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BACKGROUND: Twelve weeks of weekly isoniazid and rifapentine (3HP) prevents TB disease among people with HIV (PWH), but the costs to people of taking TB preventive treatment is not well described.METHODS: We surveyed PWH who initiated 3HP at a large urban HIV/AIDS clinic in Kampala, Uganda, as part of a larger trial. We estimated the cost of one 3HP visit from the patient perspective, including both out-of-pocket costs and estimated lost wages. Costs were reported in 2021 Ugandan shillings (UGX) and US dollars (USD; USD1 = UGX3,587)RESULTS: The survey included 1,655 PWH. The median participant cost of one clinic visit was UGX19,200 (USD5.36), or 38.5% of the median weekly income. Per visit, the cost of transportation was the largest component (median: UGX10,000/USD2.79), followed by lost income (median: UGX4,200/USD1.16) and food (median: UGX2,000/USD0.56). Men reported greater income loss than women (median: UGX6,400/USD1.79 vs. UGX3,300/USD0.93), and participants who lived further than a 30-minute drive to the clinic had higher transportation costs than others (median: UGX14,000/USD3.90 vs. UGX8,000/USD2.23).CONCLUSION: Patient-level costs to receive 3HP accounted for over one-third of weekly income. Patient-centered approaches to averting or defraying these costs are needed.

© 2015 Nankabirwa et al.Background: Household surveys are important tools for monitoring the malaria disease burden and measuring impact of malaria control interventions with parasite prevalence as the primary metric. However, estimates of parasite prevale

© 2015 Sundell et al.Background: Anti-malarial chemoprevention with dihydroartemisinin-piperaquine (DHA/PQ) is a promising tool for malaria control, but its efficacy in children may be limited by inadequate drug exposure. Methods: Children were enrolled in

BackgroundImplementation of new tuberculosis (TB) diagnostic strategies in resource-constrained settings is challenging. We measured the impact of solid and liquid mycobacterial cultures on treatment practices for patients undergoing TB evaluation in Kampala, Uganda.MethodsWe enrolled consecutive smear-negative, human immunodeficiency virus positive adults with cough of ⩾2 weeks from September 2009 to April 2010. Laboratory technicians performed mycobacterial cultures on solid and liquid media. We compared empiric treatment decisions with solid and liquid culture in terms of diagnostic yield and time to results, and assessed impact on patient management.ResultsOf 200 patients enrolled, 26 (13%) had culture-confirmed TB: 22 (85%) on solid culture alone, 2 (8%) on liquid culture alone, and 2 (8%) on both solid and liquid culture. Thirty-four patients received empiric anti-tuberculosis treatment, but only 10 (29%) were culture-positive. Median time to a positive result on solid culture was 92 days (interquartile range [IQR] 69-148) compared to 106 days (IQR 66-157) for liquid culture. No patients initiated treatment following a positive result on liquid culture.ConclusionThe introduction of mycobacterial culture did not influence care for patients undergoing evaluation for TB in Kampala, Uganda. Attention to contextual factors surrounding implementation is needed to ensure the effective introduction of new testing strategies in low-income countries.

Background: Malaria thrives in poor tropical and subtropical countries where local resources are limited. Accurate disease forecasts can provide public and clinical health services with the information needed to implement targeted approaches for malaria control that make effective use of limited resources. The objective of this study was to determine the relevance of environmental and clinical predictors of malaria across different settings in Uganda. Methods: Forecasting models were based on health facility data collected by the Uganda Malaria Surveillance Project and satellite-derived rainfall, temperature, and vegetation estimates from 2006 to 2013. Facility-specific forecasting models of confirmed malaria were developed using multivariate autoregressive integrated moving average models and produced weekly forecast horizons over a 52-week forecasting period. Results: The model with the most accurate forecasts varied by site and by forecast horizon. Clinical predictors were retained in the models with the highest predictive power for all facility sites. The average error over the 52 forecasting horizons ranged from 26 to 128% whereas the cumulative burden forecast error ranged from 2 to 22%. Conclusions: Clinical data, such as drug treatment, could be used to improve the accuracy of malaria predictions in endemic settings when coupled with environmental predictors. Further exploration of malaria forecasting is necessary to improve its accuracy and value in practice, including examining other environmental and intervention predictors, including insecticide-treated nets.

