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Despite widespread use and early induction of ART among HIV\u2010infected adults, incidence of cryptococcosis remains significant in those with advanced HIV disease.\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    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.\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    person\u2010to\u2010person transmission is uncommon, and deaths related to blood infection without CNS involvement are rare. Keen to the persistent high mortality associated with HIV\u2010cryptococcal 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\u2010to\u20104\u2010fold higher in those with seizures. And high immune activation together with exacerbated inflammation and elevated PD\u20101\/PD\u2010L immune checkpoint expression is immunomodulated phenotypes elevated in CSF relative to blood. Lastly, though multiple\n                    <jats:italic>Cryptococcus<\/jats:italic>\n                    species cause disease in this setting, observations are mostly generalised to cryptococcal infection\/meningitis or regional dominant species (\n                    <jats:italic>C\u00a0neoformans<\/jats:italic>\n                    or\n                    <jats:italic>gattii complex<\/jats:italic>\n                    ) 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.\n                  <\/jats:p>","DOI":"10.1111\/myc.13122","type":"journal-article","created":{"date-parts":[[2020,5,30]],"date-time":"2020-05-30T07:20:36Z","timestamp":1590823236000},"page":"840-853","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Landmark clinical observations and immunopathogenesis pathways linked to HIV and\n                    <i>Cryptococcus<\/i>\n                    fatal central nervous system co\u2010infection"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9292-8687","authenticated-orcid":false,"given":"Samuel","family":"Okurut","sequence":"first","affiliation":[{"name":"Research Department Infectious Diseases Institute Makerere University 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