Prevalence of latent tuberculosis among refugee children in Malaysia

Discussion

The increasing transmission and incidence of tuberculosis has often been associated with refugee communities. As they flee their countries of birth to escape war, violence and persecution, they encounter all forms of stress from lack of basic needs for living to psychosocial distress, predisposing them to immune deficiency; thus, they are more prone to infectious disease [14]. For example, when millions of Syrians had to seek refuge in the neighbouring countries due to war, a notable increase in tuberculosis and LTBI cases was reported in countries bordering Syria, where extensive dissemination of tuberculosis was found among refugee population and local [15].

In this study, we detected that nearly one (12.8%) in every eight refugee children in learning centres in Malaysia had LTBI. None of the children were diagnosed with active tuberculosis. The prevalence of LTBI found in this study was higher than in two studies that both reported a figure of only 6% LTBI prevalence among refugee children arriving at Germany and the USA [16, 17]. In addition to refugee children, one of the studies also included immigrants in the screening process for tuberculosis and LTBI, yielding an overall number of 67 334 children being examined with 12% prevalence of LTBI in total [17]. The prevalence of LTBI was found to be higher among older individuals, which is expected given the longer time period and potential for exposure to individuals having tuberculosis [5, 18, 19]. Our study also did not find any significant differences in LTBI prevalence between sexes, as noted in other high-risk populations, and in concordance with the study by Taylor et al. [17] showing an identical percentage of males and females with LTBI. Studies involving children with LTBI found a higher proportion of males diagnosed with LTBI in China and Peru; those authors hypothesised that males could have spent more time socialising and interacting where the risk originated [18–20]. Our findings also suggest that children vaccinated with BCG have a 33% lower likelihood of developing LTBI (OR 0.67, 95% CI 0.37–1.21; p=0.18), albeit being nonsignificant. A study that investigated the effectiveness of BCG vaccination against LTBI indicated a lower prevalence of LTBI in BCG-vaccinated adult contacts of tuberculosis screened using IGRA. The vaccine effectiveness was reported to be 30% [21]. These results could be an indication of protective effect of BCG vaccination against LTBI. Similarly, our findings suggest that there was an association between LTBI and country of birth with high tuberculosis burden. Taken together, our study provides strong support for the policy of screening all refugee children regardless of age and country of birth. Since this is the first initiative to screen refugee children for tuberculosis and LTBI in Malaysia, the high prevalence of LTBI in the small communities of refugee participants from our study could serve as an alarm and pointer to expand the screening process for more extensive coverage of the tuberculosis preventive programme through policy improvement.

As Malaysia is not a signatory to the 1951 UN Refugee Convention, it only serves as a transitional place for refugees while they are waiting to be resettled in another country. As such, no refugee camps exist in Malaysia, with refugees having to live with the local communities. However, the refugees often face discrimination as they have limited access to subsidised health service, education and employment. The majority of these refugees live in urban settings, having to bear with overcrowded conditions without basic provision of water and sanitation as well as scarcity of food, increasing the risk of tuberculosis infection, tuberculosis reactivation and disease transmission [22, 23]. Additionally, the current national tuberculosis policy in Malaysia primarily focuses on active tuberculosis case finding; hence, LTBI is not clinically diagnosed and treated, which could be a challenge for diagnosis and treatment of LTBI to be practised among healthcare providers, not only when screening refugees, but also local [23]. Nevertheless, the findings obtained from this study can be useful evidence to prompt consideration for management of LTBI to be implemented as complementary care on top of tuberculosis for local and refugee children.

Children are particularly vulnerable to developing more severe manifestations of tuberculous diseases; therefore, those diagnosed with LTBI should be treated [24, 25]. They are potential medium of infective disease transmission as they have weaker immune systems, constant active tuberculosis contact and long times spent in high tuberculosis burden regions that could contribute to the activation of the bacteria to infective tuberculosis anytime in their life [24]. Hence, tuberculosis will be continuously progressive unless treatment can be initiated promptly for LTBI upon diagnosis before it becomes infective and causes casualties [7]. Unfortunately, tuberculosis preventive therapy is underimplemented in many high-burden countries, including Malaysia, and only 13% of children eligible for preventive therapy received treatment in 2016 [26]. A more concerted effort to target children and adolescents with LTBI is needed, in supporting the WHO's End TB Strategy to eliminate the global tuberculosis epidemic by 2035. This could include mandatory screening of all children and adolescents in countries with high tuberculosis burden and offering preventive therapy. This will ultimately help to eliminate tuberculosis seedbeds for future cases of active tuberculosis.

This study has some important limitations that warrant further discussion. Firstly, the study was limited by its sample size, which may limit the precision in determining the prevalence in the cohort of refugees as well as factors related to LTBI positivity. Secondly, the comparability between both tests was not assessed. The TST, while an easily available and relatively low-cost test, has a high false-positive rate even among those who may not be infected with M. tuberculosis, due to cross reactivity of infection with nontuberculosis mycobacteria as well as previous BCG vaccination [27, 28]. In addition, the TST requires the participant to return for a follow-up between 48 and 72 h later, and in this study, ∼1.4% had defaulted on their appointment. Finally, we relied on patient self-reported history, as accurate medical records were often unavailable among the cohort of refugees.

Despite the breadth of evidence available, most of the current policy worldwide, including in Malaysia, focuses only on the detection and screening of active tuberculosis. Nevertheless, case-finding and treatment approaches alone would be insufficient. Prioritising LTBI management requires integrated effort from the public health division together with political will for implementable strategies to be formulated in order to control the risk of tuberculosis infection in line with the End TB Strategy [29]. Evidence of the effectiveness of preventive therapy is available, and this study provides further support for a programmatic screening and treatment of LTBI to support a comprehensive and epidemiologically sound strategy for tuberculosis elimination.