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.     

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.     

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 vaccination of full-term infants with chronic intrauterine malnutrition: influence of immunization age on development of post-vaccination, delayed tuberculin hypersensitivity.

To determine the effect of intrauterine growth retardation (IUGR) on the response to BCG vaccination, we evaluated the specific delayed tuberculin hypersensitivity of 57 full-term infants with symmetric IUGR (SGA or small for gestational age) and 52 full-term infants with normal intrauterine growth (AGA or appropriate for gestational age). The infants were evaluated using post-vaccination skin tests to tuberculin purified protein derivative (PPD) and tuberculin lymphocyte transformation tests. Using a positive response to the skin test as an indicator of delayed hypersensitivity, we found that the rate of response to BCG in the SGA and AGA groups was similar. A total of 65% of infants with IUGR responded to BCG vaccination. The response rate among SGA infants who were vaccinated at 5 days of age, about 26 days of age (weight > or = 2500 g), 3 months of age, and 6 months of age was 68%, 47%, 69%, and 88%, respectively. The overall response rate for infants with no IUGR was 71%; the rate response to BCG vaccination among this group was 52% (those vaccinated at 5 days of age), 90% (3 months of age), and 80% (6 months of age). Our data suggest that the immunogenicity of BCG vaccine is similar in term infants who have normal or abnormal intrauterine growth and the presence of IUGR should not be a reason for delaying BCG vaccination.     

Influence of nutrition on postvaccinial tuberculin sensitivity

Response to BCG vaccination was studied in 261 apparently normal preschool children in a community. They were classified into different nutritional groups based on deficit in weight for age. In addition, nine children who had kwashiorkor and were admitted to the hospital were investigated. They were given 0.1 ml of BCG vaccine, and 6 months later, tuberculin sensitivity was assessed using 5 U of PPD. Blood samples were collected from 84 subjects and leukocyte migration inhibition was determined using the same antigen. After BCG vaccination, over 80% of children in the community showed positive tuberculin test, irrespective of the extent of growth retardation. There were no significant differences in the size of induration or the percentage of reactors between the various groups, indicating that the immune response to BCG vaccination is not affected by milder grades of malnutrition. However, the skin test was negative in most of the children who had had kwashiorkor. Leukocyte migration inhibition was similar in all the groups of children including those with kwashiorkor indicating that sensitisation of lymphocytes was not influenced by the nutritional status. In children with kwashiorkor, the leukocyte migration inhibition test was positive though the skin test was negative, suggesting that the former may be a better measure of assessing the response to BCG vaccination.     

Tuberculin reaction, BCG scar, and lower female mortality

BACKGROUND: Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar in response to BCG immunization were related to better overall survival in Guinea-Bissau and, if so, whether the effect was sex-specific. METHODS: Skin tests and BCG scarring were monitored at ages 2 months (n = 2332) and 6 months (n = 1817) in children born from March 2000 to July 2002. A tuberculosis (TB) surveillance system allowed us to exclude from the analysis children with likely TB exposure. The children were followed for survival until 18 months of age. RESULTS: Among children with a tuberculin skin test at 2 and 6 months of age, the mortality rate ratio for skin test reactors (>1 mm) versus nonreactors (0-1 mm) was 0.54 (95% confidence interval = 0.30-0.99). Comparing children with and without a BCG scar, the ratio was 0.55 (0.31-0.96). The effect of a skin test reaction or a BCG scar seemed stronger among girls; for those with positive reaction, the mortality ratio was 0.31 (0.11-0.88) among girls and 0.84 (0.39-1.82) among boys; and for BCG scar, the results were 0.41 (0.21-0.82) and 0.88 (0.34-2.30), respectively. CONCLUSIONS: A good response to BCG vaccination is related to lower child mortality. The effect seems most pronounced among girls. The findings may have implications for future vaccine trials and policy.     

Performance of an interferon-gamma release assay for diagnosing latent tuberculosis infection in children

Newly developed interferon-gamma release assays have become commercially available to detect tuberculosis (TB) infection in adults. However, little is known about their performance in children. We compared test results between the QuantiFERON-TB Gold test (QFT) and tuberculin skin test (TST) in young children living with pulmonary TB patients in Cambodia. Of 195 children tested with both QFT and TST, the TST-positive rate of 24% was significantly higher than the QFT-positive rate of 17%. The agreement between the test results was considerable (kappa-coefficient 0.63). Positive rates increased from 6% to 32% for QFT and from 15% to 43% for TST, according to the sputum smear grades of the index cases. The presence of Bacille Calmette-Guérin (BCG) scars did not significantly affect the results of TST or QFT in a logistic regression analysis. In conclusion, QFT can be a substitute for TST in detecting latent TB infection in childhood contacts aged 相似文献   

