BACKGROUND:
Dichlorodiphenyltrichloroethane (DDT), despite being listed under the Stockholm Convention for global phase-out due to its well-documented environmental persistence, adverse human health effects and endocrine disruptive properties, continues to be used in certain settings for malaria vector control. Global malaria control and elimination progress has stagnated, particularly in sub-Saharan Africa, where South Africa and parts of the Southern African Development Community (SADC) region face ongoing transmission risks(1). Although global DDT production and use have declined and alternative vector control tools have expanded, flooding and climate challenges increasing malaria risk. Ongoing DDT use reflects malaria risk, cost, and policy pressures, raising doubts about whether it is evidence-driven or politically constrained.

METHODS:
Human biomonitoring and molecular epidemiology studies conducted in Limpopo Province, South Africa, and comparative cohorts from Greenland assessed associations between serum p,p′-DDE levels and sperm epigenetic profiles. Sperm DNA methylation and histone H3K4me3 enrichment were assessed using MethylC-Capture sequencing and chromatin immunoprecipitation sequencing (ChIP-seq)(2). Evidence is contextualised within current malaria control strategies in South Africa and SADC.

RESULTS:
Higher exposure to DDT and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) was associated with dose-responsive alterations in sperm DNA methylation and H3K4me3 enrichment at genomic regions involved in fertility, development, neurological function, and disease susceptibility. A subset of these epigenetic changes occurred in regions predicted to persist in the early embryo, indicating potential intergenerational transmission. These molecular findings are consistent with existing epidemiological evidence linking DDT exposure to adverse reproductive, developmental, and endocrine outcomes.

DISCUSSION:
While DDT is used for malaria control, growing evidence highlights significant long-term health and environmental risks. Amid stagnated malaria progress, its continued use reflects complex scientific, economic, and policy trade-offs. Public health strategies must balance immediate malaria prevention with environmental protection and intergenerational equity, prioritising investment in safer, sustainable vector control alternatives to advance malaria elimination for current and future generations.