Williams · The Journal of infectious diseases 2005 · prospective cohort study · n=?

Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases.

Cited 338 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective observational cohort study evaluating disease incidence in children with and without sickle cell trait.

PubMed 15942909 · doi:10.1086/430744 · record verified 2026-08-26

What was done

Researchers tracked the incidence of *Plasmodium falciparum* malaria and other childhood illnesses across two cohorts of children living on the coast of Kenya to evaluate the clinical protection conferred by sickle cell trait (HbAS).

What was found

The protective effect of HbAS was entirely specific to *P. falciparum* malaria, with no significant impact on other childhood diseases. HbAS did not alter the prevalence of asymptomatic parasitemia, but provided approximately 50% protection against mild clinical malaria, 75% protection against hospital admission for malaria, and nearly 90% protection against severe or complicated malaria. The trait also suppressed parasite densities during clinical episodes.

Why it matters

This study provides precise epidemiological evidence for natural selection, demonstrating that HbAS does not prevent infection but specifically suppresses parasite density to prevent severe, life-threatening malaria manifestations.

Limits

The abstract does not report the total sample size, cohort follow-up duration, or confidence intervals for the effect sizes. It is restricted to a single geographic area (coastal Kenya), and potential unmeasured confounders inherent to observational cohort designs are not detailed in the abstract.

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