CDC | TB | Fact Sheets - BCG Vaccine Fact Sheets BCG Vaccine Introduction BCG, or bacille Calmette-Guerin, is a vaccine for tuberculosis (TB) disease. Many foreign-born persons have been BCG-vaccinated. BCG is used in many countries with a high prevalence of TB to prevent childhood tuberculous meningitis and miliary disease. However, BCG is not generally recommended for use in the United States because of the low risk of infection with Mycobacterium tuberculosis, the variable effectiveness of the vaccine against adult pulmonary TB, and the vaccine’s potential interference with tuberculin skin test reactivity. The BCG vaccine should be considered only for very select persons who meet specific criteria and in consultation with a TB expert. Recommendations Children. BCG vaccination should only be considered for children who have a negative tuberculin skin test and who are continually exposed, and cannot be separated from, adults who Are untreated or ineffectively treated for TB disease (if the child cannot be given long-term treatment for infection); or Have TB caused by strains resistant to isoniazid and rifampin. Health Care Workers.

BCG vaccination of health care workers should be considered on an individual basis in settings in which A high percentage of TB patients are infected with M. tuberculosis strains resistant to both isoniazid and rifampin; There is ongoing transmission of such drug-resistant M. tuberculosis strains to health care workers and subsequent infection is likely; or Comprehensive TB infection-control precautions have been implemented, but have not been successful. Health care workers considered for BCG vaccination should be counseled regarding the risks and benefits associated with both BCG vaccination and treatment of Latent TB Infection (LTBI). Contraindications Immunosuppression. BCG vaccination should not be given to persons who are immunosuppressed (e.g., persons who are HIV infected) or who are likely to become immunocompromised (e.g., persons who are candidates for organ transplant). Pregnancy. BCG vaccination should not be given during pregnancy. Even though no harmful effects of BCG vaccination on the fetus have been observed, further studies are needed to prove its safety.

Testing for TB in BCG-Vaccinated Persons The tuberculin skin test (TST) and blood tests to detect TB infection are not contraindicated for persons who have been vaccinated with BCG. Tuberculin Skin Test (TST). BCG vaccination may cause a false-positive reaction to the TST, which may complicate decisions about prescribing treatment. The presence or size of a TST reaction in persons who have been vaccinated with BCG does not predict whether BCG will provide any protection against TB disease. Furthermore, the size of a TST reaction in a BCG-vaccinated person is not a factor in determining whether the reaction is caused by LTBI or the prior BCG vaccination. (See below for specific guidance on skin test results.) TB Blood Tests. Blood tests to detect TB infection, unlike the TST, are not affected by prior BCG vaccination and are less likely to give a false-positive result. Treatment for LTBI in BCG-Vaccinated Persons Treatment of LTBI substantially reduces the risk that TB infection will progress to disease. Careful assessment to rule out the possibility of TB disease is necessary before treatment for LTBI is started.

Evaluation of TST reactions in persons vaccinated with BCG should be interpreted using the same criteria for those not BCG-vaccinated.

Persons in the following high-risk groups should be given treatment for LTBI if their reaction to the TST is at least 5 mm of induration or they have a positive result using a TB blood test: HIV-infected persons Recent contacts to a TB case Persons with fibrotic changes on chest radiograph consistent with old TB Patients with organ transplants Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for 1 month or longer, taking TNF-a antagonists) In addition, persons in the following high-risk groups should be considered for treatment of LTBI if their reaction to the TST is at least 10 mm of induration or they have a positive result using a TB blood test: Recent arrivals (less than 5 years) from high-prevalence countries Injection drug users Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other health care facilities) Mycobacteriology laboratory personnel Persons with clinical conditions that place them at high-risk for developing TB disease (e.g., diabetes) Children less than 4 years of age, or children and adolescents exposed to adults in high-risk categories Persons with

 no known risk factors for TB may be considered for treatment of LTBI if their reaction to the tuberculin test is at least 15 mm of induration or they have a positive result using a TB blood test.

Targeted skin testing programs should only be conducted among high-risk groups. All testing activities should be accompanied by a plan for follow-up care for persons with TB infection or disease. Additional Information BCG tuberculosis (TB) vaccine - Vaccinations - NHS Choices BCG tuberculosis (TB) vaccine The BCG vaccine protects against tuberculosis, which is also known as TB. TB is a serious infection which affects the lungs and sometimes other parts of the body, such as the bones, joints and kidneys. It can also cause meningitis . Read more about tuberculosis (TB) . Who should have the BCG vaccine? The BCG vaccine (which stands for Bacillus Calmette-Guérin vaccine) is not given as part of the routine NHS vaccination schedule . It's given on the NHS only when a child or adult is thought to have an increased risk of coming into contact with TB.

BCG for babies BCG vaccination is recommended for all babies up to one year old who: are born in areas where TB rates are higher than in the rest of the country, including some parts of inner London have a parent or grandparent who was born in a country where there is a high rate of TB BCG for children BCG vaccination may also be recommended for older children who have an increased risk of developing TB, such as: children who have recently arrived from countries with high levels of TB, including those in sub-Saharan Africa, the Indian sub-continent and parts of Eastern Europe children who have come into close contact with somebody infected with respiratory TB BCG for adults BCG vaccination is rarely given to anyone over the age of 16 – and never over the age of 35, because it doesn't work very well in adults. It is, however, given to adults aged 16 to 35 who are at risk of TB through their work, such as some healthcare workers. How is the BCG vaccination given? BCG vaccination is given as an injection into the upper arm. The vaccination usually leaves a small scar. Read more about potential BCG vaccination side effects . When is the BCG vaccination given?

If it's advised that your baby has the BCG vaccine, the injection is usually offered soon after birth, while your baby is still in hospital. Alternatively, your baby can be referred to a local healthcare centre for vaccination after they've left hospital. This may not necessarily be the local GP surgery, as not all surgeries can provide this service. If you are offered BCG vaccination as an adult, it will be arranged by a local healthcare centre. How effective is BCG vaccination? The BCG vaccine is made from a weakened strain of TB bacteria. Because the bacteria in the vaccine is weak, it triggers the immune system to protect against the disease, giving good immunity to people who receive it, without actually causing the disease. The vaccine is 70-80% effective against the most severe forms of TB, such as TB meningitis in children. It is less effective in preventing respiratory disease, which is the more common form of TB in adults. There is currently a problem with the supply of BCG vaccine. Public Health England has secured a limited supply to protect babies who are eligible for the vaccine.

