Plasmodium falciparum histidine rich protein 2 (pfhrp2): an additional genetic marker suitable for anti-malarial drug efficacy trials

Malar J. 2022 Jan 4;21(1):2. doi: 10.1186/s12936-021-04014-4.


Background: Genotyping of the three Plasmodium falciparum polymorphic genes, msp1, msp2 and glurp, has been adopted as a standard strategy to distinguish recrudescence from new infection in drug efficacy clinical trials. However, the suitability of a particular gene is compromised in areas where its allelic variants distribution is significantly skewed, a phenomenon that might occur in isolated parasite populations or in areas of very low transmission. Moreover, observation of amplification bias has diminished the value of glurp as a marker.

Methods: The suitability of the polymorphic P. falciparum histidine-rich protein 2 (pfhrp2) gene was assessed to serve as an alternative marker using a PCR-sequencing or a PCR-RFLP protocol for genotyping of samples in drug efficacy clinical trials. The value of pfhrp2 was validated by side-by-side analyses of 5 admission-recrudescence sample pairs from Yemeni malaria patients.

Results: The outcome of the single pfhrp2 gene discrimination analysis has been found consistent with msp1, msp2 and glurp pool genotyping analysis for the differentiation of recrudescence from new infection.

Conclusion: The findings suggest that under the appropriate circumstances, pfhrp2 can serve as an additional molecular marker for monitoring anti-malarials efficacy. However, its use is restricted to endemic areas where only a minority of P. falciparum parasites lack the pfhrp2 gene.

Keywords: Drug efficacy clinical trial; Glurp; Malaria; Plasmodium falciparum; hrp2; msp1; msp2.

MeSH terms

  • Antigens, Protozoan / analysis*
  • Antimalarials / adverse effects*
  • Genetic Markers
  • Genotype
  • Humans
  • Malaria, Falciparum / prevention & control
  • Plasmodium falciparum / genetics*
  • Protozoan Proteins / analysis*


  • Antigens, Protozoan
  • Antimalarials
  • Genetic Markers
  • HRP-2 antigen, Plasmodium falciparum
  • Protozoan Proteins