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Post-Transplant Events

Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study

Bone Marrow Transplantation volume 46, pages 858–862 (2011)Cite this article

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Abstract

Digestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria. We identified Cryptosporidium parvum in 5 of the 52 patients (9.6%) at a median of 503 days (range 20–790) after HSCT. In those five patients, the median CD4+ cell and B lymphocyte counts were 60/mm3 (0–234) and 0/mm3 (0–96), respectively. Two patients died of invasive fungal infections. In the other three patients, diarrhoea disappeared after a median of 5 weeks following onset of bitherapy with azithromycine and nitazoxanide; they were still alive 433, 380 and 1179 days after the DC diagnosis. DC is probably under diagnosed after HSCT because it is difficult to detect during the asymptomatic phase. Early bitherapy and reduction of immunosuppression seem efficacious. In our series, DC has a seasonal pattern and is promoted by profound T lymphopenia.

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References

  1. DuPont HL, Chappell CL, Sterling CR, Okhuysen PC, Rose JB, Jakubowski W . The infectivity of Cryptosporidium parvum in healthy volunteers. N Engl J Med 1995; 332: 855–859.

    Article  CAS  PubMed  Google Scholar 

  2. Blanshard C, Jackson AM, Shanson DC, Francis N, Gazzard BG . Cryptosporidiosis in HIV-seropositive patients. Q J Med 1992; 85: 813–823.

    CAS  PubMed  Google Scholar 

  3. Hayward AR, Levy J, Facchetti F, Notarangelo L, Ochs HD, Etzioni A et al. Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM. J Immunol 1997; 158: 977–983.

    CAS  PubMed  Google Scholar 

  4. Burgner D, Pikos N, Eagles G, McCarthy A, Stevens M . Epidemiology of Cryptosporidium parvum in symptomatic paediatric oncology patients. J Paediatr Child Health 1999; 35: 300–302.

    Article  CAS  PubMed  Google Scholar 

  5. Gentile G, Venditti M, Micozzi A, Caprioli A, Donelli G, Tirindelli C et al. Cryptosporidiosis in patients with hematologic malignancies. Rev Infect Dis 1991; 13: 842–846.

    Article  CAS  PubMed  Google Scholar 

  6. Faraci M, Cappelli B, Morreale G, Lanino E, Moroni C, Bandettini R et al. Nitazoxanide or CD3+/CD4+ lymphocytes for recovery from severe Cryptosporidium infection after allogeneic bone marrow transplant? Pediatr Transplant 2007; 11: 113–116.

    Article  CAS  PubMed  Google Scholar 

  7. Manivel C, Filipovich A, Snover DC . Cryptosporidiosis as a cause of diarrhea following bone marrow transplantation. Dis Colon Rectum 1985; 28: 741–742.

    Article  CAS  PubMed  Google Scholar 

  8. Muller CI, Zeiser R, Grullich C, Finke J, Bertz H, Schmitt-Graff A et al. Intestinal cryptosporidiosis mimicking acute graft-versus-host disease following matched unrelated hematopoietic stem cell transplantation. Transplantation 2004; 77: 1478–1479.

    Article  PubMed  Google Scholar 

  9. Rio B, Le Tourneau A, Sobahni I, Audouin J, Bouvet A, Diebold J et al. Cryptosporidiosis in grafting of allogeneic bone marrow]. Presse Med 1986; 15: 1414–1416.

    CAS  PubMed  Google Scholar 

  10. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  Google Scholar 

  11. de la Cruz-Vicente F, Cerezuela Martinez P, Gil-Esparraga E, Martin Aguilera C, Aguilar Guisado M, Parody Ruiz-Berdejo R et al. Preemptive therapy for cytomegalovirus disease in allogeneic stem cell transplant recipients. Transplant Proc 2008; 40: 3102–3103.

    Article  CAS  PubMed  Google Scholar 

  12. Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H . Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009; 58: 1–207, quiz CE1-4.

    PubMed  Google Scholar 

  13. Dalle F, Roz P, Dautin G, Di-Palma M, Kohli E, Sire-Bidault C et al. Molecular characterization of isolates of waterborne Cryptosporidium spp. collected during an outbreak of gastroenteritis in South Burgundy, France. J Clin Microbiol 2003; 41: 2690–2693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Weitzel T, Dittrich S, Mohl I, Adusu E, Jelinek T . Evaluation of seven commercial antigen detection tests for Giardia and Cryptosporidium in stool samples. Clin Microbiol Infect 2006; 12: 656–659.

    Article  CAS  PubMed  Google Scholar 

  15. McLauchlin J, Amar CF, Pedraza-Diaz S, Mieli-Vergani G, Hadzic N, Davies EG . Polymerase chain reaction-based diagnosis of infection with Cryptosporidium in children with primary immunodeficiencies. Pediatr Infect Dis J 2003; 22: 329–335.

    PubMed  Google Scholar 

  16. Chappell CL, Okhuysen PC, Sterling CR, Wang C, Jakubowski W, Dupont HL . Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C parvum serum immunoglobulin G. Am J Trop Med Hyg 1999; 60: 157–164.

    Article  CAS  PubMed  Google Scholar 

  17. Stiehm ER, Chin TW, Haas A, Peerless AG . Infectious complications of the primary immunodeficiencies. Clin Immunol Immunopathol 1986; 40: 69–86.

    Article  CAS  PubMed  Google Scholar 

  18. Gait R, Soutar RH, Hanson M, Fraser C, Chalmers R . Outbreak of cryptosporidiosis among veterinary students. Vet Rec 2008; 162: 843–845.

    Article  CAS  PubMed  Google Scholar 

  19. Valderrama AL, Hlavsa MC, Cronquist A, Cosgrove S, Johnston SP, Roberts JM et al. Multiple risk factors associated with a large statewide increase in cryptosporidiosis. Epidemiol Infect 2009; 137: 1781–1788.

    Article  CAS  PubMed  Google Scholar 

  20. Semenza JC, Nichols G . Cryptosporidiosis surveillance and water-borne outbreaks in Europe. Euro Surveill 2007; 12: E13–E14.

    Article  CAS  PubMed  Google Scholar 

  21. Smith HV, Corcoran GD . New drugs and treatment for cryptosporidiosis. Curr Opin Infect Dis 2004; 17: 557–564.

    Article  CAS  PubMed  Google Scholar 

  22. Anderson VR, Curran MP . Nitazoxanide: a review of its use in the treatment of gastrointestinal infections. Drugs 2007; 67: 1947–1967.

    Article  CAS  PubMed  Google Scholar 

  23. Amadi B, Mwiya M, Musuku J, Watuka A, Sianongo S, Ayoub A et al. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial. Lancet 2002; 360: 1375–1380.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Frances Sheppard of the Clinical Investigation Centre of Besançon for correcting and improving the English of this paper.

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Authors and Affiliations

  1. Service d’Hématologie Clinique, CHU Besançon, Hôpital Jean Minjoz, Besançon, France

    F Legrand, F Larosa, E Deconinck & P S Rohrlich

  2. Laboratoire de Parasitologie-Mycologie, CHU Besançon, Besançon, France

    F Grenouillet, F Dalle & L Millon

  3. Laboratoire de Microbiologie Médicale et Moléculaire (EA 562), CHU Dijon, ,, Dijon, France

    F Dalle

  4. Inserm U-645/UFC/EFS BFC—IFR 133, Besançon, France

    P Saas, E Deconinck & P S Rohrlich

  5. CNRS-Université de Franche-Comté/UMR 6249 Chrono-environnement, Besançon, France

    L Millon

  6. Service d’Hématologie Pédiatrie,

    P S Rohrlich

  7. CHU Besançon, Besançon, France

    P S Rohrlich

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  1. F Legrand
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Correspondence to F Legrand.

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Legrand, F., Grenouillet, F., Larosa, F. et al. Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study. Bone Marrow Transplant 46, 858–862 (2011). https://doi.org/10.1038/bmt.2010.200

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