Laboratory assays for the detection of malaria transmission reducing activity.

Human malaria is a parasitic disease, which causes over 200 million clinical cases and more than one million deaths per year. Most cases occur in children aged below five and the most affected continent is Africa. Malaria is spread by sexual forms of Plasmodium parasites (gametocytes), which are transmitted by anopheline mosquitoes from infected to susceptible humans. Human subjects in endemic areas may naturally acquire immunity against the parasite stages involved in transmission. This transmission reducing activity (TRA) can be assessed by bioassays, feeding mosquitoes with blood, gametocytes and serum. The first objective was to study the association of TRA with transmission intensity in local populations in Cameroon. Transmission intensity in capital Yaoundé (34 infectious bites per man per year, ibpy) was about five times lower than in rural Koundou (previously reported 177 ibpy). The probability that gametocyte carriers showed TRA was 4.6 fold higher in Koundou than in Yaoundé. In addition, there was a trend towards higher TRA values in individuals with higher gametocytaemias. The second objective was to optimise the bioassay and the calculation method for TRA. Repeated measurements of individual sera showed some variability in TRA, which was larger between experiments than within experiments. Therefore, sera are better compared within rather than between experiments. Besides, TRA showed a strong association with concentration of anti-sexual stage antibodies, what supports the notion of reproducible TRA. The adapted bioassay was applied on sera from non-immune transmigrants in malaria endemic Papua, Indonesia. Increases of TRA and anti-sexual stage antibodies were shown after one to four infections already. TRA and antibodies are thus rapidly acquired upon exposure to infection. We expect that the adapted methods will enable more detailed studies on the development and maintenance of TRA in endemic populations