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Official reprint from UpToDate


www.uptodate.com 2015 UpToDate

BCG vaccination
Author
C Fordham von Reyn, MD

Section Editor
Daniel J Sexton, MD

Deputy Editor
Elinor L Baron, MD, DTMH

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2015. | This topic last updated: May 28, 2015.
INTRODUCTION Bacille Calmette-Gurin (BCG) is a live strain of Mycobacterium bovis developed by Calmette
and Gurin for use as an attenuated vaccine to prevent tuberculosis and other mycobacterial infections. The vaccine
was first administered to humans in 1921 and remains the only vaccine against tuberculosis in general use. Several
new vaccines against tuberculosis are also in development, and many are designed to boost the effects of BCG [1,2].
One investigational vaccine has been shown effective in a phase III trial [3].
Bacillus Calmette-Gurin vaccine is the most widely administered vaccine in the world; it has been given to over three
billion individuals, principally in the setting of routine newborn immunization (as dictated by guidelines of the World
Health Organization) [4]. There are multiple BCG vaccines in use around the world produced by different
manufacturers and administered by different schedules. In the United States, BCG was sometimes administered to
healthcare workers at risk for tuberculosis until the middle of the twentieth century but was never adopted for routine
childhood immunization. BCG has been recommended in the United States only for immune-competent children and
adults who have high risk of ongoing exposure that cannot be avoided [5].
Issues related to host immunity, vaccine efficacy, administration, safety, and policy will be reviewed here. Although the
major role of BCG is tuberculosis prevention, BCG vaccine is also effective for protection against leprosy, Buruli ulcer,
and disease due to nontuberculous mycobacteria. In addition, it is used as an immunostimulant in the treatment of
superficial carcinoma of the bladder. These topics are discussed in detail separately. (See "Epidemiology,
microbiology, clinical manifestations, and diagnosis of leprosy" and "Buruli ulcer (Mycobacterium ulcerans infection)"
and "Complications of intravesical BCG immunotherapy".)
MYCOBACTERIA AND HOST IMMUNITY Virtually any prior mycobacterial infection (whether naturally acquired or
vaccine induced) appears to produce some level of protection against subsequent disease due to tuberculosis and, in
some cases, to other mycobacteria [1]. Natural infections that confer protection against tuberculosis include prior
contained infection with Mycobacterium tuberculosis itself or prior infection with nontuberculous mycobacteria [6,7].
These observations suggest that protection is conferred by the immune response to common mycobacterial antigens.
Prior latent infection with M. tuberculosis that has been contained provides as much as 80 percent protection against
disease after subsequent exposure [8]. However, prior active disease is associated with an increased risk of a second
episode of active tuberculosis due to a different strain in both HIV-infected and HIV-uninfected persons [9-15]. (See
"Natural history, microbiology, and pathogenesis of tuberculosis", section on 'Host factors'.)
Bacille Calmette-Gurin (BCG) has also been associated with an overall reduction in childhood mortality not
attributable to tuberculosis; this effect is not fully understood but may be related to epigenetic reprogramming of the
NOD2 receptor [16-19].
BCG vaccine is administered either intradermally or intracutaneously. Since natural infection and sensitization to M.
tuberculosis in humans usually occurs by the respiratory route, research is being conducted on respiratory
administration of BCG [20,21].
EFFICACY The efficacy of Bacille Calmette-Gurin (BCG) vaccine is variable between trials and appears to depend
on several factors including the immune status of the recipient and degree of prior exposure to mycobacteria (both M.
tuberculosis and nontuberculous mycobacteria [NTM]) prior to vaccination. Prior exposure may both limit replication of
BCG ("blocking") and/or confer protection equivalent to BCG ("masking") [1,2]. Efficacy does not appear to be related

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to the particular BCG strain used in the vaccine [22]:


