Lower incidence of hospital-treated infections in infants under 3 months of age vaccinated with BCG

BackgroundLive vaccines potentially have non-specific effects that protect against other infections than those the vaccines are targeted against. The national vaccination program (NVP) in Finland was changed on September 1st, 2006: before BCG vaccine was given to all newborn babies and afterwards to babies in risk groups only. We used this natural experiment to study the non-specific effects of BCG in the frame of NVP using before-after design.MethodsWe compared the incidence of several outcomes obtained from Finnish health registers between children born between July 1st, 2004, and June 30th, 2006 (BCG-eligible) and an age- and season-matched reference cohort born between July 1st, 2007, and June 30th, 2009 (BCG-non-eligible) using Poisson regression. These cohorts were restricted to full-term children whose parents were born in Finland. Follow-up began at birth and lasted 3 months, which is the scheduled age for DTaP-IPV-Hib vaccination, and from 4 months until first birthday. The outcomes included all infections, pneumonia and injuries as a negative control outcome.ResultsThe incidence rate ratio (IRR) of the BCG-eligible cohort (N = 93,658) compared to BCG-non-eligible cohort (N = 94,712) for hospital-diagnosed infections was 0.89 (95 %Cl 0.86–0.93) for the 3-month follow-up. The decrease was mainly caused by respiratory infections. In 4–12 months follow-up the BCG-eligible had slightly more infections than BCG-non-eligible children (IRR 1.03, 1.01–1.06).ConclusionsBCG vaccination was associated with a lower incidence of all hospital-diagnosed infections during the first three months of life. The difference cannot be attributed to lung tuberculosis, since only few paediatric cases occurred in Finland during 2000s. The disappearance of non-specific effect after administration of an inactivated vaccine is compatible with previous studies.     

Bacillus Calmette–Guérin vaccine, antimalarial,age and gender relation to COVID-19 spread and mortality

COVID-19 is affecting different countries all over the world with great variation in infection rate and death ratio. Some reports suggested a relation between the Bacillus Calmette-Guérin (BCG) vaccine and the malaria treatment to the prevention of SARS-CoV-2 infection. Some reports related infant's lower susceptibility to the COVID-19. Some other reports a higher risk in males compared to females in such COVID-19 pandemic. Also, some other reports claimed the possible use of chloroquine and hydroxychloroquine as prophylactic in such a pandemic. The present commentary is to discuss the possible relation between those factors and SARS-CoV-2 infection.     

Rotavirus vaccination and stunting: Secondary Data Analysis from the Peruvian Demographic and Health Survey

Rotavirus infection is the leading cause of acute diarrhea in children and is preventable with a vaccine. Malnutrition increases the risk for the development of enteric and respiratory diseases, but also diarrhea increases the risk for stunting, having a negative effect in height-for-age Z score (HAZ). Therefore, Rotavirus can be considered as one of the contributing factors to stunting. The objective was to determine if vaccination against rotavirus was associated with changes in HAZ of children aged 6–60 months. We analyzed the data of Demographic and Health Survey (DHS) 2015–2017 for Peru, which is a nationwide representative. We fitted linear regression models controlling for complex sampling. The vaccine coverage was close to 75.5%, and the mean HAZ was −0.76 standard deviations. After adjusting by demographic, health, and household characteristics, children who received rotavirus vaccine, had a mean HAZ 0.06 standard deviations higher than children who did not receive it. Additionally, BCG vaccination, a higher education level of the mother, a higher wealth index, and treating water for drinking were positively associated with HAZ. On the other hand, we found low birth weight, lack of flush toilet, and altitude higher than 2500 m above sea level negatively associated with HAZ. Rotavirus vaccine is associated with better anthropometric measurements.     

