The effect of Bacille Calmette-Guérin vaccine on tuberculin reactivity in indigenous children from communities with high prevalence of tuberculosis

The Bacille Calmette-Guérin (BCG) vaccine is the most widely used vaccine in the world, however it may cause problems for the appropriate interpretation of the tuberculin skin test (TST). We assessed the diagnostic value of latent infection in vaccinated and unvaccinated indigenous children from communities that have a very high prevalence of adult tuberculosis (TB). A total of 997 children under 15 years old and classified in age groups (0-1.9, 2-5, 6-9 and 10-15 years old) were randomly selected and given TSTs using the Mantoux technique. TST induration values of vaccinated children (n=724) were compared with those of children unvaccinated (n=273). BCG vaccination was not an important cause of false-positive TST, except in communities with a low prevalence of active TB. In conclusion, the results suggested that a history of BCG vaccination on TST+ response after 10 years of vaccination was statistically insignificant but whether at earlier age TST+ reflects most probably the degree of exposure to TB cases than BCG vaccination should be clarified in the future.     

Immunogenicity of a new Salmonella Typhi Vi polysaccharide vaccine--vax-TyVi--in Cuban school children and teenagers

A randomized, controlled, double blind study was carried out in Cuban children and teenagers aged 9-13 years to evaluate the immunogenicity of vax-TyVi-Salmonella Typhi Vi polysaccharide vaccine-with respect control vaccines. Serum samples were taken before and 21 days after the immunization, and ELISA was used for the determination of antibodies to Vi polysaccharide. Subjects who received vax-TyVi and TYPHIM Vi (Pasteur-Mérieux) showed seroconversion rates of 85.61 and 78.36%, respectively. The geometric mean titer (GMT) values for Vi antibodies induced after vaccination were 6.27 microg/ml (5.40-7.38 microg/ml) and 5.97 microg/ml (5.01-7.10 microg/ml), respectively. In contrast, subjects receiving the tetanus toxoid vaccine showed 0% seroconversion.     

Mycobacterium tuberculosis infection in First Nations preschool children in Alberta: implications for BCG (bacille Calmette-Guérin) vaccine withdrawal

BACKGROUND: On April 1, 2004, BCG (bacille Calmette-Guérin), a tuberculosis (TB) control vaccine, was discontinued in all but four high-risk communities in Alberta. To confirm the safety of vaccine withdrawal, and for future planning, the annual risk of infection (ARI) was determined in preschool First Nations children. METHODS: First Nations children born into reserve communities in Alberta between April 1, 1998 and March 31, 2004, and still living on reserve in 2004-2005, were identified. Health centre TB histories were validated by cross-referencing the birth cohort with the provincial TB Registry. Children that were not BCG vaccinated and not known to be tuberculin skin test (TST) positive underwent a TST. Birth cohort children were grouped as follows: (i) BCG vaccinated; (ii) BCG non-vaccinated, no TST; (iii) BCG non-vaccinated, TST; (iv) BCG vaccination status unknown. The ARI was calculated and the age and community characteristics of the groups were compared. RESULTS: There were 8447 children in the 6-year birth cohort, 4699 (55.6%) vaccinated, 2696 (31.9%) non-vaccinated, and 1052 (12.5%) whose vaccination status was unknown. Of the non-vaccinated children, 1921 (71.3%) were tested and only 2 were TST positive. No other TST positive, BCG non-vaccinated children were identified in the TB Registry cross-match. The prevalence of infection in 2004-2005 was 0.1% and the ARI was 0.03%. The community risk of TB exposure was comparable in tuberculin-tested and non-tested BCG non-vaccinated children. CONCLUSION: In low BCG-uptake First Nations communities in Alberta, the ARI is low and it is safe to withdraw BCG.     

