Showing papers by "Moses R. Kamya published in 2018"
French Institute of Health and Medical Research1, University of Massachusetts Amherst2, University of California, San Francisco3, University of London4, Brigham and Women's Hospital5, Harvard University6, Makerere University7, Centers for Disease Control and Prevention8, University of California, Berkeley9, University College London10
TL;DR: Five community‐based trials have been implemented in sub‐Saharan Africa to measure the effects of various UTT strategies at population level and the contexts, research methodologies, intervention packages, themes explored, evolution of study designs and interventions related to each of these five UTT trials are described.
Abstract: DESIGN: Universal voluntary HIV counselling and testing followed by prompt initiation of antiretroviral therapy (ART) for all those diagnosed HIV-infected (universal test and treat, UTT) is now a global health standard. However, its population-level impact, feasibility and cost remain unknown. Five community-based trials have been implemented in sub-Saharan Africa to measure the effects of various UTT strategies at population level: BCPP/YaTsie in Botswana, MaxART in Swaziland, HPTN 071 (PopART) in South Africa and Zambia, SEARCH in Uganda and Kenya and ANRS 12249 TasP in South Africa. This report describes and contrasts the contexts, research methodologies, intervention packages, themes explored, evolution of study designs and interventions related to each of these five UTT trials. METHODS: We conducted a comparative assessment of the five trials using data extracted from study protocols and collected during baseline studies, with additional input from study investigators. We organized differences and commonalities across the trials in five categories: trial contexts, research designs, intervention packages, trial themes and adaptations. RESULTS: All performed in the context of generalized HIV epidemics, the trials highly differ in their social, demographic, economic, political and health systems settings. They share the common aim of assessing the impact of UTT on the HIV epidemic but differ in methodological aspects such as study design and eligibility criteria for trial populations. In addition to universal ART initiation, the trials deliver a wide range of biomedical, behavioural and structural interventions as part of their UTT strategies. The five studies explore common issues, including the uptake rates of the trial services and individual health outcomes. All trials have adapted since their initiation to the evolving political, economic and public health contexts, including adopting the successive national recommendations for ART initiation. CONCLUSIONS: We found substantial commonalities but also differences between the five UTT trials in their design, conduct and multidisciplinary outputs. As empirical literature on how UTT may improve efficiency and quality of HIV care at population level is still scarce, this article provides a foundation for more collaborative research on UTT and supports evidence-based decision making for HIV care in country and internationally.
80 citations
TL;DR: House design improved rapidly in rural Uganda and was associated with additional reductions in mosquito density and parasite prevalence following the introduction of indoor residual spraying, and changes to house design in endemic Africa might help further the gains achieved with more widely accepted malaria control interventions.
44 citations
TL;DR: Age was strongly associated with LLIN use, as were household wealth and time since the last UCC, and houses with many residents, poorer households, and school-aged children should be targeted to improve LLIN coverage and use.
Abstract: Long-lasting insecticidal nets (LLINs) are a key malaria control intervention. To investigate factors associated with ownership and use of LLINs in Uganda, a cross-sectional community survey was conducted in March–June 2017, approximately 3 years after a national Universal Coverage Campaign (UCC). Households from 104 clusters (health sub-districts) in 48 districts were randomly selected using two-staged cluster sampling; 50 households were enrolled per cluster. Outcomes were household ownership of LLINs (at least one LLIN), adequate LLIN coverage (at least one LLIN per 2 residents), and use of LLINs (resident slept under a LLIN the previous night). Associations between variables of interest and outcomes were made using multivariate logistic regression. In total, 5196 households, with 29,627 residents and 6980 bed-nets, were included in the analysis. Overall, 65.0% of households owned at least one LLIN (down from 94% in 2014). In the adjusted analysis, factors most strongly associated with LLIN ownership were living in a wealthier household (highest tercile vs lowest; adjusted odds ratio [aOR] 1.94, 95% CI 1.66–2.28, p 15 years (44.1%) were more likely to use nets than children aged 5–15 years (30.7%; 15 years: aOR 1.37, 95% CI 1.29–1.45, p < 0.001). Long-lasting insecticidal net ownership and coverage have reduced markedly in Uganda since the last net distribution campaign in 2013/14. Houses with many residents, poorer households, and school-aged children should be targeted to improve LLIN coverage and use. Trial registration This study is registered with ISRCTN (17516395)
38 citations
TL;DR: Intermittent preventive treatment of primary schoolchildren with dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the community, in Jinja, Uganda, might have a positive effect on community-level malaria indicators and be operationally feasible.
35 citations
TL;DR: This study sought to measure effects of diverse metrics of mobility on behaviours, with attention to gender, within an ongoing test‐and‐treat trial (SEARCH, NCT01864603) in sub‐Saharan Africa.
