda. Participants with <80% adherence as measured by unannounced pill count received an additional adherence counseling intervention based on Lifesteps, an evidence-based HIV treatment adherence intervention, based on principles of cognitive-behavioral theory.
FINDINGS:
Of the 1147 HIV-seronegative participants enrolled in the ancillary adherence study, 168 (14.6%) triggered the adherence intervention. Of participants triggering the intervention, 62% were men; median age was 32.5 years. The median number of adherence counseling sessions was 10. Mean adherence during the month before the intervention was 75.7% and increased significantly to 84.1% in the month after the first intervention session (P < 0.001). The most frequently endorsed adherence barriers at session 1 were travel and forgetting.
INTERPRETATION:
A PrEP adherence intervention was feasible in a clinical trial of PrEP in Uganda and PrEP adherence increased after the intervention. Future research should identify PrEP users with low adherence for enhanced adherence counseling and determine optimal implementation strategies for interventions to maximize PrEP effectiveness. |
Muhumuza, Simon; Olsen, Annette; Katahoire, Anne; Kiragga, Agnes N.; Nuwaha, Fred Effectiveness of a Pre-treatment Snack on the Uptake of Mass Treatment for Schistosomiasis in Uganda: A Cluster Randomized Trial Journal Article In: PloS Medicine, vol. 11, no. 5, 2014. @article{Muhumuza2014,
title = {Effectiveness of a Pre-treatment Snack on the Uptake of Mass Treatment for Schistosomiasis in Uganda: A Cluster Randomized Trial},
author = {Simon Muhumuza and Annette Olsen and Anne Katahoire and Agnes N. Kiragga and Fred Nuwaha
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Effectiveness-of-a-Pre-treatment-Snack-on-the-Uptake-of-mass-treatment-for-schistosomiasis-in-Uganda.pdf},
doi = {10.1371/journal.pmed.1001640},
year = {2014},
date = {2014-05-13},
journal = {PloS Medicine},
volume = {11},
number = {5},
abstract = {BACKGROUND:
School-based mass treatment with praziquantel is the cornerstone for schistosomiasis control in school-aged children. However, uptake of treatment among school-age children in Uganda is low in some areas. The objective of the study was to examine the effectiveness of a pre-treatment snack on uptake of mass treatment.
METHODS AND FINDINGS:
In a cluster randomized trial carried out in Jinja district, Uganda, 12 primary schools were randomized into two groups; one received education messages for schistosomiasis prevention for two months prior to mass treatment, while the other, in addition to the education messages, received a pre-treatment snack shortly before mass treatment. Four weeks after mass treatment, uptake of praziquantel was assessed among a random sample of 595 children in the snack schools and 689 children in the non-snack schools as the primary outcome. The occurrence of side effects and the prevalence and mean intensity of Schistosoma mansoni infection were determined as the secondary outcomes. Uptake of praziquantel was higher in the snack schools, 93.9% (95% CI 91.7%-95.7%), compared to that in the non-snack schools, 78.7% (95% CI 75.4%-81.7%) (p = 0.002). The occurrence of side effects was lower in the snack schools, 34.4% (95% CI 31.5%-39.8%), compared to that in the non-snack schools, 46.9% (95% CI 42.2%-50.7%) (p = 0.041). Prevalence and mean intensity of S. mansoni infection was lower in the snack schools, 1.3% (95% CI 0.6%-2.6%) and 38.3 eggs per gram of stool (epg) (95% CI 21.8-67.2), compared to that in the non-snack schools, 14.1% (95% CI 11.6%-16.9%) (p = 0.001) and 78.4 epg (95% CI 60.6-101.5) (p = 0.001), respectively.
CONCLUSIONS:
Our results suggest that provision of a pre-treatment snack combined with education messages achieves a higher uptake compared to the education messages alone. The use a pre-treatment snack was associated with reduced side effects as well as decreased prevalence and intensity of S. mansoni infection.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
School-based mass treatment with praziquantel is the cornerstone for schistosomiasis control in school-aged children. However, uptake of treatment among school-age children in Uganda is low in some areas. The objective of the study was to examine the effectiveness of a pre-treatment snack on uptake of mass treatment.
METHODS AND FINDINGS:
In a cluster randomized trial carried out in Jinja district, Uganda, 12 primary schools were randomized into two groups; one received education messages for schistosomiasis prevention for two months prior to mass treatment, while the other, in addition to the education messages, received a pre-treatment snack shortly before mass treatment. Four weeks after mass treatment, uptake of praziquantel was assessed among a random sample of 595 children in the snack schools and 689 children in the non-snack schools as the primary outcome. The occurrence of side effects and the prevalence and mean intensity of Schistosoma mansoni infection were determined as the secondary outcomes. Uptake of praziquantel was higher in the snack schools, 93.9% (95% CI 91.7%-95.7%), compared to that in the non-snack schools, 78.7% (95% CI 75.4%-81.7%) (p = 0.002). The occurrence of side effects was lower in the snack schools, 34.4% (95% CI 31.5%-39.8%), compared to that in the non-snack schools, 46.9% (95% CI 42.2%-50.7%) (p = 0.041). Prevalence and mean intensity of S. mansoni infection was lower in the snack schools, 1.3% (95% CI 0.6%-2.6%) and 38.3 eggs per gram of stool (epg) (95% CI 21.8-67.2), compared to that in the non-snack schools, 14.1% (95% CI 11.6%-16.9%) (p = 0.001) and 78.4 epg (95% CI 60.6-101.5) (p = 0.001), respectively.
CONCLUSIONS:
Our results suggest that provision of a pre-treatment snack combined with education messages achieves a higher uptake compared to the education messages alone. The use a pre-treatment snack was associated with reduced side effects as well as decreased prevalence and intensity of S. mansoni infection. |
Fillekes, Quirine; Kendall, Lindsay; Kitaka, Sabrina; Mugyenyi, Peter; Musoke, Philippa; Ndigendawani, Milly; Bwakura-Dangarembizi, Mutsa; Gibb, Diana M.; Burger, David; nn Sarah Walker on behalf of the ARROW Trial Team, Pharmacokinetics of Zidovudine Dosed Twice Daily According to World Health Organization Weight Bands in Ugandan HIV-infected Children Journal Article In: Pediatric Infectious Diseases Journal, vol. 33, no. 5, pp. 495-8, 2014. @article{Fillekes2014,
title = {Pharmacokinetics of Zidovudine Dosed Twice Daily According to World Health Organization Weight Bands in Ugandan HIV-infected Children},
author = {Quirine Fillekes and Lindsay Kendall and Sabrina Kitaka and Peter Mugyenyi and Philippa Musoke and Milly Ndigendawani and Mutsa Bwakura-Dangarembizi and Diana M. Gibb and David Burger and nn Sarah Walker on behalf of the ARROW Trial Team},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Pharmacokinetics-of-Zidovudine-Dosed-Twice-Daily-....pdf},
doi = {10.1097/INF.0000000000000143},
year = {2014},
date = {2014-05-01},
journal = {Pediatric Infectious Diseases Journal},
volume = {33},
number = {5},
pages = {495-8},
abstract = {ata on zidovudine pharmacokinetics in children dosed using World Health Organization weight bands are limited. About 45 HIV-infected, Ugandan children, 3.4 (2.6-6.2) years, had intensive pharmacokinetic sampling. Geometric mean zidovudine AUC0-12h was 3.0 h.mg/L, which is higher than previously observed in adults, and was independently higher in those receiving higher doses, younger and underweight children. Higher exposure was also marginally associated with lower hemoglobin},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
ata on zidovudine pharmacokinetics in children dosed using World Health Organization weight bands are limited. About 45 HIV-infected, Ugandan children, 3.4 (2.6-6.2) years, had intensive pharmacokinetic sampling. Geometric mean zidovudine AUC0-12h was 3.0 h.mg/L, which is higher than previously observed in adults, and was independently higher in those receiving higher doses, younger and underweight children. Higher exposure was also marginally associated with lower hemoglobin |
Parobek, Christian M.; Jiang, Linda Y.; Patel, Jaymin C.; Alvarez-Martínez, Miriam J.; Miro, Jose M.; Worodria, William; Andama, Alfred; Fong, Serena; Huang, Laurence; Meshnick, Steven R.; Taylor, Steve M.; Juliano, Jonathan J. Multilocus Microsatellite Genotyping Array for Investigation of Genetic Epidemiology of Pneumocystis jirovecii Journal Article In: Journal of Clinical Microbiology, vol. 52, no. 5, pp. 1391-9, 2014. @article{Parobek2014,
title = {Multilocus Microsatellite Genotyping Array for Investigation of Genetic Epidemiology of Pneumocystis jirovecii},
author = {Christian M. Parobek and Linda Y. Jiang and Jaymin C. Patel and Miriam J. Alvarez-Martínez and Jose M. Miro and William Worodria and Alfred Andama and Serena Fong and Laurence Huang and Steven R. Meshnick and Steve M. Taylor and Jonathan J. Juliano},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Multilocus-Microsatellite-Genotyping-Array-for-Investigation-of-genetic-Epidimiology-of-Pneumocytis-jirovecii.pdf},
doi = {10.1128/JCM.02531-13},
year = {2014},
date = {2014-05-01},
journal = {Journal of Clinical Microbiology},
volume = {52},
number = {5},
pages = {1391-9},
abstract = {Pneumocystis jirovecii is a symbiotic respiratory fungus that causes pneumonia (PcP) in immunosuppressed patients. Because P. jirovecii cannot be reliably cultured in vitro, it has proven difficult to study and gaps in our understanding of the organism persist. The release of a draft genome for the organism opens the door for the development of new genotyping approaches for studying its molecular epidemiology and global population structure. We identified and validated 8 putatively neutral microsatellite markers and 1 microsatellite marker linked to the dihydropteroate synthase gene (dhps), the enzymatic target of sulfa drugs used for PcP prevention and treatment. Using these tools, we analyzed P. jirovecii isolates from HIV-infected patients from three geographically distant populations: Uganda, the United States, and Spain. Among the 8 neutral markers, we observed high levels of allelic heterozygosity (average He, 0.586 to 0.842). Consistent with past reports, we observed limited global population structuring, with only the Ugandan isolates showing minor differentiation from the other two populations. In Ugandan isolates that harbored mutations in dhps, the microsatellite locus linked to dhps demonstrated a depressed He, consistent with positive directional selection for sulfa resistance mutations. Using a subset of these microsatellites, analyses of individual and paired samples from infections in San Francisco, CA, showed reliable typeability within a single infection and high discriminatory power between infections. These features suggest that this novel microsatellite typing approach will be an effective tool for molecular-epidemiological investigations into P. jirovecii population structure, transmission, and drug resistance.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pneumocystis jirovecii is a symbiotic respiratory fungus that causes pneumonia (PcP) in immunosuppressed patients. Because P. jirovecii cannot be reliably cultured in vitro, it has proven difficult to study and gaps in our understanding of the organism persist. The release of a draft genome for the organism opens the door for the development of new genotyping approaches for studying its molecular epidemiology and global population structure. We identified and validated 8 putatively neutral microsatellite markers and 1 microsatellite marker linked to the dihydropteroate synthase gene (dhps), the enzymatic target of sulfa drugs used for PcP prevention and treatment. Using these tools, we analyzed P. jirovecii isolates from HIV-infected patients from three geographically distant populations: Uganda, the United States, and Spain. Among the 8 neutral markers, we observed high levels of allelic heterozygosity (average He, 0.586 to 0.842). Consistent with past reports, we observed limited global population structuring, with only the Ugandan isolates showing minor differentiation from the other two populations. In Ugandan isolates that harbored mutations in dhps, the microsatellite locus linked to dhps demonstrated a depressed He, consistent with positive directional selection for sulfa resistance mutations. Using a subset of these microsatellites, analyses of individual and paired samples from infections in San Francisco, CA, showed reliable typeability within a single infection and high discriminatory power between infections. These features suggest that this novel microsatellite typing approach will be an effective tool for molecular-epidemiological investigations into P. jirovecii population structure, transmission, and drug resistance. |
Iwai, Shoko; Huang, Delphine; Fong, Serena; Jarlsberg, Leah G.; Worodria, William; Yoo, Samuel; Cattamanchi, Adithya; Davis, J. Lucian; Kaswabuli, Sylvia; Segal, Mark; Huang, Laurence; Lynch, Susan V. The Lung Microbiome of Ugandan HIV-Infected Pneumonia Patients Is Compositionally and Functionally Distinct from That of San Franciscan Patients Journal Article In: PloS One, vol. 9, no. 4, 2014. @article{Iwai2014,
title = {The Lung Microbiome of Ugandan HIV-Infected Pneumonia Patients Is Compositionally and Functionally Distinct from That of San Franciscan Patients},
author = {Shoko Iwai and Delphine Huang and Serena Fong and Leah G. Jarlsberg and William Worodria and Samuel Yoo and Adithya Cattamanchi and J. Lucian Davis and Sylvia Kaswabuli and Mark Segal and Laurence Huang and Susan V. Lynch},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-Lung-Microbiome-of-Ugandan-HIV-Infected....pdf},
doi = {10.1371/journal.pone.0095726},
year = {2014},
date = {2014-04-21},
journal = {PloS One},
volume = {9},
number = {4},
abstract = {Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome was significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome was significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population |
Nakiwogga-Muwanga, Alice; Musaazi, Joseph; Katabira, Elly; Alamo-Talisuna, Stella; Colebunders, Robert Early Tracking after a Missed Return Visit Reduces the Proportion of Untraceable Patients at a Large HIV Clinic in Kampala, Uganda Journal Article In: Journal of the International Association of Providers of AIDS Care, vol. 15, no. 4, pp. 338-44, 2014. @article{Nakiwogga-Muwanga2014,
title = {Early Tracking after a Missed Return Visit Reduces the Proportion of Untraceable Patients at a Large HIV Clinic in Kampala, Uganda},
author = {Alice Nakiwogga-Muwanga and Joseph Musaazi and Elly Katabira and Stella Alamo-Talisuna and Robert Colebunders},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Early-Tracking-after-a-Missed-Return....-1.pdf},
doi = {10.1177/2325957414530471},
year = {2014},
date = {2014-04-09},
journal = {Journal of the International Association of Providers of AIDS Care},
volume = {15},
number = {4},
pages = {338-44},
abstract = {To determine the optimal time to track patients, we evaluated the outcomes of patients traced after missing their return visits at 3 periods, 8, 30, or 90 days, at the Infectious Diseases Clinic in Kampala, Uganda. During the study period from January to December 2011, the proportion of untraceable patients was 2 (4%) after 8 days, 12 (10%) after 30 days, and 13 (15%) after 90 days. More than 75% of the patients who died had a CD4 count of <200 cells/mm(3) at their last visit. In conclusion, tracking patients after 1 week of a missed return visit should be the preferred method of tracking. If resources are limited, patients with CD4 counts <200 cells/mm(3) need to be targeted for tracking, as they are most at risk of dying if they interrupt treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
To determine the optimal time to track patients, we evaluated the outcomes of patients traced after missing their return visits at 3 periods, 8, 30, or 90 days, at the Infectious Diseases Clinic in Kampala, Uganda. During the study period from January to December 2011, the proportion of untraceable patients was 2 (4%) after 8 days, 12 (10%) after 30 days, and 13 (15%) after 90 days. More than 75% of the patients who died had a CD4 count of <200 cells/mm(3) at their last visit. In conclusion, tracking patients after 1 week of a missed return visit should be the preferred method of tracking. If resources are limited, patients with CD4 counts <200 cells/mm(3) need to be targeted for tracking, as they are most at risk of dying if they interrupt treatment. |
Tokman, Sofya; Barnett, Christopher F.; Jarlsberg, Leah G.; Taub, Pam R.; den Boon, Saskia; Davis, J. Lucian; Cattamanchi, Adithya; Worodria, William; Maisel, Alan; Huang, Laurence; on behalf of the International HIV-associated Opportunistic Pneumonias (IHOP) Study., Procalcitonin predicts mortality in HIV-infected Ugandan adults with lower respiratory tract infections Journal Article In: Respirology, vol. 19, no. 3, pp. 382-8, 2014. @article{Tokman2014,
title = {Procalcitonin predicts mortality in HIV-infected Ugandan adults with lower respiratory tract infections},
author = {Sofya Tokman and Christopher F. Barnett and Leah G. Jarlsberg and Pam R. Taub and Saskia den Boon and J. Lucian Davis
and Adithya Cattamanchi and William Worodria and Alan Maisel and Laurence Huang and on behalf of the International HIV-associated Opportunistic
Pneumonias (IHOP) Study.},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Procalcitonin-Predicts-Mortality-in-HIV-infected-Ugandan-Adults-.pdf},
doi = { 10.1111/resp.12237},
year = {2014},
date = {2014-04-01},
journal = {Respirology},
volume = {19},
number = {3},
pages = {382-8},
abstract = {BACKGROUND AND OBJECTIVE:
In low and middle-income countries where HIV infection is prevalent, identifying patients at high risk of dying from lower respiratory tract infections is challenging and validated prognostic models are lacking. Serum procalcitonin may be a useful prognostic tool in these settings. We sought to determine if elevated serum procalcitonin is associated with increased in-hospital mortality and to combine serum procalcitonin with available clinical characteristics to create a clinically useful prognostic model.
METHODS:
We conducted a prospective, nested case-control study of 241 HIV-infected adults admitted to Mulago Hospital in Kampala, Uganda with cough ≥2 weeks in duration. We collected demographic and clinical information, baseline serum for procalcitonin analysis, and followed patients to determine in-hospital mortality.
RESULTS:
Serum procalcitonin was a strong and independent predictor of inpatient mortality (aOR = 7.69, p = 0.01, sensitivity = 93%, negative predictive value = 97%). Best subset multivariate analysis identified 3 variables that were combined into a prognostic model to risk stratify patients; these variables included respiratory rate ≥30 breaths/minute (aOR = 2.07, p = 0.11), oxygen saturation <90% (aOR = 3.07, p = 0.02), and serum procalcitonin >0.5 ng/ml (aOR = 7.69, p = 0.01). The predicted probability of inpatient mortality ranged from 1% when no variables were present, to 42% when all variables were present.
