Parasite and gametocyte dynamics and infectivity to mosquitoes during recurrent Plasmodium vivax infections: A longitudinal study from Ethiopia.

OBJECTIVES

Plasmodium vivax relapses can lead to episodes of recurrent parasitemia. We longitudinally assessed parasite and gametocyte kinetics and infectivity to mosquitoes during P. vivax recurrent infections in Ethiopia.

METHODS

Patients presenting with clinical P. vivax infections were enrolled at Shele health center in Arba Minch Zuria district, Ethiopia. All participants received chloroquine plus 14-day primaquine for radical cure, and were subsequently followed for one year with scheduled monthly visits. Parasite and gametocyte densities were quantified using molecular assays, and infectivity was assessed through mosquito feeding assays.

RESULTS

Over the follow-up period, 54.6% (96/176) of patients experienced at least one recurrent parasitemia. Gametocyte density was similar between baseline and recurrent symptomatic episodes but lower during asymptomatic parasitemia (p<0.001). Across all mosquito feeding assays, 167 (70.2%) of 238 feedings resulted in at least one infected mosquito, with similar proportions between baseline (117 [70.5%] of 166) and recurrent symptomatic infections (50 [69.4%] of 72). Mosquito infection rates were strongly associated with both asexual parasite density (ρ=0.29; p<0.0001; n=166) and gametocyte density (ρ=0.32; p<0.0001) at baseline. Genotyping a subset of recurrent infections indicated 45.7% (42/92) of recurrences were likely to be relapses. After adjusting for gametocyte density, mosquito infection rates appeared lower when feeding on blood of relapsing infections as opposed to new infections (Odds Ratio 0.48, 95% CI 0.26-0.87, p=0.016).

CONCLUSIONS

This comprehensive assessment of parasite kinetics and transmissibility over the course of infections uncovers a high frequency of recurring episodes of parasitemia that are accompanied by infectious gametocytes. This work further supports the need to strengthen radical cure to prevent relapsing infections and sustain malaria transmission control.