Bacille Calmette-Guérin Scar Research Articles

Neonatal BCG Vaccination for Prevention of Allergy in Infants: The MIS BAIR Randomised Controlled Trial.

The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy. In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants. In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3-monthly online questionnaires and oral food challenges. Data were analysed by intention-to-treat using binary regression. gov (NCT01906853). Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI -1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI -3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration). Neonatal BCG-Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life.

Maternal BCG scars and mortality risk for male and female newborns: observational study from Guinea-Bissau.

Maternal priming with Bacille Calmette-Guérin (BCG) has been associated with reduced mortality in male offspring. We investigated this association in a cohort of healthy BCG-vaccinated neonates. Observational study within a randomized controlled trial comparing different BCG strains conducted in Guinea-Bissau from 2017-2020. As part of trial inclusion procedures, on the day of discharge from the maternity ward, maternal BCG scar status was evaluated by visual inspection, followed by offspring BCG and polio vaccination. Through mortality data collected at telephone interviews at six weeks and six months of age, we assessed all-cause mortality risk in Cox Proportional Hazards models adjusted for maternal schooling and BCG strain, providing adjusted Mortality Rate Ratios (aMRRs). 64% (11,070/17,275) of mothers had a BCG scar, which for females and overall was not associated with neither admission risk, admission severity nor all-cause mortality. By six months of age, the mortality rate (MR) was 4.1 (200 deaths/4,919 person-years) for the maternal BCG scar cohort and 5.2 (139 deaths/2,661 person-years) for no maternal scar, aMRR=0.86 (0.69-1.06). In males, six-month MRs were 4.3 (109/2,531) for maternal BCG scar vs 6.3 (87/1,376) for no scar, the maternal scar/no scar aMRR being 0.74 (0.56-0.99). In females, six-month MRs were 3.8 (91/2,388) vs 4.0 (52(1,286), the aMRR being 1.04 (0.74-1.47), p for interaction with sex=0.16. While we cannot rule out an association in females, being born to a mother with a BCG scar reduced the risk of death during early infancy for BCG-vaccinated males, reproducing findings from previous studies.

Using real-life data to model the impact of increasing BCG vaccination coverage and scar prevalence on all-cause infant mortality

PurposeEstimating the potential impact on infant mortality of increasing Bacille Calmette-Guérin (BCG) vaccination coverage and BCG scar prevalence. MethodsGuinea-Bissau Health and Demographic Surveillance System data on BCG vaccination coverage, scar status, and all-cause mortality were used for this study. Mortality risk (MR) by scar status was assessed in Cox models providing adjusted mortality rate ratios (aMRRs). Distributions were fitted for survival, vaccination coverage, and scar prevalence. Models for 12-month mortality were calculated. We utilized World Bank data on birth rates and mortality rates to assess the potential global impact of optimizing BCG vaccination programs. ResultsBCG coverage was 81% and scar prevalence 42% among 2-month-old infants, and the 1- to 12-month scar/no scar aMRR was 0.40 (0.22, 0.76). Modeling 2-month 99% vaccination coverage with 95% developing scars would change the 1- to 12-month MR by −8% (−21%, +12%). Globally, the reduction in the MR between 1- and 12-month would be −14% (−14%, −15%), corresponding to −208,075 (−214,453, −204,023) fewer infant deaths/year. ConclusionsWe confirmed previous observations: having a BCG scar markedly reduces infant MR. Increasing current global 2-month BCG vaccination coverage from 76% to 99%, and scar prevalence among vaccinated infants from 52% to 95% might reduce global infant mortality by >200,000 deaths/year. Thus, optimizing BCG vaccination programs to focus on increasing early BCG vaccination coverage and the overall scar prevalence would have major public health benefits.

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination

The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial off-target effects of BCG are proposed to be stronger amongst children who develop a BCG scar. Within an international randomised trial (‘BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers’; BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination . Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2–0.9), BCG revaccination (OR 1.7, 95%CI 1.3–2.0), female sex (OR 2.0, 95%CI 1.7–2.4), older age (OR 0.4, 95%CI 0.4–0.5) and study country (Brazil OR 1.6, 95%CI 1.3–2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (96%) did not regret having the vaccine.Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.