Abstract: Author(s): Camlin, Carol S; Akullian, Adam; Neilands, Torsten B; Getahun, Monica; Eyul, Patrick; Maeri, Irene; Ssali, Sarah; Geng, Elvin; Gandhi, Monica; Cohen, Craig R; Kamya, Moses R; Odeny, Thomas; Bukusi, Elizabeth A; Charlebois, Edwin D | Abstract: IntroductionThere are significant knowledge gaps concerning complex forms of mobility emergent in sub-Saharan Africa, their relationship to sexual behaviours, HIV transmission, and how sex modifies these associations. This study, within an ongoing test-and-treat trial (SEARCH, NCT01864603), sought to measure effects of diverse metrics of mobility on behaviours, with attention to gender.MethodsCross-sectional data were collected in 2016 from 1919 adults in 12 communities in Kenya and Uganda, to examine mobility (labour/non-labour-related travel), migration (changes of residence over geopolitical boundaries) and their associations with sexual behaviours (concurrent/higher risk partnerships), by region and sex. Multilevel mixed-effects logistic regression models, stratified by sex and adjusted for clustering by community, were fitted to examine associations of mobility with higher-risk behaviours, in past 2nyears/past 6nmonths, controlling for key covariates.ResultsThe population was 45.8% male and 52.4% female, with mean age 38.7 (median 37, IQR: 17); 11.2% had migrated in the past 2nyears. Migration varied by region (14.4% in Kenya, 11.5% in southwestern and 1.7% in eastern and Uganda) and sex (13.6% of men and 9.2% of women). Ten per cent reported labour-related travel and 45.9% non-labour-related travel in past 6nmonths-and varied by region and sex: labour-related mobility was more common in men (18.5%) than women (2.9%); non-labour-related mobility was more common in women (57.1%) than men (32.6%). In 2015 to 2016, 24.6% of men and 6.6% of women had concurrent sexual partnerships; in past 6nmonths, 21.6% of men and 5.4% of women had concurrent partnerships. Concurrency in 2015 to 2016 was more strongly associated with migration in women [aRRn=n2.0, 95% CI(1.1 to 3.7)] than men [aRRn=n1.5, 95% CI(1.0 to 2.2)]. Concurrency in past 6nmonths was more strongly associated with labour-related mobility in women [aRRn=n2.9, 95% CI(1.0 to 8.0)] than men [aRRn=n1.8, 95% CI(1.2 to 2.5)], but with non-labour-related mobility in men [aRRn=n2.2, 95% CI(1.5 to 3.4)].ConclusionsIn rural eastern Africa, both longer-distance/permanent, and localized/shorter-term forms of mobility are associated with higher-risk behaviours, and are highly gendered: the HIV risks associated with mobility are more pronounced for women. Gender-specific interventions among mobile populations are needed to combat HIV in the region.
34 citations
TL;DR: Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission.
Abstract: Background. The relationship between concentrations of antituberculosis drugs, sputum culture conversion, and treatment outcome remains unclear. We sought to determine the association between antituberculosis drug concentrations and sputum conversion among patients coinfected with tuberculosis and human immunodeficiency virus (HIV) and receiving first-line antituberculosis drugs.
Methods. We enrolled HIV-infected Ugandans with pulmonary tuberculosis. Estimation of first-line antituberculosis drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of tuberculosis treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion.
Results. We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of tuberculosis treatment (hazard ratio, 0.54; 95% confidence interval, .37–.77; P = .001) or by the end of follow-up (0.61; .44–.85; P = .003). Patients in the highest quartile for area under the rifampicin and isoniazid concentration-time curves for were twice as likely to experience sputum conversion than those in the lowest quartile. Rifampicin and isoniazid concentrations below the thresholds and weight <55 kg were both risk factors for unfavorable tuberculosis treatment outcomes. Only 4.4% of the participants had treatment failure.
Conclusion. Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission.
33 citations
TL;DR: Implementation of PrEP incorporating a population-based empiric risk score, self-identified risk, and rapid initiation, is feasible in rural East Africa, and strategies are needed to overcome barriers to PrEP uptake, particularly among women and youth.
Abstract: Background Global guidelines recommend preexposure prophylaxis (PrEP) for individuals with substantial human immunodeficiency virus (HIV) risk. Data on PrEP uptake in sub-Saharan Africa outside of clinical trials are limited. We report on "early adopters" of PrEP in the Sustainable East Africa Research in Community Health (SEARCH) study in rural Uganda and Kenya. Methods After community mobilization and PrEP education, population-based HIV testing was conducted. HIV-uninfected adults were offered PrEP based on an empirically derived HIV risk score or self-identified HIV risk (if not identified by score). Using logistic regression, we analyzed predictors of early PrEP adoption (starting PrEP within 30 days vs delayed/no start) among adults identified for PrEP. Results Of 21212 HIV-uninfected adults in 5 communities, 4064 were identified for PrEP (2991 by empiric risk score, 1073 by self-identified risk). Seven hundred and thirty nine individuals started PrEP within 30 days (11% of those identified by risk score; 39% of self-identified); 77% on the same day. Among adults identified by risk score, predictors of early adoption included male sex (adjusted odds ratio 1.53; 95% confidence interval, 1.09-2.15), polygamy (1.92; 1.27-2.90), serodiscordant spouse (3.89; 1.18-12.76), self-perceived HIV risk (1.66; 1.28-2.14), and testing at health campaign versus home (5.24; 3.33-8.26). Among individuals who self-identified for PrEP, predictors of early adoption included older age (2.30; 1.29-4.08) and serodiscordance (2.61; 1.01-6.76). Conclusions Implementation of PrEP incorporating a population-based empiric risk score, self-identified risk, and rapid initiation, is feasible in rural East Africa. Strategies are needed to overcome barriers to PrEP uptake, particularly among women and youth. Clinical trials registration NCT01864603.
28 citations
TL;DR: Submicroscopic malaria infections were associated with fever and non-febrile illness in Ugandan children, and these findings support malaria control strategies that target low-density infections.
