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Polygamy is the practice of marriage to multiple partners. Approximately 6-11% of households in Uganda and 4-11% of households in Kenya are polygamous. The complex families produced by polygamous marriage customs give rise to additional considerations for healthcare providers and public health messaging around HIV care. Using 27 in-depth, semi-structured qualitative interviews with participants in two studies in rural Kenya and Uganda, we analysed challenges and opportunities that polygamous families presented in the diagnosis, treatment and prevention of HIV, and provider roles in improving HIV outcomes in these families. Overall, prevention methods seemed more justifiable to families where co-wives live far apart than when all members live in the same household. In treatment, diagnosis of one member did not always lead to disclosure to other members, creating an adverse home environment; but sometimes diagnosis of one wife led not only to diagnosis of the other, but also to greater household support.

Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.

Objective To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA).Design Systematic review and meta-analysis.Data sources We searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022.Eligibility criteria for studies Randomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA.Data extraction and synthesis Seven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention.Results Of 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26).Conclusions A hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs.PROSPERO registration number CRD42020219363.

Economic incentives to promote health behavior change are highly efficacious for substance use disorders as well as increased medication adherence. Knowledge about participants' experiences with and perceptions of incentives is needed to understand their mechanisms of action and optimize future incentive-based interventions. The Drinkers' Intervention to Prevent Tuberculosis (DIPT) trial enrolled people with HIV (PWH) in Uganda with latent tuberculosis and unhealthy alcohol use in a 2x2 factorial trial that incentivized recent alcohol abstinence and isoniazid (INH) adherence on monthly urine testing while on INH preventive therapy. We interviewed 32 DIPT study participants across trial arms to explore their perspectives on this intervention. Participants described 1) satisfaction with incentives of sufficient size that allowed them to purchase items that improved their quality of life, 2) multiple ways in which incentives were motivating, from gamification of "winning" through support of pre-existing desire to improve health to suggesting variable effects of extrinsic and intrinsic motivation, and 3) finding value in learning results of increased clinical monitoring. To build effective incentive programs to support both reduced substance use and increased antimicrobial adherence, we recommend carefully selecting incentive magnitude as well as harnessing both intrinsic motivation to improve health and extrinsic reward of target behavior. In addition to these participant-described strengths, incorporating results of clinical monitoring related to the incentive program that provide participants more information about their health may also contribute to health-related empowerment.

Abstract Introduction Unhealthy alcohol use significantly contributes to viral non‐suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce alcohol use can improve viral suppression among PWH with unhealthy alcohol use in sub‐Saharan Africa (SSA). Methods As part of the SEARCH study (NCT04810650), we conducted an individually randomized trial in Kenya and Uganda of a brief, skills‐based alcohol intervention among PWH with self‐reported unhealthy alcohol use (Alcohol Use Disorders Identification Test–Consumption [AUDIT‐C], prior 3 months, ≥3/female; ≥4/male) and at risk of viral non‐suppression, defined as either recent HIV viral non‐suppression (≥400 copies/ml), missed visits, out of care or new diagnosis. The intervention included baseline and 3‐month in‐person counselling sessions with interim booster phone calls every 3 weeks. The primary outcome was HIV viral suppression (200 ng/ml (RR 0.97, 95% CI: 0.92–1.02). Conclusions In a randomized trial of 401 PWH with unhealthy alcohol use and risk for viral non‐suppression, a brief alcohol intervention reduced unhealthy alcohol use but did not affect viral suppression at 24 weeks. Brief alcohol interventions have the potential to improve the health of PWH in SSA by reducing alcohol use, a significant driver of HIV‐associated co‐morbidities.

Summary: Background: Malaria in pregnancy (MIP) causes higher morbidity in primigravid compared to multigravid women; however, the correlates and mechanisms underlying this gravidity-dependent protection remain incompletely understood. We aimed to compare the cellular immune response between primigravid and multigravid women living in a malaria-endemic region and assess for correlates of protection against MIP. Methods: We characterised the second trimester cellular immune response among 203 primigravid and multigravid pregnant women enrolled in two clinical trials of chemoprevention in eastern Uganda, utilizing RNA sequencing, flow cytometry, and functional assays. We compared responses across gravidity and determined associations with parasitaemia during pregnancy and placental malaria. Findings: Using whole blood RNA sequencing, no significant differentially expressed genes were identified between primigravid (n = 12) and multigravid (n = 11) women overall (log 2(FC) > 2, FDR < 0.1). However, primigravid (n = 49) women had higher percentages of malaria-specific, non-naïve CD4+ T cells that co-expressed IL-10 and IFNγ compared with multigravid (n = 85) women (p = 0.000023), and higher percentages of these CD4+ T cells were associated with greater risks of parasitaemia in pregnancy (Rs = 0.49, p = 0.001) and placental malaria (p = 0.0073). These IL-10 and IFNγ co-producing CD4+ T cells had a genomic signature of Tr1 cells, including expression of transcription factors cMAF and BATF and cell surface makers CTLA4 and LAG-3. Interpretation: Malaria-specific Tr1 cells were highly prevalent in primigravid Ugandan women, and their presence correlated with a higher risk of malaria in pregnancy. Understanding whether suppression of Tr1 cells plays a role in naturally acquired gravidity-dependent immunity may aid the development of new vaccines or treatments for MIP. Funding: This work was funded by NIH (PO1 HD059454, U01 AI141308, U19 AI089674, U01 AI155325, U01 AI150741), the March of Dimes (Basil O'Connor award), and the Bill and Melinda Gates Foundation (OPP 1113682).

