Long-Term Outcomes in Children Surviving Tropical Arboviral Encephalitis: A Systematic Review

Abstract Background Survivors of childhood encephalitis often suffer from physical and neurocognitive sequelae, particularly in tropical, resource-limited areas with a large burden of arboviral, neurotropic pathogens and limited resources with which to address chronic morbidities. Research into overall and pathogen-specific outcomes following childhood encephalitis may help identify risk factors for poor outcomes, quantify the burden of sequelae, assist with resource allocation and help focus rehabilitative efforts. However, such research is limited. To this end, we systematically reviewed the literature on this topic to identify gaps in knowledge worthy of future investigation. Methods A search of PubMed, Web of Knowledge and the Cochrane databases was performed 10 January through 20 February 2020, using 17 search terms for sequelae and 14 for tropical, arboviral pathogens. Eligible reports demonstrated post-discharge follow-up of ≥3 months and assessment of clinical outcome in a child with an arboviral encephalitis ≤18 years of age at diagnosis. Results Of 1513 articles, 35 were eligible, comprising 693 children. Japanese encephalitis accounted for 18 articles and 93.2% of all subjects (646 total). Sequelae were documented in ∼60% of subjects overall and in those with Japanese encephalitis. For non-Japanese encephalitis virus encephalitides (47 children), sequelae were found in 78.1%. No studies utilized comprehensive neurocognitive testing or assessed the efficacy of rehabilitative efforts. Only nine studies reported data from ≥1 follow-up visit. Conclusion Investigation into long-term outcomes following tropical childhood encephalitis is limited, particularly for neurocognitive sequelae, serial assessments over time and the effect of rehabilitative measures. LAY SUMMARY Encephalitis, an infection of the brain, is frequently caused by arboviruses (viruses spread via the bite of infected arthropods, such as mosquitoes) in tropical locales. Following infection, surviving children may be plagued with severe physical and cognitive deficits. Unfortunately, research into the type of deficits, their frequency and their responsiveness to rehabilitative efforts is lacking. We identified and reviewed 35 studies describing outcomes in children recovering from tropical, arboviral encephalitis at least 3 months following hospital discharge. Poor outcomes were common and found in up to 60% of children. Long-term and serial follow-up visits were rare, as was the use of comprehensive neurocognitive testing. No studies assessed the efficacy of rehabilitative measures. Further study into these areas is recommended.