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Investigation of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions and performance of a rapid diagnostic test for identifying asymptomatic malaria infection in northern Ethiopia, 2015

Journal Article · · Malaria Journal
 [1];  [2];  [3];  [4];  [5];  [6];  [6];  [7];  [8];  [8];  [5];  [5];  [4]
  1. Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States); Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States); OSTI
  2. Ethiopian Public Health Institute, Addis Ababa (Ethiopia); University of North Carolina, Chapel Hill, NC (United States). Infectious Disease Ecology and Epidemiology Laboratory
  3. Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States); Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
  4. Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States)
  5. Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States). U.S. President’s Malaria Initiative
  6. Ethiopian Public Health Institute, Addis Ababa (Ethiopia)
  7. African Society for Laboratory Medicine, Addis Ababa (Ethiopia)
  8. Ethiopian Federal Ministry of Health, Addis Ababa (Ethiopia)
+ Show Author Affiliations
Background: Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis of both symptomatic and asymptomatic infections. Although RDTs are a reliable and practical diagnostic tool, the sensitivity of histidine-rich protein 2 (HRP2)-based RDTs can be reduced if pfhrp2 or pfhrp3 (pfhrp2/3) gene deletions exist in the Plasmodium falciparum parasite population. This study evaluated dried blood spot (DBS) samples collected from a national household survey to investigate the presence of pfhrp2/3 deletions and the performance of the RDT used in the cross-sectional survey in a low transmission setting. Methods: The 2015 Ethiopia Malaria Indicator Survey tested household members by RDT and collected DBS samples. DBS (n = 2648) from three regions in northern Ethiopia were tested by multiplex bead-based antigen detection assay after completion of the survey. The multiplex assay detected pan-Plasmodium lactate dehydrogenase (LDH), pAldolase, and HRP2 antigens in samples. Samples suspected for pfhrp2/3 gene deletions (pLDH and/or pAldolase positive but low or absent HRP2) were further investigated by molecular assays for gene deletions. Antigen results were also compared to each individual’s RDT results. Dose–response logistic regression models were fit to estimate RDT level of detection (LOD) antigen concentrations at which 50, 75, 90, and 95% of the RDTs returned a positive result during this survey. Results: Out of 2,648 samples assayed, 29 were positive for pLDH or pAldolase antigens but low or absent for HRP2 signal, and 15 of these samples (51.7%) were successfully genotyped for pfhrp2/3. Of these 15 P. falciparum infections, eight showed single deletions in pfhrp3, one showed a single pfhrp2 deletion, and six were pfhrp2/3 double-deletions. Six pfhrp2 deletions were observed in Tigray and one in Amhara. Twenty-five were positive for HRP2 by the survey RDT while the more sensitive bead assay detected 30 HRP2-positive samples. A lower concentration of HRP2 antigen generated a positive test result by RDT compared to pLDH (95% LOD: 16.9 ng/mL vs. 319.2 ng/mL, respectively). Conclusions: There is evidence of dual pfhrp2/3 gene deletions in the Tigray and Amhara regions of Ethiopia in 2015. As the prevalence of malaria was very low (< 2%), it is difficult to make strong conclusions on RDT performance, but these results challenge the utility of biomarkers in household surveys in very low transmission settings.
Research Organization:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Organization:
Centers for Disease Control and Prevention (CDC); USDOE Office of Science (SC)
Grant/Contract Number:
SC0014664
OSTI ID:
1904987
Journal Information:
Malaria Journal, Journal Name: Malaria Journal Journal Issue: 1 Vol. 21; ISSN 1475-2875
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

60 APPLIED LIFE SCIENCES
Antigenemia
Gene deletions
HRP2
HRP3
Infectious diseases
Malaria
Parasitology
RDT
Tropical medicine
pLDH