Performance of Cerebrospinal Fluid (CSF) Plasmodium Falciparum Histidine-Rich Protein-2 (pfHRP-2) in Prediction of Death in Cerebral Malaria (S10.007)
Kiran Teresa Thakur, Jimmy A. Vareta, Kathryn A. Carson, Terrie Ellen Taylor, David Sullivan, Karl B. Seydel · Neurology · 2014
OBJECTIVE: We sought to determine whether pfHRP-2 levels in the CSF and the plasma/CSF pfHRP-2 ratio were predictive of mortality in patients with CM. BACKGROUND: Cerebral malaria (CM) is a rapidly developing comatose state that remains a major contributor to morbidity and mortality in malaria-endemic regions. CM may be diagnosed during life by the presence of P. falciparum parasitemia, clinical assessment and retinal changes. There is recent evidence that pfHRP-2 is present in the CSF of patients with CM. DESIGN/METHODS: We evaluated patients admitted to the Malaria Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) between 2009 and 2011 who met WHO criteria for CM and were retinopathy-positive. ELISA technique was used to test plasma and CSF pfHRP-2 levels. We performed univariable logistic regression with our primary outcome of interest being death. RESULTS: PfHRP-2 was tested in 100 CSF and 103 plasma samples from patients who met our CM case definition. Median age was 42 months (IQR 30), 48 patients (46%) were male, 4 (4%) were HIV positive, and 11 patients (10%) died during hospitalization. CSF pfHRP-2 was detectable by ELISA in 96/100 (96%) samples. In those patients who died, the geometric mean for CSF pfHRP-2 was 56.8 ng/ml (range 0-95 ng/mL) and 355.4 (range 54-568) for the plasma/CSF pfHRP-2 ratio. For those patients who survived, the geometric mean for CSF pfHRP-2 was 34.6 ng/mL (range 0-104.9 ng/mL) and 2586 (2-92,685) for the ratio of plasma/CSF pfHRP-2. In our logistic regression, we found that for a 1-log unit increase in CSF pfHRP-2, the odds of dying was 14% higher (OR=1.14; 95% CI=0.83-1.57; p=0.42). In addition, for a 1-log unit increase in the ratio of plasma/CSF pfHRP-2, there was a 13% decrease in the odds of dying (OR=0.87; 95% CI=0.59-1.29; p=0.50). CONCLUSIONS: Elevation of CSF pfHRP-2 and lower plasma/CSF pfHRP-2 ratios were seen in CM patients who died though further studies are needed to determine the significance of CSF pfHRP-2.