Clinical epidemiology and high genetic diversity amongst Cryptococcus spp. isolates infecting people living with HIV in Kinshasa, Democratic Republic of Congo.
Antifungal Agents; Antifungal Agents/pharmacology; Antifungal Agents/therapeutic use; Basidiomycota; Democratic Republic of the Congo/epidemiology; Genetic Variation; Genotype; Humans; Multilocus Sequence Typing; Mycological Typing Techniques; Cryptococcosis/drug therapy; Cryptococcosis/epidemiology; Cryptococcosis/microbiology; Cryptococcus neoformans; HIV Infections/complications; HIV Infections/drug therapy; HIV Infections/epidemiology; Multidisciplinary
Abstract :
[en] Neuromeningeal cryptococcosis (NMC) is a life-threatening opportunistic infection in advanced HIV disease patients (AHDP). It is caused by Cryptococcus spp. complexes and mainly occurs in sub-Saharan Africa. In this study, we performed molecular characterization and antifungal susceptibility profiling of Cryptococcus isolates from AHDP in Kinshasa (DRC). Additionally, we investigated a possible association between NMC severity factors and the Cryptococcus neoformans (Cn) 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 (< 50 mg/dL), increased cerebral spinal fluid opening pressure (> 30 cm H2O), and poor therapeutic outcome were compared with the Cn MLST sequences type (ST). Twenty-three out of 29 Cryptococcus isolates were identified as serotype A using PCR serotyping (79.3%; 95% IC: 65.5-93.1), while six (20.7%; 95% IC: 6.9-34.5) were not serotypable. The 29 isolates were identified by ITS sequencing as follows: Cryptococcus neoformans (23/29, 79.3%), Cutaneotrichosporon curvatus (previously called Cryptococcus curvatus) (5/29, 17.2%), and Papiliotrema laurentii (Cryptococcus laurentii) (1/29, 3.5%). Using the ISHAM MLST scheme, all Cn 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 Papiliotrema laurentii was resistant to amphoterin B (1/29, 3.5%), 6.8% (2/29) were resistant to 5-flucytosine (the single Papiliotrema laurentii strain and one Cryptococcus neoformans isolate), and 13.8% (4/29) to fluconazole, including two of five (40%) Cutaneotrichosporon curvatus and two of 23 (8.7%) C. neoformans 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%, p = 0.02). Molecular analysis of Cryptococcus spp. isolates showed a wide species diversity and genetic heterogenicity of Cn within the VNI molecular type. Furthermore, it is worrying that among included strains we found resistances to several of the commonly used antifungals.
Research Center/Unit :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Disciplines :
Immunology & infectious disease Laboratory medicine & medical technology
Author, co-author :
Zono, Bive ✱; Université de Liège - ULiège > Faculté de Médecine > Doct. sc. bioméd. & pharma. (paysage) ; Université de Liège - ULiège > Faculté de Médecine > Form. doct. sc. biomed. & pharma. (paysage) ; Université de Kinshasa > Sciences de base > Biologie Moléculaire
SACHELI, Rosalie ✱; Centre Hospitalier Universitaire de Liège - CHU > > Service de microbiologie clinique
Situakibanza Nani-Tuma, Hippolyte ✱; Faculty of Medicine, Department of Internal Medicine/Department of Tropical Medicine, Infectious Diseases Service, University of Kinshasa, Kinshasa, The Democratic Republic of Congo
Kabututu Zakayi, Pius ✱; Faculty of Medicine, Department of Basic Sciences, Molecular Biology Service, University of Kinshasa, Kinshasa, The Democratic Republic of Congo
Ka, Alex ✱; Molecular Mycology Research Laboratory, Faculty of Medicine and Health, Centre for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Clinical School, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead Hospital-Research and Education Network, Westmead Institute for Medical Research, Sydney, Australia
Mbula Mambimbi, Marcel ✱; Faculty of Medicine, Department of Internal Medicine/Department of Tropical Medicine, Infectious Diseases Service, University of Kinshasa, Kinshasa, The Democratic Republic of Congo
Muendele, Gaultier ✱; Internal Medicine Department, Advanced HIV Disease Management Unit, Centre Hospitalier Mère et Enfant de NGABA, Kinshasa, The Democratic Republic of Congo
BOREUX, Raphaël ✱; Centre Hospitalier Universitaire de Liège - CHU > > Service de microbiologie clinique
Landu, Nicole ✱; Internal Medicine Department, Advanced HIV Disease Management Unit, Centre Médical et Evangélique Révérend LUYINDU, Kinshasa, The Democratic Republic of Congo
Nzanzu Mudogo, Celestin ✱; Faculty of Medicine, Department of Basic Sciences, Molecular Biology Service, University of Kinshasa, Kinshasa, The Democratic Republic of Congo
M'Buze, Pierre-Robert ✱; Internal Medicine Department, Advanced HIV Disease Management Unit, Centre Hospitalier Roi Baudouin 1er, Kinshasa, The Democratic Republic of Congo
MOUTSCHEN, Michel ✱; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne
Meyer, Wieland ✱; Molecular Mycology Research Laboratory, Faculty of Medicine and Health, Centre for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Clinical School, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead Hospital-Research and Education Network, Westmead Institute for Medical Research, Sydney, Australia ; Curtin Medical School, Curtin University, Perth, Australia
Mvumbi Lelo, Georges ✱; Faculty of Medicine, Department of Basic Sciences, Molecular Biology Service, University of Kinshasa, Kinshasa, The Democratic Republic of Congo
HAYETTE, Marie-Pierre ✱; Centre Hospitalier Universitaire de Liège - CHU > > Service de microbiologie clinique
✱ These authors have contributed equally to this work.
Language :
English
Title :
Clinical epidemiology and high genetic diversity amongst Cryptococcus spp. isolates infecting people living with HIV in Kinshasa, Democratic Republic of Congo.
Alternative titles :
[fr] Épidémiologie clinique et grande diversité génétique parmi les isolats de Cryptococcus spp. infectant les personnes vivant avec le VIH à Kinshasa, République démocratique du Congo
Original title :
[es] Epidemiología clínica y alta diversidad genética entre los aislados de Cryptococcus spp. que infectan a personas que viven con el VIH en Kinshasa, República Democrática del Congo.
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