Moderne Diagnostik und Therapie opportunistischer Infektionen bei AIDS

T. Rosenkranz

doi:10.1055/s-0038-1627339

Nervenheilkunde, Table of Contents

Nervenheilkunde 2008; 27(10): 903-911
DOI: 10.1055/s-0038-1627339

Originaler Artikel

Schattauer GmbH

Moderne Diagnostik und Therapie opportunistischer Infektionen bei AIDS

Diagnosis and treatment of AIDS-related opportunistic infections

T. Rosenkranz

¹Asklepios Klinik St. Georg, Hamburg

› Author Affiliations

Abstract

Zusammenfassung

Mit Einführung der hochaktiven antiretroviralen Therapie (HAART) ist die Inzidenz der opportunistischen Infektionen (OI) stark gesunken. Heute erkranken meist nur noch Patienten, denen ihre HIV-Infektion unbekannt ist, die sie nicht haben behandeln lassen oder die trotz HAART einen schlechten Immunstatus haben. Dadurch nimmt das allgemeine Wissen um Diagnostik und Therapie dieser Erkrankungen ab und es wird immer weniger an die Möglichkeit einer zerebralen OI gedacht. Dabei sind OI noch immer lebensbedrohliche Erkrankungen und die Mortalität in den ersten Wochen ist seit der prä-HAART-Ära unverändert geblieben. Daher sollte jeder, der neurologische Notfälle behandelt, mit den wichtigsten diagnostischen Schritten und den aktuellen Therapien der zerebralen OI vertraut bleiben. Es wird ein Überblick über den aktuellen Stand der Diagnostik und Behandlung der wichtigsten OI gegeben: zerebrale Toxoplasmose, progressive multifokale Leukenzephalopathie, Cytomegalievirus-Enzephalitis, Kryptokokken- Meningitis und primär zerebrales Lymphom als HIV-assoziiertes Malignom.

Summary

The incidence of opportunistic infections (OI) in the western world has declined with the introduction of highly active antiretroviral therapy (HAART). Today, OI are only seen in patients with unknown HIV-status, patients without HAART and patients with a severe immunodeficiency despite HAART. Thus, the knowledge of diagnosis and treatment of OI and the awareness of these particular cerebral diseases are more and more reduced. But OI are still life-threatening diseases and the mortality during the first weeks has not changed since the pre-HAART era. The outcome during the first weeks is mainly depending on an early treatment start. Thus, also nowadays, every physician treating neurological emergencies must be familiar with the main diagnostic steps and treatment of central nervous system OI. This review provides an overview on recent developments in diagnosis and treatment of the most important OI: cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, cytomegalovirus encephalitis, cryptococcus meningitis and primary central nervous system lymphoma as HIV-associated malignoma.

