2015
|
Claudia Disqué Freddie Bwanga, Michael G Lorenz Higher blood volumes improve the sensitivity of direct PCR diagnosis of blood stream tuberculosis among HIV-positive patients: an observation study Journal Article In: BMC Infectious Diseases, vol. 13, 2015. @article{Bwanga2015,
title = {Higher blood volumes improve the sensitivity of direct PCR diagnosis of blood stream tuberculosis among HIV-positive patients: an observation study},
author = {Freddie Bwanga, Claudia Disqué, Michael G Lorenz, Vera Allerheiligen, William Worodria, Allan Luyombya, Irene Najjingo & Michael Weizenegger },
doi = {https://doi.org/10.1186/s12879-015-0785-3},
year = {2015},
date = {2015-02-06},
journal = {BMC Infectious Diseases},
volume = {13},
abstract = {Background
Blood stream tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) is common among HIV-positive patients, turning rapidly fatal unless detected and treated promptly. Blood culture is currently the standard test for the detection of MTB in whole blood but results take weeks; patients deteriorate markedly and often die before a diagnosis of blood stream TB is made. Rapid molecular tests on whole blood, with potential for same day diagnosis of blood stream TB usually show low sensitivity due to the problem of insufficient MTB DNA template when extraction is performed directly on low blood volumes. This study assessed the influence of blood volume on the sensitivity of a HyBeacon PCR assay-the FluoroType® MTB (Hain Lifescience, Nehren, Germany) on direct detection of MTB in whole blood.
Methods
Prospective recruitment of HIV-positive patients with clinical suspicion of blood stream TB but not on anti-TB or HIV drug treatment was done. Venous blood samples were collected and DNA extracted using the MolYsis (Molzym, Bremen, Germany) methods; for study A, from duplicate 1 ml (42 patients) and for study B (31 patients) from 9 ml EDTA blood samples. The FluoroType® MTB PCR assay targeting an IS6110 sequence was performed and results compared with blood culture.
Results
The diagnostic sensitivity and specificity of the FluoroType® MTB PCR in study A was 33% and 97%, respectively. Corresponding values in study B were 71% and 96%, respectively. In both studies, one case each of blood culture-negative blood stream TB was detected with the FluoroType® MTB PCR assay. The median time to positivity of blood culture was 20.1 (range 12–32) for study A and 19.9 days (range 15–30) for study B.
Conclusion
Larger blood volumes (9 ml) improved and gave acceptable sensitivity of direct PCR diagnosis of blood stream TB.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Blood stream tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) is common among HIV-positive patients, turning rapidly fatal unless detected and treated promptly. Blood culture is currently the standard test for the detection of MTB in whole blood but results take weeks; patients deteriorate markedly and often die before a diagnosis of blood stream TB is made. Rapid molecular tests on whole blood, with potential for same day diagnosis of blood stream TB usually show low sensitivity due to the problem of insufficient MTB DNA template when extraction is performed directly on low blood volumes. This study assessed the influence of blood volume on the sensitivity of a HyBeacon PCR assay-the FluoroType® MTB (Hain Lifescience, Nehren, Germany) on direct detection of MTB in whole blood.
Methods
Prospective recruitment of HIV-positive patients with clinical suspicion of blood stream TB but not on anti-TB or HIV drug treatment was done. Venous blood samples were collected and DNA extracted using the MolYsis (Molzym, Bremen, Germany) methods; for study A, from duplicate 1 ml (42 patients) and for study B (31 patients) from 9 ml EDTA blood samples. The FluoroType® MTB PCR assay targeting an IS6110 sequence was performed and results compared with blood culture.
Results
The diagnostic sensitivity and specificity of the FluoroType® MTB PCR in study A was 33% and 97%, respectively. Corresponding values in study B were 71% and 96%, respectively. In both studies, one case each of blood culture-negative blood stream TB was detected with the FluoroType® MTB PCR assay. The median time to positivity of blood culture was 20.1 (range 12–32) for study A and 19.9 days (range 15–30) for study B.
Conclusion
Larger blood volumes (9 ml) improved and gave acceptable sensitivity of direct PCR diagnosis of blood stream TB. |
Joshua Rhein James E. Scriven, Katherine Huppler Hullsiek Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial Journal Article In: The Journal of Infectious Diseases, vol. 212, no. 5, pp. 769–778, 2015. @article{Scriven2015,
title = {Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial},
author = { James E. Scriven, Joshua Rhein, Katherine Huppler Hullsiek, Maximilian von Hohenberg, Grace Linder, Melissa A. Rolfes, Darlisha A. Williams, Kabanda Taseera, David B. Meya, Graeme Meintjes, David R. Boulware COAT Team},
doi = {https://doi.org/10.1093/infdis/jiv067},
year = {2015},
date = {2015-02-04},
journal = {The Journal of Infectious Diseases},
volume = {212},
number = {5},
pages = {769–778},
abstract = {Abstract
Introduction.
Earlier antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality compared with deferred ART initiation (1–2 weeks vs 5 weeks postmeningitis diagnosis). We hypothesized this was due to ART-associated immune pathology, without clinically recognized immune reconstitution inflammatory syndrome.
Methods.
Three macrophage activation markers and 19 cytokines/chemokines were measured from cryopreserved cerebrospinal fluid (CSF) and serum during the Cryptococcal Optimal ART Timing (COAT) trial. Comparisons were made between trial arms (early vs deferred) at 1, 8, 14, and 21 days following meningitis diagnosis.
Results.
More participants with early ART initiation had CSF white cell count (WCC) ≥5/µL at day 14 (58% vs 40%; P = .047), after a median of 6-days ART. Differences were mainly driven by participants with CSF WCC <5/µL at meningitis diagnosis: 28% (10/36) of such persons in the early ART group had CSF WCC ≥5/µL by day 14, compared with 0% (0/27) in the deferred arm (P = .002). Furthermore, Kampala participants (the largest site) receiving early ART had higher day-14 CSF levels of interleukin-13 (P = .04), sCD14 (P = .04), sCD163 (P = .02), and CCL3/MIP-1α (P = .02), suggesting increased macrophage/microglial activation.
Conclusions.
Early ART initiation in cryptococcal meningitis increased CSF cellular infiltrate, macrophage/microglial activation, and T helper 2 responses within the central nervous system. This suggests that increased mortality from early ART in the COAT trial was immunologically mediated.
Key Terms
AIDS, cryptococcal meningitis, HIV, immunology, IRIS, macrophage, randomized controlled trial, sCD14, sCD163
Topic:
cytokine meningitis central nervous system chemokines cryptococcal meningitis cryopreservation interleukin-13 leukocytes macrophages arm cerebrospinal fluid cryptococcus diagnosis macrophage activation mortality pathology anti-retroviral agents immune reconstitution inflammatory syndrome csf pleocytosis infiltrates
Issue Section:
Fungi },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Abstract
Introduction.
Earlier antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality compared with deferred ART initiation (1–2 weeks vs 5 weeks postmeningitis diagnosis). We hypothesized this was due to ART-associated immune pathology, without clinically recognized immune reconstitution inflammatory syndrome.
Methods.
Three macrophage activation markers and 19 cytokines/chemokines were measured from cryopreserved cerebrospinal fluid (CSF) and serum during the Cryptococcal Optimal ART Timing (COAT) trial. Comparisons were made between trial arms (early vs deferred) at 1, 8, 14, and 21 days following meningitis diagnosis.
Results.
More participants with early ART initiation had CSF white cell count (WCC) ≥5/µL at day 14 (58% vs 40%; P = .047), after a median of 6-days ART. Differences were mainly driven by participants with CSF WCC <5/µL at meningitis diagnosis: 28% (10/36) of such persons in the early ART group had CSF WCC ≥5/µL by day 14, compared with 0% (0/27) in the deferred arm (P = .002). Furthermore, Kampala participants (the largest site) receiving early ART had higher day-14 CSF levels of interleukin-13 (P = .04), sCD14 (P = .04), sCD163 (P = .02), and CCL3/MIP-1α (P = .02), suggesting increased macrophage/microglial activation.
Conclusions.
Early ART initiation in cryptococcal meningitis increased CSF cellular infiltrate, macrophage/microglial activation, and T helper 2 responses within the central nervous system. This suggests that increased mortality from early ART in the COAT trial was immunologically mediated.
Key Terms
AIDS, cryptococcal meningitis, HIV, immunology, IRIS, macrophage, randomized controlled trial, sCD14, sCD163
Topic:
cytokine meningitis central nervous system chemokines cryptococcal meningitis cryopreservation interleukin-13 leukocytes macrophages arm cerebrospinal fluid cryptococcus diagnosis macrophage activation mortality pathology anti-retroviral agents immune reconstitution inflammatory syndrome csf pleocytosis infiltrates
Issue Section:
Fungi |
Stephen Walimbwa Mohammed Lamorde, Pauline Byakika-Kibwika Steady-state pharmacokinetics of rilpivirine under different meal conditions in HIV-1-infected Ugandan adults Journal Article In: Journal of Antimicrobial Chemotherapy, vol. 70, no. 5, pp. 1482–1486, 2015. @article{Lamorde2015,
title = {Steady-state pharmacokinetics of rilpivirine under different meal conditions in HIV-1-infected Ugandan adults},
author = {Mohammed Lamorde, Stephen Walimbwa, Pauline Byakika-Kibwika, Michael Katwere, Lillian Mukisa, Joseph B. Sempa, Laura Else, David J. Back, Saye H. Khoo, Concepta Merry},
doi = {https://doi.org/10.1093/jac/dku575},
year = {2015},
date = {2015-02-03},
journal = {Journal of Antimicrobial Chemotherapy},
volume = {70},
number = {5},
pages = {1482–1486},
abstract = {Objectives
To investigate the effect of food on the steady-state pharmacokinetics of rilpivirine when administered as a fixed-dose combination tablet containing tenofovir disoproxil fumarate, emtricitabine plus rilpivirine (TDF/FTC/RPV) in HIV-1-infected Ugandan patients.
Methods
This was an open-label, three-period, longitudinal pharmacokinetic study with patients serving as their own controls. Fifteen consenting and virologically suppressed HIV-1-infected adults were switched from an efavirenz-based regimen to TDF/FTC/RPV for 56 days. Enrolled patients underwent 24 h blood sampling with TDF/FTC/RPV dosing in the fasted state (day 42), with a low-fat meal (11 g of fat/353 kcal, day 49) and with a moderate-fat meal (19 g of fat/589 kcal, day 56; reference). A viral load assessment was performed on day 56.
Results
Rilpivirine AUC0–24 was significantly decreased by 16% (geometric mean ratio, 90% CI: 0.84, 0.73–0.96) during administration in the fasted state when compared with AUC0–24 during administration with a moderate-fat meal. Similarly, rilpivirine C24 was significantly decreased by 21% (0.79, 0.65–0.97) in the fasted state compared with a moderate-fat meal. Pharmacokinetic parameters were unchanged during administration with a low-fat meal, except for C24, which was significantly increased by 15% (1.15, 1.01–1.31) when compared with the moderate-fat meal. Rilpivirine Cmax was similar under the three meal conditions. Virological suppression was unchanged at the end of the study.
Conclusions
A food effect was observed for steady-state pharmacokinetic parameters of rilpivirine (AUC0–24 and C24) when TDF/FTC/RPV was administered in the fasted state compared with the moderate-fat meal. The TDF/FTC/RPV formulation can be administered with either a low-fat or moderate-fat meal.
Key Terms
Complera, food–drug interactions, sub-Saharan Africa
Topic:
hiv steady state efavirenz adult food tablet dosage form pharmacokinetics tenofovir emtricitabine tenofovir/emtricitabine rilpivirine },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objectives
To investigate the effect of food on the steady-state pharmacokinetics of rilpivirine when administered as a fixed-dose combination tablet containing tenofovir disoproxil fumarate, emtricitabine plus rilpivirine (TDF/FTC/RPV) in HIV-1-infected Ugandan patients.
Methods
This was an open-label, three-period, longitudinal pharmacokinetic study with patients serving as their own controls. Fifteen consenting and virologically suppressed HIV-1-infected adults were switched from an efavirenz-based regimen to TDF/FTC/RPV for 56 days. Enrolled patients underwent 24 h blood sampling with TDF/FTC/RPV dosing in the fasted state (day 42), with a low-fat meal (11 g of fat/353 kcal, day 49) and with a moderate-fat meal (19 g of fat/589 kcal, day 56; reference). A viral load assessment was performed on day 56.
Results
Rilpivirine AUC0–24 was significantly decreased by 16% (geometric mean ratio, 90% CI: 0.84, 0.73–0.96) during administration in the fasted state when compared with AUC0–24 during administration with a moderate-fat meal. Similarly, rilpivirine C24 was significantly decreased by 21% (0.79, 0.65–0.97) in the fasted state compared with a moderate-fat meal. Pharmacokinetic parameters were unchanged during administration with a low-fat meal, except for C24, which was significantly increased by 15% (1.15, 1.01–1.31) when compared with the moderate-fat meal. Rilpivirine Cmax was similar under the three meal conditions. Virological suppression was unchanged at the end of the study.
Conclusions
A food effect was observed for steady-state pharmacokinetic parameters of rilpivirine (AUC0–24 and C24) when TDF/FTC/RPV was administered in the fasted state compared with the moderate-fat meal. The TDF/FTC/RPV formulation can be administered with either a low-fat or moderate-fat meal.
Key Terms
Complera, food–drug interactions, sub-Saharan Africa
Topic:
hiv steady state efavirenz adult food tablet dosage form pharmacokinetics tenofovir emtricitabine tenofovir/emtricitabine rilpivirine |
Timothy D. Walker Fredrick Kateera, Leon Mutesa Hepatitis B and C seroprevalence among health care workers in a tertiary hospital in Rwanda Journal Article In: Transactions of The Royal Society of Tropical Medicine and Hygiene, vol. 109, no. 3, pp. 203–208, 2015. @article{Kateera2015,
title = {Hepatitis B and C seroprevalence among health care workers in a tertiary hospital in Rwanda},
author = {Fredrick Kateera, Timothy D. Walker, Leon Mutesa, Vincent Mutabazi, Emmanuel Musabeyesu, Constance Mukabatsinda, Pascal Bihizimana, Patrick Kyamanywa, Ben Karenzi, Judy T. Orikiiriza},
doi = {https://doi.org/10.1093/trstmh/trv004},
year = {2015},
date = {2015-01-30},
journal = {Transactions of The Royal Society of Tropical Medicine and Hygiene},
volume = {109},
number = {3},
pages = {203–208},
abstract = {Background
Hepatitis B (HBV) and hepatitis C (HCV) are significant global public health challenges with health care workers (HCWs) at especially high risk of exposure in resource-poor settings. We aimed to measure HBV and HCV prevalence, identify exposure risks and evaluate hepatitis-related knowledge amongst Rwandan tertiary hospital HCWs.
Methods
A cross sectional study involving tertiary hospital employees was conducted from October to December 2013. A pre-coded questionnaire was used to collect data on HCWs' socio-demographics, risk factors and knowledge of blood-borne infection prevention. Blood samples were drawn and screened for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies.
Results
Among 378 consenting HCWs, the prevalence of HBsAg positivity was 2.9% (11/378; 95% CI: 1.9 to 4.6%) and anti-HCV positivity 1.3% (5/378; 95% CI: 0.7 to 2.7%). Occupational exposure to blood was reported in 57.1% (216/378). Of the 17 participants (4.5%; 17/378) who reported having received the HBV vaccine, only 3 participants (0.8%) had received the three-dose vaccination course. Only 42 HCWs (42/378; 11.1%) were aware that a HBV vaccine was available. Most HCW (95.2%; 360/378) reported having been tested for HIV in the last 6 months.
Conclusions
Despite their high workplace exposure risk, HBV and HCV sero-prevalence rates among HCWs were low. The low HBV vaccination coverage and poor knowledge of preventative measures among HCWs suggest low levels of viral hepatitis awareness despite this high exposure.
Key Terms
Health care workers, Hepatitis B, Hepatitis C, Rwanda
Topic:
hiv hepatitis hepatitis b hepatitis c demography health personnel hepatitis b surface antigens hepatitis c antibodies occupational exposure rwanda vaccination hepatitis b virus hepatitis b virus measurement public health medicine viral hepatitis hepatitis b vaccines hepatitis c virus infection prophylaxis seroprevalence lack of medical resources employee },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Hepatitis B (HBV) and hepatitis C (HCV) are significant global public health challenges with health care workers (HCWs) at especially high risk of exposure in resource-poor settings. We aimed to measure HBV and HCV prevalence, identify exposure risks and evaluate hepatitis-related knowledge amongst Rwandan tertiary hospital HCWs.
Methods
A cross sectional study involving tertiary hospital employees was conducted from October to December 2013. A pre-coded questionnaire was used to collect data on HCWs' socio-demographics, risk factors and knowledge of blood-borne infection prevention. Blood samples were drawn and screened for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies.
Results
Among 378 consenting HCWs, the prevalence of HBsAg positivity was 2.9% (11/378; 95% CI: 1.9 to 4.6%) and anti-HCV positivity 1.3% (5/378; 95% CI: 0.7 to 2.7%). Occupational exposure to blood was reported in 57.1% (216/378). Of the 17 participants (4.5%; 17/378) who reported having received the HBV vaccine, only 3 participants (0.8%) had received the three-dose vaccination course. Only 42 HCWs (42/378; 11.1%) were aware that a HBV vaccine was available. Most HCW (95.2%; 360/378) reported having been tested for HIV in the last 6 months.
Conclusions
Despite their high workplace exposure risk, HBV and HCV sero-prevalence rates among HCWs were low. The low HBV vaccination coverage and poor knowledge of preventative measures among HCWs suggest low levels of viral hepatitis awareness despite this high exposure.
Key Terms
Health care workers, Hepatitis B, Hepatitis C, Rwanda
Topic:
hiv hepatitis hepatitis b hepatitis c demography health personnel hepatitis b surface antigens hepatitis c antibodies occupational exposure rwanda vaccination hepatitis b virus hepatitis b virus measurement public health medicine viral hepatitis hepatitis b vaccines hepatitis c virus infection prophylaxis seroprevalence lack of medical resources employee |
Victor Musiime Mutsawashe Bwakura-Dangarembizi, Alexander J. Szubert; Kusum Nathoo, for the ARROW Trial Team Prevalence of Lipodystrophy and Metabolic Abnormalities in HIV-infected African Children after 3 Years on First-line Antiretroviral Therapy Journal Article In: The Pediatric Infectious Disease Journal, vol. 34, no. 2, pp. e23–e31, 2015. @article{Bwakura-Dangarembizi2015,
title = {Prevalence of Lipodystrophy and Metabolic Abnormalities in HIV-infected African Children after 3 Years on First-line Antiretroviral Therapy},
author = {Mutsawashe Bwakura-Dangarembizi, Victor Musiime, Alexander J. Szubert, Andrew J. Prendergast, Dphil, Zvenyika A. Gomo, Margaret J. Thomason, Cuthbert Musarurwa, Peter Mugyenyi, Patricia Nahirya, Adeodata Kekitiinwa, Diana M. Gibb, Ann S. Walker and Kusum Nathoo, for the ARROW Trial Team},
doi = {doi: 10.1097/INF.0000000000000491},
year = {2015},
date = {2015-01-26},
journal = {The Pediatric Infectious Disease Journal},
volume = {34},
number = {2},
pages = {e23–e31},
abstract = {Background:
Most pediatric lipodystrophy data come from high-income/middle-income countries, but most HIV-infected children live in sub-Saharan Africa, where lipodystrophy studies have predominantly investigated stavudine-based regimens.
Methods:
Three years after antiretroviral therapy (ART) initiation, body circumferences and skinfold thicknesses were measured (n = 590), and fasted lipid profile assayed (n = 325), in children from 2 ARROW trial centres in Uganda/Zimbabwe. Analyses compared randomization to long-term versus short-term versus no zidovudine from ART initiation [unadjusted; latter 2 groups receiving abacavir+lamivudine+non-nucleoside-reverse-transciptase-inhibitor (nNRTI) long-term], and nonrandomized (confounder-adjusted) receipt of nevirapine versus efavirenz.
Results:
Body circumferences and skinfold thicknesses were similar regardless of zidovudine exposure (P > 0.1), except for subscapular and supra-iliac skinfolds-for-age which were greater with long-term zidovudine (0.006 < P < 0.047). Circumferences/skinfolds were also similar with efavirenz and nevirapine (adjusted P > 0.09; 0.02 < P < 0.03 for waist/waist-hip-ratio). Total and high-density lipoprotein (HDL)-cholesterol, HDL/triglyceride-ratio (P < 0.0001) and triglycerides (P = 0.01) were lower with long-term zidovudine. Low-density lipoprotein (LDL)-cholesterol was higher with efavirenz than nevirapine (P < 0.001). Most lipids remained within normal ranges (75% cholesterol, 85% LDL and 100% triglycerides) but more on long-term zidovudine (3 NRTI) had abnormal HDL-cholesterol (88% vs. 40% short/no-zidovudine, P < 0.0001). Only 8/579(1.4%) children had clinical fat wasting (5 grade 1; 3 grade 2); 2(0.3%) had grade 1 fat accumulation.
Conclusions:
Long-term zidovudine-based ART is associated with similar body circumferences and skinfold thicknesses to abacavir-based ART, with low rates of lipid abnormalities and clinical lipodystrophy, providing reassurance where national programs now recommend long-term zidovudine. Efavirenz and nevirapine were also similar; however, the higher LDL observed with efavirenz and lower HDL observed with zidovudine suggests that zidovudine+lamivudine+efavirenz should be investigated in future.
Keywords:
HIV, Africa, children, antiretroviral therapy, lipodystrophy, lipids},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background:
Most pediatric lipodystrophy data come from high-income/middle-income countries, but most HIV-infected children live in sub-Saharan Africa, where lipodystrophy studies have predominantly investigated stavudine-based regimens.
Methods:
Three years after antiretroviral therapy (ART) initiation, body circumferences and skinfold thicknesses were measured (n = 590), and fasted lipid profile assayed (n = 325), in children from 2 ARROW trial centres in Uganda/Zimbabwe. Analyses compared randomization to long-term versus short-term versus no zidovudine from ART initiation [unadjusted; latter 2 groups receiving abacavir+lamivudine+non-nucleoside-reverse-transciptase-inhibitor (nNRTI) long-term], and nonrandomized (confounder-adjusted) receipt of nevirapine versus efavirenz.
Results:
Body circumferences and skinfold thicknesses were similar regardless of zidovudine exposure (P > 0.1), except for subscapular and supra-iliac skinfolds-for-age which were greater with long-term zidovudine (0.006 < P < 0.047). Circumferences/skinfolds were also similar with efavirenz and nevirapine (adjusted P > 0.09; 0.02 < P < 0.03 for waist/waist-hip-ratio). Total and high-density lipoprotein (HDL)-cholesterol, HDL/triglyceride-ratio (P < 0.0001) and triglycerides (P = 0.01) were lower with long-term zidovudine. Low-density lipoprotein (LDL)-cholesterol was higher with efavirenz than nevirapine (P < 0.001). Most lipids remained within normal ranges (75% cholesterol, 85% LDL and 100% triglycerides) but more on long-term zidovudine (3 NRTI) had abnormal HDL-cholesterol (88% vs. 40% short/no-zidovudine, P < 0.0001). Only 8/579(1.4%) children had clinical fat wasting (5 grade 1; 3 grade 2); 2(0.3%) had grade 1 fat accumulation.
Conclusions:
Long-term zidovudine-based ART is associated with similar body circumferences and skinfold thicknesses to abacavir-based ART, with low rates of lipid abnormalities and clinical lipodystrophy, providing reassurance where national programs now recommend long-term zidovudine. Efavirenz and nevirapine were also similar; however, the higher LDL observed with efavirenz and lower HDL observed with zidovudine suggests that zidovudine+lamivudine+efavirenz should be investigated in future.
Keywords:
HIV, Africa, children, antiretroviral therapy, lipodystrophy, lipids |
Willy Ssengooba Bruce J Kirenga, Catherine Muwonge Tuberculosis risk factors among tuberculosis patients in Kampala, Uganda: implications for tuberculosis control Journal Article In: BMC Public Health, vol. 15, no. 13, 2015. @article{Kirenga2015,
title = {Tuberculosis risk factors among tuberculosis patients in Kampala, Uganda: implications for tuberculosis control},
author = {Bruce J Kirenga, Willy Ssengooba, Catherine Muwonge, Lydia Nakiyingi, Stephen Kyaligonza, Samuel Kasozi, Frank Mugabe, Martin Boeree, Moses Joloba & Alphonse Okwera },
doi = {https://doi.org/10.1186/s12889-015-1376-3},
year = {2015},
date = {2015-01-21},
journal = {BMC Public Health},
volume = {15},
number = {13},
abstract = {Background
Slow decline in the incidence of tuberculosis (TB) has been observed in most high TB burden countries. Knowledge of the prevalence of different TB risk factors can help expand TB control strategies. However with the exception of Human Immunodeficiency Virus (HIV) the prevalence of the other TB risk factors are poorly studied in Uganda. We aimed to determine the prevalence of different TB risk factors and TB disease presentation among TB patients in Kampala Uganda.
Methods
We assessed 365 adult TB patients and used descriptive statistics to summarize their socio-demographic, clinical, radiological, sputum mycobacteriology and TB risk factors (HIV, diabetes, TB contact, alcohol use, tobacco smoking, poverty and overcrowding) data.
