Browsing by Author "Kamya, Moses R."
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Item Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial(The Lancet Global Health, 2013) Wanyenze, Rhoda K.; Kamya, Moses R.; Fatch, Robin; Mayanja-Kizza, Harriet; Baveewo, Steven; Szekeres, Gregory; Bangsberg, David; Coates, Thomas; Hahn, Judith A.HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its eff ect on HIV risk is uncertain and methods to improve linkage to care have not been studied. We did this factorial randomised controlled study at Mulago Hospital, Uganda. Participants were randomly assigned to abbreviated or traditional HIV counselling and testing; HIV-infected patients were randomly assigned to enhanced linkage to care or standard linkage to care. All study personnel except counsellors and the data offi cer were masked to study group assignment. Participants had structured interviews, given once every 3 months. We compared sexual risk behaviour by counselling strategy with a 6·5% non-inferiority margin. We used Cox proportional hazards analyses to compare HIV outcomes by linkage to care over 1 year and tested for interaction by sex. This trial is registered with ClinicalTrials.gov (NCT00648232). We enrolled 3415 participants; 1707 assigned to abbreviated counselling versus 1708 assigned to traditional. Unprotected sex with an HIV discordant or status unknown partner was similar in each group (232/823 [27·9%] vs 251/890 [28·2%], diff erence –0·3%, one-sided 95% CI 3·2). Loss to follow-up was lower for traditional counselling than for abbreviated counselling (adjusted hazard ratio [HR] 0·61, 95% CI 0·44–0·83). 1003 HIV-positive participants were assigned to enhanced linkage (n=504) or standard linkage to care (n=499). Linkage to care did not have a signifi cant eff ect on mortality or receipt of co-trimoxazole. Time to treatment in men with CD4 cell counts of 250 cells per μL or fewer was lower for enhanced linkage versus standard linkage (adjusted HR 0·60, 95% CI 0·41–0·87) and time to HIV care was decreased among women (0·80, 0·66–0·96).Item Acceptability and Feasibility of Serial HIV Antibody Testing During Pregnancy/Postpartum and Male Partner Testing in Tororo, Uganda(AIDS care, 2014) Kim, Lena H.; Arinaitwe, Emmanuel; Nzarubara, Bridget; Kamya, Moses R.; Clark, Tamara D.; Okonge, Pius; Charlebois, Edwin D.; Havlir, Diane V.; Cohan, DeborahOur objective was to determine whether serial HIV testing during pregnancy and the postpartum period as well as male partner testing are acceptable and feasible in Tororo, Uganda. This was a prospective study of pregnant women at the Tororo District Hospital (TDH) Antenatal Clinic. Patients presenting for routine antenatal care were asked to participate in a serial HIV testing integrated into standard antenatal and postpartum/child immunization visits, and to invite their male partners for HIV testing. Serial testing was defined as ≥2 tests during pregnancy and ≥2 tests within 24 weeks postpartum. Of the 214 enrolled women, 80 (37%) completed serial testing, 176 (82%) had ≥2 tests, and 147 (69%) had ≥3 tests during the study period. One hundred eighty-two women (85%) accepted male partner testing, but only 19 men (10%) participated. One woman seroconverted during the study, for a cumulative HIV incidence of 0.5% (1/214). In multivariable logistic regression analysis, longer distance between home and clinic (aOR 0.87 [95% CI 0.79–0.97]) and not knowing household income (aOR 0.30 [95% CI 0.11–0.84]) were predictive of not completing serial testing. Higher level of education was associated with completing serial testing (linear trend p value = 0.05). In conclusion, partial serial HIV testing was highly acceptable and feasible, but completion of serial testing and male partner testing had poor uptake.Item Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda(The American journal of tropical medicine and hygiene, 2015) Mbabazi, Phoebe; Hopkins, Heidi; Osilo, Emmanuel; Kalungu, Michael; Byakika-Kibwika, Pauline; Kamya, Moses R.Malaria rapid diagnostic tests (RDTs) may improve fever management in areas without microscopy. We compared the accuracy of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as a gold standard, for initial diagnosis, treatment monitoring, and diagnosis of recurrent malaria in a cohort of children followed longitudinally in a high transmission area in Uganda. For 305 initial fever episodes, sensitivity was 98% for HRP2 and 87% for pLDH, whereas specificity was 55% and 96%, respectively. The HRP2 gave 51% false-positive results on Day 28, whereas pLDH gave no false positives after Day 7. For 59 recurrent fever episodes during follow-up, sensitivity was 100% for HRP2 and 91% for pLDH, whereas