Purpose – The purpose of this paper is to examine the influence of innovation indicators: Internet usage, patent rights, innovation in exporting countries and innovation in the importing country on the export competitiveness of firms in the East African Community (EAC). Design/methodology/approach – The study adopted the structural gravity model and the Poisson Pseudo Maximum Likelihood a nonlinear estimation method that was applied in STATA on balanced panel data from 2007 to 2018. Data were obtained from World Bank International Trade Center and World Bank development indicators. Findings – Results show that innovation in the importing country, innovation in the exporting country and patent rights of exports are positive and significant predictors of export competitiveness in developing countries. While Internet usage is an insignificant predictor in the EAC. Research limitations/implications – There is a need to examine the complicated nature of the EAC economy to further this study's findings. Practical implications – Exporting countries need to take deeper reforms as regards structural transformation to enable firms to integrate into the Global Value Chains (GVCs) to enable them to increase their productivity by reviewing the existing policies to match the changes in the market. Originality/value – This study explains the complex dynamic interactions of technological innovation indicators in the EAC using quantitative data and that this interaction has an effect on the export competitiveness in import-oriented countries with less harmonization in their trade policies.

Despite being key drivers of protective antibodies against malaria, little is known regarding the host and parasite factors that influence CD4 T-follicular helper cell and antibody development. Authors utilise samples from a study of children living in an area of high malaria transmission in Uganda, to characterize Tfh cells and functional antibodies to multiple parasites stages.

Abstract Background People living with HIV (PLHIV) have an increased risk of developing active tuberculosis (TB). To reduce the burden of TB among PLHIV, the World Health Organization (WHO) recommends systematic TB screening followed by (1) confirmatory TB testing for all who screen positive and (2) TB preventive therapy (TPT) for all TPT-eligible PLHIV who screen negative. Symptom-based screening remains the standard of care in most high TB burden settings, including Uganda. Despite having high sensitivity for active TB among antiretroviral-naïve PLHIV, symptom screening has poor specificity; as such, many high-risk PLHIV without active TB are not referred for TPT. C-reactive protein (CRP) is a promising alternative strategy for TB screening that has comparable sensitivity and higher specificity than symptom screening, and was endorsed by WHO in 2021. However, the impact of CRP-based TB screening on TB burden for PLHIV remains unclear. Methods TB SCRIPT (TB Screening Improves Preventive Therapy Uptake) is a phase 3, multi-center, single-blinded, individual (1:1) randomized controlled trial evaluating the effectiveness of CRP-based TB screening on clinical outcomes of PLHIV. The trial aims to compare the effectiveness of a TB screening strategy based on CRP levels using a point-of-care (POC) assay on 2-year TB incidence and all-cause mortality (composite primary trial endpoint) and prevalent TB case detection and uptake of TPT (intermediate outcomes), relative to symptom-based TB screening (current practice). Discussion This study will be critical to improving selection of eligible PLHIV for TPT and helping guide the scale-up and integration of TB screening and TPT activities. This work will enable the field to improve TB screening by removing barriers to TPT initiation among eligible PLHIV, and provide randomized evidence to inform and strengthen WHO guidelines. Trial registration ClinicalTrials.gov NCT04557176. Registered on September 21, 2020.

Causes of non-malarial fevers in sub-Saharan Africa remain understudied. We hypothesized that metagenomic next-generation sequencing (mNGS), which allows for broad genomic-level detection of infectious agents in a biological sample, can systematically identify potential causes of non-malarial fevers. The 212 participants in this study were of all ages and were enrolled in a longitudinal malaria cohort in eastern Uganda. Between December 2020 and August 2021, respiratory swabs and plasma samples were collected at 313 study visits where participants presented with fever and were negative for malaria by microscopy. Samples were analyzed using CZ ID, a web-based platform for microbial detection in mNGS data. Overall, viral pathogens were detected at 123 of 313 visits (39%). SARS-CoV-2 was detected at 11 visits, from which full viral genomes were recovered from nine. Other prevalent viruses included Influenza A (14 visits), RSV (12 visits), and three of the four strains of seasonal coronaviruses (6 visits). Notably, 11 influenza cases occurred between May and July 2021, coinciding with when the Delta variant of SARS-CoV-2 was circulating in this population. The primary limitation of this study is that we were unable to estimate the contribution of bacterial microbes to non-malarial fevers, due to the difficulty of distinguishing bacterial microbes that were pathogenic from those that were commensal or contaminants. These results revealed the co-circulation of multiple viral pathogens likely associated with fever in the cohort during this time period. This study illustrates the utility of mNGS in elucidating the multiple potential causes of non-malarial febrile illness. A better understanding of the pathogen landscape in different settings and age groups could aid in informing diagnostics, case management, and public health surveillance systems.