© 2015 by The American Society of Tropical Medicine and Hygiene.Bacteremia may be inappropriately treated as malaria in children admitted with a febrile illness in Africa. We determined the prevalence, clinical features, and spectrum of bacteremia among fe

Understanding the current epidemiology of malaria and the relationship between intervention coverage, transmission intensity, and burden of disease is important to guide control activities. We aimed to determine the prevalence of anemia, parasitemia, and s

A better understanding of case management practices is required to improve inpatient pediatric care in resource-limited settings. Here we utilize data from a unique health facility-based surveillance system at six Ugandan hospitals to evaluate the quality

Background: Improving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse. Objective: To describe the current practices and quality of TB evaluation for

The emergence of resistance to artemisinin derivatives in Southeast Asia, manifested as delayed clearance of Plasmodium falciparum following treatment with artemisinins, is a major concern. Recently, the artemisinin resistance phenotype was attributed to m

Background: Alcohol use has a detrimental impact on the HIV epidemic, especially in sub-Saharan Africa. HIV counseling and testing (HCT) may provide a contact opportunity to intervene with hazardous alcohol use; however, little is known about how alcohol c

Intermittent preventive treatment (IPT) in schoolchildren offers a promising option for malaria control. However, the optimal drug and dosing regimens for IPT remain to be determined. Methods. We conducted a randomized, double-blind, placebo-controlled tri

Background: Reliable measures of anti-malarial resistance are crucial for malaria control. Resistance is typically a complex trait: multiple mutations in a single parasite (a haplotype or genotype) are necessary for elaboration of the resistant phenotype.

Background: Malaria remains a major public health problem, and its control has been hampered by drug resistance. For a number of drugs, Plasmodium falciparum single nucleotide polymorphisms (SNPs) are associated with altered drug sensitivity and can be use

Background: Hypertension is one of the largest causes of preventable morbidity and mortality worldwide. There are few population-based studies on hypertension epidemiology to guide public health strategies in sub-Saharan Africa. Using a community-based str

Background: HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its effect on HIV risk is uncertain and methods to improve linkage to care have not been

Background: The burden of malaria has decreased in parts of Africa following the scaling up of control interventions. However, similar data are limited from high transmission settings. Methods. A cohort of 100 children, aged six weeks to 10 months of age,

Background: The high burden of undiagnosed HIV in sub-Saharan Africa limits treatment and prevention efforts. Community-based HIV testing campaigns can address this challenge and provide an untapped opportunity to identify non-communicable diseases (NCDs).

