Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia

Details

• Alternative Title:
  Nat Microbiol
• Personal Author:
  Feleke, Sindew M. ; Reichert, Emily N. ; Mohammed, Hussein ; Brhane, Bokretsion G. ; Mekete, Kalkidan ; Mamo, Hassen ; Petros, Beyene ; Solomon, Hiwot ; Abate, Ebba ; Hennelly, Chris ; Denton, Madeline ; Keeler, Corinna ; Hathaway, Nicholas J. ; Juliano, Jonathan J. ; Bailey, Jeffrey A. ; Rogier, Eric ; Cunningham, Jane ; Aydemir, Ozkan ; Parr, Jonathan B.
• Description:
  In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia's borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5-11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa.
• Subjects:
  Adolescent Adult Antigens, Protozoan Child Cross-Sectional Studies Diagnostic Tests, Routine Ethiopia Evolution, Molecular Female Gene Deletion Genotype Geography Humans Malaria, Falciparum Male Plasmodium Falciparum Prevalence Prospective Studies Protozoan Proteins Selection, Genetic Young Adult

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• Source:
  Nat Microbiol. 6(10):1289-1299
• Pubmed ID:
  34580442
• Pubmed Central ID:
  PMC8478644
• Document Type:
  Journal Article
• Funding:
  001/World Health OrganizationInternational/ ; K24 AI134990/AI/NIAID NIH HHSUnited States/ ; R01 AI132547/AI/NIAID NIH HHSUnited States/ ; EPHI5405/Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund)/
• Volume:
  6
• Issue:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:5e5b948f82b899fe76776df64378c97eb9e5a4303040d9cfd2888557cad145f0
• Download URL:
  https://stacks.cdc.gov/view/cdc/111636/cdc_111636_DS1.pdf
• File Type:
  [PDF - 5.66 MB ]