Tools for monitoring antimalarial drug efficacy
Routine monitoring of antimalarial drug efficacy is necessary for effective case management and detection of resistance. WHO has developed a series of tools to facilitate the work of national malaria programmes and other partners involved in routine testing of antimalarial drug efficacy.
Template protocol for therapeutic efficacy studies
The template protocol for therapeutic efficacy studies (TES) translates the standard protocol into a practical format that can be used by national malaria programmes seeking approval from ethics committees or funding from donors. It can easily be adapted to meet local conditions and needs, while still maintaining standardization and interpretation of data.
Template protocol in English | Template protocol in French
This template is an updated version of the template published in Annex 1 of the Methods for surveillance of antimalarial drug efficacy. It has been reviewed by the WHO Research Ethics Review Committee and adheres to current ICH guidelines.
Polymerase chain reaction (PCR) for identifying parasite populations
TES treatment outcomes are determined based on an assessment of parasitological and clinical outcomes. Genotyping of parasite populations, or PCR-correction, allows for study investigators to distinguish between true recrudescence (i.e. when the parasites which caused the initial infection escape the treatment and resurface) and a new infection, which can occur when antimalarial drug concentrations fall below the level required to suppress a new infection. PCR-corrected treatment failure rates are now the preferred end-point in regulatory clinical trials and for monitoring antimalarial drug efficacy. An informal consultation on the methodology used to distinguish reinfection from recrudescence in high malaria transmission areas was held in May 2021 to revise the previous guidance from 2007.
Informal consultation on methodology to distinguish reinfection from recrudescence in high malaria transmission...
This report summarizes the findings and conclusions of a virtual meeting on the methodology to distinguish reinfection from recrudescence in high malaria...
WHO data entry and analysis tool
In conjunction with the WHO standard protocol for monitoring antimalarial drug efficacy, WHO has developed an electronic data collection form to standardize data entry and analysis of therapeutic efficacy study data. Separate versions are available for the 28-day and 42-day studies. The program can be used in areas of both high and low-to-moderate malaria transmission. Instructions are provided within the Excel program, on the reference guide worksheet.
Data entry forms 28-day studies
Data entry form in English | Data entry form in French
Data entry forms 42-day studies
Data entry form in English | Data entry form in French
Quality control monitoring is an essential part of the conduct of high quality therapeutic efficacy studies. By visiting study sites at the beginning, during and at the end of a study, quality control monitors help to ensure that a study site is appropriate, that clinical and laboratory resources are adequate, that data processing is complete and that reporting is underway.
To facilitate this process, WHO has developed 3 separate template checklists for quality control monitoring. The templates can be used as provided or adapted according to local conditions and sponsor requirements.
Pre-study visit monitoring checklist
Pre visit checklist in English | Pre visit checklist in French
Interim visit monitoring checklist
Interim visit checklist in English | Interim visit checklist in French
Study close visit monitoring checklist
Study close visit checklist in English | Study close visit checklist in French
Parasite clearance estimator
Artemisinin resistance typically refers to a delay in the clearance of malaria parasites from the bloodstream following treatment with an artemisinin-based combination therapy (ACT). WHO has developed a parasite clearance estimator tool, which provides additional information regarding the changes to the clearance rate. This Excel-based tool incorporates all phases of the parasite clearance curve: the initial lag phase, the slope, and the terminal tail phase. Each phase of the curve is considered to represent key biological processes, and may also be useful if the genetic heritability of artemisinin resistance is confirmed. This tool remains valid even when the parasite count is low.
Parasite clearance estimator | User's guide
Chemoprevention efficacy studies (CPES)
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.
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.
A new publication, Malaria chemoprevention efficacy study protocol, 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. An update of this document will be done when additional experience is gained from studies of chemoprevention efficacy.
Malaria chemoprevention efficacy study protocol
Chemoprevention is the use of medicines, either alone or in combination, to prevent malaria infection and its consequences. This publication provides standardized...