ABSTRACT
Nodding syndrome (NS) is a debilitating yet often neglected neurological disease affecting thousands of children in several sub-Saharan African countries. The cause of NS remains unknown, and effective treatment options are lacking. Moreover, knowledge regarding NS is scarce and is based on a limited number of publications, with no comprehensive overview published to date. Therefore, the aim of this scoping review was to summarise the current evidence and identify existing knowledge gaps in order to help clinicians, scientists, and policymakers develop guidelines for prioritising this severe condition. We searched the Medline (Ovid), Embase (Ovid), Scopus, and Global Health Library databases in accordance with the PRISMA extension for scoping review guidance and in accordance with the Joanna Briggs Institute guidelines and methodology for a scoping review, using keywords describing NS. We then extracted and presented the original data regarding the epidemiology, aetiology, pathophysiology, clinical features, diagnosis, management, and outcomes of NS, as well as community perceptions and the psychosocial and economic impact of NS. Out of 1470 identified articles, a total of 69 were included in this scoping review. Major gaps exist in understanding the aetiology and pathogenesis of NS. Future research is urgently needed not only to address these gaps, but also to study the treatment options, epidemiology, and psychosocial and economic impacts of NS. Innovative interventions and rehabilitation programmes designed to address the psychosocial and economic burdens associated with NS are also urgently needed.
ABSTRACT
The Orthobunyavirus genus comprises a wide range of arthropod-borne viruses which are prevalent worldwide and commonly associated with central nervous system (CNS) disease in humans and other vertebrates. Several orthobunyaviruses have recently emerged and increasingly more will likely do so in the future. Despite this large number, an overview of these viruses is currently lacking, making it challenging to determine importance from a One Health perspective. Causality is a key feature of determining importance, yet classical tools are unfit to evaluate the causality of orthobunyaviral CNS disease. Therefore, we aimed to provide an overview of orthobunyaviral CNS disease in vertebrates and objectify the causality strength of each virus. In total, we identified 27 orthobunyaviruses described in literature to be associated with CNS disease. Ten were associated with disease in multiple host species of which seven included humans. Seven viruses were associated with both congenital and postnatal CNS disease. CNS disease-associated orthobunyaviruses were spread across all known Orthobunyavirus serogroups by phylogenetic analyses. Taken together, these results indicate that orthobunyaviruses may have a common tendency to infect the CNS of vertebrates. Next, we developed six tailor-made causality indicators and evaluated the causality strength of each of the identified orthobunyaviruses. Nine viruses had a 'strong' causality score and were deemed causal. Eight had a 'moderate' and ten a 'weak' causality score. Notably, there was a lack of case-control studies, which was only available for one virus. We, therefore, stress the importance of proper case-control studies as a fundamental aspect of proving causality. This comprehensible overview can be used to identify orthobunyaviruses which may be considered causal, reveal research gaps for viruses with moderate to low causality scores, and provide a framework to evaluate the causality of orthobunyaviruses that may newly emerge in the future.