specificity was 33% and 100%, respectively. The HRP2-based RDTs are useful for initial diagnosis of malaria caused by superior sensitivity; however, as a result of superior specificity, pLDH-based RDTs are more appropriate to monitor treatment and diagnose recurrent malaria.Item The Age-specific Burden and Household and School-Based Predictors of Child and Adolescent Tuberculosis Infection in Rural Uganda(PloS one, 2020) Mwangwa, Florence; Charlebois, Edwin D.; Ayieko, James; Olio, Winter; Kwarisiima, Dalsone; Kabami, Jane; Kapogiannis, Bill; Kamya, Moses R.; Havlir, Diane V.; Ruel, Theodore D.The age-specific epidemiology of child and adolescent tuberculosis (TB) is poorly understood, especially in rural areas of East Africa. We sought to characterize the age-specific prevalence and predictors of TB infection among children and adolescents living in rural Uganda, and to explore the contribution of household TB exposure on TB infection. From 2015–2016 we placed and read 3,121 tuberculin skin tests (TST) in children (5–11 years old) and adolescents (12–19 years old) participating in a nested household survey in 9 rural Eastern Ugandan communities. TB infection was defined as a positive TST (induration ≥10mm or ≥5mm if living with HIV). Age-specific prevalence was estimated using inverse probability weighting to adjust for incomplete measurement. Generalized estimating equations were used to assess the association between TB infection and multi-level predictors. The adjusted prevalence of TB infection was 8.5% (95%CI: 6.9–10.4) in children and 16.7% (95% CI:14.0–19.7) in adolescents. Nine percent of children and adolescents with a prevalent TB infection had a household TB contact. Among children, having a household TB contact was strongly associated with TB infection (aOR 5.5, 95% CI: 1.7–16.9), but the strength of this association declined among adolescents and did not meet significance (aOR 2.3, 95% CI: 0.8–7.0). The population attributable faction of TB infection due to a household TB contact was 8% for children and 4% among adolescents. Mobile children and adolescents who travel outside of their community for school had a 1.7 (95% CI 1.0–2.9) fold higher odds of TB infection than those who attended school in the community. Children and adolescents in this area of rural eastern Uganda suffer a significant burden of TB. The majority of TB infections are not explained by a known household TB contact. Our findings underscore the need for community-based TB prevention interventions, especially among mobile youth.Item Anti-malarial prescription practices among outpatients with laboratory-confirmed malaria in the setting of a health facility-based sentinel site surveillance system in Uganda(Malaria journal, 2013) Sears, David; Kigozi, Ruth; Mpimbaza, Arthur; Kakeeto, Stella; Sserwanga, Asadu; Staedke, Sarah G.; Chang, Michelle; Kapella, Bryan K.; Rubahika, Denis; Kamya, Moses R.; Dorsey, GrantMost African countries have adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. The World Health Organization now recommends limiting anti-malarial treatment to those with a positive malaria test result. Limited data exist on how these policies have affected ACT prescription practices. Methods: Data were collected from all outpatients presenting to six public health facilities in Uganda as part of a sentinel site malaria surveillance programme. Training in case management, encouragement of laboratory-based diagnosis of malaria, and regular feedback were provided. Data for this report include patients with laboratory confirmed malaria who were prescribed anti-malarial therapy over a two-year period. Patient visits were analysed in two groups: those considered ACT candidates (defined as uncomplicated malaria with no referral for admission in patients ≥ 4 months of age and ≥ 5 kg in weight) and those who may not have been ACT candidates. Associations between variables of interest and failure to prescribe ACT to patients who were ACT candidates were estimated using multivariable logistic regression. Results: A total of 51,355 patient visits were included in the analysis and 46,265 (90.1%) were classified as ACT candidates. In the ACT candidate group, 94.5% were correctly prescribed ACT. Artemether-lumefantrine made up 97.3% of ACT prescribed. There were significant differences across the sites in the proportion of patients for whom there was a failure to prescribe ACT, ranging from 3.0-9.3%. Young children and woman of childbearing age had higher odds of failure to receive an ACT prescription. Among patients who may not have been ACT candidates, the proportion prescribed quinine versus ACT differed based on if the patient had severe malaria or was referred for admission (93.4% vs 6.5%) or was below age or weight cutoffs for ACT (41.4% vs 57.2%). Conclusions: High rates of compliance with recommended ACT use can be achieved in resource-limited settings. The unique health facility-based malaria surveillance system operating at these clinical sites may provide a framework for improving appropriate ACT use at other sites in sub-Saharan Africa.Item Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treating Uncomplicated Malaria: A Randomized Trial to Guide Policy in Uganda(PloS one, 2008) Yeka, Adoke; Dorsey, Grant; Kamya, Moses R.; Talisuna, Ambrose; Lugemwa, Myers; Rwakimari, John Bosco; Staedke, Sarah G.; Rosenthal, Philip J.; Mangen, Fred Wabwire; Bukirwa, HasifaUganda recently adopted artemether-lumefantrine (AL) as the recommended first-line treatment for uncomplicated malaria. However, AL has several limitations, including a twice-daily dosing regimen, recommendation for administration with fatty food, and a high risk of reinfection soon after therapy in high transmission areas. Dihydroartemisinin-piperaquine (DP) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect. We compared the efficacy and safety of AL with DP in Kanungu, an area of moderate malaria transmission.Patients aged 6 months to 10 years with uncomplicated falciparum malaria were randomized to therapy and followed for 42 days. Genotyping was used to distinguish recrudescence from new infection. Of 414 patients enrolled, 408 completed follow-up. Compared to patients treated with artemether-lumefantrine, patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia (33.2% vs. 12.2%; risk difference = 20.9%, 95% CI 13.0–28.8%) but no statistically significant difference in the risk of treatment failure due to recrudescence (5.8% vs. 2.0%; risk difference = 3.8%, 95% CI −0.2–7.8%). Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy (4.2% vs. 10.6%, p = 0.01). Both drugs were safe and well tolerated.DP is highly efficacious, and operationally preferable to AL because of a less intensive dosing schedule and requirements. Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Uganda.Item Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial(PLoS clinical trials, 2007) Kamya, Moses R.; Yeka, Adoke; Bukirwa, Hasifa; Lugemwa, Myers; Rwakimari, John B.; Staedke, Sarah G.; Talisuna, Ambrose O.; Mangen, Fred WabwireTo compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.Randomized single-blinded clinical trial.Apac, Uganda, an area of very high malaria transmission intensity.Children aged 6 mo to 10 y with uncomplicated falciparum malaria.Treatment of malaria with AL or DP, each following standard 3-d dosing regimens.Risks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.Of 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d (11% versus 29%; risk difference [RD] 18%, 95% confidence interval [CI] 11%–26%) and 42 d (43% versus 53%; RD 9.6%, 95% CI 0%–19%) of follow-up. Similarly, the risk of recurrent parasitemia due to possible recrudescence (adjusted by genotyping) was significantly lower for participants treated with DP than for those treated with AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%–12%) and 42 d (6.9% versus 16%; RD 9.5%, 95% CI 2.8%–16%). Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species, development of gametocytemia, and higher mean increase in hemoglobin compared to patients treated with AL. Both drugs were well tolerated; serious adverse events were uncommon and unrelated to study drugs.DP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia, and provided improved hemoglobin recovery. DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit of artemisinin-based combination therapy in Africa, treatment should be integrated with aggressive strategies to reduce malaria transmission intensity.Item Artemisinin Combination Therapies for Treatment of Uncomplicated Malaria in Uganda(PLoS clinical trials, 2006) Bukirwa, Hasifa; Yeka, Adoke; Kamya, Moses R.; Talisuna, Ambrose; Banek, Kristin; Bakyaita, Nathan; Rwakimari, John Bosco; Rosenthal, Philip J.; Mangen, Fred Wabwire; Dorsey, Grant; Staedke, Sarah G.To compare the efficacy and safety of artemisinin combination therapies for the treatment of uncomplicated falciparum malaria in Uganda.Randomized single-blind controlled trial.Tororo, Uganda, an area of high-level malaria transmission.Children aged one to ten years with confirmed uncomplicated P. falciparum malaria.Amodiaquine + artesunate or artemether–lumefantrine.Risks of recurrent symptomatic malaria and recurrent parasitemia at 28 days, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.Of 408 participants enrolled, 403 with unadjusted efficacy outcomes were included in the per-protocol analysis. Both treatment