Indonesia is a TB endemic country and the BCG vaccine has been prioritized to prevent TB disease. It is mandatory according to the National Program given to newborn babies up to 12 weeks, however, only 86.6% newborn babies came for BCG vaccination in our study. Despite the home visit from the cadre or health employee of the primary health care, some mothers refused to take the baby for routine vaccination. Furthermore, the older mothers were significantly more likely to attend the primary health care for BCG vaccination compared to the younger age (p < 0.034). In addition, a study in Malaysia has shown that several factors may play a role, including the assumption that vaccines have no effect, doubts about its contents, religious influence, and personal belief.[9] Therefore, education and awareness programs for pregnant women during their antenatal care need to be strengthened. Furthermore, the basic education of mothers and the birthplace have no significant associations with the willingness to allow vaccination for their children. The reason why mothers refuse vaccination for their babies needs further exploration.
As Indonesia ranks second in the global TB prevalence list, a national TB emergency is required, therefore, an active TB case detection program plays an important role.[10] This study has shown that active TB cases (2.3%) were identified and not all the individuals were on TB therapy (Table 3). Furthermore, TB is a chronic disease with clinical symptoms, which include coughing for over 3 weeks. Also, the health-promoting behaviour of people with chronic cough appears to be a burden. Some of the reasons include stigma in the community, lack of awareness, and knowledge of TB.[11] Moreover, there is a spectrum of TB infection, ranging from latent to active TB. Individuals who are able to contain MTB infection are known as latent TB and may also harbour a low-grade, subclinical infection. These individuals are at a higher risk of reactivation.[12] The reason behind infected individuals who do not visit health care providers need further clarification.
This study explored latent TB infection among newborns and family members living in the same house in an overcrowded area. Various studies have explored the usefulness of IGRA for the diagnosis of LTBI.[13 This study, particularly showed that family members living with active TB have 2.69 times higher chance of positive IGRA (95% CI 1.22–5.94) compared to those without (Table 4). In addition, it is well known that the chance of being infected with MTB among individuals living in the same house is higher.[1] Also, positive IGRA among individuals who do not live in the same house with TB patients indicates that the infection is transmitted outside the house as well. The isolation of TB patients in a sanatorium or other institution in Indonesia is not possible, however, greater measures are required to reduce MTB transmission.
Furthermore, this study revealed that male has a higher chance of having positive IGRA compared to female (OR 1.68; CI95% 1.07–2.64) (Table 4). This is due to their frequent outdoor activities and contact with others. Interestingly, male is more susceptible to TB disease as shown in a previous genetic study in Indonesia.[14] The variation in Toll Like Receptor TLR8 gene, located in chromosome X, has been related to the susceptibility to TB.[14] This finding suggests the role of host genetic factor in immune response differences. Moreover, since only half of the family members showed IGRA positivity, the immune response may play a role in the development of TB infection.[12].
Children under 5 years old, especially those who live with active TB family members have a relatively higher risk to develop active TB. This depends on various factors, such as the proximity of contact with the index case, the MTB virulence, the environmental conditions of the house, which include solar radiation and air circulation as well as several other factors.[5] It is therefore important to detect LTBI cases and treat them early. Previously, TST was used to screen TB in adolescents, who have contact with TB patients.[15] However, a study has shown that IGRA is quite sensitive in children younger than 15 years old. Interestingly, the IGRA sensitivity is reduced compared to TST in children younger than 2 years old.[16] Furthermore, IGRA seems to offer alternative LTBI detection, especially babies living with TB parents.[17] This study has shown that the newborns were still negative for IGRA 12 weeks after BCG vaccination, suggesting that BCG may stimulate immune response and play a protective role against TB disease.[18]
Most importantly, the study traced active TB individuals with no treatment, therefore, an active case finding is needed in all family members living in the same house and using proper diagnostic tools for possible LTBI, followed by preventive therapy. Furthermore, education was given to the family members and active TB individuals who were also assigned for TB therapy. LTBI treatment requires a long period of therapy, for example, Isoniazid (INH) needs to be given for 6 or 9 months.[5] Interestingly, the population in Indonesia are predominantly intermediate acetylators.[19] Therefore, drug induced liver intoxication should be considered when giving positive IGRA individuals a long period of INH[20] and adherence as well as compliance, need to be well monitored. In addition, good education and awareness from the health care provider are required to ensure that positive IGRA individuals adhere to LTBI treatment for at least 6 months. This study further shows that 32.6% of the respondents are LTBI as indicted by IGRA positivity, compared to Singapore that detects LTBI for 12.7%.[21] This gives valuable information to the authority to set up preventive therapy for INH.
This study encountered several limitations, including the temporary address of some mothers, which was untraceable after delivery of the baby, as a result, some are lost to follow-up care. This issue needs to be raised to the authority to improve the population registration system. Also, education and awareness about TB and immunization need to be properly given, to ensure that they have their babies vaccinated. Furthermore, a longer cohort study will provide more information on how the IGRA positivity in babies develops after exposure to active TB individuals. The data of TB exposed babies and family members as well as others with IGRA positivity were given to the local health care providers for INH preventive therapy. Finally, good monitoring on this program requires the commitment of stakeholders.