The human immunome in the post-schistosomiasis mass drug administration era.

Helminths have co-evolved with humans and developed sophisticated mechanisms to manipulate the host immune system, allowing them to persist for years. During chronic disease, helminths typically shift immune responses toward a Th2 profile-supporting antibody production and tissue repair-while suppressing Th1/Th17 responses that are crucial for combating viruses and intracellular pathogens. Additionally, they elevate regulatory T cells and anti-inflammatory cytokines such as IL-10 and TGF-β, dampening inflammation, compromising host immunity to other infections, and, in some cases, reducing vaccine efficacy. Further, both experimental and clinical studies have shown that anthelminthic treatment can reverse parasite host immunomodulation. However, there is evidence that helminth-induced immune changes may persist months after parasite clearance. With the widespread rollout of preventive chemotherapy via mass drug administration (MDA) across the continent, many African populations have now received at least one round of deworming treatment. This raises critical questions about the nature, persistence, and public health significance of anthelminthic treatment-related immunological shifts in endemic settings with repeated exposures. In Africa, which bears a disproportionate share of the global helminth burden, there is growing interest in how these factors shape immune responses. In this review, we summarise current knowledge and key research gaps regarding mechanisms that contribute to immune variation in helminth-endemic populations and the broader implications for disease control, vaccine response, and health policy in endemic settings.