Results
A total of 158 (43.3%) patients were male and the median age was 29 (IQR 28–30). Majority of the patients (89.2%) had pulmonary TB, 86.9% were new and 13.2% were retreatment. Wasting (i.e. body mass index of <18.5 kg/m2) was found in 38.5% of the patients and 63% presented with cough. Constitutional symptoms (fever, anorexia, night sweats and weight loss) were reported by 32.1%. Most patients (78.6%) presented with non-cavity lung parenchyma disease (infiltrates, nodules, masses) but 35.2% had cavity disease. Pleural disease was detected in 19.3% of patients. Positive smear microscopy and culture (irrespective of month of treatment) was found in 52.7% and 36.5% of patients respectively. Any drug resistance was detected in 21.1% of patients while multidrug resistance (MDR) TB defined as resistance to rifampicin and isoniazid was detected in 6.3% of patients. All MDR patients were new patients.
The prevalence of TB risk factors were as follows: HIV 41.4%, diabetes 5.4%, close contact 11.5%, family history 17.5%, smoking 26.37%, poverty 39.5%, overcrowding 57.3% and alcohol use 50.7%. Overcrowding increased smear positive rate, prevalence ratio 1.22, p = 0.09 but all the other studied risk factors did not affect clinical, radiological and mycobacteriological study patient characteristics.
Conclusions
Among TB patients in Kampala, Uganda, there is high prevalence of the known TB risk factors. Targeting reducing their prevalence may lead to better TB control in the country. Tuberculosis, risk factors, Uganda.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Slow decline in the incidence of tuberculosis (TB) has been observed in most high TB burden countries. Knowledge of the prevalence of different TB risk factors can help expand TB control strategies. However with the exception of Human Immunodeficiency Virus (HIV) the prevalence of the other TB risk factors are poorly studied in Uganda. We aimed to determine the prevalence of different TB risk factors and TB disease presentation among TB patients in Kampala Uganda.
Methods
We assessed 365 adult TB patients and used descriptive statistics to summarize their socio-demographic, clinical, radiological, sputum mycobacteriology and TB risk factors (HIV, diabetes, TB contact, alcohol use, tobacco smoking, poverty and overcrowding) data.
Results
A total of 158 (43.3%) patients were male and the median age was 29 (IQR 28–30). Majority of the patients (89.2%) had pulmonary TB, 86.9% were new and 13.2% were retreatment. Wasting (i.e. body mass index of <18.5 kg/m2) was found in 38.5% of the patients and 63% presented with cough. Constitutional symptoms (fever, anorexia, night sweats and weight loss) were reported by 32.1%. Most patients (78.6%) presented with non-cavity lung parenchyma disease (infiltrates, nodules, masses) but 35.2% had cavity disease. Pleural disease was detected in 19.3% of patients. Positive smear microscopy and culture (irrespective of month of treatment) was found in 52.7% and 36.5% of patients respectively. Any drug resistance was detected in 21.1% of patients while multidrug resistance (MDR) TB defined as resistance to rifampicin and isoniazid was detected in 6.3% of patients. All MDR patients were new patients.
The prevalence of TB risk factors were as follows: HIV 41.4%, diabetes 5.4%, close contact 11.5%, family history 17.5%, smoking 26.37%, poverty 39.5%, overcrowding 57.3% and alcohol use 50.7%. Overcrowding increased smear positive rate, prevalence ratio 1.22, p = 0.09 but all the other studied risk factors did not affect clinical, radiological and mycobacteriological study patient characteristics.
Conclusions
Among TB patients in Kampala, Uganda, there is high prevalence of the known TB risk factors. Targeting reducing their prevalence may lead to better TB control in the country. Tuberculosis, risk factors, Uganda. |
Simon Walker Paul A. Revill, Travor Mabugu; Gibb, Diana M. Opportunities for improving the efficiency of paediatric HIV treatment programmes Journal Article In: AIDS, vol. 29, no. 2, pp. 201–210, 2015. @article{Revill2015,
title = {Opportunities for improving the efficiency of paediatric HIV treatment programmes},
author = {Paul A. Revill, Simon Walker, Travor Mabugu,b Kusum J. Nathoo, Peter Mugyenyi, Adeodata Kekitinwa, Paula Munderi, Mutsawashe Bwakura-Dangarembizi, Victor Musiime, Sabrina Bakeera-Kitaka, Patricia Nahirya-Ntege, A. Sarah Walker, Mark J. Sculpher and Diana M. Gibb},
doi = {doi: 10.1097/QAD.0000000000000518},
year = {2015},
date = {2015-01-14},
journal = {AIDS},
volume = {29},
number = {2},
pages = {201–210},
abstract = {Objectives:
To conduct two economic analyses addressing whether to: routinely monitor HIV-infected children on antiretroviral therapy (ART) clinically or with laboratory tests; continue or stop cotrimoxazole prophylaxis when children become stabilized on ART.
Design and methods:
The ARROW randomized trial investigated alternative strategies to deliver paediatric ART and cotrimoxazole prophylaxis in 1206 Ugandan/Zimbabwean children. Incremental cost-effectiveness and value of implementation analyses were undertaken. Scenario analyses investigated whether laboratory monitoring (CD4+ tests for efficacy monitoring; haematology/biochemistry for toxicity) could be tailored and targeted to be delivered cost-effectively. Cotrimoxazole use was examined in malaria-endemic and non-endemic settings.
Results:
Using all trial data, clinical monitoring delivered similar health outcomes to routine laboratory monitoring, but at a reduced cost, so was cost-effective. Continuing cotrimoxazole improved health outcomes at reduced costs. Restricting routine CD4+ monitoring to after 52 weeks following ART initiation and removing toxicity testing was associated with an incremental cost-effectiveness ratio of $6084 per quality-adjusted life-year (QALY) across all age groups, but was much lower for older children (12+ years at initiation; incremental cost-effectiveness ratio = $769/QALY). Committing resources to improve cotrimoxazole implementation appears cost-effective. A healthcare system that could pay $600/QALY should be willing to spend up to $12.0 per patient-year to ensure continued provision of cotrimoxazole.
Conclusion:
Clinically driven monitoring of ART is cost-effective in most circumstances. Routine laboratory monitoring is generally not cost-effective at current prices, except possibly CD4+ testing amongst adolescents initiating ART. Committing resources to ensure continued provision of cotrimoxazole in health facilities is more likely to represent an efficient use of resources.
Keywords: Africa, children, cotrimoxazole, HIV, laboratory monitoring},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objectives:
To conduct two economic analyses addressing whether to: routinely monitor HIV-infected children on antiretroviral therapy (ART) clinically or with laboratory tests; continue or stop cotrimoxazole prophylaxis when children become stabilized on ART.
Design and methods:
The ARROW randomized trial investigated alternative strategies to deliver paediatric ART and cotrimoxazole prophylaxis in 1206 Ugandan/Zimbabwean children. Incremental cost-effectiveness and value of implementation analyses were undertaken. Scenario analyses investigated whether laboratory monitoring (CD4+ tests for efficacy monitoring; haematology/biochemistry for toxicity) could be tailored and targeted to be delivered cost-effectively. Cotrimoxazole use was examined in malaria-endemic and non-endemic settings.
Results:
Using all trial data, clinical monitoring delivered similar health outcomes to routine laboratory monitoring, but at a reduced cost, so was cost-effective. Continuing cotrimoxazole improved health outcomes at reduced costs. Restricting routine CD4+ monitoring to after 52 weeks following ART initiation and removing toxicity testing was associated with an incremental cost-effectiveness ratio of $6084 per quality-adjusted life-year (QALY) across all age groups, but was much lower for older children (12+ years at initiation; incremental cost-effectiveness ratio = $769/QALY). Committing resources to improve cotrimoxazole implementation appears cost-effective. A healthcare system that could pay $600/QALY should be willing to spend up to $12.0 per patient-year to ensure continued provision of cotrimoxazole.
Conclusion:
Clinically driven monitoring of ART is cost-effective in most circumstances. Routine laboratory monitoring is generally not cost-effective at current prices, except possibly CD4+ testing amongst adolescents initiating ART. Committing resources to ensure continued provision of cotrimoxazole in health facilities is more likely to represent an efficient use of resources.
Keywords: Africa, children, cotrimoxazole, HIV, laboratory monitoring |
Gertrude Namale Yukari C Manabe, Elizabeth Nalintya Integration of antenatal syphilis screening in an urban HIV clinic: a feasibility study Journal Article In: BMC Infectious Diseases , 2015. @article{Manabe2015,
title = {Integration of antenatal syphilis screening in an urban HIV clinic: a feasibility study},
author = {Yukari C Manabe, Gertrude Namale, Elizabeth Nalintya, Joseph Sempa, Rosalind Parkes Ratanshi, Nadine Pakker & Elly Katabira },
doi = {https://doi.org/10.1186/s12879-014-0739-1},
year = {2015},
date = {2015-01-13},
journal = {BMC Infectious Diseases },
abstract = {Background
Syphilis infection during pregnancy leads to avoidable morbidity and mortality and remains a significant problem in sub-Saharan Africa. Despite global initiatives to increase the proportion of pregnant women screened, implementation has been slow. We sought to investigate the feasibility of adding syphilis screening within an integrated antenatal HIV clinic.
Methods
Pregnant women attending the HIV antenatal clinic were sequentially enrolled and consenting participants answered a questionnaire on sexual behavior and previous pregnancies, provided sociodemographic data, and were tested using rapid plasmin reagin (RPR). If positive, participants were treated with benzathine penicillin. All were given a partner notification slip and were followed up after delivery to determine birth outcomes.
Results
584 of 606 (95.7%) women approached and consented to test for syphilis. 570 women were enrolled (median age 29 (IQR 25–32) with a median (IQR) CD4 of 372 (257–569) cells/μL). Of the 5.1% (29/570) with a positive RPR, all were asymptomatic, were successfully contacted, and treated with benzathine penicillin without adverse reactions. Overall, 61 (12.1%) of the participants had an adverse birth outcome. In the bivariate analysis, only age was significantly different between those with and without a positive RPR (RR = 1.15, 95% CI 1.065-1.248; p < 0.001). Partners of only 10 (34.5%) participants returned for treatment.
Conclusions
Structural interventions such as opt-out testing for syphilis within integrated HIV-antenatal care clinics are feasible and capitalize on the excellent care programs that have already been established for HIV care. Novel approaches are required for partner notification.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Syphilis infection during pregnancy leads to avoidable morbidity and mortality and remains a significant problem in sub-Saharan Africa. Despite global initiatives to increase the proportion of pregnant women screened, implementation has been slow. We sought to investigate the feasibility of adding syphilis screening within an integrated antenatal HIV clinic.
Methods
Pregnant women attending the HIV antenatal clinic were sequentially enrolled and consenting participants answered a questionnaire on sexual behavior and previous pregnancies, provided sociodemographic data, and were tested using rapid plasmin reagin (RPR). If positive, participants were treated with benzathine penicillin. All were given a partner notification slip and were followed up after delivery to determine birth outcomes.
Results
584 of 606 (95.7%) women approached and consented to test for syphilis. 570 women were enrolled (median age 29 (IQR 25–32) with a median (IQR) CD4 of 372 (257–569) cells/μL). Of the 5.1% (29/570) with a positive RPR, all were asymptomatic, were successfully contacted, and treated with benzathine penicillin without adverse reactions. Overall, 61 (12.1%) of the participants had an adverse birth outcome. In the bivariate analysis, only age was significantly different between those with and without a positive RPR (RR = 1.15, 95% CI 1.065-1.248; p < 0.001). Partners of only 10 (34.5%) participants returned for treatment.
Conclusions
Structural interventions such as opt-out testing for syphilis within integrated HIV-antenatal care clinics are feasible and capitalize on the excellent care programs that have already been established for HIV care. Novel approaches are required for partner notification. |
Mohammed Lamorde Abdulrazaq G. Habib, Mahmood M. Dalhat Cost-effectiveness of Antivenoms for Snakebite Envenoming in Nigeria Journal Article In: PLOS Neglected Tropical Diseases, vol. 9, no. 1, pp. e3381, 2015. @article{Habib2015,
title = {Cost-effectiveness of Antivenoms for Snakebite Envenoming in Nigeria},
author = {Abdulrazaq G. Habib, Mohammed Lamorde, Mahmood M. Dalhat, Zaiyad G. Habib, Andreas Kuznik},
doi = {https://doi.org/10.1371/journal.pntd.0003381},
year = {2015},
date = {2015-01-08},
journal = {PLOS Neglected Tropical Diseases},
volume = {9},
number = {1},
pages = {e3381},
abstract = {Background
Snakebite envenoming is a major public health problem throughout the rural tropics. Antivenom is effective in reducing mortality and remains the mainstay of therapy. This study aimed to determine the cost-effectiveness of using effective antivenoms for Snakebite envenoming in Nigeria.
Methodology
Economic analysis was conducted from a public healthcare system perspective. Estimates of model inputs were obtained from the literature. Incremental Cost Effectiveness Ratios (ICERs) were quantified as deaths and Disability-Adjusted-Life-Years (DALY) averted from antivenom therapy. A decision analytic model was developed and analyzed with the following model base-case parameter estimates: type of snakes causing bites, antivenom effectiveness to prevent death, untreated mortality, risk of Early Adverse Reactions (EAR), mortality risk from EAR, mean age at bite and remaining life expectancy, and disability risk (amputation). End-user costs applied included: costs of diagnosing and monitoring envenoming, antivenom drug cost, supportive care, shipping/freezing antivenom, transportation to-and-from hospital and feeding costs while on admission, management of antivenom EAR and free alternative snakebite care for ineffective antivenom.
Principal Findings
We calculated a cost/death averted of ($2330.16) and cost/DALY averted of $99.61 discounted and $56.88 undiscounted. Varying antivenom effectiveness through the 95% confidence interval from 55% to 86% yield a cost/DALY averted of $137.02 to $86.61 respectively. Similarly, varying the prevalence of envenoming caused by carpet viper from 0% to 96% yield a cost/DALY averted of $254.18 to $78.25 respectively. More effective antivenoms and carpet viper envenoming rather than non-carpet viper envenoming were associated with lower cost/DALY averted.
Conclusions/Significance
Treatment of snakebite envenoming in Nigeria is cost-effective with a cost/death averted of $2330.16 and cost/DALY averted of $99.61 discounted, lower than the country's gross domestic product per capita of $1555 (2013). Expanding access to effective antivenoms to larger segments of the Nigerian population should be a considered a priority.
Author Summary
Snake bite is a major public health problem throughout rural communities in West Africa and leads to a significant number of deaths and disabilities per year. Even though effective antivenoms exist against the locally prevalent carpet viper and other poisonous snakes, they are generally not available in community settings, possibly because of their high acquisition cost. We evaluated the cost-effectiveness of making antivenom more broadly available in Nigeria by comparing the treatment costs associated with antivenom therapy against their medical benefit in reducing the risk of mortality. We find that the incremental cost effectiveness ratio (ICER) associated with making antivenom available in Nigeria was $2,330 per death averted and $100 per disability adjusted life year (DALY) averted. Both of these suggest that snakebite antivenom is highly cost-effective in Nigeria and they also compare very favorably against other commonly funded health interventions for which similar estimates exist. Since a substantial reduction in mortality and DALYs could be achieved at a relatively modest upfront cost, expanding access to antivenom to broader parts of the population should be a priority consideration for future investments in healthcare.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Snakebite envenoming is a major public health problem throughout the rural tropics. Antivenom is effective in reducing mortality and remains the mainstay of therapy. This study aimed to determine the cost-effectiveness of using effective antivenoms for Snakebite envenoming in Nigeria.
Methodology
Economic analysis was conducted from a public healthcare system perspective. Estimates of model inputs were obtained from the literature. Incremental Cost Effectiveness Ratios (ICERs) were quantified as deaths and Disability-Adjusted-Life-Years (DALY) averted from antivenom therapy. A decision analytic model was developed and analyzed with the following model base-case parameter estimates: type of snakes causing bites, antivenom effectiveness to prevent death, untreated mortality, risk of Early Adverse Reactions (EAR), mortality risk from EAR, mean age at bite and remaining life expectancy, and disability risk (amputation). End-user costs applied included: costs of diagnosing and monitoring envenoming, antivenom drug cost, supportive care, shipping/freezing antivenom, transportation to-and-from hospital and feeding costs while on admission, management of antivenom EAR and free alternative snakebite care for ineffective antivenom.
Principal Findings
We calculated a cost/death averted of ($2330.16) and cost/DALY averted of $99.61 discounted and $56.88 undiscounted. Varying antivenom effectiveness through the 95% confidence interval from 55% to 86% yield a cost/DALY averted of $137.02 to $86.61 respectively. Similarly, varying the prevalence of envenoming caused by carpet viper from 0% to 96% yield a cost/DALY averted of $254.18 to $78.25 respectively. More effective antivenoms and carpet viper envenoming rather than non-carpet viper envenoming were associated with lower cost/DALY averted.
Conclusions/Significance
Treatment of snakebite envenoming in Nigeria is cost-effective with a cost/death averted of $2330.16 and cost/DALY averted of $99.61 discounted, lower than the country's gross domestic product per capita of $1555 (2013). Expanding access to effective antivenoms to larger segments of the Nigerian population should be a considered a priority.
Author Summary
Snake bite is a major public health problem throughout rural communities in West Africa and leads to a significant number of deaths and disabilities per year. Even though effective antivenoms exist against the locally prevalent carpet viper and other poisonous snakes, they are generally not available in community settings, possibly because of their high acquisition cost. We evaluated the cost-effectiveness of making antivenom more broadly available in Nigeria by comparing the treatment costs associated with antivenom therapy against their medical benefit in reducing the risk of mortality. We find that the incremental cost effectiveness ratio (ICER) associated with making antivenom available in Nigeria was $2,330 per death averted and $100 per disability adjusted life year (DALY) averted. Both of these suggest that snakebite antivenom is highly cost-effective in Nigeria and they also compare very favorably against other commonly funded health interventions for which similar estimates exist. Since a substantial reduction in mortality and DALYs could be achieved at a relatively modest upfront cost, expanding access to antivenom to broader parts of the population should be a priority consideration for future investments in healthcare. |
J Musaazi A Nakiwogga-Muwanga, E Katabira Patients who return to care after tracking remain at high risk of attrition: experience from a large HIV clinic, Uganda Journal Article In: International Journal of STDs & AIDS, vol. 26, no. 1, pp. 42-7, 2015. @article{Nakiwogga-Muwanga2015,
title = {Patients who return to care after tracking remain at high risk of attrition: experience from a large HIV clinic, Uganda },
author = {A Nakiwogga-Muwanga, J Musaazi, E Katabira, W Worodria, S Alamo Talisuna, R Colebunders},
doi = {https://doi.org/10.1177/0956462414529098},
year = {2015},
date = {2015-01-02},
journal = {International Journal of STDs & AIDS},
volume = {26},
number = {1},
pages = {42-7},
abstract = {We determined the retention rate of patients infected with HIV who resumed care after being tracked at the Infectious Diseases Clinic (IDC) in Kampala, Uganda. Between April 2011 and September 2013, patients who missed their clinic appointment for 8–90 days were tracked, and those who returned to the clinic within 120 days were followed up. The proportion of patients retained among tracked patients, and those who resumed care before tracking started was compared. At 18 months of follow up, 33 (39%) of the tracked patients and 72 (61%) of those who had resumed care before tracking started were retained in care. The most important cause of attrition among the traceable was self-transfer to another clinic (38 [73%] patients), whereas among those who resumed care before tracking was loss to follow up (LTFU) (32 [71%] patients). Tracked patients who resume care following a missed appointment are at high risk of attrition. To increase retention, antiretroviral therapy clinics need to adopt a chronic care model which takes into consideration patients’ changing needs and their preference for self-management.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We determined the retention rate of patients infected with HIV who resumed care after being tracked at the Infectious Diseases Clinic (IDC) in Kampala, Uganda. Between April 2011 and September 2013, patients who missed their clinic appointment for 8–90 days were tracked, and those who returned to the clinic within 120 days were followed up. The proportion of patients retained among tracked patients, and those who resumed care before tracking started was compared. At 18 months of follow up, 33 (39%) of the tracked patients and 72 (61%) of those who had resumed care before tracking started were retained in care. The most important cause of attrition among the traceable was self-transfer to another clinic (38 [73%] patients), whereas among those who resumed care before tracking was loss to follow up (LTFU) (32 [71%] patients). Tracked patients who resume care following a missed appointment are at high risk of attrition. To increase retention, antiretroviral therapy clinics need to adopt a chronic care model which takes into consideration patients’ changing needs and their preference for self-management. |
Halidou Tinto Vito Baraka, Innocent Valea In Vivo Selection of Plasmodium falciparum Pfcrt and Pfmdr1 Variants by Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine in Burkina Faso Journal Article In: ASM Journals/ Antimicrobial Agents and Chemotherapy, vol. 59, no. 1, pp. 734-737, 2015. @article{Baraka2015,
title = {In Vivo Selection of Plasmodium falciparum Pfcrt and Pfmdr1 Variants by Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine in Burkina Faso},
author = {Vito Baraka, Halidou Tinto, Innocent Valea, Robert Fitzhenry, Christopher Delgado-Ratto, Martin K. Mbonye, Chantal Van Overmeir, Anna Rosanas-Urgell, Jean-Pierre Van geertruyden, Umberto D'Alessandro, Annette Erhart},
doi = {https://doi.org/10.1128/AAC.03647-14 Check for updates on crossmark},
year = {2015},
date = {2015-01-01},
journal = {ASM Journals/ Antimicrobial Agents and Chemotherapy},
volume = {59},
number = {1},
pages = {734-737},
abstract = {Plasmodium falciparum Pfcrt-76 and Pfmdr1-86 gene polymorphisms were determined during a clinical trial in Burkina Faso comparing the efficacies of dihydroartemisinin-piperaquine (DHA-PPQ) and artemether-lumefantrine (AL). Significant selection of Pfcrt-K76 was observed after exposure to AL and DHA-PPQ, as well as selection of Pfmdr1-N86 after AL but not DHA-PPQ treatment, suggesting reverse selection on the Pfcrt gene by PPQ. These results support the rational use of DHA-PPQ in settings where chloroquine (CQ) resistance is high.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Plasmodium falciparum Pfcrt-76 and Pfmdr1-86 gene polymorphisms were determined during a clinical trial in Burkina Faso comparing the efficacies of dihydroartemisinin-piperaquine (DHA-PPQ) and artemether-lumefantrine (AL). Significant selection of Pfcrt-K76 was observed after exposure to AL and DHA-PPQ, as well as selection of Pfmdr1-N86 after AL but not DHA-PPQ treatment, suggesting reverse selection on the Pfcrt gene by PPQ. These results support the rational use of DHA-PPQ in settings where chloroquine (CQ) resistance is high. |
2014
|
Rolfes, Melissa A.; Hullsiek, Kathy Huppler; Rhein, Joshua; Nabeta, Henry W.; Taseera, Kabanda; Schutz, Charlotte; Musubire, Abdu; Rajasingham, Radha; Williams, Darlisha A.; Thienemann, Friedrich; Muzoora, Conrad; Meintjes, Graeme; Meya, David B.; Boulware, David R. The Effect of Therapeutic Lumbar Punctures on Acute Mortality From Cryptococcal Meningitis Journal Article In: Clinival Infectious Diseases, vol. 60, no. 9, 2014. @article{Rolfes2014,
title = {The Effect of Therapeutic Lumbar Punctures on Acute Mortality From Cryptococcal Meningitis},
author = {Melissa A. Rolfes and Kathy Huppler Hullsiek and Joshua Rhein and Henry W. Nabeta and Kabanda Taseera and Charlotte Schutz and Abdu Musubire and Radha Rajasingham and Darlisha A. Williams and Friedrich Thienemann and Conrad Muzoora and Graeme Meintjes and David B. Meya and David R. Boulware},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-Effect-of-Therapeutic-Lumbar-Punctures-on.pdf},
doi = {10.1093/cid/ciu596},
year = {2014},
date = {2014-12-30},
journal = {Clinival Infectious Diseases},
volume = {60},
number = {9},
abstract = {Introduction. Cryptococcal meningitis is the most common cause of adult meningitis in sub-Saharan Africa. Raised intracranial pressure (ICP) is common in cryptococcosis. Prior studies suggest elevated ICP is associated with mortality, and guidelines recommend frequent lumbar punctures (LPs) to control ICP. However, the magnitude of the impact of LPs on cryptococcal-related mortality is unknown.
Methods. In sum, 248 individuals with human immunodeficiency virus (HIV)-associated cryptococcal meningitis, screened for the Cryptococcal Optimal ART Timing (COAT) trial in Uganda and South Africa, were observed. Individuals received an LP to diagnose meningitis, and subsequent therapeutic LPs were recommended for elevated ICP (>250 mmH2O) or new symptoms. We compared survival, through 11 days, between individuals receiving at least 1 therapeutic LP with individuals not receiving therapeutic LPs. The COAT trial randomized subjects at 7–11 days; thus, follow-up stopped at time of death, randomization, or 11 days.
Results. Seventy-five (30%) individuals had at least 1 therapeutic LP. Individuals receiving therapeutic LPs had higher cerebrospinal fluid (CSF) opening pressures, higher CSF fungal burdens, and were more likely to have altered mental status at baseline than those with no therapeutic LPs. Thirty-one deaths (18%) occurred among 173 individuals without a therapeutic LP and 5 deaths (7%) among 75 with at least 1 therapeutic LP. The adjusted relative risk of mortality was 0.31 (95% confidence interval: .12–.82). The association was observed regardless of opening pressure at baseline.
