No abstract

Objective:The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccine demonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes.Design: P. falciparum DNA from isolates collected during the trial was used for genotype studies.Setting:The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004.Participants:Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection.Outcome:Divergence of DNA sequence encoding the CSP T cell–epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined.Results:We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at study month 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p = 0.035, p = 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p = 0.478).Conclusions:RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections.

No abstract

We evaluated the impact of intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP), which was given at ages 3, 4, and 9 months through the Expanded Program on Immunization (EPI), on the development of antibody responses to Plasmodium falciparum in Mozambique. Immunoglobulin M (IgM) and IgG subclass antibodies specific to whole asexual parasites and to recombinant MSP-1 19 , AMA-1, and EBA-175 were measured at ages 5, 9, 12, and 24 months for 302 children by immunofluorescence antibody tests and by enzyme-linked immunosorbent assays. Antibody responses did not significantly differ between children receiving IPTi with SP and those receiving a placebo at any time point measured, with the exception of the responses of IgG and IgG1 to AMA-1 and/or MSP-1 19 , which were significantly higher in the SP-treated group than in the placebo group at ages 5, 9, and/or 24 months. IPTi with SP given through the EPI reduces the frequency of malarial illness while allowing the development of naturally acquired antibody responses to P. falciparum antigens.Malaria remains one of the major infectious diseases globally, causing up to 3 million deaths and close to 5 billion episodes of clinical illness per year (7). In areas characterized by hyperendemic transmission, the greatest burden of malaria occurs in children less than 12 months of age (38); consequently, infants in sub-Saharan Africa are the main target population for any malaria control tool.Intermittent preventive treatment in infants (IPTi) that consists of the administration of a full dose of an antimalarial within the Expanded Program on Immunization (EPI) has proven to reduce the risk of malaria in this vulnerable group (37). This strategy has gained increasing interest, and several intervention trials evaluating the efficacy of IPTi in the reduction of malaria morbidity have been and are still being carried out in several sub-Saharan countries (Tanzania, Ghana, Senegal, Mozambique, Gabon, and Kenya) as part of an international consortium (www.ipti-malaria.org). However, before setting any policy recommendation for the large-scale implementation of IPTi for malaria control, it is necessary to fully evaluate the consequences that this early preventive intervention may have later in life.An important issue that needs to be considered is the impact that IPTi may have on the development of naturally acquired immunity to malaria. Early studies of continuous malaria chemoprophylaxis raised concerns regarding the loss of or delay in the acquisition of protective immunity (16,23,34). Weekly chemoprophylaxis between 2 and 11 months of age in infants in Tanzania significantly reduced the incidence of malaria and anemia during the first year of life, but the risk increased in the second year after stopping the intervention (26), suggesting that protection against Plasmodium falciparum infection during infancy had delayed the development of immunity to malaria. However, subsequent studies of IPTi in Tanzania (37) and Mozambique (24) showed that, as ...