Pfhrp2-Deleted Plasmodium falciparum Parasites in the Democratic Republic of the Congo: A National Cross-sectional Survey.
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.



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.



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 = .046, p ≤ .00001).



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.
Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA.
Jonathan B
JB
Parr
Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom.
Robert
R
Verity
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Stephanie M
SM
Doctor
Department of Geography, University of North Carolina, Chapel Hill, NC 27599, USA.
Mark
M
Janko
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Kelly
K
Carey-Ewend
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Breanna J
BJ
Turman
Department of Geography, University of North Carolina, Chapel Hill, NC 27599, USA.
Corinna
C
Keeler
Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom.
Hannah C
HC
Slater
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Amy N
AN
Whitesell
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.|University of Kinshasa School of Public Health, Kinshasa, Democratic Republic of Congo.
Kashamuka
K
Mwandagalirwa
Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom.
Azra C
AC
Ghani
Programme National de la Lutte contre le Paludisme, Kinshasa, Democratic Republic of Congo.
Joris L
JL
Likwela
University of Kinshasa School of Public Health, Kinshasa, Democratic Republic of Congo.
Antoinette K
AK
Tshefu
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.|Department of Geography, University of North Carolina, Chapel Hill, NC 27599, USA.
Michael
M
Emch
Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA.|Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Jonathan J
JJ
Juliano
Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC 27599, USA.|Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Steven R
SR
Meshnick
D000953:Antigens, Protozoan / Q000235:genetics*; D001499:Bayes Theorem; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016054:DNA, Protozoan / Q000302:isolation & purification; D015023:Democratic Republic of the Congo; D003955:Diagnostic Tests, Routine; D017353:Gene Deletion; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000453:epidemiology*; D018895:Microsatellite Repeats; D010963:Plasmodium falciparum / Q000235:genetics*; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics*
D000953:Antigens, Protozoan; D016054:DNA, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins
RDT; deletion; diagnostic resistance; false-negative; histidine-rich protein 2; hrp2; hrp3; malaria; pfhrp3; rapid diagnostic tests