Conclusions. Therapeutic LPs were associated with a 69% relative improvement in survival, regardless of initial intracranial pressure. The role of therapeutic LPs should be reevaluated.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction. Cryptococcal meningitis is the most common cause of adult meningitis in sub-Saharan Africa. Raised intracranial pressure (ICP) is common in cryptococcosis. Prior studies suggest elevated ICP is associated with mortality, and guidelines recommend frequent lumbar punctures (LPs) to control ICP. However, the magnitude of the impact of LPs on cryptococcal-related mortality is unknown.
Methods. In sum, 248 individuals with human immunodeficiency virus (HIV)-associated cryptococcal meningitis, screened for the Cryptococcal Optimal ART Timing (COAT) trial in Uganda and South Africa, were observed. Individuals received an LP to diagnose meningitis, and subsequent therapeutic LPs were recommended for elevated ICP (>250 mmH2O) or new symptoms. We compared survival, through 11 days, between individuals receiving at least 1 therapeutic LP with individuals not receiving therapeutic LPs. The COAT trial randomized subjects at 7–11 days; thus, follow-up stopped at time of death, randomization, or 11 days.
Results. Seventy-five (30%) individuals had at least 1 therapeutic LP. Individuals receiving therapeutic LPs had higher cerebrospinal fluid (CSF) opening pressures, higher CSF fungal burdens, and were more likely to have altered mental status at baseline than those with no therapeutic LPs. Thirty-one deaths (18%) occurred among 173 individuals without a therapeutic LP and 5 deaths (7%) among 75 with at least 1 therapeutic LP. The adjusted relative risk of mortality was 0.31 (95% confidence interval: .12–.82). The association was observed regardless of opening pressure at baseline.
Conclusions. Therapeutic LPs were associated with a 69% relative improvement in survival, regardless of initial intracranial pressure. The role of therapeutic LPs should be reevaluated. |
Mugasha, Christine; Kigozi, Joanita; Kiragga, Agnes; Muganzi, Alex; Sewankambo, Nelson; Coutinho, Alex; Nakanjako, Damalie Intra-Facility Linkage of HIV-Positive Mothers and HIV-Exposed Babies into HIV Chronic Care: Rural and Urban Experience in a Resource Limited Setting Journal Article In: PloS One, vol. 9, no. 12, 2014. @article{Mugasha2014,
title = {Intra-Facility Linkage of HIV-Positive Mothers and HIV-Exposed Babies into HIV Chronic Care: Rural and Urban Experience in a Resource Limited Setting},
author = {Christine Mugasha and Joanita Kigozi and Agnes Kiragga and Alex Muganzi and Nelson Sewankambo and Alex Coutinho and Damalie Nakanjako},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/pone.0115171.pdf},
doi = {1371/journal.pone.0115171},
year = {2014},
date = {2014-12-29},
journal = {PloS One},
volume = {9},
number = {12},
abstract = {Introduction:
Linkage of HIV-infected pregnant women to HIV care remains critical
for improvement of maternal and child outcomes through prevention of maternal-to-
child transmission of HIV (PMTCT) and subsequent chronic HIV care. This study
determined proportions and factors associated with intra-facility linkage to HIV care
and Early Infant Diagnosis care (EID) to inform strategic scale up of PMTCT
programs.
Methods:
A cross-sectional review of records was done at 2 urban and 3 rural
public health care facilities supported by the Infectious Diseases Institute (IDI). HIV-
infected pregnant mothers, identified through routine antenatal care (ANC) and HIV-
exposed babies were evaluated for enrollment in HIV clinics by 6 weeks post-
delivery.
Results:
Overall, 1,025 HIV-infected pregnant mothers were identified during ANC
between January and June, 2012; 267/1,025 (26%) in rural and 743/1,025 (74%) in
urban facilities. Of these 375/1,025 (37%) were linked to HIV clinics [67/267(25%)
rural and 308/758(41%) urban]. Of 636 HIV-exposed babies, 193 (30%) were linked
to EID. Linkage of mother-baby pairs to HIV chronic care and EID was 16% (101/
636); 8/179 (4.5%)] in rural and 93/457(20.3%) in urban health facilities. Within rural
facilities, ANC registration
,
28 weeks-of-gestation was associated with mothers’
linkage to HIV chronic care [AoR, 2.0 95% CI, 1.1–3.7, p
5
0.019] and mothers’
multi-parity was associated with baby’s linkage to EID; AoR 4.4 (1.3–15.1),
p
5
0.023. Stigma, long distance to health facilities and vertical PMTCT services
affected linkage in rural facilities, while peer mothers, infant feeding services, long
patient queues and limited privacy hindered linkage to HIV care in urban settings
Conclusion:
Post-natal linkage of HIV-infected mothers to chronic HIV care and
HIV-exposed babies to EID programs was low. Barriers to linkage to HIV care vary
in urban and rural settings. We recommend targeted interventions to rapidly
improve linkage to antiretroviral therapy for elimination of MTCT.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction:
Linkage of HIV-infected pregnant women to HIV care remains critical
for improvement of maternal and child outcomes through prevention of maternal-to-
child transmission of HIV (PMTCT) and subsequent chronic HIV care. This study
determined proportions and factors associated with intra-facility linkage to HIV care
and Early Infant Diagnosis care (EID) to inform strategic scale up of PMTCT
programs.
Methods:
A cross-sectional review of records was done at 2 urban and 3 rural
public health care facilities supported by the Infectious Diseases Institute (IDI). HIV-
infected pregnant mothers, identified through routine antenatal care (ANC) and HIV-
exposed babies were evaluated for enrollment in HIV clinics by 6 weeks post-
delivery.
Results:
Overall, 1,025 HIV-infected pregnant mothers were identified during ANC
between January and June, 2012; 267/1,025 (26%) in rural and 743/1,025 (74%) in
urban facilities. Of these 375/1,025 (37%) were linked to HIV clinics [67/267(25%)
rural and 308/758(41%) urban]. Of 636 HIV-exposed babies, 193 (30%) were linked
to EID. Linkage of mother-baby pairs to HIV chronic care and EID was 16% (101/
636); 8/179 (4.5%)] in rural and 93/457(20.3%) in urban health facilities. Within rural
facilities, ANC registration
,
28 weeks-of-gestation was associated with mothers’
linkage to HIV chronic care [AoR, 2.0 95% CI, 1.1–3.7, p
5
0.019] and mothers’
multi-parity was associated with baby’s linkage to EID; AoR 4.4 (1.3–15.1),
p
5
0.023. Stigma, long distance to health facilities and vertical PMTCT services
affected linkage in rural facilities, while peer mothers, infant feeding services, long
patient queues and limited privacy hindered linkage to HIV care in urban settings
Conclusion:
Post-natal linkage of HIV-infected mothers to chronic HIV care and
HIV-exposed babies to EID programs was low. Barriers to linkage to HIV care vary
in urban and rural settings. We recommend targeted interventions to rapidly
improve linkage to antiretroviral therapy for elimination of MTCT. |
Duda, Stephany N; Farr, Amanda M; Lindegren, Mary Lou; Blevins, Meridith; Wester, C William; Wools-Kaloustian, Kara; Ekouevi, Didier K; Egger, Matthias; Hemingway-Foday, Jennifer; Coope, David A; Moore, Richard D; McGowan, Catherine C; Nas, Denis; the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration, Characteristics and comprehensiveness of adult HIV care and treatment programmes in Asia-Pacific, sub-Saharan Africa and the Americas: results of a site assessment conducted by the International epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration Journal Article In: Journal of the Intrernational AIDS society, vol. 17, no. 1, 2014. @article{Duda2014,
title = {Characteristics and comprehensiveness of adult HIV care and treatment programmes in Asia-Pacific, sub-Saharan Africa and the Americas: results of a site assessment conducted by the International epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration},
author = {Stephany N Duda and Amanda M Farr and Mary Lou Lindegren and Meridith Blevins and C William Wester and Kara Wools-Kaloustian and Didier K Ekouevi and Matthias Egger and Jennifer Hemingway-Foday and David A Coope and Richard D Moore and Catherine C McGowan and Denis Nas and the International Epidemiologic Databases to
Evaluate AIDS (IeDEA) Collaboration},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Characteristics-and-comprehensiveness-of-adult-HIV-care-and.pdf},
doi = {10.7448/IAS.17.1.19045},
year = {2014},
date = {2014-12-15},
journal = {Journal of the Intrernational AIDS society},
volume = {17},
number = {1},
abstract = {Introduction
: HIV care and treatment programmes worldwide are transforming as they push to deliver universal access to
essential prevention, care and treatment services to persons living with HIV and their communities. The characteristics and
capacity of these HIV programmes affect patient outcomes and quality of care. Despite the importance of ensuring optimal
outcomes, few studies have addressed the capacity of HIV programmes to deliver comprehensive care. We sought to describe
such capacity in HIV programmes in seven regions worldwide.
Methods
: Staff from 128 sites in 41 countries participating in the International epidemiologic Databases to Evaluate AIDS completed
a site survey from 2009 to 2010, including sites in the Asia-Pacific region (
n
20), Latin America and the Caribbean (
n
7),
North America (
n
7), Central Africa (
n
12), East Africa (
n
51), Southern Africa (
n
16) and West Africa (
n
15). We com-
puted a measure of the comprehensiveness of care based on seven World Health Organization-recommended essential HIV services.
Results
: Most sites reported serving urban (61%; region range (rr): 33
100%) and both adult and paediatric populations (77%;
rr: 29
96%). Only 45% of HIV clinics that reported treating children had paediatricians on staff. As for the seven essential
services, survey respondents reported that CD4
cell count testing was available to all but one site, while tuberculosis (TB)
screening and community outreach services were available in 80 and 72%, respectively. The remaining four essential services
nutritional support (82%), combination antiretroviral therapy adherence support (88%), prevention of mother-to-child
transmission (PMTCT) (94%) and other prevention and clinical management services (97%)
were uniformly available.
Approximately half (46%) of sites reported offering all seven services. Newer sites and sites in settings with low rankings on the
UN Human Development Index (HDI), especially those in the President’s Emergency Plan for AIDS Relief focus countries, tended
to offer a more comprehensive array of essential services. HIV care programme characteristics and comprehensiveness varied
according to the number of years the site had been in operation and the HDI of the site setting, with more recently established
clinics in low-HDI settings reporting a more comprehensive array of available services. Survey respondents frequently identified
contact tracing of patients, patient outreach, nutritional counselling, onsite viral load testing, universal TB screening and the
provision of isoniazid preventive therapy as unavailable services.
Conclusions
: This study serves as a baseline for on-going monitoring of the evolution of care delivery over time and lays the
groundwork for evaluating HIV treatment outcomes in relation to site capacity for comprehensive care},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction
: HIV care and treatment programmes worldwide are transforming as they push to deliver universal access to
essential prevention, care and treatment services to persons living with HIV and their communities. The characteristics and
capacity of these HIV programmes affect patient outcomes and quality of care. Despite the importance of ensuring optimal
outcomes, few studies have addressed the capacity of HIV programmes to deliver comprehensive care. We sought to describe
such capacity in HIV programmes in seven regions worldwide.
Methods
: Staff from 128 sites in 41 countries participating in the International epidemiologic Databases to Evaluate AIDS completed
a site survey from 2009 to 2010, including sites in the Asia-Pacific region (
n
20), Latin America and the Caribbean (
n
7),
North America (
n
7), Central Africa (
n
12), East Africa (
n
51), Southern Africa (
n
16) and West Africa (
n
15). We com-
puted a measure of the comprehensiveness of care based on seven World Health Organization-recommended essential HIV services.
Results
: Most sites reported serving urban (61%; region range (rr): 33
100%) and both adult and paediatric populations (77%;
rr: 29
96%). Only 45% of HIV clinics that reported treating children had paediatricians on staff. As for the seven essential
services, survey respondents reported that CD4
cell count testing was available to all but one site, while tuberculosis (TB)
screening and community outreach services were available in 80 and 72%, respectively. The remaining four essential services
nutritional support (82%), combination antiretroviral therapy adherence support (88%), prevention of mother-to-child
transmission (PMTCT) (94%) and other prevention and clinical management services (97%)
were uniformly available.
Approximately half (46%) of sites reported offering all seven services. Newer sites and sites in settings with low rankings on the
UN Human Development Index (HDI), especially those in the President’s Emergency Plan for AIDS Relief focus countries, tended
to offer a more comprehensive array of essential services. HIV care programme characteristics and comprehensiveness varied
according to the number of years the site had been in operation and the HDI of the site setting, with more recently established
clinics in low-HDI settings reporting a more comprehensive array of available services. Survey respondents frequently identified
contact tracing of patients, patient outreach, nutritional counselling, onsite viral load testing, universal TB screening and the
provision of isoniazid preventive therapy as unavailable services.
Conclusions
: This study serves as a baseline for on-going monitoring of the evolution of care delivery over time and lays the
groundwork for evaluating HIV treatment outcomes in relation to site capacity for comprehensive care |
Christine, Sekaggya Wiltshire; Mohammed, Lamorde; Alexandra, Scherrer; Musaazi, Joseph; Natascia, Corti; Buzibye, Allan; Rita, Nakijoba; Damalie, Nalwanga; Lars, Henning; Von Braun, Amrei; Solome, Okware; Barbara, Castelnuovo; Andrew, Kambugu; Fehr, Jan Low isoniazid and rifampicin concentrations in TB/HIV co-infected patients in Uganda Journal Article In: Journal of the intrantional AIDS society, 2014. @article{Christine2014,
title = {Low isoniazid and rifampicin concentrations in TB/HIV co-infected patients in Uganda},
author = {Sekaggya Wiltshire Christine and Lamorde Mohammed and Scherrer Alexandra and Musaazi, Joseph and Corti Natascia and Allan Buzibye and Nakijoba Rita and Nalwanga Damalie and Henning Lars and Von Braun, Amrei and Okware Solome
and Castelnuovo Barbara and Kambugu Andrew and Fehr, Jan},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Wiltshire_et_al-2014-Journal_of_the_International_AIDS_Society-1.pdf},
doi = {10.7448/IAS.17.4.19585},
year = {2014},
date = {2014-12-14},
journal = {Journal of the intrantional AIDS society},
abstract = {
Introduction
There is limited data available on exposure to anti‐tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti‐TB drugs in the HIV/TB co‐infected population in Sub‐Saharan Africa. Our objective is to describe the concentration of anti‐TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB.
Methods
This study is an ongoing study carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti‐TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti‐TB treatment using ultraviolet high‐performance liquid chromatography (UV‐HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al. referenced in other studies.
Results
We started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years, of which 52% were male with a median BMI of 19 kg/m2 and a median CD4 cell count of 142 cells/µL. In 90% of the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H and R.
Levels of H were found to be below the reference ranges (3–6 µg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. Rif levels were also found to be below the reference ranges (8–24 µg/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8 and 24, respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.2±SD2.1 µg/mL and 4.0±SD3.1 µg/mL for E and 41.6±SD13.1 µg/mL and 42.6±SD16.4 µg/mL for Z.
Conclusion
We observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co‐infected patients. The implications of these findings are not yet clear. We therefore need to correlate our findings with the response to TB treatment.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction
There is limited data available on exposure to anti‐tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti‐TB drugs in the HIV/TB co‐infected population in Sub‐Saharan Africa. Our objective is to describe the concentration of anti‐TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB.
Methods
This study is an ongoing study carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti‐TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti‐TB treatment using ultraviolet high‐performance liquid chromatography (UV‐HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al. referenced in other studies.
Results
We started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years, of which 52% were male with a median BMI of 19 kg/m2 and a median CD4 cell count of 142 cells/µL. In 90% of the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H and R.
Levels of H were found to be below the reference ranges (3–6 µg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. Rif levels were also found to be below the reference ranges (8–24 µg/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8 and 24, respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.2±SD2.1 µg/mL and 4.0±SD3.1 µg/mL for E and 41.6±SD13.1 µg/mL and 42.6±SD16.4 µg/mL for Z.
Conclusion
We observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co‐infected patients. The implications of these findings are not yet clear. We therefore need to correlate our findings with the response to TB treatment.
|
Cox, Janneke A; Lukande, Robert L; Kalungi, Sam; de Vijver, Koen Van; Marck, Eric Van; Nelson, Ann M; Munema, Asafu; Manabe, Yukari C; Colebunders, Robert Practice of percutaneous needle autopsy; a descriptive study reporting experiences from Uganda Journal Article In: BMC Clincal Pathology, vol. 14, no. 1, 2014. @article{Cox2014b,
title = {Practice of percutaneous needle autopsy; a descriptive study reporting experiences from Uganda},
author = {Janneke A Cox and Robert L Lukande and Sam Kalungi and Koen Van de Vijver and Eric Van Marck and Ann M Nelson and Asafu Munema and Yukari C Manabe and Robert Colebunders
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Practice-of-percutaneous-needle-autopsy....pdf},
doi = { doi: 10.1186/1472-6890-14-44},
year = {2014},
date = {2014-12-03},
journal = {BMC Clincal Pathology},
volume = {14},
number = {1},
abstract = {BACKGROUND:
Percutaneous needle autopsy can overcome a number of barriers that limit the use of complete autopsies. We performed blind-and ultrasound guided needle autopsies in HIV-infected adults in Uganda. In this study we describe in detail the methods we used, the ability of both procedures to obtain sufficient tissue for further examination and the learning curve of the operators over time.
METHODS:
If written informed consent was granted from the next of kin, we first performed a blind needle autopsy, puncturing brain, heart, lungs, liver, spleen and kidneys using predefined surface marking points. We then performed an ultrasound guided needle autopsy puncturing heart, liver, spleen and kidneys. The number of attempts, expected success and duration of the procedure were noted. A pathologist read the slides and indicated if the target tissue was present and of sufficient quality for pathological review. We report the predicted and true success rates, compare the yield of blind to ultrasound guided needle biopsies and evaluate the failure rate over time.
RESULTS:
Two operators performed 96 blind needle autopsies and 95 ultrasound guided needle autopsies. For blind needle biopsies true success rates varied from 56-99% and predicted success rates from 89-99%. For ultrasound guided needle biopsies true success rates varied from 72-100% and predicted success rates from 84-98%. Ultrasound guidance led to a significantly higher success rate in heart and left kidney. A learning curve was observed over time with decreasing failure rates with increasing experience and a shorter duration of the needle autopsy.
CONCLUSION:
Needle autopsy can successfully obtain tissue for further pathological review in the vast majority of cases, with a decrease in failure rate with increasing experience of the operator. The benefit of ultrasound guidance will depend on the population, the disease and organ of interest and the local circumstances. Our results justify further evaluation of needle autopsies as a method to establish a cause of death.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Percutaneous needle autopsy can overcome a number of barriers that limit the use of complete autopsies. We performed blind-and ultrasound guided needle autopsies in HIV-infected adults in Uganda. In this study we describe in detail the methods we used, the ability of both procedures to obtain sufficient tissue for further examination and the learning curve of the operators over time.
METHODS:
If written informed consent was granted from the next of kin, we first performed a blind needle autopsy, puncturing brain, heart, lungs, liver, spleen and kidneys using predefined surface marking points. We then performed an ultrasound guided needle autopsy puncturing heart, liver, spleen and kidneys. The number of attempts, expected success and duration of the procedure were noted. A pathologist read the slides and indicated if the target tissue was present and of sufficient quality for pathological review. We report the predicted and true success rates, compare the yield of blind to ultrasound guided needle biopsies and evaluate the failure rate over time.
RESULTS:
Two operators performed 96 blind needle autopsies and 95 ultrasound guided needle autopsies. For blind needle biopsies true success rates varied from 56-99% and predicted success rates from 89-99%. For ultrasound guided needle biopsies true success rates varied from 72-100% and predicted success rates from 84-98%. Ultrasound guidance led to a significantly higher success rate in heart and left kidney. A learning curve was observed over time with decreasing failure rates with increasing experience and a shorter duration of the needle autopsy.
CONCLUSION:
Needle autopsy can successfully obtain tissue for further pathological review in the vast majority of cases, with a decrease in failure rate with increasing experience of the operator. The benefit of ultrasound guidance will depend on the population, the disease and organ of interest and the local circumstances. Our results justify further evaluation of needle autopsies as a method to establish a cause of death. |
Harriet Nabudere, Ekwaro Obuku; Lamorde, Mohammed ADVANCING PALLIATIVE CARE IN THE UGANDA HEALTH SYSTEM: AN EVIDENCE-BASED POLICY BRIEF Journal Article In: International Journal of Technology Assessment in Health Care, vol. 30, no. 6, pp. 621 - 625, 2014. @article{Nabudere2014,
title = {ADVANCING PALLIATIVE CARE IN THE UGANDA HEALTH SYSTEM: AN EVIDENCE-BASED POLICY BRIEF},
author = {Harriet Nabudere, Ekwaro Obuku and Mohammed Lamorde},
doi = {https://doi.org/10.1017/S0266462314000750},
year = {2014},
date = {2014-12-01},
journal = {International Journal of Technology Assessment in Health Care},
volume = {30},
number = {6},
pages = {621 - 625},
abstract = {Objectives:
This paper describes the development and findings for a policy brief on “Advancing the Integration of Palliative Care into the National Health System” and the subsequent use of this report.
Methods:
Key stakeholders involved with palliative care helped identify the problem and potential policy solutions to scale up these services within the health system. A working group of national stakeholder representatives and external reviewers commented on and contributed to successive drafts of the report. Research describing the problem, policy options and implementation considerations was identified by reviewing government documents, routinely collected data, electronic literature searches, contact with key informants, and reviewing the reference lists of relevant documents that were retrieved.
Results:
The palliative burden is not only high but increasing due to the rise in population and life expectancy. A few options for holistic, supportive care include: Home-based care increases chances of a peaceful death for the terminally ill surrounded by their loved ones; supporting informal caregivers improves their quality of life and discharge planning reduces unscheduled admissions and has the potential to free up capacity for acute care services. A combination of strategies is needed to effectively implement the proposed options as discussed further in this article.
Conclusions:
The policy brief report was used as a background document for two stakeholder dialogues whose main outcome was that a comprehensive national palliative care policy should be instituted to include all the options, which need to be integrated within the public health system. A draft policy is now in process.
Keywords
Palliative, Terminal, End-of-life, Uganda},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objectives:
This paper describes the development and findings for a policy brief on “Advancing the Integration of Palliative Care into the National Health System” and the subsequent use of this report.
Methods:
Key stakeholders involved with palliative care helped identify the problem and potential policy solutions to scale up these services within the health system. A working group of national stakeholder representatives and external reviewers commented on and contributed to successive drafts of the report. Research describing the problem, policy options and implementation considerations was identified by reviewing government documents, routinely collected data, electronic literature searches, contact with key informants, and reviewing the reference lists of relevant documents that were retrieved.
Results:
The palliative burden is not only high but increasing due to the rise in population and life expectancy. A few options for holistic, supportive care include: Home-based care increases chances of a peaceful death for the terminally ill surrounded by their loved ones; supporting informal caregivers improves their quality of life and discharge planning reduces unscheduled admissions and has the potential to free up capacity for acute care services. A combination of strategies is needed to effectively implement the proposed options as discussed further in this article.
Conclusions:
The policy brief report was used as a background document for two stakeholder dialogues whose main outcome was that a comprehensive national palliative care policy should be instituted to include all the options, which need to be integrated within the public health system. A draft policy is now in process.
Keywords
Palliative, Terminal, End-of-life, Uganda |
Semeere, Aggrey Semwendero; Lwanga, Isaac; Sempa, Joseph; Parikh, Sujal; Nakasujja, Noeline; Cumming, Robert; Kambugu, Andrew; Mayanja-Kizz, Harriet Mortality and immunological recovery among older adults on antiretroviral therapy at a large urban HIV clinic in Kampala, Uganda Journal Article In: Journal of Acquired Imune Dificiency syndrome, vol. 67, no. 4, pp. 382-9, 2014. @article{Semeere2014,
title = {Mortality and immunological recovery among older adults on antiretroviral therapy at a large urban HIV clinic in Kampala, Uganda},
author = {Aggrey Semwendero Semeere and Isaac Lwanga and Joseph Sempa and Sujal Parikh and Noeline Nakasujja and Robert Cumming and Andrew Kambugu and Harriet Mayanja-Kizz},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Mortality-and-immunological-recovery-among-older-adults-on-antiretroviral-therapy-at-a-large-urban-HIV-clinic-in-Kampala-Uganda..pdf},
doi = {10.1097/QAI.0000000000000330.},
year = {2014},
date = {2014-12-01},
journal = {Journal of Acquired Imune Dificiency syndrome},
volume = {67},
number = {4},
pages = {382-9},
abstract = {BACKGROUND:
We describe older (>50 years) HIV-infected adults after antiretroviral therapy (ART) initiation, evaluating immunological recovery by age category, considering individual trajectories based on the pretreatment CD4. We also describe mortality on ART and its risk factors by age category including the contribution of poor immunological recovery at a large urban clinic in Kampala, Uganda.
METHODS:
We performed a cohort analysis of adult (>18 years) HIV-infected patients who initiated ART between January 1, 2004 and January 3, 2012. Immunological response was evaluated using mixed-effects linear regression. We described mortality using Kaplan-Meier survival methods analyzing for risk factors of mortality using multivariate Weibull survival regression stratified by age category.