CONCLUSIONS:
Elevated serum procalcitonin >0.5 ng/ml is an independent predictor of in-hospital mortality. Elevated serum procalcitonin, tachypnea, and hypoxemia may be combined into a prognostic model to identify patients at high risk of dying in the hospital. This model may be used to estimate the probability of death and to guide triage and treatment decisions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND OBJECTIVE:
In low and middle-income countries where HIV infection is prevalent, identifying patients at high risk of dying from lower respiratory tract infections is challenging and validated prognostic models are lacking. Serum procalcitonin may be a useful prognostic tool in these settings. We sought to determine if elevated serum procalcitonin is associated with increased in-hospital mortality and to combine serum procalcitonin with available clinical characteristics to create a clinically useful prognostic model.
METHODS:
We conducted a prospective, nested case-control study of 241 HIV-infected adults admitted to Mulago Hospital in Kampala, Uganda with cough ≥2 weeks in duration. We collected demographic and clinical information, baseline serum for procalcitonin analysis, and followed patients to determine in-hospital mortality.
RESULTS:
Serum procalcitonin was a strong and independent predictor of inpatient mortality (aOR = 7.69, p = 0.01, sensitivity = 93%, negative predictive value = 97%). Best subset multivariate analysis identified 3 variables that were combined into a prognostic model to risk stratify patients; these variables included respiratory rate ≥30 breaths/minute (aOR = 2.07, p = 0.11), oxygen saturation <90% (aOR = 3.07, p = 0.02), and serum procalcitonin >0.5 ng/ml (aOR = 7.69, p = 0.01). The predicted probability of inpatient mortality ranged from 1% when no variables were present, to 42% when all variables were present.
CONCLUSIONS:
Elevated serum procalcitonin >0.5 ng/ml is an independent predictor of in-hospital mortality. Elevated serum procalcitonin, tachypnea, and hypoxemia may be combined into a prognostic model to identify patients at high risk of dying in the hospital. This model may be used to estimate the probability of death and to guide triage and treatment decisions. |
Rajasingham, Radha; Williams, Darlisha; Meya, David B.; Meintjes, Graeme; Boulware, David R.; Scriven, James Nosocomial Drug-Resistant Bacteremia in 2 Cohorts with Cryptococcal Meningitis, Africa Journal Article In: Emerging Infectious Diseases, vol. 20, no. 4, pp. 722-4, 2014. @article{Rajasingham2014b,
title = {Nosocomial Drug-Resistant Bacteremia in 2 Cohorts with Cryptococcal Meningitis, Africa},
author = {Radha Rajasingham and Darlisha Williams and David B. Meya and Graeme Meintjes and David R. Boulware and James Scriven},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Nosocomial-....pdf},
doi = {10.3201/eid2004.131277},
year = {2014},
date = {2014-04-01},
journal = {Emerging Infectious Diseases},
volume = {20},
number = {4},
pages = {722-4},
abstract = {ryptococcal meningitis is the second leading cause of AIDS-related deaths in Africa. The prolonged hospitalization necessary for optimal management may predispose severely immunocompromised persons to hospital-acquired infections. Limited data are available for sub-Saharan Africa regarding multidrug-resistant infections (1,2). We hypothesized that bacteremia was a major cause of death.
We reviewed bacteremia episodes in cryptococcal meningitis cohorts in Kampala, Uganda (n = 115 episodes) and Cape Town, South Africa (n = 72) during November 2010–April 2013. Data were obtained from the prospective cryptococcal optimal antiretroviral therapy timing trial (www.clinicaltrials.gov:NCT01075152), a randomized strategy trial assessing optimal antiretroviral therapy timing (n = 142) and another prospective observational cohort in Cape Town (n = 45).
We enrolled HIV-infected adults who had a first episode of cryptococcal meningitis diagnosed by cerebrospinal fluid culture or cryptococcal antigen testing. Standardized treatment was in accordance with World Health Organization (WHO) guidelines: amphotericin deoxycholate, 0.7–1.0 mg/kg/d for 14 days, and fluconazole, 800 mg/d, requiring a minimum 14-day hospitalization (3). Each person provided written informed consent. Institutional review board approval was obtained.
Blood cultures were obtained in accordance with physician discretion, typically with new onset fever (>38°C) unrelated to amphotericin. Two aerobic blood cultures were obtained from 1 peripheral site and not from central catheters. BACTEC (Becton Dickinson, Franklin Lakes, NJ, USA) or BacT/ALERT (BioMérieux, Durham, NC, USA) bottles were incubated at 37°C in automated instruments for 5 days. Drugs were given empirically at physician discretion and adjusted after culture/susceptibility results were obtained.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
ryptococcal meningitis is the second leading cause of AIDS-related deaths in Africa. The prolonged hospitalization necessary for optimal management may predispose severely immunocompromised persons to hospital-acquired infections. Limited data are available for sub-Saharan Africa regarding multidrug-resistant infections (1,2). We hypothesized that bacteremia was a major cause of death.
We reviewed bacteremia episodes in cryptococcal meningitis cohorts in Kampala, Uganda (n = 115 episodes) and Cape Town, South Africa (n = 72) during November 2010–April 2013. Data were obtained from the prospective cryptococcal optimal antiretroviral therapy timing trial (www.clinicaltrials.gov:NCT01075152), a randomized strategy trial assessing optimal antiretroviral therapy timing (n = 142) and another prospective observational cohort in Cape Town (n = 45).
We enrolled HIV-infected adults who had a first episode of cryptococcal meningitis diagnosed by cerebrospinal fluid culture or cryptococcal antigen testing. Standardized treatment was in accordance with World Health Organization (WHO) guidelines: amphotericin deoxycholate, 0.7–1.0 mg/kg/d for 14 days, and fluconazole, 800 mg/d, requiring a minimum 14-day hospitalization (3). Each person provided written informed consent. Institutional review board approval was obtained.
Blood cultures were obtained in accordance with physician discretion, typically with new onset fever (>38°C) unrelated to amphotericin. Two aerobic blood cultures were obtained from 1 peripheral site and not from central catheters. BACTEC (Becton Dickinson, Franklin Lakes, NJ, USA) or BacT/ALERT (BioMérieux, Durham, NC, USA) bottles were incubated at 37°C in automated instruments for 5 days. Drugs were given empirically at physician discretion and adjusted after culture/susceptibility results were obtained. |
Shah, Maunank; Ssengooba, Willy; Armstrong, Derek; Holshouser, Lydia Nakiyingi Molly; Ellner, Jerrold J.; Joloba, Moses; andSusan E. Dorman, Yukari C. Manabe Comparative performance of urinary lipoarabinomannan assays and Xpert MTB/RIF in HIV-infected individuals with suspected tuberculosis in Uganda Journal Article In: AIDS (London, England), vol. 28, no. 9, pp. 1307-1314, 2014. @article{Shah2014b,
title = {Comparative performance of urinary lipoarabinomannan assays and Xpert MTB/RIF in HIV-infected individuals with suspected tuberculosis in Uganda},
author = {Maunank Shah and Willy Ssengooba and Derek Armstrong and Lydia Nakiyingi Molly Holshouser and Jerrold J. Ellner and Moses Joloba and Yukari C. Manabe andSusan E. Dorman
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Comparative-performance-of-urinary-lipoarabinomannan-assays...in-uganda.pdf},
doi = {10.1097/QAD.0000000000000264 },
year = {2014},
date = {2014-03-15},
journal = {AIDS (London, England)},
volume = {28},
number = {9},
pages = {1307-1314},
abstract = {Background—
Xpert MTB/RIF (‘Xpert’) and urinary lipoarabinomannan (LAM) assays offer
rapid tuberculosis (TB) diagnosis, but have suboptimal sensitivity when used individually in HIV-
positive patients. The yield of these tests used in combination for the diagnosis of active TB
among HIV-infected TB suspects is unknown.
Design—
Study of comparative diagnostic accuracy nested into a prospective study of HIV-
infected individuals with signs and/or symptoms of TB in Uganda.
Methods—
Xpert testing of archived sputum was conducted for culture-confirmed TB cases and
TB suspects in whom a diagnosis of TB was excluded. Additional testing included sputum smear
microscopy, sputum culture (solid and liquid media), mycobacterial blood culture, and urinary
testing for LAM using a lateral flow test (‘LF-LAM’) and an enzyme-linked immunosorbance
assay (‘ELISA-LAM’).
Results—
Among 103 participants with culture-confirmed TB, sensitivity of Xpert was 76%
(95% confidence interval, CI 0.66–0.84), and was superior to that of LF-LAM (49%, 95% CI
0.39–0.59,
P
<0.001). Specificity was greater than 97% for both tests among 105 individuals
without TB. The combination of smear microscopy and LF-LAM identified 67% (95% CI 0.57–
0.76) of culture-confirmed TB cases and approached sensitivity of Xpert testing alone (
P
=0.15).
The sensitivity of the combination of Xpert and LF-LAM was 85% (88/103 95% CI 0.77–0.92),
which was superior to either test alone (
P
<0.05) and approached sensitivity of sputum liquid
culture testing (94%, 95% CI 0.88–0.98,
P
=0.17)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background—
Xpert MTB/RIF (‘Xpert’) and urinary lipoarabinomannan (LAM) assays offer
rapid tuberculosis (TB) diagnosis, but have suboptimal sensitivity when used individually in HIV-
positive patients. The yield of these tests used in combination for the diagnosis of active TB
among HIV-infected TB suspects is unknown.
Design—
Study of comparative diagnostic accuracy nested into a prospective study of HIV-
infected individuals with signs and/or symptoms of TB in Uganda.
Methods—
Xpert testing of archived sputum was conducted for culture-confirmed TB cases and
TB suspects in whom a diagnosis of TB was excluded. Additional testing included sputum smear
microscopy, sputum culture (solid and liquid media), mycobacterial blood culture, and urinary
testing for LAM using a lateral flow test (‘LF-LAM’) and an enzyme-linked immunosorbance
assay (‘ELISA-LAM’).
Results—
Among 103 participants with culture-confirmed TB, sensitivity of Xpert was 76%
(95% confidence interval, CI 0.66–0.84), and was superior to that of LF-LAM (49%, 95% CI
0.39–0.59,
P
<0.001). Specificity was greater than 97% for both tests among 105 individuals
without TB. The combination of smear microscopy and LF-LAM identified 67% (95% CI 0.57–
0.76) of culture-confirmed TB cases and approached sensitivity of Xpert testing alone (
P
=0.15).
The sensitivity of the combination of Xpert and LF-LAM was 85% (88/103 95% CI 0.77–0.92),
which was superior to either test alone (
P
<0.05) and approached sensitivity of sputum liquid
culture testing (94%, 95% CI 0.88–0.98,
P
=0.17) |
Kityo, Cissy; Gibb, Diana M.; Gilks, Charles F.; Goodall, Ruth L.; Mambule, Ivan; Kaleebu, Pontiano; Pillay, Deenan; Kasirye, Ronnie; Mugyenyi, Peter; Walker, A. Sarah; Dunn, David T.; on behalf of the DART Trial Team, High Level of Viral Suppression and Low Switch Rate to Second-Line Antiretroviral Therapy among HIV-Infected Adult Patients Followed over Five Years: Retrospective Analysis of the DART Trial Journal Article In: PloS One, vol. 9, no. 3, 2014. @article{Kityo2014,
title = {High Level of Viral Suppression and Low Switch Rate to Second-Line Antiretroviral Therapy among HIV-Infected Adult Patients Followed over Five Years: Retrospective Analysis of the DART Trial},
author = {Cissy Kityo and Diana M. Gibb and Charles F. Gilks and Ruth L. Goodall and Ivan Mambule and Pontiano Kaleebu and
Deenan Pillay and Ronnie Kasirye and Peter Mugyenyi and A. Sarah Walker and David T. Dunn and on behalf of the
DART Trial Team},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/High-Level-of-Viral-Suppression-and-Low-Switch-Rate...Retrospective-Analysis-of-the-DART-Trail.pdf},
doi = {10.1371/journal.pone.0090772},
year = {2014},
date = {2014-03-13},
journal = {PloS One},
volume = {9},
number = {3},
abstract = {In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without
virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line
antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM) versus routine laboratory (CD4/
haematology/biochemistry) and clinical monitoring (LCM) in HIV-infected adults initiating therapy. There was no virological
monitoring in either study group during follow-up, but viral load was measured in Ugandan participants at trial closure. Two
thousand three hundred and seventeen (2317) participants from this country initiated antiretroviral therapy with
zidovudine/lamivudine plus tenofovir (n = 1717), abacavir (n = 300), or nevirapine (n = 300). Of 1896 (81.8%) participants who
were alive and in follow-up at trial closure (median 5.1 years after therapy initiation), 1507 (79.5%) were on first-line and 389
(20.5%) on second-line antiretroviral therapy. The overall switch rate after the first year was 5.6 per 100 person-years; the
rate was substantially higher in participants with low baseline CD4 counts (
,
50 cells/mm
3
). Among 1207 (80.1%) first-line
participants with viral load measured, HIV RNA was
,
400 copies/ml in 963 (79.8%), 400–999 copies/ml in 37 (3.1%), 1,000–
9,999 copies/ml in 110 (9.1%), and
$
10,000 copies/ml in 97 (8.0%). The proportion with HIV RNA
,
400 copies/ml was
slightly lower (difference 7.1%, 95% CI 2.5 to 11.5%) in CDM (76.3%) than in LCM (83.4%). Among 252 (64.8%) second-line
participants with viral load measured (median 2.3 years after switch), HIV RNA was
,
400 copies/ml in 226 (89.7%), with no
difference between monitoring strategies. Low switch rates and high, sustained levels of viral suppression are achievable
without viral load or CD4 count monitoring in the context of high-quality clinical care},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without
virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line
antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM) versus routine laboratory (CD4/
haematology/biochemistry) and clinical monitoring (LCM) in HIV-infected adults initiating therapy. There was no virological
monitoring in either study group during follow-up, but viral load was measured in Ugandan participants at trial closure. Two
thousand three hundred and seventeen (2317) participants from this country initiated antiretroviral therapy with
zidovudine/lamivudine plus tenofovir (n = 1717), abacavir (n = 300), or nevirapine (n = 300). Of 1896 (81.8%) participants who
were alive and in follow-up at trial closure (median 5.1 years after therapy initiation), 1507 (79.5%) were on first-line and 389
(20.5%) on second-line antiretroviral therapy. The overall switch rate after the first year was 5.6 per 100 person-years; the
rate was substantially higher in participants with low baseline CD4 counts (
,
50 cells/mm
3
). Among 1207 (80.1%) first-line
participants with viral load measured, HIV RNA was
,
400 copies/ml in 963 (79.8%), 400–999 copies/ml in 37 (3.1%), 1,000–
9,999 copies/ml in 110 (9.1%), and
$
10,000 copies/ml in 97 (8.0%). The proportion with HIV RNA
,
400 copies/ml was
slightly lower (difference 7.1%, 95% CI 2.5 to 11.5%) in CDM (76.3%) than in LCM (83.4%). Among 252 (64.8%) second-line
participants with viral load measured (median 2.3 years after switch), HIV RNA was
,
400 copies/ml in 226 (89.7%), with no
difference between monitoring strategies. Low switch rates and high, sustained levels of viral suppression are achievable
without viral load or CD4 count monitoring in the context of high-quality clinical care |
Kirenga, Bruce J.; Levin, Jonathan; Ayakaka, Irene; Worodria, William; Reil, Nancy; Mumbowa, Francis; Nabanjja, Helen; Nyakoojo, Grace; Fennelly, Kevin; Nakubulwa, Susan; Joloba, Moses; Okwera, Alphonse; Eisenach, Kathleen D.; McNerney, Ruth; Elliott, Alison M.; Mugerwa, Roy D.; Smith, Peter G.; Ellner, Jerrold J.; Jones-Lopez, Edward C. Treatment Outcomes of New Tuberculosis Patients Hospitalized in Kampala, Uganda: A Prospective Cohort Study Journal Article In: PloS One, vol. 9, no. 3, 2014. @article{Kirenga2014,
title = {Treatment Outcomes of New Tuberculosis Patients Hospitalized in Kampala, Uganda: A Prospective Cohort Study},
author = {Bruce J. Kirenga and Jonathan Levin and Irene Ayakaka and William Worodria and Nancy Reil and Francis Mumbowa and Helen Nabanjja and Grace Nyakoojo and Kevin Fennelly and Susan Nakubulwa and Moses Joloba and Alphonse Okwera and Kathleen D. Eisenach and Ruth McNerney and Alison M. Elliott and Roy D. Mugerwa and Peter G. Smith and Jerrold J. Ellner and Edward C. Jones-Lopez
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Treatment-Outcomes-of-New-Tuberculosis-Patients-Hospital-in-Kampala-Uganda.pdf},
doi = {10.1371/journal.pone.0090614},
year = {2014},
date = {2014-03-07},
journal = {PloS One},
volume = {9},
number = {3},
abstract = {BACKGROUND:
In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda.
METHODS AND FINDINGS:
Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045).
CONCLUSION:
Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda.
METHODS AND FINDINGS:
Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045).