regimens were highly efficacious; no recrudescences occurred in patients treated with amodiaquine + artesunate, and only two occurred in those treated with artemether–lumefantrine. However, recurrent malaria due to new infections was common. The unadjusted risk of recurrent symptomatic malaria was significantly lower for participants treated with artemether–lumefantrine than for those treated with amodiaquine + artesunate (27% versus 42%, risk difference 15%, 95% CI 5.9%–24.2%). Similar results were seen for the risk of recurrent parasitemia (51% artemether–lumefantrine versus 66% amodiaquine + artesunate, risk difference 16%, 95% CI 6.2%–25.2%). Amodiaquine + artesunate and artemether–lumefantrine were both well-tolerated. Serious adverse events were uncommon with both regimens.Amodiaquine + artesunate and artemether–lumefantrine were both highly efficacious for treatment of uncomplicated malaria. However, in this holoendemic area, despite the excellent performance of both regimens in terms of efficacy, many patients experienced recurrent parasitemia due to new infections. Artemether–lumefantrine was superior to amodiaquine + artesunate for prevention of new infections. To maximize the benefit of artemisinin combination therapy in Africa, treatment should be integrated with strategies to prevent malaria transmission. The impact of frequent repeated therapy on the efficacy, safety, and cost-effectiveness of new artemisinin regimens should be further investigated.Item Artemisinin-Based Combination Therapies Are Efficacious and Safe for Treatment of Uncomplicated Malaria in HIV-Infected Ugandan Children(Clinical infectious diseases, 2014) Kakuru, Abel; Achan, Jane; Muhindo, Mary K.; Ikilezi, Gloria; Arinaitwe, Emmanuel; Mwangwa, Florence; Ruel, Theodore; Clark, Tamara D.; Charlebois, Edwin; Kamya, Moses R.; Tappero, Jordan W.; Dorsey, GrantArtemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)–infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited. We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in 2 cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children <6 years of age were randomized to lopinavir/ritonavir (LPV/r) or nonnucleoside reverse transcriptase inhibitor–based ART and treated with AL for uncomplicated malaria. In another cohort, children <12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes. There were 773 and 165 treatments for malaria with AL and DP, respectively. Initial response to therapy was excellent, with 99% clearance of parasites and <1% risk of repeat therapy within 3 days. Recurrent parasitemia within 28 days was common following AL treatment. The risk of recurrent parasitemia was significantly lower among children taking LPV/r-based ART compared with children taking nevirapine-based ART following AL treatment (15.3% vs 35.5%, P = .009), and those treated with DP compared with AL (8.6% vs 36.2%, P < .001). Both ACT regimens were safe and well tolerated. Treatment of uncomplicated malaria with AL or DP was efficacious and safe in HIV-infected children taking ART. However, there was a high risk of recurrent parasitemia following AL treatment, which was significantly lower in children taking LPV/r-based ART compared with nevirapine-based ART.Item Assessing the Quality of Tuberculosis Evaluation for Children with Prolonged Cough Presenting to Routine Community Health Care Settings in Rural Uganda(PloS one, 2014) Marquez, Carina; Davis, J. Lucian; Katamba, Achilles; Haguma, Priscilla; Ochomi, Emmanuel; Ayakaka, Irene; Chamie, Gabriel; Dorsey, Grant; Kamya, Moses R.; Charlebois, Edwin; Havlir, Diane V.; Cattamanchi, AdithyaImproving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse. Objective: To describe the current practices and quality of TB evaluation for children with cough $2 weeks’ duration presenting to community health centers in Uganda. Methods: Cross-sectional analysis of children (,15 years) receiving care at five Level IV community health centers in rural Uganda for any reason between 2009–2012. Quality of TB care was assessed using indicators derived from the International Standards of Tuberculosis Care (ISTC). Results: From 2009–2012, 1713 of 187,601 (0.9%, 95% CI: 0.4–1.4%) children presenting to community health centers had cough $ 2 weeks’ duration. Of those children, only 299 (17.5%, 95% CI: 15.7–19.3%) were referred for sputum microscopy, but 251 (84%, 95% CI: 79.8–88.1%) completed sputum examination if referred. The yield of sputum microscopy was only 3.6% (95% CI: 1.3–5.9%), and only 55.6% (95% CI: 21.2–86.3%) of children with acid-fast bacilli positive sputum were started on treatment. Children under age 5 were less likely to be referred for sputum examination and to receive care in