Bacillus Calmette-Guerin (BCG) Vaccine: MedlinePlus Drug Information Bacillus Calmette-Guerin (BCG) Vaccine URL of this page: Bacillus Calmette-Guerin (BCG) Vaccine Other names WHY is this medicine prescribed? BCG vaccine provides immunity or protection against tuberculosis (TB). The vaccine may be given to persons at high risk of developing TB. It is also used to treat bladder tumors or bladder cancer. This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information. HOW should this medicine be used? Your doctor or a health care provider will administer this medicine. When used to protect against TB, it is injected into the skin. Keep the vaccination area dry for 24 hours after receiving the vaccine, and keep the area clean until you cannot tell the vaccination area from the skin around it. When used for bladder cancer, the medicine flows into your bladder through a tube or catheter. Avoid drinking fluids for 4 hours before your treatment. You should empty your bladder before treatment. During the first hour after the medication is infused, you will lie on your stomach, back, and sides for 15 minutes each.

Then you will stand, but you should keep the medication in your bladder for another hour. If you cannot keep the medication in your bladder for the entire 2 hours, tell your health care provider. At the end of 2 hours you will empty your bladder in a seated manner for safety reasons. Your urine should be disinfected for 6 hours after the medication is administered. Pour a similar amount of undiluted bleach in the toilet after you urinate. Let it stand for 15 minutes before flushing. Various dosing schedules may be used. Your doctor will schedule your treatment. Ask your doctor to explain any directions you do not understand. When the vaccine is given to protect against TB, it usually is given only one time but may be repeated if there is not a good response in 2-3 months. Response is measured by a TB skin test. What SPECIAL PRECAUTIONS should I follow? Before receiving BCG vaccine, tell your doctor and pharmacist if you are allergic to BCG vaccine or any other drugs. tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially antibiotics, cancer chemotherapy agents, steroids, tuberculosis medications, and vitamins.

tell your doctor if you have had a recent smallpox vaccination or if you have had a positive TB test. tell your doctor if you have an immune disorder, cancer, fever, an infection, or an area of severe burns on your body. tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking BCG vaccine, call your doctor immediately. What SIDE EFFECTS can this medicine cause? BCG vaccine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: swollen lymph nodes small red areas at the site of injection. (These usually appear 10-14 days after injection and slowly decrease in size. They should disappear after about 6 months.) fever Tuberculosis BCG vaccination Tuberculosis BCG vaccination Tuberculosis BCG vaccination What is BCG? BCG is a vaccine against tuberculosis (TB). It uses a live TB germ that has been modified in the laboratory so that it will not cause disease in a healthy person. The BCG vaccination is not part of the WA routine vaccination program it is only given in restricted circumstances.

The BCG 10 Anti-Tuberculosis Vaccine is supplied as an unregistered therapeutic good under section 19(5) of the Therapeutic Goods Act 1989 How is the BCG vaccine given? It is injected between the layers of skin on the upper arm near the shoulder by a Registered Nurse who has been trained in providing the vaccination. Is the vaccine safe? In most circumstances the vaccine is safe. As with any vaccination, BCG can result in severe adverse reactions and you should discuss this with the nurse before vaccination. Are there any side effects? Possible side effects include: Pustule or ulceration at site of injection Pain, redness and swelling around the injection site Swelling of the glands in the armpit and/ or neck Rare side effects: Severe allergic reactions How effective is the vaccine? BCG vaccination reduces the risk of tuberculosis in people who are not already infected with TB. The vaccine does not always prevent disease. It is more effective in children < 6yrs old, providing 50 to 80 % protection against meningeal and miliary TB. Protection against TB will only start 6-8 weeks after the vaccination has been given and lasts for about 10 years.

Revaccination is not recommended. BCG vaccination is not recommended for adults Who could be vaccinated? Children less than 6 years old who are; Going to live in another country with a high incidence of tuberculosis (defined as an annual incidence of > 40 per 100 000 population) for more than 3 months or Will be making repeated visits to a country with a high incidence of tuberculosis that is likely to be for a cumulative period of more than 3 months. For country specific incidence rates see the World Health Organisation TB country profile website (external site) . Newborn children of migrants who have arrived from countries with a high incidence of tuberculosis (see definition above) in the last 5 years, or newborn children who have household contact with people who have arrived from a high incidence country in the last 5 years. Newborn children of parents with Leprosy or a family history of Leprosy. Children less than 6 years old who have not previously been vaccinated with BCG and are household contacts of newly diagnosed Leprosy case. Who should not be vaccinated with BCG 10 Anti-Tuberculosis Vaccine? Infants with a body mass below 2,000g.

Newborn children with suspected congenital immune deficiencies Persons who have had a tuberculin skin test (TST) reaction. Persons who have TB disease now, or have had TB disease in the past. Persons with HIV infection; including newborn children of mothers infected with HIV until this infection is ruled out in the child. Newborn children of mothers treated in their third trimester with medications such as anti-TNF-alpha monoclonal antibodies. Persons with primary or secondary immune deficiencies (including interferon-gamma deficiency and DiGeorge syndrome) Persons who take anti-cancer or steroid drugs such as cortisone or immunosuppressive drugs(including anti-TNF-alpha monoclonal antibodies such as infliximab) or are undergoing radiotherapy Patients after bone marrow stem cell transplantation or organ transplantation Persons who have had a serious illness such as kidney disease. Patients with malignant diseases (e.g. leukaemia, Hodgkin lymphoma, lymphoma, or other carcinoma of the reticuloendothelial system); Patients after bone marrow stem cell transplantation or organ transplantation; People with generalised skin diseases such as eczema or other exudative inflammatory dermatological conditions People with known hypersensitivity to any component of the vaccine.

Pregnant women Persons with serious diseases (including severe malnutrition) When should BCG vaccination be delayed? If another live vaccine (excluding oral Rotavirus) has been given within 4 weeks (measles, mumps, rubella, yellow fever, or varicella) Infection with a fever Aggravation of a chronic disease Premature newborn children in an unstable clinical condition, until their general condition has improved IMPORTANT INFORMATION POST VACCINATION PLEASE KEEP THESE INSTRUCTIONS UNTIL THE SORE HAS COMPLETELY HEALED What to expect after BCG Vaccination BCG vaccination is given into the skin on the upper arm. Immediately after the injection a white lump is seen for a few minutes A red spot / small swelling will appear in 2– 4 weeks’ time This may develop into a pustule This pustule / lesion will heal spontaneously 2 – 3 months after vaccination. A scar usually remains at the site of the injection What to do if a sore appears Leave the sore alone and ensure it remains exposed to the air. This helps it to heal quickly.

Keep the affected site clean What not to do Do not scratch, squeeze or disturb the sore or scab Do not apply ointment Do not apply antiseptics Do not apply sticking plaster or a tight sealed dressing as these can delay healing The child’s arm where the BCG vaccine has been administered should not be used for at least 3 months after the BCG vaccination for any other vaccines. If your child experiences an adverse event after the BCG please report this to the WA Department of Health (external site) . Phone: (08) 9321 1312 Where can I get more information? If you have any questions please telephone the WA TB Control Program at the Anita Clayton Centre between 08:15 and 4:15pm Monday to Friday on (08) 9222 8500 to talk to a Registered Nurse. Acknowledgements Anita Clayton Centre (WA Tuberculosis Control Program) This publication is provided for education and information purposes only. It is not a substitute for professional medical care. Information about a therapy, service, product or treatment does not imply endorsement and is not intended to replace advice from your healthcare professional.

Readers should note that over time currency and completeness of the information may change. All users should seek advice from a qualified healthcare professional for a diagnosis and answers to their medical questions.

Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis | The BMJ Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis CCBYNC Open access Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis BMJ 2014; 349 doi: (Published 05 August 2014) Cite this as: BMJ 2014;349:g4643 A Roy, senior scientist 1 , M Eisenhut, consultant paediatrician 2 , R J Harris, statistician 1 , L C Rodrigues, professor of epidemiology 3 , S Sridhar, research associate 4 , S Habermann, junior doctor 2 , L Snell, junior doctor 2 , P Mangtani, senior lecturer 3 , I Adetifa, paediatrician and medical epidemiologist 5 , A Lalvani, professor of infectious disease 4 , I Abubakar, professor of infectious disease epidemiology 1 6 1Centre for Infectious Disease Surveillance and Control, Public Health England, London NW9

 5EQ, UK 2Luton and Dunstable University Hospital, NHS Foundation Trust, Luton, UK 3London School of Hygiene and Tropical Medicine, London, UK 4Tuberculosis Research Centre, Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, UK 5Medical Research Council, Fajara, Gambia 6Centre for Infectious Disease Epidemiology and MRC Clinical Trials Unit, University College London, London, UK Correspondence to: I Abubakar i.abubakar{at}ucl.ac.uk Accepted 11 July 2014 Abstract Objectives To determine whether BCG vaccination protects against Mycobacterium tuberculosis infection as assessed by interferon γ release assays (IGRA) in children.

Design Systematic review and meta-analysis. Searches of electronic databases 1950 to November 2013, checking of reference lists, hand searching of journals, and contact with experts. Setting Community congregate settings and households. Inclusion criteria Vaccinated and unvaccinated children aged under 16 with known recent exposure to patients with pulmonary tuberculosis. Children were screened for infection with M tuberculosis with interferon γ release assays. Data extraction Study results relating to diagnostic accuracy were extracted and risk estimates were combined with random effects meta-analysis. Results The primary analysis included 14 studies and 3855 participants. The estimated overall risk ratio was 0.81 (95% confidence interval 0.71 to 0.92), indicating a protective efficacy of 19% against infection among vaccinated children after exposure compared with unvaccinated children. The observed protection was similar when estimated with the two types of interferon γ release assays (ELISpot or QuantiFERON).

Restriction of the analysis to the six studies (n=1745) with information on progression to active tuberculosis at the time of screening showed protection against infection of 27% (risk ratio 0.73, 0.61 to 0.87) compared with 71% (0.29, 0.15 to 0.58) against active tuberculosis. Among those infected, protection against progression to disease was 58% (0.42, 0.23 to 0.77). Conclusions BCG protects against M tuberculosis infection as well as progression from infection to disease. Trial registration PROSPERO registration No CRD42011001698 ( ). Introduction BCG vaccine has been the subject of numerous efficacy trials and epidemiological studies conducted over several decades. These trials indicate that BCG has 60-80% protective efficacy against severe forms of tuberculosis in children, particularly meningitis, 1 2 and its efficacy against pulmonary diseases varies geographically.

3 4 5 BCG does not seem to protect against disease when it is given to people already infected or sensitised to environmental mycobacteria, which could explain the geographical variation. 6 7 8 Until recently it was not possible to establish whether the protective effect of BCG vaccination against disease was from its action in preventing acquisition of infection or limited to prevention of progression from infection to clinical disease. The scarcity of evidence on whether the vaccine is effective against Mycobacterium tuberculosis infection was because of limitations of the tuberculin skin test. This test cannot distinguish a positive response caused by M tuberculosis infection from that caused by BCG vaccination or non-tuberculous mycobacterial infection. 9 The recently developed T cell based interferon γ release assays (IGRA) can detect M tuberculosis infection and discriminate this from previous BCG vaccination and most non-tuberculous mycobacterial infections, 10 allowing investigation of whether BCG protects against M tuberculosis infection. 11 12 13 If BCG is found to protect against infection, it will have key implications for its use in current immunisation programmes 14 as well as in the future development of new improved tuberculosis vaccines.

In this systematic review we examined the evidence for the protective effect of BCG against M tuberculosis infection, as opposed to against disease, in settings where children can be presumed to have been exposed to M tuberculosis. This therefore assesses the degree to which BCG vaccination before exposure is associated with a subsequent negative result on an interferon γ release assay. We also looked at factors that could alter the measured protective effect of BCG: latitude, the recommended age of vaccination in the area where the study was conducted, type of assay, and study quality. When there was sufficient information, we determined protection against early progression from infection to disease during screening. Methods Search and Data Extraction We searched Embase (1980 until November 2013), Medline (1950 until November 2013), and the Cochrane Library as well as reference lists of retrieved articles and conference abstracts. The search strategy was not restricted by language or year. We used the following search terms, adapted for each database when appropriate: BCG, Bacillus Calmette Guerin, tuberculosis, TB, interferon γ release assay, IGRA, ELI Spot, T-Spot TB, and QuantiFERON.

We also reviewed the personal libraries of the research team. Two reviewers (AR and ME) independently screened the titles and abstracts (when available) from the search results and identified studies for assessment of full text. Disagreements were resolved by asking the opinion of a third reviewer (IA) for resolution until consensus was reached at each stage of the screening process. Information extracted onto pretested data forms included study details (authors, year, geographical area, study design, sample size), the population (mean age, sex, and setting), exposure (method of assessment and timing), and two outcomes measures: interferon γ release assays (as a proxy for tuberculosis infection) and active tuberculosis (when reported). When relevant information was missing, we contacted study authors by email. For some studies, the stated primary outcome was not M tuberculosis infection but data on results of interferon γ release assays had been collected. For these studies, we contacted the authors to obtain the raw data. Inclusion and exclusion criteria Studies meeting the following criteria were included: Participants had known recent exposure to people with pulmonary tuberculosis. We assumed that in such studies, a reduced rate of infection in vaccinated versus unvaccinated children could be attributed to protection by vaccination rather than lack of exposure.

Participants were children aged under 16, including those who had and had not been vaccinated with BCG. All children were screened for infection with M tuberculosis with interferon γ release assays; either in tube γ interferon quantification (QuantiFERON) or enumeration of γ interferon releasing T cells (ELISpot). We excluded all studies in which interferon γ release assays was used only in children with positive results from tuberculin skin test or in which participants were not tested by interferon γ release assays or when the study reported on active tuberculosis or results of tuberculin skin test only or where the study was conducted in animals. Quality assessment for individual studies Two reviewers (AR and ME) assessed aspects of the quality of each selected study using a modified version of the Newcastle-Ottawa scale for assessment of observational cohort studies. 15 This scale awards a maximum of nine points to each study: four points for the adequate selection of participants, two points for comparability of the studies based on the design and analysis, and three points for the adequate ascertainment of outcome.

We defined studies of high quality as those that scored ≥66.6%, moderate for 33.3-66.6%, and low for those <33.3%. Discrepancy in quality assessment was discussed and resolved by the two reviewers. Definitions Exposure to tuberculosis was defined as close contact with people with active pulmonary tuberculosis as identified by the treating physicians. Infection was defined as any positive results of interferon γ release assays in contacts irrespective of whether they had evidence of active tuberculosis or not. Participants with an indeterminate status were excluded from the analysis. Disease was defined as presence of active tuberculosis (according to the authors) with or without a positive result on interferon γ release assays. Outcomes of both infection and active disease were identified at the point of screening for infection after exposure. A small number of additional cases might have been included as some outbreak investigations were undertaken over a period of several weeks. Synthesis of results Primary analysis—protection against infection Our primary analysis focused on whether BCG vaccination administered before exposure was associated with a subsequent negative result on interferon γ release assay in children who had contact with infectious tuberculosis.

We used binary data to categorise participants into those who were or were not vaccinated with BCG and those who did or did not have a negative assay result (independent of progression to disease), with continuity corrections applied to zero cells. 16 To include all studies in a single analysis, we combined results from studies reporting both QuantiFERON and ELIspot. Where results of both assays were available from a study we chose the QuantiFERON result as this was most used among the selected studies. Subgroup analyses of protection against infection We used subgroup analysis to assess whether the use of different types of interferon γ release assay (ELISpot and QuantiFERON) led to different results. We also investigated the relation between the observed effect of BCG and age at which BCG vaccination was recommended in the area where the study was conducted (we used policy recommendations because we did not have timing of BCG vaccination in individuals); geographical latitude where the study was conducted: latitudes of the study location was categorised into three groups: 0-20°, 20-40°, and >40°; and study quality: we investigated the effect of study quality by application of the Newcastle-Ottawa scale.

15 Using this scale, we compared studies with a point rating on this scale equal or above and below the median of 5 points. Secondary analysis—protection against infection protection against disease In a secondary analysis, we estimated protection by BCG against active disease in a subset of six studies that reported development of active tuberculosis during screening. This was achieved by examining, in this subset, the number of children with active disease (regardless of assay status) in those who received BCG versus those who did not. In the population with tuberculosis infection determined from positive result on interferon γ release assays, we also examined the effect of BCG on progression from infection to early active disease by comparing the number with active disease in those who received BCG versus those who did not. Statistical analysis Analysis was performed with the DerSimonian and Laird random effects model, which incorporates variation between studies in the weighting. To quantify inconsistency across studies by describing percentage of the variability in effect estimates from heterogeneity we used the I2 statistic with I2 >40% representing moderate, >60% substantial, and >80% considerable heterogeneity.

17 We applied a continuity correction to zero cells to include all studies in the analysis; the approach used is designed to minimise bias, 16 although in our case the potential bias from any such correction would be extremely small as only one study contained zero counts and there were plenty of well powered studies. We assessed potential factors behind the heterogeneity with random effects meta-regression. 18 The protective effect of BCG was described with risk ratios and 95% confidence intervals. To assess potential publication bias we used funnel plots and the Harbord test. 19 Results Study selection Our literature search found 601 articles; based on a review of titles, we selected 546 abstracts for further assessment leading to the identification of 133 articles for full text review (fig 1). ⇓ After we reviewed the full text, 112 articles did not meet the inclusion criteria. The 21 remaining articles (describing 21 studies) were selected for potential inclusion. Fourteen articles stated that interferon γ release assays were carried out but did not report the results on the relation between BCG vaccination and assay. The authors were contacted and asked to provide the raw data.

For seven such studies, we received no response after repeated attempts. The analysis therefore included 14 studies (fig 1). ⇓ Fig 1 Study selection for systematic review of BCG vaccination against mycobacterium tuberculosis infection in children Discussion Principal findings This systematic review shows that BCG vaccination can protect against M tuberculosis infection and consolidates the results from recent studies showing evidence of protection against infection. 11 12 13 29 Our results support a paradigm shift in the understanding of how antimycobacterial vaccines (new and old) can work, from the view that BCG protects against disease but not against infection to one that it protects against infection itself. 31 A recent double blind randomised placebo controlled phase 2b trial of a BCG prime-MVA85A boost vaccination in infants showed no evidence of additional protection, over and above that of BCG against tuberculosis disease infection. 32 This is despite MVA85A inducing a significantly higher Ag85-specific CD4 positive T cell expression of interferon γ, TNFα, and interleukin 2 compared with placebo.

One possible explanation for this lack of increased efficacy might be that BCG conferred protection against M tuberculosis infection was sufficiently high such that an additional immunisation with MVA85A was unable to confer additional protection. The observed protection against M tuberculosis infection was independent of the assay method used for measurement. There was no evidence of protection against infection less than 40° latitude away from the equator, although the number of studies was small and the difference was not significant. If this finding is confirmed, then the effect of latitude would be consistent with the variation in protection by BCG against pulmonary disease. 8 In this case, the mechanism here could be the same: that the higher prevalence of non-tuberculous mycobacterial infection close to the equator decreases the measured protection with BCG. The limited number of studies reviewed from locations closer to the equator, however, means that firm conclusions must wait until new studies find similar results. High quality studies also showed protection by BCG vaccination against infection, while lower quality studies did not suggest that study design factors in smaller low quality studies led to the inability to detect a protective effect. This has been observed in systematic reviews of trials of BCG vaccination against tuberculosis.

8 We found evidence of progression to active tuberculosis as identified at point of screening of index cases. Our interpretation of progression at the time of screening potentially includes both early and late progressors because of uncertainty of the timing of progression to active disease. Publication of an analysis of follow-up data from a study used in this meta-analysis 13 recently reported protective efficacy of the vaccine of 67% for protection against progression from infection to active disease. 33 Similar longitudinal cohorts and randomised control trials will provide a better understanding of the protective efficacy of BCG vaccination. Limitations and strengths Our results should be treated with caution for several reasons. Data were not always complete, and we could not control for, or explore interaction with, all variables. For instance, it was assumed there was no prior infection before the documented exposure to active disease or outbreak. Such exposure, however, should affect vaccinated and unvaccinated children equally. Vaccinated children are unlikely to be different from unvaccinated children in other ways that could contribute to protection from infection. We attempted to lower the probability of prior exposure by restricting the analysis to children aged under 16.

We tried to minimise bias from differences in exposure in the two groups by limiting the review to studies among contacts—that is, to outbreaks among contacts of infectious cases or known household exposure where exposure is likely to be similar in vaccinated and unvaccinated children. It is important, however, to consider the possibility that studies included in this review had vaccine recipients who were less likely to be exposed to infection before the outbreak. Exposure can differ because of variable duration of infectiousness of the index patient and the amount of effective contact. Reduced infection rates in children immunised with BCG could also be caused by the fact that parents who are generally more aware of infection control measures are from higher educated families with lower exposure to M tuberculosis infection and have their children more comprehensively immunised, which includes BCG immunisation. A further potential source of bias relates to the greater likelihood that private paediatricians who care for children from medium and high socioeconomic levels might recommend against BCG vaccination if they consider these children to be at a lower risk of infection. We included various observational studies from settings with different socioeconomic backgrounds, potentially neutralising such bias.

We also acknowledge that further quantification of degree of exposure to tuberculosis cases, including proximity to the index case and the number of cases in close contact, was not possible in our study because the primary studies were not designed to compare exposure in children who were and were not immunised with BCG. Investigation of the effect of age at vaccination at an individual level and of time from vaccination to exposure to an infectious case would be of particular interest. The use of interferon γ release assays as an indicator of infection is still subject to some debate, although this is currently the best marker for infection and certainly discriminates well between infection with M tuberculosis and previous BCG vaccination. There are suggestions that different strains of BCG can induce a broad range of immunological response, which in turn brings about a change in the level of protection. A recent meta-analysis of trials, including 18 studies reporting on protection against pulmonary and six reporting on protection against miliary or meningeal tuberculosis, showed no evidence that efficacy of BCG was associated with vaccination strains. 8 These results are consistent with results from the UKMRC trials, which found equivalent protection by the Copenhagen strain of BCG and an M microti derived vaccine.

6 Only three 11 13 27 of the 14 studies included in our review provided information on the BCG vaccine strains used, so we also used the UK studies 11 12 13 20 21 27 from which we had information on the strains of BCG used in British school children and found no evidence of bias by vaccine strain (data not shown). We limited subgroup analyses to investigate heterogeneity because of the potential for spurious findings. Where assessed, the main differences in the subgroup analyses were for rating on the Newcastle-Ottawa scale, the P value for which was similar under the permutation test recommended by Higgins and Thompson. 17 Similarly, the small number of studies limited the power to explore whether the variation in protection by BCG against tuberculosis is mostly through variation in protection against infection. The primary aim of most (75%) studies reviewed was not to investigate BCG protection against infection. This, taken in combination with our symmetrical funnel plot, suggests that our findings are unlikely to be caused by publication or reporting bias.

Implications and conclusions The effect of BCG vaccination, and its policy implications, would be different for countries with high versus low incidence of tuberculosis especially in terms of the cost effectiveness of policies. Countries with a policy of vaccination at birth tend to be those countries with a higher incidence of tuberculosis (cut off >20/100 000 according to European Centre for Disease Prevention (ECDC)) than those countries without such vaccination policy (<20/100 000). Given the incomplete control of tuberculosis, especially in high burden countries, optimisation of use of BCG is sensible. Our analysis supports vaccinating children as soon as possible after birth to prevent infection and disease. Our results provide evidence that BCG protects against tuberculosis infection from multiple epidemiologically different settings and independent of the type of interferon γ release assay used to detect infection. Future trials of candidate vaccines need to investigate the efficacy of the new vaccine against tuberculosis infection and early progression and late progression to active disease. In addition, transparent reporting from outbreak and contact studies of individual ages and time of vaccination and exposure to tuberculosis of participants should allow future meta-analysis to investigate protection against infection.

Our results also suggest that models of BCG impact should be revised to include an effect against infection and consequently latent M tuberculosis infection and reactivation as without this the effect of BCG would be underestimated. What is already known on this topic Numerous efficacy trials indicate that BCG has 60-80% protective efficacy against severe forms of tuberculosis in children, particularly meningitis; its efficacy when given to adults against pulmonary diseases varies geographically probably because of previous infection when BCG is given The recently developed T cell based interferon γ release assays can detect M tuberculosis infection and discriminate this from previous BCG vaccination and most non-tuberculous mycobacterial infections, allowing investigation of whether BCG protects against M tuberculosis infection What this study adds In addition to protection against tuberculosis disease, BCG protects against tuberculosis infection A protective effect against tuberculosis infection was observed from multiple epidemiologically different settings and independent of the type of interferon γ release assay used to detect infection Notes Cite this as: BMJ 2014;349:g4643 Footnotes Contributors: AR and ME contributed equally to the work. IA, ME, and AR conceived idea and designed the study. AR and ME acquired the data.

SH and LS contributed to the literature search and quality assessment. RJH was responsible for the statistical analysis. RJH, IA, ME, AR, PM, LCR, and AL analysed and interpreted the data. ME and AR drafted the manuscript. All authors contributed to planning, interpretation and writing of the manuscript and critically revised the manuscript for intellectual content. IA is guarantor. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. IA is supported by the UK National Institute for Health Research and the UK MRC. Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; AL is inventor for several patents underpinning T cell based diagnosis. The ESAT-6/CFP-10 IFN-gamma ELISpot was commercialised by an Oxford University spin-out company (T-SPOT.TB, Oxford Immunotec, Abingdon, UK), in which Oxford University and AL have minority shares of equity and entitlement to royalties. Ethical approval: Not required.

Declaration of transparency: IA affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. Data sharing: Technical appendix, statistical code, and dataset are available from IA. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: . References ↵ Rodrigues LC, Mangtani P, Abubakar I. How does the level of BCG vaccine protection against tuberculosis fall over time? BMJ 2011;343:d5974. Tuberculosis and Chest Service Department of Health - What is BCG vaccination? What is BCG vaccination? Home > Information on TB > What is BCG vaccination? What is BCG vaccination?

BCG (Bacilli Calmette-Guerin) is a vaccine widely used for the protection against tuberculosis. However, the degree of protection is only partial and not 100%. The vaccine is considered efficacious in young children but not so in adults. It is a live attenuated vaccine given through the skin of one of the arms (either by intradermal injection or percutaneous inoculation). It should not be given to persons with impaired body immunity. Repeat doses of BCG vaccination are, in general, not indicated, as no additional benefit has been demonstrated. The TB & Chest Service of the Department of Health provides BCG vaccination to all newborn babies in Hong Kong. Children residing in Hong Kong, who are aged below 15 and have never received BCG before, are also advised to receive the vaccine. BCG vaccination is not required if the child has a history of proven tuberculosis or is above 15 years of age.

BCG vaccination is not recommended for children with the following health conditions: Conditions with impaired immunity: Any form of malignancy, in particular, leukaemia and lymphoma Under immunosuppressive therapy such as irradiation and treatment with cytotoxic drugs or systemic steroids; Immunodeficiency, either congenital or acquired (e.g. HIV infection) Having received live vaccine within the past four weeks (e.g. measles, mumps, rubella); BCG vaccination can be given after this interval. Febrile conditions Parents may consult any one of the chest clinics for further details. When is the BCG (TB) vaccine needed? - Vaccinations - NHS Choices When is the BCG (TB) vaccine needed? Print: Who should have the BCG (TB) vaccine? BCG vaccination is only recommended on the NHS for babies, children and adults under the age of 35 who are considered at risk of catching tuberculosis (TB). The BCG vaccine isn't given to anyone over the age of 35, as there's no evidence that it works for people in this age group.

Babies who should have the BCG vaccine BCG vaccination is recommended for all babies up to one year old who: are born in areas where the rates of TB are high have a parent or grandparent who was born in a country where there is a high rate of TB Older children who should have the BCG vaccine BCG vaccination is recommended for all older children and adults at risk of TB, including: older children with an increased risk of TB who were not vaccinated against TB when they were babies anyone under 16 who has come from an area of the world where TB is widespread anyone under 16 who has been in close contact with someone who has pulmonary TB (TB infection of the lung) Find out which countries have a high rate of TB .

Adults aged 16 to 35 who should have the BCG vaccine BCG vaccination is recommended for people aged 16 to 35 who are at occupational risk of TB exposure, including: laboratory staff who are in contact with blood, urine and tissue samples veterinary staff and other animal workers, such as abattoir workers, who work with animals that are susceptible to TB, such as cattle or monkeys prison staff who work directly with prisoners staff of care homes for the elderly staff of hostels for homeless people staff who work in facilities for refugees and asylum seekers healthcare workers with an increased risk of exposure to TB Travellers who should have the BCG vaccine The BCG vaccine is also recommended for people under the age of 16 who are going to live with local people for more than three months in an area with high rates of TB. Find out which countries have a high rate of TB . Individual requests for BCG vaccination If you want BCG vaccination for yourself or your child, you will be assessed to see if you are at high risk of catching TB. If you aren't at risk, you won't be eligible for BCG vaccination.

If you are at risk, you will be tuberculin tested and offered BCG vaccination according to local arrangements. The tuberculin skin test/Mantoux test Before you have the BCG vaccination, you should be tested to see if you are already infected with or have active TB disease. The test, called the tuberculin skin test, or Mantoux test, will be carried out before BCG vaccination if someone: is six years or over is a baby or child under six with a history of residence or a prolonged stay (more than three months) in a country with a high rate of TB has had close contact with a person with TB has a family history of TB within the last five years The Mantoux test assesses your sensitivity to a substance called a tuberculin purified protein derivative (PPD) when it's injected into your skin. The greater the reaction, the more likely it is that an individual is infected with or has active TB. In this case, the individual should not have the BCG vaccine, as it would have no clinical benefit and may cause unpleasant side effects. If you have a strongly positive Mantoux result, you should be referred to a TB specialist team for further assessment.

If the Mantoux test is negative, you can go ahead and have the BCG vaccine. Who should not have the BCG vaccination? The BCG vaccine is not recommended for: people who have already had a BCG vaccination people with a past history of TB people with a positive tuberculin skin test (Mantoux) people who have had a previous anaphylactic reaction (severe allergic reaction) to any of the substances used in the vaccine newborn babies in a household where a case of TB is suspected or confirmed people who have a septic skin condition at the site where the injection will be given people who have received another live vaccine less than three weeks earlier people with a weakened immune system, either as a result of a health condition such as HIV , treatments such as chemotherapy , or medicines that suppress the immune system, such as steroid tablets people who have cancer of the white blood cells, bone marrow or lymph nodes, such as leukaemia or lymphoma people who are seriously unwell (vaccination should be delayed until they recover) pregnant women BCG vaccinations are not usually offered to people over the age of 16 and never over the age of 35, because the vaccine doesn't work well in adults.

Read answers to the frequently asked questions about BCG . Page last reviewed: 26/04/2016 Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer: Overview of BCG Immunotherapy, Mechanism of Action of BCG, Contraindications to BCG For more information, see Bladder Cancer . Next: Mechanism of Action of BCG The mechanism of action of BCG therapy is incompletely understood. Some early studies purported that an immune response against bacillus Calmette-Guérin (BCG) surface antigens cross-reacted with putative bladder tumor antigens, and this was proposed as the mechanism for the therapeutic effect of BCG; however, multiple subsequent studies refute this claim. Once in the bladder, the live organisms enter macrophages, where they induce the same type of histologic and immunologic reaction as found in patients with tuberculosis. BCG vaccine also has been shown to have a predilection for entering bladder cancer cells, where the proteins are broken down and fragments are combined with histocompatibility antigens and displayed on the cell surface. This induces a cytokine and direct cell-to-cell cytotoxicity response, which targets these cells for destruction.

The overall response to BCG is limited if the patient is immunosuppressed. Dal Moro and collegues evaluated the influence of hypertension on the outcome of patients with noninvasive bladder cancer treated with BCG. In both univariate and multivariate analyses of 343 high-risk bladder cancer patients undergoing BCG with a median follow-up of 116 months, hypertension was a statistically significant parameter prognostic for recurrence after BCG treatment. Further study is needed to both evaluate hypertension as a possible prognostic factor to be used in selecting poor-prognosis BC patients as early candidates for surgical treatment. [ 7 ] Previous Next: Contraindications to BCG Contraindications to bacillus Calmette-Guérin (BCG) vaccine therapy include immunosuppression, cancer invading the bladder muscle, and large tumor volume. Because BCG is a live attenuated organism, it can cause an acute disseminated tuberculosislike illness if it enters the bloodstream (BCG sepsis), possibly resulting in death. Reports have described BCG vaccine organisms identified on vascular grafts in patients who have died following BCG vaccine sepsis.