Schlüsselwörter

Opportunistische Infektion - AIDS - HIV

Keywords

Opportunistic infections - AIDS - HIV

Full Text

References

Literatur
1 Abgrall S. et al. Incidence and risk factors for toxoplasmic encephalitis in HIV-infected patients before and during the HAART era. Clin Infect Dis 2001; 33: 1747-1755.
2 Aboulafia DM. Interleukin-2, ganciclovir, and high-dose zidovudine for the treatment of AIDSassociated central nervous system lymphoma. Clin Infect Dis 2002; 34: 1660-1662.
3 Albrecht H, Hoffmann C, Degen O. et al. HAART significantly improves the prognosis of patients with HIV-associated progressive multifocal leukoencephalopathy. AIDS 1998; 12: 1149-1154.
4 Anduze-Faris BM, Fillet AM, Gozlan J. et al. Induction an maintenance therapy of cytomegalovirus central nervous system infection in HIV infected patients. AIDS 2000; 14: 517-524.
5 Antinori A, Ammassari A, Giancola ML. et al. Epidemiology and prognosis of AIDS-associated progressive multifocal leukoencephalopathy in the HAART era. L Neurovirol 2001; 7: 323-328.
6 Arribas JR, Clifford DB, Fichtenbaum CJ. et al. Detection of Epstein-Barr Virus DNA in cerebrospinal fluid for diagnosis of AIDS-related central nervous system lymphoma. J Clin Microbiol 1995; 1580-1583.
7 Berger JR. et al. Neurologic disease as the presenting manifestation of acquired immunodeficiency syndrome. South Med J 1987; 80: 683-686.
8 Berger JR, Levy RM, Flomenhoft D. et al. Predictive factors for prolonged survival in AIDS-associated progressive multifocal leukoencephalopathy. Ann Neurol 1998; 44: 341-349.
9 Bernal-Cano F, Joseph JT, Koralnik IJ. Spinal cord lesions of progressive multifocal leukoencephalopathy in an acquired immunodeficiency syndrome patient. J Neurovirol 2007; 13: 474-476.
10 Bertschy S. et al. Discontinuation of maintenance therapy against toxoplasma encephalitis in AIDS patients with sustained response to anti-retroviral therapy. Clin Microbiol Infect 2006; 12: 666-671.
11 Boelaert JR. et al. Relapsing meningitis caused by persistent cryptococcal antigens and immune reconstitutionafter the iniation of highly active antiretroviral therapy. AIDS 2004; 18: 1223-1224.
12 Bonnet F. et al. Opportunistic infections as a cause of death in HIV-infected patients in the HAART era in France. Scand J Infect Dis 2005; 37: 482-487.
13 Bossi P, Caumes E, Astagneau P. Epidemiologic characteristics of cerebral toxoplasmosis in 399 HIV-infected patients followed between 19983 and 1994. Rev Med Interne 1998; 19: 313-317.
14 Bossolasco S, Calori G, Moretti F. et al. Prognostic significance of JC virus DNA levels in cerebrospinal fluid of patients with HIV-associated progressive multifocal leukoencephalopathy. Clin Infect Dis 2005; 40: 738-744.
15 Bower M, Powles T, Nelson M. Highly active antiretroviral therapy and human immunodeficiency virus-associated primary cerebral lymphoma. J Natl Cancer Inst 2006; 1088-1091.
16 Bretagne S. Molecular diagnostics in clinical parasitology and mycology: limits of the current polymerase chain reaction (PCR) assays and interest of the real time PCR-assays. Clin Microbiol Infect 2003; 9: 505-511.
17 Brouwer AE. et al. Combination antifungal therapies for HIV-assiciated cryptococcal meningitis: a randomised trial. Lancet 2004; 363: 1746-1747.
18 Camilleri-Broet S, Davi F, Feuillard J. et al. AIDSrelated primary brain lymphomas: histopathologic and immunohistochemical study of 51 cases. Hum Pathol 1997; 28: 367-374.
19 Chapagain ML, Verma S, Mercier F. Polyomavirus JC infects human brain microvascular endothelial cells independent of serotonin receptor 2A. Virol 2007; 364: 55-63.
20 Charlier C, Dromer F, Lévêque C. Cryptococcal neuroradiological lesions correlate with severity during cryptococcal meningoencephalitis in HIVpositive patients in the HAART era. PLoS ONE 2008; 3: e1950.
