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Quantification of Plasmodium falciparum Histidine-Rich Protein-2 in Cerebrospinal Spinal Fluid from Cerebral Malaria Patients

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  • W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia; Royal Darwin Hospital, Darwin Australia; Duke University and Veterans Administration Medical Centers, Durham, North Carolina; Hubert Kairuki Memorial University, Dar es Salaam, Tanzania; University of Utah School of Medicine and Veterans Administration Medical Center, Salt Lake City, Utah

A cerebrospinal fluid (CSF) biomarker for cerebral malaria (CM) has not been validated. We examined the detection, semiquantification, and clinical use of the Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) as a parasite antigen biomarker for CM. The PfHRP-2 was detected in archival CSF samples from CM patients from Tanzania both by a newly developed sensitive and specific immuno-polymerase chain reaction (72 of 73) and by rapid diagnostic tests (62 of 73). The geometric mean PfHRP-2 CSF concentration was 8.76 ng/mL with no differences in those who survived (9.2 ng/mL), those who died (11.1 ng/mL), and those with neurologic sequelae (10.8 ng/mL). All aparasitemic endemic and nonendemic control samples had undetectable CSF PfHRP-2. In a separate group of 11 matched plasma and CSF cerebral malaria patient samples, the ratio of plasma to CSF PfHRP-2 was 175. The CSF PfHRP-2 reflects elevated plasma PfHRP-2 rather than elevated CM-specific CSF ratios, falling short of a validated biomarker.

Author Notes

* Address correspondence to David J. Sullivan, Sullivan, 615 North Wolfe Street, Baltimore, MD 21205. E-mail: dsulliv7@jhmi.edu

Financial Support: The study was sponsored by a faculty JHBSPH Faculty Research Initiative Fund 1606510083. N. Anstey is supported by a Practitioner Fellowship from the Australian National Health and Medical Research Council. K. Mikita received partial support from a Japanese military grant. C. Pardo received support from the Bart McLean Fund for Neuroimmunology Research. Instrumentation for immuno-PCR was supported in part by the Bill and Melinda Gates Foundation (National Institute of Medical Research, Supplemental Project to Partnership for the Rapid Elimination of Trachoma, PRET+[48027]; Sheila West, principal investigator).

Disclosure: David Sullivan receives royalties from Alere for provision of positive control antigens for the Binax malaria rapid diagnostic test and is a named inventor and consultant for Fyodor biotechnologies who licensed a urine malaria test from Johns Hopkins University. This statement is made in the interest of full disclosure and not because the authors consider this to be a conflict of interest.

Authors' addresses: Kei Mikita and David J. Sullivan, The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mails: kmikita@jhsph.edu and dsulliv7@jhmi.edu. Kiran Thakur and Carlos A. Pardo, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, E-mails: kthakur1@jhmi.edu and cpardov1@jhmi.edu. Nicholas M. Anstey, Global Health Division, Menzies School of Health Research, Charles Darwin University, Casuarina, Australia, and the Royal Darwin Hospital, Darwin, Queensland, Australia, E-mail: Nicholas.Anstey@menzies.edu.au. Kim A. Piera, Global Health Division, Menzies School of Health Research, Charles Darwin University, Casuarina, Australia, E-mail: Kim.Piera@menzies.edu.au. J. Brice Weinberg, Duke University and Veterans Administration Medical Centers, Durham, North Carolina. E-mail: Weinberg-brice@duke.edu. Jackson Mukemba, Salvatore Florence, and Esther D. Mwaikambo, Hubert Kairuki Memorial University, Dar es Salaam, Tanzania, E-mails: jackmukemba@yahoo.fr, mukalabamu@yahoo.com, and esther.mwaikambo@gmail.com. Donald L. Granger, University of Utah School of Medicine and Veterans Administration Medical Center, Salt Lake City, Utah, E-mail: Granger-don.granger@hsc.utah.edu.

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