Factors Associated with BCG Scar of Pediatric Tuberculosis Patients at Pisangan and East Ciputat Community Health Centers

Tuberculosis (TB) is the most common cause of death in children. Prevention of TB through Bacille Calmette–Guérin (BCG) vaccination is an action to produce immunity against TB disease. After vaccination, a scar forms from the boil, which indicates a successful vaccination. This study aims to determine the factors associated with BCG Scar in pediatric TB patients. A cross-sectional design was conducted at the Pisangan and East Ciputat Community Health Centers in January-September 2020. Data collection using medical records and telephone interviews on 35 samples was taken using the probability sampling technique, simple random sampling. With inclusion criteria for pediatric TB patients (0-18 years) and exclusion criteria that do not include telephone numbers and addresses. Bivariate analysis was used with the chi-square test. The results showed a significant relationship between contact history and BCG scars in pediatric TB patients. Age, gender, nutritional status, exclusive breastfeeding, immunization, mother's education, parent's occupation, family income, and smoking history were not significantly related to BCG scar. Contact history related to BCG scar. Parents should pay more attention to and protect their children from the people around them to cut off the possibility of contact with TB sufferers even though the child has been vaccinated.

Maternal BCG primes for enhanced health benefits in the newborn

Bacille Calmette-Guérin (BCG) vaccination lowers the risk of severe infection; we tested whether effects are modulated by maternal BCG in a large cohort of BCG-vaccinated newborns from Guinea-Bissau. Maternal BCG scar status were inspected at enrolment in a BCG trial conducted from 2014 to 17 in Bissau, Guinea-Bissau. We tested associations with background factors for potential confounding; maternal age affected effect estimates >5% and accordingly, all analyses were adjusted for maternal age. Hospitalization data was collected prospectively and assessed in Cox-models providing adjusted Incidence Rate Ratios (aIRRs). In-hospital risk of death (case-fatality) risk was assessed using binomial regression providing adjusted Risk Ratios (aRRs). 60% (6,309/10,598) of mothers had a scar. The maternal-scar/no-scar admission aIRR was 0.96 (0.81-1.14) from 0 to 6 weeks and 1.12 (0.97-1.28) for 6 weeks-3 years. The 6-week in-hospital case-fatality infection aRR was 0.59 (0.34-1.05); 0.40 (0.17-0.91) for males and 0.86 (0.38-1.94) for females. Protection was especially evident against sepsis, the overall 6-week aRR=0.49 (0.26-0.91); no effect was observed for non-infectious deaths or after 6 weeks of age. Effects were similar across BCG strains and multivariate models adjusted for socioeconomic status did not affect estimates. Among BCG-vaccinated newborns, there was a trend for fewer in-hospital deaths from infection associated with maternal BCG priming, especially for males. Providing BCG to adults without a vaccination scar might enhance their offspring's capacity to handle severe infections. Brief 40-word summary: Within a trial comparing BCG strains for their overall effects on morbidity and mortality in Guinea-Bissau, vertical priming with BCG (represented by the maternal BCG scar) was associated with beneficial sex-differential effects on offspring survival.

The Effect of BCG vaccine on COVID-19 severity and mortality

Aim: To investigate the effect of Bacille Calmette-Guérin (BCG) vaccine on the severity and mortality of the disease in hospitalized patients with COVID-19 in this study.
 Methods: This study was conducted as a retrospective observational study in a tertiary reference hospital in Turkey. The patients were divided into two groups as BCG positive and negative according to the presence of BCG scar. BCG positive and negative groups were compared in terms of radiological involvement, presence of hypoxia, need for intensive care unit (ICU) and intubation, and mortality.
 Results: BCG negative patients required more inpatient treatment (p = 0.001). The radiological involvement was more severe in BCG negative group (p = 0.016). Forty-one (22.7%) patients in the BCG positive group and twenty-two (42.3%) patients in the BCG negative group were treated in the ICU, and the difference was statistically significant (p = 0.007). More patients in the BCG negative group had hypoxia than the BCG positive group (59.6% vs. 40.9%, p = 0.018). The BCG negative group needed more intubation (21.2% and 8.8%, p = 0.024). Nine (17.3%) patients in the BCG negative group and 12 (6.6%) patients in the BCG positive group died, and the difference was statistically significant (p = 0.027).
 Conclusion: The length of hospital stay was longer, radiological involvement was more severe, the need for ICU and intubation, hypoxia and mortality were higher in BCG-unvaccinated patients with COVID-19.

