[en] Cryptococcosis is a common opportunistic infection associated with HIV/AIDS. The present review systematically describes the clinical and biological aspects of cryptococcosis in the Democratic Republic of Congo (DRC) and estimates its 2020 burden in people living with HIV (PLHIV). Following PRISMA guidelines, we searched online databases for records of cryptococcosis/Cryptococcus spp. in the DRC. Meta-analysis was then performed to estimate summary statistics and the corresponding 95% confidence intervals (CI). A total of 30 studies were included. These included 1,018 cryptococcosis patients, including 80.8% with neuromeningeal cryptococcosis (NMC) and predominantly immunocompromised due to HIV/AIDS (97.6%). The NMC mean prevalence was estimated at 9.63% (95% CI: 5.99-14.07). More than one in two patients (52.7%) under treatment died. Monotherapy with fluconazole was the main treatment administered (80.6%). Furthermore, we estimate that about 9,265 (95% CI: 5,763-13,537) PLHIV had cryptococcosis in 2020, in DRC; of which about 4,883 (95% CI: 3,037-7,134) would have died in the same year. Among isolates in all included studies, 74 strains have been characterised. Of these, 82.4% concerned Cryptococcus neoformans sensu lato (s.l) (exclusively of serotype A and mostly of molecular types VNI and VNII) and 17.6% concerned Cryptotoccus gattii s.l (belonging to serotype B/molecular type VGI). Cryptococcosis remains common with an unacceptably high mortality rate. A large number of PLHIV affected by and dying from cryptococcosis in 2020 demonstrates its heavy burden among the Congolese PLHIV. To mitigate this burden, it is important to improve the quality and accessibility of care for all PLHIV.
Research center :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège Laboratoire de Biologie Moléculaire de la Faculté de Médecine/Université de Kinshasa
Disciplines :
Immunology & infectious disease Laboratory medicine & medical technology
Author, co-author :
Zono, Bive ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Molecular Biology Service, Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, the Democratic Republic of Congo
Kasumba, Dacquin Muhandwa; Molecular Biology Service, Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, the Democratic Republic of Congo
Situakibanza Nani-Tuma, Hippolyte; Department of Internal Medicine/Department of Tropical Medicine, Faculty of Medicine, University of Kinshasa, Kinshasa, the Democratic Republic of Congo
Bepouka Izizag, Ben; Department of Internal Medicine/Department of Tropical Medicine, Faculty of Medicine, University of Kinshasa, Kinshasa, the Democratic Republic of Congo
Yambayamba Kapenga, Marc; Department of Epidemiology and Biostatistics, Kinshasa School of Public Health, University of Kinshasa, Kinshasa, the Democratic Republic of Congo
Nsuka Yanga, Ruth ; Université de Liège - ULiège > Faculté de Médecine > Doct. sc. bioméd. & pharma. (paysage) ; Molecular Biology Service, Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, the Democratic Republic of Congo
Tshimanga Yona, Tshimy; Department of Medical Biology, Higher Institute of Medical Techniques-Kinshasa, Kinshasa, the Democratic Republic of Congo
Kamangu Ntambwe, Erick; Molecular Biology Service, Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, the Democratic Republic of Congo
HAYETTE, Marie-Pierre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de microbiologie clinique
Mvumbi Lelo, Georges; Molecular Biology Service, Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, the Democratic Republic of Congo
Language :
English
Title :
Cryptococcosis in the Democratic Republic of Congo from 1953 to 2021: A systematic review and meta-analysis.
Molez J. SIDA et cryptococcose en Afrique centrale. Cah Santé. 1992;2:270-273.
Hagen F, Khayhan K, Theelen B, et al. Recognition of seven species in the Cryptococcus gattii / Cryptococcus neoformans species complex. Fungal Genet Biol. 2015;78:16-48. doi:10.1016/j.fgb.2015.02.009
Francisco EC, de Jong AW, Hagen F. Cryptococcosis and Cryptococcus. Mycopathologia. 2021;186(5):729-731. doi:10.1007/s11046-021-00577-7
Campbell LT, Simonin AR, Chen C, et al. Cryptococcus strains with different pathogenic potentials have diverse protein secretomes. Eukaryot Cell. 2015;14(6):554-563. doi:10.1128/EC.00052-15
Maziarz EK, Perfect JR. Cryptococcosis. Infect Dis Clin North Am. 2016;30(1):179-206. doi:10.1007/978-3-540-75387-2_123
Rajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017;17(8):873-881. doi:10.1016/S1473-3099(17)30243-8
UNAIDS and AIDSinfo. 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. Unaids. 2021:1-6. https://aidsinfo.unaids.org/%0D
Medecins Sans Frontières SA. Les Négligés de l’infection Au VIH Patients En Stade VIH Avancé : Une Prise En Charge Adaptée et Gratuite Est Leur Seule Chance de Survie. Ghizlaine; 2017. https://samumsf.org/sites/default/files/2017-08/MSF Kinshasa Reportdigital_0pdf.
Gatti F, Eeckels R. An atypical strain of Cryptococcus neofromans (san Felice) Vuillemin 1894. Ann Soc Belge Med Trop. 1970;50(6):689-694.
Swinne D, Kayembe K, Niyimi M. Isolation of saprophytic Cryptococcus neoformans var. neoformans in Kinshasa, Zaïre. Ann La Socièté Belge Médecine Trop. 1986;66:57-61.
Kapend'a K, Komichelo K, Swinne D, Vandepitte J. Meningitis due to Cryptococcus neoformans biovar gattii in a Zairean AIDS patient. Eur J Clin Microbiol. 1987;6(3):320-321.
Muyembe Tamfum JJ, Mupapa Kibadi D, Nganda L, et al. Cryptococcosis caused by Cryptococcus neoformans var. gattii. A case report with an AIDS association observed in Kinshasa (Zaire). Med Trop. 1992;52(4):435-438.
Kamwiziku GK, Makangara JC, Orefuwa E, Denning DW. Serious fungal diseases in Democratic Republic of Congo – incidence and prevalence estimates. Mycoses. 2021;64(10):1159-1169.
Moher D, Liberati A, Tetzlaff J, Altman DG, Grp P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement (Reprinted from Annals of Internal Medicine). Phys Ther. 2009;89(9):873-880. doi:10.1371/journal.pmed.1000097
Mwamba Claude. Cryptococcose chez les personnes vivant avec le VIH : IRIS. 2014.
Jérémie M, Edidi S, Butel C, et al. Resistance to antiretroviral drugs in treated and drug-naive patients in the Democratic Republic of Congo. J Acq. 2011;57:27-33.
Kamangu EN. Estimation of clinical, immunological and virological failure of first line antiretroviral treatment in Kinshasa, Democratic Republic of Congo. Open Access Libr J. 2018;5:1-8. doi:10.4236/oalib.1104560
Rosen S, Fox MP, Gill CJ. Patient retention in antiretroviral therapy programs in sub-Saharan Africa: A systematic review. PLoS Medicine. 2007;4(10):1691-1701. doi:10.1371/journal.pmed.0040298
Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009;23(4):525-530. doi:10.1097/QAD.0b013e328322ffac
Stijns J, Royer P. Un cas de méningite à Torulopsis au Congo Belge. Ann Soc Belge Med 1953;33:484-486.
Michaux J, Vandepitte J, Hennebert P, Sonnet J. Aspects cliniques et thérapeutiques de la cryptococcose chez le Bantou : A propos de trois cas traités par l’Amphotéricine B. Ann Soc Belge Med Trop. 1963;5:751-776.
Lamey B, Melameka N. Clinical and epidemiologic aspects of cryptococcosis in Kinshasa. Apropos of 15 personal cases. Med Trop (Mars). 1982;42(5):507-50711.
Vandepitte J, Verwilghen R, Zachee P. AIDS and cryptococcosis (ZAIRE). Lancet. 1983;1:925-926.
Odio W, Kapita B, Mbendi N, et al. Le syndrome d’immunodéficience acquise (SIDA) à Kinshasa, Zaïre : Observation cliniques et épidémiologique. Ann Soc Belge Méd Trop. 1985;65:357-361.
Situakibanza H, Kapita B, Mbendi M, et al. Etiologie de la fièvre au cours du SIDA : à propos de 64 cas. Panor Medicale. 1996;16(5):842-845. doi:10.1016/S0399-077X(86)80236-0
Kornaszewski W, Kornaszewska M, Skotnicki A. Acquired immunodeficiency syndrome (AIDS) in Africa. Postep Hig Med Dosw. 1986;40(3):331-346.
Colebunders R, Lusakumuni K, Nelson AM, et al. Persistent diarrhoea in Zairian AIDS patients: An endoscopic and histological study. Gut. 1988;29(12):1687-1691. doi:10.1136/gut.29.12.1687
Perriëns JH, Moussa M, Luabeya MK, et al. Complications neurologiques des patients hospitalisés en médecine interne VIH-1 séropositifs à Kinshasa, Zaïre. J Acquir Immune Defic Syndr. 1988;5(4):333-340.
