Natural infection of guinea pigs exposed to patients with highly drug-resistant tuberculosis

被引:68
作者
Dharmadhikari, Ashwin S. [1 ,2 ]
Basaraba, Randall J. [3 ]
Van Der Walt, Martie L. [4 ]
Weyer, Karin [5 ]
Mphahlele, Matsie [4 ]
Venter, Kobus [4 ]
Jensen, Paul A. [6 ]
First, Melvin W. [7 ]
Parsons, Sydney
McMurray, David N. [8 ]
Orme, Ian M. [3 ]
Nardell, Edward A. [1 ,2 ,7 ]
机构
[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA
[3] Colorado State Univ, Dept Microbiol Immunol & Pathol, Coll Vet Med & Biomed Sci, Ft Collins, CO 80523 USA
[4] S African MRC, TB Epidemiol & Intervent Res Unit, ZA-0001 Pretoria, South Africa
[5] WHO, CH-1211 Geneva, Switzerland
[6] CDC, Atlanta, GA 30333 USA
[7] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA
[8] Texas A&M Hlth Sci Ctr, Dept Microbial & Mol Pathogenesis, College Stn, TX 77843 USA
基金
英国医学研究理事会;
关键词
MDR/XDR tuberculosis; Guinea pig model; Natural infection; Skin test reactivity; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; ANIMAL-MODELS; TRANSMISSION; FITNESS; AIR; EPIDEMIOLOGY; STRATEGIES; DISEASE;
D O I
10.1016/j.tube.2011.03.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:329 / 338
页数:10
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