Abstract: Submicroscopic malaria parasitaemia is common in both high- and low-endemicity settings, but its clinical consequences are unclear. A cohort of 364 children (0.5–10 years of age) and 106 adults was followed from 2011 to 2016 in Tororo District, Uganda using passive surveillance for malaria episodes and active surveillance for parasitaemia. Participants presented every 90 days for routine visits (n = 9075); a subset was followed every 30 days. Participants who presented with fever and a positive blood smear were treated for malaria. At all routine visits microscopy was performed and samples from subjects with a negative blood smear underwent loop-mediated isothermal amplification for detection of plasmodial DNA. Submicroscopic parasitaemia was common; the proportion of visits with submicroscopic parasitemia was 25.8% in children and 39.2% in adults. For children 0.5–10 years of age, but not adults, having microscopic and submicroscopic parasitaemia at routine visits was significantly associated with both fever (adjusted risk ratios [95% CI], 2.64 [2.16–3.22], 1.67 [1.37–2.03]) and non-febrile illness (aRR [CI], 1.52 [1.30–1.78], 1.26 [1.09–1.47]), compared to not having parasitaemia. After stratifying by age, significant associations were seen between submicroscopic parasitaemia and fever in children aged 2–< 5 and 5–10 years (aRR [CI], 1.42 [1.03–1.98], 2.01 [1.49–2.71]), and submicroscopic parasitaemia and non-febrile illness in children aged 5–10 years (aRR [CI], 1.44 [1.17–1.78]). These associations were maintained after excluding individuals with a malaria episode within the preceding 14 or following 7 days, and after adjusting for household wealth. Submicroscopic malaria infections were associated with fever and non-febrile illness in Ugandan children. These findings support malaria control strategies that target low-density infections.
28 citations
TL;DR: Hypertension is starkly prevalent in Uganda, and numerous more people, including young adults are at increased risk, and the potential additional impact of epidemiological shifts, including diet and lifestyle changes, on the development of hypertension is explored.
Abstract: Background Hypertension accounts for more than 212 million global disability-adjusted life-years, and more than 15 million in sub-Saharan Africa. Identifying factors underlying the escalating burden of hypertension in sub-Saharan Africa may inform delivery of targeted public health interventions. Methods As part of the cross-sectional nationally representative Uganda National Asthma Survey conducted in 2016, we measured blood pressure (BP) in the general population across five regions of Uganda. We defined hypertension as systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg, or on-going use of medications for the purpose of lowering BP among adults (≥18 years of age); pre-hypertension as systolic BP between 120 and 140 mmHg and/or diastolic BP bteween 80 and 90 mmHg among adolescents and adults (≥12 years of age). Findings Of 3416 participants who met inclusion criteria, 38.9% were male, and mean age ± SD was 33.8 ± 16.9 years. The age- and sex-adjusted prevalence of hypertension was 31.5% (95% confidence interval [CI] 30.2 to 32.8). The adjusted prevalence of hypertension was highest in the Central Region (34.3%; 95% CI 32.6 to 36.0), and it was comparable to that in the West and East Regions. However, compared with the Central Region, hypertension was significantly less prevalent in the North (22.0%; 95 CI 19.4 to 24.6) and West Nile Regions (24.1%; 95% CI 22.0 to 26.3). Adjustment for demographic characteristics (occupation, monthly income, and educational attainment) of participants did not account for the significantly lower prevalence of hypertension in the North and West Nile Regions. The prevalence of pre-hypertension was 38.8% (95% CI 37.7 to 39.8), and it was highly prevalent among young adults (21–40 years of age: 42.8%; 95% CI 41.2–44.5%) in all regions. Conclusions Hypertension is starkly prevalent in Uganda, and numerous more people, including young adults are at increased risk. The burden of hypertension is highest in the Central, Western, and Eastern regions of the country; demographic characteristics did not fully account for the disparate regional burden of hypertension. Future studies should explore the potential additional impact of epidemiological shifts, including diet and lifestyle changes, on the development of hypertension.
25 citations
TL;DR: 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.
Abstract: Author(s): Shade, Starley B; Osmand, Thomas; Luo, Alex; Aine, Ronald; Assurah, Elly; Mwebaza, Betty; Mwai, Daniel; Owaraganise, Asiphas; Mwangwa, Florence; Ayieko, James; Black, Douglas; Brown, Lillian B; Clark, Tamara D; Kwarisiima, Dalsone; Thirumurthy, Harsha; Cohen, Craig R; Bukusi, Elizabeth A; Charlebois, Edwin D; Balzer, Laura; Kamya, Moses R; Petersen, Maya L; Havlir, Diane V; Jain, Vivek | Abstract: OBJECTIVES/DESIGN:As 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. METHODS: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. RESULTS: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. CONCLUSIONS: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.
23 citations
TL;DR: Overall, neither offering incentives via lotteries nor framing incentives as losses resulted in significant increases in HIV testing compared with standard gain- Framed incentives, however, when offering low-cost incentives to promote HIV testing, providing lottery-based rewards may be a better strategy than gain-framed incentives.
Abstract: Objective:To assess the comparative effectiveness of alternative incentive-based interventions to promote HIV testing among men.Design:Randomized clinical trial.Methods:We enumerated four Ugandan parishes and enrolled men at least 18 years. Participants were randomized to six groups that received in
TL;DR: Preventing malaria in pregnancy with IPTp-DP in the context of chemoprevention with DP during infancy does not lead to a reduced incidence of malaria in childhood; in this setting, it may be associated with an increased incidence in females in females with biologicalero drug exposure.
Abstract: Background
Intermittent preventive treatment of malaria in pregnancy (IPTp) with dihydroartemisinin-piperaquine (IPTp-DP) has been shown to reduce the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (IPTp-SP). However, limited data exist on how IPTp regimens impact malaria risk during infancy. We conducted a double-blinded randomized controlled trial (RCT) to test the hypothesis that children born to mothers given IPTp-DP would have a lower incidence of malaria during infancy compared to children born to mothers who received IPTp-SP.