21 Cingolani A. et al. Minimally invasive diagnosis of acquired immunodeficiency syndrome-related primary central nervous system lymphoma. J Natl Cancer Inst 1998; 90: 364-369.
22 Cinque P, Scarpellini P, Vago L. et al. Diagnosis of central nervous system complications in HIV-infected patients: cerebrospinal fluid analysis by the polymerase chain reaction. AIDS 1997; 11: 1-17.
23 Cinque P, Cleator GM, Weber T. Diagnosis and clinical management of neurological disorders caused by cytomegalovirus in AIDS patients. J Neurovirol 1998; 4: 120-132.
24 Clifford DB. et al. Magnetic resonance brain imaging lacks sensitivity for AIDS associated cytomegalovirus encephalitis. J Neurovirol 1996; 2: 397-403.
25 Clifford DB. et al. HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy. Neurology 1999; 52: 623-625.
26 Co JK, Verma S, Gurjav U. Interferon-alpha and –beta restrict polyomavirus JC replication in primary human fetal glial cells: implications for progressive multifocal leukoencephalopathy therapy. J Infect Dis 2007; 196: 712-718.
27 Cosottini M, Tavarelli C, del Bono L. Diffusionweighted imaging in patients with progressive multifocal leukoencephalopathy. Eur Radiol 2008; 18: 1024-1030.
28 D’Amico R. et al. Immune reconstitution after potent antiretroviral therapy in AIDS patients with progressive multifocal leukoencephalopathy. Scand J Infect Dis 2007; 39: 347-350.
29 Dedicoat M, Livesley N. Treatment of cerebral toxoplasmosis in HIV infected individuals in resource poor settings. Cochrane Database Systematic Review 2006; 3: CD005420.
30 De Luca A. et al. Potent anti-retroviral therapy with or without cidofovir for AIDS-associated progressive multifocal leukoencephalopathy: Extended follow-up of an observational study. J Neurovirol 2001; 7: 364-368.
31 Dörries K, Sbiera S, Drews K. et al. Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals. J Neurovirol 2003; 9: (suppl 1): 81-87.
32 Dubois V, Dutronc H, Lafon ME. et al. Latency and reactivation of JC virus in peripheral blood of human immunodeficiency virustype 1-infected patients. J Clin Microbiol 1997; 35: 2288-2292.
33 Du Pasquier RA, Koralnik IJ. Inflammatory reaction in progressive multifocal leukoencephalopathy: harmful or beneficial?. J Neurovirol 2003; 9 (Suppl. 01) 25-31.
34 Duval X, Pajot O, Le Moing V. et al. Maintenance therapy with cotrimoxazole for toxoplasmic encephalitis in the era of highly active antiretroviral therapy. AIDS 2004; 18: 1342-1344.
35 Elphick GF, Querbes W, Jordan JA. et al. The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science 2004; 306: 1380-1383.
36 Fine HA, Mayer RJ. Primary central nervous system lymphoma. Ann Intern Med 1993; 119: 1093-1104.
37 Gasnault J, Kousignian P, Kahraman M. Cidofovir in AIDS-associated progressive multifocal leukoencephalopathy: A monocenter observational study with clinical and JC virus load monitoring. J Neurovirol 2001; 7: 375-381.
38 Giancola ML. et al. Progressive multifocal leukoencephalopathy in HIV-infected patients in the era of HAART: radiological features at diagnosis and follow-up and correlation with clinical variables. AIDS Res Hum Retroviruses 2008; 24: 155-162.
39 Gianotti N. et al. Diagnosis of toxoplasmic encephalitis in HIV-infected patients. AIDS 1997; 11: 1529-1530.
40 Griffiths P. Cytomegalovirus infection of the central nervous system. Herpes 2004; 11: 94A-104A.
41 Hoffmann C. et al. Survival of AIDS patients with primary central nervous system lymphoma is dramatically improved by HAART-induced immune recovery. AIDS 2001; 15: 2119-2127.
42 Hoffmann C. et al. Evolving characteristics of toxoplasmosis in patients infected with human immunodeficiency virus-1: clinical course and Toxoplasma gondii-specific immune responses. Clin Microbiol Infect 2007; 13: 510-515.
