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We evaluated the relationship between immune response markers and the multiplicity of Plasmodium falciparum infections in order to assess the validity of the latter as an indicator of the acquisition of anti-malarial immunity. Parasite populations present during malaria episodes of 64 Gabonese children who presented with at least 4 such attacks during active follow-up over a 7-year period were characterized using MSP-1 and MSP-2 PCR-based methods. Plasma samples taken at healthy and parasite-free phase were used to measure P. falciparum antigen-specific antibody and cytokine activity. We found evidence of intra- and inter-individual variation in the number of parasite genotypes present in different malaria episodes, although in 72% of isolates no more than 2 parasite genotypes were detectable. Samples with the highest multiplicity were from children with significantly lower (p < 0.03) antibody responses to specific asexual stage antigens. Additionally, the whole blood interferon-gamma production capacity was significantly higher (p < 0.02) in those with lower infection multiplicity. Malaria episodes with multiple clones indeed reflect a low level of acquired immunity and a consequently poor capacity to control the infection. These findings suggest that the multiplicity of falciparum infection may be a potentially useful parameter in the evaluation of malaria control interventions.

Congo-Brazzaville has recently adopted artesunate-amodiaquine as the first-line antimalarial drug to replace chloroquine. Before the implementation of this new strategy, we conducted several clinical studies to assess the therapeutic efficacy of former, classical first-line antimalarial drugs in the city of Brazzaville, in which reside about 30% of the Congolese population. From 2003 to 2005, non-randomised trials were conducted to evaluate the efficacy of sulfadoxine-pyrimethamine (SP) (n=97 patients), amodiaquine (AQ) (n=62 patients), and the combination of sulfadoxine-pyrimethamine-amodiaquine (n=54 patients) in children aged between 6 months and 5 years with uncomplicated malaria using the 2003 WHO guidelines during the 28-day follow-up period. After excluding new infections by PCR, the proportion of treatment failure on day 28 was 30.2% (95% confidence interval, 19.2-43.0%) for sulfadoxine-pyrimethamine, 34.8% (95% confidence interval, 21.4-50.2%) for amodiaquine, and 14.2% (95% confidence interval, 5.9-27.2%) for sulfadoxine-pyrimethamine+amodiaquine combination. Treatment with sulfadoxine-pyrimethamine was associated with an increase of gametocyte charge. These results suggest that neither sulfadoxine-pyrimethamine nor amodiaquine is efficacious as monotherapy and that their combination may not remain effective in the coming years. Based on our results, the implementation of artemisinin-based combination therapy appears to be urgent in the country.

Chloroquine (CQ) resistance in Plasmodium falciparum has been particularly associated with mutations in the pfcrt gene. The present study was carried out in the malaria hyperendemic town of Brazzaville (Republic of Congo, Central Africa) where CQ is still recommended and used as a first-line drug for P. falciparum malaria. We assessed the efficacy of CQ in vivo, and the association between pfcrt mutation at codon 76 and treatment outcome in 50 children with uncomplicated malaria. The failure rate on day 28 was 95.7% and the pfcrt K76T mutation was present in 100% of isolates. No variation in the multiplicity of infection was observed in pre- and post-treatment isolates. In further 87 isolates from uncomplicated patients not treated with CQ, the mutation was detected in 98.5% of isolates. This study confirms the high level of in vivo resistance to CQ and shows the high prevalence of pfcrt K76T mutation in the Republic of Congo.