Revisiting the Chingleput BCG vaccination trial for the impact of BCG revaccination on the incidence of tuberculosis disease

Background & objectives: Vaccines play a crucial role in the prevention of tuberculosis (TB). Revaccination with Bacille Calmette–Guerin (BCG) for the prevention of TB is an important strategy that is currently gaining interest. The objective of this study was to reanalyze the community-based Chingleput BCG vaccination trial for protective efficacy of BCG revaccination against incident TB disease. Methods: A retrospective analysis of the Chingleput BCG vaccination trial (conducted in 1968) data was carried out. Data on participants with evidence of prior BCG vaccination at trial intake and randomized to BCG vaccine [low dose (0.01 mg), high dose (0.1 mg)] and placebo arms were analyzed. The incidence of TB disease, which was based on sputum culture and/or chest X-ray was compared between the BCG and placebo arms over a 15 yr follow up period. Results: Of the 269,727 individuals randomized in the trial; 263,158 had no evidence of TB at baseline, of which 4436 (1.68%) had evidence of BCG vaccination at trial intake (2890 in the BCG vaccine and 1546 in the placebo arms, respectively). There were 77 (190 per 100,000) and 64 (296 per 100,000) incident TB cases in the BCG and placebo arm, respectively, at 15 yr post-vaccination. The incidence of TB disease was significantly lower in the BCG arm [Hazard ratio of BCG arm (95% confidence interval): 0.64 (0.46-0.89)]. Interpretation & conclusions: Retrospective data analysis of this community-based trial revealed that BCG revaccination in a community offered modest protection against the development of TB disease at the end of 15 years which, however, requires further evaluation.

Efficacy of a second dose measles-mumps-rubella vaccine in children in Xicheng District, Beijing, China in 2016 / 中华微生物学和免疫学杂志

Objective To analyze the efficacy of a second dose of measles-mumps-rubella (MMR) vaccine in children aged 6 to 7 years in Xicheng District, Beijing, China in 2016.Methods Serum samples were collected in duplicate from 41 children aged 6 to 7 years before and one month after immunization with a second dose of MMR vaccine.ELISA was performed to detect IgG antibodies against measles, rubella and mumps in serum samples.Results The positive rates of antibodies against measles, rubella and mumps in the 41 children before immunization with a second dose of MMR vaccine were 95.12%, 90.24% and 92.68% and the antibody titers were (825.88±499.91), (53.83±32.48) and (697.83±535.82) IU/ml, respectively.The positive rates of the three antibodies were 100%, 97.56% and 100% after revaccination with MMR vaccine and the antibody titers were (1 102.98±356.77), (95.08±26.88) and (3 383.85±1 903.06) IU/ml.Titers of antibodies against measles, rubella and mumps increased significantly following revaccination (P0.05).Conclusion The second dose immunization of MMR vaccine achieves a high successful rate in children in Xicheng District of Beijing.It would be an effective immunization strategy to protect children from measles, rubella and mumps.

Kinetics of rabies antibodies as a strategy for canine active immunization

Rabies, a zoonosis found throughout the globe, is caused by a virus of the Lyssavirus genus. The disease is transmitted to humans through the inoculation of the virus present in the saliva of infected mammals. Since its prognosis is usually fatal for humans, nationwide public campaigns to vaccinate dogs and cats against rabies aim to break the epidemiological link between the virus and its reservoirs in Brazil. During 12 months we evaluated the active immunity of dogs first vaccinated (booster shot at 30 days after first vaccination) against rabies using the Fuenzalida-Palácios modified vaccine in the urban area of Botucatu city, São Pauto state, Brazil. Of the analyzed dogs, 54.7% maintained protective titers (≥0.5 IU/mL) for 360 days after the first vaccination whereas 51.5% during all the study period. The present results suggest a new vaccination schedule for dogs that have never been vaccinated. In addition to the first dose of vaccine, two others are recommended: the second at 30 days after the first and the third dose at 180 days after the first for the maintenance of protective titers during 12 months.