Context: Combination therapy is now widely advocated as first-line treatment for uncomplicated malaria in Africa. However, it is not clear which treatment regimens are optimal or how to best assess comparative efficacies in highly endemic areas.Objective: To compare the efficacy and safety of 3 leading combination therapies for the treatment of uncomplicated malaria.Design, Setting, and Participants: Single-blind randomized clinical trial, conducted between November 2004 and June 2006, of treatment for all episodes of uncomplicated malaria in children in an urban community in Kampala, Uganda. A total of 601 healthy children (aged 1-10 years) were randomly selected and were followed up for 13 to 19 months, receiving all medical care at the study clinic.Interventions: Study participants were randomized to receive 1 of 3 combination therapies (amodiaquine plus sulfadoxine-pyrimethamine, amodiaquine plus artesunate, or artemether-lumefantrine) when diagnosed with their first episode of uncomplicated malaria. The same assigned treatment was given for all subsequent episodes.Main Outcome Measure: 28-Day risk of parasitological failure (unadjusted and adjusted by genotyping to distinguish recrudescence from new infection) for each episode of uncomplicated malaria treated with study drugs.Results: Of enrolled children, 329 of 601 were diagnosed with at least 1 episode of uncomplicated malaria, and 687 episodes of Plasmodium falciparum malaria were treated with study drugs. The 28-day risk of treatment failure (unadjusted by genotyping) for individual episodes of malaria were 26.1% (95% CI, 21.1%-32.1%) for amodiaquine plus sulfadoxine-pyrimethamine, 17.4% (95% CI, 13.1%-23.1%) for amodiaquine plus artesunate, and 6.7% (95% CI, 3.9%-11.2%) for artemether-lumefantrine (P<.05 for all pairwise comparisons). When only recrudescent treatment failures were considered, the risks of failure were 14.1% (95% CI, 10.3%-19.2%), 4.6% (95% CI, 2.5%-8.3%), and 1.0% (95% CI, 0.3%-4.0%) for the same order of study drugs, respectively (P< or =.008 for all pairwise comparisons, except amodiaquine plus artesunate vs artemether-lumefantrine, P = .05). There were no deaths or cases of severe malaria. Significant reductions in anemia (9.3% [95% CI, 7.0%-12.0%] at enrollment vs 0.6% [95% CI, 0.1%-2.2%] during the last 2 months of follow-up; P<.001) and asymptomatic parasitemia (18.6% [95% CI, 15.5%-22.1%] at enrollment vs 2.3% [95% CI, 1.5%-3.5%] during the last 2 months of follow-up; P<.001) were observed according to routine testing.Conclusions: Artemether-lumefantrine was the most efficacious treatment for uncomplicated malaria in the study population. With all study regimens, the provision of prompt and reasonably effective facility-based treatment was associated with good outcomes in long-term health measures.Trial Registration: isrctn.org Identifier: ISRCTN37517549. [ABSTRACT FROM AUTHOR]

Background: Home management of malaria-the presumptive treatment of febrile children with antimalarial drugs-is advocated to ensure prompt effective treatment of the disease. We assessed the effect of home delivery of artemether-lumefantrine on the incidence of antimalarial treatment and on clinical outcomes in children from an urban setting with fairly low malaria transmission.Methods: In Kampala, Uganda, 437 children aged between 1 and 6 years from 325 households were randomly assigned by a computer-generated sequence to receive home delivery of prepackaged artemether-lumefantrine for presumptive treatment of febrile illnesses (n=225) or current standard of care (n=212). Randomisation was done by household after a pilot period of 1 month. After randomisation, study participants were followed up for an additional 12 months and information on their health and treatment of illnesses was obtained by use of monthly questionnaires and household diaries, which were completed by the participants' carers. The primary outcome was treatment incidence density per person-year. Analysis of the primary outcome was done on the modified intention-to-treat population, which included all participants apart from those excluded before data collection. This trial is registered with ClinicalTrials.gov, number NCT00115921.Findings: Eight participants in the home management group and four in the standard care group were excluded before data collection; therefore, the primary analysis was done in 217 and 208 participants, respectively. The home management group received nearly twice the number of antimalarial treatments as the standard care group (4.66 per person-year vs 2.53 per person-year; incidence rate ratio [IRR] 1.72, 95% CI 1.43-2.06, p<0.0001), and nearly five times the number given to children with microscopically confirmed malaria in a comparable cohort of children (4.66 per person-year vs 1.03 per person-year, IRR 5.19, 95% CI 4.24-6.35, p<0.0001). Clinical data were available for 189 children in the home management group and 176 in the control group at study end; the main reasons for exclusion were movement out of the study area or loss to follow-up. The proportion of participants with parasitaemia at final assessment in the intervention group was lower than in the control group (four [2%] vs 17 [10%], p=0.006), but there were no other differences in standard malariometric indices, including anaemia. Serious adverse events were captured retrospectively. One child died in each group (home management-severe pneumonia and possible septicaemia; standard care-presumed respiratory failure).Interpretation: Although home management of malaria led to prompt treatment of fever, there was little effect on clinical outcomes. The substantial over-treatment suggests that artemether-lumefantrine provided in the home might not be appropriate for large urban areas or settings with fairly low malaria transmission.Funding: Gates Malaria Partnership. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Mulago and Mbarara hospitals are large tertiary hospitals in Uganda with a high HIV/AIDS burden. Until recently, HIV testing was available only upon request and payment. From November 2004, routine free HIV testing and counselling has been offered to improve testing coverage and the clinical management of patients. All patients in participating units who had not previously tested HIV-positive were offered HIV testing. Family members of patients seen at the hospitals were also offered testing. METHODS: Data collected at the 25 participating wards and clinics between 1 November 2004 and 28 February 2006 were analysed to determine the uptake rate of testing and the HIV seroprevalence among patients and their family members. FINDINGS: Of the 51,642 patients offered HIV testing, 50,649 (98%) accepted. In those who had not previously tested HIV-positive, the overall HIV prevalence was 25%, with 81% being tested for the first time. The highest prevalence was found in medical inpatients (35%) and the lowest, in surgical inpatients (12%). The prevalence of HIV was 28% in the 39,037 patients who had never been tested before and 9% in those who had previously tested negative. Of the 10,439 family members offered testing, 9720 (93%) accepted. The prevalence in family members was 20%. Among 1213 couples tested, 224 (19%) had a discordant HIV status. CONCLUSION: In two large Ugandan hospitals, routine HIV testing and counselling was highly acceptable and identified many previously undiagnosed HIV infections and HIV-discordant partnerships among patients and their family members. Copyright © 2008 World Health Organization [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is the leading cause of fatal upper gastrointestinal bleeding among adults in East Africa. The prevalence among school-aged children in villages along the Albert-Nile shoreline in North-Western Uganda is estimated at 85%. Efforts to control schistosomiasis in low- and-middle-income countries remain limited due to an incomplete understanding of the pathogenesis, disease manifestations, transmission mechanisms, preventive measures and interventions. In addition, there is insufficient capacity to analyse, model and predict relevant clinical case management systems, biological interventions and disease control efforts. We conducted a needs assessment for schistosomiasis research training at academic and research institutions in Uganda to inform the development of a structured training programme to build capacity to conduct locally relevant research to control the disease., Methods: Using an online survey, we collected data on training needs, potential trainees, available resources including local and international collaborations, as well as priority areas for schistosomiasis research and training at academic and research institutions in Uganda. Data were analysed and presented in frequency tables and figures., Results: Overall, schistosomiasis had the lowest number of studies conducted, based on the studies approved by research ethics committees at the two leading medical schools in Uganda: Makerere University College of Health Sciences (MakCHS) and Mbarara University of Science and Technology (MUST) between 2016 and 2022. The top ranked schistosomiasis focus areas of interest, by scientists at MakCHS, MUST, the Vector Borne and Neglected Tropical Diseases Division of the Ministry of Health and the Uganda Virus Research Institute (UVRI), were schistosomiasis prevention and transmission, vector biology, diagnostics, treatment and clinical trials, respectively. The top ranked training needs were schistosomiasis prevention and control, research ethics, data analysis, epidemiology and research methods (quantitative and qualitative), malacology, infectious diseases modelling, scientific writing and communication skills., Conclusion: Priority areas for schistosomiasis research and training will be utilised to develop a robust, collaborative, multidisciplinary schistosomiasis research training programme, to increase the critical mass of scientists with the competencies required to design, execute and utilise schistosomiasis biology, clinical, laboratory and epidemiology research to advance disease control interventions and minimise/eliminate schistosomiasis-associated morbidity and mortality in sub-Saharan Africa., (© 2025 The Authors Tropical Medicine & International Health published by John Wiley & Sons Ltd.)