不同浓度卡介苗接种后免疫效果观察

目的探讨不同浓度卡介苗接种后的免疫效果。方法采取随机抽样的研究方法,将正常新生儿分成2组,对照组278例,实验组为300例,用改变菌液浓度来增加接种的有效卡介苗量。具体为对照组每支卡介苗溶解稀释时用0.5ml注射用水配制,取0.1ml菌液接种,每支卡介苗接种5人;实验组每支卡介苗溶解稀释时用0.75ml注射用水配制,取0.15ml菌液接种,每支卡介苗接种5人。将两组新生儿卡介苗接种免疫效果进行比较。结果实验组卡介苗阳转率明显高于对照组(P(0.05)。结论本研究实验组的方法保证了新生儿卡介苗接种的有效量,从而提高了卡介苗接种后PPD的阳转率及卡疤成功率,对临床工作具有指导意义。     

The effect of bacille Calmette-Guérin vaccination at birth on immune response in China

Bacille Calmette-Guérin (BCG) vaccine is still the most effective approach to prevent tuberculosis in childhood. In order to provide protection against severe forms of childhood tuberculosis, it is customary to give BCG vaccination at birth in China. Tuberculin skin testing after vaccination is usually used to evaluate the immunogenic activity and protective efficacy of the BCG. We report the results of a multi-site prospective cohort study to evaluate the immunological reactivity against BCG in four prefectural cities in China. A total of 59,022 newborn infants were vaccinated between January 2011 and March 2012, and follow-up data on 27,517 vaccinated infants were available for this study. Of these, 679 (2.5%) had PPD readings of 0–5 mm, 17,072 (62.0%) had PPD readings of 5–10 mm of induration, 8864 (32.2%) had readings of 10–15 mm, 815 (3.0%) had readings of 15–20 mm, and 87 (0.3%) had readings of >20 mm of induration. The size of PPD reaction varied significantly with the geographic location, gender, season of vaccination, and grade of hospital administering the BCG vaccine (P < 0.001). 97.8% of the infants with a BCG scar of >1 mm had a positive TST reaction. However, only 56.9% of infants without a BCG scar had a positive PPD reaction. Our results demonstrate that the BCG immunization among newborn infants in China induces satisfactory immune response. In addition, BCG scars provide a useful indicator of vaccination response in Chinese infants.     

BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens.

To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria-tetanus-pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40-4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25-2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02-1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens (OR=0.42 (0.28-0.63), OR=0.77 (0.60-0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19-2.19)). DTP vaccination was associated with less anergy to diphtheria-tetanus antigens (OR=0.40 (0.32-0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens (OR=0.36 (0.26-0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens (OR=0.40 (0.16-0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.     

BCG osteomyelitis caused by the BCG Tokyo strain and confirmed by molecular method

Bacille Calmette-Guérin (BCG) osteitis is a rare complication of BCG vaccination. We describe two cases of BCG osteomyelitis developed in Korean infants who were given multipuncture BCG vaccination. The cultures of bone curettage specimens grew mycobacteria. The isolates were identified as BCG Tokyo strains by the deletion of the region of difference 1 (RD1) and characterization of RD8 and RD14 using the multiplex polymerase chain reaction.     

Complex cytokine profiles induced by BCG vaccination in UK infants

IFNγ plays an important part in immunity to tuberculosis (TB), but although it is necessary, it is not on its own sufficient for protection against TB. To identify other cytokines that play a role in the protection against TB induced by BCG vaccination, immune responses were compared between vaccinated and unvaccinated infants from the UK where BCG is known to provide protection. Twenty-one cytokines and chemokines were tested in supernatants from diluted whole blood cultures that had been stimulated for 6 days with Mycobacterium tuberculosis PPD. For 15 out of 21 of the cytokines tested responses were much higher in BCG vaccinated infants than in unvaccinated infants. These included: pro-inflammatory cytokines; IFNγ (median 1705 pg/ml vs. 1.6 pg/ml in vaccinated and unvaccinated infants, respectively), TNFα (median 226 pg/ml vs. 18 pg/ml), as well as IL-2, IL-1α and IL-6; TH2 cytokines: IL-4, IL-5 and IL-13 (median 104 pg/ml vs. 1.6 pg/ml); the regulatory cytokine IL-10 (median response 96 pg/ml vs. 8 pg/ml); the TH17 cytokine IL-17, chemokines (IP-10, MIP-1α and IL-8) and growth factors (GM-CSF and G-CSF). The greatest increase in cytokine production in BCG vaccinees compared to unvaccinated infants was seen with IFNγ. While responses for many cytokines were correlated with the IFNγ response, others including IL-17 and IL-10 were not. The pattern of cytokine induction following BCG vaccination is complex and measurement of one of two cytokines does not reveal the whole picture of vaccine-induced protection.     

Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000-2002

The rates of positive tuberculin skin test (TST) reactions and BCG scarring after BCG vaccination vary between studies and populations. Tuberculin reactivity and BCG scarring may be related to better child survival in low-income countries. We therefore studied determinants for TST reaction and scarring in Guinea-Bissau. In a cohort of children born in suburban Bissau from March 2000 to July 2002, we assessed a Mantoux test with Purified protein derivative (PPD) (SSI, 2 T.U.) at 2 (2689 children), 6 (N=2148) and 12 months (N=1638) of age, and BCG scar was assessed at 2 (N=2698) and 6 months (N=2225) of age. In a subgroup of the children the vaccination technique was monitored by direct observation of post-vaccination wheal and route of administration. Three different types of BCG vaccine supplied by the local Extended Programme on Immunization were used. At 6 months of age the rate of PPD reactors (>1mm) after BCG vaccination was 25% and the rate of scarring was 89%. One BCG strain was associated with fewer PPD reactors (OR=0.54 (0.31-0.91)) and BCG scars (OR=0.13 (0.05-0.37)) and larger post-vaccination wheals produced more PPD reactions (OR 1.21 (95% CI 1.02-1.43)) and BCG scars (OR 1.66 (1.24-2.21)). In the multivariable analyses of BCG-vaccinated children assessed at 6 months of age, monitoring of vaccination technique and type of BCG vaccine were important. This was not changed by control for other determinants, including sex, season, vaccination place, birthplace, ethnic group, low birth weight, place of residence, education and civil status of mother. We reason that vaccination technique and BCG strain are important for PPD reaction and scarring in response to BCG vaccination. Considering that these responses are associated with better infant survival, the importance of monitoring vaccination technique and of different BCG strains should be evaluated with respect to infant mortality.     

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.     

Neonatal Bacille Calmette-Guérin vaccination and tuberculin skin test reactions at 2- and 6-months: Effects on mortality up to 1 year of age

BackgroundIn randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have also been associated with reduced all-cause mortality. We aimed to assess the association between TST responses and subsequent mortality in three birth cohorts and conducted a meta-analysis of existing studies.MethodsObservational study within three Guinea-Bissau BCG trial birth cohorts (conducted 2002–04, 2009–2013 and 2014–18) that encompassed children who were BCG-vaccinated within 28 days with TSTs performed at 2- (n = 1389) and 6-months (n = 2635) of age. We evaluated TST reaction determinants by binomial regression and assessed the association between TSTs > 1 mm (reactors) vs. ≤ 1 mm (non-reactors) and subsequent mortality risk up to age 12 months in Cox-models providing Mortality Rate Ratios (MRRs). We searched PubMed for studies to calculate meta-estimates of the association between TST reactivity by age 2- and 6-months and all-cause mortality.ResultsLarge post-vaccination wheal size was associated with 6-month TST positivity and so was receiving BCG-Denmark or BCG-Japan, compared with BCG-Russia. By age 2 months, 22% (302/1389) of infants were TST reactors with a 2–12-month mortality risk of 1.7% (5/302) vs. 3.3% (36/1087) for non-reactors, the corresponding reactor/non-reactor MRR = 0.49 (0.19–1.26). By age 6 months, 44% (1149/2635) of infants were reactors and the 6–12-month mortality risk was 0.4% (4/1149) vs. 0.6% (9/1486) for non-reactors, the MRR = 0.87 (0.27–2.86). The literature search provided 3 studies. The meta-analysis revealed a uniform pattern of reduced mortality associated with TST reactivity, a TST response by 2 months being associated with an MRR of 0.59 (0.39–0.90); for 6-month TST responses the MRR was 0.65 (0.43–1.00).ConclusionAmong BCG-vaccinated infants, TST reactions were associated with markedly reduced mortality. Improved vaccination technique and using certain BCG strains could lead to a higher TST reaction prevalence, which would enhance BCG’s beneficial non-specific effects.     

