Associations between Season and Gametocyte Dynamics in Chronic Plasmodium falciparum Infections

Introduction: In a markedly seasonal malaria setting, the transition from the transmission-free dry season to the transmission season depends on the resurgence of the mosquito population following the start of annual rains. The sudden onset of malaria outbreaks at the start of the transmission season suggests that parasites persist during the dry season and respond to either the reappearance of vectors, or correlated events, by increasing the production of transmission stages. Here, we investigate whether Plasmodium falciparum gametocyte density and the correlation between gametocyte density and parasite density show seasonal variation in chronic (largely asymptomatic) carriers in eastern Sudan. Materials and Methods: We recruited and treated 123 malaria patients in the transmission season 2001. We then followed them monthly during four distinct consecutive epidemiological seasons: transmission season 1, transmission-free season, pre-clinical period, and transmission season 2. In samples collected from 25 participants who fulfilled the selection criteria of the current analysis, we used quantitative PCR (qPCR) and RT-qPCR to quantify parasite and gametocyte densities, respectively. Results and Discussion: We observed a significant increase in gametocyte density and a significantly steeper positive correlation between gametocyte density and total parasite density during the pre-clinical period compared to the preceding transmission-free season. However, there was no corresponding increase in the density or prevalence of total parasites or gametocyte prevalence. The increase in gametocyte production during the pre-clinical period supports the hypothesis that P. falciparum may respond to environmental cues, such as mosquito biting, to modulate its transmission strategy. Thus, seasonal changes may be important to ignite transmission in unstable-malaria settings

Correlation between parasite and gametocyte densities across seasons.

<p>The correlation between gametocyte and parasite densities varied across the seasons (i.e. there is a season by parasite density interaction). During the pre-clinical period, a strong and positive correlation was observed. This suggests that a larger proportion of total parasites are gametocytes during the pre-clinical season, compared to the other 3 seasons. Points represent raw data; lines represent the best-fit between values of log₁₀ parasite and gametocytes densities as classified by season. Arbitrary numbers are used to present gametocyte and total parasite densities, denoted as blood_RNA and blood_DNA, to account for sample processing differences that might result in the appearance that some samples contain more gametocytes than total parasites.</p

Seasonality of annual rains, mosquito abundance, and categorisation of seasons.

<p>(A) Monthly average rainfall in mm (blue line), maximum (red line) and minimum (green line) temperature in the study area between November 2001 and December 2002 (Meteorological Authority, Sudan). Mosquito symbols indicate the expected appearance of mosquitoes (July 2002) and peak mosquito densities (October 2002). (B) Distinct epidemiological phases of malaria transmission; transmission season 1 (November to December 2001), transmission-free season (January to July 2002), pre-clinical period (August and September 2002) and transmission season 2 (October and December 2002).</p

Prevalence and densities of total parasites and gametocytes in samples taken from 25 individuals selected during transmission 1.

<p>Prevalence and densities of total parasites and gametocytes in samples taken from 25 individuals selected during transmission 1.</p