Long-lasting insecticidal nets (LLINs) are the cornerstone of malaria control, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic, cluster-randomised trial into Uganda's national LLIN distribution campaign in 2020-2021, comparing pyrethroid-piperonyl butoxide (PBO) LLINs to pyrethroid-pyriproxyfen LLINs. Target communities surrounding public health facilities (clusters, n=64), covering 32 districts were included. Clusters were randomised 1:1 in blocks of two by district to receive: (1) pyrethroid-PBO LLINs (PermaNet 3.0, n=32) or (2) pyrethroid-pyriproxyfen LLINs (Royal Guard, n=32). LLINs were delivered from 7 November 2020 to 26 March 2021. Malaria surveillance data were collected from health facilities from 1 November 2019 until 31 March 2023. Cluster-level estimates of malaria incidence in residents of all ages (primary outcome) were generated from enhanced health facility surveillance data. Cross-sectional community surveys were conducted in randomly selected households (at least 50 per cluster) at 12-months (24 November 2021 to 1 April 2022) and 24-months (23 November 2022 to 21 March 2023) post-LLIN distribution. Overall, 186,364 clinical malaria episodes were diagnosed in cluster residents during 398,931 person-years of follow-up. At 24-months, malaria incidence was lower than baseline in both arms (pyrethroid-PBO: 465 vs 676 episodes per 1000 person-years; pyrethroid-pyriproxyfen: 469 vs 674 episodes per 1000 person-years); but there was no evidence of a difference between the arms (incidence rate ratio 1.06, 95% confidence interval [CI] 0.91-1.22, p=0.47). Two years post-distribution, ownership of at least one LLIN for every two household residents was low in both arms (41.1% pyrethroid-PBO vs 38.6% pyrethroid-pyriproxyfen). Parasite prevalence in children aged 2-10 years was no different between the arms in either survey (24-months: 26.1% pyrethroid-PBO; 29.5% pyrethroid-pyriproxyfen; odds ratio 1.29 [95% CI: 0.81-2.05], p=0.29). The effectiveness of pyrethroid-PBO LLINs and pyrethroid-pyriproxyfen LLINs was no different in Uganda, but two years after mass distribution, LLIN coverage was inadequate. Trial registration: NCT04566510. Registered 28 September 2020, https://clinicaltrials.gov/ct2/show/NCT04566510., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Gonahasa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Depression among adolescents and young adults with HIV affects both their wellbeing and clinical care outcomes. Integrated care models are needed. We hypothesized that the SEARCH-Youth intervention, a life-stage-based care model that improved viral suppression, would reduce depressive symptoms as compared to the standard of care. We conducted a mixed-methods study of youth with HIV aged 15-24 years in SEARCH-Youth, a cluster-randomized trial in rural Uganda and Kenya (NCT03848728). Depression was assessed cross-sectionally with the PHQ-9 screening tool and compared by arm using targeted minimum loss-based estimation. In-depth semi-structured interviews with young participants, family members, and providers were analyzed using a modified framework of select codes pertaining to depression. We surveyed 1,234 participants (median age 21 years, 80% female). Having any depressive symptoms was less common in the intervention arm (53%) compared to the control (73%), representing a 28% risk reduction (risk ratio: 0.72; CI: 0.59-0.89). Predictors of at least mild depression included pressure to have sex, physical threats, and recent major life events. Longitudinal qualitative research among 113 participants found that supportive counseling from providers helped patients build confidence and coping skills. Integrated models of care that address social threats, adverse life events, and social support can be used to reduce depression among adolescents and young adults with HIV.