The effect of tuberculin skin test and BCG vaccination on the expansion of PPD-specific IFN-gamma producing cells ex vivo

Understanding the immunogenicity of BCG in a population where it has failed will facilitate the design of new TB vaccines. We assessed the immunogenicity of M. bovis BCG over 12 months by ELISPOT assay. Forty-one adolescents and young Gambian male adults received a tuberculin skin test (TST) which was followed one week later by BCG vaccination, but the 23 control subjects received neither of these. TST alone significantly induced PPD-specific IFN-γ producing cells. Twenty-three percent of subjects did not respond to BCG, which was associated with higher pre-existing ex vivo response to PPD. Paradoxically, amongst BCG responders there was a correlation between pre-existing response and subsequent response to BCG. We conclude that BCG is immunogenic, but this effector response is short-lived and can be limited in higher pre-existing anti-mycobacterial immunity, suggesting a possible threshold beyond which BCG immunogenicity is inhibited.     

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.     

Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-beta production

The only vaccine available against tuberculosis (TB), BCG, so effective in experimental animal models, has been under scrutiny for a long time owing to its variable efficacy against pulmonary tuberculosis in adults. In this study, we evaluated whether anti-helminthic therapy prior to BCG vaccination could increase the immunogenicity of BCG vaccination in helminth infected population. We recruited volunteers with evidence of prior mycobacterial infection and who were asymptomatic carriers of helminths. The subjects were randomized to receive either anti-helminthic drugs or placebo. Three months later, BCG vaccination was administered to volunteers. Mycobacterial antigen-specific cytokine responses were assessed 2 months after vaccination. The results show that peripheral blood mononuclear cells obtained from the placebo group were found to have a lower frequency of IFN-gamma (129 vs 191, p=0.03) and IL-12 (149 vs 243, p=0.013) producing cells per 2 x 10(5) PBMC (peripheral blood mononuclear cells) when stimulated in vitro with a mycobacterial antigen mixture (purified protein derivative (PPD)) compared to those from the dewormed group. On the other hand the placebo group had higher frequency of TGF-beta producing cells in response to PPD (152 vs 81.3, p=0.002) or the T cell mitogen concanavalin A (Con A) (210 vs 157, p=0.03). However, no detectable IL-4 or IL-5 producing cells were observed when cells were stimulated with PPD. Comparable numbers of both cytokine producing cells were induced in both groups upon stimulation with concanavalin A (IL-4 217 vs 191, p=0.08) and IL-5 (131 vs 103, p=0.14). The data presented here demonstrate that chronic worm infection reduces the immunogenicity of BCG in humans and this was associated with increased TGF-beta production but not with enhanced Th2 immune response.     

The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age

Background

Bacille Calmette-Guérin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination.

Methods

Children were randomized to BCG or nothing. Blood was sampled 6–11 weeks after randomization (early sample group) or 5–9 months later (late sample group). In vitro cytokine responses (interferon (IFN)-γ, interleukin (IL)-13, tumor-necrosis-factor (TNF)-α, and IL-10) were assessed in whole blood cultures stimulated with lipopolysaccharide (LPS), purified protein derivative (PPD) or phytohaemagglutinin (PHA). Effect-modification by sex, DTP-booster vaccination and MN was studied.

Results

Cytokines were measured in 345 infants. BCG was associated with significantly increased IFN-γ (geometric mean ratio (GMR) = 4.54 (95% confidence interval: 3.13–6.58)) and IL-13 (GMR = 1.43 (1.00–2.05)) PPD responses, the effect being strongest in the early sample group. Across all three conditions BCG tended to increase IL-10 (LPS, PHA, PPD: GMR = 1.20, 1.12, 1.20), most pronounced in the late sample group. BCG reduced the TNF-α/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without (interaction test: p = 0.03). In children without MN, BCG was associated with reduced TNF-α response in the early sample group (p = 0.006), and increased IL-10 in the late sample group (p = 0.03).

Conclusion

BCG revaccination resulted in a strong IFN-γ response to PPD, which waned slightly over time. BCG also affected the pro-/anti-inflammatory balance, with reduced TNF-α and increased IL-10 responses to LPS, PHA and PPD. This effect depended on sex, DTP-booster vaccination and micronutrient supplementation, being most pronounced in children who had received DTP-booster before enrolment and children who had not received MN, i.e. the group of children which also had lower mortality after BCG revaccination.     

天津市汉沽区儿童卡介苗免疫接种效果分析

目的了解天津市汉沽辖区近3年内结核菌素儿童卡介苗接种的免疫效果。方法对4 281名已初种卡介苗儿童结核菌素（PPD）试验结果进行分析。结果 3个月～3岁、4～5岁和6～7岁3个年龄组PPD试验阳性率,2008、2009和2010年分析为97.3%～85.7%、97.1%～83.3%和97.2%～90.0%。结论汉沽近3年儿童卡介苗接种免疫效果较好,接种质量较高。抓好新生儿卡介苗初种质量,是提高卡介苗接种成功率的关键。     

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.     