The protective efficacy of BCG appears to depend on the extent of prior exposure to mycobacteria, which in turn
is a function of age. Thus, mycobacteria-nave newborns appear to benefit more from BCG vaccination than
older individuals [23].
Older children and adults living in areas endemic for tuberculosis (TB) appear to have higher background immune
responses to mycobacterial antigens than those living in nonendemic areas (other than newborns), a factor that
may influence relative efficacy of BCG when administered to older children and adults living in TB-endemic
regions [24].
Both mycobacterial infections and live or inactivated whole cell mycobacterial vaccines confer protection against
tuberculosis, including infections and vaccines derived from both M. tuberculosis and NTM [25]. Absence of
species-specific protection may explain the lack of correlation between BCG efficacy and BCG strain potency.
Some have suggested a correlation between BCG efficacy and distance from the equator [22]; however, no
well-designed studies among mycobacteria-nave infants (the population in which BCG is most effective) have
been conducted in southern latitudes.
Tuberculosis
Active disease A widely cited meta-analysis suggests that BCG vaccination reduces the risk of active TB by
about 50 percent, although this figure does not reflect the important differences in efficacy in different age groups [26].
Primary vaccination of newborns and infants appears to confer protection in about 80 percent of cases, whereas
primary vaccination of older children and adults is considerably less effective [26-28].
The greatest benefit of BCG appears to be diminished risk of tuberculous meningitis and disseminated disease in
children (75 to 86 percent efficacy) [26-29]. However, studies that have evaluated these outcomes are limited by
biases in design and/or inadequate statistical power.
Mycobacteria-nave infants and newborns The efficacy of BCG immunization in providing protection
against subsequent tuberculosis in mycobacteria-nave newborns and infants has been evaluated in four prospective
trials conducted before effective treatment of TB was available [29-34]. Collectively, these trials demonstrated an
efficacy of 73 percent for protection against active disease and 87 percent against death [29]. One of these studies
was a randomized trial conducted in Chicago in the 1930s in which approximately 3400 infants 3 months of age were
randomized to receive percutaneous BCG or placebo [33]. Follow-up (ranging from 12 to 23 years) demonstrated
protective efficacy of 73 percent.
Mycobacteria-experienced older children and adults Many studies have failed to demonstrate protective
efficacy for administration of BCG vaccination to individuals more than a year of age who may have already been
infected with or exposed to mycobacteria, including both TB and NTM. Two factors may be relevant: first, natural
mycobacterial infection may provide protection equal to BCG; and second, BCG may have reduced replication (and
therefore reduced efficacy) in the face of prior mycobacterial immunity. The latter hypothesis is supported by an animal
model in which prior infection with NTM blocks the protective effects of BCG [35].
Notable data for mycobacteria-experienced individuals may be summarized as follows:
A trial in South India initiated in 1980 is often cited to demonstrate that BCG is not effective. This large
randomized, controlled trial was designed to investigate the efficacy of BCG against tuberculosis [36,37]. The
study objectives of this trial were twofold: (1) to compare the efficacy of different BCG strains and doses and (2)
to assess the efficacy of BCG in individuals with and without prior latent tuberculosis (determined by baseline
tuberculin skin testing).
In reality, however, the trial was largely a study of the effect of BCG in older children and adults, many of whom
were already tuberculin positive and all of whom lived in an area of high leprosy prevalence. Over 270,000
subjects were enrolled, but only 1500 (0.6 percent) were mycobacteria-nave newborns. Surveillance for