BackgroundStool is a potential sample for diagnosing Mycobacterium tuberculosis (Mtb) in patients with difficulty in expectorating. However, high mycobacterial culture contamination rates and Xpert MTB/RIF Ultra test error rates on stool samples have limited its use. OMNIgene SPUTUM (OM-S) is a sample transport reagent with characteristics of sputum decontamination while maintaining viable Mtb. We evaluated the impact of OM-S on Mtb diagnostic yield from stool using smear microscopy, Xpert MTB/RIF Ultra, and culture among presumptive TB patients.MethodsPaired stool and expectorated sputum samples were collected from consecutive Ugandan adults undergoing diagnostic evaluation for pulmonary TB between June 2018 and June 2019. Stool was divided into 2 portions: one was homogenized in OM-S (OM-S stool) and the other in PBS (PBS stool) as control. Both sputum and processed stool were tested for Mtb using concentrated smear fluorescence microscopy (CFM), Xpert MTB/RIF Ultra (Xpert) and Mycobacteria Growth Indicator Tube (MGIT) culture. Sensitivity, specificity, and predictive values for each test were calculated against sputum MGIT culture as the reference standard.ResultsOf the 200 participants, 120 (60%) were male, 73 (37%) were HIV positive (median CD4 120 cells/uL (IQR 43-297)) and 128 (64%) had confirmed pulmonary TB by sputum MGIT culture. Seven (4%) OM-S stool Xpert samples reported errors while 47 (25%) and 103 (61%) were contaminated on OM-S stool MGIT and PBS stool MGIT, respectively. OM-S stool MGIT was able to accurately diagnose 56 of the contaminated PBS stool MGIT samples compared to only 5 of the contaminated OM-S stool MGIT samples diagnosed by PBS stool MGIT. Sensitivity (95% Confidence Interval, CI) 89% (83-94) for OM-S stool Xpert was higher compared to that of OM-S stool MGIT 60% (51-69) and PBS stool MGIT 42% (32-52). Specificity (95%CI) 91% (82-97) was also higher for OM-S stool Xpert compared to OM-S stool MGIT 64% (51-75) and PBS stool MGIT 26% (16-38).ConclusionStool processed with OM-S showed potential to improve Mtb diagnostic yield and reduce rates of indeterminate results when tested on Xpert and MGIT culture. The method may thus be of value in Mtb detection among patients with difficulty to expectorate.

Purpose – The purpose of this paper is to examine the influence of export logistics components: shipment arrangements, timely delivery, customs quality, trade infrastructure, and tracking and tracing on export competitiveness of firms in the East African Community (EAC). Design/methodology/approach – The study adopted the Structural Gravity Model and the Poisson pseudo-maximum likelihood (PPML). PPML a nonlinear estimation method was applied in STATA on a balanced panel data for the period of 2007–2018. Data were obtained from World Bank International Trade Centre (ITC), World Bank Logistics Performance Index (LPI) and World Bank development indicators. Findings – Results show that timely delivery and tracking and tracing of exports are positive and significant predictors of export competitiveness in EAC countries. Conversely, shipment arrangements, customs quality and trade infrastructure have no influence on export competitiveness. Research limitations/implications – The results of this study show that export logistics components of shipment arrangements, customs quality and trade infrastructure do not matter at the present in improving export competitiveness in the EAC. There is a need to examine the intricate nature of the EAC economy to further this study's findings. Practical implications – The EAC partner states should embrace deep integration by removing the behind the border trade barriers in addition to other trade restrictions, to create a common economic space among member states. This will further shrink the delivery time and the tracking and tracing of exports hence improving the competitiveness of EAC exports within the region and outside. Also, common and harmonized trade policies and regulations should be implemented through mutual recognition agreements where countries agree to recognize one another's conformity assessments. Originality/value – This study explains the complex dynamic interactions of export logistics factors in the EAC using quantitative data and that this interaction has an effect on the export competitiveness in import-dominated countries with less harmonization in their trade policies.

Abstract Background Intensive malaria control may have additional benefits beyond reducing the incidence of symptomatic malaria. We compared antibiotic treatment of children before and after the implementation of highly effective malaria control interventions in Tororo, a historically high transmission area of Uganda. Methods Two successive cohorts of children, aged 0.5 to 10 years, were followed from September 2011 to October 2019 in a dedicated study clinic. Universal distribution of long-lasting insecticidal nets was conducted in 2013 and 2017. Sustained indoor residual spraying of insecticide (IRS) was initiated in December 2014. Generalized linear mixed-effects models were used to compare the incidence of antimalarial and antibiotic treatments before and after vector control measures were implemented. Results Comparing the period prior to the implementation of IRS to the period after IRS had been sustained for 4–5 years, the adjusted incidence of malaria treatments decreased from 2.68 to 0.05 per person-year (incidence rate ratio [IRR] = 0.02, 95% CI 0.01–0.03, p < 0.001), and the adjusted incidence of antibiotic treatments decreased from 4.14 to 1.26 per person-year (IRR = 0.30, 95% CI 0.27–0.34, p < 0.001). The reduction in antibiotic usage was primarily associated with fewer episodes of symptomatic malaria and fewer episodes of fever with sub-microscopic parasitemia, both of which were frequently treated with antibiotics. Conclusions In a historically high transmission setting, the implementation of highly effective vector control interventions was followed by a marked reduction in antibiotic treatment of children. This added benefit of malaria control could have important implications for antibiotic prescribing practices, efforts to curtail antimicrobial resistance, and health system costs.

Introduction There is a high burden of hypertension (HTN) among HIV-infected people in Uganda. However, capacity to prevent, diagnose and treat HTN is suboptimal. This study seeks to leverage the existing HIV-related infrastructure in primary care health facilities (HFs) using the integrated HIV/HTN care model to improve health outcomes of patients with HIV and HTN.Methods and analysis Integrated HIV/HTN study a type-1 effectiveness/implementation cluster randomised trial, will evaluate the effectiveness of a multicomponent model intervention in 13 districts randomised to the intervention arm compared with 13 districts randomised to control. Two randomly selected HFs per district and their patients will be eligible to participate. The intervention will comprise training of primary healthcare (PHC) providers followed by regular supervision, integration of HTN care into HIV clinics, improvement of the health management information system, IT-based messaging to improve communication among frontline PHCs and district-level managers. HTN care guidelines, sphygmomanometers, patient registers and a buffer stock of essential drugs will be provided to HFs in both study arms. We will perform cross-sectional surveys at baseline, 12 and 24 months, on a random sample of patients attending HFs to measure effectiveness of the integrated care model between 2021 and 2024. We will perform in-depth interviews of providers, patients and healthcare managers to assess barriers and facilitators of integrated care. We will measure the cost of the intervention through microcosting and time-and-motion studies. The outcomes will be analysed taking the clustered structure of the data set into account.Ethics and dissemination Ethics approval has been obtained from the Research Ethics Committees at London School of Hygiene and Tropical Medicine, and Makerere University School of Medicine. All participants will provide informed consent prior to study inclusion. Strict confidentiality will be applied throughout. Findings will be disseminated to public through meetings, and publications.Trial registration number NCT04624061

