Bacille Calmette-Guérin policy change and childhood mycobacterial infections in Finland

The World Health Organization declared tuberculosis (TB) a global emergency over 25 years ago, yet TB remains a significant public health concern and a leading infectious killer of our time. Young children are especially vulnerable to rapid and debilitating TB disease, and infected children should be identified and therapy initiated rapidly. Nontuberculous mycobacteria (NTM) infections have also emerged in Western countries. Childhood NTM infections predominantly manifest as prolonged cervical lymphadenitis, which is a diagnostic challenge for the clinician due to the limitations of NTM cultures. Bacille Calmette-Guérin (BCG) vaccine effectively prevents severe TB disease forms in young children. Some studies have further suggested that BCG might also offer protection against childhood NTM infections. In Finland, BCG coverage of infants was very high until the vaccination policy changed in 2006 to a risk group-based approach. Subsequently, for the first time since the 1940s, a generation of children has grown in Finland without the protection of BCG against mycobacterial diseases. Furthermore, the healthcare and national surveillance registries allowing retrospective evaluation of TB and NTM cases in Finland are exceptional and provide a rare look into paediatric TB and NTM epidemiology with or without universal BCG vaccinations. In addition, a novel in-house diagnostic test developed in the Hospital District of Helsinki and Uusimaa (HUS) laboratory has shown potential in childhood NTM lymphadenitis diagnostics but has not been evaluated. In the first study, we evaluated the performance of the novel modified T.SPOT.TB test in children under five years of age with culture-confirmed NTM lymphadenitis and compared the results to a control group of healthy children. The estimated sensitivity and specificity of the modified T-SPOT.TB test were 1.00 and 0.81, respectively. The modified T.SPOT. TB was a promising noninvasive diagnostic test for childhood NTM lymphadenitis. In the second study, we identified native-born children aged 0–4 years infected with NTM between 1995 and 2016 from the Finnish National Infectious Diseases Register (NIDR) and estimated the NTM incidence rate change between birth cohorts born during universal or selective BCG vaccination policy. We identified 97 native-born children infected with NTM under the age of five. The estimated incidence rates of NTM in universal-BCG and selective-BCG cohorts were 0.2 and 3.9 per 100,000 person-years, respectively. The incidence rate ratio (IRR) of selective-BCG cohorts compared to universal-BCG cohorts was 19.03 (95% confidence interval [CI], 8.82–41.07). Childhood NTM infections increased drastically after the infant BCG coverage decreased, suggesting that BCG offers protection against childhood NTM lymphadenitis. In the third study, we identified all newly diagnosed active TB cases under 15 years of age in Finland 1995–2015 by linking data from the NIDR, Finnish Care Register for Health Care, medical patient records, and Finnish Population Information System. We compared the under-five TB incidence rate ratio of birth cohorts with universal and selective BCG vaccinations. We identified a total of 139 paediatric TB cases. The under-five TB rate of birth cohorts with selective-BCG compared to birth cohorts with universal-BCG remained stable (IRR 1.3; 95% CI, 0.7–2.3). Paediatric TB in Finland was concentrated in families with an immigrant background from high TB incidence countries. The native under-five TB morbidity did not increase after the BCG vaccination policy change in Finland, suggesting that well-implemented selective vaccinations can prevent TB in the most vulnerable age group effectively in low-incidence settings. In the fourth study, we retrospectively reviewed paediatric TB contact tracing results from 2012 to 2016 in the HUS area. The yield for TB disease or infection was 4.6% and 12.8% for household contacts, 0.5% and 0% for contacts exposed in a congregate setting, and 1.4% and 5.0% for other contacts, respectively. Contact tracing in the HUS area identified exposed young children quickly: most of the TB infections among the children under five years of age were found before progression to disease, and none had severe disease forms. The maximum delay until the first contact investigation visit among the household contacts under five years of age with either TB disease or infection was seven days from the index case diagnosis. Contacts born in a TB endemic country (adjusted odds ratio [aOR] 3.07; 95% CI, 1.10–8.57), with household exposure (aOR 2.96; 95% CI, 1.33–6.58), or a sputum smear-positive index case (aOR 3.96; 95% CI, 1.20–13.03) were more likely to have TB disease or infection. The yield for TB disease or infection of large-scale investigations after exposure in a congregate setting was very low, and investigations in such events should be cautiously targeted. In summary, the epidemiological landscape of childhood mycobacterial infections in Finland has changed. The BCG vaccination policy change in 2006 resulted in an increase in childhood NTM infections, but childhood TB infections did not increase, and restarting universal BCG vaccinations seems unwarranted. Childhood TB, however, remains an essential public health issue, and future surveillance is vital. The focus of childhood TB prevention in Finland should be further targeted to those with an immigrant background from high TB burden countries.