Reactivation of latent tuberculosis

Variations on the cornell murine model

Charles A. Scanga, V. P. Mohan, Heather Joseph, Keming Yu, John Chan, Joanne L. Flynn

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Mycobacterium tuberculosis causes active tuberculosis in only a small percentage of infected persons. In most cases, the infection is clinically latent, although immunosuppression can cause reactivation of a latent M. tuberculosis infection. Surprisingly little is known about the biology of the bacterium or the host during latency, and experimental studies on latent tuberculosis suffer from a lack of appropriate animal models. The Cornell model is a historical murine model of latent tuberculosis, in which mice infected with M. tuberculosis are treated with antibiotics (isoniazid and pyrazinamide), resulting in no detectable bacilli by organ culture. Reactivation of infection during this culture-negative state occurred spontaneously and following immunosuppression. In the present study, three variants of the Cornell model were evaluated for their utility in studies of latent and reactivated tuberculosis. The antibiotic regimen, inoculating dose, and antibiotic-free rest period prior to immunosuppression were varied. A variety of immunosuppressive agents, based on immunologic factors known to be important to control of acute infection, were used in attempts to reactivate the infection. Although reactivation of latent infection was observed in all three variants, these models were associated with characteristics that limit their experimental utility, including spontaneous reactivation, difficulties in inducing reactivation, and the generation of altered bacilli. The results from these studies demonstrate that the outcome of Cornell model-based studies depends critically upon the parameters used to establish the model.

Original languageEnglish (US)
Pages (from-to)4531-4538
Number of pages8
JournalInfection and Immunity
Volume67
Issue number9
StatePublished - 1999

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Latent Tuberculosis
Immunosuppression
Anti-Bacterial Agents
Infection
Mycobacterium tuberculosis
Bacillus
Pyrazinamide
Organ Culture Techniques
Isoniazid
Immunologic Factors
Mycobacterium
Immunosuppressive Agents
Infection Control
Tuberculosis
Animal Models
Outcome Assessment (Health Care)
Bacteria

ASJC Scopus subject areas

  • Immunology

Cite this

Scanga, C. A., Mohan, V. P., Joseph, H., Yu, K., Chan, J., & Flynn, J. L. (1999). Reactivation of latent tuberculosis: Variations on the cornell murine model. Infection and Immunity, 67(9), 4531-4538.

Reactivation of latent tuberculosis : Variations on the cornell murine model. / Scanga, Charles A.; Mohan, V. P.; Joseph, Heather; Yu, Keming; Chan, John; Flynn, Joanne L.

In: Infection and Immunity, Vol. 67, No. 9, 1999, p. 4531-4538.

Research output: Contribution to journalArticle

Scanga, CA, Mohan, VP, Joseph, H, Yu, K, Chan, J & Flynn, JL 1999, 'Reactivation of latent tuberculosis: Variations on the cornell murine model', Infection and Immunity, vol. 67, no. 9, pp. 4531-4538.
Scanga CA, Mohan VP, Joseph H, Yu K, Chan J, Flynn JL. Reactivation of latent tuberculosis: Variations on the cornell murine model. Infection and Immunity. 1999;67(9):4531-4538.
Scanga, Charles A. ; Mohan, V. P. ; Joseph, Heather ; Yu, Keming ; Chan, John ; Flynn, Joanne L. / Reactivation of latent tuberculosis : Variations on the cornell murine model. In: Infection and Immunity. 1999 ; Vol. 67, No. 9. pp. 4531-4538.
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