Positive QuantiFERON test and the severity of COVID-19 disease: A prospective study

BackgroundA strong negative correlation is reported between the Bacille Calmette Guerin (BCG) index and COVID-19 mortality. The present study explored if frequent exposure to strong Th1 antigens like Mycobacteria or Salmonella have any effect on the progression of the disease in COVID-19 patients. MethodsThis prospective comparative study comprised of 3 groups of 20 each of mild or asymptomatic COVID-19 patients (A), severely ill patients (S) and healthy volunteers with a COVID Negative report (H). ResultsQuantiFERON TB Gold (QFT) which is interferon gamma release assay (IGRA) against Mtb antigen was used to quantify immunity status of patients against the tuberculosis. Group S showed positive QFT in only 15% patients as against 50% QFT positive patients in group A and H. All fourteen patients in group S with QFT negative report died while 5 of six survived patients showed positive QFT report either on initial or repeat testing done at 6 weeks. The sixth survived patient was QFT negative but showed high antibody titre against H antigen (TH) on Widal test. All severely ill group S patients showed huge reduction of IGRA even to the mitogen stimulus thus suggesting gross general unresponsiveness of T cells. Presence of BCG scar showed no correlation with prevalence or progression of the disease. ConclusionPopulation in an endemic area of tuberculosis and typhoid with good community exposure to these antigen is likely to withstand COVID -19 better and show reduced mortality following it.

Determinants of Bacille Calmette-Guérin scarification in Danish children

BackgroundStudies in low-income countries have shown that among Bacille Calmette-Guérin (BCG) vaccinated children, those who develop a BCG-scar have significantly better survival than those who do not develop a scar. In a Danish multicenter randomized clinical trial we assessed determinants for developing a BCG-scar and for BCG scar size following neonatal BCG vaccination. MethodsAt three Danish hospitals, newborns were randomized 1:1 to BCG vaccination or no BCG vaccination. The infants were invited for a clinical examination at the ages of 3 and 13 months. At 13 months, the scar site was inspected and scar size measured. We investigated three groups of determinants; external, parental, and individual-level determinants on relative scar prevalence and differences in median scar sizes. ResultsAmong 2118 BCG vaccinated infants, 2039 (96 %) were examined at 13 months; 1857 of these (91 %) had developed a BCG-scar. Compared with Copenhagen University Hospital, Hvidovre (85 %), Copenhagen University Hospital, Rigshospitalet had a scar prevalence of 95 % (adjusted Prevalence ratio (aPR) = 1.24 [CI 95 %: 1.18 to 1.30]); it was 93 % at Kolding Hospital (aPR 1.27 [CI 95 %: 1.19 to 1.35]). Increasing vaccine experience was positively associated with developing a scar and with scar size. ConclusionAcross multiple potential determinants of BCG scaring and size, logistical factors dominated. The results support that injection technique is an important determinant of developing a scar. Given the strong link between having a BCG scar and subsequent health, improved BCG vaccination technique could play a major role for child health.

Factors Associated with Latent Tuberculosis Infection among the Hospital Employees in a Tertiary Hospital of Northeastern Thailand.

