In:
Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 71, No. 8 ( 2020-11-05), p. 1883-1893
Abstract:
Bacille Calmette-Guérin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) have demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects. Methods This was a parallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2851 randomized, 2840 analyzed) vs BCG-Russia (2845 randomized, 2837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and purified protein derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3191 neonates randomized, 3184 analyzed) with BCG-Russia (3170 randomized, 3160 analyzed). Mortality and morbidity data were collected by telephone, at home visits, and at the National Hospital and assessed in Cox models providing 6-week mortality rate ratios (MRRs) and hospitalization incidence rate ratios (IRRs). Results By age 6 weeks, there were 140 and 130 admissions among neonates vaccinated with BCG-Denmark and BCG-Russia, respectively (IRR, 1.08 [95% confidence interval {CI}, .84–1.37]). For BCG-Japan, there were 185 admissions vs 161 admissions for BCG-Russia (IRR, 1.15 [95% CI, .93–1.43] ). The 6-week mortality did not differ: BCG-Denmark/BCG-Russia (MRR, 1.15 [95% CI, .74–1.80]); BCG-Japan/BCG-Russia (MRR, 0.71 [95% CI, .43–1.19] ). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia. Conclusions BCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study. Clinical Trials Registration NCT02447536.
Type of Medium:
Online Resource
ISSN:
1058-4838
,
1537-6591
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2002229-3
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