The introduction of BCG vaccination to neonates in Northern Sweden, 1927–31: Re-analysis of historical data to understand the lower mortality among BCG-vaccinated children

BackgroundFollowing the introduction of oral Bacille Calmette-Guérin (BCG) a century ago, Albert Calmette suggested that BCG both provided protection against death from tuberculosis (TB) and other causes. The findings were not pursued. Today, there is considerable evidence that intradermal BCG have beneficial non-specific effects (NSEs). We re-analyzed data from BCG’s introduction 1927–1931 in Sweden hypothesizing that BCG reduced infectious deaths.MethodsIn three papers published by Dr Carl Näslund, the progress of oral neonatal BCG rollout provided free-of-charge and the effects on child mortality in the highly TB-prevalent region Norrbotten was sequentially updated. We analyzed cause-specific post-neonatal mortality by vaccination status excluding deaths from congenital conditions. Due to apparent differences in effects during study years, effects were assessed overall and separately in two periods (1927–1929, 1930–1931).ResultsAccording to Näslund, TB households were slightly more likely to accept vaccination; fewer newborns that were sick or had congenital problems were vaccinated. BCG coverage was 28.3% (5659/20,012); 8.7% (1746/20,012) died. The BCG/unvaccinated Risk Ratio (RR) of post-neonatal childhood death was 0.53 (0.45–0.62). BCG was associated with 80% (49–92%) reduced mortality from TB. From 1927 to 29, BCG appeared to protect strongly against deaths from all diseases, including the non-infectious, RR = 0.09 (0.02–0.36), presumably reflecting selection bias. From 1930 to 1931, there was no protection against non-infectious deaths, RR = 0.92 (0.49–1.70) indicating less bias (p = 0.004 for same effect). During 1930–1931, BCG was associated with reductions in non-TB infectious deaths (RR = 0.75 (0.58–0.97)); 2/3 were caused by respiratory infections, against which the BCG/unvaccinated RR was 0.61 (0.43–0.84). Other causes of death were less frequent and provided no clear pattern, except that BCG was associated with more meningitis deaths, RR = 6.85 (2.20–21.4).ConclusionHealthy vaccinee bias, particularly in 1927–1929, resulted in strongly beneficial overall BCG effects. However, the 1930–1931 data provided some support that BCG both protected against TB deaths and deaths from respiratory infections.     

穴位注射卡介菌多糖核酸治疗支气管哮喘疗效观察

目的:观察卡介菌多糖核酸不同给药途径对支气管哮喘疗效的差异。方法:将60例支气管哮喘患者随机分为穴位注射组30例和肌肉注射组30例。穴位注射组将卡介菌多糖核酸注射液于双侧肺俞穴处行穴位注射,前15d每日1次,双侧肺俞穴各注射1mL,15d以后隔日注射1次,连续用药3个月;肌肉注射组将卡介菌多糖核酸注射液2mL注射于一侧臀部,给药时间同穴位注射组。比较治疗后两组肺功能及免疫球蛋白情况及停药3个月后两组症状、体征积分及哮喘控制测试(ACT)得分。结果:两组治疗后肺功能、IgE、IgG、症状体征积分、ACT得分均较治疗前改善(P0.01),但穴位注射组的改善作用优于肌肉注射组(P0.01,0.05),停药3个月后穴位注射组症状体征积分、ACT得分仍优于肌肉注射组(P0.01)。结论:穴位注射较肌肉注射卡介菌多糖核酸能更快速、持久控制患者症状、体征,能更显著改善肺功能、降低IgE,是治疗支气管哮喘的有效方案。     

Disseminated cutaneous tuberculosis from BCG vaccination site in an immunocompetent child

A healthy 4‐month‐old girl presented with widespread scaly papules and a nodule over the site of BCG immunization. A diagnosis of disseminated cutaneous tuberculosis in an immunocompetent child was confirmed with biopsy. The child was treated with antituberculosis therapy without recurrence.     

