Citation
Feleke, Sindew M.; Reichert, Emily N.; Mohammed, Hussein; Brhane, Bokretsion G.; Mekete, Kalkidan; Mamo, Hassen; Petros, Beyene; Solomon, Hiwot; Abate, Ebba; & Hennelly, Chris, et al. (2021). Plasmodium Falciparum is Evolving to Escape Malaria Rapid Diagnostic Tests in Ethiopia. Nature Microbiology, 6(10), 1289-1299. PMCID: PMC8478644Abstract
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.URL
http://dx.doi.org/10.1038/s41564-021-00962-4Reference Type
Journal ArticleYear Published
2021Journal Title
Nature MicrobiologyAuthor(s)
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.