Background The gold standard measure of malaria exposure is the entomological inoculation rate (EIR), or the number of infectious bites an individual receives over a given period. Nevertheless, it is unclear whether household EIR reflects heterogeneity in individual infection risk. Methods To investigate this relationship, we used data collected from a cohort of 439 children aged 0.5-5 years in 239 households from 2011-2017 in three Ugandan districts: low-EIR Jinja, intermediate-EIR Kanungu and high-EIR Tororo. Participants underwent passive and quarterly active surveillance for clinical malaria, defined as fever with positive thick blood smear. Monthly vector densities and sporozoite rates in participating households were estimated using CDC light traps. We assessed the association between spatiotemporally smoothed household log 2 -transformed EIR and individual malaria incidence using Poisson generalized additive mixed effects models. Results Comparison across sites suggested an increasing relationship between average EIR and malaria incidence. Within-site relationships, however, varied by site, with a positive association in Kanungu (incidence rate ratio [IRR] 1.09, 95% credible interval 1.04-1.14) but none in Jinja (1.02, 0.774-1.26) or Tororo (1.02, 0.986-1.06). Conclusions These results show the relationship between measured EIR and malaria incidence may depend on local transmission dynamics and be strongest at intermediate EIR, while underscoring the challenges of using household-level measures of exposure.

Background: Cardiovascular disease (CVD) morbidity and mortality is increasing in Africa, largely due to undiagnosed and untreated hypertension. Approaches that leverage existing primary health systems could improve hypertension treatment and reduce CVD, but cost-effectiveness is unknown. We evaluated the cost-effectiveness of population-level hypertension screening and implementation of chronic care clinics across eastern, southern, central, and western Africa., Methods and Findings: We conducted a modeling study to simulate hypertension and CVD across 3,000 scenarios representing a range of settings across eastern, southern, central, and western Africa. We evaluated 2 policies compared to current hypertension treatment: (1) expansion of HIV primary care clinics into chronic care clinics that provide hypertension treatment for all persons regardless of HIV status (chronic care clinic or CCC policy); and (2) CCC plus population-level hypertension screening of adults ≥40 years of age by community health workers (CHW policy). For our primary analysis, we used a cost-effectiveness threshold of US $500 per disability-adjusted life-year (DALY) averted, a 3% annual discount rate, and a 50-year time horizon. A strategy was considered cost-effective if it led to the lowest net DALYs, which is a measure of DALY burden that takes account of the DALY implications of the cost for a given cost-effectiveness threshold. Among adults 45 to 64 years, CCC implementation would improve population-level hypertension control (the proportion of people with hypertension whose blood pressure is controlled) from mean 4% (90% range 1% to 7%) to 14% (6% to 26%); additional CHW screening would improve control to 44% (35% to 54%). Among all adults, CCC implementation would reduce ischemic heart disease (IHD) incidence by 10% (3% to 17%), strokes by 13% (5% to 23%), and CVD mortality by 9% (3% to 15%). CCC plus CHW screening would reduce IHD by 28% (19% to 36%), strokes by 36% (25% to 47%), and CVD mortality by 25% (17% to 34%). CHW screening was cost-effective in 62% of scenarios, CCC in 31%, and neither policy was cost-effective in 7% of scenarios. Pooling across setting-scenarios, incremental cost-effectiveness ratios were $69/DALY averted for CCC and $389/DALY averted adding CHW screening to CCC., Conclusions: Leveraging existing healthcare infrastructure to implement population-level hypertension screening by CHWs and hypertension treatment through integrated chronic care clinics is expected to reduce CVD morbidity and mortality and is likely to be cost-effective in most settings across Africa., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Hickey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Molecular surveillance of drug-resistant Plasmodium falciparum is crucial for malaria control in endemic regions. Two targeted-resequencing tools, the Molecular Inversion Probe (MIP) drug resistance panel DR23K and the Multiplexed Amplicons for Drugs, Diagnostics, Diversity, and Differentiation using High-Throughput Targeted Resequencing (MAD 4 HatTeR) panel, are widely used to detect resistance genotypes. However, comparisons of their performance for genotyping drug resistance polymorphisms in malaria parasites and their comparative utility for other use cases is lacking., Methods: To compare the performance of DR23K and MAD 4 HatTeR in terms of sequencing depth, sensitivity to minor alleles, and precision, each platform was used to evaluate SNP alleles and microhaplotypes in double- and triple-strain mixtures of well-characterized laboratory parasites at densities of 10, 100, 1,000, and 10,000 parasites/µL. In addition, 67 Ugandan field samples collected in 2022 were genotyped using each platform to assess performance and concordance., Results: Across the four parasite densities, MAD 4 HatTeR exhibited superior sequencing depth (mean reads per locus: 144, 992, 1,153, and 1,300) compared to DR23K (mean unique molecular identifiers [UMIs] per locus: 1, 4, 49, and 364). For SNP detection, MAD 4 HatTeR achieved 100% sensitivity at 2% within-sample allele frequency (WSAF) at 1,000 and 10,000 parasites/µL, whereas DR23K achieved 100% sensitivity at 40% and 5% WSAF at these densities, respectively. Microhaplotype sensitivity was lower for both assays; MAD4HatTeR reached 69% sensitivity at 10 parasites/µL when WSAF was ≥ 10%, increasing to 100% sensitivity at 2% WSAF and 100 parasites/µL. DR23K had < 50% sensitivity at 10 and 100 parasites/µL. In field samples, which commonly contain polyclonal infections, high concordance was observed between the two methods for all SNPs (94%, 1,848/1,969) and polymorphic SNPs (88%, 898/1,019). All discrepancies were attributed to varied detection of minority alleles in mixed genotype infections., Conclusions: MAD 4 HatTeR demonstrated higher sensitivity than DR23K, particularly at low parasite densities. Both assays showed strong concordance for genotyping key resistance mutations in field samples, supporting their reliability. These findings suggest MAD 4 HatTeR as the preferred assay for low-density parasite studies and microhaplotype analysis, while DR23K may be appropriate for specific applications with high-parasite density samples, where detection of minority alleles is not prioritized, or when more comprehensive genome coverage is required.

