Abstract

The direct impact and sequelae of infections in children and adults result in significant morbidity and mortality especially when they involve the central (CNS) or peripheral nervous system (PNS). The historical understanding of the pathophysiology has been mostly focused on the direct impact of the various pathogens through neural tissue invasion. However, with the better understanding of neuroimmunology, there is a rapidly growing realization of the contribution of the innate and adaptive host immune responses in the pathogenesis of many CNS and PNS diseases.The balance between the protective and pathologic sequelae of immunity is fragile and can easily be tipped towards harm for the host. The matter of immune privilege and surveillance of the CNS/PNS compartments and the role of the blood-brain barrier (BBB) and blood nerve barrier (BNB) makes this even more complex. Our understanding of the pathogenesis of many post-infectious manifestations of various microbial agents remains elusive, especially in the diverse African setting. Our exploration and better understanding of the neuroimmunology of some of the infectious diseases that we encounter in the continent will go a long way into helping us to improve their management and therefore lessen the burden.Africa is diverse and uniquely poised because of the mix of the classic, well described, autoimmune disease entities and the specifically “tropical” conditions. This review explores the current understanding of some of the para- and post-infectious autoimmune manifestations of CNS and PNS diseases in the African context. We highlight the clinical presentations, diagnosis and treatment of these neurological disorders and underscore the knowledge gaps and perspectives for future research using disease models of conditions that we see in the continent, some of which are not uniquely African and, where relevant, include discussion of the proposed mechanisms underlying pathogen-induced autoimmunity. This review covers the following conditions as models and highlight those in which a relationship with COVID-19 infection has been reported: a) Acute Necrotizing Encephalopathy; b) Measles-associated encephalopathies; c) Human Immunodeficiency Virus (HIV) neuroimmune disorders, and particularly the difficulties associated with classical post-infectious autoimmune disorders such as the Guillain-Barré syndrome in the context of HIV and other infections. Finally, we describe NMDA-R encephalitis, which can be post-HSV encephalitis, summarise other antibody-mediated CNS diseases and describe myasthenia gravis as the classic antibody-mediated disease but with special features in Africa.

Highlights

  • Africa is a diverse continent, rich with opportunities

  • This review explores the current understanding of the postinfectious autoimmune manifestations of central nervous system (CNS) and PNS diseases in the African context

  • 2.1.3 Human Immunodeficiency Virus (HIV) Infection and Autoimmunity Southern Africa is the epicentre of the HIV/AIDS pandemic that has ravaged the world since the condition was first recognised clinically in 1981 [47]

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Summary

INTRODUCTION

Africa is a diverse continent, rich with opportunities. It has a predominantly young population demography with varied socioeconomic backgrounds and human potential. “Of 25 countries highly exposed to infectious diseases reported by Infectious Disease Vulnerability Index in 2016, 22 were from the African region” [4] Some of these infections could be prevented with more widespread vaccination or treatments. The list of infections with devastating neurological consequences includes Influenza virus, Malaria, Ebola virus, other zoonotic viruses, Onchocerciasis with its recently reported Nodding syndrome, Nakalanga syndrome and other neurological sequelae [1, 7] The interplay between these infectious threats and the peculiar challenges faced by many African countries will result in disastrous consequences, with significant morbidity and loss of life. We discuss the proposed mechanisms underlying pathogen-induced autoimmunity, highlight the clinical presentation, diagnosis and treatment of these neurological disorders and underscore the knowledge gaps and perspectives for future research using disease models of conditions that we see in the continent. The lessons learnt from the past must be used to impart tools and skills to the generation of neuroscientists and clinicians for dealing with future challenges in the field of neuroinflammation and autoimmunity

Neurological Complications of Influenza
Acute Necrotizing Encephalopathy
Pathophysiology
Treatment There are currently no evidence-based treatments for ANE
Covid-19 (SARS-Cov-2) Associated ANE
Gaps in Knowledge
Neurological Complications of Measles (Wild Type) Virus (MeV)
Acute Post-Infectious Measles Encephalitis (APME/ADEM)
Measles-Inclusion Body
Subacute Sclerosing
HIV Infection and Autoimmunity Southern
Autoimmune Neurological Diseases
Research Priorities This review identified major knowledge gaps
The Interplay Between the Organisms and the Immune System in the CNS, and the
Value of Neuroimmune Changes in Diagnostics and Therapeutics
Knowledge Gaps
Guillain-Barre Syndrome (GBS)
Differential Diagnosis of GBS
Treatment and Management of GBS
NMDAR-Antibody Encephalitis
Triggers and Neuroimmunology
Myasthenia Gravis
Management and Treatment of MG in Sub-Saharan
Findings
CONCLUSION
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