As far as we knew, this is the first large-scale investigation to evaluate the prevalence of LTBI among individuals with fibrotic radiological lesions by means of screening in rural China. Around one thirds (34.16%, 762/2,231) of registered prior TB cases showed hint of fibrotic radiological lesions, while it was about 3% (2.81%, 1,230/4,3670) in the general population without a history of anti-TB treatment. Among participants with such radiographic abnormalities, QFT-GIT positivity was 50.39% (384/762) and 25.44% (313/1,230) for those with and without anti-TB treatment history, respectively.
The prevalence of QFT-GIT positivity in the general rural adults from the same study site was observed to be 19.0% (801/4,223) [13], which was remarkably lower than in individuals with fibrotic scarring particular and a record of anti-TB treatment. It was difficult to clarify whether such higher QFT-GIT positivity was caused by the persistent adaptive immune response to last un-cleared TB infection or newly acquired immune response to reinfection as exogenous reinfection is still common in China [14]. However, such re-exposure could not fully explain the difference between individuals with and without record of anti-tuberculosis treatment. It was most likely caused by differences in exposure gradient and host protective immunity. Those self-cured individuals might experience lower-level exposure or had stronger immune response to clear the infection, but those developed active disease and acquired anti-TB treatment might be incapable of clearing the infection.
It is well known that individuals with fibrotic lesions consistent with inactive TB were high-priority candidates for LTBI testing and treatment [9–10, 15]. It was noted that in most guidelines such targets were restricted to be self-cured or not regularly treated, which meant those accepted standard treatment was not suggested to be considered for LTBI management [9]. However, such evidences coming from regions with lower risk of reinfection might not be consistent in regions where new infection was common. Therefore, LTBI management guidelines should be developed according to local epidemiological characteristics of active TB and LTBI. Generally, persons at high risk for developing TB disease fall into two broad categories: recent infections or persons with clinical conditions or other factors associated with an increased risk of progression from LTBI to TB disease. In high-burden countries, individuals with fibrotic radiological lesions should be attached importance for LTBI testing and treatment as they face dual risks of MTB exposure and active disease progression. Thus, a previous a history of anti-TB treatment should not be a contraindication for preventive treatment in case of exposure occurred. Longitudinal studies are needed to identify whether fibrotic radiological lesion was associated with significantly increased risk of developing active TB among those with anti-TB treatment history.
Our previous findings suggested that increasing age was associated with increased risk of LTBI in rural China, as older persons might have more social contact with active TB patients at old age as well. Furthermore, the attenuation of immunity among the elderly might predict lower infection clearance capability and higher risk of persistent infection as compared to young people [13, 16]. However, to our surprise, for individuals with treatment record, a negative relation between increasing age and QFT-GIT positivity was found. Classified analysis by previous active TB diagnostic time and the smear results didn’t change the trend. The attenuated test sensitivity among elderly might be one potential underlying explanation. The ability of IGRA to identify TB infection was suggested to be decreased with age because of the waned immune response of lymphocytes to TB-specific antigens. Consistently, several previous studies have observed declined sensitivity of IGRAs along with age among patients with active TB [17–18]. Our previous prospective study also identified incident cases during follow-up among middle aged and elderly subgroups with negative QFT-GIT results [8]. Of course, the influence of reinfection could not be completely excluded. For those relatively young subjects, the more social activity means more risks of re-exposure. In any case, it is noteworthy that the sensitivity of LTBI testing needs to be improved in the elderly.
When interpreting the results, several limitations of our study should be kept in mind. First, the size and location of the studied fibrotic scarring were not documented in the current study which might be associated with the risks of LTBI and active disease [19]. Second, although fibrosis has been regarded as typical patterns of old healed TB, the interpretation could be inaccurate in some cases as radiographic lesions suggestive of TB may also be present in conditions such as histoplasmosis, pneumoconiosis and hypersensitivity pneumonitis [20]. Third, detailed information on clinical characteristics of the participants and other potential factors associated with TB infection, such as TB contact history and socioeconomic information, were not completely collected, it limited stratified analysis to explore the relations between fibrotic radiological lesions and LTBI status. Forth, information bias can’t be avoided for individuals with self-reported history of TB as official TBIMS built until 2005.