A non-randomized controlled trial to assess the protective effect of SMC in the context of high parasite resistance in Uganda.

BACKGROUND: Until recently, due to widespread prevalence of molecular markers associated with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance in east and southern Africa, seasonal malaria chemoprevention (SMC) has not been used at scale in this region. This study assessed the protective effectiveness of monthly administration of SP + AQ (SPAQ) to children aged 3-59 months in Karamoja sub-region, Uganda, where parasite resistance is assumed to be high and malaria transmission is seasonal. METHODS: A two-arm quasi-experimental, open-label prospective non-randomized control trial (nRCT) was conducted in three districts. In two intervention districts, 85,000 children aged 3-59 months were targeted to receive monthly courses of SMC using SPAQ during the peak transmission season (May to September) 2021. A third district served as a control, where SMC was not implemented. Communities with comparable malaria attack rates were selected from the three districts, and households with at least one SMC-eligible child were purposively selected. A total cohort of 600 children (200 children per district) were selected and followed using passive surveillance for breakthrough confirmed malaria episodes during the five-month peak transmission season. Malaria incidence rate per person-months and number of malaria episodes among children in the two arms were compared. Kaplan-Meier failure estimates were used to compare the probability of a positive malaria test. Other factors that may influence malaria transmission and infection among children in the two arms were also assessed using multivariable cox proportional hazards regression model. RESULTS: The malaria incidence rate was 3.0 and 38.8 per 100 person-months in the intervention and control groups, respectively. In the intervention areas 90.0% (361/400) of children did not experience any malaria episodes during the study period, compared to 15% (29/200) in the control area. The incidence rate ratio was 0.078 (95% CI 0.063-0.096), which corresponds to a protective effectiveness of 92% (95% CI 90.0-94.0) among children in the intervention area. CONCLUSION: SMC using SPAQ provided high protective effect against malaria during the peak transmission season in children aged 3-59 months in the Karamoja sub-region of Uganda.

Prenatal exposure to Plasmodium falciparum increases frequency and shortens time from birth to first clinical malaria episodes during the first two years of life: prospective birth cohort study.

BACKGROUND: Prenatal exposure to Plasmodium falciparum affects development of protective immunity and susceptibility to subsequent natural challenges with similar parasite antigens. However, the nature of these effects has not been fully elucidated. The aim of this study was to determine the effect of prenatal exposure to P. falciparum on susceptibility to natural malaria infection, with a focus on median time from birth to first clinical malaria episode and frequency of clinical malaria episodes in the first 2 years of life. METHODS: A prospective birth cohort study was conducted in Rufiji district in Tanzania, between January 2013 and December 2015. Infants born to mothers with P. falciparum in the placenta at time of delivery were defined as exposed, and infants born to mothers without P. falciparum parasites in placenta were defined as unexposed. Placental infection was established by histological techniques. Out of 206 infants recruited, 41 were in utero exposed to P. falciparum and 165 infants were unexposed. All infants were monitored for onset of clinical malaria episodes in the first 2 years of life. The outcome measure was time from birth to first clinical malaria episode, defined by fever (≥37 °C) and microscopically determined parasitaemia. Median time to first clinical malaria episode between exposed and unexposed infants was assessed using Kaplan-Meier survival analysis and comparison was done by log rank. Association of clinical malaria episodes with prenatal exposure to P. falciparum was assessed by multivariate binary logistic regression. Comparative analysis of mean number of clinical malaria episodes between exposed and unexposed infants was done using independent sample t test. RESULTS: The effect of prenatal exposure to P. falciparum infection on clinical malaria episodes was statistically significant (Odds Ratio of 4.79, 95 % CI 2.21-10.38, p < 0.01) when compared to other confounding factors. Median time from birth to first clinical malaria episode for exposed and unexposed infants was 32 weeks (95 % CI 30.88-33.12) and 37 weeks (95 % CI 35.25-38.75), respectively, and the difference was statistically significant (p = 0.003). The mean number of clinical malaria episodes in exposed and unexposed infants was 0.51 and 0.30 episodes/infant, respectively, and the difference was statistically significant (p = 0.038). CONCLUSIONS: Prenatal exposure to P. falciparum shortens time from birth to first clinical malaria episode and increases frequency of clinical malaria episodes in the first 2 years of life.