Background: Diabetic foot ulcer is a common cause of mortality among patients admitted to Mulago hospital. Peripheral neuropathy and peripheral arterial disease are the major risk factors for diabetic foot ulceration and the severity of these two conditions may determine treatment options and ulcer outcomes. General objective: The study assessed the clinical presentation of foot ulcers in diabetic patients and identified the common bacterial isolates from diabetic foot ulcers and their susceptibility patterns. Methods: This was a prospective study involving 60 consecutive patients with diabetic foot ulcers admitted to the endocrinology unit at Mulago hospital between July and December 2010. Patients were recruited after the provision of written informed consent. Deep tissue swabs from the ulcers were then taken at debridement for both aerobic and anaerobic cultures and susceptibility tests using standard microbiological methods. Results: Of the 60 patients, 57% had neuroischemic foot ulcers, 18% had neuropathic ulcers, 18% had ischemic ulcers and 7% had unclassified ulcers. 98.3% of the samples grew 93 aerobic bacteria and no anaerobe was isolated. Polymicrobial infection occurred in 41% of samples of which 10% had mixed growth. 80.6% of the isolates were Gram-negative aerobes, mainly E.coli Klebsiella, Pseudomonas, and Proteus while eighteen (19.4%) were Gram-positive, mainly Staphylococcus aureus and Enterococcus faecalis. The prevalence of MuMultidrug-resistant organisms (MDRO) was 84% and Methicillin-resistant staphylococcus aureus (MRSA) was 60% while Extended-spectrum beta-lactamases (ESBL) was 43.5%. Conclusion: Diabetic foot ulcers were mostly neuroischemic with moderate neuropathy severity. Infection was mostly due to aerobic Gram-negative organisms with a high prevalence of MDRO, ESBL, and MRSA. Most isolates were susceptible to vancomycin, imipenem, and ciprofloxacin. Recommendation: Deep tissue culture and sensitivity tests should be done to make appropriate antibiotic choices for diabetic patients with foot ulcers.

Abstract Background We aimed to describe the prevalence of PTSD symptoms and its associated factors in persons living with HIV (PLWH) in Uganda who engage in heavy alcohol use. Methods We analyzed baseline data from the Drinkers Intervention to Prevent Tuberculosis study which enrolls PLWH with latent tuberculosis who engage in heavy alcohol consumption. Using the primary care Post Traumatic Stress Disorder (PTSD) screening scale from the DSM-5 (PC-PTSD-5), probable PTSD was defined as reporting ≥3 of 5 assessed symptoms. We conducted the Alcohol Use Disorders Identification Test-Consumption and assessed demographics, smoking, symptoms of depression, and spirituality/religiosity. Results Of 421 participants enrolled from 2018 through 2020, the majority (68.2%) were male, median age was 40 years (interquartile range [IQR]: 32–47), and median AUDIT-C score was 6 [IQR: 4–8]. Half (50.1%) of the participants reported ever experiencing a traumatic event, and 20.7% reported ≥3 symptoms of PTSD. The most commonly reported PTSD symptoms in the past 1 month in the entire sample were avoidance (28.3%), nightmares (27.3%), and being constantly on guard (21.6%). In multivariable logistic regression analyses, level of alcohol use was not associated with probable PTSD (adjusted odds ratio [AOR] for each AUDIT-C point: (1.02; 95% CI: 0.92–1.14; p = 0.69); however, lifetime smoking (AOR 1.89; 95% CI: 1.10–3.24) and reporting symptoms of depression (AOR 1.89; 95% CI: 1.04–3.44) were independently associated with probable PTSD. Conclusions and recommendations A history of traumatic events and probable PTSD were frequently reported among persons who engage in heavy drinking, living with HIV in Uganda. Level of alcohol use was not associated with probable PTSD in this sample of PLWH with heavy alcohol use, however other behavioral and mental health factors were associated with probable PTSD. These data highlight the high prevalence of PTSD in this group, and the need for screening and interventions for PTSD and mental health problems.

Abstract Background Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. This study examined the changing pattern of Anopheles species in three areas of Uganda with markedly different transmission intensities and different levels of vector control. Methods From October 2011 to June 2016 mosquitoes were collected monthly using CDC light traps from 100 randomly selected households in three areas: Walukuba (low transmission), Kihihi (moderate transmission) and Nagongera (high transmission). LLINs were distributed in November 2013 in Walukuba and Nagongera and in June 2014 in Kihihi. IRS was implemented only in Nagongera, with three rounds of bendiocarb delivered between December 2014 and June 2015. Mosquito species were identified morphologically and by PCR (Polymerase Chain Reaction). Results In Walukuba, LLIN distribution was associated with a decline in Anopheles funestus vector density (0.07 vs 0.02 mosquitoes per house per night, density ratio [DR] 0.34, 95% CI: 0.18–0.65, p = 0.001), but not Anopheles gambiae sensu stricto (s.s.) nor Anopheles arabiensis. In Kihihi, over 98% of mosquitoes were An. gambiae s.s. and LLIN distribution was associated with a decline in An. gambiae s.s. vector density (4.00 vs 2.46, DR 0.68, 95% CI: 0.49–0.94, p = 0.02). In Nagongera, the combination of LLINs and multiple rounds of IRS was associated with almost complete elimination of An. gambiae s.s. (28.0 vs 0.17, DR 0.004, 95% CI: 0.002–0.009, p