Methods and findings
We compared malaria metrics among children in Tororo, Uganda, born to women randomized to IPTp-SP given every 8 weeks (SP8w, n = 100), IPTp-DP every 8 weeks (DP8w, n = 44), or IPTp-DP every 4 weeks (DP4w, n = 47). After birth, children were given chemoprevention with DP every 12 weeks from 8 weeks to 2 years of age. The primary outcome was incidence of malaria during the first 2 years of life. Secondary outcomes included time to malaria from birth and time to parasitemia following each dose of DP given during infancy. Results are reported after adjustment for clustering (twin gestation) and potential confounders (maternal age, gravidity, and maternal parasitemia status at enrolment).The study took place between June 2014 and May 2017. Compared to children whose mothers were randomized to IPTp-SP8w (0.24 episodes per person year [PPY]), the incidence of malaria was higher in children born to mothers who received IPTp-DP4w (0.42 episodes PPY, adjusted incidence rate ratio [aIRR] 1.92; 95% CI 1.00–3.65, p = 0.049) and nonsignificantly higher in children born to mothers who received IPT-DP8w (0.30 episodes PPY, aIRR 1.44; 95% CI 0.68–3.05, p = 0.34). However, these associations were modified by infant sex. Female children whose mothers were randomized to IPTp-DP4w had an apparently 4-fold higher incidence of malaria compared to female children whose mothers were randomized to IPTp-SP8w (0.65 versus 0.20 episodes PPY, aIRR 4.39, 95% CI 1.87–10.3, p = 0.001), but no significant association was observed in male children (0.20 versus 0.28 episodes PPY, aIRR 0.66, 95% CI 0.25–1.75, p = 0.42). Nonsignificant increases in malaria incidence were observed among female, but not male, children born to mothers who received DP8w versus SP8w. In exploratory analyses, levels of malaria-specific antibodies in cord blood were similar between IPTp groups and sex. However, female children whose mothers were randomized to IPTp-DP4w had lower mean piperaquine (PQ) levels during infancy compared to female children whose mothers received IPTp-SP8w (coef 0.81, 95% CI 0.65–1.00, p = 0.048) and male children whose mothers received IPTp-DP4w (coef 0.72, 95% CI 0.57–0.91, p = 0.006). There were no significant sex-specific differences in PQ levels among children whose mothers were randomized to IPTp-SP8w or IPTp-DP8w. The main limitations were small sample size and childhood provision of DP every 12 weeks in infancy.
Conclusions
Contrary to our hypothesis, preventing malaria in pregnancy with IPTp-DP in the context of chemoprevention with DP during infancy does not lead to a reduced incidence of malaria in childhood; in this setting, it may be associated with an increased incidence of malaria in females. Future studies are needed to better understand the biological mechanisms of in utero drug exposure on drug metabolism and how this may affect the dosing of antimalarial drugs for treatment and prevention during infancy.
Trial registration
ClinicalTrials.gov number NCT02163447.
TL;DR: Rates of asthma exacerbations and mortality are high in Uganda and are associated with poor asthma control, and health systems should be strengthened to care for asthma patients.
Abstract: Data on asthma treatment outcomes in Africa are limited. 449 patients with asthma (age 5-93 years) in Uganda were followed up for 2 years to determine rates of exacerbations and mortality and associated factors. During follow-up the median number of exacerbations per patient was 1 (IQR 0-5) and 17 patients died (3.7%, 27.3 deaths per 1000 person years). Considering only the first year of follow-up, 59.6% of the patients experienced at least one exacerbation, 32.4% experienced three or more exacerbations. A multivariable model showed that the likelihood of experiencing at least one exacerbation in the first year of follow-up was lower with better baseline asthma control (higher asthma control test (ACT) score), with OR 0.87 (95% CI: 0.82 to 0.93, P=0.000), and was higher with more exacerbations in the year prior to enrolment (OR for log number of exacerbations 1.28, 95% CI: 1.04 to 1.57, P=0.018). Better asthma control (OR 0.93, 95% CI: 0.88 to 0.99, P=0.021) and number of baseline exacerbations (OR 1.35,95% CI: 1.11 to 1.66, P=0.005) were also the only factors that were independently associated with experiencing three or more exacerbations during the first year of follow-up. The only factor found to be associated with all-cause mortality was FEV1, with higher recent FEV1 associated with lower all-cause mortality (OR 0.30, 95% CI: 0.14 to 0.65; P=0.002). Rates of asthma exacerbations and mortality are high in Uganda and are associated with poor asthma control. Health systems should be strengthened to care for asthma patients.
TL;DR: A cross-cutting approach was used to improve surveillance and laboratory capacity in Uganda by leveraging an existing pediatric inpatient malaria sentinel surveillance system to collect data on expanded causes of illness, facilitate development of real-time surveillance, and provide data on antimicrobial resistance.