Protective effect of Bacillus Calmette-Guerin (BCG) vaccination in children with extra-pulmonary tuberculosis, but not the pulmonary disease. A case-control study in Rosario, Argentina

A hospital-based case-control study was carried out at the Vilela Children's Hospital in Rosario, Argentina, to measure the protection conferred by BCG vaccination against tuberculosis (TB). The study included 148 newly diagnosed cases of TB (75 males and 73 females, mean age 3.34+/-2.97 years, S.D.), 134 of them with pulmonary TB and 14 cases with extra-pulmonary disease. Controls (425 males and 357 females, 3.39+/-2.98 years) were selected randomly among children who attended to the Hospital showing, neither respiratory diseases nor any other infectious illnesses. Information on BCG vaccination history was assessed from scars or immunisation records. All participants were negative to human immunodeficiency virus and belonged to the lower and upper-lower socioeconomic status, being similar in place of residence and ethnic characteristics. Rate of vaccinated children was 92.6% of cases and 94.5% of controls (3.4 and 3.9% of them without scars, respectively). Regarding the total cases, the protective association between BCG and TB was statistically insignificant, as was for the pulmonary form. Among cases with extra-pulmonary disease, vaccine effectiveness attained significance [79% (95% CI=26-94)], no matter their age, sex or nutritional status. BCG vaccination exerted a beneficial role in extra-pulmonary TB, even in children not seriously undernourished.     

荆州市沙市城区卡介苗初免儿童结核菌素试验结果分析

[目的]了解我市卡介苗初免儿童的免疫状况,为改善卡介苗接种工作提供依据。[方法]应用结核菌素试验(PPD),对我市沙市城区730名卡介苗接种3个月后的3个月～1岁儿童,进行PPD阳性率调查与影响因素分析。[结果]本组儿童PPD阳性率91.5%,无性别差异;分析影响本组试验阳性率的因素有:有卡介苗接种史者高于其接种史不详者;有卡疤者高于无卡疤者;在接种门诊与医院产房接种卡介苗者高于村镇卫生室与街道卫生院接种;有结核病接触史者高于一般人群。[结论]PPD监测结果表明,本组儿童卡介苗接种质量较高。消除影响PPD试验阳性率的因素,可提高卡介苗免疫质量。     

Variation in yield of needle scars with multipuncture BCG vaccination

PURPOSE: BCG vaccination using the multipuncture percutaneous method has long been employed in Japan. The purpose of this study is to clarify whether the number of needle scars achieved the BCG vaccination differs with the vaccinating physician. METHODS: A total of 218 babies who were vaccinated at the age of 4 months by different physicians at the Public Health Centres of Katsushika-Ward, Tokyo, were examined at the age of 3 years, in the three-year-old health check-up programme. The BCG vaccination with the multipuncture method generates 18 needle scars at a maximum. We examined each child for how many needle scars after BCG vaccination were visible, with reference to the vaccinating physician. RESULTS: The mean number of the visible scars was 9.23 (SD 6.11), and significantly smaller (P < 0.01) than that for all 22 Wards (12.18 +/- 5.64) investigated with the same method. The mean number of needle scars of the babies in Katsushika Ward was the third smallest among the 22 Wards and significantly smaller (P < 0.05) than the national average as determined in the nationwide survey conducted in 2000. Significant differences were evident among the 7 physicians performing the vaccination, the best and second best means being 15.26 (SD3.62) and 14.59 (SD3.58) respectively, and significantly larger (P < 0.01) than the means for the 7 physicians. The worst mean was 3.43 (SD4.46), significantly smaller (P < 0.01) than the mean for the 7 physicians. CONCLUSION: The mean number of needle scars after BCG vaccination of babies significantly differed with the 7 physicians in the present study. Poor technique was presumed responsible for small numbers of scars and technical training is therefore necessary in order to improve the BCG vaccination outcome.     

