Submicroscopic Plasmodium falciparum gametocytaemia and the contribution of malaria transmission.

Plasmodium falciparum malaria parasites can be transmitted from man to mosquito when mosquitoes ingest the sexual parasite stages (gametocytes) during blood feeding. These gametocytes occur in relatively small numbers when detected by microscopy, but malaria is transmitted efficiently. We have developed a molecular technique (QT-NASBA) for quantification of various stages of P. falciparum parasites, based on real-time RNA amplification, that is considered more sensitive than microscopy and more practical in use than other methods. QT-NASBA was used to study parasite dynamics in volunteers with experimental P. falciparum infections. It was demonstrated that sexual development starts immediately during bloodstage infection, although without subsequent maturation into full-grown gametocytes. The efficacy of drug treatment and its effect on gametocytes was studied in Kenyan children with P. falciparum malaria. Three different drug regimens, all had a higher clinical efficacy than sulphadoxine-pyrimethamine (SP). Additionally, a reduction of gametocytes was observed after artemisinin combination therapy. Although artesunate combination therapy resulted in significantly lower prevalence and density of gametocytes compared to SP monotherapy, it did not eliminate all gametocytes. Many children harboured gametocytes both before and after treatment with SP or SP + artesunate, often at densities below the microscopical detection limit. The frequent presence of submicroscopic gametocytaemia was confirmed in individuals of all ages in Burkina Faso.To investigate the epidemiological importance of submicroscopic gametocytes, various concentrations of gametocytes were fed to mosquitoes both in the laboratory and in the field and subsequent mosquito infections were monitored. Even though the probability of mosquito infection increases with the gametocyte density, submicroscopical gametocyte densities can still infect mosquitoes. With the large number of Kenyan children with submicroscopic gametocytaemia, this group may be responsible for approximately half of the transmission.