Kinetics of rabies antibodies as a strategy for canine active immunization

Background Rabies, a zoonosis found throughout the globe, is caused by a virus of theLyssavirus genus. The disease is transmitted to humans through the inoculation of the virus present in the saliva of infected mammals. Since its prognosis is usually fatal for humans, nationwide public campaigns to vaccinate dogs and cats against rabies aim to break the epidemiological link between the virus and its reservoirs in Brazil.Findings During 12 months we evaluated the active immunity of dogs first vaccinated (booster shot at 30 days after first vaccination) against rabies using the Fuenzalida-Palácios modified vaccine in the urban area of Botucatu city, São Pauto state, Brazil. Of the analyzed dogs, 54.7% maintained protective titers (≥0.5 IU/mL) for 360 days after the first vaccination whereas 51.5% during all the study period.Conclusions The present results suggest a new vaccination schedule for dogs that have never been vaccinated. In addition to the first dose of vaccine, two others are recommended: the second at 30 days after the first and the third dose at 180 days after the first for the maintenance of protective titers during 12 months.(AU)

Enhancement of vitamin A combined vitamin D supplementation on immune response to Bacille Calmette-Guérin vaccine revaccinated in Chinese infants

OBJECTIVE@#To investigate whether there is an association between diameter of bacille Calmette-Guérin (BCG) scars and effect of purified protein derivative (PPD) reaction and to determine whether vitamin A (VA) combined vitamin D (VD) supplementation influences the immune response to BCG revaccinated in Chinese infants.@*METHODS@#A cross-section and 3-month community-randomised trial was conducted. A total of 5 629 infants at 3, 6 and 12 months of age in Junan County of China were examined for BCG scar formation. Then, 597 revaccinated infants were randomly assigned to supplementation (n=307) and control (n=290) groups. The supplementation group were daily assigned to 1 500 IU VA and 500 IU VD for 3 months. Then all infants were subjected to skin test with PPD.@*RESULTS@#The diameter of BCG scars was positively correlated with diameter of skin indurations of PPD (r=0.17, P<0.05) in the 5 629 infants. The rate of positive response to PPD was higher in the supplementation group than in the control group (96.1% versus 89.7%, P<0.05, prevalence ratio 1.07, 95% CI 1.02-1.12). The prevalence ratio of PPD response for the supplementation group compared with that for the control group was 1.07 (95% CI 1.01-1.13) for the males and 1.08 (95% CI 1.00-1.17) for the females. For the supplementation group, the males got larger tuberculin induration than the females [(0.73±0.21) cm versus (0.67±0.20) cm, P<0.05) after intervention.@*CONCLUSIONS@#The diameter of BCG scars was effectively correlated with PPD response, which indicates BCG scar formation may be an useful tool to evaluate the effect of tuberculosis prevention. VA combined VD supplementation may play an immuno-regulatory role in BCG revaccination. This may contribute to the prevention of childhood tuberculosis.

BCG vaccination scars of internally displaced children in the north of Sri Lanka.

Objective: To study the BCG vaccination scars among the under 5 year old internally displaced children in Vavuniya district. Study design: Cross sectional descriptive study Setting: Temporary settlement camps in Vavuniya district Method: All children between 6 to 60 months attending paediatric clinics held in the temporary settlement camps from 1st April to 15th May 2009 were included in the study. The interviewer administered questionnaire and examination of the child for the BCG scar were used to collect data. Results: One thousand and six children attending the clinics during the study period were analyzed. Nine hundred and seventy five children received BCG vaccination whilst vaccination data for 31 patients was not available. One hundred and fifty three children did not have a visible scar. Conclusion: Fifteen percent of under 5 year old internally displaced children in Vavuniya district did not have BCG scars.

BCG vaccinaton scars of childen under five years in a tertiary care hospital.