43 Jacomet C. et al. Intravenous methotrexate for primary central nervous system non-Hodgkin’s lymphoma in AIDS. AIDS 1997; 11: 1725-1730.
44 Jarvis JN, Harrison TS. HIV-associated cryptococcal meningitis. AIDS 2007; 21: 2119-2129.
45 Katlama C. Diagnosis and treatment of toxoplasmosis of the CNS in patients with AIDS. CNS Drugs 1996; 5: 331-343.
46 Koralnik IJ, Wüthrich C, Dang X. JC virus granule cell neuronopathy: a novel clinical syndrome distinct from progressive multifocal leukoencephalopathy. Ann Neurol 2005; 57: 576-580.
47 Kraemer C, Evers S, Nolting T. Cidofovir in combination with HAART and survival in AIDS-associated progressive multifocal leukoencephalopathy. J Neurol 2008; 255: 526-531.
48 Lesho E. Evidence base for using corticosteroids to treat HIV-associated immune reconstitution syndrome. Expert Rev Anti Infect Ther 2006; 4: 469-478.
49 Lima MA, Drislane FW, Koralnik IJ. Seizures and their outcome in progressive multifocal leukoencephalopathy. Neurology 2006; 66: 262-264.
50 Lortholary O. et al. Long-term outcome of AIDSassociated cryptococcosis in the era of combination antiretroviral therapy. AIDS 2006; 20: 2183-2191.
51 Luft BJ, Chua A. Central nervous system toxoplasmosis in HIV. Pathogenesis, diagnosis, and therapy. Curr Infect Dis Rep 2000; 2: 358-362.
52 Matoba T, Orba Y, Suzuki T. et al. An siRNA against JC virus (JCV) agnoprotein inhibits JCV infection in JCV-producing cells inoculated in nude mice. Neuropathology 2008; 28: 286-294.
53 McCutchan JA. Cytomegalovirus infections of the nervous system in patients with AIDS. Clin Infect Dis 1995; 20: 747-754.
54 McGowan JP, Shah S. Long-term remission of AIDS-related PCNSL associated with HAART. AIDS 1998; 952-954.
55 Miralles P. et al. Inflammatory reactions in progressive multifocal leukoencephalopathy after HAART. AIDS 2001; 15: 1900-1902.
56 Monaco MC. et al. Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection. J Virol 1998; 72: 9918-9923.
57 Nath A. et al. Progression of progressive multifocal leukoencephalopathy despite treatment with beta-interferon. Neurology 2006; 66: 149-150.
58 Newell ME. et al. Human immunodeficiency virus– related primary central nervous system lymphoma: factors influencing survival in 111 patients. Cancer 2004; 100: 2627-2636.
59 Nutall JJ. et al. Progressive multifocal leukoencephalopathy after initiation oh highly active antiretroviral therapy in a child with advanced HIV infection: a case of immune reconstitution inflammatory syndrome. Pediatr Infect Dis J 2004; 23: 683-685.
60 O’Hara BA, Atwood WJ. Interferon beta1-a and selective anti-5HT(2a) receptor antagonist inhibit infection of human glial cells by JC virus. Virus Res 2008; 132: 97-103.
61 Padgett BL. et al. Cultivation of papova-like virus from human bran with progressive multifocal leukoencephalopathy. Lancet 1971; 1257-1260.
62 Palella FJ. et al. Declining morbidity among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853-860.
63 Perfect JR. et al. Voriconazole treatment for lesscommon, emerging, or refractory fungal infections. Clin Infect Dis 2003; 36: 1122-1131.
64 Pierce MA, Johnson MD, Maciunas RJ. et al. Evaluating contrast-enhancing brain lesions in patients with AIDS by using positron emission tomography. Ann Intern Med 1995; 123: 594-598.
65 Pitisuttithum P. et al. Activity of posaconazole in the treatment of central nervous system fungal infection. J Antimicrob Chemother 2005; 56: 745-755.
66 Pöhlmann C. et al. Chlorpromazine combined with cidofovir for treatment of patient suffering from progressive multifocal leukoencephalopathy. Intervirology 2007; 50: 412-417.
67 Raez L, Cabral L, Cai JP. et al. Treatment of AIDSrelated primary central nervous system lymphoma with zidovudine, ganciclovir, and interleukin-2. AIDS Res Hum retroviruses 1999; 15: 713-719.