CONCLUSION:
Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART. |
Brown, Gordon D.; Meintjes, Graeme; Kolls, Jay K.; Gray, Clive; Horsnell, William AIDS-related mycoses: the way forward Journal Article In: Trends in Microbiology, vol. 22, no. 3, pp. 107-9, 2014. @article{Brown2014,
title = {AIDS-related mycoses: the way forward},
author = {Gordon D. Brown and Graeme Meintjes and Jay K. Kolls and Clive Gray and William Horsnell
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/HIV-Associated-Anemia-After-96-Weeks-on-Therapy...-1.pdf},
doi = {10.1016/j.tim.2013.12.008},
year = {2014},
date = {2014-03-01},
journal = {Trends in Microbiology},
volume = {22},
number = {3},
pages = {107-9},
abstract = {The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is
largely unrecognized. A recent meeting highlighted several priorities that need to be urgently
addressed, including improved epidemiological surveillance, increased availability of existing
diagnostics and drugs, more training in the field of medical mycology, and better funding for
research and provision of treatment, particularly in developing countries.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is
largely unrecognized. A recent meeting highlighted several priorities that need to be urgently
addressed, including improved epidemiological surveillance, increased availability of existing
diagnostics and drugs, more training in the field of medical mycology, and better funding for
research and provision of treatment, particularly in developing countries. |
Marcia R. Weaver Arianna Rubin Means, Sarah M. Burnett Correlates of Inappropriate Prescribing of Antibiotics to Patients with Malaria in Uganda Journal Article In: PLOS ONE, vol. 9, no. 2, pp. e90179, 2014. @article{Means2014,
title = {Correlates of Inappropriate Prescribing of Antibiotics to Patients with Malaria in Uganda},
author = {Arianna Rubin Means, Marcia R. Weaver, Sarah M. Burnett, Martin K. Mbonye, Sarah Naikoba, R. Scott McClelland},
doi = {https://doi.org/10.1371/journal.pone.0090179},
year = {2014},
date = {2014-02-28},
journal = {PLOS ONE},
volume = {9},
number = {2},
pages = {e90179},
abstract = {Background
In many rural areas of Uganda, febrile patients presenting to health facilities are prescribed both antimalarials and antibiotics, contributing to the overuse of antibiotics. We identified the prevalence and correlates of inappropriate antibiotic management of patients with confirmed malaria.
Methods
We utilized individual outpatient data from 36 health centers from January to September 2011. We identified patients who were prescribed antibiotics without an appropriate clinical indication, as well as patients who were not prescribed antibiotics when treatment was clinically indicated. Multivariate logistic regression models were used to identify clinical and operational factors associated with inappropriate case management.
Findings
Of the 45,591 patients with parasitological diagnosis of malaria, 40,870 (90%) did not have a clinical indication for antibiotic treatment. Within this group, 17,152 (42%) were inappropriately prescribed antibiotics. The odds of inappropriate prescribing were higher if the patient was less than five years old (aOR 1.96, 95% CI 1.75–2.19) and if the health provider had the fewest years of training (aOR 1.86, 95% CI 1.05–3.29). The odds of inappropriate prescribing were lower if patients had emergency triage status (aOR 0.75, 95% CI 0.59–0.96) or were HIV positive (aOR 0.31, 95% CI 0.20–0.45). Of the 4,721 (10%) patients with clinical indications for antibiotic treatment, 521 (11%) were inappropriately not prescribed antibiotics. Clinical officers were less likely than medical officers to inappropriately withhold antibiotics (aOR 0.54, 95% CI 0.29–0.98).
Conclusion
Over 40% of the antibiotic treatment in malaria positive patients is prescribed despite a lack of documented clinical indication. In addition, over 10% of patients with malaria and a clinical indication for antibiotics do not receive them. These findings should inform facility-level trainings and interventions to optimize patient care and slow trends of rising antibiotic resistance.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
In many rural areas of Uganda, febrile patients presenting to health facilities are prescribed both antimalarials and antibiotics, contributing to the overuse of antibiotics. We identified the prevalence and correlates of inappropriate antibiotic management of patients with confirmed malaria.
Methods
We utilized individual outpatient data from 36 health centers from January to September 2011. We identified patients who were prescribed antibiotics without an appropriate clinical indication, as well as patients who were not prescribed antibiotics when treatment was clinically indicated. Multivariate logistic regression models were used to identify clinical and operational factors associated with inappropriate case management.
Findings
Of the 45,591 patients with parasitological diagnosis of malaria, 40,870 (90%) did not have a clinical indication for antibiotic treatment. Within this group, 17,152 (42%) were inappropriately prescribed antibiotics. The odds of inappropriate prescribing were higher if the patient was less than five years old (aOR 1.96, 95% CI 1.75–2.19) and if the health provider had the fewest years of training (aOR 1.86, 95% CI 1.05–3.29). The odds of inappropriate prescribing were lower if patients had emergency triage status (aOR 0.75, 95% CI 0.59–0.96) or were HIV positive (aOR 0.31, 95% CI 0.20–0.45). Of the 4,721 (10%) patients with clinical indications for antibiotic treatment, 521 (11%) were inappropriately not prescribed antibiotics. Clinical officers were less likely than medical officers to inappropriately withhold antibiotics (aOR 0.54, 95% CI 0.29–0.98).
Conclusion
Over 40% of the antibiotic treatment in malaria positive patients is prescribed despite a lack of documented clinical indication. In addition, over 10% of patients with malaria and a clinical indication for antibiotics do not receive them. These findings should inform facility-level trainings and interventions to optimize patient care and slow trends of rising antibiotic resistance.
|
Woodd, Susannah L.; Grosskurth, Heiner; Levin, Jonathan; Amuron, Barbara; Namara, Geoffrey; Birunghi, Josephine; Coutinho, Alex; Jaffar, Shabbar Home-based versus clinic-based care for patients starting antiretroviral therapy with low CD4+ cell counts: findings from a cluster-randomized trial Journal Article In: AIDS (London, England), vol. 28, no. 4, pp. 569-76, 2014. @article{Woodd2014,
title = {Home-based versus clinic-based care for patients starting antiretroviral therapy with low CD4+ cell counts: findings from a cluster-randomized trial},
author = {Susannah L. Woodd and Heiner Grosskurth and Jonathan Levin and Barbara Amuron and Geoffrey Namara and Josephine Birunghi and Alex Coutinho and Shabbar Jaffar},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Home-based-versus-clinic-based-care-for-patients-starting-antiretroviral-therapy-with-ow-CD4-cell-count.pdf},
doi = {10.1097/QAD.0000000000000056},
year = {2014},
date = {2014-02-20},
journal = {AIDS (London, England)},
volume = {28},
number = {4},
pages = {569-76},
abstract = {OBJECTIVES:
African health services have shortages of clinical staff. We showed previously, in a cluster-randomized trial, that a home-based strategy using trained lay-workers is as effective as a clinic-based strategy. It is not known whether home-based care is suitable for patients with advanced HIV disease.
METHODS:
The trial was conducted in Jinja, Uganda. One thousand, four hundred and fifty-three adults initiating ART between February 2005 and January 2009 were randomized to receive either home-based care or routine clinic-based care, and followed up for about 3 years. Trained lay workers, supervised by clinical staff based in a clinic, delivered the home-based care. In this sub-analysis, we compared survival between the two strategies for those who presented with CD4⁺ cell count less than 50 cells/μl and those who presented with higher CD4⁺ cell counts. We used Kaplan-Meier methods and Poisson regression.
RESULTS:
Four hundred and forty four of 1453 (31%) participants had baseline CD4⁺ cell count less than 50 cells/μl. Overall, 110 (25%) deaths occurred among participants with baseline CD4⁺ cell count less than 50 cells/μl and 87 (9%) in those with higher CD4⁺ cell count. Among participants with CD4 cell count less than 50 cells/μl, mortality rates were similar for the home and facility-based arms; adjusted mortality rate ratio 0.80 [95% confidence interval (CI) 0.53-1.18] compared with 1.22 (95% CI 0.78-1.89) for those who presented with higher CD4⁺ cell count.
CONCLUSION:
HIV home-based care, with lay workers playing a major role in the delivery of care including providing monthly adherence support, leads to similar survival rates as clinic-based care even among patients who present with very low CD4⁺ cell count. This emphasises the critical role of adherence to antiretroviral therapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES:
African health services have shortages of clinical staff. We showed previously, in a cluster-randomized trial, that a home-based strategy using trained lay-workers is as effective as a clinic-based strategy. It is not known whether home-based care is suitable for patients with advanced HIV disease.
METHODS:
The trial was conducted in Jinja, Uganda. One thousand, four hundred and fifty-three adults initiating ART between February 2005 and January 2009 were randomized to receive either home-based care or routine clinic-based care, and followed up for about 3 years. Trained lay workers, supervised by clinical staff based in a clinic, delivered the home-based care. In this sub-analysis, we compared survival between the two strategies for those who presented with CD4⁺ cell count less than 50 cells/μl and those who presented with higher CD4⁺ cell counts. We used Kaplan-Meier methods and Poisson regression.
RESULTS:
Four hundred and forty four of 1453 (31%) participants had baseline CD4⁺ cell count less than 50 cells/μl. Overall, 110 (25%) deaths occurred among participants with baseline CD4⁺ cell count less than 50 cells/μl and 87 (9%) in those with higher CD4⁺ cell count. Among participants with CD4 cell count less than 50 cells/μl, mortality rates were similar for the home and facility-based arms; adjusted mortality rate ratio 0.80 [95% confidence interval (CI) 0.53-1.18] compared with 1.22 (95% CI 0.78-1.89) for those who presented with higher CD4⁺ cell count.
CONCLUSION:
HIV home-based care, with lay workers playing a major role in the delivery of care including providing monthly adherence support, leads to similar survival rates as clinic-based care even among patients who present with very low CD4⁺ cell count. This emphasises the critical role of adherence to antiretroviral therapy. |
Aujo, Judith Caroline; Bakeera-Kitaka, Sabrina; Kiguli, Sarah; Mirembe, Florence No difference in sexual behavior of adolescent girls following Human Papilloma Virus vaccination: a case study two districts in Uganda; Nakasongola and Luwero Journal Article In: BMC Public Health, vol. 15, no. 1, 2014. @article{Aujo2014,
title = {No difference in sexual behavior of adolescent girls following Human Papilloma Virus vaccination: a case study two districts in Uganda; Nakasongola and Luwero},
author = {Judith Caroline Aujo and Sabrina Bakeera-Kitaka and Sarah Kiguli and Florence Mirembe},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/No-difference-in-sexual-behavior-...-Nakasongola-and-Luwero.pdf},
doi = {10.1186/1471-2458-14-155},
year = {2014},
date = {2014-02-12},
journal = {BMC Public Health},
volume = {15},
number = {1},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Bayigga, Lois; Sekiziyivu, Rose Nabatanzi Prossy Naluyima; Mayanja-Kizza, Harriet; Kamya, Moses R; Kambugu, Andrew; Olobo, Joseph; Kiragga, Agnes; Kirimunda, Sam; Joloba, Moses; Nakanjako, Damalie High CD56 ++ CD16 - natural killer (NK) cells among suboptimal immune responders after four years of suppressive antiretroviral therapy in an African adult HIV treatment cohort Journal Article In: BMC Immunology, vol. 15, 2014. @article{Bayigga2014,
title = {High CD56 ++ CD16 - natural killer (NK) cells among suboptimal immune responders after four years of suppressive antiretroviral therapy in an African adult HIV treatment cohort},
author = {Lois Bayigga and Rose Nabatanzi Prossy Naluyima Sekiziyivu and Harriet Mayanja-Kizza and Moses R Kamya and Andrew Kambugu and Joseph Olobo and Agnes Kiragga and Sam Kirimunda and Moses Joloba and Damalie Nakanjako
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/High-CD56CD16-natural-killer-cell-among-suboptimal-immune-responders-....pdf},
doi = {10.1186/1471-2172-15-2.},
year = {2014},
date = {2014-01-31},
journal = {BMC Immunology},
volume = {15},
abstract = {BACKGROUND:
Up to 40% of HIV-infected individuals receiving Highly Active Antiretroviral Therapy (HAART) have poor CD4+ T-cell recovery. The role of natural killer (NK) cells in immune recovery during HAART is not well understood. We described the profiles of NK cell subsets and their expression of activating receptor, NKG2D and cytotoxicity receptor NKp46 among suboptimal immune responders to despite four years of suppressive HAART.
METHODS:
A case control study utilized frozen peripheral blood mononuclear cells (PBMC) from a cohort of HIV-infected adults that initiated HAART in 2004/5, at CD4 < 200 cells/μl. Cases were 'suboptimal' responders; patients within the lowest quartile of CD4+ T-cell reconstitution, with a median CD4 count increase of 129 (-43-199) cells/μl (difference between CD4 count at baseline and after 4 years of HAART) and controls were 'super-optimal' responders; patients within the highest quartile of CD4 T-cell reconstitution with a median CD4 count increase of 528 (416-878) cells/μl). Expression of NK cell lineage markers (CD56+/-CD16+/-) and receptors NKG2D and NKp46, was measured among PBMC from 29 cases of 'suboptimal' responders' and 23 controls of 'super-optimal responders', and compared among 'suboptimal' and 'super-optimal' responders. NK cell populations were compared using the Holm Sidak multiple comparison test and p values < 0.05 were considered statistically significant. Data was analyzed using FLOWJO and GraphPad Prism 6.
RESULTS:
'Suboptimal responders' had a higher proportion of cytokine producing CD56(++)CD16(+/-) (CD56bri) NK cells than the 'super-optimal responders' p = 0.017, and CD56(neg) NK cells were lower among suboptimal than super-optimal responders (p = 0.007). The largest NK cell subset, CD56(dim), was comparable among suboptimal responders and 'super-optimal immune responders'. Expression of NKG2D and NKp46 receptors on NK cell subsets (CD56(bri), CD56(neg) and CD56(dim)), was comparable among 'suboptimal' and 'super-optimal' immune responders.
CONCLUSIONS:
The pro-inflammatory CD56++CD16-- NK cells were higher among 'suboptimal' responders relative to 'super-optimal' responders, despite four years of suppressive HAART. Alteration of NK cell populations could inhibit host immune responses to infections among suboptimal responders. We recommend further analysis of NK cell function among suboptimal immune responders in order to inform targeted interventions to optimize immune recovery among HAART-treated adults},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Up to 40% of HIV-infected individuals receiving Highly Active Antiretroviral Therapy (HAART) have poor CD4+ T-cell recovery. The role of natural killer (NK) cells in immune recovery during HAART is not well understood. We described the profiles of NK cell subsets and their expression of activating receptor, NKG2D and cytotoxicity receptor NKp46 among suboptimal immune responders to despite four years of suppressive HAART.
METHODS:
A case control study utilized frozen peripheral blood mononuclear cells (PBMC) from a cohort of HIV-infected adults that initiated HAART in 2004/5, at CD4 < 200 cells/μl. Cases were 'suboptimal' responders; patients within the lowest quartile of CD4+ T-cell reconstitution, with a median CD4 count increase of 129 (-43-199) cells/μl (difference between CD4 count at baseline and after 4 years of HAART) and controls were 'super-optimal' responders; patients within the highest quartile of CD4 T-cell reconstitution with a median CD4 count increase of 528 (416-878) cells/μl). Expression of NK cell lineage markers (CD56+/-CD16+/-) and receptors NKG2D and NKp46, was measured among PBMC from 29 cases of 'suboptimal' responders' and 23 controls of 'super-optimal responders', and compared among 'suboptimal' and 'super-optimal' responders. NK cell populations were compared using the Holm Sidak multiple comparison test and p values < 0.05 were considered statistically significant. Data was analyzed using FLOWJO and GraphPad Prism 6.
RESULTS:
'Suboptimal responders' had a higher proportion of cytokine producing CD56(++)CD16(+/-) (CD56bri) NK cells than the 'super-optimal responders' p = 0.017, and CD56(neg) NK cells were lower among suboptimal than super-optimal responders (p = 0.007). The largest NK cell subset, CD56(dim), was comparable among suboptimal responders and 'super-optimal immune responders'. Expression of NKG2D and NKp46 receptors on NK cell subsets (CD56(bri), CD56(neg) and CD56(dim)), was comparable among 'suboptimal' and 'super-optimal' immune responders.
CONCLUSIONS:
The pro-inflammatory CD56++CD16-- NK cells were higher among 'suboptimal' responders relative to 'super-optimal' responders, despite four years of suppressive HAART. Alteration of NK cell populations could inhibit host immune responses to infections among suboptimal responders. We recommend further analysis of NK cell function among suboptimal immune responders in order to inform targeted interventions to optimize immune recovery among HAART-treated adults |
Galukande, Moses; Duffy, Kevin; Bitega, Jean Paul; Rackara, Sam; Bbaale, Denis Sekavuga; Nakaggwa, Florence; Nagaddya, Teddy; Wooding, Nick; Dea, Monica; Coutinho, Alex Adverse Events Profile of PrePex a Non-Surgical Device for Adult Male Circumcision in a Ugandan Urban Setting Journal Article In: PloS One, vol. 9, no. 1, 2014. @article{Galukande2014b,
title = {Adverse Events Profile of PrePex a Non-Surgical Device for Adult Male Circumcision in a Ugandan Urban Setting},
author = {Moses Galukande and Kevin Duffy and Jean Paul Bitega and Sam Rackara and Denis Sekavuga Bbaale and Florence Nakaggwa and Teddy Nagaddya and Nick Wooding and Monica Dea and Alex Coutinho
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Adverse-Events-Profile-of-PrePex-a-Non-Surgical-Device-for-Adult-male-circumcision-in-a-Ugandan-Urban-Setting-.pdf},
doi = {10.1371/journal.pone.0086631},
year = {2014},
date = {2014-01-28},
journal = {PloS One},
volume = {9},
number = {1},
abstract = {Background:
Safe Male Circumcision is a proven approach for partial HIV prevention. Several sub Saharan African countries
have plans to reach a prevalence of 80% of their adult males circumcised by 2015. These targets require out of ordinary
organization, demand creation, timely execution and perhaps the use of SMC devices.
Objective:
To profile Adverse Events rate and acceptance of PrePex, a non surgical device for adult male circumcision.
Methods:
A prospective study, conducted at International Hospital Kampala, Uganda, between August and October 2012.
Ethical approval was obtained from Uganda National Council of Science and Technology.
