ReviewViral infections of the central nervous system in Africa
Introduction
Viral infections comprise one of the most important causes of neurological illness with major impact on the global burden of human disease. The estimated incidence of central nervous system (CNS) viral infections is 20–30/100,000 per year (Michos et al., 2007), roughly three times as common as bacterial infections. In resource-limited countries, especially Africa, CNS viral infections are a significant cause of long term neurological dysfunction, mortality and economic burden. On the whole, the prevalence of CNS viral infections in Africa is not known and most likely underestimated, due in part to the limitations in diagnostic tools and poor demographic censuses.
A diverse spectrum of viruses with the capacity to invade the CNS cause devastating acute to chronic neurological disease, sometimes associated with severe disability and/or mortality. Despite the CNS having a highly complex barrier system, a wide variety of viruses elude it, gaining access and inducing disease. The routes of viral entry as well as the specificity of the virus for a particular host tissue and the associated immune responses influence the disease outcome. Based on the distinct anatomic site of the inflammation and the entry site of viral pathogens, infection results in meningitis, encephalitis, myelitis, or a combination of these pathologic features. In the case of multiple site involvement, the terms meningoencephalitis or encephalomyelitis are used (Swanson and McGavern, 2015). Paradoxically, the host’s immune system initially mobilized to defend the CNS from the viral invader, can sometimes turn traitor by contributing to the devastating pathological reactions and subsequent neurological sequelae affecting mobility, sensory organs, and cognitive functions.
The data and relevant information for this review was obtained through an electronic search of the PubMed database using free text and Medical Subject Headings terms for articles on the selected viruses with respect to Africa, and published in English from January 1980 to August 2018. We used the search term “viral infections” AND “central nervous system” OR “Zika virus”, OR “West Nile virus”, OR “Chikungunya virus”, OR “Ebola virus” OR “Marburg virus” OR “Human immunodeficiency virus” OR “Rift Valley virus” OR “Rabies virus” OR “Herpes Simplex virus”. Additional materials were found by manual searches of the reference lists of selected articles, textbooks, and relevant disease-specific guidelines.
This review does not cover several other viruses of relevance to the pathogenesis of nervous system disease and global burden of disease such as but not limited to measles virus, Human-T-Lymphotropic virus type I (HTLV-I), and enteroviruses (poliovirus), extensively reviewed elsewhere (Buchanan and Bonthius, 2012; Khan et al., 2017; Huang and Shih, 2015).The aim of this review is to provide an overview of key viruses involved in CNS infection that are of major public health concern with respect to Africa. These include Flaviviruses- Zika, West Nile and Chikungunya viruses, Filoviruses-Ebola and Marburg viruses, Lentivirus-Human immunodeficiency virus (HIV), Phlebovirus- Rift Valley virus, Lyssavirus-Rabies and the Herpes Simplex viruses. We highlight their epidemiology, key neurological features, different mechanisms involved in the pathogenesis and perspectives for future research.
Section snippets
Flaviviridae: Zika virus and West Nile virus infections
Zika virus (ZIKV) is a flavivirus that can cause disease similar to Dengue and Yellow fever. It is a single strand enveloped RNA enclosed by a capsid protein that encodes structural and non-structural proteins. The first reporting of the virus occurred in the Zika Forest of Uganda using a sentinel monkey in 1947 (Dick et al., 1952).
Transmission of ZIKV to humans is primarily through mosquito-bites of the Aedes genus including: A. aegypti and A. albopictus, which usually bite during the daytime
Clinical features and diagnosis
In general, the infections with the arboviruses (Flaviviridae, Togaviridae, and Bunyaviridae) differ in clinical presentation with some patients being completely asymptomatic, while others may have florid encephalitis with seizures, coma, and death (See Table 2).
Mechanisms of pathogenesis
The CNS is protected from most pathogens by the activation of effective immune responses and the presence of multi-layer barriers to its invasion. Despite this setting, viruses can replicate with unique strategies to relocate into the CNS, where they induce acute to subacute and/or persistent, potentially life-threatening infections. Mechanisms leading to CNS damage may be related to virus-activated mechanisms or any other type of indirect mechanism including systemic organ failure, whether
Future perspectives
Further insights into the epidemiological, biological and molecular fingerprints of CNS viral infections are required in order to provide a clear understanding of mechanisms, prevention tools, and therapies for infection-related CNS damage. Epidemiological studies should focus on the ecology of pathogens, changes in ecosystems that may coincide with virus translocation into human populations, human behaviour and individual risk factors. Basic science research should be focusing on understanding
Conflict of interest
None.
Acknowledgement
AKM is supported by DELTAS Africa Initiative grant # DEL-15-011 to THRiVE-2. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust grant # 107742/Z/15/Z and the UK government. The views expressed in this publication are those of the
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