Background: Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine combined with amodiaquine (SPAQ) effectively protects eligible children from malaria in areas of high and seasonal transmission. However, concerns about parasite resistance to sulfadoxine-pyrimethamine in East and Southern Africa necessitate evaluating alternative drug regimens. This study assessed the effectiveness of SPAQ and dihydroartemisinin-piperaquine for SMC in Uganda., Methods: This three-arm, open-label, non-inferiority and superiority, cluster-randomised, controlled trial was conducted in Karamoja subregion, Uganda, among children aged 3-59 months and 6-59 months for SPAQ and dihydroartemisinin-piperaquine, respectively. Of 427 villages, 380 were randomly assigned (1:1) to the SPAQ group and dihydroartemisinin-piperaquine group, and 47 were assigned to the control group (no SMC). The superiority component compared the SPAQ and dihydroartemisinin-piperaquine groups with the control group, whereas the non-inferiority component compared the dihydroartemisinin-piperaquine group with the SPAQ group. The primary endpoint was confirmed malaria incidence using rapid diagnostic tests or microscopy. Survival analyses were done on an intention-to-treat basis (in all randomised participants), with adjustments made for covariate imbalances at baseline. Additionally, molecular markers associated with resistance to sulfadoxine-pyrimethamine and amodiaquine were analysed on 750 malaria-positive blood samples from children younger than 5 years before and after five SMC cycles. This trial was registered with ClinicalTrials.gov, NCT05323721, and has been completed., Findings: During June 18-30, 2022, 3881 children were enrolled; 1755 in SPAQ, 1736 in dihydroartemisinin-piperaquine, and 390 in control villages. Of these children, 3629 were analysed. Incidence rates were 0·90 cases per 100 person-months in the SPAQ group, 0·80 cases per 100 person-months in the dihydroartemisinin-piperaquine group, and 18·26 cases per 100 person-months in the control group. SPAQ and dihydroartemisinin-piperaquine reduced malaria risk by 94% (hazard ratio [HR] 0·06 [95% CI 0·04-0·08]; p<0·001) and 96% (0·04 [0·03-0·06]; p<0·001), respectively. Based on the prespecified non-inferiority margin of 1·4, there was non-inferiority between the protective effectiveness of dihydroartemisinin-piperaquine and that of SPAQ (HR 0·90 [95% CI 0·58-1·39]). Prevalence of mutations linked to moderate (Plasmodium falciparum dihydrofolate reductase [PfDHFR] and P falciparum dihydropteroate synthetase reductase [PfDHPS]) and high (PfDHFR Ile164Leu and PfDHPS Ala581Gly) sulfadoxine-pyrimethamine resistance were more than 88% and less than 5%, respectively. Mutations associated with 4-aminoquinolone resistance (P falciparum multidrug resistance protein-1 [PfMDR1] Asp1246Tyr and PfMDR1 Asn86Tyr) were less than 1%. There was no significant increase in the prevalence of antifolate and artemisinin partial resistance-associated mutations, but a decrease was observed for key aminoquinoline resistance-associated alleles: P falciparum chloroquine resistance transporter protein Lys76Thr, P falciparum multidrug resistance protein Asn86Tyr, and PfMDR1 Asp1246Tyr (p<0·001). No serious or fatal adverse events were reported., Interpretation: SPAQ and dihydroartemisinin-piperaquine effectively reduced malaria in children younger than 5 years, with no safety concerns. There was no evidence of resistance selection by SMC. Although these findings support