Masengo-Bwanga, Bula Bula A, Tambwe Mbuyi M, Nday M, Kalenga B, Luboya N. Acquired immunodeficiency syndrome (AIDS) in Lubumbashi. clinical and epidemiological observations. Bull Soc Pathol Exot Filiales. 1988;81(2):159-162.http://www.ncbi.nlm.nih.gov/pubmed/3416403
Desmet P, Kayembe KD, De VC. The value of cryptococcal serum antigen screening among HIV-positive/AIDS patients in Kinshasa, Zaire. Curr Sci Ltd. 1989;3:77-78.
Cheesbrough JS, Morse AP, Green SDR. Meningococcal meningitis and carriage in western Zaire: A hypoendemic zone related to climate? Epidemiol Infect. 1995;114:75-92.
Mwanza JC, Nyamabo LK, Tylleskär T, Plant GT. Neuro-ophthalmological disorders in HIV infected subjects with neurological manifestations. Br J Ophthalmol. 2004;88(11):1455-1459. doi:10.1136/bjo.2004.044289
Kivukuto Mutendela J, Mashupe S, Bihehe Masemo D, Mitima Kashosi T. HIV screening among patients followed for cryptococcal meningitis in developing countriesnd: data from Bukavu in the Democratic Republic of Congo. African J Microbiol Res. 2014;8(7):721-723. doi:10.5897/ajmr2013.5420
Mbayo L, Katabwa K, Kalumba K, Mukeng AK, Ilunga K, Okitosholo W. Journal of emerging diseases and virology Congo: clinical expressions and diagnostic. Jpurnal Emerg Dis Virol. 2016;2(3):4-7.
Numbi GY, Mwad BK, Mukuku O, Mwamba CM Cryptococcus neoformans meningitis in an immunocompetent adult: A case report. Adv Gen Pract Med. 2020;3(1):23-25. doi:10.25082/agpm.2020.01.002
Zono B, Kamangu E, Situakibanza H, et al. Epidemiological, clinical and biological profile of neuromeningeal cryptococcosis among people living with HIV in Kinshasa (DRC). Pan Afr Med J. 2020;37(302):205-221. doi:10.11604/pamj.2020.37.302.20521
Mbula M, Situakibanza H, Mananga L, et al. Profils clinique et biologique du VIH à Kinshasa Clinical and biological profile of people living with HIV/AIDS followed in the Infectious Diseases Service of the University Hospital of Kinshasa (Democratic Republic of the Congo) Arti. Rev Mali Infect Mirobiol. 2020;15:21-29.
Katabwa JK, Mukuku O, Lwamba GK, Wembonyama SO. Neuromeningeal cryptococcosis in HIV-infected patients in Lubumbashi, Democratic Republic of the Congo. J Neurol Stroke. 2021;11(3):73-77. doi:10.15406/jnsk.2021.11.00459
Ngoy DK, Kange DM, Kakwaba SK, et al. Mortalité liée à la Cryptococcose chez les Personnes Vivant avec l ’infection à VIH/SIDA à Lubumbashi. Rev L’infirmier Congo. 2021;5(1):56-62.
Manga RD, Bulanda BI, Makoka SK, Bongenya BI, Kamangu EN. Epidemiological and clinical profile and management of Neuromeningeal Cryptococcosis in people living with HIV in Kinshasa: case of N’Djili general reference hospital. Oalib. 2021;08(09):1-5. doi:10.4236/oalib.1107800
Swinne D, Nkurikiyinfura JB, Muyembe TL. Clinical Isolates of Cryptococcus neoformans from Zaire. Eur J Clin Microbiol. 1986;5(1):50-51.
Varma A, Swinne D, Staib F, Bennett JE, Kwon-Chung KJ. Diversity of DNA fingerprints in Cryptococcus neoformans. J Clin Microbiol. 1995;33(7):1807-1814. doi:10.1128/jcm.33.7.1807-1814.1995
Boekhout T, Theelen B, Diaz M, et al. Hybrid genotypes in the pathogenic yeast Cryptococcus neoformans. Microbiology. 2001;147(4):891-907. doi:10.1099/00221287-147-4-891
Litvintseva AP, Thakur R, Vilgalys R, Mitchell TG. Multilocus sequence typing reveals three genetic subpopulations of Cryptococcus neoformans var. grubii (Serotype A), including a unique population in Botswana. Genet Soc Am. 2006;2238(April):2223-2238. doi:10.1534/genetics.105.046672
Onusida. Statistiques mondiales sur le Vih en 2018. Onusida. 2018;6:http://www.unaids.org/fr
Onusida. Statistiques mondiales sur le Vih en 2020. Onusida. 2021;6:http://www.unaids.org/fr
Unaids. Rapport D’Activite 2015 Sur La Riposte Au SIDA Dans Le Monde. Unaids; 2015.
