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Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of Congo: A national cross-sectional survey
Authors: Jonathan B. Parr, Robert Verity, Stephanie M. Doctor, Mark Janko, Kelly Carey-Ewend, Breanna J. Turman, Corinna Keeler, Hannah C. Slater, Amy N. Whitesell, Kashamuka Mwandagalirwa, Azra C. Ghani, Joris L. Likwela, Antoinette K. Tshefu, Michael Emch, Jonathan J. Juliano, and Steven R. Meshnick
Source: Journal of Infectious Diseases , First published online: November 14, 2016; doi: 10.1093/infdis/jiw538
Topic(s): Malaria
Country: Africa
  Congo Democratic Republic
Published: NOV 2016
Abstract: Background Rapid diagnostic tests (RDTs) account for more than two-thirds of malaria diagnoses in Africa. Deletions of the Plasmodium falciparum hrp2 (pfhrp2) gene cause false-negative RDT results and have never been investigated on a national level. Spread of pfhrp2-deleted P. falciparum mutants, resistant to detection by HRP2-based RDTs, would represent a serious threat to malaria elimination efforts. Methods Using a nationally representative cross-sectional study of 7,137 children under five years of age from the Democratic Republic of Congo (DRC), we tested 783 subjects with RDT-/PCR+ results using PCR assays to detect and confirm deletions of the pfhrp2 gene. Spatial and population genetic analyses were employed to examine the distribution and evolution of these parasites. Results We identified 149 pfhrp2-deleted parasites, representing 6.4% of all P. falciparum infections country-wide (95% confidence interval 5.1-8.0%). Bayesian spatial analyses identified statistically significant clustering of pfhrp2 deletions near Kinshasa and Kivu. Population genetic analysis revealed significant genetic differentiation between wild-type and pfhrp2-deleted parasite populations (GST = 0.046, p = 0.00001). Conclusions Pfhrp2-deleted P. falciparum is a common cause of RDT-/PCR+ malaria among asymptomatic children in the DRC and appears to be clustered within select communities. Surveillance for these deletions is needed, and alternatives to HRP2-specific RDTs may be necessary.