title: Natural infection of guinea pigs exposed to patients with highly drug-resistant tuberculosis.
abstract: A natural TB infection model using guinea pigs may provide useful information for investigating differences in transmission efficiency and establishment of active disease by clinical TB strains in a highly susceptible host under controlled environmental conditions. We sought to examine the capacity of naturally transmitted multidrug-resistant Mycobacterium tuberculosis to establish infection and produce active disease in guinea pigs. Guinea pigs were continuously exposed for 4 months to the exhaust air of a 6-bed multidrug-resistant tuberculosis inpatient hospital ward in South Africa. Serial tuberculin skin test reactions were measured to determine infection. All animals were subsequently evaluated for histologic disease progression at necropsy. Although 75% of the 362 exposed guinea pigs had positive skin test reactions [≥6 mm], only 12% had histopathologic evidence of active disease. Reversions (≥6 mm change) in skin test reactivity were seen in 22% of animals, exclusively among those with reactions of 6-13 mm. Only two of 86 guinea pigs with reversion had histological evidence of disease compared to 47% (31/66) of guinea pigs with large, non-reverting reactions. Immunosuppression of half the guinea pigs across all skin test categories did not significantly accelerate disease progression. In guinea pigs that reverted a skin test, a second positive reaction in 27 (33%) of them strongly suggested re-infection due to ongoing exposure. These results show that a large majority of guinea pigs naturally exposed to human-source strains of multidrug-resistant tuberculosis became infected, but that many resolved their infection and a large majority failed to progress to detectable disease.
authors.affiliation: Division of Pulmonary and Critical Care Medicine and Division of Global Health Equity, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. adharmadhikari@partners.org
authors.forename: Ashwin S
authors.initials: AS
authors.lastname: Dharmadhikari
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Basaraba
authors.forename: Martie L
authors.initials: ML
authors.lastname: Van Der Walt
authors.forename: Karin
authors.initials: K
authors.lastname: Weyer
authors.forename: Matsie
authors.initials: M
authors.lastname: Mphahlele
authors.forename: Kobus
authors.initials: K
authors.lastname: Venter
authors.forename: Paul A
authors.initials: PA
authors.lastname: Jensen
authors.forename: Melvin W
authors.initials: MW
authors.lastname: First
authors.forename: Sydney
authors.initials: S
authors.lastname: Parsons
authors.forename: David N
authors.initials: DN
authors.lastname: McMurray
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
authors.forename: Edward A
authors.initials: EA
authors.lastname: Nardell
mesh_terms: D000391:Air Microbiology; D016902:Air Pollution, Indoor; D000818:Animals; D003428:Cross Infection; D054908:Extensively Drug-Resistant Tuberculosis / Q000382:microbiology / Q000635:transmission*; D005260:Female; D006168:Guinea Pigs; D006799:Housing, Animal; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D013019:South Africa; D014374:Tuberculin Test; D014691:Ventilation