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tuberculosis was based on positive chest radiographs, which were only performed at age 5 years; those with
positive radiographs had sputum microbiology. Criteria for tuberculosis were limited to positive sputum culture or
positive acid-fast bacilli (AFB) stain, and there were no methods for detecting extrapulmonary tuberculosis.
These methods would be insensitive for the diagnosis of TB in children. Further, the observed rate of tuberculosis
in this large study cohort was half the predicted rate. At most, this trial demonstrated that BCG vaccination of
mycobacteria-experienced older children and adults in India does not lead to a reduction in pulmonary
tuberculosis among persons with positive sputum cultures and chest radiographs.
A trial of BCG vaccination conducted between 1935 and 1938 among Native Americans had the study with the
longest period of follow-up of all BCG vaccine trials reported to date [30]. This trial was a randomized, placebocontrolled study of 3287 individuals ages newborns to 20 years (28 percent 5 years) with baseline tuberculin
screening to exclude those with prior mycobacterial exposure.
Evaluation of vaccine recipients 11 years after vaccine administration demonstrated 75 percent reduction in
radiographically diagnosed tuberculosis; evaluation at 20 years demonstrated an 82 percent reduction in overall
mortality due to tuberculosis. The protective efficacy of BCG against active disease due to TB was 70 percent.
Evaluation of vaccine recipients 60 years after vaccine administration (the longest follow-up period of any BCG
trial) included data for 1998 of the original participants and demonstrated vaccine efficacy of 52 percent against
active tuberculosis disease [38].
Similar findings were described in a trial initiated in the 1950s that involving over 25,000 British teenage students
(with baseline tuberculin screening to exclude those with prior mycobacterial exposure) [39]. Follow-up at 15
years demonstrated vaccine efficacy of 76 percent against active tuberculosis disease.
Baseline data from a large cluster randomization study of BCG revaccination in Brazil have been analyzed to
compare the efficacy of initial neonatal versus initial school-age immunization. Estimated efficacy of neonatal
BCG was similar in two diverse communities (36 versus 40 percent), while efficacy of school-age BCG differed
(8 percent versus 34 percent). These findings may be due to regional differences in mycobacterial sensitization
[40].
Mycobacteria-nave older children and adults There are older children and adults in some settings who
remain sufficiently mycobacteria nave to respond to BCG. In a subsequent analysis of the South India trial, BCG was
found to be 32 percent effective in subjects who had negative NTM skin test results (PPD-B) at baseline [41] In a study
from Brazil, where approximately 70 percent of children are tuberculin negative, BCG efficacy was 25 percent in
subjects who received their first BCG vaccine at age 7 to 14 [42].
Latent infection Most studies have evaluated the efficacy of BCG for protection against active (rather than
latent) tuberculosis. Latent infection is not generally used as an efficacy endpoint since the presence of latent infection
is assessed by tuberculin skin test (whose utility is limited since BCG itself can sometimes induce a positive tuberculin
test). (See "Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-uninfected adults".)
However, interferon gamma release assays (IGRAs) have been shown to be useful tools for evaluating the efficacy of
BCG in preventing latent infection. This was illustrated in a Turkish study in which 979 children with exposure to
pulmonary tuberculosis were evaluated for latent TB infection using a T cellbased enzyme-linked immunospot assay
(ELISpot) [43]. BCG vaccination was protective for latent tuberculosis infection (odds ratio 0.60; 95% CI 0.43-0.83).
Additional studies using IGRAs have now shown protection against infection [44,45] (see "Interferon-gamma release
assays for diagnosis of latent tuberculosis infection"). A systematic review and meta-analysis of 14 studies that
assessed the protective effect of BCG against infection noted an overall protective efficacy of 19 percent (risk ratio
[RR] 0.81; 95% CI 0.71-0. 92) [46]. Restriction of the analysis to studies in which BCG was administered at birth
showed a protective efficacy of 28 percent (RR 0.72; 95% CI 0.56-0.93). Collectively, these data support the
protective effect of BCG against both TB disease and acquisition of TB infection.
Reinfection BCG may confer protection against multiple episodes of tuberculosis. In a long-term efficacy study
among Native Americans, the rate of two or more episodes of TB was 34 per 100,000 person-years in the placebo