accordance with ISTC. The proportion of children evaluated in accordance with ISTC increased over time (4.6% in 2009 to 27.9% in 2012, p = 0.03), though this did not result in increased case-detection. Conclusion: The quality of TB evaluation was poor for children with cough $2 weeks’ duration presenting for health care. Referrals for sputum smear microscopy and linkage to TB treatment were key gaps in the TB evaluation process, especially for children under the age of five.Item Assessment of the accuracy of malaria microscopy in private health facilities in Entebbe Municipality, Uganda: a cross‑sectional study(Malaria Journal, 2021) Mutabazi, Tobius; Sendaula, Emmanuel; Kakeeto, Alex; Okimat, Paul; Orishaba, Philip; Katongole, Simon Peter; Mpimbaza, Arthur; Byakika‑Kibwika, Pauline; Karamagi, Charles; Nakayaga Kalyango, Joan; Kamya, Moses R.; Dorsey, Grant; Nankabirwa, Joaniter I.Although microscopy remains the gold standard for malaria diagnosis, little is known about its accuracy in the private health facilities in Uganda. This study evaluated the accuracy of malaria microscopy, and factors associated with inaccurate smear results at private health facilities in Entebbe Municipality, Uganda. Methods: Between April and May 2018, all patients referred for a malaria smear in 16 private health facilities in Entebbe municipality were screened, and 321 patients were enrolled. A questionnaire was administered to collect demographic and clinical information, facility-based smear results were recorded from the participant’s consultation notes, and a research slide was obtained for expert microscopy during exit interview. A health facility assessment was conducted, and information on experience in performing malaria microscopy was collected from all facility personnel reading smears and the data was linked to the participant’s clinic visit.Item Associations between environmental covariates and malaria incidence in high transmission settings of Uganda: A distributed non-linear lagged ecological analysis(Research Square, 2021) Okiring, Jaffer; Routledge, Isobel; Esptein, Adrienne; Namuganga, Jane F.; Kamya, Emmanuel V.; Odei Obeng-Amoako, Gloria; Maiteki-Sebuguzi, Catherine; Rutazaana, Damian; Kalyango, Joan N.; Kamya, Moses R.; Dorsey, Grant; Wesonga, Ronald; Kiwuwa, Steven M.; Nankabirwa, Joaniter I.Environmental factors such as temperature, rainfall, and vegetation cover play a critical role in malaria transmission. However, quantifying the relationships between environmental factors and measures of disease burden relevant for public health can be complex as effects are often non-linear and subject to temporal lags between when changes in environmental factors lead to changes in the incidence of symptomatic malaria. The study aim was to investigate the associations between environmental covariates and malaria incidence in high transmission settings of Uganda. Methods This study leveraged data from seven malaria reference centres (MRCs) located in high transmission settings of Uganda over a 24-month period (January 2019 - December 2020). Estimates of monthly malaria incidence (MI) were derived from MRCs’ catchment areas. Environmental data including monthy average measures of temperature, rainfall, and normalized difference vegetation index (NDVI) were obtained from remote sensing sources. A distributed non-linear lagged model was used to investigate the quantitative relationship between environmental covariates and malaria incidence. Results Overall, the median (range) monthly temperature was 30oC (26-47), rainfall 133.0 mm (3.0-247), NDVI 0.66 (0.24-0.80) and MI was 790 per 1000 person-years (73-3973). A non-linear relationship between environmental covariates and malaria incidence was observed. An average monthly temperature of 35oC was associated with significant increases in malaria incidence compared to the median observed temperature (30oC) at month lag 2 (IRR: 2.00, 95% CI: 1.42-2.83) and the cumulative increases in MI significantly at month lags 1-4, with the highest cumulative IRR of 8.16 (95% CI: 3.41-20.26) at lag month 4. An average monthly rainfall of 200mm was associated with significant increases in malaria incidence compared to the median observed rainfall (133mm) at lag month 0 (IRR: 1.24, 95% CI: 1.01-1.52) and the cumulative IRR increases of malaria at month lags 1-4, with the highest cumulative IRR of 1.99(95% CI: 1.22-2.27) at lag month 4. An average NVDI of 0.72 was associated with significant cumulative increases in IRR of malaria as compared to the median observed NDVI (0.66) at month lag 2-4, with the highest cumulative IRR of 1.57(95% CI: 1.09-2.25) at lag month 4. The rate of increase in cumulative IRR of malaria was highest within lag months 