Recombinant Mycobacterium bovis bacillus Calmette–Guérin expressing Ag85B-IL-7 fusion protein enhances IL-17A-producing innate γδ T cells

Interleukin 7 (IL-7) has an important function in the development and maintenance of IL-17A+ γδ T cells. We here constructed a recombinant Mycobacterium bovis bacillus Calmette–Guérin expressing antigen 85B (Ag85B)-IL-7 fusion protein (rBCG-Ag85B-IL-7). The Ag85B-IL-7 fusion protein and IL-7 were detected in the bacterial lysate of rBCG-Ag85B-IL-7. rBCG-Ag85B-IL-7 was the same in number as control rBCG expressing Ag85B (rBCG-Ag85B) in the lung at the early stage after intravenous inoculation, whereas the numbers of IL-17A+ γδ T cells and Ag-specific Th1 cells were significantly higher in the lungs of mice inoculated with rBCG-Ag85B-IL-7 than those inoculated with rBCG-Ag85B. The Ag-specific Th1 cell response was impaired in mice lacking IL-17A+ γδ T cells after inoculation with rBCG-Ag85B-IL-7. Thus, rBCG-Ag85B-IL-7 increases the pool size of IL-17A+ γδ T cells, which subsequently augment the Th1 response to mycobacterial infection.     

IL-12RB1基因突变致孟德尔遗传易感分枝杆菌病2例临床特点及基因分析

目的　研究白细胞介素12受体B1基因（IL-12RB1）突变所致孟德尔遗传易感分枝杆菌病的基因资料及临床特点，提高对该病的认识。方法　检测2016—2018年中国医学科学院北京协和医院就诊的2例播散性卡介苗感染患儿基因并分析结果，同时总结患儿的临床资料。结果　2例患儿分别为11月龄和13月龄男性儿童，均于出生后接种卡介苗，接种后3个月出现同侧腋下淋巴结肿大，病原学检查提示抗酸杆菌生长。均否认结核病接触史。基因检测分析结果显示2例患儿均为IL-12RB1复合杂合基因突变，分别为c.1561C＞T，p.R521X；c.632G＞C，p.R211P；c.339-340 del CT，p.L113Lfs*15和c.1791+2T＞G。其中c.339-340 del CT，p.L113Lfs*15未见报道，是新突变。结论　对于接种卡介苗后出现感染性播散的患儿，应进行原发性免疫缺陷基因检测，相关基因突变的识别，可为早期治疗及遗传咨询提供依据。     

MicroRNA expression profiling of PPD-B stimulated PBMC from M. bovis-challenged unvaccinated and BCG vaccinated cattle

There is an urgent need to identify additional diagnostic biomarkers for bovine TB to complement existing read-out systems such as interferon-gamma and for predictive markers of vaccine efficacy to accelerate vaccine development. To evaluate the potential of miRNAs as such biomarkers, we have analysed their expression in bovine PPD stimulated PBMC isolated from unvaccinated and BCG vaccinated cattle before and following Mycobacterium bovis (M. bovis) infection. Using a bovine microRNA microarray, miR-155 was found to show a significant up-regulation in expression in early (week 2) and late (week 11) M. bovis post-infection samples from unvaccinated cattle, while in BCG vaccinated cattle up-regulation was observed only in late post-infection samples. No differential expression of miR-155 was observed in pre-infection samples from unvaccinated and vaccinated cattle. These observations suggest that miR-155 could be exploited as a marker distinguishing vaccinated from infected animals (DIVA). Analysis by TaqMan RT-PCR, verified the up-regulation of miR-155 in unvaccinated cattle post-infection. Significant correlation was found between the degree of pathology and miR-155 induction in the experimentally infected cattle, suggesting miR-155 is a biomarker of disease development and/or severity. Induction of miR155 expression in cattle sourced from farms with confirmed bTB that tested positive in the tuberculin skin or interferon-gamma blood test was found to be significantly higher in cattle presenting with more advanced pathology (defined by the presence of visible TB lesions) compared to infected cattle without visible pathology and thus likely to be of lower infectivity than those with more advanced disease. In conclusion, our data indicate that miR-155 has potential both as a diagnostic and prognostic biomarker that could be used to identify animals with advanced pathology and as a DIVA test read-out. Its role in the immune biology of bovine TB will also be discussed.