Anti-malarial drugs: how effective are they against Plasmodium falciparum gametocytes?

Abstract

Background: Recent renewed emphasis on the eradication of malaria has highlighted the need for more tools with which to achieve this ambitious goal. One high priority area is the need to determine the gametocytocidal activity of both currently used anti-malarial drugs and those in the development pipeline. However, testing the activity of compounds against Plasmodium falciparum gametocytes is technically challenging both in vivo and in vitro.

Methods: Here the use of a simple robust assay to screen a panel of currently used and experimental anti-malarial drugs against mature P. falciparum gametocytes is described.

Results: Eight of 44 compounds tested reduced gametocyte viability by at least 50% and three showed IC50 values in nM range.

Conclusions: There is a need to identify new compounds with activity against late stage gametocytes and the information provided by this in vitro assay is a valuable first step, which can guide future clinical studies.

Figure 1

A: The activity of a panel of currently used and experimental anti-malarial drugs against late stage Plasmodium falciparum gametocytes. Bars with diagonal lines indicate compounds which resulted in a greater than 50% reduction in ATP production as compared to the control. All drugs were tested at a concentration of 10 μM. B: IC₅₀ values were determined for compounds which demonstrated a greater than 50% reduction in ATP production.