HRP2 – Overview

Malaria remains a major public health problem, with an estimated 241 million cases and 627,000 deaths in 2020. In endemic countries, it is crucial to test every suspected case and treat every confirmed case with a quality antimalarial drug to prevent deaths. Current diagnostic tools include microscopy and rapid diagnostic tests (RDTs). RDTs offer significant advantages over microscopy, including speed, simplicity and ease of use, and have become essential in endemic areas. Around 90% of available RDTs target Plasmodium falciparum’s histidine-rich protein 2 (PfHRP2), with some also detecting PfHRP3 by cross-reactivity.
 
However, Plasmodium strains with Pfhrp2  gene deletions, which escape detection by PfHRP2-based RDTs, have been reported in Peru, Mali and other African countries. This situation could compromise malaria case management and threaten the effectiveness of current RDTs. WHO recommends that deletion-affected countries and their neighbors monitor deletions, especially in symptomatic patients, and switch to non-PfHRP2-based RDTs if the prevalence of deletion-affected parasites reaches 5%. Since Pfhrp2/3 deletions were first detected in Mali in 2012 in asymptomatic individuals, there have been no systematic studies of their impact in symptomatic patients.
 
The traditional method for molecular assays is to use filter papers for capillary blood samples, known as dried blood spots (DBS). However, several studies have shown that Plasmodium DNA extracted from used RDTs is of comparable quality and quantity to that from DBS, and is suitable for molecular analysis even after prolonged storage at room temperature. The use of used RDTs offers significant advantages, including simplified sample collection, drying, storage and shipping, with minimal risk of cross-contamination.
 
In this context, we propose to map the distribution of Pfhrp2 deletions to guide decisions on optimal diagnostic tests for malaria. This study will identify areas requiring diagnostic adjustments and those requiring future surveillance.
 
The project is led by Professor Abdoulaye Djimde of the University of Science, Techniques and Technologies of Bamako (USTTB), in collaboration with the head of epidemiological surveillance at Mali’s National Malaria Control Program (NMCP).
This partner was chosen for its expertise in malaria genomics research and its laboratory facilities.  
 
The results will be communicated to the PNLP to inform the choice of local RDTs, and to the WHO.

Overall objective

Determine the prevalence of Plasmodium falciparum hrp2/3 gene deletions in symptomatic patients in Mali and use these data to guide rapid diagnostic testing strategies.

Specific objectives

  1. To measure the prevalence of suspected pfhrp2/pfhrp3 gene deletions in symptomatic patients infected with P. falciparum.
  2. Evaluate the frequency of pfhrp2/3 gene deletions.
  3. Identify districts where the prevalence of pfhrp2/3 gene deletions reaches or exceeds 5%.

Methodology

This project will determine the prevalence of hrp2/3 deletions in Plasmodium falciparum parasites in Mali and evaluate the effectiveness of RDTs currently used in the country, which will benefit malaria patients in Mali.

Scroll to Top