Surveillance of tuberculosis and treatment outcomes following screening and therapy interventions among marriage-migrants and labor-migrants from high TB endemic countries in Taiwan

Introduction

Taiwan, with a population of approximately 23.4 million, is a country with moderate TB incidence ranged 46–53 per 100,000 population in 2012–2015 (Taiwan Centers for Disease Control, 2018) and has gradually decreased over time. Nevertheless, TB disproportionately affects the foreign-born population from TB high-risk countries, with an incidence in this population that is several times higher than that among the Taiwanese-born population (Global Tuberculosis Report, 2018; The World Bank, 2018; Taiwan Centers for Disease Control, 2018). The reasons for the TB burden in the migrant population are likely to be the reactivation of remotely acquired LTBI following migration from high TB burden countries to lower TB burden countries (Global Tuberculosis Report, 2018; The World Bank, 2018; Taiwan Centers for Disease Control, 2018). TB control measures for the foreign-born population from high endemic countries in Taiwan occur within the scopes of the TB medical surveillance program. All newly arriving residents and temporary residents with high risk undergo an immigration medical examination before arrival. This examination consists of a physical examination which includes chest X-ray (CXR), syphilis test, HIV serology and other routine tests. If there is a radiographic evidence of TB, three sputum smears and mycobacterial cultures are examined (Taiwan Centers for Disease Control, 2018). Following the pre-entry screening, mandatory TB screening of either four rounds during the first 3 years (Kuan, 2018) or 1–2 rounds during the first 4 years (Kuan, Yang & Wu, 2014) are required post-entry for labor migrants or marriage migrants, respectively, who come from Southeast Asian (including Indonesia, Vietnam, Philippines, and Thailand) or China. Applicants with active TB are required to complete treatment before entering Taiwan. Before 2013, migrant workers with TB were repatriated; since 2014, these individuals are allowed to stay in Taiwan for treatment except multiple drug-resistant TB (MDR-TB) patients. A study showed that TB case with smear-positive sputum was more infectious than those with smear-negative sputum (Kuan, 2018). Our previous studies revealed that a 30.2% (Kuan, Yang & Wu, 2014) and 14.3% (Kuan, 2018) smear-positive sputum among marriage migrants vs. labor migrants in Taiwan. In term of TB control targeting high TB incidence migrants, it should be taken into consideration along with screening the differences in pathogen exposure due to their origins, the ethnic socio-economic disparities and the experience of migration itself (Hayward et al., 2018); moreover, to overcome the cultural and structural barriers to accessing healthcare (Hayward et al., 2018) is also critical. Thus, a friendly TB therapy policy may prompt access to treatment for a migrant in the new residing country. This study retrospectively analyzed a cohort from 2012–2015 aimed to analyze the impact on TB incidence and clinical characteristics following the enhanced screening interventions among these high-risk migrants. Also, the treatment outcomes following the concurrent TB intervention programs as well as the effectiveness of introducing a friendly TB therapy policy in 2014 targeting labor migrants was assessed.

Materials and Methods

Results

Discussion

Multiple initial screenings with CXR could identify more SS− TB cases at an early stage with low infectivity and result in a higher incidence. For migrants who come from high TB burden regions, a pre-entry initial screening with a CXR is required and follow by mandatory 1–2 rounds of post-entry screening for marriage migrants or four rounds for labor migrants in Taiwan, respectively. This initiative resulted in a higher incidence with more SS− TB among labor migrants and a lower incidence but more SS+ TB or more CXR cavitation TB cases among marriage-migrants (Tables 1 and 2). Moreover, the higher annual TB incidence rates in labor migrants were significantly (R²: 0.55, P <0.0001) associated with the WHO estimated TB incidence rates (Taiwan Centers for Disease Control, 2018) of their original countries and there were significantly fewer severe cases, that is, fewer SS+ TB cases or fewer CXR cavitation TB cases, among the labor migrants. On the other hand, relatively lower annual TB incidence rates among marriage migrants were less significantly associated with the WHO-estimated TB incidence rates (Taiwan Centers for Disease Control, 2018) of their original countries (R² = 0.42, P = 0.0125), and there were significantly more severe cases, that is, more SS+ TB cases (OR: 4.82), or more CXR abnormal with cavitation TB (OR: 2.90) (Table 2). Thus, these results indicated that the greater number (four rounds) of mandatory post-entry screenings for labor migrants vs. the 1–2 rounds for marriage migrants could screen out more TB cases; although the incidence rate appeared higher, but more cases had early-stage disease with SS− TB. Also, these results corroborate previous findings that multiple TB screenings in individuals with initial abnormal CXRs result in the detection and identification of more SS− TB cases at an early disease stage (Kuan, 2018), which might benefit for timely therapy initiation; thus, might increase the success of treatment and reduce disease burden including blocking the potential disease dissemination. However, the high proportion of bacteriological negativity that is, of >35% with B- TB in both groups, for example, 56.4% in labor migrants vs. 39.2% in marriage migrants (Table 1), has suggested the multiple TB screenings might be of over-detection (Kuehne et al., 2018; Aldridge et al., 2016). While the reasons for the high TB burden in the migrant population are likely to be the reactivation of remotely acquired LTBI following migration from high TB burden countries to lower TB burden countries (Global Tuberculosis Report, 2018; The World Bank, 2018; Taiwan Centers for Disease Control, 2018). Therefore, it is important that applying a LTBI screening combined with prevention treatment (PT) at a pre- or post- entry in the very beginning will save a lot of efforts in later stages, for example, multiple screenings (The New York Times Editorial Board, 2018) and might meet the core of an earlier TB mitigation strategy for TB control intervention targeting at high-risk migrants even including BCG-vaccinated individuals (Olivieri et al., 2016); for example, a 2-step LTBI screening: performing an expensive interferon-gamma release assay (IGRA) after positivity on the economical tuberculin skin test (TST), then combined with PT (Olivieri et al., 2016). Thus, antibiotics can effectively and economically eliminate tuberculosis, before they become contagious, that is, to treat individuals who are still invisibly sick. In several countries, such as the United States, Britain, and Canada, LTBI screenings combined with PT strategies have long since become public health norms for migrants (The New York Times Editorial Board, 2018).