Latent tuberculosis infection (LTBI) can develop into tuberculosis (TB). The WHO requires the discovery and management of LTBI among high-risk groups. Health care workers (HCWs) constitute a high-risk group. Factors associated with LTBI among HCWs in Thailand need further study. The current study aimed to explore the factors related to LTBI among Thai HCWs. A hospital-based, matched case-control study was conducted. All cases and controls were HCWs at a tertiary hospital in northeastern Thailand. Between 2017 and 2019, a total of 85 cases of interferon-γ release assays (IGRAs)-proven LTBI, and 170 control subjects were selected from a hospital (two controls per case). The two recruited controls were individually matched with LTBI cases by sex and age (±5 years). Secondary data were obtained from the occupational health and safety office. Case HCWs had a higher proportion of significant factors than control HCWs (i.e., working closely with pulmonary TB—94.1% vs. 88.8%, and working in the area of aerosol-generating procedures (AGPs) 81.2% vs. 69.4%). The bivariate conditional logistic regression showed that the occurrence of LTBI in HCWs was statistically significant (p-value < 0.05), particularly with respect to: workplaces of AGPs (crude OR = 1.90, 95% CI: 1.01–3.58, p = 0.041); among HCWs performing AGPs (crude OR = 2.04, 95% CI: 1.20, 3.48, p = 0.007); and, absent Bacille Calmette-Guérin (BCG) scar (crude OR = 2.59, 95% CI: 1.50–4.47, p = 0.001). Based on the multivariable conditional logistics analysis, HCWs who performed AGPs while contacting TB cases had a statistically significant association with LTBI (adjusted OR = 1.82, 95% CI: 1.04–3.20, p = 0.035). HCWs who reported the absence of a BCG scar had a statistically significant association with LTBI (adjusted OR = 2.49, 95% CI: 1.65–5.36, p = 0.001), whereas other factors including close contact with TB (adjusted OR = 2.44, 95% CI: 0.74, 8.09, p = 0.123) were not significantly associated with LTBI. In conclusion, HCWs who performed AGPs and were absent a BCG scar had a significant association with LTBI, while other factors played a less critical role.

BCG scar, socioeconomic and nutritional status: a study of newborns in urban area of Makassar, Indonesia.

SummaryObjectiveTo investigate factors that determine the response to Bacille Calmette–Guérin (BCG) vaccination in urban environments with respect to socioeconomic status (SES), prenatal exposure to infections or newborn's nutritional status.MethodsThe study was conducted in an urban area, in Makassar, Indonesia. At baseline, 100 mother and newborns pair from high and low SES communities were included. Intestinal protozoa, soil transmitted helminths, total IgE, anti‐Hepatitis A Virus IgG and anti‐Toxoplasma IgG were measured to determine exposure to infections. Information on gestational age, birth weight/height and delivery status were collected. Weight‐for‐length z‐score, a proxy for newborns adiposity, was calculated. Leptin and adiponectin from cord sera were also measured. At 10 months of age, BCG scar size was measured from 59 infants. Statistical modelling was performed using multiple linear regression.ResultsBoth SES and birth nutritional status shape the response towards BCG vaccination at 10 months of age. Infants born to low SES families have smaller BCG scar size compared to infants born from high SES families and total IgE contributed to the reduced scar size. On the other hand, infants born with better nutritional status were found to have bigger BCG scar size but this association was abolished by leptin levels at birth.ConclusionThis study provides new insights into the importance of SES and leptin levels at birth on the development of BCG scar in 10 months old infants.

TST, QuantiFERON-TB Gold test and T-SPOT.TB test for detecting latent tuberculosis infection in patients with rheumatic disease prior to anti-TNF therapy.