Abstract: Global health security depends on effective surveillance for infectious diseases. In Uganda, resources are inadequate to support collection and reporting of data necessary for an effective and responsive surveillance system. We used a cross-cutting approach to improve surveillance and laboratory capacity in Uganda by leveraging an existing pediatric inpatient malaria sentinel surveillance system to collect data on expanded causes of illness, facilitate development of real-time surveillance, and provide data on antimicrobial resistance. Capacity for blood culture collection was established, along with options for serologic testing for select zoonotic conditions, including arboviral infection, brucellosis, and leptospirosis. Detailed demographic, clinical, and laboratory data for all admissions were captured through a web-based system accessible at participating hospitals, laboratories, and the Uganda Public Health Emergency Operations Center. Between July 2016 and December 2017, the expanded system was activated in pediatric wards of 6 regional government hospitals. During that time, patient data were collected from 30,500 pediatric admissions, half of whom were febrile but lacked evidence of malaria. More than 5,000 blood cultures were performed; 4% yielded bacterial pathogens, and another 4% yielded likely contaminants. Several WHO antimicrobial resistance priority pathogens were identified, some with multidrug-resistant phenotypes, including Acinetobacter spp., Citrobacter spp., Escherichia coli, Staphylococcus aureus, and typhoidal and nontyphoidal Salmonella spp. Leptospirosis and arboviral infections (alphaviruses and flaviviruses) were documented. The lessons learned and early results from the development of this multisectoral surveillance system provide the knowledge, infrastructure, and workforce capacity to serve as a foundation to enhance the capacity to detect, report, and rapidly respond to wide-ranging public health concerns in Uganda.
TL;DR: The protective efficacy of IPTp with DHA-PQ was strongly associated with higher drug exposure and modeling suggests that daily or weekly administration of lower dosages of PQ, compared to standard dosing, will maintain PQ trough levels above target concentrations with reduced PQ peak levels, potentially limiting toxicity.
Abstract: Background Dihydroartemisinin-piperaquine (DHA-PQ) is highly efficacious as intermittent preventive therapy for malaria during pregnancy (IPTp). Determining associations between piperaquine (PQ) exposure, malaria risk, and adverse birth outcomes informs optimal dosing strategies. Methods Human immunodeficiency virus-uninfected pregnant women (n = 300) were enrolled in a placebo-controlled trial of IPTp at 12-20 weeks' gestation and randomized to sulfadoxine-pyrimethamine every 8 weeks, DHA-PQ every 8 weeks, or DHA-PQ every 4 weeks during pregnancy. Pharmacokinetic sampling for PQ was performed every 4 weeks, and an intensive pharmacokinetic substudy was performed in 30 women at 28 weeks' gestation. Concentration-effect relationships were assessed between exposure to PQ; the prevalence of Plasmodium falciparum infection during pregnancy; outcomes at delivery including placental malaria, low birth weight, and preterm birth; and risks for toxicity. Simulations of new dosing scenarios were performed. Results Model-defined PQ target venous plasma concentrations of 13.9 ng/mL provided 99% protection from P. falciparum infection during pregnancy. Each 10-day increase in time above target PQ concentrations was associated with reduced odds of placental parasitemia, preterm birth, and low birth weight, though increases in PQ concentrations were associated with QT interval prolongation. Modeling suggests that daily or weekly administration of lower dosages of PQ, compared to standard dosing, will maintain PQ trough levels above target concentrations with reduced PQ peak levels, potentially limiting toxicity. Conclusions The protective efficacy of IPTp with DHA-PQ was strongly associated with higher drug exposure. Studies of the efficacy and safety of alternative DHA-PQ IPTp dosing strategies are warranted. Clinical trials registration NCT02163447.
TL;DR: For HIV-infected pregnant women receiving efavirenz, low daily DHA-PQ dosing was predicted to improve protection against parasitemia and reduce risk of toxicity compared to monthly dosing.
Abstract: Background A monthly treatment course of dihydroartemisinin-piperaquine (DHA-PQ) effectively prevents malaria during pregnancy. However, a drug-drug interaction pharmacokinetic (PK) study found that pregnant human immunodeficiency virus (HIV)-infected women receiving efavirenz-based antiretroviral therapy (ART) had markedly reduced piperaquine (PQ) exposure. This suggests the need for alternative DHA-PQ chemoprevention regimens in this population. Methods Eighty-three HIV-infected pregnant women who received monthly DHA-PQ and efavirenz contributed longitudinal PK and corrected QT interval (QTc) (n = 25) data. Population PK and PK-QTc models for PQ were developed to consider the benefits (protective PQ coverage) and risks (QTc prolongation) of alternative DHA-PQ chemoprevention regimens. Protective PQ coverage was defined as maintaining a concentration >10 ng/mL for >95% of the chemoprevention period. Results PQ clearance was 4540 L/day. With monthly DHA-PQ (2880 mg PQ), 96% of women, respectively. All regimens were safe, with ≤2% of women predicted to have ≥30 msec QTc increase. Conclusions For HIV-infected pregnant women receiving efavirenz, low daily DHA-PQ dosing was predicted to improve protection against parasitemia and reduce risk of toxicity compared to monthly dosing. Clinical trials registration NCT02282293.
TL;DR: The systems capacity building approach to PhD training is an efficient and productive training model that allowed strong outputs at lower cost and with relatively few additional mentors to rapidly achieve a critical mass of independent scientists able to conduct original research and mentor others.
