Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric cerebral malaria

Malar J. 2018 Mar 23;17(1):125. doi: 10.1186/s12936-018-2272-y.


Background: Cerebral malaria (CM) causes a rapidly developing coma, and remains a major contributor to morbidity and mortality in malaria-endemic regions. This study sought to determine the relationship between cerebrospinal fluid (CSF) Plasmodium falciparum histidine rich protein-2 (PfHRP-2) and clinical, laboratory and radiographic features in a cohort of children with retinopathy-positive CM.

Methods: Patients included in the study were admitted (2009-2013) to the Pediatric Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) meeting World Health Organization criteria for CM with findings of malarial retinopathy. Enzyme-linked immunosorbent assay was used to determine plasma and CSF PfHRP-2 levels. Wilcoxon rank-sum tests and multivariable logistic regression analysis assessed the association of clinical and radiographic characteristics with the primary outcome of death during hospitalization.

Results: In this cohort of 94 patients, median age was 44 (interquartile range 29-62) months, 53 (56.4%) patients were male, 6 (7%) were HIV-infected, and 10 (11%) died during hospitalization. Elevated concentrations of plasma lactate (p = 0.005) and CSF PfHRP-2 (p = 0.04) were significantly associated with death. On multivariable analysis, higher PfHRP-2 in the CSF was associated with death (odds ratio 9.00, 95% confidence interval 1.44-56.42) while plasma PfHRP-2 was not (odds ratio 2.05, 95% confidence interval 0.45-9.35).

Conclusions: Elevation of CSF, but not plasma PfHRP-2, is associated with death in this paediatric CM cohort. PfHRP-2 egress into the CSF may represent alteration of blood brain barrier permeability related to the sequestration of parasitized erythrocytes in the cerebral microvasculature.

Keywords: Cerebrospinal fluid; Coma; Parasitic infections.

MeSH terms

  • Antigens, Protozoan / cerebrospinal fluid*
  • Child, Preschool
  • Female
  • Humans
  • Malaria, Cerebral / cerebrospinal fluid*
  • Malaria, Cerebral / mortality
  • Malaria, Cerebral / pathology
  • Malaria, Falciparum / cerebrospinal fluid*
  • Malaria, Falciparum / mortality
  • Malaria, Falciparum / pathology
  • Male
  • Plasmodium falciparum
  • Protozoan Proteins / cerebrospinal fluid*
  • Retrospective Studies


  • Antigens, Protozoan
  • HRP-2 antigen, Plasmodium falciparum
  • Protozoan Proteins