Before starting tumour necrosis factor (TNF)-α blocking agents, standard tests should be used for the diagnosis of tuberculosis infection. The specificity of traditional tuberculin skin test (TST) is low in immunosuppressed patients due to prior Bacille Calmette Guérin (BCG) vaccination, non-tuberculous mycobacteria infections, false positive and negative results. In this study, we aimed to compare TST and Interferon-Gamma Release Assay (IGRA) tests for detecting latent tuberculosis infection in patients with rheumatic disease planned to receive TNF-α blocking agents. One hundred and nine patients (45 male, 64 female) with the diagnosis of rheumatoid arthritis (RA) (n= 70) and ankylosing spondylitis (AS) (n= 39) were included in the study. Age, sex, number of BCG scar, results of TST (using the Mantoux method), QuantiFERON-TB Gold test and T-SPOT.TB test were recorded for all patients. Correlation between the tests was assessed by Pearson correlation coefficient. The mean age of RA and AS patients were 50 ± 13 (19-78 years). The prevalence of latent tuberculosis was 43.1% for TST, 39.4% for QuantiFERON-TB Gold test and 13.8% for T-SPOT.TB test, compared with the evaluation using the composite criteria such as close contact with active tuberculosis infection and/or suspicious fibrotic/calcific lesions on chest X-Ray without active tuberculosis infection. There was a moderate correlation between BCG scar number and TST (p< 0.001, r= 0.495), T-SPOT.TB test and QuantiFERON-TB Gold test (p= 0.007, r= 0.406), T-SPOT.TB test and composite criteria (p= 0.024, r= 0.343). The specificity of QuantiFERON-TB Gold test was 85.7%, and sensitivity was 73.9% for all patients with rheumatic disease. It was 73.5% and 66.7% for T-SPOT.TB test, respectively. The specificity of TST was 60.3% and sensitivity was 47.8% for TST. IGRA tests are not affected prior vaccination and useful for detecting latent tuberculosis infection in patients treated with corticosteroid due to lack of correlation between test negativity and corticosteroid therapy. Also, they are useful tests for diagnosis of latent tuberculosis infection as an alternative to TST due to their specificity and sensitivity.

Can colony-forming unit testing be used to extend the shelf life of BCG vaccines?

A recent shortage in supply of Bacille Calmette-Guérin (BCG), the live attenuated vaccine given to protect against tuberculosis (TB) caused major disruption to global vaccination programs. In this study, we assessed whether quantification of viable bacteria, could be used to inform the use of the BCG vaccine beyond its manufacturer-assigned expiration date. The viability of a single batch of BCG-Denmark was tested in three independent laboratories. There was high inter-vial and inter-laboratory variability in viability counts, however all three laboratories detected a decrease in BCG viability over time. Despite this, there was no difference in the rate of BCG scar formation in infants who were vaccinated with this batch of BCG before and after its manufacturer-assigned expiration date. This study demonstrates the potential for using BCG viability counts to guide the use of BCG vaccine beyond the manufacturer-assigned expiration date.

An Overview of Coverage of BCG Vaccination and Its Determinants Based on Data from the Coverage Survey in Zhejiang Province.

To assess the Bacille Calmette-Guérin (BCG) vaccination coverage in Zhejiang province and to investigate predictors of the BCG vaccination, we used data from the 2017 Zhejiang provincial coverage survey. Demographic and immunization data on the selected children, their mothers, and their families were also collected by using a pre-tested questionnaire. BCG scars were verified among children who were available at the moment of survey. Coverage of BCG and other expanded program on immunization (EPI) vaccines scheduled before the first year of life was calculated. BCG coverage through the scar assessment and timeliness of BCG were also presented. Multivariate analyses of the predictors associated with the BCG vaccination and its timeliness were conducted separately. In total, 1393 children agreed to participate in the survey and presented the immunization cards. Of them, the coverage of BCG was 92.0% and 88.3% received the BCG within the first 28 days after birth. Besides this, 1282 out of the 1393 children were screened for the BCG scars and 97.1% of them had developed the scars. The multivariable logistic regression analyses indicated that hospital delivery, higher maternal education, a mother with no job, and a resident child were positively associated with the higher BCG vaccination coverage and its timely administrations. BCG coverage was optimal and it was administered in a timely manner. The majority of children vaccinated with BCG developed scars. Tailored interventions should be more greatly focused on and targeted to children with the risk factors identified in this study.

Reaction of the BCG Scar in the Acute Phase of Kawasaki Disease in Mexican Children.

