Immunity to the sexual stages of Plasmodium falciparum is induced during natural infections and can significantly reduce the transmission of parasites to mosquitoes (transmission reducing activity; TRA) but little is known about how these responses develop with increasing age/exposure to malaria. Routinely TRA is measured in the standard membrane feeding assay (SMFA). Sera were collected from a total of 199 gametocyte carriers (median age 4 years, quartiles 2 and 9 years) near Ifakara, Tanzania; 128 samples were tested in the SMFA and generated TRA data classified as a reduction of > 50% and > 90% of transmission. TRA of > 50% was highest in young children (aged 1-2) with a significant decline with age (chi(2) trend = 5.79, P = 0.016) and in logistic regression was associated with prevalence of antibodies to both Pfs230 and Pfs48/45 (OR 4.03, P = 0.011 and OR 2.43 P = 0.059, respectively). A TRA of > 90% reduction in transmission was not age related but was associated with antibodies to Pfs48/45 (OR 2.36, P = 0.055). Our data confirm that antibodies are an important component of naturally induced TRA. However, whilst a similar but small proportion of individuals at all ages have TRA > 90%, the gradual deterioration of TRA > 50% with age suggests decreased antibody concentration or affinity. This may be due to decreased exposure to gametocytes, probably as a result of increased asexual and/or gametocyte specific immunity.

Separate studies carried out in Farafenni, The Gambia and Ifakara, Tanzania in 1990-94 provided comparative data on population age structure, population gametocyte prevalences and gametocyte carrier infectivity. The percentage of the population estimated to be infective to mosquitoes was 5.5% and 3.8% in The Gambia and Tanzania, respectively. The age groups 1-4 years, 5-9 years, 10-19 years and 20 years or more comprised 17.5%, 21.7%, 22.2% and 37.9%, respectively, of the infectious population in The Gambia; the corresponding figures for Tanzania were 30.9%, 25.2%, 15.7% and 28.1%. These figures are in broad agreement with those from other published studies which estimated the infectious reservoir directly and suggest that adults contribute significantly to the infectious reservoir of malaria, particularly in areas of intense seasonal transmission. Control measures aimed at reduction of transmission may have only a limited effect in areas of moderate seasonal transmission if directed only at children.

To further characterize protective-type (IgG1/IgG3) antibody responses to Plasmodium falciparum blood stage in putatively immune individuals' plasma, we have tested for various analogs of the 19 kDa C-terminus of the MSP1 antigen obtained as secreted recombinant proteins from Saccharomyces cerevisiae. One of four proteins was then identified on the basis of consistent IgG3, along with less variable IgG1 recognition. This protein has thus been selected for further functional assays of IgG1/IgG3 antibodies.

Abstract. We investigated the dynamics of Plasmodium falciparum gametocytemia in symptomatic patients attending a local dispensary in the Kilombero district, Tanzania. Consenting individuals aged one and above, with varying asexual and sexual parasitemias were treated appropriately and asked to return weekly for 28 days. Gametocyte prevalence was highest on Day 7 of follow-up in all age groups (overall 30.5%). Multifactorial analysis showed that young age ( 2 ϭ 18.4; P ϭ 0.004), high asexual parasitemia on presentation ( 2 ϭ 19.4; P ϭ 0.0007) and gametocyte positivity on presentation ( 2 ϭ 29.4; P ϭ 0.001) were all significantly associated with the presence of gametocytes on Days 7 and 14 of follow-up. High presentation of asexual parasitemia alone was positively correlated with higher gametocyte densities on both days of follow-up (F 4, 297 ϭ 2.0; P ϭ 0.049). Gametocyte incidence rates decreased significantly with age ( 2 ϭ 7.6, P Ͻ 0.005). In summary, in this group of chloroquine-treated individuals, gametocyte prevalence and incidence rates decreased with age, while densities remained relatively constant.

SummarySub-Saharan Africa faces increasing levels of resistance of Plasmodium falciparum parasites to the firstline drug pyrimethamine-sulphadoxine (SP). Successful treatment with SP is reported to induce gametocytes and drug resistance may further increase gametocytaemia after treatment. Treatment success, gametocyte prevalence and gametocyte density were determined in 224 asymptomatic children in western Kenya on day 7 after treatment with SP. Treatment failure (R2 or R3 resistance) was observed in 22% of the children. The relative risk to show gametocytes on day 7 after treatment in children with treatment failure was 4.1 (95% CI 1.4-11.6) times higher compared to children with a sensitive infection, after adjustment for age and trophozoite density at the start of treatment. In addition, the gametocyte density was also higher upon SP treatment failure. These findings are reason for concern, as the increased gametocyte prevalence and density after SP treatment failure may increase the spread of SP-resistant strains in the population.

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