Results:
Of 1,040 men received to undergo SMC, 678 opted for PrePex, 36 were excluded at an initial physical examination
screening. 642 were enrolled and consented, and another 17 were excluded before device placement. 625 underwent the
procedure. Average age was 24 years (
6
7). Twelve moderate AEs occurred among 10 participants 12/625, (1.9%). These
were all reversible. Five had device displacement, one had an everted foreskin; five had bleeding after the device was
removed and one had voiding difficulties. The majority (279 out of 300) of men interviewed complained of some pain within
the week of placement. Mean pain score at device placement (using visual analogue scale) was 0.5, at device removal 4.5
and within 2 min of removal the pain score was 1.4. Over 70% of the devices were placed and removed by non-physician
clinicians. Presented with a choice, 60% of men chose PrePex over surgical SMC. Close to 90% would recommend the device
to their friends. Odour from the necrotic skin was a concern. Removals done 1–2 days earlier than day 7 were beneficial and
conferred no extra risk.
Conclusion:
AEs of a moderate or severe nature associated with PrePex were low and reversible. PrePex is feasible for mass
safe male circumcision scaling up},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background:
Safe Male Circumcision is a proven approach for partial HIV prevention. Several sub Saharan African countries
have plans to reach a prevalence of 80% of their adult males circumcised by 2015. These targets require out of ordinary
organization, demand creation, timely execution and perhaps the use of SMC devices.
Objective:
To profile Adverse Events rate and acceptance of PrePex, a non surgical device for adult male circumcision.
Methods:
A prospective study, conducted at International Hospital Kampala, Uganda, between August and October 2012.
Ethical approval was obtained from Uganda National Council of Science and Technology.
Results:
Of 1,040 men received to undergo SMC, 678 opted for PrePex, 36 were excluded at an initial physical examination
screening. 642 were enrolled and consented, and another 17 were excluded before device placement. 625 underwent the
procedure. Average age was 24 years (
6
7). Twelve moderate AEs occurred among 10 participants 12/625, (1.9%). These
were all reversible. Five had device displacement, one had an everted foreskin; five had bleeding after the device was
removed and one had voiding difficulties. The majority (279 out of 300) of men interviewed complained of some pain within
the week of placement. Mean pain score at device placement (using visual analogue scale) was 0.5, at device removal 4.5
and within 2 min of removal the pain score was 1.4. Over 70% of the devices were placed and removed by non-physician
clinicians. Presented with a choice, 60% of men chose PrePex over surgical SMC. Close to 90% would recommend the device
to their friends. Odour from the necrotic skin was a concern. Removals done 1–2 days earlier than day 7 were beneficial and
conferred no extra risk.
Conclusion:
AEs of a moderate or severe nature associated with PrePex were low and reversible. PrePex is feasible for mass
safe male circumcision scaling up |
Kaadaaga, Henry Francisco; JudithAjeani,; Ononge, Sam; Alele, Paul E; Nakasujja, Noeline; YukariCManabe,; Kakaire, Othman Prevalence and factors associated with use of herbal medicine among women attending an infertility clinic in Uganda Journal Article In: BMC Complementary and Alternative Medicine, vol. 14, 2014. @article{Kaadaaga2014,
title = {Prevalence and factors associated with use of herbal medicine among women attending an infertility clinic in Uganda},
author = {Henry Francisco Kaadaaga and JudithAjeani and Sam Ononge and Paul E Alele and Noeline Nakasujja and YukariCManabe and Othman Kakaire},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Prevalence-and-factors-associated-with-use-of-herbal-medicine-among-women-attending-an-infertility-clinic-in-Uganda.pdf},
doi = {10.1186/1472-6882-14-27},
year = {2014},
date = {2014-01-16},
journal = {BMC Complementary and Alternative Medicine},
volume = {14},
abstract = {BACKGROUND:
Infertility is a public health problem associated with devastating psychosocial consequences. In countries where infertility care is difficult to access, women turn to herbal medicines to achieve parenthood. The aim of this study was to determine the prevalence and factors associated with herbal medicine use by women attending the infertility clinic.
METHODS:
This was a cross-sectional study of 260 women attending the infertility clinic at Mulago hospital. The interviewer administered questionnaire comprised socio-demographic characteristics, infertility-related aspects and information on herbal medicine use. The main outcome measure was herbal medicines use for infertility treatment. Determinants of herbal medicine use were assessed using multivariable logistic regression.
RESULTS:
The majority (76.2%) of respondents had used herbal medicines for infertility treatment. The mean age of the participants was 28.3 years ± 5.5. Over 80% were married, 59.6% had secondary infertility and 2/3 of the married participants were in monogamous unions. In a multivariable model, the variables that were independently associated with increased use of herbal medicine among infertile patients were being married (OR 2.55, CI 1.24-5.24), never conceived (OR 4.08 CI 1.86-8.96) and infertility for less than 3 years (OR 3.52 CI 1.51-8.821). Factors that were associated with less use of herbal medicine among infertile women were being aged 30 years or less (OR 0.18 CI 0.07-0.46), primary and no education (OR 0.12 CI 0.05-0.46) and living with partner for less than three years (OR 0.39 CI 0.16-0.93).
CONCLUSIONS:
The prevalence of herbal medicine use among women attending the infertility clinic was 76.2%. Herbal medicine use was associated with the participants' age, level of education, marital status, infertility duration, nulliparity, and duration of marriage. Medical care was often delayed and the majority of the participants did not disclose use of herbal medicines to the attending physician. Health professionals should enquire about use of herbal medicines. This may help in educating the patients about the health risks of using herbal medicine and may reduce delays in seeking appropriate care. Collaboration of health professionals with herbal medicine practitioners would help identify the common herbal medicines used for infertility treatment, their potential benefits and harm.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Infertility is a public health problem associated with devastating psychosocial consequences. In countries where infertility care is difficult to access, women turn to herbal medicines to achieve parenthood. The aim of this study was to determine the prevalence and factors associated with herbal medicine use by women attending the infertility clinic.
METHODS:
This was a cross-sectional study of 260 women attending the infertility clinic at Mulago hospital. The interviewer administered questionnaire comprised socio-demographic characteristics, infertility-related aspects and information on herbal medicine use. The main outcome measure was herbal medicines use for infertility treatment. Determinants of herbal medicine use were assessed using multivariable logistic regression.
RESULTS:
The majority (76.2%) of respondents had used herbal medicines for infertility treatment. The mean age of the participants was 28.3 years ± 5.5. Over 80% were married, 59.6% had secondary infertility and 2/3 of the married participants were in monogamous unions. In a multivariable model, the variables that were independently associated with increased use of herbal medicine among infertile patients were being married (OR 2.55, CI 1.24-5.24), never conceived (OR 4.08 CI 1.86-8.96) and infertility for less than 3 years (OR 3.52 CI 1.51-8.821). Factors that were associated with less use of herbal medicine among infertile women were being aged 30 years or less (OR 0.18 CI 0.07-0.46), primary and no education (OR 0.12 CI 0.05-0.46) and living with partner for less than three years (OR 0.39 CI 0.16-0.93).
CONCLUSIONS:
The prevalence of herbal medicine use among women attending the infertility clinic was 76.2%. Herbal medicine use was associated with the participants' age, level of education, marital status, infertility duration, nulliparity, and duration of marriage. Medical care was often delayed and the majority of the participants did not disclose use of herbal medicines to the attending physician. Health professionals should enquire about use of herbal medicines. This may help in educating the patients about the health risks of using herbal medicine and may reduce delays in seeking appropriate care. Collaboration of health professionals with herbal medicine practitioners would help identify the common herbal medicines used for infertility treatment, their potential benefits and harm. |
Nakanjako, Damalie; Katamba, Achilles; Kaye, Dan K; Okello, Elialilia; Kamya, Moses R; Sewankambo, Nelson; Mayanja-Kizza, Harriet Doctoral training in Uganda: evaluation of mentoring best practices at Makerere university college of health sciences Journal Article In: BMC Medical Education, vol. 14, no. 1, 2014. @article{Nakanjako2014c,
title = {Doctoral training in Uganda: evaluation of mentoring best practices at Makerere university college of health sciences},
author = {Damalie Nakanjako and Achilles Katamba and Dan K Kaye and Elialilia Okello and Moses R Kamya and Nelson Sewankambo and Harriet Mayanja-Kizza},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Doctoral-training-in-Uganda....pdf},
doi = {10.1186/1472-6920-14-9},
year = {2014},
date = {2014-01-13},
journal = {BMC Medical Education},
volume = {14},
number = {1},
abstract = {BACKGROUND:
Good mentoring is a key variable for determining success in completing a doctoral program. We identified prevailing mentoring practices among doctoral students and their mentors, identified common challenges facing doctoral training, and proposed some solutions to enhance the quality of the doctoral training experience for both candidates and mentors at Makerere University College of Health Sciences (MakCHS).
METHODS:
This cross-sectional qualitative evaluation was part of the monitoring and evaluation program for doctoral training. All doctoral students and their mentors were invited for a half-day workshop through the MakCHS mailing list. Prevailing doctoral supervision and mentoring guidelines were summarised in a one-hour presentation. Participants were split into two homogenous students' (mentees') and mentors' groups to discuss specific issues using a focus group discussion (FGD) guide, that highlighted four main themes in regard to the doctoral training experience; what was going well, what was not going well, proposed solutions to current challenges and perceived high priority areas for improvement. The two groups came together again and the note-takers from each group presented their data and discussions were recorded by a note-taker.
RESULTS:
Twelve out of 36 invited mentors (33%) and 22 out of 40 invited mentees (55%) attended the workshop. Mentors and mentees noted increasing numbers of doctoral students and mentors, which provided opportunities for peer mentorship. Delays in procurement and research regulatory processes subsequently delayed students' projects. Similarly, mentees mentioned challenges of limited; 1) infrastructure and mentors to support basic science research projects, 2) physical office space for doctoral students and their mentors, 3) skills in budgeting and finance management and 4) communication skills including conflict resolution. As solutions, the team proposed skills' training, induction courses for doctoral students-mentor teams, and a Frequently Asked Questions' document, to better inform mentors', mentees' expectations and experiences.
CONCLUSION:
Systemic and infrastructural limitations affect the quality of the doctoral training experience at MaKCHS. Clinical and biomedical research infrastructure, in addition to training in research regulatory processes, procurement and finance management, communication skills and information technology, were highlighted as high priority areas for strategic interventions to improve mentoring within doctoral training of clinician scientists.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Good mentoring is a key variable for determining success in completing a doctoral program. We identified prevailing mentoring practices among doctoral students and their mentors, identified common challenges facing doctoral training, and proposed some solutions to enhance the quality of the doctoral training experience for both candidates and mentors at Makerere University College of Health Sciences (MakCHS).
METHODS:
This cross-sectional qualitative evaluation was part of the monitoring and evaluation program for doctoral training. All doctoral students and their mentors were invited for a half-day workshop through the MakCHS mailing list. Prevailing doctoral supervision and mentoring guidelines were summarised in a one-hour presentation. Participants were split into two homogenous students' (mentees') and mentors' groups to discuss specific issues using a focus group discussion (FGD) guide, that highlighted four main themes in regard to the doctoral training experience; what was going well, what was not going well, proposed solutions to current challenges and perceived high priority areas for improvement. The two groups came together again and the note-takers from each group presented their data and discussions were recorded by a note-taker.
RESULTS:
Twelve out of 36 invited mentors (33%) and 22 out of 40 invited mentees (55%) attended the workshop. Mentors and mentees noted increasing numbers of doctoral students and mentors, which provided opportunities for peer mentorship. Delays in procurement and research regulatory processes subsequently delayed students' projects. Similarly, mentees mentioned challenges of limited; 1) infrastructure and mentors to support basic science research projects, 2) physical office space for doctoral students and their mentors, 3) skills in budgeting and finance management and 4) communication skills including conflict resolution. As solutions, the team proposed skills' training, induction courses for doctoral students-mentor teams, and a Frequently Asked Questions' document, to better inform mentors', mentees' expectations and experiences.
CONCLUSION:
Systemic and infrastructural limitations affect the quality of the doctoral training experience at MaKCHS. Clinical and biomedical research infrastructure, in addition to training in research regulatory processes, procurement and finance management, communication skills and information technology, were highlighted as high priority areas for strategic interventions to improve mentoring within doctoral training of clinician scientists. |
Mbonye, Martin Kayitale; Burnett, Sarah M.; Burua, Aldomoro; Colebunders, Robert; Crozier, Ian; Kinoti, Stephen N.; Ronald, Allan; Naikoba, Sarah; Rubashembusya, Timothy; geertruyden, Jean-Pierre Van; Willis, Kelly S.; Weaver, Marcia R. Effect of Integrated Capacity-Building Interventions on Malaria Case Management by Health Professionals in Uganda: A Mixed Design Study with Pre/Post and Cluster Randomized Trial Components Journal Article In: PloS One, vol. 9, no. 1, 2014. @article{Mbonye2014c,
title = {Effect of Integrated Capacity-Building Interventions on Malaria Case Management by Health Professionals in Uganda: A Mixed Design Study with Pre/Post and Cluster Randomized Trial Components},
author = {Martin Kayitale Mbonye and Sarah M. Burnett and Aldomoro Burua and Robert Colebunders and Ian Crozier and Stephen N. Kinoti and Allan Ronald and Sarah Naikoba and Timothy Rubashembusya and Jean-Pierre Van
geertruyden and Kelly S. Willis and Marcia R. Weaver
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Effect-of-Integrated-Capacity-Building-Interventions-on.....pdf},
doi = {10.1371/journal.pone.0084945},
year = {2014},
date = {2014-01-08},
journal = {PloS One},
volume = {9},
number = {1},
abstract = {BACKGROUND:
The Integrated Infectious Diseases Capacity Building Evaluation (IDCAP) designed two interventions: Integrated Management of Infectious Disease (IMID) training program and On-Site Support (OSS). We evaluated their effects on 23 facility performance indicators, including malaria case management.
METHODOLOGY:
IMID, a three-week training with two follow-up booster courses, was for two mid- level practitioners, primarily clinical officers and registered nurses, from 36 primary care facilities. OSS was two days of training and continuous quality improvement activities for nine months at 18 facilities, to which all health workers were invited to participate. Facilities were randomized as clusters 1∶1 to parallel OSS "arm A" or control "arm B". Outpatient data on four malaria case management indicators were collected for 14 months. Analysis compared changes before and during the interventions within arms (relative risk = RR). The effect of OSS was measured with the difference in changes across arms (ratio of RR = RRR).
FINDINGS:
The proportion of patients with suspected malaria for whom a diagnostic test result for malaria was recorded decreased in arm B (adjusted RR (aRR) = 0.97; 99%CI: 0.82,1.14) during IMID, but increased 25% in arm A (aRR = 1.25; 99%CI:0.94, 1.65) during IMID and OSS relative to baseline; (aRRR = 1.28; 99%CI:0.93, 1.78). The estimated proportion of patients that received an appropriate antimalarial among those prescribed any antimalarial increased in arm B (aRR = 1.09; 99%CI: 0.87, 1.36) and arm A (aRR = 1.50; 99%CI: 1.04, 2.17); (aRRR = 1.38; 99%CI: 0.89, 2.13). The proportion of patients with a negative diagnostic test result for malaria prescribed an antimalarial decreased in arm B (aRR = 0.96; 99%CI: 0.84, 1.10) and arm A (aRR = 0.67; 99%CI: 0.46, 0.97); (aRRR = 0.70; 99%CI: 0.48, 1.00). The proportion of patients with a positive diagnostic test result for malaria prescribed an antibiotic did not change significantly in either arm.
INTERPRETATION:
The combination of IMID and OSS was associated with statistically significant improvements in malaria case management.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
The Integrated Infectious Diseases Capacity Building Evaluation (IDCAP) designed two interventions: Integrated Management of Infectious Disease (IMID) training program and On-Site Support (OSS). We evaluated their effects on 23 facility performance indicators, including malaria case management.
METHODOLOGY:
IMID, a three-week training with two follow-up booster courses, was for two mid- level practitioners, primarily clinical officers and registered nurses, from 36 primary care facilities. OSS was two days of training and continuous quality improvement activities for nine months at 18 facilities, to which all health workers were invited to participate. Facilities were randomized as clusters 1∶1 to parallel OSS "arm A" or control "arm B". Outpatient data on four malaria case management indicators were collected for 14 months. Analysis compared changes before and during the interventions within arms (relative risk = RR). The effect of OSS was measured with the difference in changes across arms (ratio of RR = RRR).
FINDINGS:
The proportion of patients with suspected malaria for whom a diagnostic test result for malaria was recorded decreased in arm B (adjusted RR (aRR) = 0.97; 99%CI: 0.82,1.14) during IMID, but increased 25% in arm A (aRR = 1.25; 99%CI:0.94, 1.65) during IMID and OSS relative to baseline; (aRRR = 1.28; 99%CI:0.93, 1.78). The estimated proportion of patients that received an appropriate antimalarial among those prescribed any antimalarial increased in arm B (aRR = 1.09; 99%CI: 0.87, 1.36) and arm A (aRR = 1.50; 99%CI: 1.04, 2.17); (aRRR = 1.38; 99%CI: 0.89, 2.13). The proportion of patients with a negative diagnostic test result for malaria prescribed an antimalarial decreased in arm B (aRR = 0.96; 99%CI: 0.84, 1.10) and arm A (aRR = 0.67; 99%CI: 0.46, 0.97); (aRRR = 0.70; 99%CI: 0.48, 1.00). The proportion of patients with a positive diagnostic test result for malaria prescribed an antibiotic did not change significantly in either arm.
