Plasma concentrations of parasite histidine-rich protein 2 distinguish between retinopathy-positive and retinopathy-negative cerebral malaria in Malawian children.
BACKGROUND
Brain histology and ophthalmoscopy suggest that approximately 25% of children with World Health Organization-defined cerebral malaria (CM) have a nonmalarial cause of death. Misclassification complicates clinical care, confounds studies of association, and may obfuscate successes in malaria control. Retinopathy predicts intracerebral parasite sequestration with >90% sensitivity and specificity, but detecting retinopathy requires well-trained personnel and expensive equipment.


METHODS
We investigated the utility of plasma concentrations of parasite histidine-rich protein 2 (pHRP2), a Plasmodium-specific protein, as a predictor of intracerebral parasite sequestration at autopsy and of malaria retinopathy on clinical examination in patients with clinically defined CM.


RESULTS
In 64 autopsy cases, 47 of whom had histological evidence of sequestration, the sensitivity and specificity of a plasma pHRP2 level of >1700 ng/mL were 98% and 94%, respectively, and the area under the receiver operating characteristic (AUROC) curve was 0.98. In a separate, prospectively studied group of 101 children with clinically defined CM, of whom 71 had retinopathy, the same pHRP2 cutoff predicted retinopathy-positivity with a sensitivity of 90% and specificity of 87% (AUROC, 0.90).


CONCLUSIONS
Elevated plasma pHRP2 concentrations can identify Malawian children with histologically confirmed or retinopathy-positive CM and is a more field-friendly approach to confirming the diagnosis than post mortem sampling or ophthalmoscopy.
Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre. seydel@msu.edu
Karl B
KB
Seydel
Lindsay L
LL
Fox
Simon J
SJ
Glover
Mathew J
MJ
Reeves
Paul
P
Pensulo
Alice
A
Muiruri
Ashley
A
Mpakiza
Malcolm E
ME
Molyneux
Terrie E
TE
Taylor
D000953:Antigens, Protozoan / Q000097:blood*; D001344:Autopsy; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000097:blood* / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D008295:Malawi / Q000453:epidemiology; D008297:Male; D015800:Protozoan Proteins / Q000097:blood*; D012164:Retinal Diseases / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D012680:Sensitivity and Specificity
D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins