Scar size and effectiveness of Bacillus Calmette Guerin (BCG) vaccination in the prevention of tuberculosis and leprosy: a case-control study.

BACKGROUND: The study was undertaken to estimate the effectiveness of BCG vaccination in relation to scar size in the prevention of tuberculosis and leprosy. METHODS: The present study was designed as hospital-based pair-matched case-control study and was carried out at Government Medical College Hospital, Nagpur, Maharashtra, India. It included 877 cases of tuberculosis and 292 cases of leprosy (diagnosed by WHO criteria), born onwards 1962. Each case was pair-matched with one control for age, sex and socio-economic status. BCG vaccination status was assessed by examination for the presence of BCG scar, immunisation records if available and information from subjects/parents of children. Subjects uncertain about BCG vaccination were not included. The diameter of the BCG scar was measured both across and along the arm in millimeters using a plastic ruler. The average was then calculated. RESULTS: A significant protective association between BCG vaccination and tuberculosis (OR=0.38, 95% CI 0.31-0.47) and leprosy (OR = 0.38, 95% CI 0.26-0.55) was observed. The overall vaccine effectiveness (VE) was 62% (95% CI 53-69) against tuberculosis and 62% (95% CI 45- against leprosy. Vaccine effectiveness against tuberculosis and leprosy was non-significantly greater in the group who had BCG scar size < or =5 mm as compared to subjects who had BCG scar size > 5 mm. Thus there was no clear association between BCG scar size and its effectiveness. CONCLUSION: The current study did not identify any significant association between BCG scar size and its effectiveness against tuberculosis or leprosy.

BCG vaccine: efficacy and indications for vaccination and revaccination.

OBJECTIVES: To review the protective efficacy of the first and second doses of BCG vaccine and to assess its major indications and contraindications. SOURCES OF DATA: A systematic review of the literature was made by searching PubMed and selecting studies carried out in the last 50 years. The studies were grouped according to their design (clinical trials, case-control studies, and meta-analyses) and the results were presented separately for each type of study. Other relevant topics such as BCG and HIV/AIDS, use of tuberculin skin test, issues related to vaccine scars and to the development of new vaccines were also reviewed. SUMMARY OF THE FINDINGS: BCG vaccine has been used since 1921. However, the data concerning its use are variable and inconsistent. The protective efficacy of the first dose of BCG vaccine against miliary tuberculosis or tuberculous meningitis is remarkably important. Nevertheless, results regarding pulmonary tuberculosis have been inconsistent, either showing no efficacy or a protective efficacy rate around 80%. There is some evidence that a second dose of BCG vaccine does not increase its protective efficacy. Studies have shown that BCG vaccine protects against leprosy. The development of new vaccines to replace BCG in the future has been investigated. CONCLUSIONS: Despite the hope that a new vaccine against tuberculosis will be available in the future, BCG vaccine, in spite of its deficiencies, is today and will be for many years to come an important tool in controlling the harmful effects of tuberculosis, especially in countries where this disease has moderate to high levels of incidence.

Vacina BCG: eficácia e indicações da vacinação e da revacinação / BCG vaccine: efficacy and indications for vaccination and revaccination

OBJETIVOS: Revisar aspectos relacionados ao efeito protetor da primeira e segunda doses da vacina BCG e discutir as suas principais indicações e contra-indicações. FONTES DOS DADOS: Utilizando o PubMed, foi realizada uma revisão sistemática da literatura abrangendo um período de, aproximadamente, 50 anos. Os estudos foram agrupados por tipo de desenho, apresentando-se separadamente os principais resultados de ensaios clínicos, estudos de caso-controle e meta-análises. Outros tópicos relevantes, como a BCG e HIV/AIDS, o uso do teste tuberculínico, aspectos relacionados à cicatriz vacinal e ao desenvolvimento de novas vacinas, dentre outros, foram também revistos. SíNTESE DOS DADOS: A vacina BCG é utilizada desde 1921. Apesar disso, ainda apresenta controvérsias e aspectos não esclarecidos. O efeito protetor da primeira dose da vacina BCG contra a tuberculose na forma miliar ou na meningite é bastante significativa. No entanto, em relação à forma pulmonar, os resultados são discordantes, variando de ausência de efeito a níveis próximos a 80 por cento. Há evidências de que uma segunda dose da BCG não aumenta o seu efeito protetor. Estudos demonstram proteção da vacina contra a hanseníase. Pesquisas sobre novas vacinas que, no futuro, poderão vir a substituir a BCG estão sendo realizadas. CONCLUSÕES:Apesar da expectativa de que, no futuro, venhamos a ter uma nova vacina para a tuberculose, no presente e ainda por muitos anos, a vacina BCG, apesar de suas deficiências, mantém-se como um importante instrumento nos esforços para controle dos efeitos danosos da tuberculose, sobretudo em países em que essa doença ocorre em médias e elevadas taxas de incidência.

Quality control tests for vaccines in leprosy vaccine trial, Avadi.

All the vaccines supplied for the large scale comparative leprosy vaccine trial of ICRC bacilli, M.w, BCG plus killed M. leprae (candidate vaccines), BCG and normal saline (control arms) at CJIL Field Unit, Chennai were tested for quality control by the suppliers following the procedures laid down in the WHO protocol for killed M. leprae. Quality control for BCG was carried out at BCG vaccine laboratory as per protocol. Toxicity and sterility tests were done on all the vaccine batches/lots received. As part of the quality control, bacterial count, and protein estimation were also done. Studies showed that the bacterial content and protein concentration were comparable with the original preparations. Vaccines were free from micro-organisms, toxic materials and safe for human use. Thus the quality of all vaccine preparations was satisfactory.

Improving on BCG.

BCG is the only vaccine for tuberculosis and leprosy known to be effective in at least some places. Unfortunately it tends to be less successful in just those areas of the developing world where a vaccine is most needed. Although molecular biology offers the prospect of alternatives, these still lie in the indefinite future, and the best use has to be made of BCG. A number of preparations are available from different manufacturers, and a vaccine should be selected with good evidence of efficacy, and a low incidence of complications. Selection of the optimal age for administering BCG should be based on factors pertaining in the area where it is to be used. The influence of contact with environmental mycobacteria, the age at which mycobacterial diseases occur, and the logistics of vaccine delivery must be taken into account. The addition of a suspension of killed Mycobacterium vaccae to BCG may increase its efficacy. Skin test data show that recognition of antigens common to all mycobacterial species and thought to be the first step in the protective immune response, is significantly enhanced by the additive. M. vaccae also contains a substance, or substances, "switching off" the tissue destructive aspect of the Koch phenomenon that is part of the immunopathology of tuberculosis. A suspension of killed M. vaccae alone can be used to enhance immune responses of persons unsuitable for BCG vaccination, such as those already tuberculin positive, and those with scars of earlier BCG vaccination.

BCG vaccination in leprosy: final results of the trial in Karimui, Papua New Guinea, 1963-79.

The efficacy of BCG vaccine in preventing the clinical manifestations of leprosy in a tuberculosis-free area of Papua New Guinea is reported. Between 1963 and 1966 a total of 5356 subjects, randomized to receive BCG or saline inoculations, were examined for leprosy before the vaccination and surveillance was continued until 1979. BCG afforded 48% protection against clinical leprosy, being most effective against borderline tuberculoid leprosy and in children vaccinated when under 15 years old. Protection was evident within 12 months in those vaccinated between the ages of 10 and 15 years but was delayed in other age groups. There was evidence for accelerated manifestations of tuberculoid leprosy in children vaccinated when under 5 years of age. Tuberculin sensitivity was more likely to be sustained following multiple BCG inoculations; vaccinees with sustained tuberculin sensitivity had the lowest incidence of leprosy, but protection was also evident in tuberculin-negative vaccinees. These results may have implications for ongoing trials of leprosy vaccine incorporating BCG.

BCG vaccination in leprosy: Final results of the trial in Karimui, Papua New Guinea, 1963-79

The efficacy of BCG vaccine in preventing the clinical manifestations of leprosy in a tuberculosis-free area of Papua New Guinea is reported. Between 1963 and 1966 a total of 5356 subjects, randomized to receive BCG or saline inoculations. were examined for leprosy before the vaccination and surveillance was continued until 1979

BCG afforded 48 per cent protection against clinical leprosy, being most effective against borderline tuberculoid leprosy and in children vaccinated when under 15 years old. Protection was evident within 12 months in those vaccinated between the ages of 10 and 15 years but was delayed in other age groups. There was evidence for accelerated manifestations of tuberculoid leprosy in children vaccinated when under 5 years of age. Tuberculin sensitivity was more likely to be sustained following multiple BCG inoculations; vaccines with sustained tuberculin sensitivity had the lowest incidence of leprosy, but protection was also evident in tuberculin-negative vaccinees. These results may have implications for ongoing trials of leprosy vaccine incorporating BCG(AU)

Influencia del B.C.G. sobre a posibilidad de la leprominorreaccion

El trabajo esta dividido en dos parte. En el primera se tratam em forma somera los puntos más importantes sobre la leprominorreacción, la classificación de la lepra y las relaciones entre esta enfermedad y la tuberculosis. Posteriormente se hace una breve síntesis de la historia del B.C.G. en el mundo y en particular en nuestro país, para terminar con una revisión de los trabajos más importantes en se ha empleado la vacuna B.C.G. en relación con la lepra. En la segunda parte se expone nuestra experiencia: a 107 contactos de enfermos de lepra se les practicó intradermorreacciones de Mantoux y Mitsuda. A los que dieron negativa esta ultima se lesvacunó con B.C.G. por vía intradérmica y se le repitió la leprominorreacción un año después de afectuada la vacunación. Un 71 por cento de los vacunados viraron su Mitsuda a la positividade