Abstract
BackgroundThe impact of the age of first Plasmodium falciparum infection on the rate of acquisition of immunity to malaria and on the immune correlates of protection has proven difficult to elucidate. A randomized, double-blind, placebo-controlled trial using monthly chemoprophylaxis with sulphadoxine-pyrimethamine plus artesunate was conducted to modify the age of first P. falciparum erythrocytic exposure in infancy and assess antibodies and malaria risk over two years.MethodsParticipants (n = 349) were enrolled at birth to one of three groups: late exposure, early exposure and control group, and were followed up for malaria morbidity and immunological analyses at birth, 2.5, 5.5, 10.5, 15 and 24 months of age. Total IgG, IgG subclasses and IgM responses to MSP-119, AMA-1, and EBA-175 were measured by ELISA, and IgG against variant antigens on the surface of infected erythrocytes by flow cytometry. Factors affecting antibody responses in relation to chemoprophylaxis and malaria incidence were evaluated.ResultsGenerally, antibody responses did not vary significantly between exposure groups except for levels of IgM to EBA-175, and seropositivity of IgG1 and IgG3 to MSP-119. Previous and current malaria infections were strongly associated with increased IgG against MSP-119, EBA-175 and AMA-1 (p < 0.0001). After adjusting for exposure, only higher levels of anti-EBA-175 IgG were significantly associated with reduced clinical malaria incidence (IRR 0.67, p = 0.0178).ConclusionsOverall, the age of first P. falciparum infection did not influence the magnitude and breadth of IgG responses, but previous exposure was critical for antibody acquisition. IgG responses to EBA-175 were the strongest correlate of protection against clinical malaria.Trial registrationClinicalTrials.gov: NCT00231452.
Highlights
The impact of the age of first Plasmodium falciparum infection on the rate of acquisition of immunity to malaria and on the immune correlates of protection has proven difficult to elucidate
Comparison of antibody responses between chemoprophylaxis groups The magnitude of antibody responses was compared between study groups during the intervention period and after the intervention period
Results of linear regression analyses were similar after adjusting for previous episodes of clinical malaria
Summary
The impact of the age of first Plasmodium falciparum infection on the rate of acquisition of immunity to malaria and on the immune correlates of protection has proven difficult to elucidate. Malaria is among the leading causes of morbidity and death in children, despite being a preventable disease. Under similar levels of exposure to Plasmodium falciparum different individuals experience different outcomes; while some may die of severe malaria others may experience mild disease to asymptomatic infection [2,3]. The acquisition of partial immunity to severe forms of the disease is observed relatively early in life [2], whereas immunity to parasitaemia and mild clinical malaria appear to take longer to develop and may require repeated parasite exposure for maintenance [5,6]. Parasite genetic variability and parasite-induced immunosuppression influence the acquisition of immunity [7,8]
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