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Background <p>Approximately 74% of malaria diagnoses worldwide rely on <i>Plasmodium falciparum</i> histidine-rich protein 2 (PfHRP2)-based rapid diagnostic tests (RDTs), whose accuracy can be compromised by deletions in its encoding <i>pfhrp2</i> gene and its paralogous <i>pfhrp3</i> genes. Estimating the burden of false-negative RDT results due to pfhrp2 deletion among individuals with malaria symptoms is critical for guiding the continued use of PfHRP2 tests.</p> Methods <p>This cross-sectional survey obtained 5394 samples from individuals presenting with symptoms of malaria at selected health facilities in ten counties, Kenya. Each participant was tested using both PfHRP2-based and P. falciparum lactate dehydrogenase (PfLDH)-based RDT. Samples that tested positive by PfLDH and negative by PfHRP2 were scored as discordant. All discordant samples, plus a random subset of the Plasmodium positive samples, were sequenced to characterize HRP2/3 gene deletion as well as polymorphisms in the Plasmodium falciparum kelch 13 (pfk13) propeller gene.</p> Results <p>The HRP2- and PfLDH-based RDTs showed similar positivity rates (44% vs. 45%), with 1.26% discordance. Discordance was highest in Nairobi, Trans Nzoia, and Kisumu, and minimal in Kwale and Tana River. None of the discordant samples carried pfhrp2 deletions, although 5.4% (3/56) had single pfhrp3 deletions, comparable to concordant infections. Among 598 samples that were sequenced, single pfhrp2 and pfhrp3 deletion prevalences were 4.5% and 12.4%, respectively, with no double-deletions detected. Nairobi exhibited the highest prevalence of pfhrp2-only deletions. Tana River, Garissa, Kirinyaga, and Kisii had the highest pfhrp3-only deletions. Among discordant samples, PfLDH-based RDTs identified P. ovale and P. malariae. Finally, sequencing of pfk13 in a subset of P. falciparum infections revealed 0.7% mutation prevalence, comprising A578S (<i>n</i> = 2) Kisumu and A675V (<i>n</i> = 2) each from Nairobi and Kirinyaga counties.</p> Conclusions <p>Although single pfhrp2 and pfhrp3 deletions were observed across Kenya, they do not appear to be the primary cause of false-negative HRP2-based RDT results. Continued absence of parasites with double pfhrp2/pfhrp3 deletions supports the ongoing reliability of HRP2-based RDTs for <i>P</i>. <i>falciparum</i> detection. Routine molecular surveillance remains critical to monitor emerging deletion trends. The detection of the A675V mutation, a WHO-validated marker of partial artemisinin resistance in two counties, suggests limited spread of artemisinin resistance.</p>

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Absence of false negative RDT results due to pfhrp2 deletion among symptomatic malaria infections in Kenya: findings from the 2022 Kenya national longitudinal surveillance of pfhrp2/3 deletions

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Hoseah M. Akala,
  • Regina Kandie,
  • George N. Githuka,
  • Rosebella Kiplagat,
  • Omar Ahmeddin,
  • Kibor Keitany,
  • James Kiarie,
  • Andrew Wamari,
  • Beatrice Machini,
  • Elvis Oyugi,
  • Sammy Mahugu,
  • James D. Otieno,
  • Timothy E. Egbo,
  • Dennis W. Juma,
  • Luis Pow Sang,
  • Robert C. Haynes,
  • Victor Osoti,
  • Brian A. Vesely,
  • David Smith,
  • Jye Travis,
  • Jane Cunningham,
  • Qin Cheng,
  • Isabella Oyier,
  • Bernhards Ogutu

摘要

Background

Approximately 74% of malaria diagnoses worldwide rely on Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-based rapid diagnostic tests (RDTs), whose accuracy can be compromised by deletions in its encoding pfhrp2 gene and its paralogous pfhrp3 genes. Estimating the burden of false-negative RDT results due to pfhrp2 deletion among individuals with malaria symptoms is critical for guiding the continued use of PfHRP2 tests.

Methods

This cross-sectional survey obtained 5394 samples from individuals presenting with symptoms of malaria at selected health facilities in ten counties, Kenya. Each participant was tested using both PfHRP2-based and P. falciparum lactate dehydrogenase (PfLDH)-based RDT. Samples that tested positive by PfLDH and negative by PfHRP2 were scored as discordant. All discordant samples, plus a random subset of the Plasmodium positive samples, were sequenced to characterize HRP2/3 gene deletion as well as polymorphisms in the Plasmodium falciparum kelch 13 (pfk13) propeller gene.

Results

The HRP2- and PfLDH-based RDTs showed similar positivity rates (44% vs. 45%), with 1.26% discordance. Discordance was highest in Nairobi, Trans Nzoia, and Kisumu, and minimal in Kwale and Tana River. None of the discordant samples carried pfhrp2 deletions, although 5.4% (3/56) had single pfhrp3 deletions, comparable to concordant infections. Among 598 samples that were sequenced, single pfhrp2 and pfhrp3 deletion prevalences were 4.5% and 12.4%, respectively, with no double-deletions detected. Nairobi exhibited the highest prevalence of pfhrp2-only deletions. Tana River, Garissa, Kirinyaga, and Kisii had the highest pfhrp3-only deletions. Among discordant samples, PfLDH-based RDTs identified P. ovale and P. malariae. Finally, sequencing of pfk13 in a subset of P. falciparum infections revealed 0.7% mutation prevalence, comprising A578S (n = 2) Kisumu and A675V (n = 2) each from Nairobi and Kirinyaga counties.

Conclusions

Although single pfhrp2 and pfhrp3 deletions were observed across Kenya, they do not appear to be the primary cause of false-negative HRP2-based RDT results. Continued absence of parasites with double pfhrp2/pfhrp3 deletions supports the ongoing reliability of HRP2-based RDTs for P. falciparum detection. Routine molecular surveillance remains critical to monitor emerging deletion trends. The detection of the A675V mutation, a WHO-validated marker of partial artemisinin resistance in two counties, suggests limited spread of artemisinin resistance.