Impact of genetic complexity on longevity and gametocytogenesis of Plasmodium falciparum during the dry and transmission-free season of eastern Sudan
Introduction
Reproductive success is a central life history determinant of the evolutionary fitness of living organisms. For malaria parasites (Plasmodium spp.), the production of mosquito-infective gametocytes is important not only for propagation, but also for generation of new strains—e.g. those capable of evading human immune responses and anti-malarial drug pressure. An understanding of the biology of gametocytogenesis is therefore critical when considering control strategies aimed at limiting the reproductive success of the malaria parasite.
Plasmodium falciparum clones have been found to vary significantly in their capacity to produce gametocytes in culture, and gametocytogenesis has been suggested to be a stable, genetically determined characteristic (Graves et al., 1984). In vertebrates, malaria infection is initiated by mosquito-delivered sporozoites that invade the liver, then differentiate and rapidly multiply as asexual forms in the circulation. Some asexual parasites differentiate into gametocytes, forms that cannot replicate but can be transmitted to mosquitoes. It takes approximately 9–12 days for gametocytes to be produced from asexual forms. Once mature, gametocyte longevity and their infectivity to mosquitoes probably vary over time (Hawking et al., 1971, Smalley et al., 1981). Therefore, consistent gametocyte production by individual parasite clones is critical for transmission.
The low density of P. falciparum gametocytes in natural infections appears to contradict the apparently high transmission success of this parasite in nature (Taylor and Read, 1997). The recent advent of molecular diagnosis of gametocytes has in part resolved this paradox by demonstrating the occurrence of numerous sub-microscopic gametocyte reservoirs in people living in endemic areas (Menegon et al., 2000, Abdel-Wahab et al., 2002), and has also identified multiple gametocyte genotypes within a single infection (Abdel-Wahab et al., 2002).
In the present study, we have exploited these molecular techniques to examine the longevity of gametocytogenesis of P. falciparum during the transmission-free season of eastern Sudan. In this region, malaria transmission is limited to the short rainy season, and pauses over a period of 7–9 months during the dry season (Hamad et al., 2002). Previous studies have indicated that P. falciparum appearing in the transmission season gives rise to asymptomatic sub-patent asexual parasitaemia that persists throughout the dry season. Furthermore, genotypes of different clones can survive together in individual infections and fluctuate through this period (Babiker et al., 1998). Limited cross-sectional surveys have suggested that some of these long lasting infections are capable of sustaining gametocyte production during the dry season (Abdel-Wahab et al., 2002). The aim of this study was to elucidate the longevity of individual P. falciparum infections, and to examine the impact of clonal multiplicity on longevity and gametocytogenesis among clones that survive the dry season as chronic asymptomatic infections.
Section snippets
Study area
The study was carried out in Asar village (longitude 35°.30′ E and latitude 13°.30′ N), Gedaref state, eastern Sudan, where malaria transmission is short and distinctly seasonal following the annual rains (July–November), reaching a peak in October. However, by January, the number of malaria cases drops substantially and entomological surveys have shown no evidence of transmission during the long dry season (Hamad et al., 2002). P. falciparum is the predominant malaria parasite accounting for
P. falciparum infection and gametocytes among the cohort
At the start of the study in November 2001 (transmission season), all 121 patients recruited to the study harboured microscopically detectable P. falciparum asexual infections. Following chloroquine treatment, both asexual parasite and gametocyte densities dropped dramatically and by the beginning of March 2002, none of the patients harboured microscopically visible asexual forms or gametocytes (Fig. 1(A)).
Polymerase chain reaction (PCR) and RT-PCR were carried out on 494 blood samples
Discussion
We have exploited the unique malaria epidemiology setting of eastern Sudan to examine P. falciparum gametocytogenesis and longevity during the lengthy dry and transmission-free season (Hamad et al., 2002). We have investigated within-host survival and transmission potential (gametocytogenesis) of individual P. falciparum clones during this period, and whether they are influenced by clonal multiplicity. The longevity of P. falciparum infection and gametocyte carriage varied markedly between
Acknowledgements
The work described here would not have been possible without the continuous co-operation of the villagers of Asar, the Malaria research group of the Biochemistry Department, Faculty of Medicine, Khartoum University, the Malaria Administration of the Sudanese Ministry of Health and the staff of Gedaref Hospital, Sudan.
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