1-2 as compared to lag months 3-4 for all the environmental covariates. Conclusions In high-malaria transmission settings, high values of environmental covariates were associated with cumulative increases in the incidence of malaria, with peak associations occurring after variable lag times. The complex associations identified are valuable for designing strategies for early warning, prevention, and control of seasonal malaria surges and epidemics.Item Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study(Malaria Journal, 2020) Kakande, Elijah; Greenhouse, Bryan; Bajunirwe, Francis; Drakeley, Chris; Nankabirwa, Joaniter I.; Walakira, Andrew; Nsobya, Samuel L.; Katureebe, Agaba; Rek, John; Arinaitwe, Emmanuel; Rosenthal, Philip J.; Kamya, Moses R.; Dorsey, Grant; Rodriguez‑Barraquer, IsabelMultiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear. Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A—(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes.Item Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial(Tropical medicine & international health, 2015) Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D.; Kamya, Moses R.; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, HarrietT-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.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.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.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.Item Bacteremia among Febrile Ugandan Children Treated with Antimalarials Despite a Negative Malaria Test(The American journal of tropical medicine and hygiene, 2015) Kibuuka, Afizi; Byakika-Kibwika, Pauline; Achan, Jane; Yeka, Adoke; Nalyazi, Joan N.; Mpimbaza, Arthur; Rosenthal, Philip J.; Kamya, Moses R.Bacteremia may be inappropriately treated as malaria in children admitted with a febrile illness in Africa. We determined the prevalence, clinical features, and spectrum of bacteremia among febrile children younger than 5 years of age admitted with a negative malaria test, but prescribed antimalarials at a referral hospital in Jinja, Uganda. After initial evaluation, a blood sample was drawn from 250 children for a complete blood count and bacterial culture. Of 250 samples cultured, 15 grew organisms presumed to be skin contaminants, and of the remaining 235 samples, 45 (19.1%) had bacteremia. Staphylococcus aureus (42%), non-typhoidal Salmonella (24%), Pseudomonas aeruginosa (11%), and Streptococcus pneumoniae (9%) were the most common bacterial isolates. On multivariate analysis, history of weight loss (odds ratio [OR] = 2.75; 95% confidence interval [CI] = 1.27–5.95), presence of pulmonary crackles (OR = 3.63; 95% CI = 1.40–9.45), and leukocytosis (OR = 2.21; 95% CI = 1.09–4.47) were independent predictors of bacteremia. At a hospital in Uganda, bacteremia was a remarkably common finding in children with febrile illness who were treated for malaria despite negative malaria test results.Item Characteristics of HIV Seroconverters in the Setting of Universal Test and Treat: Results from the SEARCH trial in rural Uganda and Kenya(PloS one, 2021) Nyabuti, Marilyn N.; Maya, L. Petersen; Bukusi, Elizabeth A.; Kamya, Moses R.; Mwangwa, Florence; Kabami, Jane; Charlebois, Edwin D.; Tamara, D. Clark; Chamie, Gabriel; Havlir, Diane V.; Ayieko, JamesAdditional progress towards HIV epidemic control requires understanding who remains at risk of HIV infection in the context of high uptake of universal testing and treatment (UTT). We sought to characterize seroconverters and risk factors in the SEARCH UTT trial (NCT01864603), which achieved high uptake of universal HIV testing and ART coverage in 32 communities of adults (≥15 years) in rural Uganda and Kenya. In a pooled cohort of 117,114 individuals with baseline HIV negative test results, we described those who seroconverted within 3 years, calculated gender-specific HIV incidence rates, evaluated adjusted risk ratios (aRR) for seroconversion using multivariable targeted maximum likelihood estimation, and assessed potential infection sources based on self-report. Of 704 seroconverters, 63% were women. Young (15–24 years) men comprised a larger proportion of seroconverters in Western Uganda (18%) than Eastern Uganda (6%) or Kenya (10%). After adjustment for other risk factors, men who were mobile [≥1 month of prior year living outside community] (aRR:1.68; 95%CI:1.09,2.60) or who HIV tested at home vs. health fair (aRR:2.44; 95%CI:1.89,3.23) were more likely to seroconvert. Women who were aged ≤24 years (aRR:1.91; 95%CI:1.27,2.90), mobile (aRR:1.49; 95%CI:1.04,2.11), or reported a prior HIV test (aRR:1.34; 95%CI:1.06,1.70), or alcohol use (aRR:2.07; 95%CI:1.34,3.22) were more likely to seroconvert. Among