In vitro effects of 1,25-dihydroxyvitamin D3 on interferon-gamma and tumor necrosis factor-alpha secretion by blood leukocytes from young and adult cattle vaccinated with Mycobacterium bovis BCG

Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are critical in the development of an effective immune response. Vitamin D, essential in short-term calcium homeostasis and recently shown to modulate proliferation and function of blood mononuclear cells from adult dairy cattle, may be an effective modulator of the calf's immune system. Effects of antigen sensitization and 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] on cytokine secretion by cells from calves vaccinated with Bacille Calmette-Guérin (BCG) were examined. One-week-old dairy calves (n = 6) and yearling heifers (n = 4) were vaccinated concurrently with BCG and boosted six weeks later. Ten weeks after primary vaccination, cells from vaccinated calves and adults, and nonvaccinated, age-matched calves (n = 4) were evaluated in vitro for their capacity to produce IFN-gamma and TNF-alpha. Cells were stimulated with pokeweed mitogen (PWM) or recall antigen [Mycobacterium bovis-derived purified protein derivative (PPD)] in the presence of 0, 0.1, 1.0, and 10 nM of 1,25-(OH)2D3 for 20, 44, and 68 hours, respectively. IFN-gamma and TNF-alpha concentrations in culture supernatants harvested at these times were quantified by enzyme-linked immunosorbent assay (ELISA). PPD-induced IFN-gamma and TNF-alpha responses of cells from vaccinated calves and adults were greater than responses of autologous unstimulated cells. In contrast, PPD-specific responses of calf and adult cells collected immediately before primary vaccination were substantially lower and comparable to responses in resting (i.e., unstimulated) cultures. At ten weeks, the PPD-specific response of vaccinates exceeded the response of nonvaccinated calves; however, responses of vaccinated calves were more vigorous than corresponding responses of vaccinated adults. Incubation period also influenced the magnitude of both IFN-gamma and TNF-alpha, responses in PPD- and PWM-stimulated cultures. Effects of 1,25-(OH)2D3 on antigen-induced secretion of IFN-gamma and TNF-alpha were marginal. Only IFN-gamma responses of vaccinated adults were affected by 1,25-(OH)2D3. Vitamin D caused a concentration-dependent decrease in IFN-gamma response and an increase in TNF-alpha response in PWM-stimulated cultures. These results indicate that animal maturity (i.e., age) and antigenic experience affect IFN-gamma and TNF-alpha secretion by bovine leukocytes and suggest that 1,25-(OH)2D3 can alter secretion of both cytokines under specific conditions of culture.     

A survey of latent tuberculosis infection among laboratory healthcare workers in New York City.

OBJECTIVE: To determine the prevalence of positive tuberculin skin tests (TSTs), incidence of TST conversion, risk factors for positive TSTs, and history of active TB among HCWs in microbiology laboratories in New York City. DESIGN: Two-year survey from May 1999 to June 2001. SETTING: Nineteen microbiology laboratories. RESULTS: During the first year, interviews were conducted with 345 laboratory HCWs (mean, 18 HCWs per site; range, 2 to 51) to assess the prevalence of positive TSTs, but 3 (1%) could not recall their result and were excluded from further analyses. The mean age of the remaining 342 HCWs was 48 years; 68% (n = 233) were female, 54% (n = 183) received bacille Calmette-Guerin (BCG) vaccination, and 71% (n = 244) were foreign born. The prevalence of a positive TST was 57% (n = 196), but only 20% (n = 39) of the HCWs received isoniazid. The incidence of TST conversion in the second year of the study was 1% (1 of 108). Multivariate analysis identified age (odds ratio [OR] per year, 1.05; 95% confidence interval [CI95], 1.02-1.08), foreign birth (OR, 3.80; CI95, 1.98-7.28), BCG immunization (OR, 4.89; CI95, 2.72-8.80), and employment in a mycobacteriology laboratory (OR, 2.14; CI95, 1.25-3.68) as risk factors for a positive TST. Only one HCW had been treated for active TB. CONCLUSIONS: The prevalence of positive TSTs was high among laboratory HCWs, but the TST conversion rate was low. Higher rates of treatment for latent TB infection are desirable.     

