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Malaria chemoprevention efficacy study protocol

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INTRODUCTION

Preventive chemotherapy is the use of medicines, either alone or in combination, to prevent malaria infection and its consequences. It requires giving a full treatment course of an antimalarial medicine, often at predefined intervals to individuals who have not been diagnosed with malaria.
By providing antimalarial medicine to vulnerable populations, existing undiagnosed malaria infections are treated, and the medicine provides a period of protection against new infections.
Chemoprevention strategies currently recommended by the World Health Organization (WHO) and covered by this guidance are described in Annex 1.
These include intermittent preventive treatment of malaria in pregnancy (IPTp), perennial malaria chemoprevention (PMC), seasonal malaria chemoprevention (SMC), and intermittent preventive treatment of malaria in school-aged children (IPTsc) (1).

Information on the efficacy of the medicines as used in these malaria chemoprevention strategies is critical for ensuring that the strategies remain effective in different settings with different levels of drug resistance.
WHO has prepared a standard protocol for therapeutic efficacy studies (TES), and tools for data analysis and monitoring the parasitological and therapeutic responses to treatment (2). TES are prospective evaluations of patients’ clinical and parasitological responses to treatment for uncomplicated malaria. TES are considered the gold standard for assessing antimalarial drug treatment efficacy, and the resulting data are used to inform national malaria treatment policy in malariaendemic countries. Unfortunately, systematic reviews have demonstrated that even when TES are done at the same time and place, they do not accurately predict the efficacy of chemoprevention strategies (3). In TES, the therapeutic efficacy in clearing asexual blood-stage parasites is assessed in subjects with uncomplicated malaria. In chemoprevention, the drug regimen given can work by clearing both asexual bloodstage parasites and pre-erythrocytic stage parasites in asymptomatic subjects. In both treatment and chemoprevention, many factors other than drug resistance impact the efficacy, including immunity, drug absorption and metabolism. A mutation that can significantly impact the efficacy of a drug in clearing asexual blood-stage parasites may have a different impact on the drug’s efficacy in clearing pre-erythrocytic stage parasites. Additionally, a lower number of asexual blood-stage parasites in an asymptomatic recipient of chemoprevention may be easier for a drug to clear compared to a high number of asexual blood-stage parasites in a symptomatic patient enrolled in TES. Specific protocols are therefore needed for monitoring chemoprevention efficacy.

This document is intended as a guide for studies of chemoprevention efficacy and was developed based on reviews of protocols of ongoing studies. The document adapts some of the principles and practices underlying treatment efficacy monitoring to provide standardized approaches for monitoring and evaluating the efficacy of medicines used for malaria chemoprevention. This guide will be updated once additional experience is gained from studies of chemoprevention efficacy.