BCG vaccination scar associated with better childhood survival in Guinea-Bissau

BACKGROUND: Recent studies have suggested that Bacille Calmette-Guerin (BCG) vaccination may have a non-specific beneficial effect on infant survival and that a BCG scar may be associated with lower child mortality. No study has previously examined the influence of BCG vaccination on cause of death. METHODS: Two cohorts (A and B) were used to describe the mortality pattern for children with and without BCG scar and to determine specific causes of death. In cohort A (n = 1813), BCG scar was assessed at 6 months of age and as previously described children with a BCG scar had lower mortality over the next 12 months than children with no BCG scar. In cohort B, 1617 children aged 3 months to 5 years of age had their BCG scar status assessed in a household-based survey and mortality was assessed during a 12-month period. Causes of death were determined by verbal autopsy (VA) and related to BCG scar status in a cause-specific hazard function. RESULTS: Controlling for background factors associated with mortality, there was lower mortality for children with a BCG scar than without in cohort B, the mortality ratio (MR) being 0.45 (95% CI 0.21-0.96). Exclusion of children exposed to TB did not have any impact on the result. In a combined analysis of cohorts A and B, the MR was 0.43 (95% CI 0.28-0.65) controlling for background factors. There were no large differences in distribution of the five major causes of death (malaria, pneumonia, acute diarrhoea, chronic diarrhoea, and meningitis/encephalitis) according to BCG scar status in the two cohorts. Having a BCG scar significantly reduced the risk of death from malaria [MR 0.32 (95% CI 0.13-0.76)]. CONCLUSIONS: A BCG scar is a marker of better survival among children in countries with high child mortality. BCG vaccination may affect the response to several major infections including malaria.     

Effect of dietary protein and zinc on anti-mycobacterial antibody responses in guinea pigs

An enzyme immunoassay was developed to quantify the levels of antibodies reactive with purified protein derivative (PPD) at 3, 4, 5 and 6 wks following vaccination with Mycobacterium bovis BCG and initiation of diets deficient in either protein (LP) or zinc (LZ). Significant antibody levels were detected in all groups as early as 3 wks post-vaccination compared to non-vaccinated animals. Both LP and LZ guinea pigs had higher levels of antibody than animals consuming an adequate diet at 3 and 4 wks, respectively. By 6 wks post-vaccination, animals on the low protein diet had the highest antibody titers, followed by control, chow and LZ guinea pigs in order of decreasing titers. A highly significant positive correlation was detected between the levels of anti-mycobacterial antibodies and the number of viable BCG recovered from the lymph nodes draining the vaccination site. A significant inverse correlation was seen between antibody levels and PPD skin reactions. High-titer sera from protein-deficient, but not zinc-deficient, BCG-vaccinated pigs significantly suppressed the tuberculin reactions when passively transferred into normal, PPD-positive recipients.     

Relationship between bacille Calmette-Guérin vaccination, Mantoux test positivity, and geohelminth infection

To investigate the potential protective effects of Bacille Calmette-Guerin (BCG) vaccination scar and sensitization to tuberculin against geohelminth infections, we conducted a cross-sectional study among school age children in rural communities in Pichincha Province in Ecuador where BCG vaccination is routinely given at birth. A total of 944 children aged 8-14 years were evaluated for the presence of BCG scars and sensitization to tuberculin, and underwent faecal examination for geohelminth parasites. BCG scars were present in 88.2% of children and positive Mantoux tests were observed in 19.1% of children. Geohelminth prevalence was high with 70.3% infected with any parasite, 52.1% with Ascaris lumbricoides, 52.3% with Trichuris trichiura, 7.6% with Ancylostoma duodenale, and 3.0% with Strongyloides stercoralis. In multivariate analyses, the presence of BCG vaccine scars was not significantly associated with infections with any geohelminth parasite (adjusted odds ratio [AOR] = 0.74, 95% CI 0.43-1.28, P = 0.28), but an inverse association was observed for infections with S. stercoralis that was of borderline statistical significance (AOR = 0.38, 95% CI 0.15-1.00, P = 0.05). There were no associations between sensitization to tuberculin and infection with geohelminth parasites. The data provide little support for an important protective role of neonatal BCG vaccination or current mycobacterial sensitization against geohelminth infections.     

Sensitivity and specificity of the BCG scar reading

OBJECTIVE: To validate the BCG scar as a marker of BCG vaccination status. METHODS: A cross-sectional survey was carried out among 53,348 schoolchildren aged 6-14 years who underwent BCG scar examination as part of a large BCG vaccine trial taking place in the city of Manaus, Brazil. Results of BCG scar reading were compared with information on vaccine status of their vaccination cards or provided by parents or guardians. Double-reading was performed in a sub-sample. Data analysis was conducted using Stata 7 and Kappa coefficient. RESULTS: Of 52,348 schoolchildren studied, vaccine status information from parents/guardian letters was available for 29,254 and from vaccination cards for 4,947. There was found a high agreement between the double-readings of the scars (Kappa=0.81). When the agreement between letter and card information was the gold standard, the sensitivity of BCG scar readings was 96.6% (95%CI 96.0-97.1) and the specificity was 71.1% (95%CI 55.7-83.7). The sensitivity was 96.1%, 97.3% and 95.3% for children vaccinated up to one month of age, four months and one year, respectively. CONCLUSIONS: Sensitivity and specificity did not show an association with the child's age at the scar reading. BCG scar was a good marker of BCG vaccination status regardless of age - from the first years of life up to 14 years old.