Objective To study the BCG vaccination scars of under 5 year old children who were admitted to a tertiary care hospital Design Cross sectional descriptive study Setting Ward 3, Lady Ridgeway Hospital for Children (LRH) Method All children between 6 and 60 months of age, admitted to ward 3 LRH from October 15th to December 30th 2006, were included in the study. The interviewer-administered questionnaire and examination of the child for BCG scar were the methods used to collect the data. Results: Of 1010 patients admitted to ward 3 LRH during the study period, 923 were analysed. BCG vaccine had been given to all patients. Whilst 821 (89%) patients had the BCG scar, 102 (11%) did not have it. Among patients with the BCG scar, 20% had received BCG vaccine in non tertiary care hospitals, whereas in patients with absent BCG scar, this figure was 35% (p=0.003; p < 0.05). In the Child Health Development Record (CHDR), the BCG scar column had been marked in only 554 (64%). Among 102 patients with absent BCG scar, revaccination was not indicated in 20 (21%) because the BCG scar had been marked as positive in the CHDR. However, 96 had not been revaccinated. Common reasons for non revaccination were: unawareness of mothers regarding absent BCG scar (38.5%) and postponement of revaccination (24%). Conclusion There was a significant number of patients with absent BCG scars indicating need for larger scale studies.

Comparison of the seroconversion rate after primary hepatitis B vaccination and after revaccination of non-responders in full-term infants according to mother's HBsAg seropositivity / 소아과

PURPOSE: This study aimed to identify the true extent of non-responsiveness in full-term infants born from HBsAg-negative or HBsAg-positive mothers and vaccinated against hepatitis B virus (HBV) at 0, 1, and 6 months of age and to evaluate the effect of revaccination among non-responders. METHODS: The study included 716 full-term infants born in 2004-2007. Of 716, 662 infants (A group) were born to HBsAg- negative mothers and 54 infants (B group: 50, except HBsAg-positive infants) were born to HBsAg-positive mothers. All infants were administered DNA recombinant vaccines at 0, 1, and 6 months of age. B group infants received hepatitis B immunoglobulin at birth. Anti-HBs titers were tested at 7-12 and 9-15 months in A and B groups, respectively. Three revaccination doses were administered to non-responders whose anti-HBs titers were under 10 mIU/ml; revaccinated infants were retested at 1-3 months after last vaccination. The association between HBeAg seropositivity of mother and the failure of HBV immunoprophylaxis was evaluated. RESULTS: The seroconversion rates after primary hepatitis B vaccination were higher in A group (94.1%) than in B group (78%, P<0.001). The seroconversion rates were high in revaccinated infants (A group non-responders: 96.9%, B group non- responders: 87.5%). The failure of HBV immunoprophylaxis was significantly associated with maternal HBeAg seropositivity (P<0.001). CONCLUSION: The seroconversion rates after primary hepatitis B vaccination were low in B group infants. Revaccination of non-responders in B group was very effective. Therefore, anti-HBs testing and revaccination of B group is very important. Revaccination of non-responders in A group was also very effective. Thus, testing the immune status of infants born to HBsAg-negative mothers even after primary hepatitis B vaccination should be considered. However, to realize this, further studies on the cost-effectiveness of anti-HBs testing in healthy full-term infants are necessary.

INTRAMUSCULAR VERSUS INTRADERMAL HEPATITIS B REVACCINATION IN HEALTHY NON-RESPONDER CHILDREN:A 5-YEAR PROSPECTIVE RANDOMIZED STUDY / 药物分析学报

