The plasticity of Plasmodium falciparum gametocytaemia in relation to age in Burkina Faso

BACKGROUND: Malaria transmission depends on the presence of gametocytes in the peripheral blood. In this study, the age-dependency of gametocytaemia was examined by microscopy and molecular tools. METHODS: A total of 5,383 blood samples from individuals of all ages were collected over six cross sectional surveys in Burkina Faso. One cross-sectional study used quantitative nucleic acid sequence based amplification (QT-NASBA) for parasite quantification (n = 412). The proportion of infections with concurrent gametocytaemia and median proportion of gametocytes among all parasites were calculated. RESULTS: Asexual parasite prevalence and gametocyte prevalence decreased with age. Gametocytes made up 1.8% of the total parasite population detected by microscopy in the youngest age group. This proportion gradually increased to 18.2% in adults (p < 0.001). Similarly, gametocytes made up 0.2% of the total parasite population detected by QT-NASBA in the youngest age group, increasing to 5.7% in adults (p < 0.001). This age pattern in gametocytaemia was also evident in the proportion of gametocyte positive slides without concomitant asexual parasites which increased from 13.4% (17/127) in children to 45.6% (52/114) in adults (OR 1.55, 95% CI 1.38-1.74, p < 0.001). CONCLUSIONS: The findings of this study suggest that although gametocytes are most commonly detected in children, the proportion of asexual parasites that is committed to develop into gametocytes may increase with age. These findings underscore the importance of adults for the human infectious reservoir for malaria

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

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