McClelland EE, Hobbs LM, Rivera J, et al. The role of host gender in the pathogenesis of Cryptococcus neoformans infections. PLoS One. 2013;8(5):1-7. doi:10.1371/journal.pone.0063632
Lortholary O, Improvisi L, Fitting C, Cavaillon JM, Dromer F. Influence of gender and age on course of infection and cytokine responses in mice with disseminated Cryptococcus neoformans infection. Clin Microbiol Infect. 2002;8(1):31-37. doi:10.1046/j.1469-0691.2002.00375.x
Saijo T, Chen J, Chen SCA, et al. Anti-granulocyte-macrophage colony-stimulating factor autoantibodies are a risk factor for central nervous system infection by Cryptococcus gattii in otherwise immunocompetent patients. MBio. 2014;5(2): doi:10.1128/mBio.00912-14
Rosen LB, Freeman AF, Yang LM, et al. Anti–GM-CSF autoantibodies in patients with cryptococcal meningitis. J Immunol. 2013;190(8):3959-3966. doi:10.4049/jimmunol.1202526
Herkert PF, Hagen F, Pinheiro RL, Muro MD, Meis JF, Queiroz-Telles F. Ecoepidemiology of Cryptococcus gattii in developing countries. J Fungi. 2017;3(4): doi:10.3390/jof3040062
Cuetara MS, Jusdado Ruiz-Capillas JJ, Nuñez-Valentin MP, et al. Successful Isavuconazole salvage therapy for a Cryptococcus deuterogattii (AFLP6/VGII) disseminated infection in a European immunocompetent patient. Mycopathologia. 2021;186(4):507-518. doi:10.1007/s11046-021-00566-w
Bielska E, May RC. What makes Cryptococcus gattii a pathogen? FEMS Yeast Res. 2015;16(1):1-12. doi:10.1093/femsyr/fov106
Saleem F, Fasih N, Zafar A Cryptococcus neoformans and Streptococcus pneumoniae co-infection in posttraumatic meningitis in a patient with unknown HIV status. J Pak Med Assoc. 2015;65(10):1122-1124.
Togola M. L’épidémiologie de la cryptococcose neuroméningée en milieu hospitalier de Bamako. Univ Bamako; 2007.
Saha DC, Xess I, Biswas A, Bhowmik DM, Padma MV. Detection of Cryptococcus by conventional, serological and molecular methods. J Med Microbiol. 2009;58(8):1098-1105. doi:10.1099/jmm.0.007328-0
Perfect JR, Cox GM. Drug resistance in Cryptococcus neoformans. Drug Resist Updat. 1999;2:259-269. doi:10.1007/978-1-59745-180-2_41
Faria NR, Rambaut A, Suchard MA, et al. The early spread and epidemic ignition of HIV-1 in human populations. Science (80-). 2014;346(6205):56-61. doi:10.1126/science.1256739
D’Souza C, Kronstad J, Taylor G, et al. Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts. MBio. 2011;2(1):1-11. doi:10.1128/mBio.00342-10
Kwon-Chung KJ, Varma A. Do major species concepts support one, two or more species within Cryptococcus neoformans? FEMS Yeast Res. 2006;6(4):574-587. doi:10.1111/j.1567-1364.2006.00088.x
Cogliati M. Global molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii : an atlas of the molecular types. Scientifica (Cairo). 2013;2013(serotype D):1-23. doi:10.1155/2013/675213
Amona FM, Denning DW, Moukassa D, Hennequin C. Current burden of serious fungal infections in Republic of Congo. Mycoses. 2020;63(6):543-552. doi:10.1111/myc.13075
Parkes-Ratanshi R, Achan B, Kwizera R, Kambugu A, Meya D, Denning DW. Cryptococcal disease and the burden of other fungal diseases in Uganda; Where are the knowledge gaps and how can we fill them? Mycoses. 2015;58:85-93. doi:10.1111/myc.12387
Gangneux JP, Bougnoux ME, Hennequin C, et al. Estimation du poids épidémiologique des infections fongiques graves en France. J Mycol Med. 2016;26(4):385-390. doi:10.1016/j.mycmed.2016.11.001
Rodriguez-Tudela JL, Alastruey-Izquierdo A, Gago S, et al. Burden of serious fungal infections in Spain. Clin Microbiol Infect. 2015;21(2):183-189. doi:10.1016/j.cmi.2014.07.013
Taj-Aldeen SJ, Chandra P, Denning DW. Burden of fungal infections in Qatar. Mycoses. 2015;58:51-57. doi:10.1111/myc.12386