RESULTS:
Among 9806 individuals who initiated ART, mean age was 37 years (SD: 8.8), average follow-up 5.7 years (SD: 1.7), and median baseline CD4 was 115 cells per cubic millimeter (interquartile range: 42-184). Adults younger than 50 years had on average a higher CD4 increase of 45 cells per cubic millimeter (95% confidence interval: 17 to 72; P = 0.001) compared with counterparts aged 60 years and older. Mortality was highest among older adults compared with younger counterparts. Only CD4 count <100 cells per cubic millimeter after 1 year on ART and a CD4 count less than baseline were associated with a statistically significant higher rate of death among older adults.
CONCLUSIONS:
Older adults had a slower immunological response, which was associated with mortality, but this mortality was not typically associated with opportunistic infections. Future steps would require more evaluation of possible causes of death among these older individuals if survival on ART is to be further improved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
We describe older (>50 years) HIV-infected adults after antiretroviral therapy (ART) initiation, evaluating immunological recovery by age category, considering individual trajectories based on the pretreatment CD4. We also describe mortality on ART and its risk factors by age category including the contribution of poor immunological recovery at a large urban clinic in Kampala, Uganda.
METHODS:
We performed a cohort analysis of adult (>18 years) HIV-infected patients who initiated ART between January 1, 2004 and January 3, 2012. Immunological response was evaluated using mixed-effects linear regression. We described mortality using Kaplan-Meier survival methods analyzing for risk factors of mortality using multivariate Weibull survival regression stratified by age category.
RESULTS:
Among 9806 individuals who initiated ART, mean age was 37 years (SD: 8.8), average follow-up 5.7 years (SD: 1.7), and median baseline CD4 was 115 cells per cubic millimeter (interquartile range: 42-184). Adults younger than 50 years had on average a higher CD4 increase of 45 cells per cubic millimeter (95% confidence interval: 17 to 72; P = 0.001) compared with counterparts aged 60 years and older. Mortality was highest among older adults compared with younger counterparts. Only CD4 count <100 cells per cubic millimeter after 1 year on ART and a CD4 count less than baseline were associated with a statistically significant higher rate of death among older adults.
CONCLUSIONS:
Older adults had a slower immunological response, which was associated with mortality, but this mortality was not typically associated with opportunistic infections. Future steps would require more evaluation of possible causes of death among these older individuals if survival on ART is to be further improved. |
Turiho, Andrew Kampikaho; Okello, Elialilia S.; Muhwezi, Wilson W.; Harvey, Steve; Byakika-Kibwika, Pauline; Meya, David; Katahoire, Anne R. Effect of School-based Human Papillomavirus (HPV) Vaccination on Adolescent Girls’ Knowledge and Acceptability of the HPV Vaccine in Ibanda District in Uganda Journal Article In: African Journal of Reproductive health, vol. 18, no. 4, pp. 45-53, 2014. @article{Turiho2014,
title = {Effect of School-based Human Papillomavirus (HPV) Vaccination on Adolescent Girls’ Knowledge and Acceptability of the HPV Vaccine in Ibanda District in Uganda},
author = {Andrew Kampikaho Turiho and Elialilia S. Okello and Wilson W. Muhwezi and Steve Harvey and Pauline Byakika-Kibwika
and David Meya and Anne R. Katahoire},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Effect-of-School-based-Human-Papillomavirus-HPV-Vaccination-on-Adolescent-Girls’-Knowledge-and-Acceptability-of-the-HPV-Vaccine-in-Ibanda-District-in-Uganda.pdf},
year = {2014},
date = {2014-12-01},
journal = {African Journal of Reproductive health},
volume = {18},
number = {4},
pages = {45-53},
abstract = {From 2008 to 2011, schoolgirls were vaccinated against HPV in two districts in Uganda following
sensitization. This study assessed girls’ knowledge of cervical cancer and HPV vaccine, and their
acceptance of future vaccination of friends and hypothetical daughters. The cross-sectional, mixed
methods comparative study was conducted in two districts. Univariate, bivariate, logistic
regression and thematic analyses were done. HPV vaccination was positively associated with
knowledge (Crude OR: 5.31, CI: 3.19–8.86;
p
= 0.000); but knowledge (Adjusted OR: 1.13, CI:
0.56–2.28;
p
= 0.73) and HPV vaccination (Adjusted OR: 0.92, CI: 0.16–5.36;
p
= 0.93) did not
predict vaccine acceptability. Seemingly important motivations for vaccine acceptance were: its
role in cancer prevention and advancement of reproductive health, minimal side effects, and
positive peer role models. Major deterrents to vaccine acceptance were: rumours and
misconceptions about possible side effects, perceived inadequate information about vaccine, and
fear of side effects},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
From 2008 to 2011, schoolgirls were vaccinated against HPV in two districts in Uganda following
sensitization. This study assessed girls’ knowledge of cervical cancer and HPV vaccine, and their
acceptance of future vaccination of friends and hypothetical daughters. The cross-sectional, mixed
methods comparative study was conducted in two districts. Univariate, bivariate, logistic
regression and thematic analyses were done. HPV vaccination was positively associated with
knowledge (Crude OR: 5.31, CI: 3.19–8.86;
p
= 0.000); but knowledge (Adjusted OR: 1.13, CI:
0.56–2.28;
p
= 0.73) and HPV vaccination (Adjusted OR: 0.92, CI: 0.16–5.36;
p
= 0.93) did not
predict vaccine acceptability. Seemingly important motivations for vaccine acceptance were: its
role in cancer prevention and advancement of reproductive health, minimal side effects, and
positive peer role models. Major deterrents to vaccine acceptance were: rumours and
misconceptions about possible side effects, perceived inadequate information about vaccine, and
fear of side effects |
Segamwenge, Innocent Lule; Kagimu, Magid; Ocama, Ponsiano; Opio, Kenneth The Utility of the helicobacter pylori stool antigen test in managing dyspepsia: an experience from a low resource setting Journal Article In: African Health Sciences, vol. 14, no. 4, pp. 829-34, 2014. @article{Segamwenge2014,
title = {The Utility of the helicobacter pylori stool antigen test in managing dyspepsia: an experience from a low resource setting},
author = {Innocent Lule Segamwenge and Magid Kagimu and Ponsiano Ocama and Kenneth Opio},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-Utility-of-the-helicobacter-pylori-stool-antigen-test-in-managing-dyspepsia.pdf},
doi = {10.4314/ahs.v14i4.9},
year = {2014},
date = {2014-12-01},
journal = {African Health Sciences},
volume = {14},
number = {4},
pages = {829-34},
abstract = {Background:
Dyspepsia is defined as a chronic or recurrent pain or discomfort centered in the upper abdomen. Endos
-
copy is the best strategy for confirming the cause of dyspepsia. Non- invasive strategies would be more appropriate in low
resource countries where endoscopy is not readily available. However, there is concern that these strategies may miss seri
-
ous disease like gastric cancer. One test that needs to be assessed in this regard is the Helicobacter pylori stool antigen test
(HPSAT).
Objective:
To determine the validity of the stool antigen test in predicting H. pylori associated disease among patients with
dyspepsia.
Methods:
In this prospective study patients with dyspepsia attending Mulago Hospital were recruited consecutively. Helico
-
bacter pylori was determined using the Rapid Strip HpSA ®, endoscopy and gastric mucosal biopsy were done.
Results:
167 patients with dyspepsia were recruited into the study. There were ninety six (57.5%) females and seventy one
(42.5%) males with an average age of 48.1(±18.1) years. Patients presenting with dyspepsia in Mulago hospital were more
likely to come from the Central 60 (36%) and western tribes 55 (33%). The commonest endoscopic finding was
oesophagitis 25 (15%). Peptic ulcer disease was found in 32 (19.2%) and 54 (32.3%) had normal endoscopy findings. H
pylori was found in 33.5% and 32.5% using the HPSAT and histology respectively. The validity of the HPSAT in predicting
H.pylori associated diseases was generally low with an overall sensitivity of 55.8%, and specificity of 74.2%. However, the
validity was higher in predicting the diagnosis of peptic ulcer disease with a sensitivity 59.4% and specificity 72.6%.
Conclusion and recommendations:
The HPSAT may be used in the test and treat strategy for young patients with dyspep
-
sia without alarm signs and symptoms in low resource settings. However, because of its low validity in predicting H.pylori
associated disease, it is important to follow up patients so that if symptoms persist or recur endoscopy is performed
Keywords:
helicobacter pylori, stool antigen, dyspepsia, low resource setting},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background:
Dyspepsia is defined as a chronic or recurrent pain or discomfort centered in the upper abdomen. Endos
-
copy is the best strategy for confirming the cause of dyspepsia. Non- invasive strategies would be more appropriate in low
resource countries where endoscopy is not readily available. However, there is concern that these strategies may miss seri
-
ous disease like gastric cancer. One test that needs to be assessed in this regard is the Helicobacter pylori stool antigen test
(HPSAT).
Objective:
To determine the validity of the stool antigen test in predicting H. pylori associated disease among patients with
dyspepsia.
Methods:
In this prospective study patients with dyspepsia attending Mulago Hospital were recruited consecutively. Helico
-
bacter pylori was determined using the Rapid Strip HpSA ®, endoscopy and gastric mucosal biopsy were done.
Results:
167 patients with dyspepsia were recruited into the study. There were ninety six (57.5%) females and seventy one
(42.5%) males with an average age of 48.1(±18.1) years. Patients presenting with dyspepsia in Mulago hospital were more
likely to come from the Central 60 (36%) and western tribes 55 (33%). The commonest endoscopic finding was
oesophagitis 25 (15%). Peptic ulcer disease was found in 32 (19.2%) and 54 (32.3%) had normal endoscopy findings. H
pylori was found in 33.5% and 32.5% using the HPSAT and histology respectively. The validity of the HPSAT in predicting
H.pylori associated diseases was generally low with an overall sensitivity of 55.8%, and specificity of 74.2%. However, the
validity was higher in predicting the diagnosis of peptic ulcer disease with a sensitivity 59.4% and specificity 72.6%.
Conclusion and recommendations:
The HPSAT may be used in the test and treat strategy for young patients with dyspep
-
sia without alarm signs and symptoms in low resource settings. However, because of its low validity in predicting H.pylori
associated disease, it is important to follow up patients so that if symptoms persist or recur endoscopy is performed
Keywords:
helicobacter pylori, stool antigen, dyspepsia, low resource setting |
Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; and Lois Bayigga,; Kiragga, Agnes; Kaleebu, Moses Joloba Pontiano; Kambugu, Andrew D.; Kamya, Moses R.; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial Journal Article In: Tropical Medicine & International Health, vol. 20, no. 3, pp. 380-90, 2014. @article{Nakanjako2014,
title = {Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial},
author = {Damalie Nakanjako and Isaac Ssinabulya and Rose Nabatanzi and and Lois Bayigga and Agnes Kiragga and Moses Joloba
Pontiano Kaleebu and Andrew D. Kambugu and Moses R. Kamya and Rafick Sekaly and Alison Elliott and Harriet Mayanja-Kizza
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Atorvastatin-reduces-T-cell-activation-and-exhaustion-among-......pdf},
doi = {10.1111/tmi.12442},
year = {2014},
date = {2014-11-29},
journal = {Tropical Medicine & International Health},
volume = {20},
number = {3},
pages = {380-90},
abstract = {OBJECTIVE—
T-cell activation independently predicts mortality, poor immune recovery and
non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-
immune activation effects among HIV-infected cART-naïve individuals. We investigated whether
adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal
immune recovery.
METHODS—
A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80
mg daily
vs.
placebo for 12 weeks, was conducted among individuals with CD4 increase <295
cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 +
CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using
flow cytometry.
RESULTS—
Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28%
greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction);
P
=
0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo
(49%
vs.
14%,
P
= 0.0009), CD4 T-cell exhaustion (27%
vs.
17% in placebo),
P
= 0.001 and CD8
T-cell exhaustion (27%
vs.
16%),
P
= 0.004. There was no carry-over/period effect. Expected
adverse events were comparable in both groups, and no serious adverse events were reported.
CONCLUSION—
Atorvastatin reduced T-cell immune activation and exhaustion among cART-
treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy
to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE—
T-cell activation independently predicts mortality, poor immune recovery and
non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-
immune activation effects among HIV-infected cART-naïve individuals. We investigated whether
adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal
immune recovery.
METHODS—
A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80
mg daily
vs.
placebo for 12 weeks, was conducted among individuals with CD4 increase <295
cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 +
CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using
flow cytometry.
RESULTS—
Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28%
greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction);
P
=
0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo
(49%
vs.
14%,
P
= 0.0009), CD4 T-cell exhaustion (27%
vs.
17% in placebo),
P
= 0.001 and CD8
T-cell exhaustion (27%
vs.
16%),
P
= 0.004. There was no carry-over/period effect. Expected
adverse events were comparable in both groups, and no serious adverse events were reported.
CONCLUSION—
Atorvastatin reduced T-cell immune activation and exhaustion among cART-
treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy
to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa. |
Rhein, Joshua; Bahr, Nathan C.; Morawski, Bozena M.; Schutz, Charlotte; Zhang, Yonglong; Finkelman, Malcolm; Meya, David B.; Meintjes, Graeme; Boulware, David R. Detection of High Cerebrospinal Fluid Levels of (1→3)-β-d-Glucan in Cryptococcal Meningitis Journal Article In: Open Forum Infectious Diseases, vol. 1, no. 3, 2014. @article{Rhein2014,
title = {Detection of High Cerebrospinal Fluid Levels of (1→3)-β-d-Glucan in Cryptococcal Meningitis},
author = {Joshua Rhein and Nathan C. Bahr and Bozena M. Morawski and Charlotte Schutz and Yonglong Zhang and Malcolm Finkelman and David B. Meya and Graeme Meintjes and David R. Boulware},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Detection-of-High-Cerebrospinal-Fluid-Levels-of-1→3-β-D-Glucan-in-Cryptococcal-Meningitis.pdf},
doi = {10.1093/ofid/ofu105},
year = {2014},
date = {2014-11-26},
journal = {Open Forum Infectious Diseases},
volume = {1},
number = {3},
abstract = {ackground
.
(1
→
3)-
β
-
D
-Glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections.
However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of BDG as an ad-
junct diagnostic tool for patients infected with human immunode
fi
ciency virus (HIV) and presenting with suspected
cryptococcal meningitis.
Methods
.
The Fungitell assay was used to measure BDG concentrations in cerebrospinal
fl
uid (CSF) (
n
= 177)
and serum (
n
= 109) of HIV-infected Ugandans and South Africans with suspected meningitis. Correlations between
BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18
different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudi-
nal changes in CSF BDG concentrations. Survival analyses were used to evaluate BDG
’
s relationship with mortality.
Results
.
The Fungitell BDG assay provided 89% sensitivity and 85% speci
fi
city in CSF for cryptococcal menin-
gitis. Serum sensitivity was suboptimal (79%). Cerebrospinal
fl
uid BDG concentrations at diagnosis were median
(interquartile range) 343 (200
–
597) pg/mL in cryptococcal patients and 37 (23
–
46) pg/mL in patients without cryp-
tococcosis. Sensitivity in CSF improved to 98% (53 of 54) when initial fungal burdens were
≥
10 000 colony-forming
units/mL. (1
→
3)-
β
-
D
-Glucan normalized rapidly after initiating antifungal therapy. Baseline BDG concentrations
correlated with CSF fungal burden (rho = 0.820;
P
< .001), CSF CRAG lateral
fl
ow assay titers (rho = 0.780,
P
< .001), and monocyte chemotactic protein-1 levels in CSF (
P
= .047). In patients with cryptococcal meningitis,
BDG
≥
500 pg/mL at diagnosis was associated with increased 10-week mortality.
Conclusions
.
(1
→
3)-
β
-
D
-Glucan is detectable in the CSF of HIV-infected patients with
Cryptococcus
, and it may
provide useful prognostic information. Sensitivity is less than CRAG; however, BDG normalizes rapidly, unlike
CRAG, making BDG potentially useful in diagnosing recurrent episodes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
ackground
.
(1
→
3)-
β
-
D
-Glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections.
However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of BDG as an ad-
junct diagnostic tool for patients infected with human immunode
fi
ciency virus (HIV) and presenting with suspected
cryptococcal meningitis.
Methods
.
The Fungitell assay was used to measure BDG concentrations in cerebrospinal
fl
uid (CSF) (
n
= 177)
and serum (
n
= 109) of HIV-infected Ugandans and South Africans with suspected meningitis. Correlations between
BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18
different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudi-
nal changes in CSF BDG concentrations. Survival analyses were used to evaluate BDG
’
s relationship with mortality.
Results
.
The Fungitell BDG assay provided 89% sensitivity and 85% speci
fi
city in CSF for cryptococcal menin-
gitis. Serum sensitivity was suboptimal (79%). Cerebrospinal
fl
uid BDG concentrations at diagnosis were median
(interquartile range) 343 (200
–
597) pg/mL in cryptococcal patients and 37 (23
–
46) pg/mL in patients without cryp-
tococcosis. Sensitivity in CSF improved to 98% (53 of 54) when initial fungal burdens were
≥
10 000 colony-forming
units/mL. (1
→
3)-
β
-
D
-Glucan normalized rapidly after initiating antifungal therapy. Baseline BDG concentrations
correlated with CSF fungal burden (rho = 0.820;
P
< .001), CSF CRAG lateral
fl
ow assay titers (rho = 0.780,
P
< .001), and monocyte chemotactic protein-1 levels in CSF (
P
= .047). In patients with cryptococcal meningitis,
BDG
≥
500 pg/mL at diagnosis was associated with increased 10-week mortality.
Conclusions
.
(1
→
3)-
β
-
D
-Glucan is detectable in the CSF of HIV-infected patients with
Cryptococcus
, and it may
provide useful prognostic information. Sensitivity is less than CRAG; however, BDG normalizes rapidly, unlike
CRAG, making BDG potentially useful in diagnosing recurrent episodes. |
Parkes-Ratanshi, Rosalind; Katende, David; Levin, Jonathan; Wakeham, Katie; Heiner, Grosskurth; Kamali, Anatoli; Lalloo, David G Development of severe anaemia and changes in Haemoglobin (Hb) in a cohort of HIV infected Ugandan Adults receiving Zidovudine, Stavudine and Tenofovir containing antiretroviral regimens Journal Article In: journal of the International Association of Providers of AIDS Care, vol. 14, no. 5, pp. 455-62, 2014. @article{Parkes-Ratanshi2014b,
title = {Development of severe anaemia and changes in Haemoglobin (Hb) in a cohort of HIV infected Ugandan Adults receiving Zidovudine, Stavudine and Tenofovir containing antiretroviral regimens},
author = {Rosalind Parkes-Ratanshi and David Katende and Jonathan Levin and Katie Wakeham and Grosskurth Heiner and Anatoli Kamali and David G Lalloo},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Development-of-severe-anaemia-and-changes-in-Haemoglobin-Hb-in-a-cohort-of-HIV-infected-Ugandan-Adults-receiving-Zidovudine-Stavudine-and-Tenofovir-containing-antiretroviral-regimens.pdf},
doi = {10.1177/2325957414557264},
year = {2014},
date = {2014-11-25},
journal = {journal of the International Association of Providers of AIDS Care},
volume = {14},
number = {5},
pages = {455-62},
abstract = {Introduction—
Anaemia is a common problem in HIV in sub-Saharan Africa. We describe the
contribution of ART regimen on the incidence of anaemia and changes in haemoglobin in
Ugandan patients.
Methods—
This study was nested in a prevention of cryptococcal disease trial (CRYPTOPRO;
ISCRTN7648152). Patients received three different nucleoside reverse transcriptase inhibitor
backbones in a non-randomised manner.
Results—
Of 852 patients (161 on zidovudine, 628 on stavudine and 63 on tenofovir (all received
lamuvidine), the risk of developing grade 4 anaemia was higher (aHR 2.7) for those taking
zidovudine compared with stavudine. Those taking stavudine had a greater average increase in
haemoglobin than those taking zidovudine (p=0.024) or tenofovir (p=0.014).
Conclusion—
In this observational study zidovudine was associated with higher levels of severe
anaemia than stavudine or tenofovir; those receiving zidovudine and tenofovir had smaller },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction—
Anaemia is a common problem in HIV in sub-Saharan Africa. We describe the
contribution of ART regimen on the incidence of anaemia and changes in haemoglobin in
Ugandan patients.
Methods—
This study was nested in a prevention of cryptococcal disease trial (CRYPTOPRO;
ISCRTN7648152). Patients received three different nucleoside reverse transcriptase inhibitor
backbones in a non-randomised manner.
Results—
Of 852 patients (161 on zidovudine, 628 on stavudine and 63 on tenofovir (all received
lamuvidine), the risk of developing grade 4 anaemia was higher (aHR 2.7) for those taking
zidovudine compared with stavudine. Those taking stavudine had a greater average increase in
haemoglobin than those taking zidovudine (p=0.024) or tenofovir (p=0.014).
Conclusion—
In this observational study zidovudine was associated with higher levels of severe
anaemia than stavudine or tenofovir; those receiving zidovudine and tenofovir had smaller |
Goovaerts, Odin; Jennes, Wim; Massinga-Loembe, Marguerite; Ceulemans, Ann; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc; for the TB-IRIS Study Group, Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS Journal Article In: PloS One, vol. 9, no. 11, 2014. @article{Goovaerts2014b,
title = {Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS},
author = {Odin Goovaerts and Wim Jennes and Marguerite Massinga-Loembe and Ann Ceulemans and William Worodria and Harriet Mayanja-Kizza and Robert Colebunders and Luc Kestens and for the TB-IRIS Study Group},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Antigen-Specific-Interferon-Gamma.pdf},
doi = {10.1371/journal.pone.0113101},
year = {2014},
date = {2014-11-21},
journal = {PloS One},
volume = {9},
number = {11},
abstract = {Background:
Tuberculosis-associated immune reconstitution inflammatory
syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients
receiving antiretroviral therapy (ART). TB-IRIS could be associated with an
exaggerated immune response to TB-antigens. We compared the recovery of IFN
c
responses to recall and TB-antigens and explored in vitro innate cytokine
production in TB-IRIS patients.
Methods:
In a prospective cohort study of HIV-TB co-infected patients treated for
TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18
non-IRIS controls matched for age, sex and CD4 count. We analyzed IFN
c
ELISpot
responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV
and LPS stimulated ELISpot supernatants were subsequently evaluated for
production of IL-12p70, IL-6, TNF
a
and IL-10 by Luminex.
Results:
Before ART, all responses were similar between TB-IRIS patients and
non-IRIS controls. During TB-IRIS, IFN
c
responses to TB and influenza antigens
were comparable between TB-IRIS patients and non-IRIS controls, but responses
to CMV and LPS remained significantly lower in TB-IRIS patients. Production of
innate cytokines was similar between TB-IRIS patients and non-IRIS controls.
However, upon LPS stimulation, IL-6/IL-10 and TNF
a
/IL-10 ratios were increased in
TB-IRIS patients compared to non-IRIS controls
Conclusion:
TB-IRIS patients did not display excessive IFN
c
responses to TB-
antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in
the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the
innate cytokine balance. These data are in support of a prominent role of the innate
immune system in TB-IRIS},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background:
Tuberculosis-associated immune reconstitution inflammatory
syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients
receiving antiretroviral therapy (ART). TB-IRIS could be associated with an
exaggerated immune response to TB-antigens. We compared the recovery of IFN
c
responses to recall and TB-antigens and explored in vitro innate cytokine
production in TB-IRIS patients.
Methods:
In a prospective cohort study of HIV-TB co-infected patients treated for
TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18
non-IRIS controls matched for age, sex and CD4 count. We analyzed IFN
c
ELISpot
responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV
and LPS stimulated ELISpot supernatants were subsequently evaluated for
production of IL-12p70, IL-6, TNF
a
and IL-10 by Luminex.
Results:
Before ART, all responses were similar between TB-IRIS patients and
non-IRIS controls. During TB-IRIS, IFN
c
responses to TB and influenza antigens
were comparable between TB-IRIS patients and non-IRIS controls, but responses
to CMV and LPS remained significantly lower in TB-IRIS patients. Production of
innate cytokines was similar between TB-IRIS patients and non-IRIS controls.