Kawasaki disease (KD) is an acute self-limited systemic vasculitis that primarily affects children <5 years old. There is no specific diagnostic test. A reaction at the Bacille Calmette-Guérin (BCG) inoculation site has been reported as a common finding in patients with KD where BCG vaccination is mandatory. The purpose of this study was to evaluate the frequency of reactivation of the BCG in Mexican children diagnosed with KD. A retrospective study of all patients diagnosed with KD from August 1, 1995, to August 31, 2015, at our Institution was performed. The clinical profile, laboratory results, treatment used and coronary artery abnormalities in the BCG reactive and the BCG nonreactive groups were analyzed and compared. We included 399 patients with KD. Ninety-seven (24.3%) had BCG reaction at the inoculation site. The BCG(+) group was younger than the BCG(-) group (P < 0.000). There were 18 (18.55%) incomplete cases in the BCG(+) group compared with 65 (21.52%) in the BCG(-) group without statistical significance. The BCG+ group developed coronary artery aneurysms in 37 cases and the BCG(-) group developed coronary artery aneurysms in 111 cases without statistical significance. Multivariate analysis showed that younger age at diagnosis was the only variable associated with a reaction at the BCG inoculation site in patients with KD. In Mexico, a country with a National BCG Vaccination Program and a low incidence of KD, reaction at the BCG inoculation site could be a useful diagnostic sign of KD.

Role of bacille Calmette-Guérin in preventing tuberculous infection.

Rural community in South India. To determine the role of bacille Calmette-Guérin (BCG) in preventing tuberculous infection in children. A prevalence survey was undertaken in 1999-2001 in a representative rural population in Tiruvallur District in South India using cluster sampling. Tuberculin testing was performed among all children aged <15 years, and all adults aged 15 years were questioned about chest symptoms and underwent radiography, followed by sputum examinations, if indicated. In children living in households with a tuberculosis case, the proportion with evidence of tuberculous infection was 35.5% of 200 in the absence of a BCG scar and 27.0% of 100 in its presence, a reduction of 24% (P = 0.14). In very young children (age <5 years), the corresponding proportions were 29.1% of 55 and 11.9% of 42, a reduction of 59%; the difference was statistically significant (P = 0.048). There is a possible role for BCG in preventing tuberculous infection in very young children.

Risk of tuberculous infection in adolescents and adults in a rural community in Ethiopia.

The incidence of tuberculosis (TB) in sub-Saharan Africa is one of the highest in the world. To evaluate the prevalence of TB, the annual risk of tuberculous infection (ARTI) and associated risk factors in rural Ethiopia. A tuberculin skin test was performed among 2743 individuals in a rural community of Ethiopia around Ginci town, west of Addis Ababa, to estimate the prevalence of tuberculin reactivity and to assess factors associated with tuberculous infection. Among 2743 volunteer participants, test results were available for 2640, 691 (26.2%) of whom had an identifiable bacille Calmette-Guérin (BCG) scar; 221 (8.3%) reported household contact with a known TB case. The overall prevalence of TST reactions of ⩾ 10 mm was 29.7%. The ARTI was estimated at 1.7%. Tuberculin reactivity varied with age, sex, income and history of household contact with a TB case. Presence of BCG scar was not related to tuberculin reactivity. Our findings indicate that despite an effective TB control programme, TB transmission rates are still high in rural Ethiopia. Provision of isoniazid prophylaxis in close contacts of active TB cases among the poorest population groups may reduce TB incidence.

Tuberculin reaction and BCG scar: association with infant mortality.

To test the hypothesis that having a scar and a positive tuberculin skin test (TST) response after vaccination with Bacille Calmette-Guérin (BCG) is associated with reduced infant mortality. We studied cohorts of 2709 normal-birthweight (NBW) and 1102 low-birthweight (LBW) infants in Guinea-Bissau. Children were enrolled in randomised trials between year 2002 and 2008 and received BCG vaccination at birth. BCG scars and TST responses were assessed at 2 and 6 months of age. The infants were followed for mortality to 12 months of age, and survival was analysed using Cox regression. At age 2 months, 88% of NBW children and 91% of LBW children had a BCG scar, and 36% and 17% had a TST response, respectively. The LBW infants had nearly twofold higher mortality (4.5%) than the NBW infants (2.8%) between 2 and 12 months of age. In the LBW cohort, the adjusted mortality rate ratio (MRR) comparing children with a BCG scar with those without was 0.42 (95% CI = 0.19; 0.93). There was a similar tendency for TST positivity: MRR = 0.47 (95% CI = 0.14; 1.54). For LBW children who had both a positive TST reaction and a scar, the MRR was 0.22 (95% CI = 0.05; 0.87). For NBW children, a scar and a positive TST were associated with 20% reductions in mortality, which did not reach statistical significance. We confirmed previous observations that having a scar and a TST response after BCG vaccination is associated with lower mortality risk. The possibility of revaccinating scar-negative children should be considered.

