External quality assurance of malaria nucleic acid testing for clinical trials and eradication surveillance.
Nucleic acid testing (NAT) for malaria parasites is an increasingly recommended diagnostic endpoint in clinical trials of vaccine and drug candidates and is also important in surveillance of malaria control and elimination efforts. A variety of reported NAT assays have been described, yet no formal external quality assurance (EQA) program provides validation for the assays in use. Here, we report results of an EQA exercise for malaria NAT assays. Among five centers conducting controlled human malaria infection trials, all centers achieved 100% specificity and demonstrated limits of detection consistent with each laboratory's pre-stated expectations. Quantitative bias of reported results compared to expected results was generally <0.5 log10 parasites/mL except for one laboratory where the EQA effort identified likely reasons for a general quantitative shift. The within-laboratory variation for all assays was low at <10% coefficient of variation across a range of parasite densities. Based on this study, we propose to create a Molecular Malaria Quality Assessment program that fulfills the need for EQA of malaria NAT assays worldwide.
Department of Laboratory Medicine and Center for Emerging and Re-Emerging Infectious Diseases, University of Washington (UW), Seattle, Washington, United States of America.
Sean C
SC
Murphy
Department of Medical Microbiology, Radboud University Medical Center (RUMC), Nijmegen, The Netherlands.
Cornelus C
CC
Hermsen
The Jenner Institute, University of Oxford, Oxford, United Kingdom.
Alexander D
AD
Douglas
The Jenner Institute, University of Oxford, Oxford, United Kingdom.
Nick J
NJ
Edwards
European Vaccine Initiative (EVI), Heidelberg, Germany.
Ines
I
Petersen
Department of Laboratory Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
Gary A
GA
Fahle
Center for Vaccine Development and Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Matthew
M
Adams
Center for Vaccine Development and Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Andrea A
AA
Berry
Department of Laboratory Medicine and Center for Emerging and Re-Emerging Infectious Diseases, University of Washington (UW), Seattle, Washington, United States of America.
Zachary P
ZP
Billman
The Jenner Institute, University of Oxford, Oxford, United Kingdom.
Sarah C
SC
Gilbert
Center for Vaccine Development and Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Matthew B
MB
Laurens
European Vaccine Initiative (EVI), Heidelberg, Germany.
Odile
O
Leroy
Center for Vaccine Development and Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Kristen E
KE
Lyke
Center for Vaccine Development and Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Christopher V
CV
Plowe
Department of Laboratory Medicine and Center for Emerging and Re-Emerging Infectious Diseases, University of Washington (UW), Seattle, Washington, United States of America.
Annette M
AM
Seilie
Center for Vaccine Development and Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Kathleen A
KA
Strauss
Department of Medical Microbiology, Radboud University Medical Center (RUMC), Nijmegen, The Netherlands.
Karina
K
Teelen
The Jenner Institute, University of Oxford, Oxford, United Kingdom.
Adrian V S
AV
Hill
Department of Medical Microbiology, Radboud University Medical Center (RUMC), Nijmegen, The Netherlands.
Robert W
RW
Sauerwein
D060740:Disease Eradication / Q000379:methods*; D062665:Epidemiological Monitoring; D006801:Humans; D008288:Malaria / Q000175:diagnosis* / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000592:standards; D011785:Quality Assurance, Health Care / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000592:standards; D012680:Sensitivity and Specificity