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Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co‐infection

Cryptococcal meningitis remains one of the leading causes of death among HIV‐infected adults in the fourth decade of HIV era in sub‐Saharan Africa, contributing to 10%–20% of global HIV‐related deaths. Despite widespread use and early induction of ART among HIV‐infected adults, incidence of cryptoco...

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Autores principales: Okurut, Samuel, Boulware, David R., Olobo, Joseph, Meya, David B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416908/
https://www.ncbi.nlm.nih.gov/pubmed/32472727
http://dx.doi.org/10.1111/myc.13122
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author Okurut, Samuel
Boulware, David R.
Olobo, Joseph
Meya, David B.
author_facet Okurut, Samuel
Boulware, David R.
Olobo, Joseph
Meya, David B.
author_sort Okurut, Samuel
collection PubMed
description Cryptococcal meningitis remains one of the leading causes of death among HIV‐infected adults in the fourth decade of HIV era in sub‐Saharan Africa, contributing to 10%–20% of global HIV‐related deaths. Despite widespread use and early induction of ART among HIV‐infected adults, incidence of cryptococcosis remains significant in those with advanced HIV disease. Cryptococcus species that causes fatal infection follows systemic spread from initial environmental acquired infection in lungs to antigenaemia and fungaemia in circulation prior to establishment of often fatal disease, cryptococcal meningitis in the CNS. Cryptococcus person‐to‐person transmission is uncommon, and deaths related to blood infection without CNS involvement are rare. Keen to the persistent high mortality associated with HIV‐cryptococcal meningitis, seizures are common among a third of the patients, altered mental status is frequent, anaemia is prevalent with ensuing brain hypoxia and at autopsy, brain fibrosis and infarction are evident. In addition, fungal burden is 3‐to‐4‐fold higher in those with seizures. And high immune activation together with exacerbated inflammation and elevated PD‐1/PD‐L immune checkpoint expression is immunomodulated phenotypes elevated in CSF relative to blood. Lastly, though multiple Cryptococcus species cause disease in this setting, observations are mostly generalised to cryptococcal infection/meningitis or regional dominant species (C neoformans or gattii complex) that may limit our understanding of interspecies differences in infection, progression, treatment or recovery outcome. Together, these factors and underlying mechanisms are hypotheses generating for research to find targets to prevent infection or adequate therapy to prevent persistent high mortality with current optimal therapy.
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spelling pubmed-74169082020-09-25 Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co‐infection Okurut, Samuel Boulware, David R. Olobo, Joseph Meya, David B. Mycoses Review Articles Cryptococcal meningitis remains one of the leading causes of death among HIV‐infected adults in the fourth decade of HIV era in sub‐Saharan Africa, contributing to 10%–20% of global HIV‐related deaths. Despite widespread use and early induction of ART among HIV‐infected adults, incidence of cryptococcosis remains significant in those with advanced HIV disease. Cryptococcus species that causes fatal infection follows systemic spread from initial environmental acquired infection in lungs to antigenaemia and fungaemia in circulation prior to establishment of often fatal disease, cryptococcal meningitis in the CNS. Cryptococcus person‐to‐person transmission is uncommon, and deaths related to blood infection without CNS involvement are rare. Keen to the persistent high mortality associated with HIV‐cryptococcal meningitis, seizures are common among a third of the patients, altered mental status is frequent, anaemia is prevalent with ensuing brain hypoxia and at autopsy, brain fibrosis and infarction are evident. In addition, fungal burden is 3‐to‐4‐fold higher in those with seizures. And high immune activation together with exacerbated inflammation and elevated PD‐1/PD‐L immune checkpoint expression is immunomodulated phenotypes elevated in CSF relative to blood. Lastly, though multiple Cryptococcus species cause disease in this setting, observations are mostly generalised to cryptococcal infection/meningitis or regional dominant species (C neoformans or gattii complex) that may limit our understanding of interspecies differences in infection, progression, treatment or recovery outcome. Together, these factors and underlying mechanisms are hypotheses generating for research to find targets to prevent infection or adequate therapy to prevent persistent high mortality with current optimal therapy. John Wiley and Sons Inc. 2020-06-19 2020-08 /pmc/articles/PMC7416908/ /pubmed/32472727 http://dx.doi.org/10.1111/myc.13122 Text en © 2020 The Authors. Mycoses published by Blackwell Verlag GmbH This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Articles
Okurut, Samuel
Boulware, David R.
Olobo, Joseph
Meya, David B.
Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co‐infection
title Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co‐infection
title_full Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co‐infection
title_fullStr Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co‐infection
title_full_unstemmed Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co‐infection
title_short Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co‐infection
title_sort landmark clinical observations and immunopathogenesis pathways linked to hiv and cryptococcus fatal central nervous system co‐infection
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416908/
https://www.ncbi.nlm.nih.gov/pubmed/32472727
http://dx.doi.org/10.1111/myc.13122
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