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. 2022 Sep;46(3):729-743.
doi: 10.1007/s12639-022-01492-4. Epub 2022 May 11.

Assessment of Plasmodium falciparum histidine rich protein 2 and /3 (pfhrp 2&/ pfhrp 3) gene deletion or mutation in Plasmodium falciparum positive blood samples in a tertiary care centre in South India

Monika Sivaradjy  1 , Abdoul Hamide  2 , Sriram Krishnamoorthy  3 , Nonika Rajkumari  1 , Vamsi Mohan  1 , Ferdina Marie Sharmila  1
Affiliations

Assessment of Plasmodium falciparum histidine rich protein 2 and /3 (pfhrp 2&/ pfhrp 3) gene deletion or mutation in Plasmodium falciparum positive blood samples in a tertiary care centre in South India

Monika Sivaradjy et al. J Parasit Dis. 2022 Sep.

Abstract

Rapid diagnostic card tests (RDTs) enable timely and appropriate diagnosis of malaria especially in remote areas. Plasmodium falciparum histidine rich protein 2 (PFHRP2) is the most targeted antigen for the detection of Plasmodium falciparum infections by rapid diagnostic card test. Genetic mutations and gene deletions are important emerging factors for false-negative RDTs, which may delay the provision of life-saving treatment for the patients. Hence, we would like to evaluate for the existence of pfhrp2/3 gene deleted P. falciparum parasites in our health care setting. This study was conducted for a period of 2 years in a tertiary care centre in South India. Blood samples that are microscopically confirmed as P. falciparum but negative by RDT were assessed for the presence of pfhrp2, pfhrp3, and their flanking genes using conventional PCR. Follow up of the clinical outcomes were also done for these patients. Of the 63 positive samples collected (50 /63) 79.4% were P.vivax and (13/63) 20.6% were P.falciparum by PCR. Among the 13 P. falciparum positive samples, 4 samples (4/13), (95% CI -10.36% to 61.11%) were found to be RDT negative but microscopically positive.Pfhrp2,pfhrp3 and their flanking genes were amplified for these 4 samples. All 4 samples were found to be negative for both pfhrp2-2 & pfhrp2-3 exon regions and also varying patterns of flanking gene deletions were also noted.This study provides molecular evidence for the existence of pfhrp2 & pfhrp3 deleted P. falciparum parasites in a tertiary care centre in South India warranting periodic evaluation of pfhrp2 based RDT use. Only pfhrp2/3 RDT based decision on diagnosis of P.falciparum malaria should always be reconsidered especially in remote areas.

Keywords: Gene deletion; Pfhrp2; Pfhrp3; Plasmodium falciparum; Rapid diagnostic card test.

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Conflict of interest statement

Conflict of interestThe authors have no relevant financial or non financial interests to disclose.

Figures

Fig. 1
Fig. 1
Work flow chart
Fig. 2
Fig. 2
Various clinical manifestations of malaria in the study population (Clinical features in Y axis and number of patients in X axis)
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Fig. 3
Plasmodium speciation PCR results
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Fig. 4
Speciation PCR–Plasmodium falciparum
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Fig. 5
Speciation PCR–Plasmodium vivax
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Fig. 6
Pfhrp2-2 and Pfhrp3-2 PCR
Fig. 7
Fig. 7
Pfhrp2 flanking gene PCR
Fig. 8
Fig. 8
Pfhrp 3 flanking gene PCR
See this image and copyright information in PMC

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