1887

Abstract

Leptospirosis is caused by pathogenic species of The aim of this study was to determine and characterize the pathogenicity of four dominant isolates prevailing among rats in the Philippines. The isolates were serovar Manilae strain K64, serovar Losbanos strain K37, serovar Ratnapura strain K5 and serovar Javanica strain K6. Pathogenicities were studied using hamsters, which reproduce severe human leptospirosis. The minimum lethal doses were 10 ( = 1) leptospires for K64, K37 and K5, and 10 leptospires for K6. Weight loss amongst the -infected hamsters was observed from 1 day before death (K64-, K37- and K5-infected hamsters) to as much as 1 week before death for K6-infected hamsters. Similar and varied gross and microscopic lesions were observed amongst infected hamsters, even for strains belonging to the same species (i.e. ). The most significant and common histopathological findings were congestion of the glomerulus, disarrangement of hepatic cords and erythrophagocytosis. Other findings were foamy splenic macrophages for K6, severe petechial pulmonary haemorrhage for K64, and hematuria and severe pulmonary congestion for K37. Immunostaining and culture revealed the presence of leptospires in different organs of the infected hamsters. Based on these results, isolates from rats in the Philippines were shown to be highly virulent, causing pulmonary haemorrhage, severe hepato-renal damage and death in hamsters even at lower doses. The present findings on experimental leptospirosis support clinical data showing that patients with severe manifestations of leptospirosis, such as pulmonary haemorrhage, are increasing in the Philippines. These findings may serve as a basis to strengthen the early diagnosis and treatment of human leptospirosis.

Funding
This study was supported by the:
  • Ministry of Education, Culture, Sports, Science, and Technology
  • MEXT
  • Japan Science and Technology Agency
  • JST
  • Japan International Cooperation Agency
  • JICA
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2014-02-01
2024-03-29
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References

  1. Amilasan A. S., Ujiie M., Suzuki M., Salva E., Belo M. C., Koizumi N., Yoshimatsu K., Schmidt W. P., Marte S. & other authors ( 2012). Outbreak of leptospirosis after flood, the Philippines, 2009. Emerg Infect Dis 18:91–94 [View Article][PubMed]
    [Google Scholar]
  2. Arean V. M. ( 1962). The pathologic anatomy and pathogenesis of fatal human leptospirosis (Weil’s disease). Am J Pathol 40:393–423[PubMed]
    [Google Scholar]
  3. Arean V. M., Sarasin G., Green J. H. ( 1964). The pathogenesis of leptospirosis: toxin production by Leptospira icterohaemorrhagiae. Am J Vet Res 25:836–843[PubMed]
    [Google Scholar]
  4. Baseman J. B., Cox C. D. ( 1969). Intermediate energy metabolism of Leptospira. J Bacteriol 97:992–1000[PubMed]
    [Google Scholar]
  5. Coutinho M. L., Choy H. A., Kelley M. M., Matsunaga J., Babbitt J. T., Lewis M. S., Aleixo J. A., Haake D. A. ( 2011). A LigA three-domain region protects hamsters from lethal infection by Leptospira interrogans. PLoS Negl Trop Dis 5:e1422 [View Article][PubMed]
    [Google Scholar]
  6. De Brito T., Menezes L. F., Lima D. M., Lourenço S., Silva A. M., Alves V. A. ( 2006). Immunohistochemical and in situ hybridization studies of the liver and kidney in human leptospirosis. Virchows Arch 448:576–583 [View Article][PubMed]
    [Google Scholar]
  7. Evangelista K. V., Coburn J. ( 2010). Leptospira as an emerging pathogen: a review of its biology, pathogenesis and host immune responses. Future Microbiol 5:1413–1425 [View Article][PubMed]
    [Google Scholar]
  8. Faine S., Adler B., Bolin C., Perolat P. ( 1999). Leptospira and Leptospirosis , 2nd edn. Melbourne: MediSci;
    [Google Scholar]
  9. Feigin R. D., Anderson D. C., Heath C. W. ( 1975). Human leptospirosis. CRC Crit Rev Clin Lab Sci 5:413–467 [View Article][PubMed]
    [Google Scholar]
  10. Fisman D. N. ( 2000). Hemophagocytic syndromes and infection. Emerg Infect Dis 6:601–608 [View Article][PubMed]
    [Google Scholar]
  11. Gouveia E. L., Metcalfe J., De Carvalho A. L., Aires T. S., Villasboas-Bisneto J. C., Queirroz A., Santos A. C., Salgado K., Reis M. G., Ko A. I. ( 2008). Leptospirosis-associated severe pulmonary hemorrhagic syndrome, Salvador, Brazil. Emerg Infect Dis 14:505–508 [View Article][PubMed]
    [Google Scholar]
  12. Haake D. A. ( 2006). Hamster model of leptospirosis. Current Protocols in Microbiology12E.2.1–12E.2.13 Coico R. T., Kowalik T. F., Quarles J., Stevenson B., Taylor R. Hoboken, NJ: Wiley; [View Article]
    [Google Scholar]
  13. Inada R., Ido Y., Hoki R., Kaneko R., Ito H. ( 1916). The etiology, mode of infection, and specific therapy of Weil’s disease (spirochaetosis icterohaemorrhagica).. J Exp Med 23:377–402 [View Article][PubMed]
    [Google Scholar]
  14. Isogai E., Isogai H., Kurebayashi Y., Ito N. ( 1986). Biological activities of leptospiral lipopolysaccharide. Zentralbl Bakteriol Mikrobiol Hyg [A] 261:53–64[PubMed]
    [Google Scholar]
  15. Kalayoglu M. V., Byrne G. I. ( 1998). Induction of macrophage foam cell formation by Chlamydia pneumoniae. J Infect Dis 177:725–729 [View Article][PubMed]
    [Google Scholar]
  16. Kobayashi Y. ( 2005). Human leptospirosis: management and prognosis. J Postgrad Med 51:201–204[PubMed]
    [Google Scholar]
  17. Kuriyama T., Takenaka K., Kohno K., Yamauchi T., Daitoku S., Yoshimoto G., Kikushige Y., Kishimoto J., Abe Y. & other authors ( 2012). Engulfment of hematopoietic stem cells caused by down-regulation of CD47 is critical in the pathogenesis of hemophagocytic lymphohistiocytosis. Blood 120:4058–4067 [View Article][PubMed]
    [Google Scholar]
  18. Levett P. N. ( 2001). Leptospirosis. Clin Microbiol Rev 14:296–326 [View Article][PubMed]
    [Google Scholar]
  19. Levett P. N. ( 2004). Leptospirosis: a forgotten zoonosis. Clin Appl Immunol Rev 4:435–448 [View Article]
    [Google Scholar]
  20. Matsui M., Rouleau V., Bruyère-Ostells L., Goarant C. ( 2011). Gene expression profiles of immune mediators and histopathological findings in animal models of leptospirosis: comparison between susceptible hamsters and resistant mice. Infect Immun 79:4480–4492 [View Article][PubMed]
    [Google Scholar]
  21. McBride A. J., Athanazio D. A., Reis M. G., Ko A. I. ( 2005). Leptospirosis. Curr Opin Infect Dis 18:376–386 [View Article][PubMed]
    [Google Scholar]
  22. Miller N. G., Allen J. E., Wilson R. B. ( 1974). The pathogenesis of hemorrhage in the lung of the hamster during acute leptospirosis. Med Microbiol Immunol (Berl) 160:269–278 [View Article][PubMed]
    [Google Scholar]
  23. Nally J. E., Chantranuwat C., Wu X. Y., Fishbein M. C., Pereira M. M., Da Silva J. J., Blanco D. R., Lovett M. A. ( 2004). Alveolar septal deposition of immunoglobulin and complement parallels pulmonary hemorrhage in a guinea pig model of severe pulmonary leptospirosis. Am J Pathol 164:1115–1127 [View Article][PubMed]
    [Google Scholar]
  24. Noguchi H. ( 1917). Spirochaeta icterohaemorrhagiae in American wild rats and its relation to the Japanese and European strains: first paper. J Exp Med 25:755–763 [View Article][PubMed]
    [Google Scholar]
  25. Oliva R., Infante J. F., González M., Pérez V., Sifontes S., Marrero O., Valdés Y., Fariñas M., Estévez L., González I. ( 1994). Pathologic-clinical characterization of leptospirosis in a golden Syrian hamster model. Arch Med Res 25:165–170[PubMed]
    [Google Scholar]
  26. Portugal L. R., Fernandes L. R., Pietra Pedroso V. S., Santiago H. C., Gazzinelli R. T., Alvarez-Leite J. I. ( 2008). Influence of low-density lipoprotein (LDL) receptor on lipid composition, inflammation and parasitism during Toxoplasma gondii infection. Microbes Infect 10:276–284 [View Article][PubMed]
    [Google Scholar]
  27. Rouphael N. G., Talati N. J., Vaughan C., Cunningham K., Moreira R., Gould C. ( 2007). Infections associated with haemophagocytic syndrome. Lancet Infect Dis 7:814–822 [View Article][PubMed]
    [Google Scholar]
  28. Russell D. G., Cardona P. J., Kim M. J., Allain S., Altare F. ( 2009). Foamy macrophages and the progression of the human tuberculosis granuloma. Nat Immunol 10:943–948 [View Article][PubMed]
    [Google Scholar]
  29. Salyers A. A., Whitt D. D. ( 2002). Bacterial Pathogenesis: a Molecular Approach, 2nd edn. Washington, DC: American Society for Microbiology;
    [Google Scholar]
  30. Shimizu T., Matsusaka E., Takayanagi K., Masuzawa T., Iwamoto Y., Morita T., Mifuchi I., Yanagihara Y. ( 1987). Biological activities of lipopolysaccharide-like substance (LLS) extracted from Leptospira interrogans serovar canicola strain Moulton. Microbiol Immunol 31:727–735 [View Article][PubMed]
    [Google Scholar]
  31. Silva E. F., Santos C. S., Athanazio D. A., Seyffert N., Seixas F. K., Cerqueira G. M., Fagundes M. Q., Brod C. S., Reis M. G. & other authors ( 2008). Characterization of virulence of Leptospira isolates in a hamster model. Vaccine 26:3892–3896 [View Article][PubMed]
    [Google Scholar]
  32. Silva-Herzog E., Detweiler C. S. ( 2008). Intracellular microbes and haemophagocytosis. Cell Microbiol 10:2151–2158 [View Article][PubMed]
    [Google Scholar]
  33. Stern N., Shenberg E., Tietz A. ( 1969). Studies on the metabolism of fatty acids in Leptospira: the biosynthesis of Δ9- and Δ11-monounsaturated acids. Eur J Biochem 8:101–108 [View Article][PubMed]
    [Google Scholar]
  34. Tajiki H., Salomão R. ( 1996). Association of plasma levels of tumor necrosis factor alpha with severity of disease and mortality among patients with leptospirosis. Clin Infect Dis 23:1177–1178 [View Article][PubMed]
    [Google Scholar]
  35. Trevejo R. T., Rigau-Pérez J. G., Ashford D. A., McClure E. M., Jarquín-González C., Amador J. J., de los Reyes J. O., Gonzalez A., Zaki S. R. & other authors ( 1998). Epidemic leptospirosis associated with pulmonary hemorrhage – Nicaragua, 1995. J Infect Dis 178:1457–1463 [View Article][PubMed]
    [Google Scholar]
  36. Vernel-Pauillac F., Goarant C. ( 2010). Differential cytokine gene expression according to outcome in a hamster model of leptospirosis. PLoS Negl Trop Dis 4:e582 [View Article][PubMed]
    [Google Scholar]
  37. Villanueva S. Y., Ezoe H., Baterna R. A., Yanagihara Y., Muto M., Koizumi N., Fukui T., Okamoto Y., Masuzawa T. & other authors ( 2010). Serologic and molecular studies of Leptospira and leptospirosis among rats in the Philippines. Am J Trop Med Hyg 82:889–898 [View Article][PubMed]
    [Google Scholar]
  38. Vinetz J. M. ( 2001). Leptospirosis. Curr Opin Infect Dis 14:527–538 [View Article][PubMed]
    [Google Scholar]
  39. Wagenaar J. F., Goris M. G., Gasem M. H., Isbandrio B., Moalli F., Mantovani A., Boer K. R., Hartskeerl R. A., Garlanda C., van Gorp E. C. ( 2009). Long pentraxin PTX3 is associated with mortality and disease severity in severe Leptospirosis. J Infect 58:425–432 [View Article][PubMed]
    [Google Scholar]
  40. WHO ( 1999). Leptospirosis worldwide, 1999. Wkly Epidemiol Rec 74:237–242[PubMed]
    [Google Scholar]
  41. WHO ILS ( 2003). Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control Geneva: World Health Organization and International Leptospirosis Society;
    [Google Scholar]
  42. Yanagihara Y., Villanueva S. Y., Yoshida S., Okamoto Y., Masuzawa T. ( 2007). Current status of leptospirosis in Japan and Philippines. Comp Immunol Microbiol Infect Dis 30:399–413 [View Article][PubMed]
    [Google Scholar]
  43. Zuerner R. L., Alt D. P., Palmer M. V. ( 2012). Development of chronic and acute golden Syrian hamster infection models with Leptospira borgpetersenii serovar Hardjo. Vet Pathol 49:403–411 [View Article][PubMed]
    [Google Scholar]
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