Editorial Commentary: Different Strains of Bacillus Calmette–Guérin Vaccine Have Very Different Effects on Tuberculosis and on Unrelated Infections

Bacillus Calmette–Guérin (BCG) vaccine provides good protection against disseminated mycobacterial diseases such as miliary tuberculosis, tuberculous meningitis, and leprosy [1, 2] but weaker protection against pulmonary tuberculosis, especially in rural areas near the equator [3]. In high-mortality countries, until a different vaccine is given, BCG vaccine also provides nonspecific (heterologous) protection against diseases other than tuberculosis and leprosy (mainly respiratory infections and sepsis) [4]. In randomized trials in Guinea-Bissau, vaccination with BCG–Danish vaccine reduced neonatal mortality in low-birthweight babies by 48% (95% confidence interval [CI], 18%–67%) [5, 6], and revaccination reduced all-cause mortality by 64% (95% CI, 1%–87%) in children aged 19 months who had received a booster dose of diphtheria–tetanus–pertussis vaccine [7]. BCG vaccine may also have important nonspecific effects in high-income countries. In a cohort study in Spain, BCG–Danish vaccine reduced nontuberculous hospital admissions in infants by 32% (95% CI, 31%–34%) for respiratory infections and by 53% (95% CI, 44%–61%) for sepsis [8]. In this issue of Clinical Infectious Diseases, Storgaard and colleagues report the results of a study based on a remarkable surveillance system that has prospectively monitored a representative sample of rural Guinea-Bissau since 1990. This is an extraordinary database. The study found a scar in only 52% of children given BCG–Moscow vaccine, the same rate as BCG–Moscow vaccine in Uganda [9] but much lower than the 72%–97% scar rate after BCG–Danish vaccine was given in urban Guinea-Bissau [10–13]. The low scar rate in rural Guinea-Bissau may be due to the fact that the BCG– Moscow vaccine is less likely to produce a scar than the BCG–Danish vaccine (as suggested by the similar result in Uganda), but it may also be due to disruption of the cold chain in rural areas or poor vaccination techniques. An important finding in the study in rural Guinea-Bissau was that among infants who had received BCG–Moscow vaccine, those with a scar had a 52% (95% CI, 10%–74%) lower mortality rate than those with no scar. The authors present evidence that the lower mortality was unlikely to be explained by healthier children being more likely to form a scar, and the results are consistent with previous studies showing a relationship between BCG–Danish vaccine scar and survival [10–13]. Clearly, it would be desirable to test whether revaccination with BCG vaccine reduces all-cause mortality in children who do not develop a scar after a single dose. In addition, in the randomized trial in Guinea-Bissau that showed reduced mortality after revaccination at age 19 months, 77% of the children had a scar [7]. Consequently, further randomized trials are needed to test the effects of revaccination on all-cause mortality in children who have a scar following BCG vaccination at birth, as well as those without a scar. Revaccination with BCG vaccine confers little or no extra protection against tuberculosis but it may improve protection against leprosy and increase the beneficial nonspecific effects of BCG vaccine [14]. Although thepresence of aBCGvaccine scar is associated with reduced mortality from diseases other than tuberculosis, it Received 29 May 2015; accepted 1 June 2015; electronically published 9 June 2015. Correspondence: Frank Shann, DMedSc, FRACP, Intensive Care Unit, Royal Children’s Hospital, Department of Paediatrics, University of Melbourne, Parkville 3052, Australia ([email protected]). Clinical Infectious Diseases 2015;61(6):960–2 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of thework, in anymedium, provided theoriginalwork is not altered or transformed in anyway, and that thework is properly cited. For commercial re-use, please contact journals.permissions@oup. com. DOI: 10.1093/cid/civ454