survey responders (N = 607, 86%), suspected infection source was more likely for women than men to be ≥10 years older (28% versus 8%) or a spouse (51% vs. 31%) and less likely to be transactional sex (10% versus 16%). In the context of universal testing and treatment, additional strategies tailored to regional variability are needed to address HIV infection risks of young women, alcohol users, mobile populations, and those engaged in transactional sex to further reduce HIV incidence rates.Item Closing the Gap: A Novel Metric of Change in Performance(East African journal of applied health monitoring and evaluation, 2019) Katuramu, Richard; Wallenta, Jeanna; Semitala, Fred C.; Amanyire, Gideon; Kampiire, Leatitia; Namusobya, Jennifer; Kamya, Moses R.; Havlir, Diane; Geng, ElvinInterventions to improve performance of global programs in the HIV cascade of care are widespread and increasing the focus of implementation science. At present, however, there is no clear consensus on how to conceptualize their improvement at the program level. The commonly used measures of association, based on ratios of probabilities (or odds), have well-known defects in public health applications. They yield large effect sizes even when the absolute effects, and therefore the public health impact, are small. On the other hand, risk differences create problems because settings with higher baseline values are penalized. We aim to examine ways of quantifying improvement in each health center of a cluster-randomized trial in Uganda to accelerate antiretroviral therapy initiation among HIV-infected adults.Item Completion of isoniazid–rifapentine (3HP) for tuberculosis prevention among people living with HIV: Interim analysis of a hybrid type 3 effectiveness–implementation randomized trial(PLoS Med, 2021) Semitala, Fred C.; Kadota, Jillian L.; Musinguzi, Allan; Nabunje, Juliet; Welishe, Fred; Nakitende, Anne; Akello, Lydia; Kamya, Moses R.; Handley, Margaret A.; Katahoire, Anne; Berger, Christopher A.; Kiwanuka, Noah; Katamba, Achilles; Dowdy, David W.; Cattamanchi, AdithyaScaling up shorter regimens for tuberculosis (TB) prevention such as once weekly isoniazid–rifapentine (3HP) taken for 3 months is a key priority for achieving targets set forth in the World Health Organization’s (WHO) END TB Strategy. However, there are few data on 3HP patient acceptance and completion in the context of routine HIV care in sub-Saharan Africa. Methods and findings The 3HP Options Trial is a pragmatic, parallel type 3 effectiveness–implementation randomized trial comparing 3 optimized strategies for delivering 3HP—facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between DOT and SAT using a shared decision-making aid—to people receiving care at a large urban HIV clinic in Kampala, Uganda. Participants and healthcare providers were not blinded to arm assignment due to the nature of the 3HP delivery strategies. We conducted an interim analysis of participants who were enrolled and exited the 3HP treatment period between July 13, 2020 and April 30, 2021. The primary outcome, which was aggregated across trial arms for this interim analysis, was the proportion who accepted and completed 3HP (�11 of 12 doses within 16 weeks of randomization). We used Bayesian inference analysis to estimate the posterior probability that this proportion would exceed 80% under at least 1 of the 3HP delivery strategies, a coprimary hypothesis of the trial. Through April 2021, 684 participants have been enrolled, and 479 (70%) have exited the treatment period. Of these 479 participants, 309 (65%) were women, mean age was 41.9 years (standard deviation (SD): 9.2), and mean time on antiretroviral therapy (ART) was 7.8 years (SD: 4.3). In total, 445 of them (92.9%, 95% confidence interval (CI): [90.2 to 94.9]) accepted and completed 3HP treatment. There were no differences in treatment acceptance and completion by sex, age, or time on ART. Treatment was discontinued due to a documented adverse event (AE) in 8 (1.7%) patients. The probability that treatment acceptance and completion exceeds 80% under at least 1 of the three 3HP delivery strategies was greater than 99%. The main limitations are that the trial was conducted at a single site, and the interim analysis focused on aggregate outcome data to maintain blinding of investigators to arm-specific outcomes. Conclusions 3HP was widely accepted by people living with HIV (PLHIV) in Uganda, and very high levels of treatment completion were achieved in a programmatic setting. These findings show that 3HP can enable effective scale-up of tuberculosis preventive therapy (TPT) in high-burden countries, particularly when delivery strategies are tailored to target known barriers to