Download PDF
Aktuelle Neurologie 2018; 45(05): 370-380
DOI: 10.1055/s-0043-118923
Neues in der Neurologie
© Georg Thieme Verlag KG Stuttgart · New York

Neues zu opportunistischen Infektionen des zentralen Nervensystems bei iatrogener Immunsuppression

Opportunistic Infections of the Central Nervous System in Patients with Iatrogenic Immunosuppression: an Update
Gabriele Arendt
1   Neurologische Klinik der Universität Düsseldorf, Medizinische Fakultät
,
Matthias Maschke
2   Neurologische Abteilung des Krankenhauses der Barmherzigen Brüder, Trier
› Author Affiliations
Further Information

Publication History

Publication Date:
23 November 2017 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Opportunistische Infektionen des zentralen Nervensystems (ZNS) mit infolge einer iatrogenen Immunsuppression auftretenden Virus-, Parasiten-, Pilz- oder Bakterien-induzierten Erkrankungen sind bei der steigenden Zahl an Patienten mit Organtransplantationen oder immunmodulierenden Therapien von großer medizinischer Bedeutung. Hauptsächliche Anwender dieser modernen Behandlungsformen sind neben der Transplantationsmedizin die Dermatologie (Interferone, Rituximab, Fingolimod u. a.), Hämato-/Onkologie (Rituximab u. a.), Neurologie (Beta-Interferon, Glatirameracetat, Natalizumab, Rituximab, Teriflunomid, Fingolimod, Alemtuzumab, Daclizumab u. a.) und Rheumatologie (Rituximab u. a.).

Das Keimspektrum bei iatrogener Immunsuppression in Europa umfasst in der Hauptsache Viren der Herpesgruppe sowie insbesondere bei immunmodulatorisch behandelten Patienten das JC-Virus (JCV); an Pilzerregern sind Aspergillus fumigatus, Candida albicans und Cryptococcus neoformans von Bedeutung. Eine wichtige parasitäre Infektion ist die mit Toxoplasma gondii (T. g.). Typische bakterielle Infektionen des iatrogen immunkompromittierten Patienten werden durch Nocardia asteroides, Listeria monocytogenes und Mycobacterium tuberculosis hervorgerufen.

Es werden typische diagnostische Konstellationen und Therapien vorgestellt.

Abstract

Opportunistic infections of the central nervous system (CNS) with bacteria, parasites, funghi or viruses due to iatrogenic immunosupppression are of immense importance because of the rising numbers of organtransplantations and immunomodulating treatments. Most frequently involved medical subdisciplines are except from transplantation medicine dermatology (interferons, rituximab, fingolimod, a.o.), hemato-oncology (rituximab, a.o.), neurology (beta-interferon, glatiramer acetat, natalizumab, rituximab, teriflunomide, fingolimod, alemtuzumab, daclizumab, a.o.) and rheumatology (rituximab).

In Europe, typical infectious bodies affecting the immunocompromised host are herpes viruses and especially in immunomodulated patients JC-virus (JCV); frequently occurring funghi are Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans. An important parasite is Toxoplasma gondii (T. g.). Typical bacterial infections of the immunocompromised patient are provoked by Nocardia asteroides, Listeria monocytogenes and Mycobacterium tuberculosis.

Modern diagnostic and therapeutic procedures are described.

Schlüsselwörter

opportunistische Infektionen - zentrales Nervensystem (ZNS) - iatrogene Immunsuppression und -modulation - typische Erreger

Keywords

opportunistic infections - central nervous system (CNS) - iatrogenic immunosuppression and -modulation - typical infectious bodies
 