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group and 4 per 100,000 person-years in the BCG group, consistent with a vaccine efficacy of 89 percent (95% CI
53-99 percent) [38].
Durability of protection The duration of BCG-induced protection against tuberculosis is generally believed to be
approximately 10 to 15 years; this is the period for which BCG has been shown to be protective against childhood
tuberculosis. However, the duration may vary; long-term follow-up of patients in a trial of BCG vaccination initiated in
the 1930s among American Indians and Alaskan natives demonstrated that partial protection may last 50 to 60 years
[38].
Several studies have demonstrated that BCG boosters do not increase the efficacy of protection against tuberculosis
[24,47,48]. The host immune response induced by the initial BCG dose may prevent replication of organisms
administered in a subsequent vaccine dose ("blocking") [35].
All-cause mortality Neonatal BCG administration provides protection against tuberculosis and reduces all-cause
mortality among neonates and infants. A study in Guinea-Bissau showed that BCG reduced all-cause neonatal
mortality by >40 percent in low birthweight infants [49]. Protection against septicemia and respiratory infection has
been observed [50], and cytokine profiles have been interpreted to indicate that BCG accelerates the development of
Th-1related and inflammatory innate immune responses ("trained innate immunity") [51].
Areas of uncertainty The efficacy of BCG vaccination has not been studied in the setting of drug-resistant
tuberculosis, although antibiotic susceptibility would not be expected to influence the efficacy of BCG.
There are no definitive prospective data on the efficacy of BCG for healthcare workers or travelers [52,53]. (See
'Groups to consider for vaccination' below.)
ADMINISTRATION There is no consensus among experts as to whether one strain of Bacille Calmette-Gurin
(BCG) is preferable or superior for use in formulating a BCG vaccine. Numerous strains of BCG have been used to
produce BCG vaccine, and none of these strains is demonstrably superior in terms of their efficacy or immunogenicity.
In the United States, two manufacturers are licensed to distribute BCG: Organon Teknika (Tice) and Sanofi Pasteur
(Mycobax, Connaught strain).
Dose The standard dose of BCG vaccine is 0.1 mg in 1 mL. Other childhood vaccines can be administered
simultaneously with BCG.
BCG can be administered intradermally (ID) or by multiple percutaneous puncture (MP) using a device with multiple
tines. The World Health Organization favors intradermal administration, although percutaneous administration is an
acceptable alternative [54].
Although intradermal administration appears to result in greater in vitro immunogenicity, skin test conversion, and
scarring than percutaneous administration [55], the clinical efficacy of these routes appears comparable [54]. This was
illustrated in a study of 11,680 newborn infants in South Africa randomized to receive intradermal or percutaneous
BCG; the rate of tuberculosis was equivalent between the groups in the first two years of life [54].
Tuberculin skin test (TST) conversion should not be used as an indicator of BCG vaccine efficacy among vaccine
recipients [47,48,56].
Safety and adverse effects Localized skin reactions following BCG vaccination are common. More serious
adverse effects include osteitis, osteomyelitis, and disseminated infection. Potential factors affecting the rate of
adverse reactions include the BCG dose, vaccine strain, and method of vaccine administration.
As many as 95 percent of BCG recipients have a local reaction at the site of inoculation characterized by formation of
a bluish-red pustule accompanied by pain, swelling, and erythema within two to three weeks after vaccination.
Ulceration with drainage occurs at the vaccine site in about 70 percent of cases, and about 75 percent of vaccinees
experience myalgias. After about six weeks, the pustule ulcerates, forming a lesion approximately 5 mm in diameter.
Lesions typically heal by three months with permanent residual scarring at the puncture site (picture 1).
Less common manifestations include abscess and regional lymphadenitis (1 to 2 percent). These may be accompanied