However, upon LPS stimulation, IL-6/IL-10 and TNF
a
/IL-10 ratios were increased in
TB-IRIS patients compared to non-IRIS controls
Conclusion:
TB-IRIS patients did not display excessive IFN
c
responses to TB-
antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in
the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the
innate cytokine balance. These data are in support of a prominent role of the innate
immune system in TB-IRIS |
Lamorde, Mohammed; Schapiro, Jonathan M.; Burger, David; Backd, David J. Antiretroviral drugs for prevention of mother-to-child transmission: pharmacologic considerations for a public health approach Journal Article In: Journal of the Intrernational AIDS society, vol. 28, no. 17, pp. 2551-2563, 2014. @article{Lamorde2014,
title = {Antiretroviral drugs for prevention of mother-to-child transmission: pharmacologic considerations for a public health approach},
author = {Mohammed Lamorde and Jonathan M. Schapiro and David Burger and David J. Backd
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Antiretroviral-drugs-for-prevention-of-mother-to-child-transmission-....pdf},
doi = {10.1097/QAD.0000000000000439},
year = {2014},
date = {2014-11-13},
journal = {Journal of the Intrernational AIDS society},
volume = {28},
number = {17},
pages = {2551-2563},
abstract = {Objective: Efavirenz-based antiretroviral therapy is recommended for prevention of mother-to-child transmission of HIV with two programmatic options: lifelong therapy for all women or treatment until cessation of breastfeeding. However, the risk of HIV resistance emerging after discontinuing efavirenz-based antiretroviral therapy is unclear. We review present knowledge surrounding the emergence of resistance after stopping efavirenz-based antiretroviral regimens. Design: An expert review. Methods: A literature review was conducted to identify studies assessing risk for emergence of efavirenz-related resistance following discontinuation of efavirenz-based antiretroviral regimens containing either lamivudine and zidovudine or tenofovir disoproxil fumarate and lamivudine. Discontinuation strategies including the use of ‘pharmacologic tails’ are discussed in the light of what is known about the pharmacology of the drugs. Results: Wefoundnohead-to-headcomparisonsbetweenzidovudine,lamivudineand efavirenz and tenofovir disoproxil fumarate, lamivudine and efavirenz. The risk for HIV resistance exists, even with a 5–7 day tail of zidovudine and lamivudine. For tenofovir disoproxil fumarate, lamivudine and efavirenz, we found no clinical data to inform a recommendation for a tail. Conclusion: In order to prevent emergence of resistance, a tail of at least 2 weeks in duration may be required when discontinuing efavirenz in a regimen containing zidovudine and lamivudine. Studies are needed to characterize the risk of resistance among women who discontinue tenofovir disoproxil fumarate, lamivudine and efavirenz. 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objective: Efavirenz-based antiretroviral therapy is recommended for prevention of mother-to-child transmission of HIV with two programmatic options: lifelong therapy for all women or treatment until cessation of breastfeeding. However, the risk of HIV resistance emerging after discontinuing efavirenz-based antiretroviral therapy is unclear. We review present knowledge surrounding the emergence of resistance after stopping efavirenz-based antiretroviral regimens. Design: An expert review. Methods: A literature review was conducted to identify studies assessing risk for emergence of efavirenz-related resistance following discontinuation of efavirenz-based antiretroviral regimens containing either lamivudine and zidovudine or tenofovir disoproxil fumarate and lamivudine. Discontinuation strategies including the use of ‘pharmacologic tails’ are discussed in the light of what is known about the pharmacology of the drugs. Results: Wefoundnohead-to-headcomparisonsbetweenzidovudine,lamivudineand efavirenz and tenofovir disoproxil fumarate, lamivudine and efavirenz. The risk for HIV resistance exists, even with a 5–7 day tail of zidovudine and lamivudine. For tenofovir disoproxil fumarate, lamivudine and efavirenz, we found no clinical data to inform a recommendation for a tail. Conclusion: In order to prevent emergence of resistance, a tail of at least 2 weeks in duration may be required when discontinuing efavirenz in a regimen containing zidovudine and lamivudine. Studies are needed to characterize the risk of resistance among women who discontinue tenofovir disoproxil fumarate, lamivudine and efavirenz. 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
|
Kiwuwa-Muyingoa, Sylvia; Kikairea, Bernard; Mambuleb, Ivan; Musanac, Helen; Musorod, Godfrey; Gilkse, Charles F.; Levina, Jonathan B.; Walke, Anne Sarah Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial Journal Article In: Journal of the Intrernational AIDS society, vol. 28, no. 17, pp. 2579-2588, 2014. @article{Kiwuwa-Muyingoa2014,
title = {Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial},
author = {Sylvia Kiwuwa-Muyingoa and Bernard Kikairea and Ivan Mambuleb and Helen Musanac and Godfrey Musorod and Charles F. Gilkse and Jonathan B. Levina and Anne Sarah Walke},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Prevalence-incidence-and-predictors-of-peripheral-neuropathy-in-African-adults-with-HIV-infection-within-the-DART-trial.pdf},
doi = { 10.1097/QAD.0000000000000447},
year = {2014},
date = {2014-11-13},
journal = {Journal of the Intrernational AIDS society},
volume = {28},
number = {17},
pages = {2579-2588},
abstract = {
Objectives: We investigated the prevalence, incidence and predictors of new peripheral neuropathy episodes in previously untreated, symptomatic HIV-infected Ugandan/Zimbabwean adults initiating zidovudine-based antiretroviral therapy (ART).
Design: An open-label, multicentre, randomized trial.
Methods: Peripheral neuropathy was self-reported at 12-weekly clinic visits. Cox regression models (excluding participants reporting preexisting peripheral neuropathy at ART initiation), considered sex; pre-ART WHO stage, age and CD4+ cell count; CD4+ cell count versus no CD4+ cell count monitoring; and time-updated CD4+ cell count, weight and use of stavudine, isoniazid and didanosine.
Results: Four hundred and twenty-one out of 3316(13%) patients reported preexisting peripheral neuropathy at ART initiation. Median (interquartile range, IQR) follow-up in 2895 participants without preexisting peripheral neuropathy was 4.9 (4.7–5.4) years. Three hundred and fifty-four (12%) took stavudine as first-line substitution and 518 (18%) took isoniazid during follow-up. Two hundred and ninety (11%) participants developed a new peripheral neuropathy episode, an incidence of 2.12 per 100 person-years. Eighteen (0.1%) had a grade 3/4 episode. Independent predictors of peripheral neuropathy were current stavudine use [adjusted hazard ratio (a)HR 4.16 (95% confidence interval, 95% CI 3.06–5.66], current isoniazid use [aHR 1.59 (95% CI 1.02–2.47)] and current didanosine use [aHR 1.60 (95% CI 1.19–2.14)]. Higher risks were independently associated with higher pre-ART weight [aHR (per+5 kg) 1.07 (95% CI 1.01–1.13)] and older age aHR (per 10 years older) 1.29 (95% CI 1.12–1.49), but there was no significant effect of sex (P = 0.13), pre-ART CD4+ cell count (P = 0.91) or CD4+ cell count monitoring (P = 0.73).
Conclusion: Current stavudine, didanosine or isoniazid use continue to increase peripheral neuropathy risks, as does older age and weight at ART initiation; however, we found no evidence of increased risk in women in contrast to previous studies. The incidence of peripheral neuropathy may now be lower in ART programmes, as stavudine and didanosine are no longer recommended. All patients receiving isoniazid, either as part of antituberculosis (TB) chemotherapy or TB-preventive therapy, should receive pyridoxine as recommended in national guidelines.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objectives: We investigated the prevalence, incidence and predictors of new peripheral neuropathy episodes in previously untreated, symptomatic HIV-infected Ugandan/Zimbabwean adults initiating zidovudine-based antiretroviral therapy (ART).
Design: An open-label, multicentre, randomized trial.
Methods: Peripheral neuropathy was self-reported at 12-weekly clinic visits. Cox regression models (excluding participants reporting preexisting peripheral neuropathy at ART initiation), considered sex; pre-ART WHO stage, age and CD4+ cell count; CD4+ cell count versus no CD4+ cell count monitoring; and time-updated CD4+ cell count, weight and use of stavudine, isoniazid and didanosine.
Results: Four hundred and twenty-one out of 3316(13%) patients reported preexisting peripheral neuropathy at ART initiation. Median (interquartile range, IQR) follow-up in 2895 participants without preexisting peripheral neuropathy was 4.9 (4.7–5.4) years. Three hundred and fifty-four (12%) took stavudine as first-line substitution and 518 (18%) took isoniazid during follow-up. Two hundred and ninety (11%) participants developed a new peripheral neuropathy episode, an incidence of 2.12 per 100 person-years. Eighteen (0.1%) had a grade 3/4 episode. Independent predictors of peripheral neuropathy were current stavudine use [adjusted hazard ratio (a)HR 4.16 (95% confidence interval, 95% CI 3.06–5.66], current isoniazid use [aHR 1.59 (95% CI 1.02–2.47)] and current didanosine use [aHR 1.60 (95% CI 1.19–2.14)]. Higher risks were independently associated with higher pre-ART weight [aHR (per+5 kg) 1.07 (95% CI 1.01–1.13)] and older age aHR (per 10 years older) 1.29 (95% CI 1.12–1.49), but there was no significant effect of sex (P = 0.13), pre-ART CD4+ cell count (P = 0.91) or CD4+ cell count monitoring (P = 0.73).
Conclusion: Current stavudine, didanosine or isoniazid use continue to increase peripheral neuropathy risks, as does older age and weight at ART initiation; however, we found no evidence of increased risk in women in contrast to previous studies. The incidence of peripheral neuropathy may now be lower in ART programmes, as stavudine and didanosine are no longer recommended. All patients receiving isoniazid, either as part of antituberculosis (TB) chemotherapy or TB-preventive therapy, should receive pyridoxine as recommended in national guidelines.
|
Sebunya, Robert; Musiime, Victor; Kitaka, Sabrina Bakeera; Ndeezi, Grace Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic Journal Article In: AIDS Research and Therapy , vol. 10, no. 1, 2014. @article{Sebunya2014,
title = {Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic},
author = {Robert Sebunya and Victor Musiime and Sabrina Bakeera Kitaka and Grace Ndeezi},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Incidence-and-risk-factors-for-first-line-anti-retroviral-treatment-failure-among-Ugandan-children-attending-an-urban-HIV-clinic.pdf},
doi = { 10.1186/1742-6405-10-25},
year = {2014},
date = {2014-11-11},
journal = {AIDS Research and Therapy },
volume = {10},
number = {1},
abstract = {BACKGROUND:
Early recognition of antiretroviral therapy (ART) failure in resource limited settings is a challenge given the limited laboratory facilities and trained personnel. This study aimed at describing the incidence, risk factors and the resistance associated mutations (RAMs) of first line treatment failure among HIV-1-infected children attending the Joint Clinical Research Centre (JCRC), Kampala, Uganda.
METHODS:
A retrospective cohort of 701 children who had been initiated on ART between January 2004 and September 2009 at the JCRC was studied. Data of children aged 6 months up to 18 years who had been started on ART for at least 6 months was extracted from the clinic charts. The children who failed the first-line ART were taken as cases and those who did not fail as the controls. Data was analysed using STATA version10.
RESULTS:
Of 701 children, 240(34%) failed on first line ART (cases) and 461(66%) did not fail (controls). The overall median time (IQR) to first line ART failure was 26.4 (18.9 - 39.1) months. The factors associated with treatment failure were poor adherence [(OR = 10, 95 CI: 6.4 - 16.7) p < 0.001], exposure to single dose nevirapine (sdNVP) [(OR = 4.2, 95% CI:1.8-9.4), p = 0.005] and a NVP containing regimen [(OR = 2.2,95% CI:1.4-3.6), p < 0.001]. Of 109 genotypic resistance profiles analyzed, the commonest non nucleoside reverse transcriptase inhibitor (NNRTI) resistance associated mutations (RAM) were: K103N (59; 54%)), Y181C (36; 27%)) and G190A (26; 24%)) while the commonest nucleoside reverse transcriptase inhibitor (NRTI) RAM was the M184V (89; 81%). Thymidine analogue- mutations (TAMs) were detected in 20% of patients.
CONCLUSIONS:
One in three children on first-line ART are likely to develop virological treatment failure after the first 24 months of therapy. Poor adherence to ART, a NVP based first-line regimen, prior exposure to sdNVP were associated with treatment failure.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
Early recognition of antiretroviral therapy (ART) failure in resource limited settings is a challenge given the limited laboratory facilities and trained personnel. This study aimed at describing the incidence, risk factors and the resistance associated mutations (RAMs) of first line treatment failure among HIV-1-infected children attending the Joint Clinical Research Centre (JCRC), Kampala, Uganda.
METHODS:
A retrospective cohort of 701 children who had been initiated on ART between January 2004 and September 2009 at the JCRC was studied. Data of children aged 6 months up to 18 years who had been started on ART for at least 6 months was extracted from the clinic charts. The children who failed the first-line ART were taken as cases and those who did not fail as the controls. Data was analysed using STATA version10.
RESULTS:
Of 701 children, 240(34%) failed on first line ART (cases) and 461(66%) did not fail (controls). The overall median time (IQR) to first line ART failure was 26.4 (18.9 - 39.1) months. The factors associated with treatment failure were poor adherence [(OR = 10, 95 CI: 6.4 - 16.7) p < 0.001], exposure to single dose nevirapine (sdNVP) [(OR = 4.2, 95% CI:1.8-9.4), p = 0.005] and a NVP containing regimen [(OR = 2.2,95% CI:1.4-3.6), p < 0.001]. Of 109 genotypic resistance profiles analyzed, the commonest non nucleoside reverse transcriptase inhibitor (NNRTI) resistance associated mutations (RAM) were: K103N (59; 54%)), Y181C (36; 27%)) and G190A (26; 24%)) while the commonest nucleoside reverse transcriptase inhibitor (NRTI) RAM was the M184V (89; 81%). Thymidine analogue- mutations (TAMs) were detected in 20% of patients.
CONCLUSIONS:
One in three children on first-line ART are likely to develop virological treatment failure after the first 24 months of therapy. Poor adherence to ART, a NVP based first-line regimen, prior exposure to sdNVP were associated with treatment failure. |
Radha Rajasingham, * Joshua Rhein; Klammer, Kate; Musubire, Abdu; Nabeta, Henry; Akampurira, Andrew; Mossel, Eric C.; Williams, Darlisha A.; Boxrud, Dave J.; Crabtree, Mary B.; Miller, Barry R.; Rolfes, Melissa A.; Alfred O. Andama Supatida Tengsupakul, David B. Meya; Boulware, David R. Epidemiology of Meningitis in an HIV-Infected Ugandan Cohort Journal Article In: American Journal of TropicalMedicine and Hygiene, vol. 92, no. 2, 2014, ISSN: 0002-9637 . @article{Rajasingham2014,
title = {Epidemiology of Meningitis in an HIV-Infected Ugandan Cohort},
author = {Radha Rajasingham,
*
Joshua Rhein and Kate Klammer and Abdu Musubire and Henry Nabeta and Andrew Akampurira and Eric C. Mossel and
Darlisha A. Williams and Dave J. Boxrud and Mary B. Crabtree and Barry R. Miller and Melissa A. Rolfes and Supatida Tengsupakul,
Alfred O. Andama, David B. Meya, and David R. Boulware},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Epidemiology-of-Meningitis-in-an-HIV-Infected-Ugandan-Cohort.pdf},
doi = {10.4269/ajtmh.14-0452},
issn = {0002-9637 },
year = {2014},
date = {2014-11-10},
journal = {American Journal of TropicalMedicine and Hygiene},
volume = {92},
number = {2},
abstract = {here is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein–Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains needed, and implementation of cryptococcal diagnostics is critical.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
here is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein–Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains needed, and implementation of cryptococcal diagnostics is critical. |
Kimberly, Scarsi; Mohammed, Lamorde; Darin, Kristin; Sujan, Dilly Penchala; Laura4, Else; Shadia, Nakalema; Pauline, Byakika-Kibwika; Saye, Khoo; Susan, Cohn; Concepta, Merry; David, Back Efavirenz‐ but not nevirapine‐based antiretroviral therapy decreases exposure to the levonorgestrel released from a sub‐dermal contraceptive implant Journal Article In: Journal of the Intrernational AIDS society, vol. 4, no. 3, 2014. @article{Kimberly2014,
title = {Efavirenz‐ but not nevirapine‐based antiretroviral therapy decreases exposure to the levonorgestrel released from a sub‐dermal contraceptive implant},
author = {Scarsi Kimberly and Lamorde Mohammed and Darin, Kristin and Dilly Penchala Sujan and Else Laura4 and Nakalema Shadia and Byakika-Kibwika Pauline and Khoo Saye and Cohn Susan and Merry Concepta and Back David},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Efavirenz‐-but-not-nevirapine‐based-antiretroviral-therapy-decreases-exposure-to-the-levonorgestrel-released-from-a-sub‐dermal-contraceptive-implant.pdf},
doi = {10.7448/IAS.17.4.19484},
year = {2014},
date = {2014-11-02},
journal = {Journal of the Intrernational AIDS society},
volume = {4},
number = {3},
abstract = {Introduction: Sub-dermal hormone implants, such as levonorgestrel (LNG), are a safe and desirable form of long-acting contraception, but their use among HIV-positive women on antiretroviral therapy (ART) may be compromised given the potential for a cytochrome P450 3A-mediated drugdrug interaction. Our study aimed to characterize the pharmacokinetics of LNG released from a sub-dermal implant over six months in HIV-positive Ugandan women on nevirapine (NVP)- or efavirenz (EFV)-based ART
Material and Methods: This non-randomized, parallel group study compared LNG pharmacokinetics between HIV-positive Ugandan women not yet eligible for ART (control group, n18) and those on stable NVP- (n20) or EFV- (n20) based ART. The two-rod (75 mg/rod) LNG sub-dermal implant was inserted at study enrolment. LNG sampling was obtained pre-implant and at weeks 1, 4, 12 and 24 post-insertion. LNG concentrations were analyzed using a validated LC-MS/MS method, with an assay calibration range of 501500 pg/mL. Safety monitoring, including a pregnancy test, was conducted at each study visit. Results: At enrolment, participants had a mean age of 31 years; CD4 cell counts were similar between the control, NVP and EFV groups (758, 645 and 568 cells/mm3, respectively; p0.09); all women in the NVP and EFV groups had an undetectable HIVRNA. Women in the control group had a higher baseline body weight (73 kg) compared to those in the NVP (63 kg; p0.03) or EFV groups (60 kg; pB0.01). By linear regression, weight was a significant predictor of LNG concentrations (1 kg increase in weight5 pg/mL decrease in LNG, p0.03). LNG concentrations are reported in the table. Conclusions: Over a 24-week period, LNG concentrations were 4054% lower in women on EFV-based ART, despite their having a significantly lower body weight, compared to those not on ART. In women on NVP-based ART, LNG concentrations were 32 39% higher than those observed in the control group, a difference partially explained by body weight. These data confirm a significant drug interaction occurs between the LNG implant and EFV, adding to growing concern for reduced contraceptive efficacy with their combined use. In contrast, these data support use of the LNG implant with NVP-based ART.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction: Sub-dermal hormone implants, such as levonorgestrel (LNG), are a safe and desirable form of long-acting contraception, but their use among HIV-positive women on antiretroviral therapy (ART) may be compromised given the potential for a cytochrome P450 3A-mediated drugdrug interaction. Our study aimed to characterize the pharmacokinetics of LNG released from a sub-dermal implant over six months in HIV-positive Ugandan women on nevirapine (NVP)- or efavirenz (EFV)-based ART
Material and Methods: This non-randomized, parallel group study compared LNG pharmacokinetics between HIV-positive Ugandan women not yet eligible for ART (control group, n18) and those on stable NVP- (n20) or EFV- (n20) based ART. The two-rod (75 mg/rod) LNG sub-dermal implant was inserted at study enrolment. LNG sampling was obtained pre-implant and at weeks 1, 4, 12 and 24 post-insertion. LNG concentrations were analyzed using a validated LC-MS/MS method, with an assay calibration range of 501500 pg/mL. Safety monitoring, including a pregnancy test, was conducted at each study visit. Results: At enrolment, participants had a mean age of 31 years; CD4 cell counts were similar between the control, NVP and EFV groups (758, 645 and 568 cells/mm3, respectively; p0.09); all women in the NVP and EFV groups had an undetectable HIVRNA. Women in the control group had a higher baseline body weight (73 kg) compared to those in the NVP (63 kg; p0.03) or EFV groups (60 kg; pB0.01). By linear regression, weight was a significant predictor of LNG concentrations (1 kg increase in weight5 pg/mL decrease in LNG, p0.03). LNG concentrations are reported in the table. Conclusions: Over a 24-week period, LNG concentrations were 4054% lower in women on EFV-based ART, despite their having a significantly lower body weight, compared to those not on ART. In women on NVP-based ART, LNG concentrations were 32 39% higher than those observed in the control group, a difference partially explained by body weight. These data confirm a significant drug interaction occurs between the LNG implant and EFV, adding to growing concern for reduced contraceptive efficacy with their combined use. In contrast, these data support use of the LNG implant with NVP-based ART.
|
Eva, Laker; Ivan, Mambule; Damalie, Nalwanga; Joseph, Musaazi; Agnes, Kiragga; Rosalind, Parkes-Ratanshi Boosted lopinavir vs boosted atazanavir in patients failing a NNRTI first line regimen in an urban clinic in Kampala Journal Article In: Journal of the Intrernational AIDS society, vol. 4, no. 3, 2014. @article{Eva2014,
title = {Boosted lopinavir vs boosted atazanavir in patients failing a NNRTI first line regimen in an urban clinic in Kampala},
author = {Laker Eva and Mambule Ivan and Nalwanga Damalie and Musaazi Joseph and Kiragga Agnes and Parkes-Ratanshi Rosalind
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Boosted-lopinavir-vs-boosted-atazanavir-in-patients-failing-a-NNRTI-first-line-regimen-in-an-urban-clinic-in-Kampala.pdf},
doi = { 10.7448/IAS.17.4.19792},
year = {2014},
date = {2014-11-02},
journal = {Journal of the Intrernational AIDS society},
volume = {4},
number = {3},
abstract = {Introduction
: In 2011 Uganda recommended boosted atazanavir (ATV/r) as the preferred PI for second line due to once daily
dosing, replacing aluvia (LPV/r) [1,2]. The evidence was based on the BMS O45 trial, of LPV/r vs ATV/r was performed in a high-
income setting, on patients with prior PI use and resistance testing [2,3]. There are no RCTs or observational studies comparing
use of ATV/r with LPV/r in patients failing NNRTI first line antiretroviral therapy in sub-Saharan Africa [3,4]. The Infectious
Diseases Institute (IDI) has a large second line cohort (
1838). This aims to compare clinical, immunologic and virologic
response of LPV/r versus ATV/r at IDI.
Methods
: Retrospective cohort analysis on routinely collected data of patients switched to second line with NRTI backbones
TDF/3TC or FTC, AZT/3TC, ABC/3TC from January 2009 to December 2013. Students T-tests and Chi-square tests were used in
this analysis.
Results
: A total of 1286 (73.5% female) patients were switched to LPV/r 991 (77%) and ATV/r 295 (23%) (p
B
0.001). NRTI
backbones were 760 on TDF/3TC (66.8% LPV/r vs 33.2% on ATV/r), 504 on AZT/3TC (93.3% vs 6.7%), and 22 on ABC/3TC (59% vs
41%). Median (IQR) time on first line for LPV/r was 21 (1
44) months and for ATV/r was 41 months (22
68). Median CD4 (IQR)
at switch to LPV/r was 181 cells/uL (66
424) and to ATV/r was 122 (57
238) (p
5
0.001). A total of 366 patients had CD4 done at
six months after switch and the mean (IQR) CD4 increase was 153 (54
241) for LPV/r versus 116 (52
171) for ATV/r (p
0.232).
Additionally, 304 had a CD4 at 12 months and the means were 172 (45
272) for LPV/r vs 179 (60
271) for ATV/r (p
0.426).
There was no significant difference in the mean increment by NRTI backbone or by stratifying to viral load (VL) at time of switch
to VL
B
100,000 and
]
100,000. Median (IQR) VL at switch was 61,000 (13,000
2,030,000) LPV/r and 51,000 (14,000_151,000)
ATV/r. 269 had a VL done in the first 12 months and 178/250 (71.2%) on LPV/r versus 16/19 (84.2%) on ATV/r were undetectable
(p
0.228). 259 (26%) LPV/r versus 33(11%) ATV/r had
]
1 opportunistic infections on second line (p
B
0.001).
Conclusions
: This is an observational study based on our experience at IDI. Like elsewhere in Africa, there is no routine viral load
testing, making it difficult to get sensitive analysis of data on ART efficacy within routine clinical practice. Nevertheless, this
observational study is reassuring in terms of efficacy of both ATV/r and LPV/r for patients failing first line therapy in our setting},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction
: In 2011 Uganda recommended boosted atazanavir (ATV/r) as the preferred PI for second line due to once daily
dosing, replacing aluvia (LPV/r) [1,2]. The evidence was based on the BMS O45 trial, of LPV/r vs ATV/r was performed in a high-
income setting, on patients with prior PI use and resistance testing [2,3]. There are no RCTs or observational studies comparing
use of ATV/r with LPV/r in patients failing NNRTI first line antiretroviral therapy in sub-Saharan Africa [3,4]. The Infectious
Diseases Institute (IDI) has a large second line cohort (
1838). This aims to compare clinical, immunologic and virologic
response of LPV/r versus ATV/r at IDI.
Methods
: Retrospective cohort analysis on routinely collected data of patients switched to second line with NRTI backbones
TDF/3TC or FTC, AZT/3TC, ABC/3TC from January 2009 to December 2013. Students T-tests and Chi-square tests were used in
this analysis.
Results
: A total of 1286 (73.5% female) patients were switched to LPV/r 991 (77%) and ATV/r 295 (23%) (p
B
0.001). NRTI
backbones were 760 on TDF/3TC (66.8% LPV/r vs 33.2% on ATV/r), 504 on AZT/3TC (93.3% vs 6.7%), and 22 on ABC/3TC (59% vs
41%). Median (IQR) time on first line for LPV/r was 21 (1
44) months and for ATV/r was 41 months (22
68). Median CD4 (IQR)
at switch to LPV/r was 181 cells/uL (66
424) and to ATV/r was 122 (57
238) (p
5
0.001). A total of 366 patients had CD4 done at
six months after switch and the mean (IQR) CD4 increase was 153 (54
241) for LPV/r versus 116 (52
171) for ATV/r (p
0.232).