INTERPRETATION:
The combination of IMID and OSS was associated with statistically significant improvements in malaria case management. |
Bwakura-Dangarembizi, Mutsawashe; Kendall, Lindsay; Bakeera-Kitaka, Sabrina; Nahirya-Ntege, Patricia; Keishanyu, Rosette; Nathoo, Kusum; Spyer, Moira J.; Kekitiinwa, Adeodata; Lutaakome, Joseph; Moira J. Spyer,; Kekitiinwa, Adeodata; Lutaakome, Joseph; Mhute, Tawanda; Kasirye, Philip; Munderi, Paula; Musiime, Victor; Gibb, Diana M.; Walker, A. Sarah; for the Antiretroviral Research for Watoto (ARROW) Trial Team, Andrew J. Prendergast D. Phil. A Randomized Trial of Prolonged Co-trimoxazole in HIV-Infected Children in Africa Journal Article In: The New England Journal of Medicine, vol. 370, no. 1, pp. 41-53, 2014. @article{Bwakura-Dangarembizi2014,
title = {A Randomized Trial of Prolonged Co-trimoxazole in HIV-Infected Children in Africa},
author = {Mutsawashe Bwakura-Dangarembizi and Lindsay Kendall and Sabrina Bakeera-Kitaka and Patricia Nahirya-Ntege and Rosette Keishanyu and Kusum Nathoo and Moira J. Spyer and Adeodata Kekitiinwa and Joseph Lutaakome and Moira J. Spyer, and Adeodata Kekitiinwa and Joseph Lutaakome and Tawanda Mhute and Philip Kasirye and Paula Munderi and Victor Musiime and Diana M. Gibb and A. Sarah Walker and Andrew J. Prendergast D.Phil. for the Antiretroviral Research for Watoto (ARROW) Trial Team },
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/A-Randomized-Trial-of-Prolonged-Co-trimoxazole-in-HIV-Infected-Children-in-Africa.pdf},
doi = {10.1056/NEJMoa1214901},
year = {2014},
date = {2014-01-02},
journal = {The New England Journal of Medicine},
volume = {370},
number = {1},
pages = {41-53},
abstract = {BACKGROUND:
Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) prophylaxis administered before antiretroviral therapy (ART) reduces morbidity in children infected with the human immunodeficiency virus (HIV). We investigated whether children and adolescents receiving long-term ART in sub-Saharan Africa could discontinue co-trimoxazole.
METHODS:
We conducted a randomized, noninferiority trial of stopping versus continuing daily open-label co-trimoxazole in children and adolescents in Uganda and Zimbabwe. Eligible participants were older than 3 years of age, had been receiving ART for more than 96 weeks, were using insecticide-treated bed nets (in malaria-endemic areas), and had not had Pneumocystis jirovecii pneumonia. Coprimary end points were hospitalization or death and adverse events of grade 3 or 4.
RESULTS:
A total of 758 participants were randomly assigned to stop or continue co-trimoxazole (382 and 376 participants, respectively), after receiving ART for a median of 2.1 years (interquartile range, 1.8 to 2.3). The median age was 7.9 years (interquartile range, 4.6 to 11.1), and the median CD4 T-cell percentage was 33% (interquartile range, 26 to 39). Participants who stopped co-trimoxazole had higher rates of hospitalization or death than those who continued (72 participants [19%] vs. 48 [13%]; hazard ratio, 1.64; 95% confidence interval [CI], 1.14 to 2.37; P = 0.007; noninferiority not shown). There was no evidence of variation across ages (P=0.93 for interaction). A total of 2 participants in the prophylaxis-stopped group (1%) died, as did 3 in the prophylaxis-continued group (1%). Most hospitalizations in the prophylaxis-stopped group were for malaria (49 events, vs. 21 in the prophylaxis-continued group) or infections other than malaria (53 vs. 25), particularly pneumonia, sepsis, and meningitis. Rates of adverse events of grade 3 or 4 were similar in the two groups (hazard ratio, 1.20; 95% CI, 0.83 to 1.72; P=0.33), but more grade 4 adverse events occurred in the prophylaxis-stopped group (hazard ratio, 2.04; 95% CI, 0.99 to 4.22; P=0.05), with anemia accounting for the largest number of events (12, vs. 2 with continued prophylaxis).
CONCLUSIONS:
Continuing co-trimoxazole prophylaxis after 96 weeks of ART was beneficial, as compared with stopping prophylaxis, with fewer hospitalizations for both malaria and infection not related to malaria. (Funded by the United Kingdom Medical Research Council and others; ARROW Current Controlled Trials number, ISRCTN24791884.).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) prophylaxis administered before antiretroviral therapy (ART) reduces morbidity in children infected with the human immunodeficiency virus (HIV). We investigated whether children and adolescents receiving long-term ART in sub-Saharan Africa could discontinue co-trimoxazole.
METHODS:
We conducted a randomized, noninferiority trial of stopping versus continuing daily open-label co-trimoxazole in children and adolescents in Uganda and Zimbabwe. Eligible participants were older than 3 years of age, had been receiving ART for more than 96 weeks, were using insecticide-treated bed nets (in malaria-endemic areas), and had not had Pneumocystis jirovecii pneumonia. Coprimary end points were hospitalization or death and adverse events of grade 3 or 4.
RESULTS:
A total of 758 participants were randomly assigned to stop or continue co-trimoxazole (382 and 376 participants, respectively), after receiving ART for a median of 2.1 years (interquartile range, 1.8 to 2.3). The median age was 7.9 years (interquartile range, 4.6 to 11.1), and the median CD4 T-cell percentage was 33% (interquartile range, 26 to 39). Participants who stopped co-trimoxazole had higher rates of hospitalization or death than those who continued (72 participants [19%] vs. 48 [13%]; hazard ratio, 1.64; 95% confidence interval [CI], 1.14 to 2.37; P = 0.007; noninferiority not shown). There was no evidence of variation across ages (P=0.93 for interaction). A total of 2 participants in the prophylaxis-stopped group (1%) died, as did 3 in the prophylaxis-continued group (1%). Most hospitalizations in the prophylaxis-stopped group were for malaria (49 events, vs. 21 in the prophylaxis-continued group) or infections other than malaria (53 vs. 25), particularly pneumonia, sepsis, and meningitis. Rates of adverse events of grade 3 or 4 were similar in the two groups (hazard ratio, 1.20; 95% CI, 0.83 to 1.72; P=0.33), but more grade 4 adverse events occurred in the prophylaxis-stopped group (hazard ratio, 2.04; 95% CI, 0.99 to 4.22; P=0.05), with anemia accounting for the largest number of events (12, vs. 2 with continued prophylaxis).
CONCLUSIONS:
Continuing co-trimoxazole prophylaxis after 96 weeks of ART was beneficial, as compared with stopping prophylaxis, with fewer hospitalizations for both malaria and infection not related to malaria. (Funded by the United Kingdom Medical Research Council and others; ARROW Current Controlled Trials number, ISRCTN24791884.). |
Rafael Van den Bergh Huyen Thi Thanh Tran, Trung Nghia Vu The role of monocytes in the development of Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome Journal Article In: Immunobiology, vol. 219, no. 1, pp. 37-44, 2014. @article{Tran2014,
title = {The role of monocytes in the development of Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome},
author = {Huyen Thi Thanh Tran, Rafael Van den Bergh, Trung Nghia Vu, Kris Laukens, William Worodria, Marguerite Massinga Loembé, Robert Colebunders, Luc Kestens, Patrick De Baetselier, Geert Raes, for the TB-IRIS Study Group},
doi = {https://doi.org/10.1016/j.imbio.2013.07.004},
year = {2014},
date = {2014-01-02},
journal = {Immunobiology},
volume = {219},
number = {1},
pages = {37-44},
abstract = {Background
Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication of combined antiretroviral therapy (cART) in HIV-TB co-infected patients. However, the disease mechanism is poorly understood, prognosis of TB-IRIS is currently impossible, and diagnosis is highly challenging. We analyzed whether the gene expression of monocytes could be correlated with TB-IRIS pathogenesis and could be used to classify patients predisposed to TB-IRIS.
Methods
Monocyte gene expression was compared between patients who developed TB-IRIS and matched controls. We carried out whole-genome expression profiling using Affymetrix GeneChip® ST 1.1 arrays at two time-points: before cART initiation (baseline) and at week two post-cART initiation. For each time-point, we used different statistical approaches to identify molecular signatures which could be used as classifiers. We also functionally mapped the modulated cellular pathways using the software package Ingenuity Pathway Analysis.
Results
At baseline, before introduction of cART and before onset of symptoms, monocyte gene expression was already perturbed in patients who subsequently developed TB-IRIS, indicating a possible involvement of monocytes in TB-IRIS predisposition. The differences in monocyte gene expression in TB-IRIS patients became even more clear after two weeks of cART (when TB-IRIS commonly occurs), with more than 100 genes for which expression showed a fold change greater than 1.5. Both at baseline and at week two post-cART initiation, a classifier of 8 and 9 genes, respectively could be built, which allowed discrimination of TB-IRIS cases and controls. Pathway analyses revealed that the majority of the dysregulated genes in TB-IRIS – at the time of the IRIS episode, but also already at baseline – are associated with infection and inflammation. Relevant biological functions which were perturbed before/during TB-IRIS included “Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses” and “Complement System”.
Conclusion
Our results indicate an involvement of monocytes in predisposition to/development of TB-IRIS, and suggest a number of functional pathways which may play a role in TB-IRIS development. This comprehensive study of gene regulation in monocytes provides baseline data for further studies into biomarkers for prognosis and diagnosis of TB-IRIS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication of combined antiretroviral therapy (cART) in HIV-TB co-infected patients. However, the disease mechanism is poorly understood, prognosis of TB-IRIS is currently impossible, and diagnosis is highly challenging. We analyzed whether the gene expression of monocytes could be correlated with TB-IRIS pathogenesis and could be used to classify patients predisposed to TB-IRIS.
Methods
Monocyte gene expression was compared between patients who developed TB-IRIS and matched controls. We carried out whole-genome expression profiling using Affymetrix GeneChip® ST 1.1 arrays at two time-points: before cART initiation (baseline) and at week two post-cART initiation. For each time-point, we used different statistical approaches to identify molecular signatures which could be used as classifiers. We also functionally mapped the modulated cellular pathways using the software package Ingenuity Pathway Analysis.
Results
At baseline, before introduction of cART and before onset of symptoms, monocyte gene expression was already perturbed in patients who subsequently developed TB-IRIS, indicating a possible involvement of monocytes in TB-IRIS predisposition. The differences in monocyte gene expression in TB-IRIS patients became even more clear after two weeks of cART (when TB-IRIS commonly occurs), with more than 100 genes for which expression showed a fold change greater than 1.5. Both at baseline and at week two post-cART initiation, a classifier of 8 and 9 genes, respectively could be built, which allowed discrimination of TB-IRIS cases and controls. Pathway analyses revealed that the majority of the dysregulated genes in TB-IRIS – at the time of the IRIS episode, but also already at baseline – are associated with infection and inflammation. Relevant biological functions which were perturbed before/during TB-IRIS included “Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses” and “Complement System”.
Conclusion
Our results indicate an involvement of monocytes in predisposition to/development of TB-IRIS, and suggest a number of functional pathways which may play a role in TB-IRIS development. This comprehensive study of gene regulation in monocytes provides baseline data for further studies into biomarkers for prognosis and diagnosis of TB-IRIS. |
Boulware, David R.; Melissa A. Rolfes,; Rajasingham, Radha; von Hohenberg, Maximilian; Qin, Zhenpeng; Taseera, Kabanda; Schutz, Charlotte; Kwizera, Richard; Butler, Elissa K.; Meintjes, Graeme; Muzoora, Conrad; Bischof, John C.; Meya, David B. Multisite Validation of Cryptococcal Antigen Lateral Flow Assay and Quantification by Laser Thermal Contrast Journal Article In: Emerging Infectious Diseases, vol. 20, no. 1, pp. 45-53, 2014. @article{Boulware2014b,
title = {Multisite Validation of Cryptococcal Antigen Lateral Flow Assay and Quantification by Laser Thermal Contrast},
author = {David R. Boulware and Melissa A. Rolfes, and Radha Rajasingham and Maximilian von Hohenberg and Zhenpeng Qin and Kabanda Taseera and Charlotte Schutz and Richard Kwizera and Elissa K. Butler and Graeme Meintjes and Conrad Muzoora and John C. Bischof and David B. Meya},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Multisite-Validation-of-Cryptococcal-Antigen-Lateral-Flow-Assay-and-Quantification-by-laser-Thermal-Contrast.pdf},
doi = {10.3201/eid2001.130906},
year = {2014},
date = {2014-01-01},
journal = {Emerging Infectious Diseases},
volume = {20},
number = {1},
pages = {45-53},
abstract = {Cryptococcal meningitis is common in sub-Saharan Africa. Given the need for data for a rapid, point-of-care cryptococcal antigen (CRAG) lateral flow immunochromatographic assay (LFA), we assessed diagnostic performance of cerebrospinal fluid (CSF) culture, CRAG latex agglutination, India ink microscopy, and CRAG LFA for 832 HIV-infected persons with suspected meningitis during 2006-2009 (n = 299) in Uganda and during 2010-2012 (n = 533) in Uganda and South Africa. CRAG LFA had the best performance (sensitivity 99.3%, specificity 99.1%). Culture sensitivity was dependent on CSF volume (82.4% for 10 μL, 94.2% for 100 μL). CRAG latex agglutination test sensitivity (97.0%-97.8%) and specificity (85.9%-100%) varied between manufacturers. India ink microscopy was 86% sensitive. Laser thermal contrast had 92% accuracy (R = 0.91, p<0.001) in quantifying CRAG titers from 1 LFA strip to within <1.5 dilutions of actual CRAG titers. CRAG LFA is a major advance for meningitis diagnostics in resource-limited settings.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cryptococcal meningitis is common in sub-Saharan Africa. Given the need for data for a rapid, point-of-care cryptococcal antigen (CRAG) lateral flow immunochromatographic assay (LFA), we assessed diagnostic performance of cerebrospinal fluid (CSF) culture, CRAG latex agglutination, India ink microscopy, and CRAG LFA for 832 HIV-infected persons with suspected meningitis during 2006-2009 (n = 299) in Uganda and during 2010-2012 (n = 533) in Uganda and South Africa. CRAG LFA had the best performance (sensitivity 99.3%, specificity 99.1%). Culture sensitivity was dependent on CSF volume (82.4% for 10 μL, 94.2% for 100 μL). CRAG latex agglutination test sensitivity (97.0%-97.8%) and specificity (85.9%-100%) varied between manufacturers. India ink microscopy was 86% sensitive. Laser thermal contrast had 92% accuracy (R = 0.91, p<0.001) in quantifying CRAG titers from 1 LFA strip to within <1.5 dilutions of actual CRAG titers. CRAG LFA is a major advance for meningitis diagnostics in resource-limited settings. |
Ssinabulyaet.al, Isaac Immunodeficiency at the start of combination antiretroviral therapy in low-, middle- and high-income countries Journal Article In: Journal of Acquired Imune Dificiency syndrome, vol. 65, no. 1, 2014. @article{Ssinabulyaet.al2014,
title = {Immunodeficiency at the start of combination antiretroviral therapy in low-, middle- and high-income countries},
author = {Isaac Ssinabulyaet.al},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Immunodeficiency-at-the-start-of-combination-antiretroviral-therapy-in-low-middle-and-high-income-countries.pdf},
doi = {doi:10.1097/QAI.0b013e3182a39979},
year = {2014},
date = {2014-01-01},
journal = {Journal of Acquired Imune Dificiency syndrome},
volume = {65},
number = {1},
abstract = {Objectives—
To describe the CD4 cell count at the start of combination antiretroviral therapy
(cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC) and
high-income (HIC) countries.
Methods—
Patients aged ≥16 years starting cART in a clinic participating in a multi-cohort
collaboration spanning six continents (International epidemiological Databases to Evaluate AIDS
and ART Cohort Collaboration) were eligible. Multi-level linear regression models were adjusted
for age, gender and calendar year; missing CD4 counts were imputed.
Findings—
379,865 patients from nine LIC, four LMIC, four UMIC and six HIC were included.
In LIC the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/
μ
l
between 2002 and 2009. Corresponding increases in LMIC, UMIC and HIC were from 87 to 155
cells/
μ
l (76% increase), 88 to 135 cells/
μ
l (53%) and 209 to 274 cells/
μ
l (31%). In 2009,
compared to LIC, median counts were 13 cells/
μ
l (95% CI -56 to +30) lower in LMIC, 22 cells/
μ
l
(-62 to +18) lower in UMIC and 112 /
μ
l (+75 to +149) higher in HIC. They were 23 cells/
μ
l (95%
CI +18 to +28) higher in women than men. Median counts were 88 cells/
μ
l (95% CI +35 to +141)
higher in countries with an estimated national cART coverage >80%, compared to countries with
<40% coverage.
Conclusions—
Median CD4 cell counts at start of cART increased 2000-2009 but remained
below 200 cells/
μ
l in LIC and MIC and below 300 cells/
μ
l in HIC. Earlier start of cART will
require substantial efforts and resources globally},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objectives—
To describe the CD4 cell count at the start of combination antiretroviral therapy
(cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC) and
high-income (HIC) countries.
Methods—
Patients aged ≥16 years starting cART in a clinic participating in a multi-cohort
collaboration spanning six continents (International epidemiological Databases to Evaluate AIDS
and ART Cohort Collaboration) were eligible. Multi-level linear regression models were adjusted
for age, gender and calendar year; missing CD4 counts were imputed.
Findings—
379,865 patients from nine LIC, four LMIC, four UMIC and six HIC were included.
In LIC the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/
μ
l
between 2002 and 2009. Corresponding increases in LMIC, UMIC and HIC were from 87 to 155
cells/
μ
l (76% increase), 88 to 135 cells/
μ
l (53%) and 209 to 274 cells/
μ
l (31%). In 2009,
compared to LIC, median counts were 13 cells/
μ
l (95% CI -56 to +30) lower in LMIC, 22 cells/
μ
l
(-62 to +18) lower in UMIC and 112 /
μ
l (+75 to +149) higher in HIC. They were 23 cells/
μ
l (95%
CI +18 to +28) higher in women than men. Median counts were 88 cells/
μ
l (95% CI +35 to +141)
higher in countries with an estimated national cART coverage >80%, compared to countries with
<40% coverage.
