Three proteins of apparent molecular weights on reducing SDS-PAGE of 255, 59, and 53 kilodaltons have been identified as the targets on gametes of P. falciparum malaria of two monoclonal antibodies (MAbs) that act synergistically to block transmission of the parasites to mosquitoes.
In the era of malaria elimination and eradication, drug-based and vaccine-based approaches to reduce malaria transmission are receiving greater attention. Such interventions require assays that reliably measure the transmission of Plasmodium from humans to Anopheles mosquitoes. We compared two commonly used mosquito feeding assay procedures: direct skin feeding assays and membrane feeding assays. Three conditions under which membrane feeding assays are performed were examined: assays with i) whole blood, ii) blood pellets resuspended with autologous plasma of the gametocyte carrier, and iii) blood pellets resuspended with heterologous control serum. 930 transmission experiments from Cameroon, The Gambia, Mali and Senegal were included in the analyses. Direct skin feeding assays resulted in higher mosquito infection rates compared to membrane feeding assays (odds ratio 2.39, 95% confidence interval 1.94–2.95) with evident heterogeneity between studies. Mosquito infection rates in membrane feeding assays and direct skin feeding assays were strongly correlated (p<0.0001). Replacing the plasma of the gametocyte donor with malaria naïve control serum resulted in higher mosquito infection rates compared to own plasma (OR 1.92, 95% CI 1.68–2.19) while the infectiousness of gametocytes may be reduced during the replacement procedure (OR 0.60, 95% CI 0.52–0.70). Despite a higher efficiency of direct skin feeding assays, membrane feeding assays appear suitable tools to compare the infectiousness between individuals and to evaluate transmission-reducing interventions. Several aspects of membrane feeding procedures currently lack standardization; this variability makes comparisons between laboratories challenging and should be addressed to facilitate future testing of transmission-reducing interventions.
Enzyme-linked immunosorbent assays (ELISA's) were compared with dissection results on mosquitoes of the Anopheles punctulatus Doenitz complex collected in Papua New Guinea. Assays were based on monoclonal antibodies developed against the immunodominant peptide repeat portion of the circumsporozoite (CS) proteins of Plasmodium falciparum (Welch) and Plasmodium vivax (Grassi & Feletti) sporozoites. Excellent correlation was observed between the two methods, with positivity rates of 4.0% for salivarygland midgut infections determined by dissection and 3.4% for the combined ELISA's. These species-specific assays, with a 10-fold increase in sensitivity over previously used ELISA's, gave geometric means of 920 P. falciparum and 460 P. vivax sporozoites per infected mosquito. Use of genetically engineered P. falciparum and synthetic P. vivax CS antigens eliminated the requirement for salivary-gland sporozoites as quantitative positive controls. Approximately 30 pg of recombinant P. falciparum and 60 pg of synthetic P. vivax CS antigen corresponded to 100 salivary-gland sporozoites in the respective ELISA.
We assessed malaria infection in relation to age, altitude, rainfall, socio-economic factors and coverage of control measures in a representative sample of 11437 people in Amhara, Oromia and SNNP regions of Ethiopia in December 2006-January 2007. Surveys were conducted in 224 randomly selected clusters of 25 households (overall sample of 27884 people in 5708 households). In 11538 blood slides examined from alternate households (83% of those eligible), malaria prevalence in people of all ages was 4.1% (95% CI 3.4-4.9), with 56.5% of infections being Plasmodium falciparum. At least one mosquito net or one long-lasting insecticidal net (LLIN) was present in 37.0% (95% CI 31.1-43.3) and 19.6% (95% CI 15.5-24.5) of households, respectively. In multivariate analysis (n=11437; 82% of those eligible), significant protective factors were: number of LLINs per household (odds ratio [OR] (per additional net)=0.60; 95% CI 0.40-0.89), living at higher altitude (OR (per 100 m)=0.95; 95% CI 0.90-1.00) and household wealth (OR (per unit increase in asset index)=0.79; 95% CI 0.66-0.94). Malaria prevalence was positively associated with peak monthly rainfall in the year before the survey (OR (per additional 10 mm rain)=1.10; 95% CI 1.03-1.18). People living above 2000 m and people of all ages are still at significant risk of malaria infection.
Summary: The proportion of blood meals taken on humans which are infectious to mosquitoes in the Madang area, Papua New Guinea was estimated by two methods. In the first, laboratory rearedAnopheles farautiwere fed on individuals of all ages at village surveys. The results showed that 3·8% of people were infectious and that the mean percentage of mosquitoes which became infected by feeding on these people was 37·9%. From the average proportion of mosquitoes infected, the probability that a mosquito feeding on a human would pick up infection was 0·013±0·005. In the second approach mosquitoes were fed on identifiedPlasmodium falciparum, P. vivaxandP. malariaegametocyte carriers. The results indicated that 46% of gametocyte carriers were infectious and that the mean probability of a mosquito becoming infected after feeding on a gametocyte carrier was 0·151±0·029. Gametocyte prevalence rates in all ages measured over 18 months in three villages averaged 3·3%P. falciparum, 4·0%P. vivaxand 0·7%P. malariae, totalling 8·0±0·7%. Combining gametocyte prevalence rates with the probability of a mosquito becoming infected from a gametocyte carrier, the probability of a mosquito becoming infected following a blood meal on a member of the human population was estimated to be 0·012±0·003.