Additionally, 304 had a CD4 at 12 months and the means were 172 (45
272) for LPV/r vs 179 (60
271) for ATV/r (p
0.426).
There was no significant difference in the mean increment by NRTI backbone or by stratifying to viral load (VL) at time of switch
to VL
B
100,000 and
]
100,000. Median (IQR) VL at switch was 61,000 (13,000
2,030,000) LPV/r and 51,000 (14,000_151,000)
ATV/r. 269 had a VL done in the first 12 months and 178/250 (71.2%) on LPV/r versus 16/19 (84.2%) on ATV/r were undetectable
(p
0.228). 259 (26%) LPV/r versus 33(11%) ATV/r had
]
1 opportunistic infections on second line (p
B
0.001).
Conclusions
: This is an observational study based on our experience at IDI. Like elsewhere in Africa, there is no routine viral load
testing, making it difficult to get sensitive analysis of data on ART efficacy within routine clinical practice. Nevertheless, this
observational study is reassuring in terms of efficacy of both ATV/r and LPV/r for patients failing first line therapy in our setting |
Reynolds, Steven J.; Sempa, Joseph B.; Kiragga, Agnes N.; Newell, Kevin; Nakigozi, Gertrude; Galiwango, Ronald; Gray, Ron; Quinn, Thomas C.; Serwadda, David; Larry Chang, Is CD4 Monitoring Needed Among Ugandan Clients Achieving a Virologic and Immunologic Response to Treatment? Journal Article In: AIDS Patient Care and STDS, vol. 28, no. 11, pp. 575-578, 2014. @article{Reynolds2014,
title = {Is CD4 Monitoring Needed Among Ugandan Clients Achieving a Virologic and Immunologic Response to Treatment?},
author = {Steven J. Reynolds and Joseph B. Sempa and Agnes N. Kiragga and Kevin Newell and Gertrude Nakigozi and Ronald Galiwango and Ron Gray and Thomas C. Quinn and David Serwadda and Larry Chang,},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Is-CD4-Monitoring-Needed-Among-Ugandan-Clients.pdf},
year = {2014},
date = {2014-11-01},
journal = {AIDS Patient Care and STDS},
volume = {28},
number = {11},
pages = {575-578},
abstract = {It is unclear whether ongoing CD4 monitoring is needed following immunologic and virologic response to
antiretroviral therapy (ART). We investigated the proportion of clients who achieved a virologic and immu-
nologic response and then had a subsequent CD4 count
<
200 cells/
l
L despite continued virologic suppression.
Included in this analysis were clients receiving ART through the Rakai Health Sciences Program between June
2004–May 2013 who achieved a CD4
‡
200 cells/
l
L and VL
£
400 copies/mL and who had three sets of CD4
and VL measurements (defined as a
sequence
) within a 390 day period. A CD4 decline was defined as any drop
in CD4 count to
<
200 cells/
l
L during a period of viral suppression. A total of 1553 clients were included, 68%
females, mean age of 35.5 years (SD 8.3), median baseline CD4 count 183 cells/
l
L (IQR 106–224). 43 (2.8%)
clients developed CD4 declines, the majority, 32/43 (74%), among individuals whose initial CD4 was
<
300
cells/
l
L. Of the 43 clients with CD4 declines, 24 had an additional CD4 measurement and 20/24 (83%)
achieved a CD4
‡
200 cell/
l
L on their next measurement (median 285 cells/
l
L; IQR 220–365). CD4 declines
were significantly greater among those with lower CD4 at sequence initiation [adjusted hazard ratio (AHR) 4.3
(95% CI 2.1, 9.0) CD4 200–249 versus
‡
350 cells/
l
L]. Clients who achieved an immunologic and virologic
response to ART were unlikely to experience a subsequent CD4 count decline to
<
200 cells/
l
L, and among
those experiencing a decline, the majority were transient in nature. Thus, ongoing CD4 monitoring could be
omitted.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
It is unclear whether ongoing CD4 monitoring is needed following immunologic and virologic response to
antiretroviral therapy (ART). We investigated the proportion of clients who achieved a virologic and immu-
nologic response and then had a subsequent CD4 count
<
200 cells/
l
L despite continued virologic suppression.
Included in this analysis were clients receiving ART through the Rakai Health Sciences Program between June
2004–May 2013 who achieved a CD4
‡
200 cells/
l
L and VL
£
400 copies/mL and who had three sets of CD4
and VL measurements (defined as a
sequence
) within a 390 day period. A CD4 decline was defined as any drop
in CD4 count to
<
200 cells/
l
L during a period of viral suppression. A total of 1553 clients were included, 68%
females, mean age of 35.5 years (SD 8.3), median baseline CD4 count 183 cells/
l
L (IQR 106–224). 43 (2.8%)
clients developed CD4 declines, the majority, 32/43 (74%), among individuals whose initial CD4 was
<
300
cells/
l
L. Of the 43 clients with CD4 declines, 24 had an additional CD4 measurement and 20/24 (83%)
achieved a CD4
‡
200 cell/
l
L on their next measurement (median 285 cells/
l
L; IQR 220–365). CD4 declines
were significantly greater among those with lower CD4 at sequence initiation [adjusted hazard ratio (AHR) 4.3
(95% CI 2.1, 9.0) CD4 200–249 versus
‡
350 cells/
l
L]. Clients who achieved an immunologic and virologic
response to ART were unlikely to experience a subsequent CD4 count decline to
<
200 cells/
l
L, and among
those experiencing a decline, the majority were transient in nature. Thus, ongoing CD4 monitoring could be
omitted. |
Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ceulemans, Ann; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc; Group, TB-IRIS Study Unbalanced Adaptive and Innate Immune Responses during TB-IRIS Journal Article In: AIDS Research and Human Retroviruses, vol. 30, no. 1, 2014. @article{Goovaerts2014,
title = {Unbalanced Adaptive and Innate Immune Responses during TB-IRIS},
author = { Odin Goovaerts and Wim Jennes and Marguerite Massinga-Loembé and Ann Ceulemans and William Worodria and Harriet Mayanja-Kizza and Robert Colebunders and Luc Kestens and TB-IRIS Study Group},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Unbalanced-Adaptive-and-Innate-Immune-Responses-during-TB-IRIS.pdf},
doi = {10.1089/aid.2014.5379.},
year = {2014},
date = {2014-10-30},
journal = {AIDS Research and Human Retroviruses},
volume = {30},
number = {1},
abstract = {Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS is thought to be associated with an exaggerated immune response to TB antigens. We compared the recovery of IFNγ responses to TB- and recall-antigens during TB-IRIS. We also explored the contribution of innate cytokine production to TB-IRIS.
Methods: From a prospective cohort study of HIV-TB co-infected patients treated for TB prior to ART initiation, we compared 18 patients who developed TB-IRIS within the first month after ART initiation with 18 non-IRIS patients matched for age, sex and baseline CD4 count. We analyzed IFNγ ELISpot responses to CMV-lysate, influenza antigen A, PPD, ESAT-6, CFP-10 and LPS at pre-ART and IRIS event. CMV, PPD and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex
Results: At baseline, before initiation of ART, all measured responses were similar between TB-IRIS group and non-IRIS controls. During the TB-IRIS event, IFNγ ELISpot responses to TB or influenza antigens were still comparable between TB-IRIS patients and the non-IRIS patients, but the responses to CMV and LPS were significantly lower in TB-IRIS patients. Production of innate cytokines was similar between IRIS patients and non-IRIS patients. However, IL-6/IL-10 and TNFα/IL-10 ratios were increased during TB-IRIS event upon LPS stimulation, compared to non-IRIS controls.
Conclusions: Our TB-IRIS patients did not display an excessive IFNγ response to TB antigens. However, the reconstitution of recall antigen responses is delayed in the TB-IRIS group. In addition, this study reveals an altered innate cytokine balance during TB-IRIS after LPS stimulation. These data provide further arguments for the involvement of the innate immune system in TB-IRIS pathogenesis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS is thought to be associated with an exaggerated immune response to TB antigens. We compared the recovery of IFNγ responses to TB- and recall-antigens during TB-IRIS. We also explored the contribution of innate cytokine production to TB-IRIS.
Methods: From a prospective cohort study of HIV-TB co-infected patients treated for TB prior to ART initiation, we compared 18 patients who developed TB-IRIS within the first month after ART initiation with 18 non-IRIS patients matched for age, sex and baseline CD4 count. We analyzed IFNγ ELISpot responses to CMV-lysate, influenza antigen A, PPD, ESAT-6, CFP-10 and LPS at pre-ART and IRIS event. CMV, PPD and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex
Results: At baseline, before initiation of ART, all measured responses were similar between TB-IRIS group and non-IRIS controls. During the TB-IRIS event, IFNγ ELISpot responses to TB or influenza antigens were still comparable between TB-IRIS patients and the non-IRIS patients, but the responses to CMV and LPS were significantly lower in TB-IRIS patients. Production of innate cytokines was similar between IRIS patients and non-IRIS patients. However, IL-6/IL-10 and TNFα/IL-10 ratios were increased during TB-IRIS event upon LPS stimulation, compared to non-IRIS controls.
Conclusions: Our TB-IRIS patients did not display an excessive IFNγ response to TB antigens. However, the reconstitution of recall antigen responses is delayed in the TB-IRIS group. In addition, this study reveals an altered innate cytokine balance during TB-IRIS after LPS stimulation. These data provide further arguments for the involvement of the innate immune system in TB-IRIS pathogenesis. |
Nabatanzi, Rose; Bayigga, Lois; Ssinabulya, Isaac; Kiragga, Agnes; Kambugu, Andrew; Olobo, Joseph; Joloba, Moses; Kamya, Moses R.; Mayanja-Kizza, Harriet; Nakanjako, Damalie Low antigen-specific CD4 T-cell immune responses despite normal absolute CD4 counts after long-term antiretroviral therapy an African cohort Journal Article In: Immunology Letters, vol. 162, no. 2 Pt B, pp. 264-72, 2014. @article{Nabatanzi2014,
title = {Low antigen-specific CD4 T-cell immune responses despite normal absolute CD4 counts after long-term antiretroviral therapy an African cohort},
author = {Rose Nabatanzi and Lois Bayigga and Isaac Ssinabulya and Agnes Kiragga and Andrew Kambugu and Joseph Olobo and Moses Joloba and Moses R. Kamya and Harriet Mayanja-Kizza and
Damalie Nakanjako},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Low-antigen-specific-CD4-T-cell-immune-responses-despite-normal-absolute-CD4-counts-after-long-term-antiretroviral-therapy-an-African-cohort.pdf},
doi = {10.1016/j.imlet.2014.09.016},
year = {2014},
date = {2014-10-26},
journal = {Immunology Letters},
volume = {162},
number = {2 Pt B},
pages = {264-72},
abstract = {ackground—
CD4 counts guide antiretroviral therapy (ART) initiation and prophylaxis for
opportunistic infections. It is unclear whether normal CD4 counts translate to normalized immune
responses among ART-treated adults. We compared antigen-specific CD4 T-cell immune
responses among ART-treated adults with CD4 ≥ 500 cells/μl, optimal immune responders (O-IR),
and their age-matched healthy HIV-negative counterparts.
Methods—
In a sample-based case–control study, cryopreserved peripheral blood mononuclear
cells from 15 O-IR after 7 years of ART and 15 healthy controls, were analyzed for CD4+ T-cell
proliferation using CFSE dye and cytokine production.
Results—
CD4 T-cell proliferation, upon stimulation with PPD and pneumococcal
polysaccharide antigen, was lower among O-IR relative to HIV-negative controls;
p
= 0.016 and
p
= 0.016 respectively. CD4 T-cell production of IL-2 was lower among O-IR relative to HIV-
negative control
p
= 0.002. CD4 T-cell proliferation upon stimulation with SEB and CMV
antigens was similar among O-IR and HIV-negative controls
p
= 0.971 and
p
= 0.480,
respectively, and so was IL-4 and IFN
γ
production;
p
= 0.528 and
p
= 0.892, respectively},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
ackground—
CD4 counts guide antiretroviral therapy (ART) initiation and prophylaxis for
opportunistic infections. It is unclear whether normal CD4 counts translate to normalized immune
responses among ART-treated adults. We compared antigen-specific CD4 T-cell immune
responses among ART-treated adults with CD4 ≥ 500 cells/μl, optimal immune responders (O-IR),
and their age-matched healthy HIV-negative counterparts.
Methods—
In a sample-based case–control study, cryopreserved peripheral blood mononuclear
cells from 15 O-IR after 7 years of ART and 15 healthy controls, were analyzed for CD4+ T-cell
proliferation using CFSE dye and cytokine production.
Results—
CD4 T-cell proliferation, upon stimulation with PPD and pneumococcal
polysaccharide antigen, was lower among O-IR relative to HIV-negative controls;
p
= 0.016 and
p
= 0.016 respectively. CD4 T-cell production of IL-2 was lower among O-IR relative to HIV-
negative control
p
= 0.002. CD4 T-cell proliferation upon stimulation with SEB and CMV
antigens was similar among O-IR and HIV-negative controls
p
= 0.971 and
p
= 0.480,
respectively, and so was IL-4 and IFN
γ
production;
p
= 0.528 and
p
= 0.892, respectively |
Galukande, Moses; Sekavuga, Dennis Bbaale; Muganzi, Alex; Coutinho, Alex Fournier ’ s gangrene after adult male circumcision Journal Article In: International Journal of Emergency Medicine, vol. 37, no. 1, 2014. @article{Galukande2014,
title = {Fournier ’ s gangrene after adult male circumcision},
author = {Moses Galukande and Dennis Bbaale Sekavuga and Alex Muganzi and Alex Coutinho
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Fournier...-1.pdf},
doi = {10.1186/s12245-014-0037-0},
year = {2014},
date = {2014-10-24},
journal = {International Journal of Emergency Medicine},
volume = {37},
number = {1},
abstract = {Background:
In the advent of mass voluntary medical male circumcision (VMMC) for the partial prevention of HIV,
previously rare adverse events associated with adult male circumcision are likely to be encountered with higher
frequency. Fournier
’
s gangrene, defined as a polymicrobial necrotizing fasciitis of the perineal, perianal or genital
areas, is one such rare and life-threatening adverse event. In this report, we present two cases that were identified
in the context of a VMMC programme over a 3-year period during which approximately 100,000 adult circumcisions
were performed.
Case presentations:
Case 1: A 19-year-old male who had VMMC performed using the dorsal slit technique
developed pain and blisters on the scrotal skin on the sixth postoperative day. He had no co-morbidities, and
serology for HIV was negative. On examination, locally he had scrotal skin necrosis with an offensive odour and was
dehydrated but afebrile. Repeated aggressive debridement was done while he stayed in a hospital for 3 weeks; at
which point, he had healthy granulation tissue and was free of infection. The wound had closed spontaneously and
completely by the fifth month.
Case 2: A 52-year-old male who had VMMC performed with the sleeve resection method developed pain and
swelling of the penis and scrotum on the fourth postoperative day. He had a low-grade fever of 37.6°C. He was not
diabetic or immunosuppressed and had a negative HIV serology. He was admitted and was given IV antibiotics, and
repeated aggressive debridement was performed. On the third week of hospitalization, he had healthy granulation
tissue and received a split skin graft on the penile shaft. At 4 months, the scrotal defect had completely closed.
Conclusion:
Fournier
’
s gangrene is a rare occurrence after adult male circumcision with associated high morbidity.
These are the first descriptions in the VMMC era.
Keywords:
Gangrene; Male; Adult; Circumcision},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background:
In the advent of mass voluntary medical male circumcision (VMMC) for the partial prevention of HIV,
previously rare adverse events associated with adult male circumcision are likely to be encountered with higher
frequency. Fournier
’
s gangrene, defined as a polymicrobial necrotizing fasciitis of the perineal, perianal or genital
areas, is one such rare and life-threatening adverse event. In this report, we present two cases that were identified
in the context of a VMMC programme over a 3-year period during which approximately 100,000 adult circumcisions
were performed.
Case presentations:
Case 1: A 19-year-old male who had VMMC performed using the dorsal slit technique
developed pain and blisters on the scrotal skin on the sixth postoperative day. He had no co-morbidities, and
serology for HIV was negative. On examination, locally he had scrotal skin necrosis with an offensive odour and was
dehydrated but afebrile. Repeated aggressive debridement was done while he stayed in a hospital for 3 weeks; at
which point, he had healthy granulation tissue and was free of infection. The wound had closed spontaneously and
completely by the fifth month.
Case 2: A 52-year-old male who had VMMC performed with the sleeve resection method developed pain and
swelling of the penis and scrotum on the fourth postoperative day. He had a low-grade fever of 37.6°C. He was not
diabetic or immunosuppressed and had a negative HIV serology. He was admitted and was given IV antibiotics, and
repeated aggressive debridement was performed. On the third week of hospitalization, he had healthy granulation
tissue and received a split skin graft on the penile shaft. At 4 months, the scrotal defect had completely closed.
Conclusion:
Fournier
’
s gangrene is a rare occurrence after adult male circumcision with associated high morbidity.
These are the first descriptions in the VMMC era.
Keywords:
Gangrene; Male; Adult; Circumcision |
Ssengooba, Willy; Nakiyingi, Lydia; Armstrong, Derek T.; Cobelens, Frank G.; Alland, David; Manabe, Yukari C.; Dorman, Susan E.; Ellner, Jerrold J.; Joloba, Moses L. Clinical Utility of a Novel Molecular Assay in Various Combination Strategies with Existing Methods for Diagnosis of HIV-Related Tuberculosis in Uganda Journal Article In: PloS One, vol. 9, no. 9, 2014. @article{Ssengooba2014,
title = {Clinical Utility of a Novel Molecular Assay in Various Combination Strategies with Existing Methods for Diagnosis of HIV-Related Tuberculosis in Uganda},
author = {Willy Ssengooba and Lydia Nakiyingi and Derek T. Armstrong and Frank G. Cobelens and David Alland and Yukari C. Manabe and Susan E. Dorman and Jerrold J. Ellner and Moses L. Joloba
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Clinical-Utility-of-a-Novel-Molecular-Assay-in-Various.pdf},
doi = {10.1371/journal.pone.0107595},
year = {2014},
date = {2014-10-15},
journal = {PloS One},
volume = {9},
number = {9},
abstract = {Background:
Low income, high-tuberculosis burden, countries are considering selective deployment of Xpert MTB/RIF assay
(Xpert) due to high cost per test. We compared the diagnostic gain of the Xpert add-on strategy with Xpert replacement
strategy for pulmonary tuberculosis diagnosis among HIV-infected adults to inform its implementation.
Methods:
The first diagnostic sputum sample of 424 HIV-infected adults (67% with CD4 counts
#
200/mm
3
) suspected for
tuberculosis was tested by direct Ziehl-Neelsen (DZN) and direct fluorescent microscopy (DFM); concentrated fluorescent
microscopy (CFM); Lowenstein-Jensen (LJ) and Mycobacterial Growth Indicator Tube (MGIT) culture; and Xpert. Overall
diagnostic yield and sensitivity were calculated using MGIT as reference comparator. The sensitivity of Xpert in an add-on
strategy was calculated as the number of smear negative but Xpert positive participants among MGIT positive participants.
Results:
A total of 123 (29.0%) participants were MGIT culture positive for
Mycobacterium tuberculosis
. The sensitivity (95%
confidence interval) was 31.7% (23.6–40.7%) for DZN, 35.0% (26.5–44.0%) for DFM, 43.9% (34.9–53.1%) for CFM, 76.4%
(67.9–83.6) for Xpert and 81.3% (73.2–87.7%) for LJ culture. Add-on strategy Xpert showed an incremental sensitivity of
44.7% (35.7–53.9%) when added to DZN, 42.3% (33.4–51.5%) to DFM and 35.0% (26.5–44.0%) to CFM. This translated to an
overall sensitivity of 76.4%, 77.3% and 79.0% for add-on strategies based on DZN, DFM and CFM, respectively, compared to
76.4% for Xpert done independently. From replacement to add-on strategy, the number of Xpert cartridges needed was
reduced by approximately 10%.
Conclusions:
Among HIV-infected TB suspects, doing smear microscopy prior to Xpert assay in add-on fashion only
identifies a few additional TB cases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background:
Low income, high-tuberculosis burden, countries are considering selective deployment of Xpert MTB/RIF assay
(Xpert) due to high cost per test. We compared the diagnostic gain of the Xpert add-on strategy with Xpert replacement
strategy for pulmonary tuberculosis diagnosis among HIV-infected adults to inform its implementation.
Methods:
The first diagnostic sputum sample of 424 HIV-infected adults (67% with CD4 counts
#
200/mm
3
) suspected for
tuberculosis was tested by direct Ziehl-Neelsen (DZN) and direct fluorescent microscopy (DFM); concentrated fluorescent
microscopy (CFM); Lowenstein-Jensen (LJ) and Mycobacterial Growth Indicator Tube (MGIT) culture; and Xpert. Overall
diagnostic yield and sensitivity were calculated using MGIT as reference comparator. The sensitivity of Xpert in an add-on
strategy was calculated as the number of smear negative but Xpert positive participants among MGIT positive participants.
Results:
A total of 123 (29.0%) participants were MGIT culture positive for
Mycobacterium tuberculosis
. The sensitivity (95%
confidence interval) was 31.7% (23.6–40.7%) for DZN, 35.0% (26.5–44.0%) for DFM, 43.9% (34.9–53.1%) for CFM, 76.4%
(67.9–83.6) for Xpert and 81.3% (73.2–87.7%) for LJ culture. Add-on strategy Xpert showed an incremental sensitivity of
44.7% (35.7–53.9%) when added to DZN, 42.3% (33.4–51.5%) to DFM and 35.0% (26.5–44.0%) to CFM. This translated to an
overall sensitivity of 76.4%, 77.3% and 79.0% for add-on strategies based on DZN, DFM and CFM, respectively, compared to
76.4% for Xpert done independently. From replacement to add-on strategy, the number of Xpert cartridges needed was
reduced by approximately 10%.
Conclusions:
Among HIV-infected TB suspects, doing smear microscopy prior to Xpert assay in add-on fashion only
identifies a few additional TB cases. |
Nathan C. Bahr Henry W. Nabeta, Joshua Rhein Accuracy of Noninvasive Intraocular Pressure or Optic Nerve Sheath Diameter Measurements for Predicting Elevated Intracranial Pressure in Cryptococcal Meningitis Journal Article In: Open Forum Infectious Diseases, vol. 1, no. 3, pp. ofu093, 2014. @article{Nabeta2014,
title = {Accuracy of Noninvasive Intraocular Pressure or Optic Nerve Sheath Diameter Measurements for Predicting Elevated Intracranial Pressure in Cryptococcal Meningitis},
author = {Henry W. Nabeta, Nathan C. Bahr, Joshua Rhein, Nicholas Fossland, Agnes N. Kiragga, David B. Meya, Stephen J. Dunlop, David R. Boulware },
doi = {https://doi.org/10.1093/ofid/ofu093},
year = {2014},
date = {2014-10-11},
journal = {Open Forum Infectious Diseases},
volume = {1},
number = {3},
pages = {ofu093},
abstract = {Background.
Cryptococcal meningitis is associated with increased intracranial pressure (ICP). Therapeutic lum-
bar puncture (LP) is recommended when the initial ICP is >250 mm H 2O, yet the availability of manometers in
Africa is limited and not always used where available. We assessed whether intraocular pressure could be a nonin-
vasive surrogate predictor to determine when additional therapeutic LPs are necessary.
Methods. Ninety-eight human immunodeficiency virus-infected Ugandans with suspected meningitis (81%
Cryptococcus) had intraocular pressure measured using a handheld tonometer (n = 78) or optic nerve sheath diam-
eter (ONSD) measured by ultrasound (n = 81). We determined the diagnostic performance of these methods for
predicting ICP vs a standard manometer.
Results.
The median ICP was 225 mm H2O (interquartile range [IQR], 135–405 mm H2O). The median intraoc-
ular pressure was 28 mm Hg (IQR, 22–37 mm Hg), and median ultrasound ONSD was 5.4 mm (IQR, 4.95–6.1 mm).
ICP moderately correlated with intraocular pressure (ρ = 0.45, P < .001) and with ultrasound ONSD (ρ = 0.44,
P < .001). There were not discrete threshold cutoff values for either tonometry or ultrasound ONSD that provided a
suitable cutoff diagnostic value to predict elevated ICP (>200 mm H2O). However, risk of elevated ICP >200 mm H2O
was increased with an average intraocular pressure >28 mm Hg (relative risk [RR] = 3.03; 95% confidence interval [CI],
1.55–5.92; P < .001) or an average of ONSD >5 mm (RR = 2.39; 95% CI, 1.42–4.03; P = .003). As either intraocular
pressure or ONSD increased, probability of elevated ICP increased (ie, positive predictive value increased).
Conclusions.
Noninvasive intraocular pressure measurements by tonometry or ultrasound correlate with cerebro-
spinal fluid opening pressure, but both are a suboptimal replacement for actual ICP measurement with a manometer.
Keywords.
cryptococcal meningitis; diagnostic techniques and procedures; point-of-care systems; HIV; intracra-
nial hypertension.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background.