Modified multiplex PCR for identification of Bacillus Calmette-Guérin substrain Tokyo among clinical isolates

When an adverse reaction occurs and a mycobacterial species is isolated from a person vaccinated with Bacillus Calmette-Guérin (BCG) or a patient receiving BCG immunotherapy, it is essential to identify whether the isolate is BCG or another mycobacterial species. However, differentiation of BCG from other members of Mycobacterium tuberculosis complex has been very difficult. Using several specific primer-pairs, Bedwell et al. [Bedwell J, Kairo SK, Behr MA, Bygraves JA. Identification of substrains of BCG vaccine using multiplex PCR. Vaccine 2001; 19: 2146-51] recently reported that they could distinguish BCG substrains. We modified their method to improve differentiation of Tokyo 172 from other members of the M. tuberculosis complex, and examined whether this modified method could be applied to clinical isolates. Our method clearly identified BCG substrain (BCG Tokyo 172) among clinical isolates and easily distinguished between M. tuberculosis and wild-type Mycobacterium bovis.     

Lymphadenitis as a complication following vaccination with Bacillus Calmette-Guérin (BCG)

A healthy 14-months-old boy developed suppurative adenitis some weeks after Bacillus Calmette Guérin (BCG) vaccination. The tumour grew rapidly, showed fluctuation and eventually incision was needed. Culture of the abscess was negative. The diagnosis was: regional lymphadenitis after BCG vaccination. This suppurative lymphadenitis is a non-serious complication of BCG vaccination and has been reported in 0.1 to 4% of those vaccinated. As the BCG vaccination is given only to the at-risk population in the Netherlands, BCG complications are rare. Non-suppurative nodal swellings are considered a normal post-vaccination reaction and do not require treatment.     

Evaluation of BCG vaccination: an intervention study in Rail Region, Saudi Arabia

Inspection of 300 infants attending a primary health care (PHC) center at Hail region showed that 18.8% of children failed to develop BCG reations. This directed attention to inspect the process of vaccination at hospitals in which 80% of deliveries and BCG vaccination took place. Defects in the process of vaccination and cold chain system were noticed. Reorganization of the process of vaccination in addition to training the staff responsible for vaccination were done. A survey was followed to evaluate failure of BCG vaccination before and after the intervention. We checked 4145 infants two to twelve months of age, for any reaction at the site of BCG vaccination. After intervention vaccination failure dropped from 20.4% to 4.9% for infants vaccinated in hospitals (p = 0.00001), and from 7.9% to 3.2% for those vaccinated in health centers (p = 0.01). Moreover, before intervention success of BCG vaccination was significantly higher in PHC centers (92.1%) than in hospitals (79.6%). This difference became insignificant after intervention because success of BCG vaccination in hospitals has increased up to 95.1% compared to 96.8% in health centers. Inspection of all infants for BCG reaction is continued as a part of routine work at PHC centers, and re-vaccination of those who failed to develop reation to BCG is conducted without any reported complications.     

Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: a beneficial effect of BCG vaccination for girls community based case-control study

Among measles unvaccinated infants in Guinea-Bissau, we tested whether case infants with acute lower respiratory tract infection (ALRI), especially ALRI caused by respiratory syncytial virus (RSV), were more likely to be Bacille Calmette Guerin (BCG)-unvaccinated and to have no scar after BCG vaccination than were control infants without symptoms of ALRI. Three hundred and eighty-six case infants with ALRI were identified at a paediatric clinic (N=84), a health centre (N=82), and in a community morbidity surveillance system (N=220). Control infants were matched on sex, age, and district and were also measles unvaccinated. In ALRI case infants, the adjusted OR of being BCG unvaccinated was 2.87 (1.31-6.32), 1.72 (0.48-6.19) in boys and 4.45 (1.48-13.4) in girls. Among BCG vaccinated ALRI case infants, the adjusted OR of having no BCG scar was 1.54 (0.86-2.75), 0.93 (0.45-1.91) in boys and 2.70 (1.21-6.02) in girls. In ALRI case infants with RSV infection, similar trends were observed. BCG vaccination may have a non-targeted protective effect against ALRI, the effect being most marked in girls.     

