Assessing the histidine-rich protein 2/3 gene deletion in Plasmodium falciparum isolates from Burkina Faso

Malar J. 2023 Nov 29;22(1):363. doi: 10.1186/s12936-023-04796-9.

Abstract

Background: Dual hrp2/hrp3 genes deletions in P. falciparum isolates are increasingly reported in malaria-endemic countries and can produce false negative RDT results leading to inadequate case management. Data on the frequency of hrp2/hrp3 deleted parasites are rarely available and it has become necessary to investigate the issue in Burkina Faso.

Methods: Plasmodium falciparum-positive dried blood spots were collected during a cross-sectional household survey of the malaria asymptomatic children from Orodara, Gaoua, and Banfora. Amplicons from the target regions (exon 2 of hrp2 and hrp3 genes) were generated using multiplexed nested PCR and sequenced according to Illumina's MiSeq protocol.

Results: A total of 251 microscopically positive parasite isolates were sequenced to detect hrp2 and hrp3 gene deletions. The proportion of RDTs negative cases among microscopy positive slides was 12.7% (32/251). The highest prevalence of negative RDTs was found in Orodara 14.3% (5/35), followed by Gaoua 13.1%(24/183), and Banfora 9.1% (3/33). The study found that 95.6% of the parasite isolates were wild type hrp2/ hrp3 while 4.4% (11/251) had a single hrp2 deletion. Of the 11 hrp2 deletion samples, 2 samples were RDT negative (mean parasitaemia was 83 parasites/ μL) while 9 samples were RDT positive with a mean parasitaemia of 520 parasites /μL (CI95%: 192-1239). The highest frequency of hrp2 deletion 4/35 (11.4%) was found in Orodara, while it was similar in the other two sites (< 3.5%). No single deletion of the hrp3 or dual deletion hrp2/3 gene was detected in this study.

Conclusion: These results demonstrate that P. falciparum isolates lacking hrp2 genes are present in 4.4% of samples obtained from the asymptomatic children population in three sites in Burkina Faso. These parasites are circulating and causing malaria, but they are also still detectable by HRP2-based RTDs due to the presence of the intact pfhrp3 gene.

Keywords: Burkina Faso; Malaria, Plasmodium falciparum; hrp2; hrp3.

MeSH terms

  • Antigens, Protozoan / analysis
  • Antigens, Protozoan / genetics
  • Burkina Faso / epidemiology
  • Child
  • Cross-Sectional Studies
  • Diagnostic Tests, Routine / methods
  • Gene Deletion
  • Histidine / genetics
  • Humans
  • Malaria, Falciparum* / parasitology
  • Plasmodium falciparum* / genetics
  • Protozoan Proteins / genetics

Substances

  • Protozoan Proteins
  • Antigens, Protozoan
  • Histidine