Abstract
BackgroundGenotyping 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.MethodsThe 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.ResultsThe 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.ConclusionThe 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.
Highlights
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
Given the short incubation period of P. falciparum, longer follow-up periods increase the likelihood of acquiring new infections, especially in areas of high malaria transmission, which can lead to an underestimate of drug efficacy through mistaken classification of newly acquired infections as drug failures
The genetic markers recommended by the World Health Organization (WHO) for polymerase chain reaction (PCR) correction are the polymorphic regions of three P. falciparum genes: merozoite surface protein 1, merozoite surface protein 2
Summary
Genotyping of the three Plasmodium falciparum polymorphic genes, msp, msp and glurp, has been adopted as a standard strategy to distinguish recrudescence from new infection in drug efficacy clinical trials. Given the short incubation period of P. falciparum, longer follow-up periods increase the likelihood of acquiring new infections, especially in areas of high malaria transmission, which can lead to an underestimate of drug efficacy through mistaken classification of newly acquired infections as drug failures. In order to counter this, molecular genotyping strategies based on polymerase chain reaction (PCR) amplification have been developed to correct estimates of drug efficacy in clinical trials by enabling a distinction between recrudescences versus new infections during the follow-up [3]. The genetic markers recommended by the World Health Organization (WHO) for PCR correction are the polymorphic regions of three P. falciparum genes: merozoite surface protein 1 (msp, block2), merozoite surface protein 2
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