Conclusions—
Median CD4 cell counts at start of cART increased 2000-2009 but remained
below 200 cells/
μ
l in LIC and MIC and below 300 cells/
μ
l in HIC. Earlier start of cART will
require substantial efforts and resources globally |
Castelnuovo, Barbara; Newell, Kevin; Manabe, Yukari C.; Robertson, Gavin Multi-Media Educational Tool Increases Knowledge of Clinical Trials in Uganda Journal Article In: Journal of clinical Research & Bioethic, vol. 5, no. 1, 2014. @article{Castelnuovo2014,
title = {Multi-Media Educational Tool Increases Knowledge of Clinical Trials in Uganda},
author = {Barbara Castelnuovo and Kevin Newell and Yukari C. Manabe and Gavin Robertson},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Multilocus-Microsatellite-Genotyping-Array-for-Investigation-of-genetic-Epidimiology-of-Pneumocytis-jirovecii-1.pdf},
year = {2014},
date = {2014-01-01},
journal = {Journal of clinical Research & Bioethic},
volume = {5},
number = {1},
abstract = {Background—
Informed consent is premised on the participants’ understanding the scope of the
research and the associated risks and benefits. The objective was to evaluate the improvement in
knowledge in a population unfamiliar with clinical trial concepts about “what it means to be part
of a clinical trial” using an innovative educational tool called the ‘Speaking Book’.
Methods—
This was a randomized controlled trial conducted at a research site in Uganda. 201
participants were randomized to: 1) clinical trials information session control arm, or 2) clinical
trials information session followed by instruction in the use of the Speaking Book with a take-
home copy (intervention arm). After the session, participants of both groups completed a 22-item
multiple-choice test on the rights and responsibilities of participants. Participants returned after
one week to complete the same test to assess knowledge retention. The mean pre- and post-test
score difference was assessed according to trial arm using an unpaired t-test of proportions.
Results—
Ninety-one (90%) participants completed both the initial and follow-up tests in the
control arm and 100 (100%) in the intervention arm. The average age of participants was 38 years,
53% were female and 67% were employed; 20% had previously been invited to participate in a
clinical trial; of these, 19% had participated. The mean difference in proportion of correct
responses from test 1 to test 2 was 2.7% (95%CI 0.3%–5.0%) for the control arm and 11.6%
(95%CI 9.3%–13.7%) for the intervention arm (t-score= −5.3, p-value<0.0001).
Conclusion—
Participants who had instruction in the use of the Speaking Book had a larger
increase in knowledge than those who had no access to this tool. To better engage patients
unfamiliar with clinical trial concepts, innovative educational techniques can assist to increase
knowledge to make an informed decision about participation in a clinical trial.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background—
Informed consent is premised on the participants’ understanding the scope of the
research and the associated risks and benefits. The objective was to evaluate the improvement in
knowledge in a population unfamiliar with clinical trial concepts about “what it means to be part
of a clinical trial” using an innovative educational tool called the ‘Speaking Book’.
Methods—
This was a randomized controlled trial conducted at a research site in Uganda. 201
participants were randomized to: 1) clinical trials information session control arm, or 2) clinical
trials information session followed by instruction in the use of the Speaking Book with a take-
home copy (intervention arm). After the session, participants of both groups completed a 22-item
multiple-choice test on the rights and responsibilities of participants. Participants returned after
one week to complete the same test to assess knowledge retention. The mean pre- and post-test
score difference was assessed according to trial arm using an unpaired t-test of proportions.
Results—
Ninety-one (90%) participants completed both the initial and follow-up tests in the
control arm and 100 (100%) in the intervention arm. The average age of participants was 38 years,
53% were female and 67% were employed; 20% had previously been invited to participate in a
clinical trial; of these, 19% had participated. The mean difference in proportion of correct
responses from test 1 to test 2 was 2.7% (95%CI 0.3%–5.0%) for the control arm and 11.6%
(95%CI 9.3%–13.7%) for the intervention arm (t-score= −5.3, p-value<0.0001).
Conclusion—
Participants who had instruction in the use of the Speaking Book had a larger
increase in knowledge than those who had no access to this tool. To better engage patients
unfamiliar with clinical trial concepts, innovative educational techniques can assist to increase
knowledge to make an informed decision about participation in a clinical trial. |
Robertson, Emma J.; Najjuka, Grace; Rolfes, Melissa A.; Akampurira, Andrew; Jain, Neena; Anantharanjit, Janani; von Hohenberg, Maximilian; Tassieri, Manlio; Carlsson, Allan; Meya, David B.; Harrison, Thomas S.; Fries, Bettina C.; Boulware, David R.; Bicanic, Tihana Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis. Journal Article In: Journal of Infectious Diseases, vol. 209, no. 1, pp. 74-82, 2014. @article{Robertson2014,
title = {Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis.},
author = {Emma J. Robertson and Grace Najjuka and Melissa A. Rolfes and Andrew Akampurira and Neena Jain and Janani Anantharanjit and Maximilian von Hohenberg and Manlio Tassieri and Allan Carlsson and David B. Meya and Thomas S. Harrison and Bettina C. Fries and David R. Boulware and Tihana Bicanic},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/jit435.pdf},
doi = {10.1093/infdis/jit435},
year = {2014},
date = {2014-01-01},
journal = {Journal of Infectious Diseases},
volume = {209},
number = {1},
pages = {74-82},
abstract = {BACKGROUND:
The Cryptococcus neoformans polysaccharide capsule is a well-characterized virulence factor with immunomodulatory properties. The organism and/or shed capsule is postulated to raise intracranial pressure (ICP) in cryptococcal meningitis (CM) by mechanical obstruction of cerebrospinal fluid (CSF) outflow. Little is known regarding capsule phenotype in human cryptococcosis. We investigated the relationship of ex vivo CSF capsular phenotype with ICP and CSF immune response, as well as in vitro phenotype.
METHODS:
In total, 134 human immunodeficiency virus (HIV)-infected Ugandan adults with CM had serial lumbar punctures with measurement of CSF opening pressures, quantitative cultures, ex vivo capsule size and shedding, viscosity, and CSF cytokines; 108 had complete data. Induced capsular size and shedding were measured in vitro for 48 C. neoformans isolates.
RESULTS:
Cryptococcal strains producing larger ex vivo capsules in the baseline (pretreatment) CSF correlated with higher ICP (P = .02), slower rate of fungal clearance (P = .02), and paucity of CSF inflammation, including decreased CSF white blood cell (WBC) count (P < .001), interleukin (IL)-4 (P = .02), IL-6 (P = .01), IL-7 (P = .04), IL-8 (P = .03), and interferon γ (P = .03). CSF capsule shedding did not correlate with ICP. On multivariable analysis, capsule size remained independently associated with ICP. Ex vivo capsular size and shedding did not correlate with that of the same isolates grown in vitro.
CONCLUSIONS:
Cryptococcal capsule size ex vivo is an important contributor to virulence in human cryptococcal meningitis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
The Cryptococcus neoformans polysaccharide capsule is a well-characterized virulence factor with immunomodulatory properties. The organism and/or shed capsule is postulated to raise intracranial pressure (ICP) in cryptococcal meningitis (CM) by mechanical obstruction of cerebrospinal fluid (CSF) outflow. Little is known regarding capsule phenotype in human cryptococcosis. We investigated the relationship of ex vivo CSF capsular phenotype with ICP and CSF immune response, as well as in vitro phenotype.
METHODS:
In total, 134 human immunodeficiency virus (HIV)-infected Ugandan adults with CM had serial lumbar punctures with measurement of CSF opening pressures, quantitative cultures, ex vivo capsule size and shedding, viscosity, and CSF cytokines; 108 had complete data. Induced capsular size and shedding were measured in vitro for 48 C. neoformans isolates.
RESULTS:
Cryptococcal strains producing larger ex vivo capsules in the baseline (pretreatment) CSF correlated with higher ICP (P = .02), slower rate of fungal clearance (P = .02), and paucity of CSF inflammation, including decreased CSF white blood cell (WBC) count (P < .001), interleukin (IL)-4 (P = .02), IL-6 (P = .01), IL-7 (P = .04), IL-8 (P = .03), and interferon γ (P = .03). CSF capsule shedding did not correlate with ICP. On multivariable analysis, capsule size remained independently associated with ICP. Ex vivo capsular size and shedding did not correlate with that of the same isolates grown in vitro.
CONCLUSIONS:
Cryptococcal capsule size ex vivo is an important contributor to virulence in human cryptococcal meningitis. |
2013
|
Kiragga, Agnes N.; Castelnuova, Barbara; Musomba, Rachel; Levin, Jonathan; Kambugu, Andrew; Manabe, Yukari C.; Yiannoutsos, Constantin T.; Kiwanuka, Noah Comparison of Methods for Correction of Mortality Estimates for Loss to Follow-Up after ART Initiation: A Case of the Infectious Diseases Institute, Uganda Journal Article In: PloS One, vol. 18, no. 12, 2013. @article{Kiragga2013,
title = {Comparison of Methods for Correction of Mortality Estimates for Loss to Follow-Up after ART Initiation: A Case of the Infectious Diseases Institute, Uganda},
author = {Agnes N. Kiragga and Barbara Castelnuova and Rachel Musomba and Jonathan Levin and Andrew Kambugu and Yukari C. Manabe and Constantin T. Yiannoutsos and Noah Kiwanuka
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Comparison-of-methods-for-correction-of-mortality-estimates-for-loss-of-follow-upafter-ART-initiation.pdf},
doi = {10.1371/journal.pone.0083524},
year = {2013},
date = {2013-12-31},
journal = {PloS One},
volume = {18},
number = {12},
abstract = {BACKGROUND:
In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainment.
METHODS:
Routinely collected data from HIV patients initiating first line antiretroviral therapy (ART) at the Infectious Diseases Institute (IDI) (Routine Cohort) was used. Three methods to estimate mortality after initiation were: 1) standard Kaplan-Meier estimation (uncorrected method) that uses passively observed data; 2) double-sampling methods by Frangakis and Rubin (F&R) where deaths obtained from patient tracing studies are given a higher weight than those passively ascertained; 3) Nomogram proposed by Egger et al. Corrected mortality estimates in the Routine Cohort, were compared with the estimates from the IDI research observational cohort (Research Cohort), which was used as the "gold-standard".
RESULTS:
We included 5,633 patients from the Routine Cohort and 559 from the Research Cohort. Uncorrected mortality estimates (95% confidence interval [1]) in the Routine Cohort at 1, 2 and 3 years were 5.5% (4.9%-6.3%), 6.6% (5.9%-7.5%) and 7.4% (6.5%-8.5%), respectively. The F&R corrected estimates at 1, 2 and 3 years were 11.2% (5.8%-21.2%), 15.8% (9.9%-24.8%) and 18.5% (12.3% -27.2%) respectively. The estimates obtained from the Research Cohort were 15.6% (12.8%-18.9%), 17.5% (14.6%-21.0%) and 19.0% (15.3%-21.9%) at 1, 2 and 3 years respectively. Using the nomogram method in the Routine Cohort, the corrected programme-level mortality estimate in year 1 was 11.9% (8.0%-15.7%).
CONCLUSION:
Mortality adjustments provided by the F&R and nomogram methods are adequate and should be employed to correct mortality for loss-to-follow-up in large HIV care centres in Sub-Saharan Africa.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainment.
METHODS:
Routinely collected data from HIV patients initiating first line antiretroviral therapy (ART) at the Infectious Diseases Institute (IDI) (Routine Cohort) was used. Three methods to estimate mortality after initiation were: 1) standard Kaplan-Meier estimation (uncorrected method) that uses passively observed data; 2) double-sampling methods by Frangakis and Rubin (F&R) where deaths obtained from patient tracing studies are given a higher weight than those passively ascertained; 3) Nomogram proposed by Egger et al. Corrected mortality estimates in the Routine Cohort, were compared with the estimates from the IDI research observational cohort (Research Cohort), which was used as the "gold-standard".
RESULTS:
We included 5,633 patients from the Routine Cohort and 559 from the Research Cohort. Uncorrected mortality estimates (95% confidence interval [1]) in the Routine Cohort at 1, 2 and 3 years were 5.5% (4.9%-6.3%), 6.6% (5.9%-7.5%) and 7.4% (6.5%-8.5%), respectively. The F&R corrected estimates at 1, 2 and 3 years were 11.2% (5.8%-21.2%), 15.8% (9.9%-24.8%) and 18.5% (12.3% -27.2%) respectively. The estimates obtained from the Research Cohort were 15.6% (12.8%-18.9%), 17.5% (14.6%-21.0%) and 19.0% (15.3%-21.9%) at 1, 2 and 3 years respectively. Using the nomogram method in the Routine Cohort, the corrected programme-level mortality estimate in year 1 was 11.9% (8.0%-15.7%).
CONCLUSION:
Mortality adjustments provided by the F&R and nomogram methods are adequate and should be employed to correct mortality for loss-to-follow-up in large HIV care centres in Sub-Saharan Africa. |
Kamya, Namutebi; Byakika-Kibwika, Causes and outcome of hospitaliza tion among HIV -inf ected adults receiving antiretroviral therapy in Mulago hospital, Uganda Journal Article In: African Health Sciences, vol. 13, no. 4, pp. 977-85, 2013. @article{Kamya2013,
title = {Causes and outcome of hospitaliza tion among HIV -inf ected adults receiving antiretroviral therapy in Mulago hospital, Uganda},
author = {Namutebi Kamya and Byakika-Kibwika },
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Causes-and-outcome-of-hospitalization-among-HIV-infected-adults-recieving-antiretroviral-therapy-in-Mulago-hospital-Uganda.pdf},
doi = {10.4314/ahs.v13i4},
year = {2013},
date = {2013-12-01},
journal = {African Health Sciences},
volume = {13},
number = {4},
pages = {977-85},
abstract = {BACKGROUND:
Cohorts describing cause specific mortality in HIV-infected patients initiating antiretroviral therapy (ART) operate on an outpatient basis. Hospitalized patients represent the spectrum and burden of severe morbidity and mortality in patients on ART.
OBJECTIVE:
To determine the causes and outcomes of hospitalization among adults receiving ART.
METHODS:
A prospective cohort study. We enrolled 201 participants (50% female) with median (IQR) age and CD4 count of 34 (28-40) years and 91(29-211) cells/uL respectively.
RESULTS:
The most frequent causes of hospitalization were tuberculosis (TB) (37, 18%), cryptococcal meningitis (22, 11%), zidovudine (AZT) - associated anemia (19, 10%), sepsis (10, 5%) and Kaposi's sarcoma (10, 5%). Forty two patients (21%) died: 10 (24%) had TB, 8 (19%) had cryptococcal meningitis and 5 (12%) had sepsis, 9 (21%) had undiagnosed neurological syndromes while 10 (24%) had other illnesses. Predictors of death included low Karnofsky performance score of < 40 (OR, 21.1; CI 1.43- 31.6) and age >34 years (OR, 7.65; CI 1.09- 53.8).
CONCLUSIONS:
Opportunistic infections, malignancy and AZT-associated anemia contributed to most hospitalizations and mortality. It is important to intensify prevention, screening, and treatment for these opportunistic diseases and early ART initiation in HIV-infected patients. Tenofovir-based regimens, unless contraindicated should be scaled up to replace AZT-based regimens as first line ART drugs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Cohorts describing cause specific mortality in HIV-infected patients initiating antiretroviral therapy (ART) operate on an outpatient basis. Hospitalized patients represent the spectrum and burden of severe morbidity and mortality in patients on ART.
OBJECTIVE:
To determine the causes and outcomes of hospitalization among adults receiving ART.
METHODS:
A prospective cohort study. We enrolled 201 participants (50% female) with median (IQR) age and CD4 count of 34 (28-40) years and 91(29-211) cells/uL respectively.
RESULTS:
The most frequent causes of hospitalization were tuberculosis (TB) (37, 18%), cryptococcal meningitis (22, 11%), zidovudine (AZT) - associated anemia (19, 10%), sepsis (10, 5%) and Kaposi's sarcoma (10, 5%). Forty two patients (21%) died: 10 (24%) had TB, 8 (19%) had cryptococcal meningitis and 5 (12%) had sepsis, 9 (21%) had undiagnosed neurological syndromes while 10 (24%) had other illnesses. Predictors of death included low Karnofsky performance score of < 40 (OR, 21.1; CI 1.43- 31.6) and age >34 years (OR, 7.65; CI 1.09- 53.8).
CONCLUSIONS:
Opportunistic infections, malignancy and AZT-associated anemia contributed to most hospitalizations and mortality. It is important to intensify prevention, screening, and treatment for these opportunistic diseases and early ART initiation in HIV-infected patients. Tenofovir-based regimens, unless contraindicated should be scaled up to replace AZT-based regimens as first line ART drugs. |
Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Worodria, Ann Ceulemans William; Mayanja-Kizza, Harriet; Colebunders, Robert; the TB-IRIS Study Group, Luc Kestens LPS-Binding Protein and IL-6 Mark Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome in HIV Patients Journal Article In: PloS One, vol. 8, no. 11, 2013. @article{Goovaerts2013,
title = {LPS-Binding Protein and IL-6 Mark Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome in HIV Patients},
author = {Odin Goovaerts and Wim Jennes and Marguerite Massinga-Loembé and Ann Ceulemans William
Worodria and Harriet Mayanja-Kizza and Robert Colebunders and Luc Kestens the TB-IRIS Study Group
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/LPS-Binding-Protein-and-IL-6-Mark-Paradoxical-Tuberculosis-Immune-Reconstitution-Inflammatory-Syndrome-in-HIV-Patients.pdf},
doi = {10.1371/journal.pone.0081856},
year = {2013},
date = {2013-11-28},
journal = {PloS One},
volume = {8},
number = {11},
abstract = {BACKGROUND:
Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB co-infected patients initiating antiretroviral therapy (ART). The role of the innate immune system in TB-IRIS is becoming increasingly apparent, however the potential involvement in TB-IRIS of a leaky gut and proteins that interfere with TLR stimulation by binding PAMPs has not been investigated before. Here we aimed to investigate the innate nature of the cytokine response in TB-IRIS and to identify novel potential biomarkers.
