Shifts in P. falciparum genetic structure and gametocyte markers in the transition to elimination

Abstract

Large-scale programs targeting Plasmodium falciparum (Pf) elimination can exert strong selection pressures on the parasite population. To better understand the impact that elimination initiatives can have on Pf genetic structure and gametocyte carriage, we applied amplicon-based sequencing of two polymorphic Pf genes and quantitative reverse-transcription PCR targeting gametocyte-specific genes to Pf isolates collected in Magude District (Southern Mozambique) before and after an elimination initiative. The 71% reduction of Pf prevalence achieved in 2 years was followed by reductions in Pf genetic diversity and increases in between-infection similarity. These genetic shifts were accompanied by increases in the relative transcript number of the female mature gametocyte marker pfs25, the pfap2g transcription factor that drives gametocytogenesis and the sexual ring marker pfgexp02, suggesting the parasite ability of adapting its sexual investment during elimination initiatives. Reactive interventions that target Pf sexual stages may be required to achieve complete interruption of transmission.

The private life of malaria parasites: Strategies for sexual reproduction

“…Sexual reproduction of malaria parasites involves huge bottlenecks in terms of parasite densities (from asexuals to gametocytes, and to subsequent ookinetes and oocysts within the mosquito vector), making the processes involved attractive targets for interventions. However, it is important to consider how the sophistication with which malaria parasites appear to optimise conversion and sex ratio could erode such interventions [ 109 , 110 ]. For example, in response to drug treatment, RR makes infections harder to clear but TI enhances short-term transmission.…”

Monthly sulfadoxine/pyrimethamine-amodiaquine or dihydroartemisinin-piperaquine as malaria chemoprevention in young Kenyan children with sickle cell anemia: A randomized controlled trial

“…These clinical factors would need to be complemented before wider policy adoption by considerations of DP resistance, which was detected as declining clinical efficacy first in Southeast Asia [26]and more recently at several sites in Africa [27,28]. Though wider use of DP will necessarily increase pressure to develop resistance, this may be mitigated by a restriction of DP use to high-risk populations like pregnant women and children with SCA, and by the observation through multiple studies [29][30][31][32] that mass-drug administration with DP across diverse populations has not reliably increased molecular markers of DP resistance.…”