Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y. Over time, ex vivo sensitivity decreased for lumefantrine and piperaquine and increased for chloroquine, the prevalences of pfcrt K76 and pfmdr1 N86 and D1246 increased, and the prevalences of pfdhfr and pfdhps polymorphisms associated with antifolate resistance were unchanged. In recurrent infections, recent prior treatment with artemether-lumefantrine was associated with decreased ex vivo lumefantrine sensitivity and increased prevalence of pfcrt K76 and pfmdr1 N86, 184F, and D1246. In children assigned chemoprevention with monthly dihydroartemisinin-piperaquine with documented circulating piperaquine, breakthrough infections had increased the prevalence of pfmdr1 86Y and 1246Y compared to untreated controls. The noted impacts of therapy and chemoprevention on parasite polymorphisms remained significant in multivariate analysis correcting for calendar time. Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda. These changes may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively. M alaria, in particular disease caused by Plasmodium falciparum, remains an overwhelming problem in most of subSaharan Africa (1, 2). Malaria control was greatly limited by resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP), leading to adoption of artemisinin-based combination therapy (ACT) as the standard treatment for uncomplicated falciparum malaria in the last decade (3). ACT consists of a rapid-acting artemisinin derivative plus a longer-acting partner drug that clears parasites not eliminated by the artemisinin component and limits selection of artemisinin resistance (4, 5). In nearly all countries in sub-Saharan Africa, either artemether-lumefantrine (AL) or artesunate-amodiaquine (AS-AQ) is recommended to treat uncomplicated malaria (6). Other ACTs are dihydroartemisinin (DHA)-piperaquine (DP), a first-line therapy in some countries in Asia, with particular promise for malaria prevention due to the extended halflife of piperaquine (7), and artesunate-mefloquine (AS-MQ), which is used in some countries in Asia and South America. In Uganda, AL was named the national ma...

Children with concurrent wasting and stunting (WaSt) and children with severe wasting have a similar risk of death. Existing evidence shows that wasting and stunting share similar causal pathways, but evidence on correlates of WaSt remains limited. Research on correlates of WaSt is needed to inform prevention strategies. We investigated the factors associated with WaSt in children 6–59 months in Karamoja Region, Uganda. We examined data for 33,054 children aged 6–59 months using June 2015 to July 2018 Food Security and Nutrition Assessment in Karamoja. We defined WaSt as being concurrently wasted (weight‐for‐height z‐scores <−2.0) and stunted (height‐for‐age z‐score <−2.0). We conducted multivariate mixed‐effect logistic regression to assess factors associated with WaSt. Statistical significance was set at p < 0.05. In multivariate analysis, being male (adjusted odds ratio [aOR] = 1.79; 95% confidence interval [CI] [1.60–2.00]), aged 12–23 months (aOR = 2.25; 95% CI [1.85–2.74]), 36–47 months (aOR = 0.65; 95% CI [0.50–0.84]) and 48–59 months (aOR = 0.71; 95% CI [0.54–0.93]) were associated with WaSt. In addition, acute respiratory infection (aOR = 1.30; 95% CI [1.15–1.48]), diarrhoea (aOR = 1.25; 95% CI [1.06–1.48]) and malaria/fever (aOR = 0.83; 95% CI [0.73–0.96]) episodes were associated with WaSt. WaSt was significantly associated with maternal underweight (body mass index <18.5 kg/m 2 ), short stature (height <160 cm), low mid‐upper arm circumference (MUAC <23 cm) and having ≥4 live‐births. WaSt was prevalent in households without livestock (aOR = 1.30; 95% CI [1.13–1.59]). Preventing the occurrence of WaSt through pragmatic and joint approaches are recommended. Future prospective studies on risk factors of WaSt to inform effective prevention strategies are recommended.

Human immunodeficiency virus (HIV)-exposed uninfected children (HEU) have an increased risk of morbidity and mortality compared with HIV-unexposed uninfected children (HUU); however, prior studies have not fully accounted for the role of both breastfeeding and age on this association. In this cohort of HEU and HUU in Uganda, non-breastfeeding HEU, from 6-11 months compared with non-breastfeeding HUU had a higher risk of hospitalizations [relative risk (RR): 10.1, 95% confidence interval (CI): 3.70-27.6], severe febrile illness (RR: 3.84, 95% CI: 2.06-7.17), severe diarrhea (RR: 6.37, 95% CI: 2.32-17.4) and severe malnutrition (RR: 18.4, 95% CI: 4.68-72.0). There were no differences between morbidity outcomes between breastfeeding HEU and HUU children, aged 6-11 months. In the 12-24 month age group, the only difference in morbidity outcomes among non-breast feeding children was an increased risk of severe malnutrition for HEU. These data suggest that the increased risk of morbidity among HEU aged 6-11 years is partially explained by early cessation of breastfeeding.