Is tuberculin skin testing useful to diagnose latent tuberculosis in BCG-vaccinated children?

BACKGROUND: The tuberculin skin test (TST) is the most commonly used tool to detect infection with Mycobacterium tuberculosis. We sought to determine whether tuberculin skin testing is useful to detect latent infection by M. tuberculosis in a population that was vaccinated with the Bacille Calmette Guérin (BCG) vaccine. METHODS: We performed a cross-sectional study during October 2000-February 2001, enrolling first and sixth graders from a random, stratified sample of public elementary schools in Orizaba, Veracruz, Mexico. We assessed the relationship between sociodemographic and epidemiological information, BCG scars, and TST reactivity. RESULTS: There were 858 children enrolled in the study with a completed questionnaire and TST result. The prevalence of a positive TST result (> or =10 mm) was 12.4%. Controlling for BCG scar, age, and other characteristics, close contact with pulmonary tuberculosis patients (odds ratio 6.56, 95% confidence interval 2.05-21.07, P = 0.001) was independently associated with TST reactivity. CONCLUSIONS: TST results helped identify children in a BCG-vaccinated population who had recent exposure to persons with pulmonary tuberculosis, were probably infected with M. tuberculosis, and could benefit from treatment for their latent tuberculosis infection.     

A study of the effect of simultaneous vaccination with BCG and smallpox vaccine in newborn infants

In order to determine whether the BCG and smallpox vaccinations of newborn infants could be combined, thus saving staff, time and money, particularly in the developing countries, 696 newborn infants in Taiwan were divided into three groups and vaccinated by one of the following three methods: simultaneous vaccination with BCG and smallpox vaccine, vaccination with BCG only, and vaccination with smallpox vaccine only. On follow-up, no difference was observed between the ”simultaneous” group and the ”smallpox only” group in respect of either no-take rate and frequency distribution by size of vaccination lesions or reactions to smallpox revaccination at 12 weeks. Tuberculin tests at 12 weeks revealed a normal distribution in the size of tuberculin reactions with a mean of 11.94 mm and 12.19 mm respectively in the ”simultaneous” group and the ”BCG only” group; in the ”smallpox only” group all the reactions were below 9 mm, the great majority being 0-3 mm. The author concludes that there is no interaction between primary BCG and smallpox vaccination when both vaccines are administered simultaneously, and that, despite the reported complications, simultaneous administration of BCG and smallpox vaccine in newborn infants is a safe procedure.     

Different effects of BCG strains – A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau

BackgroundDifferent Bacillus Calmette-Guerin (BCG) vaccine strains may have different non-specific effects. We assessed the effect of two BCG strains (Danish and Russian) on childhood morbidity and BCG scarification in Guinea-Bissau.MethodsDuring 2011–2013, infants in the Bandim Health Project’s urban study area received the Danish or Russian BCG in a natural experiment. Health center consultations were registered at point of care and scar status and size at age 4½ months. We assessed the effect of strain on consultation rates between vaccination and age 45 days in Cox proportional hazards models. Scar prevalence and size were compared using binomial regression and ranksum tests.ResultsAmong 1206 children, 18% received Danish BCG (n = 215) and 82% Russian BCG (n = 991). The adjusted hazard ratio (aHR) for consultations was 0.94 (95% CI 0.60–1.46) for Danish BCG compared with Russian BCG. Girls vaccinated with Danish BCG tended to have lower consultation rates compared with girls vaccinated with Russian BCG (aHR 0.56 (0.25–1.24)), whereas the effect was opposite for boys (aHR 1.24 (0.74–2.11)), p = 0.09. Children vaccinated with Danish BCG were more likely to develop a scar (97%) than children vaccinated with Russian BCG (87%), the relative risk (RR) being 1.11 (1.06–1.16). The effect was stronger in girls, and BCG scar size was larger among infants vaccinated with the Danish strain.ConclusionBCG strain influences scar prevalence and scar size, and may have sex differential effects on morbidity. BCG strains are currently used interchangeably, but BCG scarring has been linked to subsequent survival. Hence, more research into the health effects of different BCG strains is warranted. Small adjustments of BCG production could potentially lower childhood morbidity and mortality at low cost.