Divergent malaria exposure histories in coastal Kenya

Monthly malaria case counts from active surveillance in two adjacent regions of Kilifi County, Kenya, between 1998 and 2017. Junju (red) maintained sustained malaria transmission throughout the study period, while Ngerenya (blue) experienced a rapid collapse in transmission beginning in 2004. Points represent total cases per month; lines show LOESS-smoothed trends.

AMA1-specific IgG trajectories mirror individual and regional malaria exposure

(A–B) Longitudinal AMA1 IgG levels in individual children measured by protein microarray. Vertical red lines denote confirmed febrile malaria episodes. Panel A shows a Junju child with multiple documented infections; Panel B shows a Ngerenya child who remained malaria-free throughout follow-up. Each blue spot is a single antibody measurement. Each time point was measured in quadruplicate (C) Mean AMA1-specific IgG levels with 95% confidence intervals for all children in the microarray subset plotted by year of sampling. Junju children showed persistently elevated antibodies, while AMA1 antibody levels in Ngerenya declined sharply after 2004.

Malaria exposure is associated with reduced measles-specific antibody levels.

Example plots of temporal changes in measles-specific antibody in vaccinated and unvaccinated children are shown (A) Longitudinal IgG levels in an individual child measured by microarray. The dashed vertical red line indicates the timing of the last dose of the routine measles vaccine. (B) Shows a similar temporal trend for a child with no history of measles vaccination. (C) Longitudinal IgG responses to measles virus by cohort, measured by protein microarray in vaccinated children. Junju children exhibited consistently lower levels of measles-specific antibody than Ngerenya counterparts. The circles indicate means, and the whiskers denote 95% confidence intervals. (D) Measles-specific IgG levels in 3-year-old children from Junju and Ngerenya, measured by ELISA in children with a documented history of measles vaccination. Each dot represents an individual participant.

Broad suppression of antibody responses to diverse pathogens in malaria-exposed children

cross-sectional IgG titres at 10 years of age for a panel of pathogen and vaccine antigens, measured by protein microarray. Each dot represents an individual child; boxes indicate interquartile ranges, with the midline denoting the median. Junju children show significantly lower antibody levels across most antigens compared to Ngerenya children, including Bordetella pertussis, H1N1 influenza virus, rubella virus, measles virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), and coxsackievirus B1.

Early-life malaria exposure predicts long-term suppression of antibody responses within the same geographic region

(A) Active malaria surveillance records for children in the Ngerenya cohort. Each row represents an individual child, and each column represents a surveillance timepoint. Dark red boxes indicate one or more confirmed febrile malaria episodes; light grey boxes indicate surveillance visits without malaria detection. Children are grouped by early-life exposure status (top: malaria-naïve; bottom: previously exposed). (B) IgG levels at 10 years of age among Ngerenya children, stratified by early-life malaria exposure. Children with ≥1 confirmed febrile malaria episode during early childhood (n = 20) show significantly lower titres to multiple unrelated pathogens compared to malaria-naïve peers (n = 42). All children lived in the same geographic area and received identical vaccines and follow-up. The black dots are means and error bars are 95% confidence intervals.

A summary of the sampling frame for the study cohorts (Junju and Ngerenya).

Each vertical line represents the longitudinal time series for a single individual, and each dot represents a timepoint where a serum sample was collected.

Summary of pathogens, strains or subtypes, and corresponding antigens included in the immunoassay panel.