METHODS:
From a large prospective cohort of HIV-TB co-infected patients receiving TB treatment, we compared 40 patients who developed TB-IRIS during the first month of ART with 40 patients matched for age, sex and baseline CD4 count who did not. We analyzed plasma levels of lipopolysaccharide (LPS)-binding protein (LBP), LPS, sCD14, endotoxin-core antibody, intestinal fatty acid-binding protein (I-FABP) and 18 pro-and anti-inflammatory cytokines before and during ART.
RESULTS:
We observed lower baseline levels of IL-6 (p = 0.041), GCSF (p = 0.036) and LBP (p = 0.016) in TB-IRIS patients. At IRIS event, we detected higher levels of LBP, IL-1RA, IL-4, IL-6, IL-7, IL-8, G-CSF (p ≤ 0.032) and lower I-FABP levels (p = 0.013) compared to HIV-TB co-infected controls. Only IL-6 showed an independent effect in multivariate models containing significant cytokines from pre-ART (p = 0.039) and during TB-IRIS (p = 0.034).
CONCLUSION:
We report pre-ART IL-6 and LBP levels as well as IL-6, LBP and I-FABP levels during IRIS-event as potential biomarkers in TB-IRIS. Our results show no evidence of the possible contribution of a leaky gut to TB-IRIS and indicate that IL-6 holds a distinct role in the disturbed innate cytokine profile before and during TB-IRIS. Future clinical studies should investigate the importance and clinical relevance of these markers for the diagnosis and treatment of TB-IRIS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB co-infected patients initiating antiretroviral therapy (ART). The role of the innate immune system in TB-IRIS is becoming increasingly apparent, however the potential involvement in TB-IRIS of a leaky gut and proteins that interfere with TLR stimulation by binding PAMPs has not been investigated before. Here we aimed to investigate the innate nature of the cytokine response in TB-IRIS and to identify novel potential biomarkers.
METHODS:
From a large prospective cohort of HIV-TB co-infected patients receiving TB treatment, we compared 40 patients who developed TB-IRIS during the first month of ART with 40 patients matched for age, sex and baseline CD4 count who did not. We analyzed plasma levels of lipopolysaccharide (LPS)-binding protein (LBP), LPS, sCD14, endotoxin-core antibody, intestinal fatty acid-binding protein (I-FABP) and 18 pro-and anti-inflammatory cytokines before and during ART.
RESULTS:
We observed lower baseline levels of IL-6 (p = 0.041), GCSF (p = 0.036) and LBP (p = 0.016) in TB-IRIS patients. At IRIS event, we detected higher levels of LBP, IL-1RA, IL-4, IL-6, IL-7, IL-8, G-CSF (p ≤ 0.032) and lower I-FABP levels (p = 0.013) compared to HIV-TB co-infected controls. Only IL-6 showed an independent effect in multivariate models containing significant cytokines from pre-ART (p = 0.039) and during TB-IRIS (p = 0.034).
CONCLUSION:
We report pre-ART IL-6 and LBP levels as well as IL-6, LBP and I-FABP levels during IRIS-event as potential biomarkers in TB-IRIS. Our results show no evidence of the possible contribution of a leaky gut to TB-IRIS and indicate that IL-6 holds a distinct role in the disturbed innate cytokine profile before and during TB-IRIS. Future clinical studies should investigate the importance and clinical relevance of these markers for the diagnosis and treatment of TB-IRIS. |
Kuznik, Andreas; Lamorde, Mohammed; Nyabigambo, Agnes; Manabe, Yukari C. Antenatal Syphilis Screening Using Point-of-Care Testing in Sub-Saharan African Countries: A Cost-Effectiveness Analysis Journal Article In: PloS Medicine, vol. 10, no. 11, 2013. @article{Kuznik2013,
title = {Antenatal Syphilis Screening Using Point-of-Care Testing in Sub-Saharan African Countries: A Cost-Effectiveness Analysis},
author = {Andreas Kuznik and Mohammed Lamorde and Agnes Nyabigambo and Yukari C. Manabe
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Antenatal-Syphilis-Screening-Using-Point-of-Care-Testing-in-Sub-Saharan-African-Countries.pdf},
doi = {10.1371/journal.pmed},
year = {2013},
date = {2013-11-05},
journal = {PloS Medicine},
volume = {10},
number = {11},
abstract = {Background:
Untreated syphilis in pregnancy is associated with adverse clinical outcomes for the infant. Most syphilis
infections occur in sub-Saharan Africa (SSA), where coverage of antenatal screening for syphilis is inadequate. Recently
introduced point-of-care syphilis tests have high accuracy and demonstrate potential to increase coverage of antenatal
screening. However, country-specific cost-effectiveness data for these tests are limited. The objective of this analysis was to
evaluate the cost-effectiveness and budget impact of antenatal syphilis screening for 43 countries in SSA and estimate the
impact of universal screening on stillbirths, neonatal deaths, congenital syphilis, and disability-adjusted life years (DALYs)
averted.
Methods and Findings:
The decision analytic model reflected the perspective of the national health care system and was
based on the sensitivity (86%) and specificity (99%) reported for the immunochromatographic strip (ICS) test. Clinical
outcomes of infants born to syphilis-infected mothers on the end points of stillbirth, neonatal death, and congenital syphilis
were obtained from published sources. Treatment was assumed to consist of three injections of benzathine penicillin.
Country-specific inputs included the antenatal prevalence of syphilis, annual number of live births, proportion of women
with at least one antenatal care visit, per capita gross national income, and estimated hourly nurse wages. In all 43 sub-
Saharan African countries analyzed, syphilis screening is highly cost-effective, with an average cost/DALY averted of US
$
11
(range: US
$
2–US
$
48). Screening remains highly cost-effective even if the average prevalence falls from the current rate of
3.1% (range: 0.6%–14.0%) to 0.038% (range: 0.002%–0.113%). Universal antenatal screening of pregnant women in clinics
may reduce the annual number of stillbirths by up to 64,000, neonatal deaths by up to 25,000, and annual incidence of
congenital syphilis by up to 32,000, and avert up to 2.6 million DALYs at an estimated annual direct medical cost of US
$
20.8
million.
Conclusions:
Use of ICS tests for antenatal syphilis screening is highly cost-effective in SSA. Substantial reduction in DALYs
can be achieved at a relatively modest budget impact. In SSA, antenatal programs should expand access to syphilis
screening using the ICS test.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background:
Untreated syphilis in pregnancy is associated with adverse clinical outcomes for the infant. Most syphilis
infections occur in sub-Saharan Africa (SSA), where coverage of antenatal screening for syphilis is inadequate. Recently
introduced point-of-care syphilis tests have high accuracy and demonstrate potential to increase coverage of antenatal
screening. However, country-specific cost-effectiveness data for these tests are limited. The objective of this analysis was to
evaluate the cost-effectiveness and budget impact of antenatal syphilis screening for 43 countries in SSA and estimate the
impact of universal screening on stillbirths, neonatal deaths, congenital syphilis, and disability-adjusted life years (DALYs)
averted.
Methods and Findings:
The decision analytic model reflected the perspective of the national health care system and was
based on the sensitivity (86%) and specificity (99%) reported for the immunochromatographic strip (ICS) test. Clinical
outcomes of infants born to syphilis-infected mothers on the end points of stillbirth, neonatal death, and congenital syphilis
were obtained from published sources. Treatment was assumed to consist of three injections of benzathine penicillin.
Country-specific inputs included the antenatal prevalence of syphilis, annual number of live births, proportion of women
with at least one antenatal care visit, per capita gross national income, and estimated hourly nurse wages. In all 43 sub-
Saharan African countries analyzed, syphilis screening is highly cost-effective, with an average cost/DALY averted of US
$
11
(range: US
$
2–US
$
48). Screening remains highly cost-effective even if the average prevalence falls from the current rate of
3.1% (range: 0.6%–14.0%) to 0.038% (range: 0.002%–0.113%). Universal antenatal screening of pregnant women in clinics
may reduce the annual number of stillbirths by up to 64,000, neonatal deaths by up to 25,000, and annual incidence of
congenital syphilis by up to 32,000, and avert up to 2.6 million DALYs at an estimated annual direct medical cost of US
$
20.8
million.
Conclusions:
Use of ICS tests for antenatal syphilis screening is highly cost-effective in SSA. Substantial reduction in DALYs
can be achieved at a relatively modest budget impact. In SSA, antenatal programs should expand access to syphilis
screening using the ICS test. |
Lutwama, F.; Kagina, B. M.; Wajja, A.; Waiswa, F.; Mansoor, N.; Kirimunda, S.; Hughes, E. J.; Kiwanuka, N.; Joloba, M. L.; Musoke, P.; Scriba, T. J.; Mayanja-Kizza, H.; Day, C. L.; Hanekom, W. A. Distinct T-Cell Responses When BCG Vaccination Is Delayed From Birth to 6 Weeks of Age in Ugandan Infants Journal Article In: Journal of Infectious Diseases, vol. 209, no. 6, pp. 887-97, 2013. @article{Lutwama2013,
title = {Distinct T-Cell Responses When BCG Vaccination Is Delayed From Birth to 6 Weeks of Age in Ugandan Infants},
author = {F. Lutwama and B. M. Kagina and A. Wajja and F. Waiswa and N. Mansoor and S. Kirimunda and E. J. Hughes and N. Kiwanuka and M. L. Joloba and P. Musoke and T. J. Scriba and H. Mayanja-Kizza and C. L. Day and W. A. Hanekom
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Distinct-T-Cell-Responses-When-BCG-Vaccination-Is-Delayed-From-Birth-to-6-Weeks-of-Age-in-Ugandan-Infants.pdf},
doi = {10.1093/infdis/jit570},
year = {2013},
date = {2013-10-31},
journal = {Journal of Infectious Diseases},
volume = {209},
number = {6},
pages = {887-97},
abstract = {BACKGROUND:
In Uganda, the tuberculosis vaccine BCG is administered on the first day of life. Infants delivered at home receive BCG vaccine at their first healthcare facility visit at 6 weeks of age. Our aim was to determine the effect of this delay in BCG vaccination on the induced immune response.
METHODS:
We assessed CD4(+) and CD8(+) T-cell responses with a 12-hour whole-blood intracellular cytokine/cytotoxic marker assay, and with a 6-day proliferation assay.
RESULTS:
We enrolled 92 infants: 50 had received BCG vaccine at birth and 42 at 6 weeks of age. Birth vaccination was associated with (1) greater induction of CD4(+) and CD8(+) T cells expressing either interferon γ (IFN-γ) alone or IFN-γ together with perforin and (2) induction of proliferating cells that had greater capacity to produce IFN-γ, tumor necrosis factor α (TNF-α), and interleukin 2 together, compared with delayed vaccination.
CONCLUSIONS:
Distinct patterns of T-cell induction occurred when BCG vaccine was given at birth and at 6 weeks of age. We propose that this diversity might impact protection against tuberculosis. Our results differ from those of studies of delayed BCG vaccination in South Africa and the Gambia, suggesting that geographical and population heterogeneity may affect the BCG vaccine-induced T-cell response.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
In Uganda, the tuberculosis vaccine BCG is administered on the first day of life. Infants delivered at home receive BCG vaccine at their first healthcare facility visit at 6 weeks of age. Our aim was to determine the effect of this delay in BCG vaccination on the induced immune response.
METHODS:
We assessed CD4(+) and CD8(+) T-cell responses with a 12-hour whole-blood intracellular cytokine/cytotoxic marker assay, and with a 6-day proliferation assay.
RESULTS:
We enrolled 92 infants: 50 had received BCG vaccine at birth and 42 at 6 weeks of age. Birth vaccination was associated with (1) greater induction of CD4(+) and CD8(+) T cells expressing either interferon γ (IFN-γ) alone or IFN-γ together with perforin and (2) induction of proliferating cells that had greater capacity to produce IFN-γ, tumor necrosis factor α (TNF-α), and interleukin 2 together, compared with delayed vaccination.
CONCLUSIONS:
Distinct patterns of T-cell induction occurred when BCG vaccine was given at birth and at 6 weeks of age. We propose that this diversity might impact protection against tuberculosis. Our results differ from those of studies of delayed BCG vaccination in South Africa and the Gambia, suggesting that geographical and population heterogeneity may affect the BCG vaccine-induced T-cell response. |
Doka, Najah I.; Jacob, Shevin T.; Banura, Patrick; Moore, Christopher C.; Meya, David; Mayanja-Kizza, Harriet; Reynolds, Steven J.; Scheld, W. Michael; Yuan, Wen Enrichment of HIV-1 Subtype AD Recombinants in a Ugandan Cohort of Severely Septic Patients Journal Article In: PloS One, vol. 7, no. 10, 2013. @article{Doka2013,
title = {Enrichment of HIV-1 Subtype AD Recombinants in a Ugandan Cohort of Severely Septic Patients},
author = {Najah I. Doka and Shevin T. Jacob and Patrick Banura and Christopher C. Moore and David Meya and Harriet Mayanja-Kizza and Steven J. Reynolds and W. Michael Scheld and Wen Yuan
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Enrichment-of-HIV...-1.pdf},
doi = { 10.1371/journal.pone.0048356. Epub 2012 Oct 29},
year = {2013},
date = {2013-10-29},
journal = {PloS One},
volume = {7},
number = {10},
abstract = {BACKGROUND:
Several population-wide HIV-1 subtype distribution studies in Uganda have evaluated relatively healthy clinic patients. Given the differences in HIV-1 disease progression based on subtype, we examined HIV-1 subtype distribution and disease outcomes among hospitalized patients with severe sepsis.
METHODS:
Patients with severe sepsis were enrolled at two hospitals in Uganda. Data collected included demographics, Karnofsky scores, highly active antiretroviral therapy (HAART) use, HIV-1 serostatus, CD4+ T cell concentration, whole blood lactate concentration, and blood cultures. HIV-1 subtypes were determined by sequencing parts of the gag and env genes, followed by phylogenetic analysis.
RESULTS:
Of the 267 patients evaluated, 228 (85.4%) were HIV infected. The predominant HIV-1 subtypes were A (46%), D (17%), and AD recombinants (30%). HIV-1 subtypes B, C, and other recombinants were uncommon. Patients infected with HIV-1 subtypes A, D and AD viruses were similar in demographics, CD4(+) T cell concentration, HAART use, Karnofsky scores, whole blood lactate concentration, and positive blood cultures. There was no difference in 30-day mortality from severe sepsis between the 3 groups (p = 0.99).
CONCLUSION:
A high proportion of HIV-1 subtypes A and AD recombinants was observed in this cohort of severely septic patients. The proportion of AD recombinants was higher in this cohort than in previous cohorts of Ugandan HIV-1 patients. No difference in baseline demographics, clinical factors or 30-day mortality was seen across HIV-subtypes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Several population-wide HIV-1 subtype distribution studies in Uganda have evaluated relatively healthy clinic patients. Given the differences in HIV-1 disease progression based on subtype, we examined HIV-1 subtype distribution and disease outcomes among hospitalized patients with severe sepsis.
METHODS:
Patients with severe sepsis were enrolled at two hospitals in Uganda. Data collected included demographics, Karnofsky scores, highly active antiretroviral therapy (HAART) use, HIV-1 serostatus, CD4+ T cell concentration, whole blood lactate concentration, and blood cultures. HIV-1 subtypes were determined by sequencing parts of the gag and env genes, followed by phylogenetic analysis.
RESULTS:
Of the 267 patients evaluated, 228 (85.4%) were HIV infected. The predominant HIV-1 subtypes were A (46%), D (17%), and AD recombinants (30%). HIV-1 subtypes B, C, and other recombinants were uncommon. Patients infected with HIV-1 subtypes A, D and AD viruses were similar in demographics, CD4(+) T cell concentration, HAART use, Karnofsky scores, whole blood lactate concentration, and positive blood cultures. There was no difference in 30-day mortality from severe sepsis between the 3 groups (p = 0.99).
CONCLUSION:
A high proportion of HIV-1 subtypes A and AD recombinants was observed in this cohort of severely septic patients. The proportion of AD recombinants was higher in this cohort than in previous cohorts of Ugandan HIV-1 patients. No difference in baseline demographics, clinical factors or 30-day mortality was seen across HIV-subtypes. |
Katusiime, Christine; Schlech, Walter F.; Parkes-Ratanshi, Rosalind; Sempa, Joseph; Bstat,; MBchB Andrew Kambugu, MMED Characteristics of Sexually Transmitted Infections among High-Risk HIV-Positive Patients Attending an Urban Clinic in Uganda Journal Article In: journal of the International Association of Providers of AIDS Care, vol. 15, no. 1, pp. 36-41, 2013. @article{Katusiime2013,
title = {Characteristics of Sexually Transmitted Infections among High-Risk HIV-Positive Patients Attending an Urban Clinic in Uganda},
author = {Christine Katusiime and Walter F. Schlech and Rosalind Parkes-Ratanshi and Joseph Sempa and Bstat and Andrew Kambugu, MBchB, MMED
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/characteristics-of-Sexually-Transmitted....pdf},
doi = {10.1177/2325957413506493},
year = {2013},
date = {2013-10-21},
journal = {journal of the International Association of Providers of AIDS Care},
volume = {15},
number = {1},
pages = {36-41},
abstract = {BACKGROUND:
Sexually transmitted infections (STIs) significantly increase HIV transmission. Sexually transmitted infections may be asymptomatic and therefore remain undiagnosed in HIV-positive persons. Routine screening and treatment of STIs in HIV-positive high-risk populations in sub-Saharan Africa have not been described previously.
METHODS:
We reviewed data from an HIV-positive high-risk population at the Infectious Diseases Institute, Makerere University, a large urban HIV clinic, between July 2011 and April 2012. Our high-risk population cohort included female sex workers, long-distance drivers, barmaids, taxi drivers, commercial motorcycle "boda-boda" riders, soldiers, police officers, prison officers, security guards, prisoners, and fishermen.
