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Severe leptospirosis complicated by Epstein–Barr Virus reactivation

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Abstract

Introduction

Weil’s disease is a severe, potentially fatal illness following Leptospira interrogans infection. The reported case of a patient suffering from acute renal failure, jaundice, thrombocytopenia, rhabdomyolysis and encephalitis syndrome highlights the clinical challenge in reference to Weil syndrome complicated by Epstein–Barr Virus (EBV) reactivation.

Materials and methods

The diagnosis of leptospirosis was performed using four different diagnostic methods. Sera were analyzed with an in-house IgM and IgG enzyme-linked immunosorbent assay (ELISA) and indirect haemagglutination assay (IHA). Microscopic agglutination test (MAT) was done using 17 reference strains comprising 14 serogroups and 17 serovars. Polyvalent EBV-IgG analysis, EBV-IgG/IgM/IgA western blot analysis as well as quantitative EBV polymerase chain reaction (PCR) were performed.

Results

Leptospira IHA showed an initial titer of 1:640 (cut-off 1:320), leptospiral IgG was negative, but IgM was positive. MAT was negative at that time for all 17 strains analyzed. One week later, leptospirosis IHA titer increased to 1:20,480. Leptospiral IgG was now positive, −IgM remained positive and urine was tested negative for leptospiral DNA. The MAT showed positive results for L. interrogans serovar Bataviae, serovar Copenhageni, serovar Pyrogenes and L. borgpetersenii serovar Serjoe. During follow-up examinations, both the leptospiral IgM and IgG remained positive and MAT showed positive results for L. interrogans of different serovars. EBV IgA immunoblot taken at admission was positive for VCA-p18, quantitative EBV-PCR showed an EBV viral load of 2.8E3 copies/ml indicating acute EBV-reactivation.

Conclusion

Leptospirosis represents a neglected and re-emerging disease which is difficult to diagnose since Leptospira-PCR from whole blood or urine is frequently negative in the case of early empiric antibiotic treatment. EBV-reactivation might represent a severe complication in Weil’s disease which potentially aggravates clinical manifestations of leptospirosis including hepatitis, nephritis, and rhabdomyolysis. Thus, there might be a need for peripheral blood EBV-PCR and EBV blotting in patients suffering from complicated Weil syndrome, also in terms of the choice of antibiotic treatment.

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References

  1. Dupouey J, Faucher B, Edouard S, Richet H, Kodjo A, Drancourt M, Davoust B. Human leptospirosis: an emerging risk in Europe? Comp Immunol Microbiol Infect Dis. 2014;37:77–83.

    Article  PubMed  Google Scholar 

  2. Levett PN. Leptospirosis. Clin Microbiol Rev. 2001;14:296–326.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Vijayachari P, Sugunan AP, Shriram AN. Leptospirosis: an emerging global public health problem. J Biosci. 2008;33:557–69.

    Article  CAS  PubMed  Google Scholar 

  4. Ashford DA, Kaiser RM, Spiegel RA, Perkins BA, Weyant RS, Bragg SL, Plikaytis B, Jarquin C, De Lose Reyes JO, Amador JJ. Asymptomatic infection and risk factors for leptospirosis in Nicaragua. Am J Trop Med Hyg. 2000;63:249–54.

    CAS  PubMed  Google Scholar 

  5. WHO. Human leptospirosis: guidance for diagnosis, surveillance and control. Geneva: Switzerland; 2003.

    Google Scholar 

  6. Droulias J, Moutzouris DA, Kassimatis T, Kollia K, Apostolou T, Hadjikonstantinou V. Rhabdomyolysis-induced acute renal failure in a patient with Leptospirosis. Saudi J Kidney Dis Transpl [serial online]. 2007;18:430–1 [cited 2014 Dec 8].

    Google Scholar 

  7. Turner LH. Leptospirosis. II. Serology. Trans R Soc Trop Med Hyg. 1968;62:880–99.

    Article  CAS  PubMed  Google Scholar 

  8. Villumsen S, Pedersen R, Krogfelt KA. Jensen JS Expanding the diagnostic use of PCR in leptospirosis: improved method for DNA extraction from blood cultures. PLoS One. 2010;5:e12095. doi:10.1371/journal.pone.0012095.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Schlichting D, Nöckler K, Bahn P, Luge E, Greiner M, Müller-Graf C, Mayer-Scholl A. Estimation of the sensitivity and specificity of a Leptospira spp. in-house ELISA through Bayesian modelling. 2004; (Submitted).

  10. Levett PN. Usefulness of serologic analysis as a predictor of the infecting serovar in patients with severe leptospirosis. Clin Infect Dis. 2003;36(4):447–52.

    Article  PubMed  Google Scholar 

  11. Faine S, Adler B, Bolin C, Perolat P. Leptospira and Leptospirosis. Melbourne: Medisci Press; 1999.

    Google Scholar 

  12. Chassin C, Picardeau M, Goujon JM, Bourhy P, Quellard N, Darche S, Badell E, d’Andon MF, Winter N, Lacroix-Lamandé S, Buzoni-Gatel D, Vandewalle A, Werts C. TLR4- and TLR2-mediated B cell responses control the clearance of the bacterial pathogen, Leptospira interrogans. J Immunol. 2009;183(4):2669–77. doi:10.4049/jimmunol.0900506 (Epub 2009 Jul 27).

    Article  CAS  PubMed  Google Scholar 

  13. Craig SB, Graham GC, Burns MA, Dohnt MF, Smythe LD, McKay DB. Lymphopenia is observed regularly in the acute (leptospiraemic) phase but not the immune phase of leptospirosis. Trans R Soc Trop Med Hyg. 2009;103:958–60. doi:10.1016/j.trstmh.2009.03.019 (Epub 2009 Apr 21).

    Article  CAS  PubMed  Google Scholar 

  14. Hislop AD, Taylor GS, Sauce D, Rickinson AB. Cellular responses to viral infection in humans: lessons from Epstein–Barr virus. Annu Rev Immunol. 2007;25:587–617.

    Article  CAS  PubMed  Google Scholar 

  15. Vogl BA, Fagin U, Nerbas L, Schlenke P, Lamprecht P, Jabs WJ. Longitudinal analysis of frequency and reactivity of Epstein–Barr virus-specific T lymphocytes and their association with intermittent viral reactivation. J Med Virol. 2012;84:119–31.

    Article  CAS  PubMed  Google Scholar 

  16. Libert N, Bigaillon C, Chargari C, Bensalah M, Muller V, Merat S, de Rudnicki S. Epstein–Barr virus reactivation in critically ill immunocompetent patients. Biomed J. 2015;38(1):70–6. doi:10.4103/2319-4170.132905.

    Article  PubMed  Google Scholar 

  17. Cataudella JA, Young ID, Iliescu EA. Epstein–Barr virus-associated acute interstitial nephritis: infection or immunologic phenomenon? Nephron. 2002;92:437–9.

    Article  CAS  PubMed  Google Scholar 

  18. Osamah H, Finkelstein R, Brook JG. Rhabdomyolysis complicating acute Epstein–Barr virus infection. Infection. 1995;23:119–20.

    Article  CAS  PubMed  Google Scholar 

  19. Brett-Major DM, Coldren R. Antibiotics for leptospirosis. Cochrane Database Syst Rev. 2012;2:CD008264.

  20. Anselmo M, De Leo P, Calcagno G, Donelli E, Tirotta A, Menardo G. Ceftazidime in the treatment of Weil’s disease. Infez Med. 2003;8:106–9.

    Google Scholar 

  21. Khan SA, Dutta P, Borah J, Chowdhury P, Topno R, Baishya M, Mahanta J. Leptospirosis presenting as acute encephalitis syndrome (AES) in Assam, India. Asian Pac J Trop Dis. 2012;2:151–3.

    Article  Google Scholar 

  22. Hocqueloux L, Guinard J, Buret J, Causse X, Guigon A. Do penicillins really increase the frequency of a rash when given during Epstein–Barr Virus primary infection? Clin Infect Dis. 2013;57:1661–2.

    Article  CAS  PubMed  Google Scholar 

  23. Kularatne SA, Budagoda BD, de Alwis VK, et al. High efficacy of bolus methylprednisolone in severe leptospirosis: a descriptive study in Sri Lanka. Postgrad Med J. 2011;87:13.

    Article  CAS  PubMed  Google Scholar 

  24. Werts C. Leptospirosis: a toll road from B lymphocytes. Chang Gung Med J. 2010;33:591–601.

    PubMed  Google Scholar 

  25. Bocian J, Januszkiewicz-Lewandowska D. Utility of quantitative EBV DNA measurements in cerebrospinal fluid for diagnosis and monitoring of treatment of central nervous system EBV-associated post-transplant lymphoproliferative disorder after allogenic hematopoietic stem cell transplantation. Ann Transplant. 2014;19:253–6.

    Article  PubMed  Google Scholar 

  26. Leung SF, Chan KCA, Ma BB, Hui EP, Mo F, Chow KCK, et al. Plasma Epstein–Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma. Ann Oncol. 2014;25:1204–8. doi:10.1093/annonc/mdu117.

    Article  CAS  PubMed  Google Scholar 

  27. Wagner HJ, Cheng YC, Huls MH, Gee AP, Kuehnle I, Krance RA, et al. Prompt versus preemptive intervention for EBV lymphoproliferative disease. Blood. 2004;103:3679–81.

    Google Scholar 

Download references

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Authors and Affiliations

  1. Institute of Medical Microbiology, University Hospital of Friedrich-Schiller-University Jena, Erlanger Allee 101, 07743, Jena, Germany

    Matthias Karrasch & Eberhard Straube

  2. Department of Internal Medicine III (Nephrology), University Hospital of Friedrich-Schiller-University Jena, Jena, Germany

    Konstantin Herfurth & Martin Busch

  3. Institute of Diagnostic and Interventional Radiology, University Hospital of Friedrich-Schiller-University Jena, Jena, Germany

    Monika Kläver

  4. Department of Internal Medicine II (Hematology/Oncology), University Hospital of Friedrich-Schiller-University Jena, Jena, Germany

    Jenny Miethke

  5. German Consiliary Laboratory for Leptospirosis, Federal Institute for Risk Assessment, Berlin, Germany

    Anne Mayer-Scholl & Enno Luge

Authors
  1. Matthias Karrasch
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  2. Konstantin Herfurth
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  3. Monika Kläver
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  4. Jenny Miethke
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  6. Enno Luge
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  7. Eberhard Straube
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  8. Martin Busch
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Correspondence to Matthias Karrasch.

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Karrasch, M., Herfurth, K., Kläver, M. et al. Severe leptospirosis complicated by Epstein–Barr Virus reactivation. Infection 43, 763–769 (2015). https://doi.org/10.1007/s15010-015-0786-6

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  • DOI: https://doi.org/10.1007/s15010-015-0786-6

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