pfhrp2andpfhrp3Gene Deletions That Affect Malaria Rapid Diagnostic Tests forPlasmodium falciparum: Analysis of Archived Blood Samples From 3 African Countries

  • Thomson, Rebecca
  • Beshir, Khalid B
  • Cunningham, Jane
  • Baiden, Frank
  • Bharmal, Jameel
  • Bruxvoort, Katia J
  • Maiteki-Sebuguzi, Catherine
  • Owusu-Agyei, Seth
  • Staedke, Sarah G
  • Hopkins, Heidi
Journal of Infectious Diseases 220(9):p 1444-1452, November 1, 2019. | DOI: 10.1093/infdis/jiz335

Abstract

Background

Malaria rapid diagnostic tests (mRDTs) that target histidine-rich protein 2 (HRP2) are important tools for Plasmodium falciparum diagnosis. Parasites with pfhrp2/3 gene deletions threaten the use of these mRDTs and have been reported in Africa, Asia, and South America. We studied blood samples from 3 African countries to determine if these gene deletions were present.

Methods

We analyzed 911 dried blood spots from Ghana (n = 165), Tanzania (n = 176), and Uganda (n = 570). Plasmodium falciparum infection was confirmed by 18S rDNA polymerase chain reaction (PCR), and pfhrp2/3 genes were genotyped. True pfhrp2/3 gene deletions were confirmed if samples were (1) microscopy positive; (2) 18S rDNA PCR positive; (3) positive for merozoite surface protein genes by PCR or positive by loop-mediated isothermal amplification; or (4) quantitative PCR positive with >5 parasites/μL.

Results

No pfhrp2/3 deletions were detected in samples from Ghana, but deletions were identified in Tanzania (3 pfhrp2; 2 pfhrp3) and Uganda (7 pfhrp2; 2 pfhrp3). Of the 10 samples with pfhrp2 deletions, 9 tested negative by HRP2-based mRDT.

Conclusions

The presence of pfhrp2/3 deletions in Tanzania and Uganda, along with reports of pfhrp2/3-deleted parasites in neighboring countries, reinforces the need for systematic surveillance to monitor the reliability of mRDTs in malaria-endemic countries.

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