Abstract
BackgroundProtective immunity to malaria is acquired after repeated infections in endemic areas. Asymptomatic multiclonal P. falciparum infections are common and may predict host protection. Here, we have investigated the effect of clearing asymptomatic infections on the risk of clinical malaria.MethodsMalaria episodes were continuously monitored in 405 children (1–6 years) in an area of moderate transmission, coastal Kenya. Blood samples collected on four occasions were assessed by genotyping the polymorphic P. falciparum merozoite surface protein 2 using fluorescent PCR and capillary electrophoresis. Following the second survey, asymptomatic infections were cleared with a full course of dihydroartemisinin.ResultsChildren who were parasite negative by PCR had a lower risk of subsequent malaria regardless of whether treatment had been given. Children with ≥2 clones had a reduced risk of febrile malaria compared with 1 clone after clearance of asymptomatic infections, but not if asymptomatic infections were not cleared. Multiclonal infection was associated with an increased risk of re-infection after drug treatment. However, among the children who were re-infected, multiclonal infections were associated with a shift from clinical malaria to asymptomatic parasitaemia.ConclusionThe number of clones was associated with exposure as well as blood stage immunity. These effects were distinguished by clearing asymptomatic infection with anti-malarials. Exposure to multiple P. falciparum infections is associated with protective immunity, but there appears to be an additional effect in untreated multiclonal infections that offsets this protective effect.
Highlights
Immune protection against Plasmodium falciparum malaria is gradually acquired after repeated infections and largely dependent on exposure intensity [1]
To clarify the importance of persistent multiclonal P. falciparum infections on host immunity, we have investigated how clearance of asymptomatic infections affects the subsequent risk of clinical malaria in children (1–6 years) living on the coast of Kenya
Vaccination had no effect on the incidence of clinical malaria episodes or on prevalence of asymptomatic parasiteamias [18], nor on number of clones measured in this study (P = 0.9 by Student’s T)
Summary
Immune protection against Plasmodium falciparum malaria is gradually acquired after repeated infections and largely dependent on exposure intensity [1]. The severity and frequency of malaria episodes decrease with age in areas of high transmission. The mechanisms by which protective malaria immunity is acquired and maintained are still incompletely understood, antibodies are recognized to be important [3]. Acquired antibody responses to malaria in younger children may, be rather short lived [4,5]. The persistence of asymptomatic parasitemia reflects the non-sterilizing nature of malaria immunity, parasites may be important for the maintenance of immune responses [6] and protection against new infections [7]. Protective immunity to malaria is acquired after repeated infections in endemic areas. We have investigated the effect of clearing asymptomatic infections on the risk of clinical malaria
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