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Widespread pfhrp2/3 deletions and HRP2-based false-negative results in southern Ethiopia.
Mekonen, Bacha; Dugassa, Sisay; Feleke, Sindew Mekasha; Dufera, Boja; Gidisa, Bedasa; Adamu, Aderaw; Mandefro, Aynalem; Tasew, Geremew; Golassa, Lemu.
Afiliação
  • Mekonen B; Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia. tizumekonen@gmail.com.
  • Dugassa S; Malaria and NTDs Research Team, Bacterial, Parasitic, and Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, Addis Ababa, Ethiopia. tizumekonen@gmail.com.
  • Feleke SM; Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
  • Dufera B; Malaria and NTDs Research Team, Bacterial, Parasitic, and Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
  • Gidisa B; Malaria and NTDs Research Team, Bacterial, Parasitic, and Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
  • Adamu A; Malaria and NTDs Research Team, Armeur Hansen Research Institute, Addis Ababa, Ethiopia.
  • Mandefro A; Department of Medical Laboratory Science, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia.
  • Tasew G; Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
  • Golassa L; Malaria and NTDs Research Team, Bacterial, Parasitic, and Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
Malar J ; 23(1): 108, 2024 Apr 17.
Article em En | MEDLINE | ID: mdl-38632640
ABSTRACT

BACKGROUND:

Rapid diagnostic tests (RDTs) play a significant role in expanding case management in peripheral healthcare systems. Histidine-rich protein-2 (HRP2) antigen detection RDTs are predominantly used to diagnose Plasmodium falciparum infection. However, the evolution and spread of P. falciparum parasite strains with deleted hrp2/3 genes, causing false-negative results, have been reported. This study assessed the diagnostic performance of HRP2-detecting RDTs for P. falciparum cases and the prevalence of pfhrp2/3 deletions among symptomatic patients seeking malaria diagnosis at selected health facilities in southern Ethiopia.

METHODS:

A multi-health facilities-based cross-sectional study was conducted on self-presenting febrile patients seeking treatment in southern Ethiopia from July to September 2022. A purposive sampling strategy was used to enroll patients with microscopically confirmed P. falciparum infections. A capillary blood sample was obtained to prepare a blood film for microscopy and a RDT using the SD Bioline™ Malaria Pf/Pv Test. Dried blood spot samples were collected for further molecular analysis. DNA was extracted using gene aid kits and amplification was performed using nested PCR assay. Exon 2 of hrp2 and hrp3, which are the main protein-coding regions, was used to confirm its deletion. The diagnostic performance of RDT was evaluated using PCR as the gold standard test for P. falciparum infections.

RESULTS:

Of 279 P. falciparum PCR-confirmed samples, 249 (89.2%) had successful msp-2 amplification, which was then genotyped for hrp2/3 gene deletions. The study revealed that pfhrp2/3 deletions were common in all health centres, and it was estimated that 144 patients (57.8%) across all health facilities had pfhrp2/3 deletions, leading to false-negative PfHRP2 RDT results. Deletions spanning exon 2 of hrp2, exon 2 of hrp3, and double deletions (hrp2/3) accounted for 68 (27.3%), 76 (30.5%), and 33 (13.2%) of cases, respectively. The study findings revealed the prevalence of P. falciparum parasites lacking a single pfhrp2-/3-gene and that both genes varied across the study sites. This study also showed that the sensitivity of the SD Bioline PfHRP2-RDT test was 76.5% when PCR was used as the reference test.

CONCLUSION:

This study confirmed the existence of widespread pfhrp2/3- gene deletions, and their magnitude exceeded the WHO-recommended threshold (> 5%). False-negative RDT results resulting from deletions in Pfhrp2/3- affect a country's attempts at malaria control and elimination. Therefore, the adoption of non-HRP2-based RDTs as an alternative measure is required to avoid the consequences associated with the continued use of HRP-2-based RDTs, in the study area in particular and in Ethiopia in general.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Protozoários / Malária Falciparum Limite: Humans País/Região como assunto: Africa Idioma: En Revista: Malar J Assunto da revista: MEDICINA TROPICAL Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Etiópia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Protozoários / Malária Falciparum Limite: Humans País/Região como assunto: Africa Idioma: En Revista: Malar J Assunto da revista: MEDICINA TROPICAL Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Etiópia