Identification of malaria retinopathy improves the specificity of the clinical diagnosis of cerebral malaria: findings from a prospective cohort study

Abstract

The diagnosis of cerebral malaria (CM) is difficult to confirm in endemic regions with limited neurodiagnostics. Accurate diagnoses are critical for trials and outcomes studies. Findings from an autopsy-based study suggest that identifying malaria retinopathy in children satisfying the standard clinical case definition of CM improves our ability to accurately diagnose CM in vivo. In a post hoc analysis of a prospective exposure-control study to evaluate CM as a risk factor for epilepsy, we stratified children meeting the standard case definition by their retinopathy status (presence versus absence) and compared these groups for pre-existing risk factors for epilepsy. We also compared them to the concurrently enrolled, non-comatose controls. Children meeting the standard case definition of CM who lacked malaria retinopathy had a higher prevalence of pre-existing developmental problems and family history of epilepsy. This subset of patients may represent children with a pre-existing propensity to adverse neurologic symptoms and outcomes.

Figure 1.

CM patient with retinal whitening in the central macula and subtle orange discoloration of the blood vessels. This figure appears in color at www.ajtmh.org.

Figure 2.

CM patient with several features of CM retinopathy including macular and peripheral retinal whitening, hemorrhages, and papilledema. This figure appears in color at www.ajtmh.org.

Figure 3.

Typical CM retinopathy retinal hemorrhage with central whitening. This figure appears in color at www.ajtmh.org.

Figure 4.

Vessel whitening typical of CM retinopathy with involvement of the capillary bed as well as larger retinal vessels. Retinal whitening is also seen. This figure appears in color at www.ajtmh.org.