Tuberculosis in Malaysia: predictors of treatment outcomes in a national registry.

To determine treatment outcomes and associated predictors of all patients registered in 2012 with the Malaysian National Tuberculosis (TB) Surveillance Registry. Sociodemographic and clinical data were analysed. Unfavourable outcomes included treatment failure, transferred out and lost to follow-up, treatment defaulters, those not evaluated and all-cause mortality. In total, 21 582 patients were registered. The mean age was 42.36 ± 17.77 years, and 14.2% were non-Malaysians. The majority were new cases (93.6%). One fifth (21.5%) had unfavourable outcomes; of these, 46% died, 49% transferred out or defaulted and 1% failed treatment. Predictors of unfavourable outcomes were older age, male sex, foreign citizenship, lower education, no bacille Calmette-Guérin (BCG) vaccination scar, treatment in tertiary settings, smoking, previous anti-tuberculosis treatment, human immunodeficiency virus infection, not receiving directly observed treatment, advanced chest radiography findings, multidrug-resistant TB (MDR-TB) and extra-pulmonary TB. For all-cause mortality, predictors were similar except for rural dwelling and nationality (higher mortality among locals). Absence of BCG scar, previous treatment for TB and MDR-TB were not found to be predictors of all-cause mortality. Indigenous populations in East Malaysia had lower rates of unfavourable treatment outcomes. One fifth of TB patients had unfavourable outcomes. Intervention strategies should target those at increased risk of unfavourable outcomes and all-cause mortality.

A randomized clinical trial in adults and newborns in South Africa to compare the safety and immunogenicity of bacille Calmette-Guérin (BCG) vaccine administration via a disposable-syringe jet injector to conventional technique with needle and syringe

IntroductionIntradermal bacille Calmette-Guérin (BCG) vaccination by needle-free, disposable-syringe jet injectors (DSJI) is an alternative to the Mantoux method using needle and syringe (NS). We compared the safety and immunogenicity of BCG administration via the DSJI and NS techniques in adults and newborn infants at the South African Tuberculosis Vaccine Initiative (SATVI) research site in South Africa. MethodThirty adults and 66 newborn infants were randomized 1:1 to receive intradermal BCG vaccine (0.1mL in adults; 0.05mL in infants) via DSJI or NS. Wheal diameter (mm) and skin fluid deposition at the site of injection (SOI) were measured immediately post-vaccination. Adverse events and SOI reactogenicity data were collected 30min and 1, 2, 4, and 12 weeks after vaccination for adults and at 30min and 4, 10, and 14 weeks for infants. Blood was collected in infants at 10 and 14 weeks to assess BCG-specific T-cell immune responses. ResultsMore infant BCG vaccinations by DSJI deposited >5μL fluid on the skin surface, compared to NS (49% versus 9%, p=0.001). However, all 12 infant vaccinations that did not produce any SOI wheal occurred in the NS group (36%, p<0.001). Median wheal diameter, in participants for which an SOI wheal formed, did not differ significantly between groups in infants (combined 3.0mm IQR 2.0 to 4.0, p=0.59) or in adults (combined 9.0mm IQR 7.0 to 10.0, p=0.13). Adverse events were similar between study arms. Proportion of participants with BCG scars after three months did not differ in adults (combined 97%, p=0.67) or infants (combined 62%, p=0.13). Frequencies of BCG-specific clusters of differentiation 4 (CD4) and clusters of differentiation 8 (CD8) T-cells co-expressing IFN-γ, TNF-α, IL-2, and/or IL-17 were not different in the DSJI and NS groups. ConclusionBCG vaccination of newborn infants via DSJI was more likely to deliver an appropriate intradermal wheal at the SOI as compared to NS, despite leaving more fluid on the surface of the skin. Safety, reactogenicity, and antigen-specific T-cell immune responses did not differ between DSJI and NS techniques.