  • Literatur

  • 1 Boucher A, Herrmann JL, Morand P. et al. Epidemiology of infectious encephalitis causes in 2016. Med Mal Infect 2017; 47: 221-235
    CrossrefPubMedGoogle Scholar
  • 2 John CC, Carabin H, Montano SM. et al. Global research priorities for infections that affect the nervous system. Nature 2015; 527: 178-186
    CrossrefPubMedGoogle Scholar
  • 3 Sundaram C, Shankar SK, Thong WK. et al. Pathology and diagnosis of central nervous system infections. Patholog Res Int 2011; DOI: 10.4061/2011/878263.
    CrossrefPubMedGoogle Scholar
  • 4 Sonneville R, Magalhaes E, Meyfroidt G. Central nervous system infections in immunocompromised patients. Curr Opin Crit Care 2017; 23: 128-133
    CrossrefPubMedGoogle Scholar
  • 5 Shih RY, Koeller KK. Bacterial, fungal, and parasitic infections of the central nervous system: radiologic-pathologic correlation and historical perspectives. Radiographics 2015; 35: 1141-1169
    CrossrefPubMedGoogle Scholar
  • 6 Dibble EH, Boxerman JL, Baird GL. et al. Toxoplasmosis versus lymphoma: cerebral lesion characterization using DSC-MRI revisited. Clin Neurol Neurosurg 2017; 152: 84-89
    CrossrefPubMedGoogle Scholar
  • 7 Cunha BA. Central nervous system infections in the compromised host: a diagnostic approach. Infect Dis Clin North Am 2001; 15: 567-590
    CrossrefPubMedGoogle Scholar
  • 8 Singh N, Husain S. Infections of the central nervous system in transplant recipients. Transplant Infect Dis 2000; 2: 101-111
    CrossrefPubMedGoogle Scholar
  • 9 McTaggart LR, Doucet J, Witkowska M. et al. Antimicrobial susceptibility among clinical Nocardia species identified by multilocus sequence analysis. Antimicrob Agents Chemother 2015; 59: 269-275
    CrossrefPubMedGoogle Scholar
  • 10 Rolhion N, Cossart P. How the study of Listeria monocytogenes has led to new concepts in biology. Future Microbiol 2017; 12: 621-638
    CrossrefPubMedGoogle Scholar
  • 11 Pupo I, Lepe JA, Smani Y. et al. Comparison of the in vitro activity of ampicillin and moxifloxacin against Listeria monocytogenes at achievable concentrations in the central nervous system. J Med Microbiol 2017; 66: 713-720
    CrossrefPubMedGoogle Scholar
  • 12 Lempp JM, Zajdowicz MJ, Hankinson AL. et al. Assessment of the QuantiFERON-TB Gold In-Tube test for the detection of Mycobacterium tuberculosis infection in United States Navy recruits. PLoS One 2017; DOI: 10.1371/journal.pone.0177752.
    CrossrefPubMedGoogle Scholar
  • 13 Chaudhary V, Bano S, Garga UC. Central nervous system tuberculosis: an imaging perspective. Can Assoc Radiol J 2017; 68: 161-170
    CrossrefPubMedGoogle Scholar
  • 14 Leonard JM. Central Nervous System Tuberculosis. Microbiol Spectr 2017; DOI: 10 1128/microbiolspec. [epub ahead of print]
    CrossrefPubMedGoogle Scholar
  • 15 Hillemann D, Rusch-Gerdes S, Richter E. Feasibility of the GenoType MTBDRsl assay for fluoroquinolone, amikacin-capreomycin, and ethambutol resistance testing of mycobacterum tuberculosis strains and clinical specimens. J Clin Microbiol 2009; 47: 1767-1772
    CrossrefPubMedGoogle Scholar
  • 16 Mai NT, Thwaites GE. Recent advances in the diagnosis and management of tuberculous meningitis. Curr Opin Infect Dis 2017; 30: 123-128
    CrossrefPubMedGoogle Scholar
  • 17 Mahmoudi S, Mamishi S, Suo X. et al. Early detection of Toxoplasma gondii infection by using a interferon gamma release assay: a review. Exp Parasitol 2017; 172: 39-43
    CrossrefPubMedGoogle Scholar
  • 18 Mc CarthyMW, Walsh TJ. Molecular diagnosis of invasive mycoses of the central nervous system. Expert Rev Mol Diagn 2017; 17: 129-139
    CrossrefPubMedGoogle Scholar
  • 19 Starkey J, Moritani T, Kirby P. MRI of CNS fungal infections: review of aspergillos to histoplasmosis and everything in between. Clin Neuroradiol 2014; 24: 217-230
    CrossrefPubMedGoogle Scholar
  • 20 Baeesa SS, Bokhari RF, Alghamdi KB. et al. Invasive aspergillus sinusitis with orbitocranial extension. Asian J Neurosurg 2017; 12: 172-179
