{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T21:32:31Z","timestamp":1780695151170,"version":"3.54.1"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ARES-Belgium","award":["COOP-CONV-18-004, AI ARES UNIKIN"],"award-info":[{"award-number":["COOP-CONV-18-004, AI ARES UNIKIN"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Neuromeningeal cryptococcosis (NMC) is a life-threatening opportunistic infection in advanced HIV disease patients (AHDP). It is caused by <jats:italic>Cryptococcus<\/jats:italic> spp. complexes and mainly occurs in sub-Saharan Africa. In this study, we performed molecular characterization and antifungal susceptibility profiling of <jats:italic>Cryptococcus<\/jats:italic> isolates from AHDP in Kinshasa (DRC). Additionally, we investigated a possible association between NMC severity factors and the <jats:italic>Cryptococcus neoformans<\/jats:italic> (<jats:italic>Cn<\/jats:italic>) multilocus sequence typing (MLST) profiles. We characterized the isolates using PCR serotyping, MALDI-TOF MS, internal transcribed spacer (ITS) sequencing, and MLST. Susceptibility testing for the major antifungal drugs was performed according to the EUCAST guidelines. Parameters associated with NMC severity, such as hypoglycorrhachia (&lt; 50 mg\/dL), increased cerebral spinal fluid opening pressure (&gt; 30 cm H<jats:sub>2<\/jats:sub>O), and poor therapeutic outcome were compared with the <jats:italic>Cn<\/jats:italic> MLST sequences type (ST). Twenty-three out of 29 <jats:italic>Cryptococcus<\/jats:italic> isolates were identified as serotype A using PCR serotyping (79.3%; 95% IC: 65.5\u201393.1), while six (20.7%; 95% IC: 6.9\u201334.5) were not serotypable. The 29 isolates were identified by ITS sequencing as follows: <jats:italic>Cryptococcus neoformans<\/jats:italic> (23\/29, 79.3%), <jats:italic>Cutaneotrichosporon curvatus (<\/jats:italic>previously called <jats:italic>Cryptococcus curvatus)<\/jats:italic> (5\/29, 17.2%), and <jats:italic>Papiliotrema laurentii<\/jats:italic> (<jats:italic>Cryptococcus laurentii<\/jats:italic>) (1\/29, 3.5%). Using the ISHAM MLST scheme, all <jats:italic>Cn<\/jats:italic> isolates were identified as molecular type VNI. These comprised seven different STs: ST93 (n = 15), ST5 (n = 2), ST53 (n = 1), ST31 (n = 1), ST4 (n = 1), ST69 (n = 1), and one novel ST that has not yet been reported from other parts of the world and was subsequently assigned as ST659 (n = 2). Of the included strains, only <jats:italic>Papiliotrema laurentii<\/jats:italic> was resistant to amphoterin B (1\/29, 3.5%), 6.8% (2\/29) were resistant to 5-flucytosine (the single <jats:italic>Papiliotrema laurentii<\/jats:italic> strain and one <jats:italic>Cryptococcus neoformans<\/jats:italic> isolate), and 13.8% (4\/29) to fluconazole, including two of five (40%) <jats:italic>Cutaneotrichosporon curvatus<\/jats:italic> and two of 23 (8.7%) <jats:italic>C<\/jats:italic>. <jats:italic>neoformans<\/jats:italic> strains. We found a significative association between poor therapeutic outcome and a non-ST93 sequence type of causative strains (these concerned the less common sequence types: ST53, ST31, ST5, ST4, ST659, and ST69) (87.5% versus 40%, <jats:italic>p<\/jats:italic> = 0.02). Molecular analysis of <jats:italic>Cryptococcus<\/jats:italic> spp. isolates showed a wide species diversity and genetic heterogenicity of <jats:italic>Cn<\/jats:italic> within the VNI molecular type. Furthermore, it is worrying that among included strains we found resistances to several of the commonly used antifungals.<\/jats:p>","DOI":"10.1371\/journal.pone.0267842","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T17:53:53Z","timestamp":1652982833000},"page":"e0267842","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical epidemiology and high genetic diversity amongst Cryptococcus spp. isolates infecting people living with HIV in Kinshasa, Democratic Republic of Congo"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0084-5068","authenticated-orcid":true,"given":"Bive 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Mambimbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaultier","family":"Muendele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Boreux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Landu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celestin","family":"Nzanzu Mudogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Robert","family":"M\u2019Buze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Moutschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wieland","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Mvumbi Lelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9025-6493","authenticated-orcid":true,"given":"Marie-Pierre","family":"Hayette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"issue":"8","key":"pone.0267842.ref001","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis","volume":"17","author":"R Rajasingham","year":"2017","journal-title":"Lancet Infect Dis"},{"issue":"10","key":"pone.0267842.ref002","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/myc.13339","article-title":"Serious fungal diseases in Democratic Republic of Congo\u2013Incidence and prevalence estimates","volume":"64","author":"GK Kamwiziku","year":"2021","journal-title":"Mycoses"},{"key":"pone.0267842.ref003","first-page":"1","volume-title":"Country factsheets Democratic Republic of Congo 2020 HIV and AIDS Estimates Adults and children living with Country factsheets DRC | 2020 HIV testing and treatment cascade People living with HIV Coverage of adults and children","author":"UNAIDS and AIDSinfo","year":"2021"},{"issue":"302","key":"pone.0267842.ref004","first-page":"1","article-title":"Epidemiological, clinical and biological profile of neuromeningeal cryptococcosis among people living with HIV in Kinshasa, Democratic Republic of Congo","volume":"37","author":"B Zono","year":"2020","journal-title":"Pan Afr Med J."},{"issue":"4","key":"pone.0267842.ref005","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/cid\/cit341","article-title":"Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii","volume":"57","author":"SCA Chen","year":"2013","journal-title":"Clin 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