Cryptococcal meningitis is associated with increased intracranial pressure (ICP). Therapeutic lum-
bar puncture (LP) is recommended when the initial ICP is >250 mm H 2O, yet the availability of manometers in
Africa is limited and not always used where available. We assessed whether intraocular pressure could be a nonin-
vasive surrogate predictor to determine when additional therapeutic LPs are necessary.
Methods. Ninety-eight human immunodeficiency virus-infected Ugandans with suspected meningitis (81%
Cryptococcus) had intraocular pressure measured using a handheld tonometer (n = 78) or optic nerve sheath diam-
eter (ONSD) measured by ultrasound (n = 81). We determined the diagnostic performance of these methods for
predicting ICP vs a standard manometer.
Results.
The median ICP was 225 mm H2O (interquartile range [IQR], 135–405 mm H2O). The median intraoc-
ular pressure was 28 mm Hg (IQR, 22–37 mm Hg), and median ultrasound ONSD was 5.4 mm (IQR, 4.95–6.1 mm).
ICP moderately correlated with intraocular pressure (ρ = 0.45, P < .001) and with ultrasound ONSD (ρ = 0.44,
P < .001). There were not discrete threshold cutoff values for either tonometry or ultrasound ONSD that provided a
suitable cutoff diagnostic value to predict elevated ICP (>200 mm H2O). However, risk of elevated ICP >200 mm H2O
was increased with an average intraocular pressure >28 mm Hg (relative risk [RR] = 3.03; 95% confidence interval [CI],
1.55–5.92; P < .001) or an average of ONSD >5 mm (RR = 2.39; 95% CI, 1.42–4.03; P = .003). As either intraocular
pressure or ONSD increased, probability of elevated ICP increased (ie, positive predictive value increased).
Conclusions.
Noninvasive intraocular pressure measurements by tonometry or ultrasound correlate with cerebro-
spinal fluid opening pressure, but both are a suboptimal replacement for actual ICP measurement with a manometer.
Keywords.
cryptococcal meningitis; diagnostic techniques and procedures; point-of-care systems; HIV; intracra-
nial hypertension. |
Hoglund, Richard M.; Byakika‐Kibwika, Pauline; Lamorde, Mohammed; Merry, Concepta; Ashton, Michael; Hanpithakpong, Warunee; Day, Nicholas P. J.; White, Nicholas J.; Äbelö, Angela; Tarning, Joel Artemether‐lumefantrine co‐administration with antiretrovirals: population pharmacokinetics and dosing implications Journal Article In: British journal of clinical phamacology, vol. 79, no. 4, pp. 636-49, 2014. @article{Hoglund2014,
title = {Artemether‐lumefantrine co‐administration with antiretrovirals: population pharmacokinetics and dosing implications},
author = {Richard M. Hoglund and Pauline Byakika‐Kibwika and Mohammed Lamorde and Concepta Merry and Michael Ashton and Warunee Hanpithakpong and Nicholas P. J. Day and Nicholas J. White and Angela Äbelö and Joel Tarning},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Artemether-lumefantrine-3.pdf},
doi = {10.1111/bcp.12529.},
year = {2014},
date = {2014-10-08},
journal = {British journal of clinical phamacology},
volume = {79},
number = {4},
pages = {636-49},
abstract = {AIM:
Drug-drug interactions between antimalarial and antiretroviral drugs may influence antimalarial treatment outcomes. The aim of this study was to investigate the potential drug-drug interactions between the antimalarial drugs, lumefantrine, artemether and their respective metabolites desbutyl-lumefantrine and dihydroartemisinin, and the HIV drugs efavirenz, nevirapine and lopinavir/ritonavir.
METHOD:
Data from two clinical studies, investigating the influence of the HIV drugs efavirenz, nevirapine and lopinavir/ritonavir on the pharmacokinetics of the antimalarial drugs lumefantrine, artemether and their respective metabolites, in HIV infected patients were pooled and analyzed using a non-linear mixed effects modelling approach.
RESULTS:
Efavirenz and nevirapine significantly decreased the terminal exposure to lumefantrine (decrease of 69.9% and 25.2%, respectively) while lopinavir/ritonavir substantially increased the exposure (increase of 439%). All antiretroviral drugs decreased the total exposure to dihydroartemisinin (decrease of 71.7%, 41.3% and 59.7% for efavirenz, nevirapine and ritonavir/lopinavir, respectively). Simulations suggest that a substantially increased artemether-lumefantrine dose is required to achieve equivalent exposures when co-administered with efavirenz (250% increase) and nevirapine (75% increase). When co-administered with lopinavir/ritonavir it is unclear if the increased lumefantrine exposure compensates adequately for the reduced dihydroartemisinin exposure and thus whether dose adjustment is required.
CONCLUSION:
There are substantial drug interactions between artemether-lumefantrine and efavirenz, nevirapine and ritonavir/lopinavir. Given the readily saturable absorption of lumefantrine, the dose adjustments predicted to be necessary will need to be evaluated prospectively in malaria-HIV co-infected patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
AIM:
Drug-drug interactions between antimalarial and antiretroviral drugs may influence antimalarial treatment outcomes. The aim of this study was to investigate the potential drug-drug interactions between the antimalarial drugs, lumefantrine, artemether and their respective metabolites desbutyl-lumefantrine and dihydroartemisinin, and the HIV drugs efavirenz, nevirapine and lopinavir/ritonavir.
METHOD:
Data from two clinical studies, investigating the influence of the HIV drugs efavirenz, nevirapine and lopinavir/ritonavir on the pharmacokinetics of the antimalarial drugs lumefantrine, artemether and their respective metabolites, in HIV infected patients were pooled and analyzed using a non-linear mixed effects modelling approach.
RESULTS:
Efavirenz and nevirapine significantly decreased the terminal exposure to lumefantrine (decrease of 69.9% and 25.2%, respectively) while lopinavir/ritonavir substantially increased the exposure (increase of 439%). All antiretroviral drugs decreased the total exposure to dihydroartemisinin (decrease of 71.7%, 41.3% and 59.7% for efavirenz, nevirapine and ritonavir/lopinavir, respectively). Simulations suggest that a substantially increased artemether-lumefantrine dose is required to achieve equivalent exposures when co-administered with efavirenz (250% increase) and nevirapine (75% increase). When co-administered with lopinavir/ritonavir it is unclear if the increased lumefantrine exposure compensates adequately for the reduced dihydroartemisinin exposure and thus whether dose adjustment is required.
CONCLUSION:
There are substantial drug interactions between artemether-lumefantrine and efavirenz, nevirapine and ritonavir/lopinavir. Given the readily saturable absorption of lumefantrine, the dose adjustments predicted to be necessary will need to be evaluated prospectively in malaria-HIV co-infected patients. |
Mbonye, Martin Kayitale; and Sarah M Burnett,; Colebunders, Robert; Naikoba, Sarah; Van, Jean-Pierre; Geertruyden,; Weaver, Marcia R; Ronald, Allan Disease diagnosis in primary care in Uganda Journal Article In: BMC Family Practice, vol. 13, no. 1, 2014. @article{Mbonye2014,
title = {Disease diagnosis in primary care in Uganda},
author = {Martin Kayitale Mbonye and and Sarah M Burnett and Robert Colebunders and Sarah Naikoba and Jean-Pierre Van and Geertruyden and Marcia R Weaver and Allan Ronald
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Disease-diagnosis-in-primary-care-in-Uganda.pdf},
doi = {10.1186/1471-2296-15-165},
year = {2014},
date = {2014-10-08},
journal = {BMC Family Practice},
volume = {13},
number = {1},
abstract = {Background:
The overall burden of disease (BOD) especially for infectious diseases is higher in Sub-Saharan Africa
than other regions of the world. Existing data collected through the Health Management Information System (HMIS)
may not be optimal to measure BOD. The Infectious Diseases Capacity Building Evaluation (IDCAP) cooperated with
the Ugandan Ministry of Health to improve the quality of HMIS data. We describe diagnoses with associated clinical
assessments and laboratory investigations of outpatients attending primary care in Uganda.
Methods:
IDCAP supported HMIS data collection at 36 health center IVs in Uganda for five months (November
2009 to March 2010) prior to implementation of the IDCAP interventions. Descriptive analyses were performed on a
cross-sectional dataset of 209,734 outpatient visits during this period.
Results:
Over 500 illnesses were diagnosed. Infectious diseases accounted for 76.3% of these and over 30% of visits
resulted in multiple diagnoses. Malaria (48.3%), cough/cold (19.4%), and intestinal worms (6.6%) were the most
frequently diagnosed illnesses. Body weight was recorded for 36.8% of patients and less than 10% had other clinical
assessments recorded. Malaria smears (64.2%) and HIV tests (12.2%) accounted for the majority of 84,638 laboratory
tests ordered. Fewer than 30% of patients for whom a laboratory investigation was available to confirm the clinical
impression had the specific test performed.
Conclusions:
We observed a broad range of diagnoses, a high percentage of multiple diagnoses including true
co-morbidities, and underutilization of laboratory support. This emphasizes the complexity of illnesses to be
addressed by primary healthcare workers. An improved HMIS collecting timely, quality data is needed. This would
adequately describe the burden of disease and processes of care at primary care level, enable appropriate national
guidelines, programs and policies and improve accountability for the quality of care.
Keywords:
Primary care, Disease diagnosis, Uganda},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background:
The overall burden of disease (BOD) especially for infectious diseases is higher in Sub-Saharan Africa
than other regions of the world. Existing data collected through the Health Management Information System (HMIS)
may not be optimal to measure BOD. The Infectious Diseases Capacity Building Evaluation (IDCAP) cooperated with
the Ugandan Ministry of Health to improve the quality of HMIS data. We describe diagnoses with associated clinical
assessments and laboratory investigations of outpatients attending primary care in Uganda.
Methods:
IDCAP supported HMIS data collection at 36 health center IVs in Uganda for five months (November
2009 to March 2010) prior to implementation of the IDCAP interventions. Descriptive analyses were performed on a
cross-sectional dataset of 209,734 outpatient visits during this period.
Results:
Over 500 illnesses were diagnosed. Infectious diseases accounted for 76.3% of these and over 30% of visits
resulted in multiple diagnoses. Malaria (48.3%), cough/cold (19.4%), and intestinal worms (6.6%) were the most
frequently diagnosed illnesses. Body weight was recorded for 36.8% of patients and less than 10% had other clinical
assessments recorded. Malaria smears (64.2%) and HIV tests (12.2%) accounted for the majority of 84,638 laboratory
tests ordered. Fewer than 30% of patients for whom a laboratory investigation was available to confirm the clinical
impression had the specific test performed.
Conclusions:
We observed a broad range of diagnoses, a high percentage of multiple diagnoses including true
co-morbidities, and underutilization of laboratory support. This emphasizes the complexity of illnesses to be
addressed by primary healthcare workers. An improved HMIS collecting timely, quality data is needed. This would
adequately describe the burden of disease and processes of care at primary care level, enable appropriate national
guidelines, programs and policies and improve accountability for the quality of care.
Keywords:
Primary care, Disease diagnosis, Uganda |
Cox, Janneke A.; Lukande, Robert L.; Kalungi, Sam; Marck, Eric Van; k Koen Van de Vijver,; Andrew Kambugu,; Nelson, Ann M.; Manabe, Yukari C.; Colebunders, Robert Needle Autopsy to Establish the Cause of Death in HIV-Infected Hospitalized Adults in Uganda: A Comparison to Complete Autopsy Journal Article In: Journal of Acquired Imune Dificiency syndrome, vol. 67, no. 2, pp. 169-79, 2014. @article{Cox2014,
title = {Needle Autopsy to Establish the Cause of Death in HIV-Infected Hospitalized Adults in Uganda: A Comparison to Complete Autopsy},
author = {Janneke A. Cox and Robert L. Lukande and Sam Kalungi and Eric Van Marck and k Koen Van de Vijver and Andrew Kambugu, and Ann M. Nelson and Yukari C. Manabe and Robert Colebunders},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Needle-Autopsy-to-Establish-the-Cause-of-Death-in-HIV-Infected-Hospitalized-Adults-in-Uganda.pdf},
doi = {10.1097/QAI.0000000000000290},
year = {2014},
date = {2014-10-01},
journal = {Journal of Acquired Imune Dificiency syndrome},
volume = {67},
number = {2},
pages = {169-79},
abstract = {ntroduction: Minimal invasive but accurate methods to establish the cause of death in HIV-infected patients are needed. We studied the agreement in cause of death between blind and ultrasound-guided needle autopsy and complete autopsy in HIV-infected patients in Uganda.
Methods: We subsequently performed a blind and ultrasound-guided needle autopsy followed by a complete autopsy in HIV-infected adults who died during hospitalization. Two teams of pathologists reviewed the tissue from either the needle autopsies or the complete autopsy and formulated the major diagnoses, that is, diseases directly contributing to death. The primary outcome was concordance in major diagnosis between needle and complete autopsies.
Results: We performed 96 blind needle and complete autopsies and 95 ultrasound-guided needle autopsies. Concordance in major diagnosis between blind needle and complete autopsy was 50%. For the main major diagnosis, tuberculosis (TB) concordance was higher (71%; P < 0.01). Blind needle autopsy identified at least 1 major diagnosis in 60% of patients; and in 46%, there was complete concordance for all major diagnoses. The main reason for discordance was sampling error of the lesion. Concordance with the addition of ultrasound guidance was 52% for all major diagnoses and 79% for TB. Major diagnoses were mainly identified in tissue cores from the liver (76%) and the spleen (82%).
Discussion: Blind needle autopsy identified half of the major diagnosis. The addition of ultrasound guidance did not significantly improve the performance of needle autopsy. Needle autopsy is a valuable method to confirm causes of death in HIV-infected patients, especially for highly prevalent diseases like TB.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
ntroduction: Minimal invasive but accurate methods to establish the cause of death in HIV-infected patients are needed. We studied the agreement in cause of death between blind and ultrasound-guided needle autopsy and complete autopsy in HIV-infected patients in Uganda.
Methods: We subsequently performed a blind and ultrasound-guided needle autopsy followed by a complete autopsy in HIV-infected adults who died during hospitalization. Two teams of pathologists reviewed the tissue from either the needle autopsies or the complete autopsy and formulated the major diagnoses, that is, diseases directly contributing to death. The primary outcome was concordance in major diagnosis between needle and complete autopsies.
Results: We performed 96 blind needle and complete autopsies and 95 ultrasound-guided needle autopsies. Concordance in major diagnosis between blind needle and complete autopsy was 50%. For the main major diagnosis, tuberculosis (TB) concordance was higher (71%; P < 0.01). Blind needle autopsy identified at least 1 major diagnosis in 60% of patients; and in 46%, there was complete concordance for all major diagnoses. The main reason for discordance was sampling error of the lesion. Concordance with the addition of ultrasound guidance was 52% for all major diagnoses and 79% for TB. Major diagnoses were mainly identified in tissue cores from the liver (76%) and the spleen (82%).
Discussion: Blind needle autopsy identified half of the major diagnosis. The addition of ultrasound guidance did not significantly improve the performance of needle autopsy. Needle autopsy is a valuable method to confirm causes of death in HIV-infected patients, especially for highly prevalent diseases like TB. |
Lamorde, Mohammed; Fillekes, Quirine; Sigaloff, Kim; Kityo, Cissy; Buzibye, Allan; Kayiwa, Joshua; Merry, Concepta; Nakatudde-Katumba, Lillian; Burger, David; de Wit, Tobias F Rinke Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique Journal Article In: BMC Infectious Diseases, vol. 14, no. 1, 2014. @article{Lamorde2014b,
title = {Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique},
author = {Mohammed Lamorde and Quirine Fillekes and Kim Sigaloff and Cissy Kityo and Allan Buzibye and Joshua Kayiwa and Concepta Merry and Lillian Nakatudde-Katumba and David Burger and Tobias F Rinke de Wit},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Therapeutic-drug-monitoring-of-nevirapine-in....pdf},
doi = {10.1186/1471-2334-14-473},
year = {2014},
date = {2014-10-01},
journal = {BMC Infectious Diseases},
volume = {14},
number = {1},
abstract = {Background:
In resource limited settings access to laboratory monitoring of HIV treatment is limited and
therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in
saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma and saliva using
high performance liquid chromatography (HPLC) methods; and to correlate nevirapine plasma concentrations to
HIV treatment outcomes in Ugandan patients.
Methods:
Paired plasma and stimulated saliva samples were obtained from Ugandan, HIV-infected adults on
nevirapine-based ART. Nevirapine concentrations were measured using a validated HPLC method and a novel TLC
method. Plasma nevirapine concentrations <3.0 mg/L using HPLC were considered subtherapeutic. Negative/positive
predictive values of different thresholds for subtherapeutic nevirapine concentrations in saliva were determined.
Virologic testing and, if applicable,
HIV drug resistance testing was performed.
Results:
Median (interquartile range, IQR) age of 297 patients was 39.1 (32.8-45.2) years. Three hundred saliva
and 287 plasma samples were available for analysis. Attempts failed to determine nevirapine saliva concentrations by
TLC. Using HPLC, median (IQR) nevirapine concentrations in saliva and plasma were 3.40 (2.59-4.47) mg/L and 6.17
(4.79-7.96) mg/L, respectively. The mean (coefficient of variation,%) nevirapine saliva/plasma ratio was 0.58 (62%). A
cut-off value of 1.60 mg/L nevirapine in saliv
a was associated with a negative/positive predictive value of 0.99/
0.72 and a sensitivity/specificity of 87%/98% for predicting sub
therapeutic nevirapine plasma concentrations, respectively.
Only 5% (15/287) of patients had subtherapeutic nevirapine plasma concentrations, of which 3 patients had viral
load results > 400 copies/mL. P
atients with nevirapine con
centrations in plasma <3.0 mg/L had an Odds Ratio of
3.29 (95% CI: 1.00
–
10.74) for virological failure (viral load >400 copies/mL).
Conclusions:
The low-cost TLC technique for monitoring
nevirapine in saliva was uns
uccessful but monitoring
nevirapine saliva and plasma concentrations using HPLC was shown to be feasible in the research/specialist context
in Uganda. Further optimization and validation is required for the low-cost TLC technique.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background:
In resource limited settings access to laboratory monitoring of HIV treatment is limited and
therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in
saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma and saliva using
high performance liquid chromatography (HPLC) methods; and to correlate nevirapine plasma concentrations to
HIV treatment outcomes in Ugandan patients.
Methods:
Paired plasma and stimulated saliva samples were obtained from Ugandan, HIV-infected adults on
nevirapine-based ART. Nevirapine concentrations were measured using a validated HPLC method and a novel TLC
method. Plasma nevirapine concentrations <3.0 mg/L using HPLC were considered subtherapeutic. Negative/positive
predictive values of different thresholds for subtherapeutic nevirapine concentrations in saliva were determined.
Virologic testing and, if applicable,
HIV drug resistance testing was performed.
Results:
Median (interquartile range, IQR) age of 297 patients was 39.1 (32.8-45.2) years. Three hundred saliva
and 287 plasma samples were available for analysis. Attempts failed to determine nevirapine saliva concentrations by
TLC. Using HPLC, median (IQR) nevirapine concentrations in saliva and plasma were 3.40 (2.59-4.47) mg/L and 6.17
(4.79-7.96) mg/L, respectively. The mean (coefficient of variation,%) nevirapine saliva/plasma ratio was 0.58 (62%). A
cut-off value of 1.60 mg/L nevirapine in saliv
a was associated with a negative/positive predictive value of 0.99/
0.72 and a sensitivity/specificity of 87%/98% for predicting sub
therapeutic nevirapine plasma concentrations, respectively.
Only 5% (15/287) of patients had subtherapeutic nevirapine plasma concentrations, of which 3 patients had viral
load results > 400 copies/mL. P
atients with nevirapine con
centrations in plasma <3.0 mg/L had an Odds Ratio of
3.29 (95% CI: 1.00
–
10.74) for virological failure (viral load >400 copies/mL).
Conclusions:
The low-cost TLC technique for monitoring
nevirapine in saliva was uns
uccessful but monitoring
nevirapine saliva and plasma concentrations using HPLC was shown to be feasible in the research/specialist context
in Uganda. Further optimization and validation is required for the low-cost TLC technique. |
Parkes-Ratanshi, Rosalind; Ssekabira, Umaru; Crozier, Ian Ebola in West Africa: be aware and prepare Journal Article In: Intesive Care Medicine, vol. 40, no. 11, pp. 1742-45, 2014. @article{Parkes-Ratanshi2014,
title = {Ebola in West Africa: be aware and prepare},
author = { Rosalind Parkes-Ratanshi and Umaru Ssekabira and Ian Crozier},
url = {https://link.springer.com/article/10.1007%2Fs00134-014-3497-z},
doi = {10.1007/s00134-014-3497-z},
year = {2014},
date = {2014-09-25},
journal = {Intesive Care Medicine},
volume = {40},
number = {11},
pages = {1742-45},
abstract = {Ebola virus along with Marburg virus forms the family Filoviridae, which causes severe viral haemorrhagic fever in humans and non-human primates. Ebola virus causes Ebola virus disease (EVD), previously known as Ebola haemorrhagic fever},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ebola virus along with Marburg virus forms the family Filoviridae, which causes severe viral haemorrhagic fever in humans and non-human primates. Ebola virus causes Ebola virus disease (EVD), previously known as Ebola haemorrhagic fever |
Boulware, Antiretroviral Therapy after Cryptococcal Meningitis Journal Article In: The New England Journal of Medicine, vol. 371, no. 12, pp. 1165-7, 2014. @article{Boulware2014,
title = {Antiretroviral Therapy after Cryptococcal Meningitis},
author = {Boulware},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Antiretroviral-Therapy-after-Cryptococcal-Meningitis.pdf},
doi = {10.1056/NEJMc1409052},
year = {2014},
date = {2014-09-18},
journal = {The New England Journal of Medicine},
volume = {371},
number = {12},
pages = {1165-7},
abstract = {Boulware and colleagues found that deferring combination ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with improved survival. In the subgroup analysis, mortality was lower with deferred ART among patients with a pathogen burden of more than 100,000 colony-forming units per milliliter at diagnosis (hazard ratio, 2.44) and those with a cerebrospinal fluid (CSF) white-cell count of less than 5 cells per cubic millimeter at randomization (hazard ratio, 3.87)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Boulware and colleagues found that deferring combination ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with improved survival. In the subgroup analysis, mortality was lower with deferred ART among patients with a pathogen burden of more than 100,000 colony-forming units per milliliter at diagnosis (hazard ratio, 2.44) and those with a cerebrospinal fluid (CSF) white-cell count of less than 5 cells per cubic millimeter at randomization (hazard ratio, 3.87) |
Elmar Saathoff Rachel Kyeyune, Amara E Ezeamama Prevalence and correlates of cytopenias in HIV-infected adults initiating highly active antiretroviral therapy in Uganda Journal Article In: BMC Infectious Diseases , vol. 14, no. 496, 2014. @article{Kyeyune2014,
title = {Prevalence and correlates of cytopenias in HIV-infected adults initiating highly active antiretroviral therapy in Uganda},
author = {Rachel Kyeyune, Elmar Saathoff, Amara E Ezeamama, Thomas Löscher, Wafaie Fawzi & David Guwatudde },
doi = {https://doi.org/10.1186/1471-2334-14-496},
year = {2014},
date = {2014-09-10},
journal = {BMC Infectious Diseases },
volume = {14},
number = {496},
abstract = {Background
Cytopenias are the most common HIV-associated hematological abnormality. Cytopenias have been associated with several factors including sex, race/ethnicity, geographical location and comorbidities such as tuberculosis, hepatitis B infection, fever and oral candidiasis. Cytopenias become more prevalent as HIV progresses and are often fatal. Data from resource-limited settings about the prevalence and correlates of cytopenia are limited. Therefore we conducted this cross-sectional study to assess the prevalence and correlates of cytopenia among adult AIDS patients at initiation of HAART in Uganda.
Methods
400 HIV-infected subjects who were HAART-naïve or on HAART for ≤ 6 months were enrolled into the Multivitamins, HAART and HIV/AIDS Trial. Anemia was defined according to WHO guidelines as any hemoglobin concentration < 12 g/dl for non-pregnant females and < 13 g/dl for males. Leucopenia and thrombocytopenia were defined using study site laboratory reference ranges for lack of generally accepted definitions for these 2 cell lines as leucopenia if white blood cell count < 2.75 × 109 cells/litre and thrombocytopenia if platelets < 125 × 109 cells/litre for females and < 156 × 109 cells/litre for males. Univariate and bivariate analyses were done to describe the patient population and log-binomial regression was used to quantify the correlates of cytopenia.
Results
Sixty five percent of the 400 subjects had at least one form of cytopenia. Anemia occurred in 47.8%, leucopenia in 24.3%, thrombocytopenia in 8.3%, bicytopenia in 21.9% and only 2 had a pancytopenia. Cytopenia was more prevalent in females (prevalence ratio [PR]:1.33, 95% confidence interval [CI]:1.12-1.59); CD4 count category 50 to <200 (PR: 0.75, 95% CI: 0.64 -0.88) and CD4 count category 200 to <350 (PR: 0.74, 95% CI: 0.59 - 0.92) compared to CD4 count category <50; normal BMI (PR: 0.82, 95% CI:0.68-1.00) and overweight BMI (PR: 0.64, 95% CI:0.50- 0.82) compared to underweight BMI and those with a history or presence of oral candidiasis.