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by draining sinus tracts or fistulae; the risk for neonates is higher than for older children [57,58].
Management of local reactions consists of attentive wound care. Since viable organisms can be recovered from ulcer
drainage, vaccination sites should be covered to reduce transmission of the vaccine strain [59]. Abscess or fistula
formation may rarely require surgical drainage. In the setting of suppurative lymphadenitis, some favor
antimycobacterial therapy, although antimicrobial therapy has not been shown to be beneficial in meta-analyses
[60-63]. Nonsuppurative lesions are best managed with observation alone [60,61].
Osteitis and osteomyelitis BCG osteitis and osteomyelitis are rare; these entities may occur as a result of
direct spread from the administration site; less commonly, these may also occur as a result of dissemination.
Osteitis affecting the epiphyses of the long bones (particularly the leg) can occur 4 to 24 months after
vaccination. It has been reported in 0.01 per million vaccinees in Japan (multipuncture technique) and 30 per
million in Finland (intradermal technique) [58]. There is an increased incidence of genetic variants in the gene
encoding Toll-like receptor 2 among infants who develop BCG osteitis following vaccination, compared with those
that do not [64]. (See "Toll-like receptors: Roles in disease and therapy", section on 'TLR2/1'.)
Treatment of osteomyelitis usually consists of surgical evacuation plus administration of isoniazid (INH) and
rifampin for 6 to 12 months [58,65] (BCG is resistant to pyrazinamide and, unlike treatment of M. bovis infection,
ethambutol is not generally needed). (See "Mycobacterium bovis" and "Complications of intravesical BCG
immunotherapy".)
Disseminated disease Disseminated disease following BCG vaccination occurs most commonly in the setting of
immunosuppression. Populations at risk for dissemination include infants with severe combined immunodeficiency,
individuals with HIV infection or other immunodeficiency, and individuals who have received intravesical BCG for
bladder cancer [66]. The risk of disseminated BCG in HIV-infected infants ranges from 403 to 1300 per 100,000
doses administered. Mortality among HIV-infected children with disseminated BCG is about 75 percent, although
this figure is from studies in which most children were not on current antiretroviral therapy (ART) [67-69]. In the
pre-HIV era, the rate of disseminated BCG was reported to be between 0.19 and 1.56 per million vaccinees [67].
Although most cases of disseminated BCG have been reported in the weeks and months following childhood
immunization, case reports suggest that reactivation can occur years later in the setting of immunosuppression
[67]. Clinical manifestations and treatment of disseminated disease due to BCG are outlined separately. (See
"Complications of intravesical BCG immunotherapy", section on 'Systemic disease' and "Mycobacterium bovis",
section on 'Treatment'.)
Management Patients with disseminated disease should be treated with INH and rifampin for at least several
months. In the setting of immunosuppression, addition of ethionamide may be beneficial. This was illustrated in a small
series of HIV-infected children with BCG-induced complications for whom treatment with INH, rifampin, and
ethionamide was administered [70]. HIV-infected patients with disseminated BCG who are not already on combination
antiretroviral therapy should be started on ART. Vaccine-strain BCG is sensitive to INH and rifampin; however, some
suggest that resistance to INH or rifampin may develop in HIV-infected children treated for complications of BCG
[71,72]
HIV infection Safety of BCG administration in HIV-infected individuals is an important concern given that it is a live
vaccine. Adverse effects due to BCG vaccination may be more frequent among persons who have advanced or
symptomatic HIV infection than among persons who have asymptomatic HIV infection, are on effective antiretroviral
therapy, or are not HIV infected [73-77].
Case reports of BCG-related lymphadenitis, local ulceration, and disseminated BCG disease (which can occur several
years after BCG vaccination) have been described in HIV-infected patients. In a retrospective study of 352
HIV-infected children started on antiretroviral therapy, clinically significant complications of BCG immunization were
observed in 6 percent of cases [70]. In some cases, these reactions appeared to be due to immune reconstitution
inflammatory syndrome [69,70,78]. (See 'Safety and adverse effects' above and "Immune reconstitution inflammatory
syndrome".)

