Transmission-blocking Effects of Primaquine and Methylene Blue Suggest Plasmodium falciparum Gametocyte Sterilization Rather Than Effects on Sex Ratio

Abstract

Gametocyte density and sex ratio can predict the proportion of mosquitoes that will become infected after feeding on blood of patients receiving nongametocytocidal drugs. Because primaquine and methylene blue sterilize gametocytes before affecting their density and sex ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects.

Keywords: anopheles; infectiousness; malaria; transmission; treatment.

Figure 1.

Associations between gametocyte density, sex ratio, treatment, and the proportion of mosquitoes that developed oocysts (became infected). The association between male and female gametocyte density is presented for day 2 (A) and day 7 (B) post-initiation of treatment. The association between female gametocyte density and the proportion of infected mosquitoes is presented for individuals who received nongametocytocidal drugs (C) and gametocytocidal drugs (D). In all panels, green symbols represent observations following dihydroartemisinin-piperaquine (DP); orange, sulfadoxine-pyrimethamine and amodiaquine (SP/AQ); maroon, DP-methylene blue; and blue, SP/AQ-primaquine. Crosses represent feeding outcomes from experiments conducted on day 2 post-initiation of treatment and triangles represent feeding outcomes from experiments conducted on day 7 post-initiation of treatment. (C and D) The proportion of mosquitoes that developed oocysts prior to treatment plotted in light gray circles for all treatment arms for illustrative purposes; the black line indicates the shape of the best fit relationship between female gametocyte density and infectivity in the absence of malaria treatment as previously defined [1].