Abstract
BackgroundMan to mosquito transmission of malaria depends on the presence of the sexual stage parasites, gametocytes, that often circulate at low densities. Gametocyte densities below the microscopical threshold of detection may be sufficient to infect mosquitoes but the importance of submicroscopical gametocyte carriage in different transmission settings is unknown.Methodology/Principal FindingsMembrane feeding experiments were carried out on 80 children below 14 years of age at the end of the wet season in an area of seasonal malaria transmission in Burkina Faso. Gametocytes were quantified by microscopy and by Pfs25-based quantitative nucleic acid sequence-based amplification assay (QT-NASBA). The children's infectiousness was determined by membrane feeding experiments in which a venous blood sample was offered to locally reared Anopheles mosquitoes. Gametocytes were detected in 30.0% (24/80) of the children by microscopy compared to 91.6% (65/71) by QT-NASBA (p<0.001). We observed a strong association between QT-NASBA gametocyte density and infection rates (p = 0.007). Children with microscopically detectable gametocytes were more likely to be infectious (68.2% compared to 31.7% of carriers of submicroscopical gametocytes, p = 0.001), and on average infected more mosquitoes (13.2% compared to 2.3%, p<0.001). However, because of the high prevalence of submicroscopical gametocyte carriage in the study population, carriers of sub-microscopical gametocytes were responsible for 24.2% of the malaria transmission in this population.Conclusions/SignificanceSubmicroscopical gametocyte carriage is common in an area of seasonal transmission in Burkina Faso and contributes substantially to the human infectious reservoir. Submicroscopical gametocyte carriage should therefore be considered when implementing interventions that aim to reduce malaria transmission.
Highlights
The transmission of malaria depends on the presence of mature sexual stage parasites, gametocytes, in the human peripheral blood
The proportion of infected mosquitoes was positively associated with Pfs25 QT-NASBA gametocyte density (Spearman correlation coefficient = 0.34, p = 0.007; Figure 1) and was not influenced by a clinical malaria episode (p = 0.18) or the presence of fever (p = 0.63).The relation between the proportion of infected mosquitoes and Pfs25 QT-NASBA gametocyte density was best described by the equation Y = 0.0176Ln(X) + 0.0187 (R2 = 0.153)
It is unclear (i) how important this phenomenon is in areas of seasonal malaria [20] and (ii) how important submicroscopical gametocyte densities are for malaria transmission in the general, typically asymptomatic, population
Summary
The transmission of malaria depends on the presence of mature sexual stage parasites, gametocytes, in the human peripheral blood. Once ingested by a mosquito taking a blood meal, gametocytes develop through different mosquito-specific stages and result in infection of the mosquito salivary glands with sporozoites. This renders the mosquito infectious to humans. Molecular tools have become available to detect and quantify gametocytes at densities well below the microscopical threshold, in the order of 0.02–10 gametocytes/mL of blood [4] Using these techniques, it has become evident that the proportion of gametocyte carriers in the population has been grossly underestimated and that the gametocyte reservoir may be 2–5 fold larger than assumed based on microscopy [6,7]. Man to mosquito transmission of malaria depends on the presence of the sexual stage parasites, gametocytes, that often circulate at low densities. Gametocyte densities below the microscopical threshold of detection may be sufficient to infect mosquitoes but the importance of submicroscopical gametocyte carriage in different transmission settings is unknown
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