The repatriated labor migrants with TB were not traced in this study if they received any treatment when they returned home country. Nonetheless, both marriage migrants and labor migrants with TB who stayed in Taiwan and accepted either the standard (6–9 months) or longer regimen of TB therapy achieved a TB treatment completion rate of 87–99% (Table 1), which was above the WHO target of >85% (WHO, 2006–2015) during 2012–2015. In terms of assessing the overall treatment outcome of TB cases, it was found that cases identified among labor migrants significantly had poorer treatment completion than those among marriage-migrants in Taiwan because of a higher percentage of transferred out cases in 2012–2015 (Table 1). The treatment completion rate in Taiwan was high in marriage migrants (96–99%; Table 1). As for labor migrants, after the implementation of the therapy policy which eliminated repatriation of TB cases and allowed for therapy in the host country, the completion rates raised to 24–37% from 3.8–9.7% (Tables 1 and 3) after the implementation of the therapy policy during 2012–2015.

Overall, the improvement of an increased 4.88-fold that is, 30.9% in 2014–2015 vs. 6.7% in 2012–2013 of the TB treatment completion among labor migrants during periods post-implementation (2014–2015). It was further observed that TB cases with more SS− (OR: 7.45) or B− 44(OR: 1.48) and more SS+ (OR: 13.43) or B+ (OR: 5.83) was treatment completed since 2014 (Table 3) among labor-migrants, which demonstrates the benefit of implementing the friendly therapy policy. Also, the reducing potential structural barriers to TB treatment completion (Kourbatova et al., 2006; Datiko & Lindtjorn, 2010; Lambert et al., 2003), limited access to care (Kourbatova et al., 2006), and relocations of labor-migrants were conducted by introducing the therapy policy since 2014. Moreover, after 2014, a significant decline in transfer out TB cases was observed in both of SS- TB cases (OR: 0.61) or B− TB cases (OR: 0.58) and SS+TB cases (OR: 0.44) or B+ TB cases (OR: 0.66) among labor migrants during this study period (Table 3).

Additionally, because the higher number of SS− or B− TB cases among labor migrants than among marriage migrants was also worried as a potential risk of being delayed or untreated and then, in turn, developing TB dissemination. Since very few bacilli are sufficient to cause infection (Sepkowitz, 1996; Scandurra et al., 2020), therapy should not be delayed in labor-migrants with SS− TB according to the WHO guidelines, especially those who were to provide long-term care for vulnerable people or the elderly; therefore, the initiation rate of anti-TB treatment within 30 days of diagnosis was concerned. After introducing the friendly therapy policy, the overall treatment initiation rate within 30 days of diagnosis was significantly increasing (OR: 1.31) among labor migrants. Furthermore, the overall initiation rate of treatment exhibited higher among labor migrants with SS+ TB (93.0%) or B+ TB (83.9%) than those with SS− TB (70.9%) or B− TB (77.4%) and implicated that relatively more TB cases with SS− or B− had somehow delayed treatment than those with SS+ or B+. Nevertheless, after introducing the therapy policy for labor migrants, showed a significant increase in the initiation rate of treatment both for SS− TB of 77% vs. 71% (OR: 1.38) or B− TB of 78% vs. 77% (OR:1.64) during the post vs. pre-implementation of the policy. Relatively, this implementation was not significantly impacted the treatment initiation rate among labor immigrants with SS+ TB of between 91–89% (OR: 0.63) or B+ (OR: 0.84) (Table 3). Thus, the friendly therapy policy in Taiwan has resulted in an improved experience of reducing structural barriers to TB mitigation since its implementation in 2014, which has successfully promoted the anti-TB treatment outcomes including improvement in treatment initiation especially those who with S− TB or B− TB and increasing treatment completion for those migrants with TB stayed in Taiwan. Therefore, based on our observations, there is a need for intensifying health education that promotes TB therapy includes delivering the information of the ongoing availability of free, accessible health services for vulnerable groups such as high-risk migrants; this health education could also be a critical element in increasing treatment success (Hayward et al., 2018; Scandurra et al., 2020; Dangisso, Datiko & Lindtjørn, 2015) and early therapy for individuals with TB in receiving countries.

Conclusions

Multiple screenings following an initial abnormal CXR in migrants could detect early-stage TB cases; nevertheless, an improved therapy completion is a substantial step for TB elimination. The relatively higher odds of SS+ TB and bacterial negativity >35% among migrants might be an index of persistent TB reactivation or over-diagnosis; therefore, it is recommended that adding LTBI screening combined with preventive treatment as an alternative approach might save multiple screening effort for high-risk migrants. The friendly treatment policy for migrants, which eliminated repatriation for labor migrants with TB, could benefit in anti-TB treatment outcomes include increasing therapy initiation in SS− or B− TB cases and treatment completion for those who stayed in receiving countries.

Supplemental Information