68 Rhodes CH. et al. A comparison of polymerase chain reaction examination of cerebrospinal fluid and conventional cytology in the diagnosis of lymphomatous meningitis. Cancer 1996; 77: 543-548.
69 Rodrigues C, Pinto D, Madeiros R. Molecular epidemiology characterisation of the urinary excretion of polyomavirus in healthy individuals from Portugal-a Southern European population. J Med Virol 2007; 79: 1194-1198.
70 Rosenow JM, Hirschfeld A. Utility of brain biopsy in patients with acquired immunodeficiency syndrome before and after introduction of highly active antiretroviral therapy. Neurosurgery 2007; 61: 130-141.
71 Roullet E. et al. Cytomegalovirus multifocal neuropathy in AIDS: analysis of 15 consecutive cases. Neurology 1994; 44: 2174-2182.
72 Royal W. et al. Topotecan in the treatment of acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy. J Neurovirol 2003; 9: 411-419.
73 Sabath BF, Major EO. Traffic of JC virus from sites of initial infection to the brain: the path to progressive multifocal leukoencephalopathy. J Infect Dis 2002; 186 (Suppl. 02) S180-S186.
74 Safdar A. et al. Fatal immune restoration disease in HIV type 1-infected patients with progressive multifocal leukoencephalopathy: impact of antiretroviral therapy-associated immune reconstitution. Clin Infect Dis 2002; 35: 1250-1257.
75 Salyer WR, Salyer DC, Baker RD. Primary complex of Cryptococcus and pulmonary lymph nodes. J Infect Dis 1974; 130: 74-77.
76 Schroeder PC. et al. Analysis of the utility of diffusion- weighted MRI and apparent diffusion coefficient values in distinguishing central nervous system toxoplasmosis from lymphoma. Neuroradiology 2006; 48: 715-720.
77 Shelburne SA, Visnegarwala F, Darcourt J. et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005; 19: 399-405.
78 Shelburne SA, Montes M, Hamill RJ. Immune reconstitution inflammatory syndrome: more answers, more questions. J Antimicrob Chemother 2006; 57: 167-170.
79 Skiest D. et al. SPECT thallium-201 combined with Toxoplasma serology for the presumptive diagnosis of focal nervous system mass lesions in patients with AIDS. J Infect 2000; 40: 274-281.
80 Slobod KS. et al. Epstein-Barr virus-targeted therapy for AIDS-related primary lymphoma of central nervous system. Lancet 2000; 356: 1493-1494.
81 Sun HY, Hung CC, Chang SC. Management of cryptococcal meningitis with extremely high intracranial pressure in HIV-infected patients. Clin Infect Dis 2004; 38: 1790-1792.
82 Thunher MM. et al. Primary central nervous system lymphoma in AIDS. A wider spectrum of CT and MRI findings. Neuroradiology 2001; 43: 29-35.
83 Thwaites GE. et al. The influenceof HIV infection on clinical presentation, response to treatment, and outcome in adults with tuberculous meningitis. J Infect Dis 2005; 192: 2134-2141.
84 Verbeeck J. et al. JC viral loads in Crohn’s disease patients treated with immunosuppression: can we screen for elevated risk of PML?. Gut 2008 im Druck.
85 Verma S, Cikurel K, Koralnik IJ. Mirtazapine in progressive multifocal leukoencephalopathy associated with polycythemia vera. J Infect Dis 2007; 196: 709-711.
86 Yiannoutsos CT, Major EO, Curfman BA. Relation of JC virus DNA in the cerebrospinal fluid to survival in acquired immunodeficiency syndrome patients with biopsy-proven progressive multifocal leukoencephalopathy. Ann Neurol 1999; 45: 816-820.
87 Young RJ. et al. Lesion size determines accuracy of thallium 201 brain single-photon emission tomography in differentiating between intracranial malignancy and infection in AIDS patients. AJNR 2005; 26: 1973-1979.
88 Zangerle R. et al. High risk of developing toxoplasmic encephalitis in AIDS patients seropositive for Toxoplasma gondii . Med Micribiol 1991; 180: 59-66.