SummaryBackgroundIntermittent preventive treatment (IPT) is a well established malaria control intervention. Evidence that delivering IPT to schoolchildren could provide community-level benefits is limited. We did a cluster-randomised controlled trial to assess the effect of IPT of primary schoolchildren with dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the community, in Jinja, Uganda.MethodsWe included 84 clusters, each comprising one primary school and the 100 closest available households. The clusters were randomly assigned 1:1 to receive IPT with DP or standard care (control) by restricted randomisation to ensure balance by geography and school type. Children in intervention schools received IPT monthly for up to six rounds (June to December, 2014). We did cross-sectional community surveys in randomly selected households at baseline and in January to April, 2015, during which we measured participants' temperatures and obtained finger-prick blood smears for measurement of parasite prevalence by microscopy. We also did entomological surveys 1 night per month in households from 20 randomly selected IPT and 20 control clusters. The primary trial outcome was parasite prevalence in the final community survey. The primary entomological survey outcome was the annual entomological inoculation rate (aEIR) from July, 2014, to April, 2015. This trial is registered at ClinicalTrials.gov, number NCT02009215.FindingsAmong 23 280 students registered in the 42 intervention schools, 10 079 (43%) aged 5–20 years were enrolled and received at least one dose of DP. 9286 (92%) of 10 079 received at least one full course of DP (three doses). Community-level parasite prevalence was lower in the intervention clusters than in the control clusters (19% vs 23%, adjusted risk ratio 0·85, 95% CI 0·73–1·00, p=0·05). The aEIR was lower in the intervention group than in the control group, but not significantly so (10·1 vs 15·2 infective bites per person, adjusted incidence rate ratio 0·80, 95% CI 0·36–1·80, p=0·59).InterpretationIPT of schoolchildren with DP might have a positive effect on community-level malaria indicators and be operationally feasible. Studies with greater IPT coverage are needed.FundingUK Medical Research Council, UK Department for International Development, and Wellcome Trust.

Background Malaria in pregnancy is a major public health challenge, but its risk factors remain poorly understood in some settings. This study assessed the association between household and maternal characteristics and malaria among pregnant women in a high transmission area of Uganda. Methods A nested prospective study was conducted between 6th September 2016 and 5th December 2017 in Busia district. 782 HIV uninfected women were enrolled in the parent study with convenience sampling. Socioeconomic and house construction data were collected via a household survey after enrolment. Homes were classified as modern (plaster or cement walls, metal or wooden roof and closed eaves) or traditional (all other homes). Maternal and household risk factors were evaluated for three outcomes: (1) malaria parasitaemia at enrolment, measured by thick blood smear and qPCR, (2) malaria parasitaemia during pregnancy following initiation of IPTp, measured by thick blood smear and qPCR and (3) placental malaria measured by histopathology. Results A total of 753 of 782 women were included in the analysis. Most women had no or primary education (75%) and lived in traditional houses (77%). At enrolment, microscopic or sub-microscopic parasitaemia was associated with house type (traditional versus modern: adjusted risk ratio (aRR) 1.29, 95% confidence intervals 1.15–1.45, p < 0.001), level of education (primary or no education versus O-level or beyond: aRR 1.13, 95% confidence interval 1.02–1.24, p = 0.02), and gravidity (primigravida versus multigravida: aRR 1.10, 95% confidence interval 1.02–1.18, p = 0.009). After initiation of IPTp, microscopic or sub-microscopic parasitaemia was associated with wealth index (poorest versus least poor: aRR 1.24, 95% CI 1.10–1.39, p < 0.001), house type (aRR 1.14, 95% CI 1.01–1.28, p = 0.03), education level (aRR 1.19, 95% CI 1.06–1.34, p = 0.002) and gravidity (aRR 1.32, 95% CI 1.20–1.45, p < 0.001). Placental malaria was associated with gravidity (aRR 2.87, 95% CI 2.39–3.45, p < 0.001), but not with household characteristics. Conclusions In an area of high malaria transmission, primigravid women and those belonging to the poorest households, living in traditional homes and with the least education had the greatest risk of malaria during pregnancy.