Conclusions
Cytopenias are a frequent complication in HIV-infected adults at initiation of HAART in Uganda. The presence of any cytopenia was associated with female sex, decreasing CD4 count and decreasing body mass index. Prospective studies in resource-limited settings on the trend in HIV-related cytopenias are needed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Cytopenias are the most common HIV-associated hematological abnormality. Cytopenias have been associated with several factors including sex, race/ethnicity, geographical location and comorbidities such as tuberculosis, hepatitis B infection, fever and oral candidiasis. Cytopenias become more prevalent as HIV progresses and are often fatal. Data from resource-limited settings about the prevalence and correlates of cytopenia are limited. Therefore we conducted this cross-sectional study to assess the prevalence and correlates of cytopenia among adult AIDS patients at initiation of HAART in Uganda.
Methods
400 HIV-infected subjects who were HAART-naïve or on HAART for ≤ 6 months were enrolled into the Multivitamins, HAART and HIV/AIDS Trial. Anemia was defined according to WHO guidelines as any hemoglobin concentration < 12 g/dl for non-pregnant females and < 13 g/dl for males. Leucopenia and thrombocytopenia were defined using study site laboratory reference ranges for lack of generally accepted definitions for these 2 cell lines as leucopenia if white blood cell count < 2.75 × 109 cells/litre and thrombocytopenia if platelets < 125 × 109 cells/litre for females and < 156 × 109 cells/litre for males. Univariate and bivariate analyses were done to describe the patient population and log-binomial regression was used to quantify the correlates of cytopenia.
Results
Sixty five percent of the 400 subjects had at least one form of cytopenia. Anemia occurred in 47.8%, leucopenia in 24.3%, thrombocytopenia in 8.3%, bicytopenia in 21.9% and only 2 had a pancytopenia. Cytopenia was more prevalent in females (prevalence ratio [PR]:1.33, 95% confidence interval [CI]:1.12-1.59); CD4 count category 50 to <200 (PR: 0.75, 95% CI: 0.64 -0.88) and CD4 count category 200 to <350 (PR: 0.74, 95% CI: 0.59 - 0.92) compared to CD4 count category <50; normal BMI (PR: 0.82, 95% CI:0.68-1.00) and overweight BMI (PR: 0.64, 95% CI:0.50- 0.82) compared to underweight BMI and those with a history or presence of oral candidiasis.
Conclusions
Cytopenias are a frequent complication in HIV-infected adults at initiation of HAART in Uganda. The presence of any cytopenia was associated with female sex, decreasing CD4 count and decreasing body mass index. Prospective studies in resource-limited settings on the trend in HIV-related cytopenias are needed. |
Sanya, Richard E; Kirenga, Bruce J; Worodria, William; Okot-Nwang, Martin Risk factors for asthma exacerbation in patients presenting to an emergency unit of a national referral hospital in Kampala, Uganda. Journal Article In: African Health Sciences, vol. 14, no. 3, pp. 707-15, 2014. @article{Sanya2014,
title = {Risk factors for asthma exacerbation in patients presenting to an emergency unit of a national referral hospital in Kampala, Uganda.},
author = {Richard E Sanya and Bruce J Kirenga and William Worodria and Martin Okot-Nwang},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Risk-factors-for-asthma-exacerbation-in-patients-presenting-to-an-emergency-unit-of-a-national-referral-hospital-in-Kampala-Uganda.pdf},
doi = { doi: 10.4314/ahs.v14i3.29},
year = {2014},
date = {2014-09-01},
journal = {African Health Sciences},
volume = {14},
number = {3},
pages = {707-15},
abstract = {Background
: Asthma exacerbations are caused by a variety of risk factors. Reducing exposure to these risk factors improves
the control of asthma and reduces medication needs. Knowledge of the particular risk factors is essential in formulating
controlling and treatment protocols. This study set out to determine the risk factors for asthma exacerbations in patients
presenting to the emergency unit of Mulago Hospital.
Methods
: An unmatched case-control study involving 43 cases and 43 controls was conducted from November 2011 through
February 2012. Asthma patients with exacerbations presenting to Mulago hospital’s emergency unit were chosen as cases.
The controls were asthma patients recruited from the hospital’s outpatient department who had not had an exacerbation
in the past 7 days. The
study variables were age, sex, level of education, adherence to treatment, exercise, upper respiratory
tract infections, household pets, smoking, strong emotions, exposure to in house wood or charcoal burning, weather, use of
corticosteroids, beta-blockers and non-steroidal anti-inflammatory drugs. Univariate and multivariate statistical analysis was
done using SPSS version 16 to identify independent risk factors for exacerbations.
Results
: Lack of corticosteroid use (OR =22.109; 95% Confidence interval 6.952 to 70.315; p<0.001) and presence of
upper respiratory tract infections (OR 4.516; CI 1.258-16.213; p=0.018) were significantly associated with exacerbations.
Conclusion
: Lack of corticosteroid use and upper respiratory tract infections are associated with exacerbations in asthma
patients presenting to the Emergency unit of Mulago Hospital
Key words:
Asthma, asthma exacerbations, risk factors, corticosteroids},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
: Asthma exacerbations are caused by a variety of risk factors. Reducing exposure to these risk factors improves
the control of asthma and reduces medication needs. Knowledge of the particular risk factors is essential in formulating
controlling and treatment protocols. This study set out to determine the risk factors for asthma exacerbations in patients
presenting to the emergency unit of Mulago Hospital.
Methods
: An unmatched case-control study involving 43 cases and 43 controls was conducted from November 2011 through
February 2012. Asthma patients with exacerbations presenting to Mulago hospital’s emergency unit were chosen as cases.
The controls were asthma patients recruited from the hospital’s outpatient department who had not had an exacerbation
in the past 7 days. The
study variables were age, sex, level of education, adherence to treatment, exercise, upper respiratory
tract infections, household pets, smoking, strong emotions, exposure to in house wood or charcoal burning, weather, use of
corticosteroids, beta-blockers and non-steroidal anti-inflammatory drugs. Univariate and multivariate statistical analysis was
done using SPSS version 16 to identify independent risk factors for exacerbations.
Results
: Lack of corticosteroid use (OR =22.109; 95% Confidence interval 6.952 to 70.315; p<0.001) and presence of
upper respiratory tract infections (OR 4.516; CI 1.258-16.213; p=0.018) were significantly associated with exacerbations.
Conclusion
: Lack of corticosteroid use and upper respiratory tract infections are associated with exacerbations in asthma
patients presenting to the Emergency unit of Mulago Hospital
Key words:
Asthma, asthma exacerbations, risk factors, corticosteroids |
Nakanjako, Damalie; Otiti-Sengeri, Juliet; Ssewanyana, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kirimunda, Samuel; Joloba, Moses; Manabe, Yukari C.; Kambugu, Andrew; Colebunders, Robert; Mayanja-Kizza, Harriet CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda Journal Article In: Immunology Letters, vol. 16, no. 1, pp. 44-9, 2014. @article{Nakanjako2014b,
title = {CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda},
author = {Damalie Nakanjako and Juliet Otiti-Sengeri and Isaac Ssewanyana and Rose Nabatanzi and Lois Bayigga and Samuel Kirimunda and Moses Joloba and Yukari C. Manabe and Andrew Kambugu and Robert Colebunders and Harriet Mayanja-Kizza
},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/CD4-T-cell-activation-and-reduced-regulatory-T-cell-populations-are-associated-with-early-development-of-cataracts-among-HIVinfected-adults-in-Uganda.pdf},
doi = {10.1016/j.imlet.2014.04.011},
year = {2014},
date = {2014-09-01},
journal = {Immunology Letters},
volume = {16},
number = {1},
pages = {44-9},
abstract = {Background—
Cataracts contribute 12% of visual loss among HIV-infected adults in Uganda.
Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for
innovative therapeutic interventions among HIV-infected adults.
Methods—
In a laboratory based case-control study, nested in a clinical/surgical community
outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV
testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear
Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-
negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-
positive- adults- without-cataracts (comparative group). Treg were measured as
CD3+CD4+FoxP3+CD25+
bright
and immune activation as CD3+CD4+CD38+HALDR+ using a
Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four
groups.
Results—
Of 50 adults operated for cataracts, 24 (48%) were female, 25(50%) were HIV-
positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR);
49(44-53) years] than HIV-negative [70 (IQR 59-75) years]; p=0.0005.Treg were lower among
individuals with cataracts irrespective of HIV status; p=0.001; but comparable among younger
HIV-positive and elderly HIV-negative with cataracts; p=0.301. Immune activation levels were
comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-
positive-individuals without cataracts; p=0.012 and HIV-negative-individuals-with-cataracts
expressed higher levels of immune activation that HIV-negative-without-cataracts; p<0.0001.
Conclusion—
CD4 T-cell activation and reduced regulatory T-cell populations were associated
with cataracts among adults aging with HIV. We recommend studies on clinical relevance of
immune modulation in the prevention of early development of cataracts among adults aging with
HIV in Africa},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background—
Cataracts contribute 12% of visual loss among HIV-infected adults in Uganda.
Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for
innovative therapeutic interventions among HIV-infected adults.
Methods—
In a laboratory based case-control study, nested in a clinical/surgical community
outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV
testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear
Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-
negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-
positive- adults- without-cataracts (comparative group). Treg were measured as
CD3+CD4+FoxP3+CD25+
bright
and immune activation as CD3+CD4+CD38+HALDR+ using a
Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four
groups.
Results—
Of 50 adults operated for cataracts, 24 (48%) were female, 25(50%) were HIV-
positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR);
49(44-53) years] than HIV-negative [70 (IQR 59-75) years]; p=0.0005.Treg were lower among
individuals with cataracts irrespective of HIV status; p=0.001; but comparable among younger
HIV-positive and elderly HIV-negative with cataracts; p=0.301. Immune activation levels were
comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-
positive-individuals without cataracts; p=0.012 and HIV-negative-individuals-with-cataracts
expressed higher levels of immune activation that HIV-negative-without-cataracts; p<0.0001.
Conclusion—
CD4 T-cell activation and reduced regulatory T-cell populations were associated
with cataracts among adults aging with HIV. We recommend studies on clinical relevance of
immune modulation in the prevention of early development of cataracts among adults aging with
HIV in Africa |
Katusiime, Christine; Ocama, Ponsiano; Kambugu, Andrew Basis of selection of first and second line highly active antiretroviral therapy for HIV/ AIDS on genetic barrier to resistance: a literature review. Journal Article In: African Health Sciences, vol. 14, no. 3, pp. 679-81, 2014. @article{Katusiime2014,
title = {Basis of selection of first and second line highly active antiretroviral therapy for HIV/ AIDS on genetic barrier to resistance: a literature review.},
author = {Christine Katusiime and Ponsiano Ocama and Andrew Kambugu},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Basis-of-selection-of-first-and-second-line-highly-active-antiretroviral-therapy-for-HIV...pdf},
doi = {10.4314/ahs.v14i3.25},
year = {2014},
date = {2014-09-01},
journal = {African Health Sciences},
volume = {14},
number = {3},
pages = {679-81},
abstract = {The effectiveness of combination antiretroviral therapy (cART) continues to improve as treatment choices expand
with the development of new antiretroviral agents and regimens. However, the successful long-term treatment
of HIV/AIDS is under threat from the emergence of drug-resistant strains to multiple agents and entire drug
classes. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The effectiveness of combination antiretroviral therapy (cART) continues to improve as treatment choices expand
with the development of new antiretroviral agents and regimens. However, the successful long-term treatment
of HIV/AIDS is under threat from the emergence of drug-resistant strains to multiple agents and entire drug
classes. |
Weaver, Marcia R.; Burnett, Sarah M.; Crozier, Ian; Kinoti, Stephen N.; Kirunda, Ibrahim; Mbonye, Martin K.; Naikoba, Sarah; Ronald, Allan; Rubashembusya, Timothy; Zawedde, Stella; Willis, Kelly S. Improving Facility Performance in Infectious Disease Care in Uganda: A Mixed Design Study with Pre/Post and Cluster Randomized Trial Components Journal Article In: PloS One, vol. 9, no. 8, 2014. @article{Weaver2014,
title = {Improving Facility Performance in Infectious Disease Care in Uganda: A Mixed Design Study with Pre/Post and Cluster Randomized Trial Components},
author = {Marcia R. Weaver and Sarah M. Burnett and Ian Crozier and Stephen N. Kinoti and Ibrahim Kirunda and Martin K. Mbonye and Sarah Naikoba and Allan Ronald and Timothy Rubashembusya and Stella Zawedde and Kelly S. Willis},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Improving-Facility-Performance-in-Infectious-Disease.pdf},
doi = {10.1371/journal.pone.0103017},
year = {2014},
date = {2014-08-18},
journal = {PloS One},
volume = {9},
number = {8},
abstract = {
BACKGROUND:
The effects of two interventions, Integrated Management of Infectious Disease (IMID) training program and On-Site Support (OSS), were tested on 23 facility performance indicators for emergency triage assessment and treatment (ETAT), malaria, pneumonia, tuberculosis, and HIV.
METHODS:
The trial was implemented in 36 primary care facilities in Uganda. From April 2010, two mid-level practitioners per facility participated in IMID training. Eighteen of 36 facilities were randomly assigned to Arm A, and received OSS in 2010 (nine monthly two-day sessions); 18 facilities assigned to Arm B did not receive OSS in 2010. Data were collected from Nov 2009 to Dec 2010 using a revised Ministry of Health outpatient medical form and nine registers. We analyzed the effect of IMID training alone by measuring changes before and during IMID training in Arm B, the combined effect of IMID training and OSS by measuring changes in Arm A, and the incremental effect of OSS by comparing changes across Arms A and B.
RESULTS:
IMID training was associated with statistically significant improvement in three indicators: outpatients triaged (adjusted relative risks (aRR) = 1.29, 99%CI = 1.01,1.64), emergency and priority patients admitted, detained, or referred (aRR = 1.59, 99%CI = 1.04,2.44), and pneumonia suspects assessed (aRR = 2.31, 99%CI = 1.50,3.55). IMID training and OSS combined was associated with improvements in six indicators: three ETAT indicators (outpatients triaged (aRR = 2.03, 99%CI = 1.13,3.64), emergency and priority patients admitted, detained or referred (aRR = 3.03, 99%CI = 1.40,6.56), and emergency patients receiving at least one appropriate treatment (aRR = 1.77, 99%CI = 1.10,2.84)); two malaria indicators (malaria cases receiving appropriate antimalarial (aRR = 1.50, 99%CI = 1.04,2.17), and patients with negative malaria test results prescribed antimalarial (aRR = 0.67, 99%CI = 0.46,0.97)); and enrollment in HIV care (aRR = 1.58, 99%CI = 1.32,1.89). OSS was associated with incremental improvement in emergency patients receiving at least one appropriate treatment (adjusted ratio of RR = 1.84,99%CI = 1.09,3.12).
CONCLUSION:
The trial showed that the OSS intervention significantly improved performance in one of 23 facility indicators},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND:
The effects of two interventions, Integrated Management of Infectious Disease (IMID) training program and On-Site Support (OSS), were tested on 23 facility performance indicators for emergency triage assessment and treatment (ETAT), malaria, pneumonia, tuberculosis, and HIV.
METHODS:
The trial was implemented in 36 primary care facilities in Uganda. From April 2010, two mid-level practitioners per facility participated in IMID training. Eighteen of 36 facilities were randomly assigned to Arm A, and received OSS in 2010 (nine monthly two-day sessions); 18 facilities assigned to Arm B did not receive OSS in 2010. Data were collected from Nov 2009 to Dec 2010 using a revised Ministry of Health outpatient medical form and nine registers. We analyzed the effect of IMID training alone by measuring changes before and during IMID training in Arm B, the combined effect of IMID training and OSS by measuring changes in Arm A, and the incremental effect of OSS by comparing changes across Arms A and B.
RESULTS:
IMID training was associated with statistically significant improvement in three indicators: outpatients triaged (adjusted relative risks (aRR) = 1.29, 99%CI = 1.01,1.64), emergency and priority patients admitted, detained, or referred (aRR = 1.59, 99%CI = 1.04,2.44), and pneumonia suspects assessed (aRR = 2.31, 99%CI = 1.50,3.55). IMID training and OSS combined was associated with improvements in six indicators: three ETAT indicators (outpatients triaged (aRR = 2.03, 99%CI = 1.13,3.64), emergency and priority patients admitted, detained or referred (aRR = 3.03, 99%CI = 1.40,6.56), and emergency patients receiving at least one appropriate treatment (aRR = 1.77, 99%CI = 1.10,2.84)); two malaria indicators (malaria cases receiving appropriate antimalarial (aRR = 1.50, 99%CI = 1.04,2.17), and patients with negative malaria test results prescribed antimalarial (aRR = 0.67, 99%CI = 0.46,0.97)); and enrollment in HIV care (aRR = 1.58, 99%CI = 1.32,1.89). OSS was associated with incremental improvement in emergency patients receiving at least one appropriate treatment (adjusted ratio of RR = 1.84,99%CI = 1.09,3.12).
CONCLUSION:
The trial showed that the OSS intervention significantly improved performance in one of 23 facility indicators
|
Velamakanni, Sruti S.; Bahr, Nathan C.; Musubire, Abdu K.; andJoshua Rhein, David R. Boulware; Nabeta, Henry W. Central nervous system cryptococcoma in a Ugandan patient with Human Immunode fi ciency Virus Journal Article In: Medical Mycology Case Reports, vol. 6, pp. 10-13, 2014. @article{Velamakanni2014,
title = {Central nervous system cryptococcoma in a Ugandan patient with Human Immunode fi ciency Virus},
author = {Sruti S. Velamakanni and Nathan C. Bahr and Abdu K. Musubire and David R. Boulware andJoshua Rhein and Henry W. Nabeta},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Central-nervous-system-cryptococcoma-in-a-Ugandan-patient.pdf},
doi = { 10.1016/j.mmcr.2014.08.003},
year = {2014},
date = {2014-08-11},
journal = {Medical Mycology Case Reports},
volume = {6},
pages = {10-13},
abstract = {Central nervous system cryptococcoma in a Ugandan patient
with Human Immunode
fi
ciency Virus
Sruti S. Velamakanni
a
,
b
,
n
, Nathan C. Bahr
a
,
b
,
c
, Abdu K. Musubire
a
, David R. Boulware
b
,
c
,
Joshua Rhein
a
,
b
,
c
, Henry W. Nabeta
a
a
Infectious Disease Institute, Makerere University, Kampala, Uganda
b
Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
c
Center for Infectious Diseases
&
Microbiology Translational Research, University of Minnesota, Minneapolis, MN, USA
article info
Article history:
Received 16 June 2014
Received in revised form
3 August 2014
Accepted 3 August 2014
Keywords:
Cryptococcus meningitis
Cryptococcoma
Immunosuppressed Host
Central nervous system
Human Immunode
fi
ciency Virus
abstract
Mortality due to AIDS-related Cryptococcal meningitis (CM) is often
4
50% in low-middle income
countries. Dissemination of CM can result in intracranial mass lesions known as cryptococcoma. Patients
who develop cryptococcomas often have worse outcomes when compared to patients with cryptococ-
cosis without cryptococcoma. We describe a cryptococcoma in the central nervous system (CNS) in a
Ugandan patient with AIDS, and review the diagnosis and management with special focus on dif
fi
culties
encountered in low or middle-income countries.
&
2014 International Society for Human and Animal Mycology. International Society for Human and
Animal Mycology Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Central nervous system cryptococcoma in a Ugandan patient
with Human Immunode
fi
ciency Virus
Sruti S. Velamakanni
a
,
b
,
n
, Nathan C. Bahr
a
,
b
,
c
, Abdu K. Musubire
a
, David R. Boulware
b
,
c
,
Joshua Rhein
a
,
b
,
c
, Henry W. Nabeta
a
a
Infectious Disease Institute, Makerere University, Kampala, Uganda
b
Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
c
Center for Infectious Diseases
&
Microbiology Translational Research, University of Minnesota, Minneapolis, MN, USA
article info
Article history:
Received 16 June 2014
Received in revised form
3 August 2014
Accepted 3 August 2014
Keywords:
Cryptococcus meningitis
Cryptococcoma
Immunosuppressed Host
Central nervous system
Human Immunode
fi
ciency Virus
abstract
Mortality due to AIDS-related Cryptococcal meningitis (CM) is often
4
50% in low-middle income
countries. Dissemination of CM can result in intracranial mass lesions known as cryptococcoma. Patients
who develop cryptococcomas often have worse outcomes when compared to patients with cryptococ-
cosis without cryptococcoma. We describe a cryptococcoma in the central nervous system (CNS) in a
Ugandan patient with AIDS, and review the diagnosis and management with special focus on dif
fi
culties
encountered in low or middle-income countries.
&
2014 International Society for Human and Animal Mycology. International Society for Human and
Animal Mycology Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license |
Kruh-Garcia, Nicole A.; Wolfe, Lisa M.; Chaisson, Lelia H.; Worodria, William O.; Nahid, Payam; J. Lucian Davis 3 Jeff S. Schorey, 5 Detection of Mycobacterium tuberculosis Peptides in the Exosomes of Patients with Active and Latent M. tuberculosis Infection Using MRM-MS Journal Article In: PloS One, vol. 9, no. 7, 2014. @article{Kruh-Garcia2014,
title = {Detection of Mycobacterium tuberculosis Peptides in the Exosomes of Patients with Active and Latent M. tuberculosis Infection Using MRM-MS},
author = {Nicole A. Kruh-Garcia and Lisa M. Wolfe and Lelia H. Chaisson and William O. Worodria and Payam Nahid and Jeff S. Schorey
, J. Lucian Davis
3,5
, Karen M. Dobos},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Detection-of-Mycobacterium-tuberculosis....pdf},
doi = {10.1371/journal.pone.0103811},
year = {2014},
date = {2014-07-31},
journal = {PloS One},
volume = {9},
number = {7},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Joyce Nguna Richard Kwizera, Agnes Kiragga Performance of Cryptococcal Antigen Lateral Flow Assay Using Saliva in Ugandans with CD4 <100 Journal Article In: PLOS ONE, vol. 9, no. 7, pp. e103156, 2014. @article{Kwizera2014,
title = {Performance of Cryptococcal Antigen Lateral Flow Assay Using Saliva in Ugandans with CD4 <100},
author = {Richard Kwizera, Joyce Nguna, Agnes Kiragga, Jesca Nakavuma, Radha Rajasingham, David R. Boulware, David B. Meya},
doi = {https://doi.org/10.1371/journal.pone.0103156},
year = {2014},
date = {2014-07-30},
journal = {PLOS ONE},
volume = {9},
number = {7},
pages = {e103156},
abstract = {Background
Cryptococcal meningitis can best be diagnosed by cerebrospinal fluid India ink microscopy, cryptococcal antigen detection, or culture. These require invasive lumbar punctures. The utility of cryptococcal antigen detection in saliva is unknown. We evaluated the diagnostic performance of the point-of-care cryptococcal antigen lateral flow assay (CrAg LFA) in saliva.
Methods
We screened HIV-infected, antiretroviral therapy naïve persons with symptomatic meningitis (n = 130) and asymptomatic persons with CD4+<100 cells/µL entering into HIV care (n = 399) in Kampala, Uganda. The diagnostic performance of testing saliva was compared to serum/plasma cryptococcal antigen as the reference standard.
Results
The saliva lateral flow assay performance was overall more sensitive in symptomatic patients (88%) than in asymptomatic patients (27%). The specificity of saliva lateral flow assay was excellent at 97.8% in the symptomatic patients and 100% in asymptomatic patients. The degree of accuracy of saliva in diagnosing cryptococcosis and the level of agreement between the two sample types was better in symptomatic patients (C-statistic 92.9, κ-0.82) than in asymptomatic patients (C-statistic 63.5, κ-0.41). Persons with false negative salvia CrAg tests had lower levels of peripheral blood CrAg titers (P<0.001).
Conclusion
There was poor diagnostic performance in testing saliva for cryptococcal antigen, particularly among asymptomatic persons screened for preemptive treatment of cryptococcosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
Cryptococcal meningitis can best be diagnosed by cerebrospinal fluid India ink microscopy, cryptococcal antigen detection, or culture. These require invasive lumbar punctures. The utility of cryptococcal antigen detection in saliva is unknown. We evaluated the diagnostic performance of the point-of-care cryptococcal antigen lateral flow assay (CrAg LFA) in saliva.
Methods
We screened HIV-infected, antiretroviral therapy naïve persons with symptomatic meningitis (n = 130) and asymptomatic persons with CD4+<100 cells/µL entering into HIV care (n = 399) in Kampala, Uganda. The diagnostic performance of testing saliva was compared to serum/plasma cryptococcal antigen as the reference standard.
Results
The saliva lateral flow assay performance was overall more sensitive in symptomatic patients (88%) than in asymptomatic patients (27%). The specificity of saliva lateral flow assay was excellent at 97.8% in the symptomatic patients and 100% in asymptomatic patients. The degree of accuracy of saliva in diagnosing cryptococcosis and the level of agreement between the two sample types was better in symptomatic patients (C-statistic 92.9, κ-0.82) than in asymptomatic patients (C-statistic 63.5, κ-0.41). Persons with false negative salvia CrAg tests had lower levels of peripheral blood CrAg titers (P<0.001).
Conclusion
There was poor diagnostic performance in testing saliva for cryptococcal antigen, particularly among asymptomatic persons screened for preemptive treatment of cryptococcosis. |