Abstract: Introduction: High quality PhD training in sub-Saharan Africa is important to strengthen research evidence to advance development and health. Training a critical mass of independent investigators capable of original scientific research requires strong mentorship, research environments, and international networks. We sought to iteratively improve a PhD training model in Uganda through systems capacity building. Methods: PhD students were selected through a rigorous competitive application and selection process, which included a written proposal and a face-to-face panel interview. The program provided administrative support, paid tuition fees, tools (space, equipment, research money), skills (short research courses on study design, biostatistics, manuscript and grant writing), and infrastructure (finance, grants management support, and lab infrastructure). Guidance to identify local and international mentorship was also provided in addition to two to three group meetings per year where data was presented and progress assessed by the program leaders in addition to available local mentors. Results: Seventeen PhD students were selected, and fifteen will complete training through the MEPI-MESAU program. To date, 60% have completed, including 2 students who started 2 years into the program. So far, 169 publications have been published in the peer-reviewed literature. Our PhD students have supervised and mentored 65 Master’s students, which illustrates the cascade effect of PhD training on the academic medical school environment. Conclusions: The systems capacity building approach to PhD training is an efficient and productive training model that allowed strong outputs at lower cost and with relatively few additional mentors to rapidly achieve a critical mass of independent scientists able to conduct original research and mentor others.
TL;DR: Key outcomes of this approach have been the completion of formal training of the first interventional cardiologists and heart failure specialists in the country, establishment of 4 integrated regional centers of excellence in rheumatic heart disease care, a penicillin distribution and adherence support program focused on retention in care, access to imaging technology, and in-country capabilities to treat advanced rheatic valve disease.
Abstract: In this case study, we describe an ongoing approach to develop sustainable acute and chronic cardiovascular care infrastructure in Uganda that involves patient and provider participation. Leveraging strong infrastructure for HIV/AIDS care delivery, University Hospitals Harrington Heart and Vascular Institute and Case Western Reserve University have partnered with U.S. and Ugandan collaborators to improve cardiovascular capabilities. The collaboration has solicited innovative solutions from patients and providers focusing on education and advanced training, penicillin supply, diagnostic strategy (e.g., hand-held ultrasound), maternal health, and community awareness. Key outcomes of this approach have been the completion of formal training of the first interventional cardiologists and heart failure specialists in the country, establishment of 4 integrated regional centers of excellence in rheumatic heart disease care with a national rheumatic heart disease registry, a penicillin distribution and adherence support program focused on retention in care, access to imaging technology, and in-country capabilities to treat advanced rheumatic heart valve disease.
TL;DR: Links between MTB genotype-matched cases were only identifiable via shared locations, healthcare locations in particular, rather than named contacts, which suggests most transmission is occurring between casual contacts, and emphasizes the need for improved infection control in healthcare settings in rural Africa.
Abstract: Author(s): Chamie, Gabriel; Kato-Maeda, Midori; Emperador, Devy M; Wandera, Bonnie; Mugagga, Olive; Crandall, John; Janes, Michael; Marquez, Carina; Kamya, Moses R; Charlebois, Edwin D; Havlir, Diane V | Abstract: IntroductionIncomplete understanding of TB transmission dynamics in high HIV prevalence settings remains an obstacle for prevention. Understanding where transmission occurs could provide a platform for case finding and interrupting transmission.MethodsFrom 2012-2015, we sought to recruit all adults starting TB treatment in a Ugandan community. Participants underwent household (HH) contact investigation, and provided names of social contacts, sites of work, healthcare and socializing, and two sputum samples. Mycobacterium tuberculosis culture-positive specimens underwent 24-loci MIRU-VNTR and spoligotyping. We sought to identify epidemiologic links between genotype-matched cases by analyzing social networks and mapping locations where cases reported spending ≥12 hours over the one-month pre-treatment. Sites of spatial overlap (≤100m) between genotype-matched cases were considered potential transmission sites. We analyzed social networks stratified by genotype clustering status, with cases linked by shared locations, and compared network density by location type between clustered vs. non-clustered cases.ResultsOf 173 adults with TB, 131 (76%) were enrolled, 108 provided sputum, and 84/131 (78%) were MTB culture-positive: 52% (66/131) tested HIV-positive. Of 118 adult HH contacts, 105 (89%) were screened and 3 (2.5%) diagnosed with active TB. Overall, 33 TB cases (39%) belonged to 15 distinct MTB genotype-matched clusters. Within each cluster, no cases shared a HH or reported shared non-HH contacts. In 6/15 (40%) clusters, potential epidemiologic links were identified by spatial overlap at specific locations: 5/6 involved health care settings. Genotype-clustered TB social networks had significantly greater network density based on shared clinics (pl0.001) and decreased density based on shared marketplaces (pl0.001), compared to non-clustered networks.ConclusionsIn this molecular epidemiologic study, links between MTB genotype-matched cases were only identifiable via shared locations, healthcare locations in particular, rather than named contacts. This suggests most transmission is occurring between casual contacts, and emphasizes the need for improved infection control in healthcare settings in rural Africa.
TL;DR: The prevalence of asthma is higher in PLHIV than in those without HIV, and HIV interacts synergistically with other known asthma risk factors, and Clinicians should consider asthma as a possible diagnosis inPLHIV presenting with respiratory symptoms.
Abstract: HIV and asthma are highly prevalent diseases in Africa but few studies have assessed the impact of HIV on asthma prevalence in high HIV burden settings The objective of this analysis was to compare the prevalence of asthma among persons living with HIV (PLHIV) and those without HIV participating in the Uganda National Asthma Survey (UNAS) UNAS was a population-based survey of persons aged ≥12 years Asthma was diagnosed based on either self-reported current wheeze concurrently or within the prior 12 months; physician diagnosis; or use of asthma medication HIV was defined based on confidential self-report We used Poisson regression with robust standard errors to estimate asthma prevalence and the prevalence ratio (PR) for HIV and asthma Of 3416 participants, 2067 (605%) knew their HIV status and 103 (50%) were PLHIV Asthma prevalence was 155% among PLHIV and 91% among those without HIV, PR 172, (95%CI 107–275, p = 0025) HIV modified the association of asthma with the following factors, PLHIV vs not PLHIV: tobacco smoking (12% vs 8%, p = < 0001), biomass use (11% vs 7%, p = < 0001), allergy (17% vs 11%, p = < 0001), family history of asthma (17% vs 11%, p = < 0001), and prior TB treatment (15% vs 10%, p = < 0001) In Uganda the prevalence of asthma is higher in PLHIV than in those without HIV, and HIV interacts synergistically with other known asthma risk factors Additional studies should explore the mechanisms underlying these associations Clinicians should consider asthma as a possible diagnosis in PLHIV presenting with respiratory symptoms
TL;DR: The evidence generated from this review will help guide policy makers on the potential re-emerging role of chloroquine in malaria treatment as well as establish the extent ofchloroquine resistance reversal in malaria-endemic countries.