Abstract Background Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, relatedness of Plasmodium falciparum infections was measured in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rate of 27 infectious bites per person). Methods All infections detected via microscopy or Plasmodium-specific loop mediated isothermal amplification from passive and active case detection during August 2011-March 2012 were genotyped at 26 microsatellite loci, providing data for 349 samples from 230 participants living in 80 households. Pairwise genetic relatedness was calculated using identity by state (IBS). Results As expected, genetic diversity was high (mean heterozygosity [He] = 0.73), and the majority (76.5 %) of samples were polyclonal. Despite the high genetic diversity, fine-scale population structure was detectable, with significant spatiotemporal clustering of highly related infections. Although the difference in malaria incidence between households at higher (mean 1127 metres) versus lower elevation (mean 1015 metres) was modest (1.4 malaria cases per person-year vs. 1.9 per person-year, respectively), there was a significant difference in multiplicity of infection (2.2 vs. 2.6, p = 0.008) and, more strikingly, a higher proportion of highly related infections within households (6.3 % vs. 0.9 %, p = 0.0005) at higher elevation compared to lower elevation. Conclusions Genetic data from a relatively small number of diverse, multiallelic loci reflected fine scale patterns of malaria transmission. Given the increasing interest in applying genetic data to augment malaria surveillance, this study provides evidence that genetic data can be used to inform transmission patterns at local spatial scales even in moderate transmission areas.

Abstract Background The World Health Organization (WHO) promotes long-lasting insecticidal nets (LLIN) and indoor residual house-spraying (IRS) for malaria control in endemic countries. However, long-term impact data of vector control interventions is rarely measured empirically. Methods Surveillance data was collected from paediatric admissions at Tororo district hospital for the period January 2012 to December 2019, during which LLIN and IRS campaigns were implemented in the district. Malaria test positivity rate (TPR) among febrile admissions aged 1 month to 14 years was aggregated at baseline and three intervention periods (first LLIN campaign; Bendiocarb IRS; and Actellic IRS + second LLIN campaign) and compared using before-and-after analysis. Interrupted time-series analysis (ITSA) was used to determine the effect of IRS (Bendiocarb + Actellic) with the second LLIN campaign on monthly TPR compared to the combined baseline and first LLIN campaign periods controlling for age, rainfall, type of malaria test performed. The mean and median ages were examined between intervention intervals and as trend since January 2012. Results Among 28,049 febrile admissions between January 2012 and December 2019, TPR decreased from 60% at baseline (January 2012–October 2013) to 31% during the final period of Actellic IRS and LLIN (June 2016–December 2019). Comparing intervention intervals to the baseline TPR (60.3%), TPR was higher during the first LLIN period (67.3%, difference 7.0%; 95% CI 5.2%, 8.8%, p

Abstract Background Recently, a 3-month (12-dose) regimen of weekly isoniazid and rifapentine (3HP) was recommended by the World Health Organization for the prevention of tuberculosis (TB) among people living with HIV (PLHIV) on common antiretroviral therapy regimens. The best approach to delivering 3HP to PLHIV remains uncertain. Methods We developed a three-armed randomized trial assessing optimized strategies for delivering 3HP to PLHIV. The trial will be conducted at the Mulago Immune Suppression Syndrome (i.e., HIV/AIDS) clinic in Kampala, Uganda. We plan to recruit 1656 PLHIV, randomized 1:1 to each of the three arms (552 per arm). Using a hybrid type 3 effectiveness-implementation design, this pragmatic trial aims to (1) compare the acceptance and completion of 3HP among PLHIV under three delivery strategies: directly observed therapy (DOT), self-administered therapy (SAT), and informed patient choice of either DOT or SAT (with the assistance of a decision aid); (2) to identify processes and contextual factors that influence the acceptance and completion of 3HP under each delivery strategy; and (3) to estimate the costs and compare the cost-effectiveness of three strategies for delivering 3HP. The three delivery strategies were each optimized to address key barriers to 3HP completion using a theory-informed approach. We hypothesize that high levels of treatment acceptance and completion can be achieved among PLHIV in sub-Saharan Africa and that offering PLHIV an informed choice between the optimized DOT and SAT delivery strategies will result in greater acceptance and completion of 3HP. The design and planned evaluation of the delivery strategies were guided by the use of implementation science conceptual frameworks. Discussion 3HP—one of the most promising interventions for TB prevention—will not be scaled up unless it can be delivered in a patient-centered fashion. We highlight shared decision-making as a key element of our trial design and theorize that offering PLHIV an informed choice between optimized delivery strategies will facilitate the highest levels of treatment acceptance and completion. Trial registration ClinicalTrials.gov: NCT03934931 ; Registered 2 May 2019.

