Macroarray assay for differential diagnosis of meningoencephalitis in southern Africa

Abstract

BackgroundMany cases of acute febrile illness with nervous manifestations go undiagnosed, partly because the potential pathogens are not investigated routinely. ObjectiveTo develop a multiplex PCR-based macroarray for detection of 29 pathogens associated with febrile disease, aseptic meningitis and meningoencephalitis in southern Africa, including common viruses, bacteria, parasites and selected arboviruses. Study designPathogens were identified by hybridization of PCR amplicons to probes on a macroarray chip, followed by colorimetric detection. ResultsPositive control specimens for all 29 targets were detected with high sensitivity. Twenty-seven clinical samples previously found positive for various etiologies of febrile disease and meningoencephalitis, including less common infections such as Crimean Congo haemorrhagic fever, Rift Valley fever, West Nile and rabies were all identified. Testing of a blinded panel of 16 specimens in triplicate demonstrated high repeatability. Screening of 138 specimens from patients with febrile and/or neurological signs that could not be solved in routine investigations yielded 5 additional diagnoses. ConclusionA highly sensitive, specific and easily interpreted test was developed to detect 29 pathogens associated with febrile and nervous disease.