SPAQ-based SMC in Eastern and Southern Africa, ongoing resistance surveillance and efficacy monitoring are essential for sustained impact., Funding: GiveWell., Translation: For the Swahili translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests All authors declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Female sex workers (FSWs) have the highest HIV prevalence in Uganda. Pre-exposure prophylaxis (PrEP) has been recommended as a key component of the HIV combination prevention strategy. Although patient initiation of PrEP has improved, continuation rates remain low. This study evaluated PrEP continuation among FSWs and explored potential determinants of PrEP adherence within a public referral hospital in urban Uganda., Methods: We conducted an explanatory sequential mixed method study at Kiruddu National referral hospital in Uganda. Secondary data on socio demographic characteristics and follow up outcomes of at least one year was collected for all FSWs who were initiated PrEP between May 2020 and April 2021 and data analyzed on July 15,2023. We used Kaplan-Meier survival analysis to evaluate continuation on PrEP from time of initiation and follow-up period. The capability, opportunity, and motivation to change behaviour model was used to explore perspectives and practices of FSWs (n = 24) and health care providers (n = 8) on continuation on PrEP among FSWs, using semi structured interviews. The qualitative data was deductively coded and analyzed thematically, categorizing the themes related to PrEP continuation as facilitators and barriers., Results: Of the 292 FSWs initiated on PrEP, median age was 26 years (interquartile range, 21-29), 101 (34.6) % were active on PrEP, 137 (46.9%) were lost to follow-up, 45 (15.4%) were no longer eligible to continue PrEP, eight (2.7%) were transferred out and one (0.3%) had died. Median survival time on PrEP was 15 months (Interquartile range IQR, 3-21). The continuation rates on PrEP at six (6) and 12 months were 61.1% and 53.1%, respectively. Facilitators of PrEP continuation included awareness of risk associated with sex work, integration of PrEP with other HIV prevention services, presence of PrEP Peer support and use of Drop-in centers. The barriers included low community awareness about PrEP, high mobility of sex workers, substance abuse, and the unfavorable daytime clinic schedules. However, the quantitative findings from the multivariable Cox Proportional Hazards Model did not align with the reported findings for the qualitative evaluation., Conclusion: Continuation on PrEP remains low among FSWs. Interventions for PrEP continuation should address barriers such as low community awareness of PrEP, substance abuse and restrictive health facility policies for scale of the PrEP program among FSWs in Uganda. Integration of PrEP with other services and scale up of community PrEP delivery structures may improve its continuation., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by The AIDS Support Organization (TASO) institutional review board (IRB) number TASO- 2022–190 and Uganda National council of science and technology (UNCST) number HS2771ES. We obtained written permission from Kiruddu national referral hospital to access clients’ medical records for the quantitative component and written informed consent was obtained from participants involved in the qualitative study. The participants' information was anonymized to maintain confidentiality. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)