Abstract Background Placental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria. Methods The aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitaemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. Multivariate analyses were performed using logistic regression models. Subgroup analysis was performed based on the presence of symptomatic malaria, gravidity, and timing of infection. Results Of the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34–18.2, p

Variation within the HLA locus been shown to play an important role in the susceptibility to and outcomes of numerous infections, but its influence on immunity to P. falciparum malaria is unclear. Increasing evidence indicates that acquired immunity to P. falciparum is mediated in part by the cellular immune response, including NK cells, CD4 and CD8 T cells, and semi-invariant γδ T cells. HLA molecules expressed by these lymphocytes influence the epitopes recognized by P. falciparum-specific T cells, and class I HLA molecules also serve as ligands for inhibitory receptors including KIR. Here we assessed the relationship of HLA class I and II alleles to the risk of P. falciparum infection and symptomatic malaria in a cohort of 892 Ugandan children and adults followed prospectively via both active and passive surveillance. We identified two HLA class I alleles, HLA-B*53:01 and HLA-C*06:02, that were associated with a higher prevalence of P. falciparum infection. Notably, no class I or II HLA alleles were found to be associated with protection from P. falciparum parasitemia or symptomatic malaria. These findings suggest that class I HLA plays a role in the ability to restrict parasitemia, supporting an essential role for the cellular immune response in P. falciparum immunity. Our findings underscore the need for better tools to enable mechanistic studies of the T cell response to P. falciparum at the epitope level and suggest that further study of the role of HLA in regulating pre-erythrocytic stages of the P. falciparum life cycle is warranted.

Multiple studies have reported a male bias in incidence and/or prevalence of malaria infection in males compared to females. To test the hypothesis that sex-based differences in host-parasite interactions affect the epidemiology of malaria, we intensively followed Plasmodium falciparum infections in a cohort in a malaria endemic area of eastern Uganda and estimated both force of infection (FOI) and rate of clearance using amplicon deep-sequencing. We found no evidence of differences in behavioral risk factors, incidence of malaria, or FOI by sex. In contrast, females cleared asymptomatic infections at a faster rate than males (hazard ratio [HR]=1.82, 95% CI 1.20 to 2.75 by clone and HR = 2.07, 95% CI 1.24 to 3.47 by infection event) in multivariate models adjusted for age, timing of infection onset, and parasite density. These findings implicate biological sex-based differences as an important factor in the host response to this globally important pathogen.

RationaleThe relationship between clinical and biomarker characteristics of asthma and its severity in Africa is not well known.MethodsUsing the Expert Panel Report 3, we assessed for asthma severity and its relationship with key phenotypic characteristics in Uganda, Kenya and Ethiopia. The characteristics included adult onset asthma, family history of asthma, exposures (smoking and biomass), comorbidities (HIV, hypertension, obesity, tuberculosis (TB), rhinosinusitis, gastro-oesophageal disease (GERD) and biomarkers (fractional exhaled nitric oxide (FeNO), skin prick test (SPT) and blood eosinophils). We compared these characteristics on the basis of severity and fitted a multivariable logistic regression model to assess the independent association of these characteristics with asthma severity.ResultsA total of 1671 patients were enrolled, 70.7% women, with median age of 40 years. The prevalence of intermittent, mild persistent, moderate persistent and severe persistent asthma was 2.9%, 19.9%, 42.6% and 34.6%, respectively. Only 14% were on inhaled corticosteroids (ICS). Patients with severe persistent asthma had a higher rate of adult onset asthma, smoking, HIV, history of TB, FeNO and absolute eosinophil count but lower rates of GERD, rhinosinusitis and SPT positivity. In the multivariate model, Ethiopian site and a history of GERD remained associated with asthma severity.DiscussionThe majority of patients in this cohort presented with moderate to severe persistent asthma and the use of ICS was very low. Improving access to ICS and other inhaled therapies could greatly reduce asthma morbidity in Africa.

ObjectivePlacental malaria is a known risk factor for small for gestational age (SGA) neonates. However, currently utilized international and African birthweight standards have not controlled for placental malaria and/or lack obstetrical ultrasound dating. We developed a neonatal birthweight standard based on obstetrically dated pregnancies that excluded individuals with clinical malaria, asymptomatic parasitemia, and placental malaria infection. We hypothesized that current curves underestimate true ideal birthweight and the prevalence of SGA.Study designParticipants were pooled from two double-blind randomized control trials of intermittent preventive therapy during pregnancy in Uganda. HIV-negative women without comorbidities were enrolled from 12-20 weeks gestation. Gestational age was confirmed by ultrasound dating. Women were followed through pregnancy and delivery for clinical malaria, asymptomatic parasitemia, and placental malaria. Women without malaria, asymptomatic parasitemia, or placental malaria formed the malaria negative cohort and generated the Ugandan birthweight standard. The Ugandan standard was then used to estimate the prevalence of SGA neonates in the malaria positive cohort. These findings were compared to international (Williams, World Health Organization (WHO), and INTERGROWTH-21st) and regional standards (Tanzanian and Malawi).Results926 women had complete delivery data; 393 (42.4%) met criteria for the malaria negative cohort and 533 (57.6%) were malaria positive. The Ugandan standard diagnosed SGA in 17.1% of malaria positive neonates; similar to the INTERGROWTH-21st and Schmiegelow curves. The WHO curve diagnosed SGA in significantly more neonates (32.1%, p = ConclusionExclusion of women with subclinical placental malaria in malaria-endemic areas created birth weight norms at higher values and increased the detection of SGA. Birth weight standards that fail to account for endemic illness may underestimate the true growth potential of healthy neonates.

