Inclusion of gametocyte parameters in anti-malarial drug efficacy studies: filling a neglected gap needed for malaria elimination.

Leonardo K Basco,Mohammed A K Mahdy,John C Beier,Rashad Abdul-Ghani

doi:10.1186/s12936-015-0936-4

Leonardo K Basco, Mohammed A K Mahdy + Show 2 more

Open Access

https://doi.org/10.1186/s12936-015-0936-4

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Abstract

Standard anti-malarial drug efficacy and drug resistance assessments neglect the gametocyte parameters in their protocols. With the spread of drug resistance and the absence of clinically proven vaccines, the use of gametocytocidal drugs or drug combinations with transmission-blocking activity is a high priority for malaria control and elimination. However, the limited repertoire of gametocytocidal drugs and induction of gametocytogenesis after treatment with certain anti-malarial drugs necessitate both regular monitoring of gametocytocidal activities of anti-malarial drugs in clinical use and the effectiveness of candidate gametocytocidal agents. Therefore, updating current protocols of anti-malarial drug efficacy is needed to reflect the effects of anti-malarial drugs or drug combinations on gametocyte carriage and gametocyte density along with asexual parasite density. Developing protocols of anti-malarial drug efficacy that include gametocyte parameters related to both microscopic and submicroscopic gametocytaemias is important if drugs or drug combinations are to be strategically used in transmission-blocking interventions in the context of malaria elimination. The present piece of opinion highlights the challenges in gametocyte detection and follow-up and discuss the need for including the gametocyte parameter in anti-malarial efficacy studies.

Highlights

There are several integrated approaches for the assessment of anti-malarial drug efficacy and drug resistance: therapeutic efficacy in symptomatic patients with uncomplicated malaria, in vitro/ex vivo assays, molecular markers of drug resistance, and measurement of plasma concentration of anti-malarial drugs [1, 2]
Drug efficacy studies do not consider the drug effect on gametocyte carriage and density but focus on asexual parasite density. This is attributed to the fact that clinical presentation of malaria is a direct consequence of the asexual erythrocytic stages and that gametocytes are not responsible for the clinical disease
In line with the efforts devoted to eliminating malaria transmission, molecular detection of Plasmodium gametocytes could help in two directions: epidemiologically for uncovering the submicroscopic human reservoir and clinically for monitoring gametocytocidal activity of transmission-blocking anti-malarial drugs

Summary

Introduction

There are several integrated approaches for the assessment of anti-malarial drug efficacy and drug resistance: therapeutic efficacy in symptomatic patients with uncomplicated malaria, in vitro/ex vivo assays, molecular markers of drug resistance, and measurement of plasma concentration of anti-malarial drugs [1, 2]. Anti-malarial drugs or drug combinations should clear the asexual parasite stages responsible for clinical disease and clear the sexual stages that maintain its transmission.

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Conclusion