Application of optical imaging to study of extrapulmonary spread by tuberculosis.

The incidence of extrapulmonary tuberculosis is increasing, possibly due to the high frequency of co-infection with HIV. Extrapulmonary infections complicate diagnosis, have higher mortality rates and are more difficult to treat. Insight into the mechanisms involved in extrapulmonary spread of tuberculosis is critical to improving management. We set out to better understand extrapulmonary spread kinetics in mice and guinea pigs as well as the effects of infectious dose. We found that extrapulmonary spread occurs at a discrete time point when infected by low-dose aerosol, but at high-dose aerosol it occurs within the first 24h. The ability to follow tuberculosis in real-time during infection would allow us to better address the mechanisms involved. We found that mycobacteria can be optically imaged after pulmonary infection in the mouse lung, suggesting that this technology could be applied to study of extrapulmonary spread of tuberculosis.

[1]  H. Gallis,et al.  Miliary tuberculosis: epidemiology, clinical manifestations, diagnosis, and outcome. , 1990, Reviews of infectious diseases.

[2]  Medlar Em The pathogenesis of minimal pulmonary tuberculosis; a study of 1,225 necropsies in cases of sudden and unexpected death. , 1948 .

[3]  B. Dikici,et al.  Miliary tuberculosis in children: a clinical review. , 1998, Scandinavian journal of infectious diseases.

[4]  I. Smith,et al.  Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence , 2003, Clinical Microbiology Reviews.

[5]  N. Chaffey Red fluorescent protein , 2001 .

[6]  R. Chaisson,et al.  Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection. , 1991, The New England journal of medicine.

[7]  G. Hussey,et al.  Miliary tuberculosis in children: a review of 94 cases , 1991, The Pediatric infectious disease journal.

[8]  E. Bouza,et al.  Association between the infectivity of Mycobacterium tuberculosis strains and their efficiency for extrarespiratory infection. , 2005, The Journal of infectious diseases.

[9]  R. Long,et al.  Disseminated tuberculosis with and without a miliary pattern on chest radiograph: a clinical-pathologic-radiologic correlation. , 1997, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[10]  R. Weissleder A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

[11]  Aderele Wi Miliary tuberculosis in Nigerian children. , 1978 .

[12]  I. Siegel A clinical review , 1978 .

[13]  Nathan C Shaner,et al.  A guide to choosing fluorescent proteins , 2005, Nature Methods.

[14]  M. Gennaro,et al.  Tuberculosis immunology in children: diagnostic and therapeutic challenges and opportunities. , 2004, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[15]  R. Tsien,et al.  Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein , 2004, Nature Biotechnology.

[16]  D. Smith,et al.  Pathogenesis of tuberculosis: pathway to apical localization. , 1994, Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[17]  D. Havlir,et al.  Tuberculosis in patients with human immunodeficiency virus infection. , 1999, The New England journal of medicine.

[18]  R. Gie,et al.  The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. , 2004, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[19]  P. Barnes,et al.  Relationship of the manifestations of tuberculosis to CD4 cell counts in patients with human immunodeficiency virus infection. , 1993, The American review of respiratory disease.

[20]  C. Dascher,et al.  Dissemination of Mycobacterium tuberculosis Is Influenced by Host Factors and Precedes the Initiation of T-Cell Immunity , 2002, Infection and Immunity.

[21]  I. Campbell Miliary tuberculosis in British Columbia. , 1973, Canadian Medical Association journal.

[22]  A. Ariza,et al.  Evolution of granulomas in lungs of mice infected aerogenically with Mycobacterium tuberculosis. , 2000, Scandinavian journal of immunology.

[23]  T. Walsh,et al.  Late generalized tuberculosis: a clinical pathologic analysis and comparison of 100 cases in the preantibiotic and antibiotic eras. , 1980, Medicine.

[24]  W. Stead,et al.  Pathogenesis of tuberculosis: clinical and epidemiologic perspective. , 1989, Reviews of infectious diseases.

[25]  R. Debré [Miliary tuberculosis in children]. , 1952, Lancet.

[26]  R. Jacobs,et al.  Resurgence of tuberculosis in children. , 1992, The Journal of pediatrics.

[27]  G W Comstock,et al.  The prognosis of a positive tuberculin reaction in childhood and adolescence. , 1974, American journal of epidemiology.

[28]  P. Munt MILIARY TUBERCULOSIS IN THE CHEMOTHERAPY ERA: WITH A CLINICAL REVIEW IN 69 AMERICAN ADULTS , 1972, Medicine.

[29]  J. Starke,et al.  Tuberculosis in the pediatric population of Houston, Texas. , 1989, Pediatrics.

[30]  D. Snider,et al.  Extrapulmonary tuberculosis in the United States. , 1990, The American review of respiratory disease.

[31]  B. J. Marais Childhood turberculosis: reflections from the front line. , 2004, Pediatric annals.

[32]  D. Mitra,et al.  Miliary tuberculosis: new insights into an old disease. , 2005, The Lancet. Infectious diseases.

[33]  G. Marchal,et al.  Tuberculosis in HIV-infected patients: a comprehensive review. , 2004, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.