Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage.

OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1 148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > or = 5 mm, > or = 10 mm, and > or = 15 mm) and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > or = 15 mm). We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > or = 10 mm was 14.2% (95% confidence interval (CI) = 8.0%-20.3%) for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1%) for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0%) for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > or = 5 mm and > or = 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > or = 5 mm and > or = 10 mm did not vary with age. There was no evidence for BCG effect on the results > or = 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to estimate M. tuberculosis prevalence or to assess transmission patterns as well as in tuberculin skin testing of individuals used as an auxiliary tool in diagnosing tuberculosis. Taking this information into consideration is especially important when there is increasing BCG revaccination coverage.     

The association between parental and neonatal BCG vaccination and neonatal T helper 17 cell expansion

BackgroundBacille Calmette-Guérin (BCG) vaccination reduces the severity of neonatal infections; this effect appears enhanced if the mother has received BCG. We performed immunophenotyping of the T-cell subset and characterized T-cell proliferation responses to assess possible immune response pathways.MethodsHealthy BCG-vaccinated (n = 8) and unvaccinated (n = 9) neonates born by elective caesarean section were sampled 3 weeks after birth. We compared a wide panel of intracellular cytokine and cell surface expression markers as well as proliferation response in T-cells between BCG-vaccinated and unvaccinated neonates, stratified by parental BCG status.ResultsFor all BCG-vaccinated neonates and 3 of 9 unvaccinated neonates that served as controls, both parents had a BCG scar. Th17 (CD4 + IL-17+) prevalence as percentage of total CD4 + T-cells was expanded 4-fold in BCG-vaccinated compared to unvaccinated, being 11.6% [3.6–19.6%] vs 2.8% [1.0–6.6%]. Th17 counts for 3 unvaccinated neonates born to BCG-vaccinated parents was comparable to vaccinated neonates, and higher than remaining controls, parental BCG = 8.5% [4.4–8.9%] vs 1.8% [0.8–3.3%] for no parental BCG (median [interquartile range] for all data).ConclusionAmong neonates born to BCG-vaccinated parents, the prevalence of Th17 cells, important in the response against bacterial infections, was substantially elevated. The interaction between neonatal and parental BCG for Th17 responses and the importance remains to be further investigated.     

Delivering a selective neonatal BCG vaccination programme in a multi-ethnic community: an audit of the neonatal BCG immunisation programme in Birmingham and Solihull

Neonatal bacillus Calmette-Guérin (BCG) immunisation is a primary preventive measure against tuberculosis. Local health professionals expressed concern about the variability of knowledge regarding eligible infants and uptake of the vaccine. A questionnaire was sent out to health visitors for use at the routine visit to babies. Details requested included ethnic group and country of origin of the infant, eligibility for BCG vaccination, and vaccination status. BCG vaccination was indicated for 41% of newborns. In total 74% of these eligible infants received the vaccine with a range of 36-83% between the five maternity units. There were inconsistencies within maternity units in identifying high-risk groups by ethnicity and country of origin, resulting in low coverage in certain eligible groups. Confusion exists about which infants are at risk of tuberculosis and should be vaccinated. Current national guidelines are not specific enough for cases of interracial parenting and for the increasingly diverse countries of origin of the population. In the absence of clearer national guidelines there is a need for pragmatic local guidance.     

不同等级2所医院新生儿卡介苗接种效果及影响因素研究

目的了解常州市不同等级的2所医院新生儿卡介苗接种效果及其影响因素,为提高接种质量和人群免疫水平提供依据.方法 选择1个市级医院,1个县级医院作为哨点,监测2013年1~12月不同批次菌苗对符合条件新生儿的接种情况,3个月后进行结核菌素试验试验(PPD),观察硬结纵横径和直径,评价接种效果;采用Logistic回归模型,对接种效果进行多因素回归分析. 结果共接种卡介苗新生儿2254例,接种成功2090人,接种成功率92.7%.单因素分析显示,不同单位,季节,疫苗批次卡介苗接种成功率差异有统计学意义(P<0.05);金坛市人民医院接种成功率为95.15%,明显大于市妇幼保健院90.17%,差异有统计学意义(P < 0.05); 经组间比较,秋季接种成功率明显高于冬季(χ²=14.080, P = 0.000).疫苗批号201003a015-1接种成功率明显低于其他各批号,批号201003a012-2接种成功率明显低于批号201101a004-1和201012a083-2,差异均有统计学意义(均P = 0.000).多因素logistic回归分析,疫苗批号(OR=1.754,95%CI:1.477~2.084)是卡介苗接种成功的影响因素. 结论常州市市县不同等级医院新生儿卡介苗接种成功率均较高,疫苗不同批次是影响接种成功的影响因素.     