Abstract: Malaria remains one of the leading causes of morbidity and mortality in most low- and middle-income countries Chloroquine is a previously cheap and effective antimalarial agent whose loss to resistance resulted in more than doubling of malaria-related mortality in malaria-endemic countries Recently, chloroquine sensitivity is re-emerging among Plasmodium falciparum parasites which gives hope for malaria control and treatment efforts globally The aim of the current review is to establish the prevalence of chloroquine resistance alleles among P falciparum parasites in malaria-endemic areas after change in malaria treatment policy The articles will be obtained from search of MEDLINE via PubMed, SCOPUS, and EMBASE data bases The Mesh terms will be used in article search Boolean operators (“AND,” “OR”) will be used in article search The article search will be done independently by two librarians The PRISMA-P statement will be used to guide the conduct and reporting of the systematic review STREGA guideline will be used in developing data abstraction form for the review Data abstraction will be done by two independent reviewers, Kappa statistic will be calculated, and any discrepancies resolved by discussion Data analysis will be done using STATA ver 130 The level of heterogeneity in the articles will be established by using the I2-statistic Publication bias will be assessed using funnel plot Random effects analysis will be used The review seeks to establish the extent of chloroquine resistance reversal in malaria-endemic countries The evidence generated from this review will help guide policy makers on the potential re-emerging role of chloroquine in malaria treatment The systematic review protocol has been registered in PROSPERO with registration number CRD42018083957
TL;DR: Children in study sites with high ambient air pollution had lower lung function than those in sites with low ambient airpollution, and urban residence, underweight, exposure to biomass smoke and cough were associated withLower lung function.
Abstract: Air pollution is a major cause of sub-optimal lung function and lung diseases in childhood and adulthood. In this study we compared the lung function (measured by spirometry) of 537 Ugandan children, mean age 11.1 years in sites with high (Kampala and Jinja) and low (Buwenge) ambient air pollution levels, based on the concentrations of particulate matter smaller than 2.5 micrometres in diameter (PM2.5). Factors associated with lung function were explored in a multiple linear regression model. PM2.5 level in Kampala, Jinja and Buwenge were 177.5 µg/m³, 96.3 µg/m³ and 31.4 µg/m³ respectively (p = 0.0000). Respectively mean forced vital capacity as % of predicted (FVC%), forced expiratory volume in one second as % of predicted (FEV₁%) and forced expiratory flow 25⁻75% as % of predicted (FEF25⁻75%) of children in high ambient air pollution sites (Kampala and Jinja) vs. those in the low ambient air pollution site (Buwenge subcounty) were: FVC% (101.4%, vs. 104.0%, p = 0.043), FEV₁% (93.9% vs. 98.0, p = 0.001) and FEF25⁻75% (87.8 vs. 94.0, p = 0.002). The proportions of children whose %predicted parameters were less than 80% predicted (abnormal) were higher among children living in high ambient air pollution than those living in lower low ambient air pollutions areas with the exception of FVC%; high vs. low: FEV1 < 80%, %predicted (12.0% vs. 5.3%, p = 0.021) and FEF25⁻75 < 80%, %predicted (37.7% vs. 29.3%, p = 0.052) Factors associated with lung function were (coefficient, p-value): FVC% urban residence (-3.87, p = 0.004), current cough (-2.65, p = 0.048), underweight (-6.62, p = 0.000), and overweight (11.15, p = 0.000); FEV₁% underweight (-6.54, p = 0.000) and FEF25⁻75% urban residence (-8.67, p = 0.030) and exposure to biomass smoke (-7.48, p = 0.027). Children in study sites with high ambient air pollution had lower lung function than those in sites with low ambient air pollution. Urban residence, underweight, exposure to biomass smoke and cough were associated with lower lung function.
TL;DR: Data from a large population-representative sample of households in east Africa showed a strong association between the health of HIV-positive persons and economic outcomes and the association of high CD4 counts with improved outcomes is consistent with the hypothesis that early ART initiation can avert declines in employment and other economic outcomes.
