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Abstract
Background. The diagnosis of cerebral malaria is problematic in malaria-endemic areas because encephalopathy in patients with parasitemia may have another cause. Abnormal retinal findings are thought to increase the specificity of the diagnosis, and the level of histidine-rich protein 2 (HRP2) may reflect the parasite biomass.Methods. We examined the retina and measured plasma HRP2 levels in children with acute nontraumatic encephalopathy in Kenya. Logistic regression, with HRP2 level as an independent variable and World Health Organization–defined cerebral malaria and/or retinopathy as the outcome, was used to calculate malaria-attributable fractions (MAFs) and retinopathy-attributable fractions (RAFs).Results. Of 270 children, 140 (52%) had peripheral parasitemia, 80 (30%) had malaria retinopathy, and 164 (61%) had an HRP2 level of >0 U/mL. During 2006–2011, the incidence of HRP2 positivity among admitted children declined by 49 cases per 100 000 per year (a 78% reduction). An HRP2 level of >0 U/mL had a MAF of 93% for cerebral malaria, with a MAF of 97% observed for HRP2 levels of ≥10 U/mL (the level of the best combined sensitivity and specificity). HRP2 levels of >0 U/mL had a RAF of 77% for features of retinopathy combined, with the highest RAFs for macular whitening (99%), peripheral whitening (98%), and hemorrhages (90%).Conclusion. HRP2 has a high attributable fraction for features of malarial retinopathy, supporting its use in the diagnosis of cerebral malaria. HRP2 thresholds improve the specificity of the definition.
Highlights
The diagnosis of cerebral malaria is problematic in malaria-endemic areas because encephalopathy in patients with parasitemia may have another cause
An histidine-rich protein 2 (HRP2) level of >0 units per milliliter (U/mL) had a malaria-attributable fraction (MAF) of 93% for cerebral malaria, with a MAF of 97% observed for HRP2 levels of ≥10 U/mL
HRP2 levels of >0 U/mL had a retinal attributable fraction (RAF) of 77% for features of retinopathy combined, with the highest RAFs for macular whitening (99%), peripheral whitening (98%), and hemorrhages (90%)
Summary
We examined the retina and measured plasma HRP2 levels in children with acute nontraumatic encephalopathy in Kenya. The hospital morbidity surveillance is directly linked with a population framework referred to as the Kilifi Health Demographic Surveillance System (KHDSS) [19] This area has seen a significant reduction in hospital admissions with malaria and parasite prevalence in the community [20], both of which are good surrogate measures for a changing malaria transmission intensity. Study participants were all children admitted with coma (defined as a Blantyre coma score of ≤2 or the inability to localize a painful stimuli) [22] between July 2005 and December 2011. These children were given appropriate emergency care and treatments according to the national guidelines by clinicians and nurses at the hospital, who provide 24-hour clinical cover
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