Division of Pulmonary and Critical Care Medicine and Division of Global Health Equity, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Tuberculosis (Edinb). 2011 Jul;91(4):329-38. doi: 10.1016/j.tube.2011.03.002. Epub 2011 Apr 7.
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.
豚鼠自然感染结核模型可能为研究在高度易感宿主的受控环境条件下，临床结核菌株的传播效率差异和活性疾病的建立提供有用信息。我们试图研究天然传播的耐多药结核分枝杆菌在豚鼠中建立感染和产生活动性疾病的能力。豚鼠连续暴露于南非 6 张耐药结核病住院病房的排气中 4 个月。通过结核菌素皮肤试验反应的连续测量来确定感染。所有动物随后在尸检时均评估组织学疾病进展。尽管 362 只暴露豚鼠中有 75%（275/362）的皮肤试验反应呈阳性（≥6mm），但仅有 12%（44/362）有组织病理学证据表明患有活动性疾病。22%（80/362）的动物出现皮肤试验反应逆转（≥6mm 变化），仅见于 6-13mm 反应的动物。与 66 只非逆转反应的豚鼠中有 47%（31/66）有组织学证据表明疾病相比，有 2 只（2/86）皮肤试验逆转的豚鼠有组织学证据表明疾病。在所有皮肤试验类别中，半数豚鼠的免疫抑制并未显著加速疾病进展。在皮肤试验逆转的豚鼠中，27 只（33%）中有第二次阳性反应强烈提示由于持续暴露而再次感染。这些结果表明，大多数自然暴露于人源耐药结核分枝杆菌株的豚鼠被感染，但许多豚鼠的感染得到了缓解，而大多数豚鼠并未进展为可检测到的疾病。