treatment completion.Item Costs of Streamlined HIV Care Delivery in Rural Ugandan and Kenyan Clinics in the SEARCH Study(AIDS, 2018) Shade, Starley B.; Osmand, Thomas; Aine, Ronald; Mwebaza, Betty; Owaraganise, Asiphas; Mwangwa, Florence; Kwarisiima, Dalsone; Bukusi, Elizabeth A.; Kamya, Moses R.; Petersenk, Maya L.; Havlir, Diane V.; Jain, VivekAs antiretroviral therapy (ART) rapidly expands in sub-Saharan Africa using new efficient care models, data on costs of these approaches are lacking. We examined costs of a streamlined HIV care delivery model within a large HIV test-and-treat study in Uganda and Kenya. We calculated observed per-person-per-year (ppy) costs of streamlined care in 17 health facilities in SEARCH Study intervention communities (NCT: 01864603) via micro-costing techniques, time-and-motion studies, staff interviews, and administrative records. Cost categories included salaries, ART, viral load testing, recurring goods/services, and fixed capital/facility costs. We then modeled costs under three increasingly efficient scale-up scenarios: lowest-cost ART, centralized viral load testing, and governmental healthcare worker salaries. We assessed the relationship between community-specific ART delivery costs, retention in care, and viral suppression. Estimated streamlined HIV care delivery costs were $291/ppy. ART ($117/ppy for TDF/3TC/EFV [40%]) and viral load testing ($110/ppy for 2 tests/year [39%]) dominated costs versus salaries ($51/ppy), recurring costs ($5/ppy), and fixed costs ($7/ppy). Optimized ART scale-up with lowest-cost ART ($100/ppy), annual viral load testing ($24/ppy), and governmental healthcare salaries ($27/ppy), lowered streamlined care cost to $163/ppy. We found clinic-to-clinic heterogeneity in retention and viral suppression levels versus streamlined care delivery costs, but no correlation between cost and either retention or viral suppression. In the SEARCH Study, streamlined HIV care delivery costs were similar to or lower than prior estimates despite including viral load testing; further optimizations could substantially reduce costs further. These data can inform global strategies for financing ART expansion to achieve UNAIDS 90–90–90 targets.Item Culturally adapting a mindfulness and acceptance-based intervention to support the mental health of adolescents on antiretroviral therapy in Uganda(PLOS Global Public Health, 2023) Musanje, Khamisi; Camlin, Carol S.; Kamya, Moses R.; Kirabo, Hope; Nangendo, Joan; Kiweewa, John; White, Ross G.; Kasujja, RoscoThe dual burden of living with HIV and negotiating life stage changes has been identified as a contributing factor to lapsed adherence among adolescents with HIV in sub-Saharan Africa. While psychosocial support can promote medication adherence, most interventions in use with adolescents were originally developed for the general population creating a gap in appropriate support. Life-stage-appropriate, evidence-based psychosocial support interventions have been used with young people in high-income contexts, prompting interest in their use in low-income contexts. However, many interventions are less effective when implemented outside of their original settings, hence the need for modifications before implementation. We aimed to culturally adapt an evidence-based psychosocial support intervention designed to improve the mental health of young people for use among adolescents with HIV in a sub-Saharan African context and to explore the acceptability of the adapted intervention among adolescents. We engaged thirty stakeholders (n = 30) in Kampala, Uganda including psychologists, psychiatrists, social workers, HIV counselors, religious leaders and adolescent peers from December 2021 to April 2022 to modify an evidence-based intervention for adolescents. Key adaptations included simplifying the language, adding local practices, integrating locally relevant slang and stories into therapy, introducing racially-congruent visuals and cards representing emotions, and adjusting therapy materials for use in resource-constrained settings. We then tested the acceptability of the intervention in a small sample of service users using a qualitative approach. We recruited nine adolescents with HIV from a participating clinic in Kampala, delivered six 90-minute sessions of the adapted intervention across three weeks and conducted in-depth interviews to assess the acceptability of the intervention. We used thematic analysis to analyze the qualitative data. The adapted intervention was perceived as acceptable among adolescents with HIV, with many stating that it helped them overcome fears, increased their self-acceptance, and gave them the confidence to make careful health-enhancing decisions.