Limited Tuberculosis Progression in Guinea Pigs Naturally Exposed to Human Multidrug Resistant Strains

Details

• Personal Author:
  Basaraba R ; Dharmadhikari AS ; First M ; Jensen P ; Mphahlele M ; Nardell EA ; Palanisamy G ; Parsons S ; Venter K ; Weyer K
• Description:
  Rationale: Multidrug resistant M. tuberculosis (MDR-TB) infections are a major source of morbidity and mortality worldwide. Some laboratory and epidemiologic studies, however, suggest that MDR-TB strains display heterogeneous fitness. Animal models of TB have been used to study MDR-TB pathogenesis, but these studies have used cultivated MDR-TB strains that are aerosolized in relatively high concentrations compared to natural infection. Little is known about whether MDR-TB aerosols generated directly from humans propagate differently in sentinel animals. Methods: Using a unique airborne infections research facility in South Africa, we exposed 362 guinea pigs (GP) to exhaust air from a 6-bed MDR-TB hospital ward over a 4 month period and performed monthly tuberculin skin tests (TST) on them. To accelerate disease progression and enhance microbial recovery rate, we pharmacologically immunosuppressed half the TST positive animals after MDR-TB exposure and examined and scored lung and spleen tissues for pathology. Results: Although 74% of GPs acquired infection (e.g. had positive TST), only 15% of TST positive GPs had pathologic evidence of TB. We also noted TST reversions in more than 20% of TST positive GPs. Less pathology was found in GPs with TST reactions of the longest duration. Steroid immunosuppression did not alter disease prevalence or severity. Conclusions: Even in the highly vulnerable GP model, most (but not all) MDR-TB strains naturally generated by our patients failed to progress to disease, suggesting reduced fitness. [Description provided by NIOSH]
• Subjects:
  Aerosols Biological Factors Environmental Monitoring Epidemiology Laboratories Lung Lung Diseases Morbidity Mortality Occupational Health Respiratory System Respiratory Tract Diseases Safety Skin Ventilation Workplace

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• Keywords:
  Aerosol-generators Aerosol-particles Biological-factors Cell-biology Cell-function Disease-incidence Disease-transmission Exhaust-ventilation Exposure-assessment Exposure-levels Exposure-methods Inhalation-studies Laboratory-animals Laboratory-testing Lung-disorders Lung-irritants Mathematical-models Morbidity-rates Mortality-rates Physiological-effects Pulmonary-system-disorders Skin-tests Statistical-analysis Work-environment

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• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Colorado ; Georgia ; Massachusetts ; OSHA Region 1 ; OSHA Region 4 ; OSHA Region 8
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  179
• NIOSHTIC Number:
  nn:20036385
• Citation:
  Am J Respir Crit Care Med 2009 Apr; 179(Meeting Abstracts):A5290
• Email:
  adharmadhikari@partners.org
• Federal Fiscal Year:
  2009
• Peer Reviewed:
  False
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Meeting Abstracts
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ff011d2dc8350df71718ea560fe6cece821430eff3fcf49a19dba9c49914eaede8e56ebc19a9fb4e5cf63890c928967ff0125064f85d9d8a200fc08d9000545d
• Download URL:
  https://stacks.cdc.gov/view/cdc/187842/cdc_187842_DS1.pdf
• File Type:
  [PDF - 153.18 KB ]