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 M. 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 [≥6mm], 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 to 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.

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis

“…Testing efficacy in a natural transmission model, perhaps using guinea pigs (39), would be a more physiological test of protection. Because of limited quantities of antibody from our HCW donors, these experiments may only be possible after isolation and recombinant expression of protective mAbs from our donors.…”

Pilot study to detect airborne Mycobacterium tuberculosis exposure in a South African public healthcare facility outpatient clinic

“…18 In a recent study conducted in Witbank, South Africa, the upper room UVGI showed approximately 86% efficacy in reducing airborne TB levels. 19 Administrative controls strengthen engineering controls and provide policy and procedural support for disease prevention in HCWs. Although 55% of the workers had been trained to use a respirator, none actually used them despite being exposed to coughing patients.…”

Animal Models of Tuberculosis: Guinea Pigs

“…There is a renewed interest in understanding natural transmission of TB with a view to improving control measures. In the original natural transmission studies performed by Riley in the 1950s (Riley 1961), guinea pigs were used to sensitively "capture" tubercle bacilli, which were shed from patients with TB disease, and similar experimental systems are being developed (Dharmadhikari et al 2011) with funding initiatives such as the Bill and Melinda Gates Foundation, TB Vaccine Accelerator grants. The reliance on the guinea pig model has sparked several new initiatives to develop immunological reagents and assays to monitor responses to exposure/infection.…”