Objective With the same times of injection to compare low-dose intradermal regimen with routine-dose intramuscular inoculation in revaccination of non-responders to hepatitis B vaccine. Methods 40 healthy non-responder children collected by screening were administrated a three-dose revaccination randomly by intramuscular or intradermal route (10 vs 2 g per dose), and regularly tested for serologic markers up to five years. By the end of follow-up, a booster dose (5 μg) was given to those who had lost anti-HBs of ≥10 mIU/mL (seroprotection) and anamnestic response was estimated thereafter. Results All 17 intramuscular and 22 of 23 intradermal children effected seroprotection after revaccination. Intradermal children lost seroprotection over time significantly rapider compared with intramuscular children (Log Rank test, P= 0.029). In year 5, 50% of intramuscular but only 18.2% of intradermal children still maintained seroprotection (P=0.075). 12-14 days after the booster dose, all the eight intramuscular children developed an anamnestic response with anti-HBs titer increasing greater, but two of the 18 intradermal children failed to mount seroprotective level. Conclusion Three-routine-dose intramuscular revaccination was significantly effective than low-dose intradermal one with the same times of injection, especially in long-term immunity. We recommend routine-dose intramuscular protocol in revaccination of non-responders.

Effects of Hepatitis B Revaccination in Nonresponsive Children

PURPOSE: Hepatitis B virus infection is prevalent in Korea. Active immunization of Hepatitis B has been proceeded extensively for the last decade. This study was performed to estimate the negative rate of anti-HBs after immunization and to evaluate the effect of revaccination among Korean children between 1995 and 1997, as well as to determine a proper revaccination schedule. METHODS: Anti-HBs was measured with enzyme immunoassay. Hepatitis B revaccination was performed on nonresponders, those who were previously vaccinated and whose anti-HBs titers were under 10mIU/mL. Group A was revaccinated one dose of the same amount of the previous vaccine. Group B was given three doses of the same amount of the vaccine. Group C was given one double dose of the vaccine. The seroconversion rate and geometrical mean titer were measured one month later. RESULTS: Negative anti-HBs rate was 14.5% in children who had been vaccinated. The seroconversion rate was high in all revaccination groups(86.7-94.7%). Three doses of revaccination had no significant difference from one dose of revaccination. There was no positive effect of double dose of revaccination in comparison with the usual dose. CONCLUSION: In our study, one dose of hepatitis B vaccine is as effective as three doses or double dose of hepatitis B vaccine for the nonresponsive children. We recommend administering one dose of hepatitis B vaccine to those children whose three anti-HBs titer is under 10mIU/mL and examining of the anti-HBs titer one month later after revaccination.

The risk factors of the nonresponders after hepatitis B vaceinatio and the immunogenecity after a double-dose revaccination in the nonresponders

BACKGROUND: Korea is an endemic area of viral hepatitis B with a rate of 5~10% carrier state. Therefore, hepatitis B vaccination is performed nationwide. But 5~15% of healthy individuals fail to respond adequately to the vaccine and an approved guideline for the nonresponders has not been developed yet. This study is designed to identify risk factors for those who lack anti-HBs after hepatitis B vaccination and to document the results of a double-dose revaccination in such nonresponders to the primary vaccination. METHODS: From Feb. 1996 to Aug, 1997, we assessed 51 healthy subjects(HBs Ag negative, anti-HBs negative, anti-HBc negative and a normal LFT). All subjects were vaccinated with Hepavax- B, 1.0ml, 24 by a rapid schedule(0, 1, and 2 months) and 27 by a standard schedule(0, 1, and 6 months). Anti-HBs titers were evaluated 3 months after the third vaccine and assessed the nonre-sponders (anti-HBs titer<2mIu/ml) and the hyporesponders(2~10mK/ml). All 13 nonresponders were revaccinated with 2ml of Hepavax-B 3 months after the primary vaccination. Anti-HBs titers were evaluated 1 month later. RESULTS: The differences in age(p<0.01) and smoking amount(p<0.05) between the responders and the hypo and the nonresponders were statistically significant. There were more males and higher body mass index in the hypo and the nonresponders but not statistically significant. The seroconversion rate after the double-dose vaccination was 92.3%(12/13) with an average titer of 5K08mlU/ ml(1-132.4mIU/ml). CONCLUSIONS: Increase in age and smoking amount were the risk factors of the nonresponders after the primary vaccination. Most of the hypo and the nonresponders to the primary vaccination responded adequately to the double-dose revaccination.