RESULTS:
Of 355 participants enrolled in the high-risk population's program, 21.4% were diagnosed with an STI either clinically or microbiologically. The STIs diagnosed in this population were syphilis, hepatitis B, genital herpes, human papilloma virus infection (condylomata acuminata), nongonococcal urethritis (NGU), and gonorrhea. Rates of syphilis, hepatitis B, genital herpes, condylomata acuminata, NGU, and gonorrhea were 8.5%, 7.0%, 5.4%, 1.4%, 1.4%, and 0.3%, respectively.
CONCLUSION:
Clinical and microbiologically diagnosed STIs were diagnosed in nearly one-fourth of the HIV-positive high-risk population. HIV care programs should note our high rates of STIs among HIV-positive high-risk populations and consider routine screening and treatment algorithms for these populations in their own settings},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Sexually transmitted infections (STIs) significantly increase HIV transmission. Sexually transmitted infections may be asymptomatic and therefore remain undiagnosed in HIV-positive persons. Routine screening and treatment of STIs in HIV-positive high-risk populations in sub-Saharan Africa have not been described previously.
METHODS:
We reviewed data from an HIV-positive high-risk population at the Infectious Diseases Institute, Makerere University, a large urban HIV clinic, between July 2011 and April 2012. Our high-risk population cohort included female sex workers, long-distance drivers, barmaids, taxi drivers, commercial motorcycle "boda-boda" riders, soldiers, police officers, prison officers, security guards, prisoners, and fishermen.
RESULTS:
Of 355 participants enrolled in the high-risk population's program, 21.4% were diagnosed with an STI either clinically or microbiologically. The STIs diagnosed in this population were syphilis, hepatitis B, genital herpes, human papilloma virus infection (condylomata acuminata), nongonococcal urethritis (NGU), and gonorrhea. Rates of syphilis, hepatitis B, genital herpes, condylomata acuminata, NGU, and gonorrhea were 8.5%, 7.0%, 5.4%, 1.4%, 1.4%, and 0.3%, respectively.
CONCLUSION:
Clinical and microbiologically diagnosed STIs were diagnosed in nearly one-fourth of the HIV-positive high-risk population. HIV care programs should note our high rates of STIs among HIV-positive high-risk populations and consider routine screening and treatment algorithms for these populations in their own settings |
Fenner, Lukas; Ballif, Marie; Graber, Claire; Nhandu, Venerandah; Dusingize, Jean Claude; Cortes, Claudia P.; Carriquiry, Gabriela; Anastos, Kathryn; Garone, Daniela; Jong, Eefje; Gnokoro, Joachim Charles; Sued, Omar; Ajayi, Samuel; Diero, Lameck; Wools-Kaloustian, Kara; Kiertiburanakul, Sasisopin; Castelnuovo, Barbara; Lewden, Charlotte; Durier, Nicolas; Sterling, Timothy R.; Matthias Egger, for the International epidemiological Databases to Evaluate AIDS (IeDEA) Tuberculosis in Antiretroviral Treatment Programs in Lower Income Countries: Availability and Use of Diagnostics and Screening Journal Article In: PloS One, vol. 8, no. 10, 2013. @article{Fenner2013,
title = {Tuberculosis in Antiretroviral Treatment Programs in Lower Income Countries: Availability and Use of Diagnostics and Screening},
author = {Lukas Fenner and Marie Ballif and Claire Graber and Venerandah Nhandu and Jean Claude Dusingize and Claudia P. Cortes and Gabriela Carriquiry and Kathryn Anastos and Daniela Garone and Eefje Jong and Joachim Charles Gnokoro and Omar Sued and Samuel Ajayi and Lameck Diero and Kara Wools-Kaloustian and Sasisopin Kiertiburanakul and Barbara Castelnuovo and Charlotte Lewden and Nicolas Durier and Timothy R. Sterling and Matthias Egger, for the International epidemiological Databases to Evaluate
AIDS (IeDEA)
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Tuberculosis-in-Antiretroviral-Treatment-Programs-in-lower-inome-countries.pdf},
doi = {10.1371/journal.pone.0077697},
year = {2013},
date = {2013-10-17},
journal = {PloS One},
volume = {8},
number = {10},
abstract = {OBJECTIVES:
In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries.
METHODS AND FINDINGS:
We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%).
CONCLUSIONS:
Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES:
In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries.
METHODS AND FINDINGS:
We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%).
CONCLUSIONS:
Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge |
Mullis, Caroline E.; Laeyendecker, Oliver; Reynolds, Steven J.; Ocama, Ponsiano; Quinn, Jeffrey; Boaz, Iga; Gray, Ronald H.; Kirk, Gregory D.; Thomas, David L.; Quinn, Thomas C.; Stabinski, Lara High Frequency of False-Positive Hepatitis C Virus Enzyme-Linked Immunosorbent Assay in Rakai, Uganda Journal Article In: Clinical Infectious Diseases, vol. 57, no. 12, pp. 1747-50, 2013. @article{Mullis2013,
title = {High Frequency of False-Positive Hepatitis C Virus Enzyme-Linked Immunosorbent Assay in Rakai, Uganda},
author = {Caroline E. Mullis and Oliver Laeyendecker and Steven J. Reynolds and Ponsiano Ocama and Jeffrey Quinn and Iga Boaz and Ronald H. Gray and Gregory D. Kirk and David L. Thomas and Thomas C. Quinn and
Lara Stabinski
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/High-frequency-of-false-positive-hepatitis-C-virus-enzyme-linked-immunosirbent-assay-in-Rakai-Uganda.pdf},
doi = {10.1093/cid/cit602},
year = {2013},
date = {2013-10-17},
journal = {Clinical Infectious Diseases},
volume = {57},
number = {12},
pages = {1747-50},
abstract = {The prevalence of hepatitis C virus (HCV) infection in sub-Saharan Africa remains unclear. We tested 1000 individuals from Rakai, Uganda, with the Ortho version 3.0 HCV enzyme-linked immunosorbent assay. All serologically positive samples were tested for HCV RNA. Seventy-six of the 1000 (7.6%) participants were HCV antibody positive; none were confirmed by detection of HCV RNA.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The prevalence of hepatitis C virus (HCV) infection in sub-Saharan Africa remains unclear. We tested 1000 individuals from Rakai, Uganda, with the Ortho version 3.0 HCV enzyme-linked immunosorbent assay. All serologically positive samples were tested for HCV RNA. Seventy-six of the 1000 (7.6%) participants were HCV antibody positive; none were confirmed by detection of HCV RNA. |
Nakiyingi, Lydia; Bwanika, John Mark; Kirenga, Bruce; Nakanjako, Damalie; Katabira, Catherine; Lubega, Gloria; Sempa, Joseph; Nyesiga, Barnabas; Albert, Heidi; Manabe, Yukari C. Clinical Predictors and Accuracy of Empiric Tuberculosis Treatment among Sputum Smear-Negative HIV-Infected Adult TB Suspects in Uganda Journal Article In: PloS One, vol. 8, no. 9, 2013. @article{Nakiyingi2013,
title = {Clinical Predictors and Accuracy of Empiric Tuberculosis Treatment among Sputum Smear-Negative HIV-Infected Adult TB Suspects in Uganda},
author = {Lydia Nakiyingi and John Mark Bwanika and Bruce Kirenga and Damalie Nakanjako and Catherine Katabira and Gloria Lubega and Joseph Sempa and Barnabas Nyesiga and Heidi Albert and Yukari C. Manabe
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Clinical-Predictors-and-Accuracy-of-Empiric-Tuberculosis....pdf},
doi = {10.1371/journal.pone.0074023},
year = {2013},
date = {2013-10-13},
journal = {PloS One},
volume = {8},
number = {9},
abstract = {INTRODUCTION:
The existing diagnostic algorithms for sputum smear-negative tuberculosis (TB) are complicated, time-consuming, and often difficult to implement. The decision to initiate TB treatment in resource-limited countries is often largely based on clinical predictors. We sought to determine the clinical predictors and accuracy of empiric TB treatment initiation in HIV-infected sputum smear-negative TB suspects using sputum culture as a reference standard.
SETTING:
Out-patient HIV-TB integrated urban clinic in Kampala, Uganda.
METHODS:
HIV-infected TB suspects were screened using sputum smear microscopy, and mycobacterial sputum liquid and solid cultures were performed. Smear results were made available to the clinician who made a clinical decision on empiric TB treatment initiation for sputum smear-negative patients. Clinic records were reviewed for patients whose sputum smears were negative to collect data on socio-demographics, TB symptomatology, chest X-ray findings, CD4 cell counts and TB treatment initiation.
RESULTS:
Of 253 smear-negative TB suspects, 56% (142/253) were females, median age 38 IQR (31-44) years, with a median CD4 cell count of 291 IQR (150-482) cells/mm(3). Of the 85 (33.6%) smear-negative patients empirically initiated on TB treatment, 35.3% (n = 30) were sputum culture positive compared to only 18 (10.7%) of the 168 untreated patients (p<0.001). Abnormal chest X-ray [aOR 10.18, 95% CI (3.14-33.00), p<0.001] and advanced HIV clinical stage [aOR 3.92, 95% CI (1.20-12.85), p = 0.024] were significantly associated with empiric TB treatment initiation. The sensitivity and specificity of empiric TB treatment initiation in the diagnosis of TB in HIV-infected patients after negative smear microscopy was 62.5% and 73.7% respectively.
CONCLUSION:
In resource-limited settings, clinically advanced HIV and abnormal chest X-ray significantly predict a clinical decision to empirically initiate TB treatment in smear-negative HIV-infected patients. Empiric TB treatment initiation correlates poorly with TB cultures. Affordable, accurate and rapid point-of-care diagnostics are needed in resource-limited settings to more accurately determine which HIV-infected TB suspects have smear-negative TB.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION:
The existing diagnostic algorithms for sputum smear-negative tuberculosis (TB) are complicated, time-consuming, and often difficult to implement. The decision to initiate TB treatment in resource-limited countries is often largely based on clinical predictors. We sought to determine the clinical predictors and accuracy of empiric TB treatment initiation in HIV-infected sputum smear-negative TB suspects using sputum culture as a reference standard.
SETTING:
Out-patient HIV-TB integrated urban clinic in Kampala, Uganda.
METHODS:
HIV-infected TB suspects were screened using sputum smear microscopy, and mycobacterial sputum liquid and solid cultures were performed. Smear results were made available to the clinician who made a clinical decision on empiric TB treatment initiation for sputum smear-negative patients. Clinic records were reviewed for patients whose sputum smears were negative to collect data on socio-demographics, TB symptomatology, chest X-ray findings, CD4 cell counts and TB treatment initiation.
RESULTS:
Of 253 smear-negative TB suspects, 56% (142/253) were females, median age 38 IQR (31-44) years, with a median CD4 cell count of 291 IQR (150-482) cells/mm(3). Of the 85 (33.6%) smear-negative patients empirically initiated on TB treatment, 35.3% (n = 30) were sputum culture positive compared to only 18 (10.7%) of the 168 untreated patients (p<0.001). Abnormal chest X-ray [aOR 10.18, 95% CI (3.14-33.00), p<0.001] and advanced HIV clinical stage [aOR 3.92, 95% CI (1.20-12.85), p = 0.024] were significantly associated with empiric TB treatment initiation. The sensitivity and specificity of empiric TB treatment initiation in the diagnosis of TB in HIV-infected patients after negative smear microscopy was 62.5% and 73.7% respectively.
CONCLUSION:
In resource-limited settings, clinically advanced HIV and abnormal chest X-ray significantly predict a clinical decision to empirically initiate TB treatment in smear-negative HIV-infected patients. Empiric TB treatment initiation correlates poorly with TB cultures. Affordable, accurate and rapid point-of-care diagnostics are needed in resource-limited settings to more accurately determine which HIV-infected TB suspects have smear-negative TB. |
Ssali, Agnes; Namukwaya, Stella; Bufumbo, Leonard; Seeley, Janet; Lalloo, David G.; Kamali, Anatoli; Parkes-Ratanshi, Rosalind Pregnancy in HIV Clinical Trials in Sub Saharan Africa: Failure of Consent or Contraception? Journal Article In: PloS One, vol. 8, no. 9, 2013. @article{Ssali2013,
title = {Pregnancy in HIV Clinical Trials in Sub Saharan Africa: Failure of Consent or Contraception?},
author = {Agnes Ssali and Stella Namukwaya and Leonard Bufumbo and Janet Seeley and David G. Lalloo and Anatoli Kamali and Rosalind Parkes-Ratanshi
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Pregnancy-in-HIV-clinical-trails-in-sub-saharan-Africa....pdf},
doi = {10.1371/journal.pone.0073556},
year = {2013},
date = {2013-10-10},
journal = {PloS One},
volume = {8},
number = {9},
abstract = {Objective
Higher than expected pregnancy rates have been observed in HIV related clinical trials in Sub-Saharan Africa. We designed a qualitative study to explore the factors contributing to high pregnancy rates among participants in two HIV clinical trials in Sub-Saharan Africa.
Methods
Female and male participants enrolled in one of two clinical HIV trials in south-west Uganda were approached. The trials were a phase III microbicide efficacy trial among HIV negative women using vaginal gel (MDP); and a trial of primary prevention prophylaxis for invasive cryptococcal disease using fluconazole among HIV infected men and women in Uganda (CRYPTOPRO). 14 focus group discussions and 8 in-depth interviews were conducted with HIV positive and negative women and their male partners over a six month period. Areas explored were their experiences about why and when one should get pregnant, factors affecting use of contraceptives, HIV status disclosure and trial product use.
Results
All respondents acknowledged being advised of the importance of avoiding pregnancy during the trial. Factors reported to contribute to pregnancy included; trust that the investigational product (oral capsules/vaginal gel) would not harm the baby, need for children, side effects that led to inconsistent contraceptive use, low acceptance of condom use among male partners. Attitudes towards getting pregnant are fluid within couples over time and the trials often last for more than a year. Researchers need to account for high pregnancy rates in their sample size calculations, and consider lesser used female initiated contraceptive options e.g. diaphragm or female condoms. In long clinical trials where there is a high fetal or maternal risk due to investigational product, researchers and ethics committees should consider a review of participants contraceptive needs/pregnancy desire review after a fixed period, as need for children, partners and health status of participants may alter over time.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objective
Higher than expected pregnancy rates have been observed in HIV related clinical trials in Sub-Saharan Africa. We designed a qualitative study to explore the factors contributing to high pregnancy rates among participants in two HIV clinical trials in Sub-Saharan Africa.
Methods
Female and male participants enrolled in one of two clinical HIV trials in south-west Uganda were approached. The trials were a phase III microbicide efficacy trial among HIV negative women using vaginal gel (MDP); and a trial of primary prevention prophylaxis for invasive cryptococcal disease using fluconazole among HIV infected men and women in Uganda (CRYPTOPRO). 14 focus group discussions and 8 in-depth interviews were conducted with HIV positive and negative women and their male partners over a six month period. Areas explored were their experiences about why and when one should get pregnant, factors affecting use of contraceptives, HIV status disclosure and trial product use.
Results
All respondents acknowledged being advised of the importance of avoiding pregnancy during the trial. Factors reported to contribute to pregnancy included; trust that the investigational product (oral capsules/vaginal gel) would not harm the baby, need for children, side effects that led to inconsistent contraceptive use, low acceptance of condom use among male partners. Attitudes towards getting pregnant are fluid within couples over time and the trials often last for more than a year. Researchers need to account for high pregnancy rates in their sample size calculations, and consider lesser used female initiated contraceptive options e.g. diaphragm or female condoms. In long clinical trials where there is a high fetal or maternal risk due to investigational product, researchers and ethics committees should consider a review of participants contraceptive needs/pregnancy desire review after a fixed period, as need for children, partners and health status of participants may alter over time.
|
Parikh, Sujal M.; Obuku, Ekwaro A.; Walker, Sarah A.; Semeere, Aggrey S.; Auerbach, Brandon J.; Hakim, James G.; Mayanja-Kizza, Harriet; Mugyenyi, Peter N.; Salata, Robert A.; Kityo, Cissy M.; on behalf of the DART Trial Team, Clinical Differences between Younger and Older Adults with HIV/AIDS Starting Antiretroviral Therapy in Uganda and Zimbabwe: A Secondary Analysis of the DART Trial Journal Article In: PloS One, vol. 8, no. 10, 2013. @article{Parikh2013,
title = {Clinical Differences between Younger and Older Adults with HIV/AIDS Starting Antiretroviral Therapy in Uganda and Zimbabwe: A Secondary Analysis of the DART Trial},
author = {Sujal M. Parikh and Ekwaro A. Obuku and Sarah A. Walker and Aggrey S. Semeere and Brandon J. Auerbach and James G. Hakim and Harriet Mayanja-Kizza and Peter N. Mugyenyi and Robert A. Salata and Cissy M. Kityo and on
behalf of the DART Trial Team},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Clinical-Differences-between-Younger-and-Older-Adults-with-HIVAIDS....pdf},
doi = {10.1371/journal.pone.0076158},
year = {2013},
date = {2013-10-02},
journal = {PloS One},
volume = {8},
number = {10},
abstract = {OBJECTIVE:
Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low-income African countries.
METHODS:
SETTING:
HIV clinics in Uganda and Zimbabwe.
DESIGN:
Secondary exploratory cross-sectional analysis of the DART randomized controlled trial.
OUTCOME MEASURES:
Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger) and ≥ 50 years (older), using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART) and one without.
RESULTS:
A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7%) were ≥ 50 years and 1160 (35%) were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important) higher CD4+ cell counts and higher plasma HIV-1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis.
CONCLUSIONS:
Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE:
Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low-income African countries.
METHODS:
SETTING:
HIV clinics in Uganda and Zimbabwe.
DESIGN:
Secondary exploratory cross-sectional analysis of the DART randomized controlled trial.
OUTCOME MEASURES:
Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger) and ≥ 50 years (older), using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART) and one without.
RESULTS:
A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7%) were ≥ 50 years and 1160 (35%) were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important) higher CD4+ cell counts and higher plasma HIV-1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis.
CONCLUSIONS:
Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy. |