BackgroundIndoor residual spraying (IRS) reduces vector densities and malaria transmission, however, the most effective spraying intervals for IRS have not been well established. We estimated the optimal timing interval for IRS using a statistical approach.MethodsSix rounds of IRS were implemented in Tororo District, a historically high malaria transmission setting in Uganda, during the study period (3 rounds with bendiocarb active ingredient (Ficam®): December 2014 to December 2015, and 3 rounds with pirimiphos methyl active ingredient (Actellic 300®CS): June 2016 to July 2018). A generalized additive model was used to estimate the optimal timing interval for IRS based on the predicted malaria incidence. The model was fitted to clinical incidence data from a cohort of children aged 0.5-10 years from selected households observed throughout the study period.Results494 children, 67% aged less than 5 years at enrolment were analysed. Six-months period incidence of malaria decreased from 2.96 per person-years at the baseline to 1.74 following the first round of IRS and then to 0.02 after 6 rounds of IRS. The optimal time interval for IRS differed between bendiocarb and pirimiphos methyl and by IRS round. To retain an optimum impact, bendiocarb would require respraying 17 (95% CI: 14.2-21.0) weeks after application whereas pirimiphos methyl could remain impactful for 40 (95% CI: 37.0-42.8) weeks, although in the final year this estimates 36 (95% CI: 32.7-37.7) weeks. However, we could not estimate from the data the optimal time after the second and third rounds of bendiocarb and after the second round of pirimiphos methyl. Neither the amount of rainfall nor the EIR nor the distribution of nets were found to be statistically significant for determining the time period between spray rounds.ConclusionIn our setting, the effect of the two IRS products was distinct. Statistically, pirimiphos methyl provided a longer window of protection than bendiocarb, although impact varied between different spray rounds and years which was not explained by rainfall or EIR or distribution of nets in our statistical approach. Understanding the effectiveness of IRS and how long it lasts can help for planning campaigns, but one should consider the financial cost and insecticide resistance. Monitoring the timing of spray campaigns using clinical incidence could be repeated in future programs to help determine the average period of protectivity of these products.

Indoor residual spraying (IRS) and long-lasting insecticide-treated bednets (LLINs) are common tools for reducing malaria transmission. We studied a cohort in Uganda with universal access to LLINs after 5 years of sustained IRS to explore LLIN adherence when malaria transmission has been greatly reduced. Eighty households and 526 individuals in Nagongera, Uganda were followed from October 2017 -October 2019. Every two weeks, mosquitoes were collected from sleeping rooms and LLIN adherence the prior night assessed. Episodes of malaria were diagnosed using passive surveillance. Risk factors for LLIN non-adherence were evaluated using multi-level mixed logistic regression. An age-matched case-control design was used to measure the association between LLIN non-adherence and malaria. Across all time periods, and particularly in the last 6 months, non-adherence was higher among both children

BackgroundChronic kidney disease (CKD) may be common among individuals living in sub-Saharan Africa due to the confluence of CKD risk factors and genetic predisposition.MethodsWe ascertained the prevalence of CKD and its risk factors among a sample of 3,686 participants of a population-based HIV trial in rural Uganda and Kenya. Prevalent CKD was defined as a serum creatinine-based estimated glomerular filtration rate ResultsThe estimated CKD prevalence was 6.8% (95% CI 5.7-8.1%) overall and varied by region, being 12.5% (10.1-15.4%) in eastern Uganda, 3.9% (2.2-6.8%) in southwestern Uganda and 3.7% (2.7-5.1%) in western Kenya. Risk factors associated with greater CKD prevalence included age ≥60 years (adjusted prevalence ratio [aPR] 3.5 [95% CI 1.9-6.5] compared with age 18-29 years), HIV infection (aPR 1.6 [1.1-2.2]), and residence in eastern Uganda (aPR 3.9 [2.6-5.9]). However, two-thirds of individuals with CKD did not have HIV, diabetes, or hypertension as risk factors. Furthermore, we noted many individuals who did not have proteinuria had dipstick positive leukocyturia or hematuria.ConclusionThe prevalence of CKD is appreciable in rural East Africa and there are considerable regional differences. Conventional risk factors appear to only explain a minority of cases, and leukocyturia and hematuria were common, highlighting the need for further research into understanding the nature of CKD in sub-Saharan Africa.

Abstract Background Submicroscopic malaria parasitaemia is common in both high- and low-endemicity settings, but its clinical consequences are unclear. Methods 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. Results 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–

Abstract Background Environmental factors play a major role in transmission of malaria given their relationship to both the development and survival of the mosquito and parasite. The associations between environmental factors and malaria can be used to inform the development of early warning systems for increases in malaria burden. The objective of this study was to assess temporal relationships between rainfall, temperature and vegetation with malaria morbidity across three different transmission settings in Uganda. Methods Temporal relationships between environmental factors (weekly total rainfall, mean day time temperature and enhanced vegetation index series) and malaria morbidity (weekly malaria case count data and test positivity rate series) over the period January 2010–May 2013 in three sites located in varying malaria transmission settings in Uganda was explored using cross-correlation with pre-whitening. Sites included Kamwezi (low transmission), Kasambya (moderate transmission) and Nagongera (high transmission). Results Nagongera received the most rain (30.6 mm) and experienced, on average, the highest daytime temperatures (29.8 °C) per week. In the study period, weekly TPR and number of malaria cases were highest at Kasambya and lowest at Kamwezi. The largest cross-correlation coefficients between environmental factors and malaria morbidity for each site was 0.27 for Kamwezi (rainfall and cases), 0.21 for Kasambya (vegetation and TPR), and −0.27 for Nagongera (daytime temperature and TPR). Temporal associations between environmental factors (rainfall, temperature and vegetation) with malaria morbidity (number of malaria cases and TPR) varied by transmission setting. Longer time lags were observed at Kamwezi and Kasambya compared to Nagongera in the relationship between rainfall and number of malaria cases. Comparable time lags were observed at Kasambya and Nagongera in the relationship between temperature and malaria morbidity. Temporal analysis of vegetation with malaria morbidity revealed longer lags at Kasambya compared to those observed at the other two sites. Conclusions This study showed that temporal associations between environmental factors with malaria morbidity vary by transmission setting in Uganda. This suggests the need to incorporate local transmission differences when developing malaria early warning systems that have environmental predictors in Uganda. This will result in development of more accurate early warning systems, which are a prerequisite for effective malaria control in such a setting.

