RESEARCH PAPER
Prognosis of fungal infection of central nervous system in HIV-infected patients: a retrospective study of 77 patients
in Ukraine
1
Dnipropetrovsk Medical Academy of Health Ministry of Ukraine, Ukraine
2
Alcohol and Drug Information Centre (ADIC), Ukraine
3
School of Public Health, Babeș-Bolyai University, Cluj-Napoca, Romania
Submission date: 2018-09-25
Acceptance date: 2019-04-15
Publication date: 2019-07-11
HIV & AIDS Review 2019;18(2):92-99
KEYWORDS
opportunistic mycosescentral nervous system diseasesfatal outcomecoinfectioncandidiasisHIVantiretroviral therapyopportunistic infections
TOPICS
ABSTRACT
Introduction:
We aimed to describe the epidemiological, clinical, laboratory characteristics, and outcomes of central nervous system (CNS) mycosis in patients with human immunodeficiency virus (HIV) and to determine characteristics associated with a higher risk of death. Retrospective data from 77 case histories of HIV-infected patients with neurological symptoms caused by various fungi including Candida and Cryptococcus in Dnipro, Ukraine, were analysed as a case-control study with 40 deceased individuals considered as cases and 37 patients with favourable outcome (survivors) considered as controls.
Material and methods:
Fungi in cerebrospinal fluid (CSF) were detected with traditional culture methods. Multivariate analysis used (1) binary logistic regression with survivor/dead as a dependent variable and (2) a classification and regression tree (CRT method).
Results:
A combination of fungal infection with other infections of CNS (dual and triple coinfection) was diagnosed in most cases (n = 53, 68.8%), while the proportion of co-infection was somewhat lower among survivors (59.5%). Clinical manifestations were non-specific. Risk of death was higher among those with tuberculosis (AOR = 2.7, 95% CI: 1.0-7.5) and lower among those infected with Epstein-Barr virus (EBV) (AOR = 0.3, 95% CI: 0.1-1.0) and among patients on ART (AOR = 0.2, 95% CI: 0.1-0.8). Risk of death significantly decreased over time. The classification tree shows that among HIV-mycosis neurological patients not on ART with tuberculosis, the risk of death constituted 75%, while among patients on ART with EBV-infection, all patients survived.
Conclusions:
Opportunistic mycoses remain an important clinical challenge among immuno-compromised patients especially those who were diagnosed with HIV late, failed to get antiretroviral therapy, and developed tuberculosis.
We aimed to describe the epidemiological, clinical, laboratory characteristics, and outcomes of central nervous system (CNS) mycosis in patients with human immunodeficiency virus (HIV) and to determine characteristics associated with a higher risk of death. Retrospective data from 77 case histories of HIV-infected patients with neurological symptoms caused by various fungi including Candida and Cryptococcus in Dnipro, Ukraine, were analysed as a case-control study with 40 deceased individuals considered as cases and 37 patients with favourable outcome (survivors) considered as controls.
Material and methods:
Fungi in cerebrospinal fluid (CSF) were detected with traditional culture methods. Multivariate analysis used (1) binary logistic regression with survivor/dead as a dependent variable and (2) a classification and regression tree (CRT method).
Results:
A combination of fungal infection with other infections of CNS (dual and triple coinfection) was diagnosed in most cases (n = 53, 68.8%), while the proportion of co-infection was somewhat lower among survivors (59.5%). Clinical manifestations were non-specific. Risk of death was higher among those with tuberculosis (AOR = 2.7, 95% CI: 1.0-7.5) and lower among those infected with Epstein-Barr virus (EBV) (AOR = 0.3, 95% CI: 0.1-1.0) and among patients on ART (AOR = 0.2, 95% CI: 0.1-0.8). Risk of death significantly decreased over time. The classification tree shows that among HIV-mycosis neurological patients not on ART with tuberculosis, the risk of death constituted 75%, while among patients on ART with EBV-infection, all patients survived.
Conclusions:
Opportunistic mycoses remain an important clinical challenge among immuno-compromised patients especially those who were diagnosed with HIV late, failed to get antiretroviral therapy, and developed tuberculosis.
REFERENCES (44)
1.
Cox JA, Lukande RL, Lucas S, et al. Autopsy causes of death in HIV-positive individuals in sub-Saharan Africa and correlation with clinical diagnoses. AIDS Rev 2010; 12: 183-194.
2.
Birbeck GL. HIV neurology in the developing world. In: Handbook of Clinical Neurology. Elsevier, 2007; p. 33-43.
3.
Collazos J. Opportunistic infections of the CNS in patients with AIDS: diagnosis and management. CNS Drugs 2003; 17: 869-887.
4.
Portegies P, Berger JR. Introduction to HIV infection and neuro‐AIDS. In: Handbook of Clinical Neurology. Elsevier, 2007; p. 1-2.
5.
Mamidi A, DeSimone JA, Pomerantz RJ. Central nervous system infections in individuals with HIV-1 infection. J Neurovirol 2002; 8: 158-167.
6.
Sacktor N. The epidemiology of human immunodeficiency virus- associated neurological disease in the era of highly active antiretroviral therapy. J Neurovirol 2002; 8 Suppl 2: 115-121.
7.
Tan IL, Smith BR, von Geldern G, et al. HIV-associated opportunistic infections of the CNS. Lancet Neurol 2012; 11: 605-617.
8.
Bolokadze N, Gabunia P, Ezugbaia M, et al. Neurological complications in patients with HIV/AIDS. Georgian Med News 2008; 165: 34-38.
9.
Hakim JG, Gangaidzo IT, Heyderman RS, et al. Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS 2000; 14: 1401-1407.
10.
Marukutira T, Huprikar S, Azie N, et al. Clinical characteristics and outcomes in 303 HIV-infected patients with invasive fungal infections: data from the Prospective Antifungal Therapy Alliance registry, a multicenter, observational study. HIV AIDS (Auckl) 2014; 6: 39-47.
11.
Sharma RR. Fungal infections of the nervous system: current perspective and controversies in management. Int J Surg 2010; 8: 591-601.
12.
Rauchway AC, Husain S, Selhorst JB. Neurologic presentations of fungal infections. Neurol Clin 2010; 28: 293-309.
13.
Uppin MS, Anuradha SV, Uppin SG, et al. Fungal infections as a contributing cause of death: an autopsy study. Indian J Pathol.
15.
Richardson M, Lass-Florl C. Changing epidemiology of systemic fungal infections. Clin Microbiol Infect 2008; 14 Suppl 4: 5-24.
16.
Sims CR, Ostrosky-Zeichner L, Rex JH. Invasive candidiasis in immunocompromised hospitalized patients. Arch Med Res 2005; 36: 660-671.
17.
Tauber SC, Eiffert H, Kellner S, et al. Fungal encephalitis in human autopsy cases is associated with extensive neuronal damage but only minimal repair. Neuropathol Appl Neurobiol 2014; 40: 610-627.
18.
Henao NA, Vagner B. Infections of the central nervous system by Candida. Journal of Infectious Diseases and Immunity 2011; 3: 79-84.
19.
Murray CJ, Ortblad KF, Guinovart C, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384: 1005-1070.
20.
DeHovitz J, Uuskula A, El-Bassel N. The HIV epidemic in Eastern Europe and Central Asia. Curr HIV/AIDS Rep 2014; 11: 168-176.
21.
Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America 2016; 62: e1-e50.
22.
Moran CA, Terry Ch, Nguyen ML, et al. Use of Cerebrospinal Fluid (1, 3)-β-D-Glucan to Monitor Treatment Response in Candida albicans Meningitis in an HIV-infected Patient. Infectious Diseases in Clinical Practice 2018; 26: e70-e72.
23.
Ellepola AN, Morrison CJ. Laboratory diagnosis of invasive candidiasis. J Microbiol 2005; 43: 65-84.
24.
Jones JM. Laboratory diagnosis of invasive candidiasis. Clin Microbiol Rev 1990; 3: 32-45.
25.
Sacktor N, Nakasujja N, Skolasky RL, et al. Benefits and risks of stavudine therapy for HIV-associated neurologic complications in Uganda. Neurology 2009; 72: 165-170.
26.
Wright EJ. Neurological disease: the effects of HIV and antiretroviral therapy and the implications for early antiretroviral therapy initiation. Curr Opin HIV AIDS 2009; 4: 447-452.
27.
Yechoor VK, Shandera WX, Rodriguez P, Cate TR. Tuberculous meningitis among adults with and without HIV infection. Experience in an urban public hospital. Arch Intern Med 1996; 156: 1710-1716.
28.
Sütlaş PN, Unal A, Forta H, et al. Tuberculous meningitis in adults: review of 61 cases. Infection 2003; 31: 387-391.
29.
Lu CH, Chang WN, Chang HW. The prognostic factors of adult tuberculous meningitis. Infection 2001; 29: 299-304.
30.
Kelly MJ, Benjamin LA, Cartwright K, et al. Epstein-Barr virus coinfection in cerebrospinal fluid is associated with increased mortality in Malawian adults with bacterial meningitis. J Infect Dis 2012; 205: 106-110.
31.
Mavilio D, Benjamin J, Daucher M, et al. Natural killer cells in HIV-1 infection: dichotomous effects of viremia on inhibitory and activating receptors and their functional correlates. Proc Natl Acad Sci U S A 2003; 100: 15011-15016.
32.
Mansour I, Doinel C, Rouger P. CD16+ NK cells decrease in all stages of HIV infection through a selective depletion of the CD16+CD8+CD3- subset. AIDS Res Hum Retroviruses 1990; 6: 1451-1457.
33.
Tomkinson BE, Wagner DK, Nelson DL, Sullivan JL. Activated lymphocytes during acute Epstein-Barr virus infection. J Immunol 1987; 139: 3802-3807.
34.
Zhang Y, Wallace DL, de Lara CM, et al. In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection. Immunology 2007; 121: 258-265.
35.
Williams H, McAulay K, Macsween KF, et al. The immune response to primary EBV infection: a role for natural killer cells. Br J Haematol 2005; 129: 266-274.
36.
Beno DW, Stover AG, Mathews HL. Growth inhibition of Candida albicans hyphae by CD8+ lymphocytes. J Immunol 1995; 154: 5273-5281.
37.
Murphy JW, Hidore MR, Wong SC. Direct interactions of human lymphocytes with the yeast-like organism, Cryptococcus neoformans. J Clin Invest 1993; 91: 1553-1566.
38.
Levitz SM, Dupont MP, Smail EH. Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans. Infect Immun 1994; 62: 194-202.
39.
Huffnagle GB, Lipscomb MF, Lovchik JA, et al. The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection. J Leukoc Biol 1994; 55: 35-42.
40.
Voice RA, Bradley SF, Sangeorzan JA, Kauffman CA. Chronic candidal meningitis: an uncommon manifestation of candidiasis. Clin Infect Dis 1994; 19: 60-66.
41.
Edwards JE Jr. Candida species. In: Principles and Practice of Infectious Diseases. Bennett JE, Dolin R, Blaser MJ (eds.). Elsevier – Health Sciences Division, 2014; p. 2879-2894.
42.
Vazquez JA, Sobel JD. Candidiasis. In: Essentials of Clinical Mycology. Kauffman AC, et al. (eds.). Springer, New York, 2011; p. 167-206.
43.
Sánchez-Portocarrero J, Pérez-Cecilia E, Corral O, et al. The central nervous system and infection by Candida species. Diagn Microbiol Infect Dis 2000; 37: 169-179.
44.
Casado JL, Quereda C, Oliva J, et al. Candidal meningitis in HIV- infected patients: analysis of 14 cases. Clin Infect Dis 1997; 25: 673-676.
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