    PubMedGoogle Scholar
  • 21 Chen TK, Groncy PK, Javahery R. et al. Successful treatment of Aspergillus ventriculitis through voriconazole adaptive pharmacotherapy, immunomodulation, and therapeutic monitoring of cerebrospinal fluid (1→3)-β-D-glucan. Med Mycol 2017; 55: 109-117
    CrossrefPubMedGoogle Scholar
  • 22 Andes D. Optimizing antifungal choice and administration. Curr Med Res & Opinion 2013; (29) 1-6
    PubMedGoogle Scholar
  • 23 Li SX, Song YJ, Jiang L. et al. Synergistic effects of tetrandrine with posaconazole against aspergillus fumigatus. Microb Drug Resist 2017; DOI: 10.1089/mdr.2016.0217.
    CrossrefPubMedGoogle Scholar
  • 24 Moreno-Rodriguez AC, Torrado-Durán S, Molero G. et al. Efficacy and toxicity evaluation of new amphotericin B micelle systems for brain fungal infections. Int J Pharm 2015; 494: 17-22
    CrossrefPubMedGoogle Scholar
  • 25 Tugume L, Morawski BM, Abassi M. et al. Prognostic implications of baseline anaemia and changes in haemoglobin concentrations with amphotericin B therapy for cryptococcal meningitis. HIV Med 2017; 18: 13-20
    CrossrefPubMedGoogle Scholar
  • 26 George IA, Santos CAQ, Olsen MA. et al. Epidemiology of cryptococcosis and cryptococcal meningits in a large retrospective cohort of patients after solid organ transplantation. Open Forum Infect Dis 2017; DOI: 10 1093/ofid/ofx122. [epub ahead of print]
    CrossrefPubMedGoogle Scholar
  • 27 Lofgren S, Hullsiek KH, Morawski BM. et al. Differences in immunologic factors among patients presenting with altered mental status during cryptococcal meningitis. J Infect Dis 2017; 215: 693-697
    CrossrefPubMedGoogle Scholar
  • 28 Mishra AK, Arvind VH, Muliyil D. et al. Cerebrovascular injury in cryptococcal meningitis. Int J Stroke 2017; DOI: 10.1177/1747493017706240.
    CrossrefPubMedGoogle Scholar
  • 29 Bicanic T, Brouwer AE, Meintjes G. et al. Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures. AIDS 2009; 23: 701-706
    PubMedGoogle Scholar
  • 30 Qu J, Zhou T, Zhong C. et al. Comparison of clinical features and prognostic factors in HIV-negative adults with cryptococcal meningitis and tuberculous meningitis: a retrospective study. BMC Infect Dis 2017; DOI: 10.1186/s12879-016-2126-6.
    CrossrefPubMedGoogle Scholar
  • 31 Rigi M, Khan K, Smith SV. et al. Evaluation and management of the swollen optic disk in cryptococcal meningitis. Surv Ophthalmol 2017; 62: 150-160
    CrossrefPubMedGoogle Scholar
  • 32 Shen L, Zheng J, Wang Y. et al. Increased activity of the complement system in cerebrospinal fluid of the patients with Non-HIV Cryptococcal meningitis. BMC Infect Dis 2017; DOI: 10.1186/s12879-016-2107-.
    CrossrefPubMedGoogle Scholar
  • 33 Ćurić A, Möschwitzer JP, Fricker G. Development and characterization of novel highly-loaded itraconazole poly(butyl cyanoacrylate) polymeric nanoparticles. Eur J Pharm Biopharm 2017; 114: 175-185
    CrossrefPubMedGoogle Scholar
  • 34 Werner AC, Vuong LN, Hedges TR. et al. Immune reconstitution inflammatory syndrome causing progressive optic nerve edema in cryptococcal meningitis. Retin Cases Brief Rep 2017; DOI: 10.1097/ICB.0000000000000582.
    CrossrefPubMedGoogle Scholar
  • 35 Schmutzhard E. Viral infections of the CNS with special emphasis on herpes simplex infections. J Neurol 2001; 248: 469-477
    CrossrefPubMedGoogle Scholar
  • 36 Kennedy PGE, Chaudhuri A. Herpes simplex encephalitis. J Neurol Neurosurg Psychiatry 2002; 73: 237-238
    CrossrefPubMedGoogle Scholar
  • 37 Meyding-Lamade UK, Lamade WR, Wildemann BT. et al. Herpes simplex virus encephalitis: chronic progressive cerebral magnetic resonance imaging abnormalitis in patients despite good clinical recovery. Clin Infect Dis 1999; 128: 148-149
    PubMedGoogle Scholar
  • 38 Akkaya O, Guvenc HI, Yuksekkaya S. et al. Real-time PCR detection of the most common bacteria and viruses causing meningitis. Clin Lab 2017; 63: 827-832
    PubMedGoogle Scholar
  • 39 Mc GillF, Griffiths MJ, Solomon T. Viral meningitis: current issues in diagnosis and treatment. Curr Opin Infect Dis 2017; 30: 248-256
    CrossrefPubMedGoogle Scholar
  • 40 Van TT, Mongkolrattanothai K, Arevalo M. et al. Impact of a rapid herpes simplex virus PCR assay on duration of acyclovir therapy. J Clin Microbiol 2017; 55: 1557-1565
    CrossrefPubMedGoogle Scholar
  • 41 McLaughlin MM, Sutton SH, Jenson AO. et al. Use of high-dose oral valacyclovir during an intravenous acyclovir shortage: a retrospective analysis of tolerability and drug shortage management. Infect Dis Ther 2017; 6: 259-264
    CrossrefPubMedGoogle Scholar
  • 42 Frobert E, Burrel S, Ducastelle-Lepretre S. et al. Resistance of herpes simplex viruses to acyclovir: an update from a ten-year survey in France. Antiviral Res 2014; 111: 36-41
    CrossrefPubMedGoogle Scholar
  • 43 Renard T, Daumas-Duport B, Auffray-Calvier E. et al. Cytomegalovirus encephalitis: Undescribed diffusion-weighted imaging characteristics. Original aspects of cases extracted from a retrospective study, and from literature review. J Neuroradiol 2016; 43: 371-377
    CrossrefPubMedGoogle Scholar
  • 44 Berger JR, Miller CS, Danaher RJ. et al. Distribution and quantity of sites of John Cunningham virus persistance in immunologically healthy patients: correlation with John Cunningham virus antibody and urine John Cunningham Virus DNA. JAMA Neurol 2017; 74: 437-444
    CrossrefPubMedGoogle Scholar
  • 45 Cambron M, Hadhoum N, Duhin E. et al. JCV serology in time: 3 years of follow up. Acta Neurol Scand 2017; 136: 54-58
    CrossrefPubMedGoogle Scholar
  • 46 Elia F, Villani S, Ambrogi F. et al. JC virus infection is acquired very early in life: evidence from a longitudinal serological study. J Neurovirol 2017; 23: 99-105
    CrossrefPubMedGoogle Scholar
  • 47 Clerico M, Artusi CA, Liberto AD. et al. Natalizumab in multiple sclerosis: long-term management. Int J Mol Sci 2017; DOI: 10.3390/ijms18050940.
    CrossrefPubMedGoogle Scholar
  • 48 Gieselbach RJ, Muller-Hansma AH, Wijburg MT. et al. Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases. J Neurol 2017; 264: 1155-1164
    CrossrefPubMedGoogle Scholar
  • 49 Schneider R, Bellenberg B, Hoepner R. et al. Metabolic profiles by 1 H-magnetic resonance spectroscopy in natalizumab-associated post-PML lesions of multiple sclerosis patients who survived progressive multifocal leukoencephalopathy (PML). PloS One 2017; DOI: org/10.1371/journal pone.
    CrossrefPubMedGoogle Scholar
  • 50 Sospedra M, Schippling S, Yousef S. et al. Treating progressive multifocal leucoencephalopathy with interleukin 7 and vaccination with JC virus capsid protein VP1. Clin Infect Dis 2014; 59: 1588-1592
    CrossrefPubMedGoogle Scholar
  • 51 Clavel G, Moulignier A, Semerano L. Progressive multifocal leukoencephalopathy and rheumatoid arthritis treatments. Joint Bone Spine 2017; DOI: 10.1016/j.jbspin.2017.03.002.
    CrossrefPubMedGoogle Scholar
  • 52 Hegen H, Auer M, Bsteh G. et al. Stability and predictive value of anti-JCV antibody index in multiple sclerosis: A 6-year longitudinal study. PLoS One 2017; DOI: 10.1371/journal.pone.0174005.
    CrossrefPubMedGoogle Scholar
  • 53 Plavina T, Subramanyam M, Bloomgren G. et al. Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol 2014; 76: 802-812
    CrossrefPubMedGoogle Scholar
  • 54 Schwab N, Schneider-Hohendorf T, Melzer N. et al. Natalizumab-associated PML: Challenges with incidence, resulting risk, and risk stratification. Neurology 2017; 88: 1197-1205
    CrossrefPubMedGoogle Scholar
  • 55 Uleri E, Ibba G, Piu C. et al. JC polyomavirus expression and bell-shaped regulation of its SF2/ASF suppressor during the follow-up of multiple sclerosis patients treated with natalizumab. J Neurovirol 2017; 23: 226-238
    CrossrefPubMedGoogle Scholar
  • 56 Hoepner R, Kolb EM, Dahlhaus S. et al. Predictors of severity and functional outcome in natalizumab-associated progressive multifocal leukoencephalopathy. Mult Scler 2017; 23: 830-835
    CrossrefPubMedGoogle Scholar