Comparison of tuberculin skin test response after three modalities of neonatal BCG vaccination

The aim of this study was to determine the tuberculin skin test (TST) response to three different BCG modalities [0.1 ml Tokyo (n=104), 0.05 ml Pasteur-Mérieux (n=137) and 0.1 ml Pasteur-Mérieux (n=100)] in a cohort of healthy newborns 5 months after vaccination at birth in Santiago, Chile. Among the 341 infants, 91.2% had a response to TST, and the mean+/-SD TST reaction size was significantly larger in infants receiving the Tokyo strain than in those receiving the 0.05 ml or 0.1 ml Pasteur-Mérieux strains (4.4+/-2.0, 3.5+/-1.3 and 3.1+/-1.4 mm, respectively; P<0.0001). The mean+/-SD of the BCG scar size was significantly lower in infants vaccinated with the Tokyo strain than in those vaccinated with the 0.1 ml Pasteur-Mérieux strain (3.9+/-1.2 vs. 4.3+/-1.1 mm; P=0.03) and no significant difference was found between infants receiving the Tokyo strain and the 0.05 ml Pasteur-Mérieux strain. However, the differences in TST size induced by diverse BCG vaccination modalities may not reflect the quality of the immunologically induced response in terms of TB protection.     

A case-control study to evaluate the effectiveness of mass neonatal BCG vaccination among Canadian Indians

This paper reports a case-control study to assess the protective effect of BCG (bacille Calmette-Guérin) vaccination among Indian infants in Manitoba, Canada. A record of past BCG vaccination was found in 49 per cent of the tuberculosis cases, compared to 77 per cent of the controls, yielding a relative risk of 0.30. Stratified analysis, controlling for age, increased the relative risk to 0.39 (95% confidence interval 0.22 - 0.69). The preventive fraction was 44 per cent. Non-differential misclassification of exposure status could have occurred; if this was adjusted for, the relative risk would be reduced. If only bacteriologically confirmed cases were analyzed, the age-adjusted relative risk was 0.27. The protective effect of BCG vaccination in the newborn among Manitoba Indians is therefore at least 60 per cent. The implications for health policy in this population are further discussed.     

新生儿接种卡介苗引发淋巴结强反应56例分析

目的总结56例卡介苗所致淋巴结强反应的临床表现,评价局部治疗效果。方法收集2010年1月-2014年5月结核病门诊56例由卡介苗所致淋巴结强反应患儿,根据其临床表现,分别给予热敷、清创引流及敷药等局部治疗,并分析疗效。结果 1)分型:结节未液化型7例,液化型20例,脓肿破溃型23型,术后伤口未愈者6例。2)疗效:7例未液化型经局部热敷,5例结节缩小,2例结节液化;22(20+2)例液化型经穿刺针吸及结节内注射异烟肼,均化脓破溃;45(23+22)例脓肿破溃型经清创引流,利福平外敷,伤口愈合;6例手术后伤口未愈者经清创引流、利福平外敷,伤口愈合。结论新生儿接种卡介苗所致淋巴结强反应临床表现多样,局部治疗效果好。     

Hepatitis B vaccine co-administration influences the heterologous effects of neonatal BCG vaccination in a sex-differential manner

IntroductionBacille Calmette-Guérin (BCG) and hepatitis B (HBV) vaccines are frequently given concomitantly at birth. Neonatal BCG vaccination induces off-target immunological effects. Whether HBV vaccine has immunomodulatory effects is unknown. As off-target effects might vary when vaccines are given simultaneously, this randomised controlled trial aimed to evaluate the influence of neonatal vaccination with BCG and/or HBV on heterologous immune responses.MethodsA total of 185 neonates in Australia were randomised to receive either neonatal BCG-Denmark vaccine, HBV vaccine, both (BCG + HBV group), or none (No vaccine group). In-vitro responses to heterologous stimulants were assessed 7 days after vaccination. The influence of (i) randomisation group and (ii) sex on interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), and tumour necrosis factor-alpha (TNF-α) responses was analysed using linear regression.ResultsOverall, BCG vaccination alone or with HBV co-administration reduced IFN-γ and MCP-1 responses to heterologous stimulants. HBV vaccination alone did not alter heterologous cytokine responses. In general, males produced more IFN-γ and TNF-α than females. We observed a sex-differential effect in relation to the influence of HBV co-administration on the effect of BCG on heterologous responses. Compared with males in the No vaccine group, males in the BCG + HBV group had lower IFN-γ and MCP-1 responses. In contrast, compared with females in the No vaccine group, females in the BCG group had higher IFN-γ response and lower MCP-1 responses.ConclusionNeonatal BCG vaccination resulted in lower cytokine responses to unrelated pathogens. HBV co-administration did not have a significant impact on responses overall but influenced the heterologous effects of neonatal BCG vaccination in a sex-differential manner.