A longitudinal study of immune responses to Plasmodium falciparum sexual stage antigens in Tanzanian adults.

Next to children, adults form a substantial part of the infectious reservoir that is responsible for the spread of malaria. In this longitudinal study, we determined sexual stage immune responses to Plasmodium falciparum and infectiousness to mosquitoes in adults from an area with intense malaria transmission. A cohort of 43 Tanzanian adults was followed for 18 months. Parasitological data were collected monthly; serum once every three months. Antibody prevalences were determined for sexual stage antigens Pfs230 and Pfs48/45 and circumsporozoite protein (NANP5)(n = 199). Functional transmission reducing activity (TRA) was assessed by standard membrane feeding assay (SMFA; n = 85). Cumulative parasite prevalence was 67.4% (29/43) for asexual stages and 34.9% (15/43) for gametocytes. Enrolment antibody prevalence was 95.3% (41/43) for NANP5, 18.9% (7/37) for Pfs230 and 7% (3/43) for Pfs48/45 epitope 3. TRA > 50% reduction was seen in 48.2% (41/85) and TRA > 90% reduction in 4.7% (4/85) of the samples. Our findings of low and inconsistent sexual stage immune responses are likely to be the result of a low exposure to gametocytes in this older age group. This may in turn be caused by effective asexual stage immunity. We conclude that the infectivity of older individuals is less likely to be affected by sexual stage immunity.

Transmission-reducing immunity is inversely related to age in Plasmodium falciparum gametocyte carriers.

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.

Treatment failure of pyrimethamine-sulphadoxine and induction of Plasmodium falciparum gametocytaemia in children in western Kenya.

Sub-Saharan Africa faces increasing levels of resistance of Plasmodium falciparum parasites to the first-line 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.