Persistent Plasmodium falciparum infections enhance transmission-reducing immunity development

Area of Science:

• Malariology
• Immunology
• Infectious Diseases

Background:

• Subclinical Plasmodium falciparum infections act as reservoirs, hindering malaria control efforts.
• Understanding infection dynamics and host immunity is vital for designing effective malaria interventions.

Purpose of the Study:

• To investigate Plasmodium falciparum infection prevalence, persistence, and anti-parasite immunity over 10 weeks in a longitudinal cohort.
• To assess the relationship between immune responses to specific antigens and infection/gametocyte carriage.

Main Methods:

• Longitudinal monitoring of 100 participants for Plasmodium falciparum infection using RT-qPCR and microscopy.
• Measurement of anti-parasite immunity against gametocyte and asexual antigens (Pfs48/45.6C, Pfs230proC, EBA175RIII-V).
• Analysis of gametocyte diversity and correlation of immune responses with parasite/gametocyte densities.

Main Results:

• High infection prevalence (89% infected), with 16 participants having persistent infections and over 70% infected ≥3 times.
• Submicroscopic gametocyte prevalence was high (≥48% of carriers).
• Antigen-specific IgG titers inversely correlated with parasite and gametocyte densities, indicating partial immunity.

Conclusions:

• Ongoing Plasmodium falciparum transmission is driven by frequent, often subclinical, infections and diverse gametocyte clones, particularly in children.
• Individual-level variation in infection status highlights the need for targeted interventions.
• Focusing on children with distinct gametocyte clones is recommended for malaria control programs.