Therefore, the use of BCG is contraindicated in patients with gross hematuria, traumatic catheterization, and recent bladder tumor resection. Additionally, total bladder incontinence is a contraindication, as patients cannot retain the BCG solution. Previous Next: BCG Strains The original bacillus Calmette-Guérin (BCG) strain was developed at the Pasteur Institute from an attenuated strain of Mycobacterium bovis. Subcultures were made and sent to other parts of the world. Two BCG products are commercially available in the United States. The Tice strain, which is a substrain of the original Pasteur product, is manufactured by Organon Pharmaceuticals. The TheraCys strain is made by Aventis/Pasteur. These products, in addition to the Tokyo 172 substrain and the Danish substrain, are available in countries other than the United States. No one product has been shown to have consistent clinical superiority. BCG viability is an important consideration for the vaccine to be effective. This viability is measured in colony-forming units (CFUs). A vaccine that contains no or very few live organisms would be clinically ineffective.

One dose, either an ampule or vial, may vary in weight from one product to another, but the CFU should be similar. Tice BCG has 1-8×10-8 CFUs. TheraCys has 10.5 +/-8.7×10-8 CFUs. In a study that compared Tokyo172 with the Connaught vaccines, Ikeda et al found that the Tokyo172 vaccine had 48.77 +/-5.43 CFUs per dose, while the Connaught strain had 3.77 +/-1.45 CFUs. [ 2 ] This implies that a smaller dose of Tokyo172 is likely to be as effective as a much larger dose of the Connaught strain. Previous BCG Immunotherapy Technique Preparation The BCG solution is prepared by initially dissolving the freeze-dried powder with the diluent that comes with the preparation. This solution is diluted further with saline, so that the total volume is approximately 30 mL The individuals who prepare and administer BCG should wear gloves and avoid spilling or touching the vaccine. BCG may cause a strong local reaction in a sore or a cut.

If the vaccine is splashed into an eye, it should immediately be washed. This is a preparation that contains live organisms; care should be taken during preparation, administration, and disposal of the supplies. The BCG solution should be used within 2-3 hours. It is instilled into the bladder via a small catheter by gravity or a slow drip (not forced into the bladder). The solution should be retained for 1.5-2 hours, after which time the patient voids. The patient is encouraged to move positions every 30-45 minutes to allow the BCG solution to contact all portions of the bladder lumen. If the patient’s bladder ordinarily retains more than 60 mL of urine, the bladder may need to be drained after the BCG solution is retained for 2 hours. Patients do not have to remain in the office during the retention time. Patients should not be given antibiotics at the time of the instillation. These medications can kill the live organisms and negate the effect of the treatment. The patient should wash out the toilet with bleach following the next 3 urinations to avoid exposing other family members to the vaccine. BCG induction therapy To a BCG reaction, multiple instillations of BCG are required.

Typically, 6 weekly instillations constitute the induction phase, although some patients respond with fewer instillations and some require more. Each patient's response should be assessed each time the patient comes for an instillation. The induction phase is considered complete when the immunologic reaction has occurred. This is evident when the patient has irritative bladder symptoms, the urine contains WBCs without evidence of infection, and microscopic hematuria is present. Once the patient has been induced or vaccinated, this phase of therapy has been completed. BCG maintenance therapy When induction is completed, a course of immunoprophylaxis or maintenance therapy is begun. Prolonging the course of therapy has been shown to reduce the frequency of recurrence and progression. These intervals have varied from instillations administered monthly to every 3 months or every 6 months. The optimum frequency and duration of this therapy seems to vary, but a Southwest Oncology study found that 2-3 instillations every 3 months is effective. [ 3 ] Most experts agree that a maintenance program of at least 1 year is necessary.

From the immunologic point of view, establishing this interval is difficult because patient variability is great and this is a biologic product whose dose may differ slightly with each instillation. The products also vary. Antigenic stimulation becomes greater with consecutive instillations but decreases dramatically when the stimulation is excessive. Data from a small study conducted by Palou et al indicated that patients who are tumor-free after 6 months of therapy are likely to remain so indefinitely and do not need additional maintenance. [ 4 ] Most studies have shown the benefit of using maintenance therapy for at least one year. Tolerability of therapy Patients often have difficulty completing long-term therapy because of irritative adverse effects in the bladder. In such cases, the intervals between instillations should be lengthened; in addition, dose modification may also be necessary. Generally, a full ampule is administered, but some patients respond just as well to half or even one third of a dose and seem to have fewer adverse effects. The dose selection depends on the degree of reaction in the patient. Patients treated with the Tokyo172 substrain need only a 25% dose because of the potency of this product. The intent of the treatment is to elicit an immune response without overwhelming the immune system.

Previous Contributor Information and Disclosures Author Gary David Steinberg, MD, FACS The Bruce and Beth White Family Professor and Vice Chairman of Urology, Director of Urologic Oncology, Section of Urology, Department of Surgery, The University of Chicago Medical Center and Cancer Center Gary David Steinberg, MD, FACS is a member of the following medical societies: American Association for Cancer Research , Society of Laparoendoscopic Surgeons , American Society of Clinical Oncology , International Society of Urology , American College of Surgeons , American Urological Association , Society of Urologic Oncology Disclosure: Received consulting fee from Abbott Molecular for consulting; Received consulting fee from Endo Pharmaceuticals for consulting; Received consulting fee from Bioniche for consulting; Received consulting fee from Tengion for consulting; Received consulting fee from Archimedes for review panel membership; Received consulting fee from PhotoCure for review panel membership; Received consulting fee from Taris Biomedical for review panel membership; Received none from Cold Genesys for other; Received h for: Photocure; Taris Biomedical; Heat Biologics: Cold Genesys; Merck; Roche/Genentech; Karl Storz; Mdx Health, Telesta.

Coauthor(s) Sanjay G Patel, MD Fellow in Urologic Oncology, Department of Surgery, Section of Urology, University of Chicago Medical Center Sanjay G Patel, MD is a member of the following medical societies: Society of Urologic Oncology Disclosure: Nothing to disclose. Kush Sachdeva, MD Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner Disclosure: Nothing to disclose. Brendan Curti, MD Director, Genitourinary Oncology Research, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center Brendan Curti, MD is a member of the following medical societies: American College of Physicians , American Society of Clinical Oncology , Oregon Medical Association , Society for Immunotherapy of Cancer Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Prometheus Pharmaceuticals<br/>Received research grant from: Prometheus Pharmaceuticals.

Bagi RP Jana, MD Associate Professor of Medicine (Genitourinary Oncology), Division of Hematology and Oncology, University of Texas Medical Branch Bagi RP Jana, MD is a member of the following medical societies: American Cancer Society , American Medical Association , SWOG , American Society of Clinical Oncology Disclosure: Nothing to disclose. Specialty Editor Board Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Received salary from Medscape for employment. for: Medscape. Chief Editor Bradley Fields Schwartz, DO, FACS Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine Disclosure: Nothing to disclose. Acknowledgements Mark H Katz, MD Fellow in Urologic Oncology and Minimally Invasive Surgery, University of Chicago Medical Center Mark H Katz, MD is a member of the following medical societies: Alpha Omega Alpha , American Urological Association , Endourological Society , and Society of Urologic Oncology Disclosure: Nothing to disclose.

Dan Theodorescu, MD, PhD Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center Treatment of Drug Resistant TB BCG Vaccine – Current use, safety & skin test The BCG vaccine is the only TB vaccine currently available, although there are other TB vaccines under development. Although far from perfect, the BCG vaccine is a relatively inexpensive, safe, and readily available vaccine that is still the only vaccine available for the prevention of human forms of TB. Who is given the BCG vaccine? A child being given the BCG vaccine in their upper right arm © AMREF Demsissew Bizuwork The BCG vaccine is normally given to children as it has been shown to provide very good protection against the disseminated forms of TB in children , including TB meningitis. However the protection provided against pulmonary TB in adults is very variable.

So the BCG vaccine is not generally given to adults.1“Immunization surveillance, assessment and monitoring”, WHO The BCG vaccine is one of the most widely used of all current vaccines, and overall it reaches more than 80% of all new born children and infants in countries where it is part of the national childhood immunization programme.2“BCG vaccine”, WHO The World Health Organisation (WHO) monitors the estimated coverage of the BCG vaccine in every country. 3“Estimates of BCG coverage”, WHO //apps.who.int/immunization_monitoring/globalsummary/timeseries/tswucoveragebcg.html Not every country that could do so gives the vaccine to all children. Generally countries where there is a high level of TB use the BCG vaccine to vaccinate all children. Some countries with a low level of TB, such as the United States and England do not give all children the vaccine, but only those considered at particular risk.

The United States has never vaccinated all children, but in the United Kingdom all children were given the vaccine until 2005.4“The BCG World Atlas”, BCG vaccine for babies in the UK In the UK the BCG vaccine is recommended for all babies up to one year old who: are born in areas where the rates of TB are high have one or more parents or grandparents who were born in countries with a high incidence of TB.5“Who should have the BCG (TB) vaccine?”, NHS Choices, 2014, Newborn babies can be given the vaccine soon after birth.

Infants less than 6 months of age do not need to be tested with a tuberculin skin test (the Mantoux test) before the administration of BCG, but those over six months of age do.6“Does my baby need the BCG vaccine against Tuberculosis?”, The Portland Hospital, 2013, BCG vaccine for older children in the UK The BCG vaccination is recommended for all older children and adults at risk of TB including: older children with an increased risk of TB who were not vaccinated against TB when they were babies anyone under 16 who has come from an area where TB is widespread anyone under 16 who has been in close contact with someone who has pulmonary TB (TB infection of the lung). The BCG vaccine and the TB skin test A bottle containing BCG vaccine People who have had the BCG vaccine will often then have a positive result to a TB skin test . This makes it more difficult to establish whether someone has latent TB . This is one of the reasons that the vaccine is not used in some countries.7“When is the BCG (TB) vaccine needed? – Vaccinations – NHS Choices”, NHS choices The skin test will often be given before BCG vaccination.

If there is a positive result to the skin test indicating that the person already has some immunity to TB, then the BCG vaccination will not be given. Giving the BCG vaccine to someone who already has some immunity, provides no benefit and could cause unpleasant side effects.8“BCG (tuberculosis) vaccination – When it is needed”, NHS Choices, Shortage of BCG vaccine There has been a shortage of the BCG vaccine in the European Union since April of 2015. It is now not expected that supplies will return to normal until April 2017.9“100,000 babies lose out due to lack of TB jab”, Independent.ie, In England it is said that supplies of BCG ran out in the summer of 2016. BCG vaccine safety issues In the early years of the use of the BCG vaccine there were some concerns about safety, and there was the Lubeck disaster . Subsequently for many years there was little concern about safety. However it is now considered that the use of the BCG vaccine in children who are immune compromised, such as children with HIV, could result in them having an infection caused by the BCG vaccine itself.

This is because the BCG vaccine contains a live but very weakened form of a bacteria called Mycobacterium bovis. This is not the same bacteria though as the bacteria that causes TB in humans, which is called Mycobacterium tuberculosis.10BCG – the current vaccine for tuberculosis, WHO 11“The Difference Between Latent TB Infection and Active TB Disease”, CDC, Replacing the BCG vaccine The organisation AERAS was set up in 2003 to develop new, safe, effective and affordable vaccines to replace the BCG vaccine. A new vaccine will need to protect against all strains of TB including the different types of drug resistant TB . The vaccine will also need to be suitable for use in preventing TB in children, adolescents and adults, as well being safe for use in people who are infected with both HIV and TB .12“AERAS – Global Efforts”, AERAS AERAS is supporting the clinical testing of six possible new TB vaccines any one of which could be a suitable vaccine to replace BCG.

In October 2012 it was announced that in connection with Glaxo, AERAS will in 2013 begin a phase IIB study in Kenya, India and South Africa. It is planned that this vaccine if successful would be used alongside the existing BCG vaccine.13“Aera, GSK will test TB vaccine in India and Africa”, Vaccine News Daily, October 12 2012 vaccinenewsdaily.com Another potential TB vaccine also designed to be used in conjunction with BCG is MVA85A. In February 2013 the results were announced of a phase 2B trial of MVA85A.14“Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebos-controlled phase 2B trials”, The Lancet, February 4 2013 This disappointingly showed that MVA85A did not provide any significant effectiveness against either tuberculosis or M.

tuberculosis infection, although some people considered that: “the findings … are not a terminal prognosis for MVA85A, or for any of the other tuberculosis vaccines in development.”15“A major event for new tuberculosis vaccines”, The Lancet, February 4 2013 Read more You can read more about the history of the bcg vaccine . References

Question: BCG is an inoculation against what?
Answer: Tuberculosis