(2018). Does BCG Vaccination Protect Against Nontuberculous Mycobacterial Infection? A Systematic Review and Meta-Analysis. Journal of Infectious Diseases

Summary: The incidence of non-tuberculous mycobacterial (NTM) infections is increasing worldwide. Our systematic review and meta-analysis suggest that BCG vaccination has a protective effect against NTM lymphadenitis and Buruli ulcer. This has important implications, in particular when deciding on recommendations for discontinuation of universal BCG vaccination programmes. Abstract The incidence of non-tuberculous mycobacterial (NTM) infections is increasing worldwide, particularly NTM lymphadenitis and skin infections (Buruli ulcer). This review summarises the evidence for the protective effectiveness of Bacillus Calmette–Guérin (BCG) vaccination against NTM disease. A systematic search using PRISMA guidelines was done for controlled studies investigating the protective effectiveness of BCG vaccination against NTM disease in immunocompetent individuals. This revealed ten studies, including almost 12 million participants. Three cohort studies in industrialised countries suggest that the incidence of NTM lymphadenitis is greatly reduced among BCG-vaccinated children compared to BCG-unvaccinated children, with a risk ratio (RR) of 0.04 (95% confidence interval (CI) 0.01 to 0.21). In two randomised trials in low-income countries, BCG protected against Buruli ulcer for the first 12 months following vaccination, RR 0.50 (95% CI 0.37 to 0.69). Four case control studies had conflicting results. One cohort study found that individuals with Buruli ulcer are less likely to develop osteomyelitis if they have a BCG scar, RR 0.36 (95% CI 0.22 to 0.58). No studies have compared different BCG vaccine strains or the effect of revaccination in this setting. The protective effect of BCG vaccination against NTM should be taken into consideration when deciding on recommendations for discontinuation of universal BCG vaccination programs and in assessing new vaccines designed to replace BCG. Three studies from industrialised countries, all population-based cohort studies, compared the incidence of NTM lymphadenitis in a total of 9,888,719 BCG-vaccinated children with 1,960,572 non-BCG vaccinated children. Of these children, 445 were diagnosed with NTM disease. All three studies reported a greatly reduced incidence of NTM lymphadenitis in BCG-vaccinated compared to BCG-unvaccinated children: the overall risk ratio (RR) was 0.04 (95% confidence interval (CI) 0.01 to 0.21) (table 1 and figure 1). The number needed to treat (NNT) calculated from the three cohort studies was 4835 (95% CI 4403 to 5362). Six studies investigated the protective effectiveness of BCG vaccination against Buruli ulcer, comparing the incidence in 6,475 BCG-vaccinated adults and children with 13,612 BCG-unvaccinated adults and children. The strongest evidence comes from two randomised controlled trials (RCT) done in Uganda (table 2a and figure 2a). These reported a considerably lower incidence of Buruli ulcer in BCG-vaccinated participants compared to BCG-unvaccinated with a RR of 0.50 (95% CI 0.37 to 0.69). The number needed to treat (NNT) calculated from the three cohort studies was 4835 (95% CI 4403 to 5362). The number needed to treat (NNT) calculated from the three cohort studies was 4835 (95% CI 4403 to 5362). Protection following BCG vaccination was higher in low-incidence than in high-incidence settings (74% vs 18%, p=0.03) [19] and was only short-term (within the first year after vaccination), with an overall reduction of Buruli ulcer of 47% (p=0.007, p<0.01). [19, 20] In one of these studies, BCG-vaccinated individuals had smaller skin lesions compared with unvaccinated individuals [20].