Background: Heterogeneity in malaria transmission has household, temporal, and spatial components. These factors are relevant for improving the efficiency of malaria control by targeting heterogeneity. To quantify variation, we analyzed mosquito counts from entomological surveillance conducted at three study sites in Uganda that varied in malaria transmission intensity. Mosquito biting or exposure is a risk factor for malaria transmission. Methods: Using a Bayesian zero-inflated negative binomial model, validated via a comprehensive simulation study, we quantified household differences in malaria vector density and examined its spatial distribution. We introduced a novel approach for identifying changes in vector abundance hotspots over time by computing the Getis-Ord statistic on ratios of household biting propensities for different scenarios. We also explored the association of household biting propensities with housing and environmental covariates. Results: In each site, there was evidence for hot and cold spots of vector abundance, and spatial patterns associated with urbanicity, elevation, or other environmental covariates. We found some differences in the hotspots in rainy vs. dry seasons or before vs. after the application of control interventions. Housing quality explained a portion of the variation among households in mosquito counts. Conclusion: This work provided an improved understanding of heterogeneity in malaria vector density at the three study sites in Uganda and offered a valuable opportunity for assessing whether interventions could be spatially targeted to be aimed at abundance hotspots which may increase malaria risk. Indoor residual spraying was shown to be a successful measure of vector control interventions in Tororo, Uganda. Cement walls, brick floors, closed eaves, screened airbricks, and tiled roofs were features of a house that had shown reduction of household biting propensity. Improvements in house quality should be recommended as a supplementary measure for malaria control reducing risk of infection.

BACKGROUND:Country 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 FINDINGS:Socio-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 CD4>500 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 CD4>500 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 CD4>500 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). CONCLUSIONS: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. 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.

BACKGROUND:Despite increased antiretroviral therapy (ART) coverage and the raised CD4 threshold for starting ART, opportunistic infections (OIs) are still one of the leading causes of death in sub-Saharan Africa. There are few studies from resource-limited settings on long-term reporting of OIs other than tuberculosis. METHODS:Patients starting ART between April 2004 and April 2005 were enrolled and followed-up for 10 years in Kampala, Uganda. We report incidences, patterns and risk factors using Cox proportional hazards models of OIs among all patients and among patients with CD4 cell counts >200 cells/μL. RESULTS:Of the 559 patients starting ART, 164 patients developed a total of 241 OIs during 10 years of follow-up. The overall incidence was highest for oral candidiasis (25.4, 95% confidence interval (CI): 20.5-31.6 per 1000 person-years of follow-up), followed by tuberculosis (15.3, 95% CI: 11.7-20.1), herpes zoster (12.3, 95% CI: 9.1-16.6) and cryptococcal meningitis (3.0, 95% CI: 1.7-5.5). Incidence rates for all OIs were highest in the first year after ART initiation and decreased with the increase of the current CD4 cell count. Factors independently associated with development of OIs were baseline nevirapine-based regimens, time-varying higher viral load, time-varying lower CD4 cell count and time-varying lower hemoglobin. In patients developing OIs at a current CD4 cell count >200 cells/μL, factors independently associated with OI development were time-varying increase in viral load and time-varying decrease in hemoglobin, whereas a baseline CD4 cell count

Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART) in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004-2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1) mortality, 2) virologic failure, and 3) mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127) of participants died, 6% (n = 31) were lost-to-follow-up and 23% (107/472) experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10-year ART outcomes. A low level of formal education does not appear to be a barrier to successful long-term ART.

INTRODUCTION: diagnostic guidelines for Tuberculosis (TB) in HIV infected patients previously relied on microscopy where the value of initial antibiotic treatment for exclusion of pulmonary TB (PTB) was limited. New guidelines rely on the Xpert MTB Rif test (Xpert). However, the value of the antibiotic treatment remains unclear particularly in individuals who are smear-negative and Xpert-negative-given Xpert has only moderate sensitivity for smear-negative PTB. We assessed an algorithm involving initial treatment with antibiotics prior empiric TB treatment in HIV patients with presumptive PTB who were both smear and Xpert negative.

BACKGROUND:Good house construction may reduce the risk of malaria by limiting the entry of mosquito vectors. We assessed how house design may affect mosquito house entry and malaria risk in Uganda. METHODS:100 households were enrolled in each of three sub-counties: Walukuba, Jinja district; Kihihi, Kanungu district; and Nagongera, Tororo district. CDC light trap collections of mosquitoes were done monthly in all homes. All children aged six months to ten years (n = 878) were followed prospectively for a total of 24 months to measure parasite prevalence every three months and malaria incidence. Homes were classified as modern (cement, wood or metal walls; and tiled or metal roof; and closed eaves) or traditional (all other homes). RESULTS:A total of 113,618 female Anopheles were collected over 6,765 nights. 6,816 routine blood smears were taken of which 1,061 (15.6%) were malaria parasite positive. 2,582 episodes of uncomplicated malaria were diagnosed after 1,569 person years of follow-up, giving an overall incidence of 1.6 episodes per person year at risk. The human biting rate was lower in modern homes than in traditional homes (adjusted incidence rate ratio (IRR) 0.48, 95% confidence interval (CI) 0.37-0.64, p

Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda.Prospective cohort.HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis.Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining