• 1.

    Britton WJ, Lockwood DN, 2004. Leprosy. Lancet 363: 12091219.

  • 2.

    Shepard CC, 1976. Combinations involving dapsone, rifampicin, clofazimine and ethionamide in the treatment of M. leprae infections in mice. Int J Lepr Other Mycobact Dis 44: 135139.

    • Search Google Scholar
    • Export Citation
  • 3.

    Walsh GP, Meyers WM, Binford CH, 1986. Naturally acquired leprosy in the nine-banded armadillo: a decade of experience 1975–1985. J Leukoc Biol 40: 645656.

    • Search Google Scholar
    • Export Citation
  • 4.

    Gormus BJ, Xu K, Baskin GB, Martin LN, Bohm RP Jr, Blanchard JL, Mack PA, Ratterree MS, Meyers WM, Walsh GP, 1998. Experimental leprosy in rhesus monkeys: transmission, susceptibility, clinical and immunological findings. Lepr Rev 69: 235245.

    • Search Google Scholar
    • Export Citation
  • 5.

    Meyers WM, Gormus BJ, Walsh GP, Baskin GB, Hubbard GB, 1991. Naturally acquired and experimental leprosy in nonhuman primates. Am J Trop Med Hyg 44: 2427.

    • Search Google Scholar
    • Export Citation
  • 6.

    Meyers WM, Walsh GP, Brown HL, Binford CH, Imes GD Jr., Hadfield TL, Schlagel CJ, Fukunishi Y, Gerone PJ, Wolf RH, Gormus BJ, Martin LN, Harboe M, Imaeda T, 1985. Leprosy in a mangabey monkey—naturally acquired infection. Int J Lepr Other Mycobact Dis 53: 114.

    • Search Google Scholar
    • Export Citation
  • 7.

    Baskin GB, Wolf RH, Gormus BJ, Martin LN, Walsh GP, Binford CH, Meyers WM, Malaty R, 1985. Experimental leprosy in the mangabey (Cercocebus atys): necropsy findings. Int J Lepr Other Mycobact Dis 53: 269277.

    • Search Google Scholar
    • Export Citation
  • 8.

    Gormus BJ, Ohashi DK, Ohkawa S, Walsh GP, Meyers WM, Brennan PJ, Trygg C, 1988. Serologic responses to Mycobacterium leprae-specific phenolic glycolipid-I antigen in sooty mangabey monkeys with experimental leprosy. Int J Lepr Other Mycobact Dis 56: 537545.

    • Search Google Scholar
    • Export Citation
  • 9.

    Gormus BJ, Xu K, Baskin GB, Martin LN, Bohm RP, Blanchard JL, Mack PA, Ratterree MS, McClure HM, Meyers WM, Walsh GP, 1995. Experimental leprosy in monkeys. I. Sooty mangabey monkeys: transmission, susceptibility, clinical and pathological findings. Lepr Rev 66: 96104.

    • Search Google Scholar
    • Export Citation
  • 10.

    Gormus BJ, Xu K, Cho SN, Baskin GB, Bohm RP, Martin LN, Blanchard JL, Mack PA, Ratterree MS, Meyers WM, Walsh GP, 1995. Experimental leprosy in monkeys. II. Longitudinal serological observations in sooty mangabey monkeys. Lepr Rev 66: 105125.

    • Search Google Scholar
    • Export Citation
  • 11.

    Martin LN, Gormus BJ, Wolf RH, Gerone PJ, Meyers WM, Walsh GP, Binford CH, Hadfield TL, Schlagel CJ, 1985. Depression of lymphocyte responses to mitogens in mangabeys with disseminated experimental leprosy. Cell Immunol 90: 115130.

    • Search Google Scholar
    • Export Citation
  • 12.

    Binford CH, 1965. The inoculation of human leprosy in the chimpanzee initiation of a long-term project. Int J Lepr 33 (Suppl): 666668.

  • 13.

    Walsh DS, dela Cruz EC, Abalos RM, Walsh GP, Portaels F, Meyers WM, 2007. Limited features of Buruli ulcer in a cynomolgus monkey infected with Mycobacterium ulcerans by intradermal inoculation. Am J Trop Med Hyg 76: 132134.

    • Search Google Scholar
    • Export Citation
  • 14.

    Walsh GP, Tan EV, dela Cruz EC, Abalos RM, Villahermosa LG, Young LJ, Cellona RV, Nazareno JB, Horwitz MA, 1996. The Philippine cynomolgus monkey (Macaca fasicularis) provides a new nonhuman primate model of tuberculosis that resembles human disease. Nat Med 2: 430436.

    • Search Google Scholar
    • Export Citation
  • 15.

    Chaussinand R, 1941. Contributions in the study of leprosy, II. Inoculations of Hansen's bacilli into monkeys. Int J Lepr 9: 203208.

  • 16.

    Valverde CR, Canfield D, Tarara R, Esteves MI, Gormus BJ, 1998. Spontaneous leprosy in a wild-caught cynomolgus macaque. Int J Lepr Other Mycobact Dis 66: 140148.

    • Search Google Scholar
    • Export Citation
  • 17.

    Hastings RC, Gillis TP, Krahenbuhl JL, Franzblau SG, 1988. Leprosy. Clin Microbiol Rev 1: 330348.

  • 18.

    Cellona RV, Balagon MF, dela Cruz EC, Burgos JA, Abalos RM, Walsh GP, Topolski R, Gelber RH, Walsh DS, 2003. Long-term efficacy of 2 year WHO multiple drug therapy (MDT) in multibacillary (MB) leprosy patients. Int J Lepr Other Mycobact Dis 71: 308319.

    • Search Google Scholar
    • Export Citation
  • 19.

    Ridley DS, Jopling WH, 1966. Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis 34: 255273.

    • Search Google Scholar
    • Export Citation
  • 20.

    Bryceson A, Pfaltzgraf RE, 1990. Leprosy, 3rd Ed. New York: Churchill Livingstone.

  • 21.

    Cho SN, Cellona RV, Villahermosa LG, Fajardo TT Jr, Balagon MV, Abalos RM, Tan EV, Walsh GP, Kim JD, Brennan PJ, 2001. Detection of phenolic glycolipid I of Mycobacterium leprae in sera from leprosy patients before and after start of multidrug therapy. Clin Diagn Lab Immunol 8: 138142.

    • Search Google Scholar
    • Export Citation
  • 22.

    Gormus BJ, Baskin GB, Xu K, Ratterree MS, Martin LN, Mack PA, Bohm RP Jr, Meyers WM, Walsh GP, 2000. Antileprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations. Int J Lepr Other Mycobact Dis 68: 2739.

    • Search Google Scholar
    • Export Citation
  • 23.

    Malaty R, Meyers WM, Walsh GP, Binford CH, Zimmerman LE, Baskin GB, Gormus BJ, Martin LN, Wolf RH, 1988. Histopathological changes in the eyes of mangabey monkeys with lepromatous leprosy. Int J Lepr Other Mycobact Dis 56: 443448.

    • Search Google Scholar
    • Export Citation
  • 24.

    Gormus BJ, Baskin GB, Xu K, Ratterree MS, Mack PA, Bohm RP Jr, Meyers WM, Walsh GP, 2002. Anti-leprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: lepromin skin test results. Lepr Rev 73: 254261.

    • Search Google Scholar
    • Export Citation
  • 25.

    Gormus BJ, Baskin GB, Xu K, Ratterree MS, Martin LN, Mack PA, Bohm RP Jr, Meyers WM, Walsh GP, 2000. Antileprosy protective vaccination of sooty mangabey monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations. Int J Lepr Other Mycobact Dis 68: 434443.

    • Search Google Scholar
    • Export Citation
  • 26.

    Gormus BJ, Murphey-Corb M, Baskin GB, Uherka K, Martin LN, Marx PA, Xu K, Ratterree MS, 2000. Interactions between Mycobacterium leprae and simian immunodeficiency virus (SIV) in rhesus monkeys. J Med Primatol 29: 259267.

    • Search Google Scholar
    • Export Citation
  • 27.

    Ustianowski AP, Lawn SD, Lockwood DN, 2006. Interactions between HIV infection and leprosy: a paradox. Lancet Infect Dis 6: 350360.

  • 28.

    Gormus BJ, Murphey-Corb M, Martin LN, Zhang JY, Baskin GB, Trygg CB, Walsh GP, Meyers WM, 1989. Interactions between simian immunodeficiency virus and Mycobacterium leprae in experimentally inoculated rhesus monkeys. J Infect Dis 160: 405413.

    • Search Google Scholar
    • Export Citation
  • 29.

    Gormus BJ, Murphey-Corb M, Martin LN, Baskin GB, Mack PA, Xu K, Ratteree MS, Gerone PJ, Scollard DM, Gillis TP, 1998. Impaired responses to Mycobacterium leprae antigens in rhesus monkeys experimentally inoculated with simian immunodeficiency virus and M. leprae. Lepr Rev 69: 2439.

    • Search Google Scholar
    • Export Citation
  • 30.

    de Wit MY, Douglas JT, McFadden J, Klatser PR, 1993. Polymerase chain reaction for detection of Mycobacterium leprae in nasal swab specimens. J Clin Microbiol 31: 502506.

    • Search Google Scholar
    • Export Citation
  • 31.

    Dagur PK, Sharma B, Kumar G, Khan NA, Katoch VM, Sengupta U, Joshi B, 2010. Mycobacterial antigen(s) induce anergy by altering TCR- and TCR/CD28-induced signalling events: insights into T-cell unresponsiveness in leprosy. Mol Immunol 47: 943952.

    • Search Google Scholar
    • Export Citation
  • 32.

    Baskin GB, Gormus BJ, Martin LN, Wolf RH, Murphey-Corb M, Walsh GP, Binford CH, Meyers WM, Malaty R, 1987. Experimental leprosy in a rhesus monkey: necropsy findings. Int J Lepr Other Mycobact Dis 55: 109115.

    • Search Google Scholar
    • Export Citation
  • 33.

    Baskin GB, Gormus BJ, Martin LN, Wolf RH, Watson EA, Walsh GP, Meyers WM, Binford CH, 1986. The lepromin test in rhesus monkeys. Int J Lepr Other Mycobact Dis 54: 427436.

    • Search Google Scholar
    • Export Citation
 
 
 

 

 
 
 

 

 

 

 

 

 

Limited Susceptibility of Cynomolgus Monkeys (Macaca fascicularis) to Leprosy after Experimental Administration of Mycobacterium leprae

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  • Leonard Wood Memorial, Cebu Leprosy and Tuberculosis Research Foundation, Cebu, Philippines; Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada; Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Science, Bangkok, Thailand

Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis—importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1–19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration.

Author Notes

*Address correspondence to Douglas S. Walsh, Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, 315/6 Rajvithi Road, Bangkok, 10400, Thailand. E-mail: douglas.walsh@afrims.org†Deceased.

Authors' addresses: Gerald P. Walsh, Eduardo C. Dela Cruz, Rodolfo M. Abalos, Esterlina V. Tan, Tranquilino T. Fajardo, Laarni G. Villahermosa, Roland V. Cellona, Maria V. Balagon, and Paul R. Saunderson, Leonard Wood Memorial, Center for Leprosy Research, Cebu, Philippines, E-mail: csc_epi@yahoo.com. Valerie A. White, Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada, E-mail: val.white@vch.ca. Douglas S. Walsh, Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mail: douglas.walsh@afrims.org.

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