Plasmodium falciparum gametocyte carriage in symptomatic patients shows significant association with genetically diverse infections, anaemia, and asexual stage density

Abstract

Background Multi-genotype malaria infections are frequent in endemic area, and people commonly harbour several genetically distinct Plasmodium falciparum variants. The influence of genetic multiplicity and whether some specific genetic variants are more or less likely to invest into gametocyte production is not clearly understood. This study explored host and parasite-related risk factors for gametocyte carriage, and the extent to which some specific P. falciparum genetic variants are associated with gametocyte carriage. Methods Gametocytes and asexual forms were detected by light microscopy on thick smears collected between 2010 and 2012 in Nanoro, Burkina Faso. Merozoite surface protein 1 and 2 were genotyped by nested PCR on clinical samples. Associations between gametocyte carriage and factors, including multiplicity of infection, parasite density, patient age, gender, haemoglobin (Hb) level, and body temperature were assessed. The relationship between the presence of a particular msp1 and msp2 genetic variants and gametocyte carriage was also explored. Results Of the 724 samples positive to P. falciparum and successfully genotyped, gametocytes were found in 48 samples (6.63%). There was no effect of patient gender, age and body temperature on gametocyte carriage. However, the probability of gametocyte carriage significantly increased with increasing values of multiplicity of infection (MOI). Furthermore, there was a negative association between parasite density and gametocyte carriage. MOI decreased with parasite density in gametocyte-negative patients, but increased in gametocyte carriers. The probability of gametocyte carriage decreased with Hb level. Finally, the genetic composition of the infection influenced gametocyte carriage. In particular, the presence of RO33 increased the odds of developing gametocytes by 2 while the other allelic families K1, MAD20, FC27, and 3D7 had no significant impact on the occurrence of gametocytes in infected patients. Conclusion This study provides insight into potential factors influencing gametocyte production in symptomatic patients. The findings contribute to enhance understanding of risk factors associated with gametocyte carriage in humans. Trial registration NCT01232530.

Biology and epidemiology of Plasmodium falciparum and Plasmodium vivax gametocyte carriage: Implication for malaria control and elimination

“…Nevertheless, according to a study in Burkina Faso, parasite density was negatively associated with gametocyte carriage. The use of sensitive molecular tests in the study has been mentioned for the discrepancy with other studies ( Koepfli and Yan, 2018b ; Sondo et al, 2021 ). Gametocyte densities were strongly associated with total parasite densities for both P. falciparum (correlation coefficient= 0.83, P= 0.010), and P. vivax (correlation coefficient= 0.58, P= 0.010) ( Tadesse et al, 2017 ).…”

“…Furthermore, a high proportion of gametocyte carriers were observed among anemic individuals in studies from different areas ( Stepniewska et al, 2008 ; von Seidlein et al, 2003 ). Likewise, anemia was associated with increased odds of gametocytemia in Kenya and Burkina Faso ( Zhou et al, 2016 ; Sondo et al, 2021 ).…”

Plasmodium falciparum gametocyte production in longitudinally monitored incident infections is associated with duration of infection and human host factors

“…The presence of competing parasite clones is also considered as trigger for increased gametocyte formation 40,41 . Our findings of higher gametocyte densities in polyclonal infections appear supportive of these associations but nevertheless have to be interpreted with caution.…”

Gametocyte production in incident P. falciparum infections: a longitudinal study in a low transmission setting under intensive vector control

“…The presence of competing parasite clones is also considered as trigger for increased gametocyte formation (Nassir et al, 2005; Lamptey et al, 2018; Sondo et al, 2021). Our findings of higher gametocyte densities in polyclonal infections appear supportive of these associations but nevertheless have to be interpreted with caution.…”