title: Quantification of Plasmodium falciparum histidine-rich protein-2 in cerebrospinal spinal fluid from cerebral malaria patients.
abstract: 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.
authors: 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.
authors: Kei
authors: K
authors: Mikita
authors: 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.
authors: Kiran
authors: K
authors: Thakur
authors: 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.
authors: Nicholas M
authors: NM
authors: Anstey
authors: 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.
authors: Kim A
authors: KA
authors: Piera
authors: 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.
authors: Carlos A
authors: CA
authors: Pardo
authors: 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.
authors: J Brice
authors: JB
authors: Weinberg
authors: 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.
authors: Jackson
authors: J
authors: Mukemba
authors: 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.
authors: Salvatore
authors: S
authors: Florence
authors: 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.
authors: Esther D
authors: ED
authors: Mwaikambo
authors: 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.
authors: Donald L
authors: DL
authors: Granger
authors: 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 dsulliv7@jhmi.edu.
authors: David J
authors: DJ
authors: Sullivan
mesh_terms: D000953:Antigens, Protozoan / Q000097:blood / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000175:diagnosis* / Q000276:immunology / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction / Q000379:methods*; D015800:Protozoan Proteins / Q000097:blood / Q000134:cerebrospinal fluid*; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D013636:Tanzania
chemical_list: D000953:Antigens, Protozoan; D015415:Biomarkers; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D011933:Reagent Kits, Diagnostic