The study is the first ever study in Sikkim for any congregate living facility to describe the burden of TB as well as risk of LTBI. The cross-sectional study found that the overall LTBI positive rate was 44.2% which is comparable to the study by Kashyap et al. [9], prevalence of LTBI by QFT-G was 48% in poor ventilated high TB endemic zone in India and also comparable to the studies in other developing countries [9–12]. Another study showed 18% LTBI among Tibetan school children whereas 53% adult staff was LTBI positive [13]. Bivariate analysis of the risk factor in our study showed significant association with age, past history, BMI, occupation and travelling, multivariate regression analysis with these factors, age, BMI and past TB history, appeared strong predictor.
Household contact of index TB cases are known to be the high-risk population; indeed, all such cases in our study were LTBI positive. Several published studies have shown that the clustering of infectious TB cases within families increases the susceptibility of household contacts for LTBI and TB disease [14, 15]. The detection rate of LTBI among family contacts of TB patient ranged from 0.2%-2% in high income countries [16, 17]. In a prospective follow up study (2008–2012), in high TB burden setting in India, 76 out of 1511 household contacts developed active TB [18]. In our study no TB breakdown occurred during follow up for a span of one year.
A number of factors were found to be associated with the risk of getting LTBI in our study. Age has been regarded as important risk factor to get LTBI. Increasing trend of LTBI positivity with age was noticed in our study. Risk of TB infection with increasing age is also reported by other study from endemic zone in India [9]. We observed travelling as potential risk factor for acquiring TB infection as it increases the probability of exposure to TB causing bacilli. IGRA positivity in our study was comparatively higher in participants who used to travel to their native places more frequently, as compare to the participants travelling on yearly basis, which correlate with higher chances of getting exposure to TB infection during travel as well as in the native places. The odds for teachers were surprisingly higher. This may be due to the prolonged exposer and interaction with students during teaching classes. In addition, BMI was found to be major confounding factor in our study. It is known that underweight and obese individuals are more likely to get TB infection; there is substantial evidence that suggest malnutrition as a possible determinant of TB [19, 20]. The association between BMI and TB infection has not been comprehensively understood, despite years of research on its links with active TB disease [21, 22]. In a population based multi-centric study in rural China, BMI was found to be independently associated with host susceptibility to TB and the strength of such association was stronger at the site with high prevalence of TB [23]. It has been suggested that excess adiposity negatively impact immune function and host defense in obese individuals [24, 25].
Present study reported higher (TB2-TB1 difference, > 0.6 IU/ml) in 14% of LTBI participants, previous study have shown that TB-2 specific response elicited by CD8 + T cells have been associated with active TB both in immuno-compromised and healthy individual [26, 27]; however, in our study all such LTBI cases were asymptomatic during screening and follow up, higher TB2 response (CD4 and CD8) in these individuals could probably due to recent exposure to smear positive active TB cases [28, 29] during traveling or at their native place. However, it is very difficult to determine when and where the participants got exposed to TB, which could be at their native place, during traveling or at the monastery.
In our study no TB breakdown occurred during one year of follow-up; continued follow up for LTBI positive individual for longer period was not possible, since most of the monks return to their native place subsequent to completion of their education. Studies have reported reactivation in only small fraction (~ 5–15%), often within the first 2 to 5 years following infection [30, 31]. The understanding of the underlying reasons for LTBI reactivation is still incomplete, but it does include bacterial, host and environmental factors [32]. In a large population based prospective cohort study in UK, positive predictive values of IGRA and TST were only 3%-4% and the LTBI individual were followed up for 2.9 years (median) [33] in other wards only 3% and 4% of those with LTBI positive results progress to active TB. Various comorbidities and risk factors are associated with increased risk for reactivation and hence elevated rates of developing active TB; therefore, comorbidities and conditions associated with LTBI reactivation should be categorized as high, moderate, slightly increased, low and very low risk, depending on their associated risk factors [34] and should be treated with LTBI preventive therapy and followed up for TB outbreak.
In absence of documented evidence of BCG vaccination, the presence of a typical BCG scar was used as a substitute for written documentation of vaccination, which is quite common in many studies [35–38]. BCG scar marks were read in 49.4% (86/174), of which 46.5% were LTBI positive, in other word BCG has conferred protective immunity against Mycobacterium tuberculosis in 53.5% BCG vaccinated participants. The effectiveness of BCG against pulmonary TB are highly variable at 0–80% [39, 40]. The lower estimates of effectiveness are generally more common. Studies have reported BCG vaccination at birth protects children against disseminated and meningeal TB but is not so effective in preventing TB in adults [41–43]; in addition, there are reports of waning of BCG-induced immunity with age [44].