Abstract: Author(s): Jakubowski, Aleksandra; Snyman, Katherine; Kwarisiima, Dalsone; Sang, Norton; Burger, Rachel; Balzer, Laura; Clark, Tamara; Chamie, Gabriel; Shade, Starley; Cohen, Craig; Bukusi, Elizabeth; Charlebois, Edwin; Kamya, Moses; Petersen, Maya; Havlir, Diane; Thirumurthy, Harsha | Abstract: BackgroundCountry decisions to scale-up "test and treat" approaches for HIV depend on consideration of both the health and economic consequences of such investments. Evidence about economic impacts of expanded antiretroviral therapy (ART) provision is particularly relevant for decisions regarding foreign assistance levels for HIV/AIDS programs. We used baseline data from the Sustainable East Africa Research in Community Health (SEARCH) cluster randomized controlled trial in Kenya and Uganda to examine the association between HIV status, CD4+ T-cell counts, viral suppression, and multiple indicators of economic well-being.Methods and findingsSocio-economic surveys were conducted in households with HIV-positive and HIV-negative adults sampled after a census of 32 communities participating in the SEARCH trial (NCT01864603). Data were obtained for 11,500 individuals from 5,884 households in study communities. Participants were stratified based on their own HIV status as well as CD4 counts and viral suppression status if they were HIV-positive. HIV-negative participants residing in households with no HIV-positive adults were considered separately from HIV-negative participants residing in households with ≥1 HIV-positive adult. Generalized estimating equation models were used to examine the relationship between HIV status, CD4 counts, ART, viral suppression, and outcomes of employment, self-reported illness, lost time from usual activities due to illness, healthcare utilization, health expenditures, and hospitalizations. In all models, HIV-negative participants in households with no HIV-positive persons were the reference group. There was no significant difference in the probability of being employed between HIV-positive participants with CD4g500 and the reference group of HIV-negative participants residing in households with no HIV-positive adults (marginal effect, ME, 1.49 percentage points; 95% confidence interval, CI, -1.09, 4.08). However, HIV-positive participants with CD4 351-500 were less likely to be employed than the reference group (ME -4.50, 95% CI -7.99, -1.01), as were HIV-positive participants with CD4 ≤350 (ME -7.41, 95% CI -10.96, -3.85). Similarly, there was no significant difference in employment likelihood between HIV-negative participants who resided in households with a CD4g500 HIV-positive person and the reference group (ME -1.78, 95% CI -5.16, 1.59). HIV-negative participants residing with an HIV-positive person with CD4 351-500, however, were less likely to be employed than the reference group (ME -7.03, 95% CI -11.49, -2.57), as were people residing with a household member with CD4 ≤350 (ME -6.28, 95% CI -10.76, -1.80). HIV-positive participants in all CD4 categories were more likely to have lost time from usual activities due to illness and have incurred healthcare expenditures. Those with CD4g500 had better economic outcomes than those with CD4 351-500, even among those not virally suppressed (p = 0.004) and not on ART (p = 0.01).ConclusionsData from a large population-representative sample of households in east Africa showed a strong association between the health of HIV-positive persons and economic outcomes. The findings suggest there may be economic benefits associated with maintaining high CD4 counts, both for HIV-positive persons and their HIV-negative household members. The association of high CD4 counts with improved outcomes is consistent with the hypothesis that early ART initiation can avert declines in employment and other economic outcomes. Prospective longitudinal evaluation is needed to assess the causal impact of early ART initiation on economic functioning of households.
TL;DR: The activities undertaken by the Malaria Capacity Development Consortium (MCDC) to support the careers of PhD students and postdoctoral fellows undertaking research on malaria at five African universities are described.
Abstract: Substantial progress has been made in the control of malaria in Africa but much remains to be done before malaria elimination on the continent can be achieved. Further progress can be made by enhancing uptake of existing control tools but, in high transmission areas, additional tools will be needed. Development and evaluation of these new tools will require a substantial cadre of African scientists well trained in many different disciplines. This paper describes the activities undertaken by the Malaria Capacity Development Consortium (MCDC) to support the careers of PhD students and postdoctoral fellows undertaking research on malaria at five African universities. A systematic assessment of constraints on PhD training and research support systems was undertaken at each partner African university at the beginning of the programme and many of these constraints were remedied. The success of the programme is shown by the fact that 18 of the 21 PhD students recruited to the programme completed their theses successfully within a 4-year period and that all 27 scientists recruited to the postdoctoral programme were still working in Africa on its completion. The work of the consortium will be continued through Career Development Groups established at each partner university and at an affiliated institution at the University of Nairobi and through the Developing Excellence in Leadership, Training and Science award from the Wellcome Trust made to one of the African partners. Lessons learnt during the MCDC programme may help the planning and execution of other research capacity development programmes in Africa.
TL;DR: This review will focus on establishing the K13-gene polymorphisms among Plasmodium falciparum parasites reported from previous studies in malaria-affected countries.
Abstract: Malaria control and prevention efforts continue to rely heavily on the use of medicines especially artemisinin agents. However, currently, the emergence of artemisinin resistance threatens this effort globally. The K13-gene polymorphisms associated with artemisinin resistance have been detected in Southeast Asia. In countries outside Southeast Asia, artemisinin resistance has not yet been confirmed. The articles will be obtained from the search of MEDLINE via PubMed, Scopus, EMBASE, and LILACS/VHL databases. Mesh terms will be used in the article search. Boolean operators (“AND”, “OR”) will be used in the article search. Article search will be done independently by two librarians (RS and AK). The articles will be screened for inclusion using set criteria and following the PRISMA guidelines. Data extraction will be done by two independent reviewers (NL and BB), Kappa statistic will be calculated, and any discrepancies resolved by discussion. Heterogeneity in the articles will be established using I2 statistic. This review will focus on establishing the K13-gene polymorphisms among Plasmodium falciparum parasites reported from previous studies in malaria-affected countries. Artemisinin resistance has not been widely reported among parasites in Africa and other malaria-endemic countries outside Southeast Asia. However, several studies on artemisinin resistance have reported different K13-gene polymorphisms from the validated mutations found in Southeast Asia. This study will collate evidence from previous studies on the commonly reported K13 -gene polymorphisms among P. falciparum parasites in malaria-affected countries. PROSPERO CRD 42018084624