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Tuberculin test interpretation Most individuals who have received BCG vaccine have a TST reaction of 3 to 19
mm in size at two to three months following vaccination. The reaction wanes with time; at more than 10 years after
vaccination, it is generally <10 mm. However, with repeated tuberculin testing, such reactions may be boosted to >10
mm, as discussed below.
Childhood BCG vaccination is not a major cause of positive tuberculin skin test results in adulthood; in a study including
5952 individuals with history of BCG who underwent tuberculin skin testing 10 to 25 years later, only 8 percent had
positive results [79].
Therefore, previous BCG vaccination should NOT influence decisions regarding interpretation of TST results in
individuals vaccinated more than 10 years earlier. This is especially important since most individuals who receive BCG
vaccine come from countries where the incidence of tuberculosis is high.
In the setting of serial tuberculin testing, prior BCG vaccination may be associated with boosting. The booster
phenomenon is defined as a TST that is initially defined as negative (in a patient whose previous TST reactivity has
diminished over time) and is then boosted to a positive test by the skin testing procedure itself. If repeated tuberculin
testing is planned (such as annual screening for healthcare workers), initial two-step testing should be performed to
distinguish tuberculin conversion from boosting. (See "Diagnosis of latent tuberculosis infection (tuberculosis screening)
in HIV-uninfected adults", section on 'Booster response'.)
Interferon-gamma release assays (IGRAs) are not affected by BCG administration. Therefore, for situations in which
BCG vaccination may induce a positive TST (as in recently vaccinated persons or persons vaccinated multiple times
until their TST becomes positive), IGRA testing may permit distinction between positive tuberculin reactions due to
BCG vaccination versus tuberculosis infection. (See "Interferon-gamma release assays for diagnosis of latent
tuberculosis infection".)
GROUPS TO CONSIDER FOR VACCINATION The approach to Bacille Calmette-Gurin (BCG) vaccination policy
depends on the regional prevalence of tuberculosis (TB) and is variable around the world. In countries where the
prevalence of TB is moderate to high, neonatal vaccination is recommended by the World Health Organization (WHO)
and is administered routinely. In some circumstances, BCG is also administered for healthcare workers and close
contacts of patients with tuberculosis (particularly multidrug-resistant [MDR] TB) with negative tuberculin tests. In some
countries, BCG is given to children soon after birth with subsequent booster inoculations, although boosters have been
proven ineffective and are not recommended, even for BCG vaccine recipients who remain negative by subsequent
tuberculin testing.
In countries with a low burden of TB, universal BCG vaccination is not recommended or required. For example, routine
BCG vaccination has never been implemented in the United States; instead, TB control measures have focused on
detection and treatment of latent tuberculosis. Universal BCG vaccination was utilized for all school children at age 13
and all neonates in high-risk groups in the United Kingdom between 1953 and 2005. However, routine BCG vaccination
was discontinued in 2005 because of diminishing incidence of TB.
The WHO does not recommend use of BCG vaccine in the countries meeting the following criteria [80]:
Average annual rate of smear-positive pulmonary TB below 5 per 100,000
Average annual rate of tuberculous meningitis in children under five years below 1 per 10 million population
Average annual risk of TB infection below 0.1 percent
Children
Worldwide Newborns and infants are the demographic group with greatest potential benefit from BCG
vaccination, and this intervention has been adopted for prevention of tuberculosis worldwide. BCG vaccination is
appropriate for infants and children 5 years with high risk for exposure to individuals with active pulmonary
tuberculosis. BCG vaccination should be administered to healthy neonates as soon as possible after birth [81]. In
addition, immunization of BCG-nave school-age children (aged 7 to 14) not previously vaccinated has been shown to
confer partial protection against TB [42].

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BCG immunization practices vary by region depending on the prevalence of tuberculosis [82-84]. In countries with high
prevalence of TB, childhood BCG immunization should be administered routinely. For countries with intermediate to low
rates of tuberculosis (<5/100,000 smear-positive cases per year), selective childhood BCG immunization for children at
particular risk of TB exposure is appropriate. [83,84]. For example, BCG immunization may be reasonable for children
with exposure to drug-resistant disease.
Caution in administering BCG must be exercised in regions with high prevalence of both TB and HIV. The risk of
disseminated BCG in HIV-infected infants ranges from 403 to 1300 per 100,000 doses administered; in one series, a
mortality rate of 75 percent was reported among HIV-infected children with disseminated BCG [67-69]. Therefore,
BCG vaccination is not appropriate for infants or adults with known HIV infection (or other immunodeficiency), nor for
infants with symptoms consistent with HIV infection in the absence of laboratory confirmation of actual HIV infection
[85-88].
In contrast, BCG vaccination should be administered to asymptomatic infants born to mothers with unknown HIV status
in countries with high TB prevalence [5,68,88,89]. However, for asymptomatic infants with unknown HIV status born to
mothers known to be HIV infected, the optimal approach to BCG vaccination is uncertain [88]. In such cases, the
clinical approach should be based on local factors including TB prevalence, antiretroviral therapy use in mother and
infant and other interventions implemented to reduce mother-to-child transmission of HIV, rates of breastfeeding, and
clinical resources for HIV diagnosis and postvaccination follow-up to evaluate for disseminated BCG.
An international advisory group has recommended that routine childhood BCG immunization be continued until all
elements of an HIV testing program can be implemented [68]. Although some favor delaying BCG vaccination for
HIV-exposed infants until HIV polymerase chain reaction testing results are available, implementation of this approach
requires careful coordination [68]. In addition, delaying BCG vaccine may reduce BCG immunization rates for children
who are not HIV infected.
BCG-vaccinated infants born to known HIV-infected mothers should be followed clinically to evaluate for signs of
disseminated BCG. For infants with exposure to smear-positive pulmonary TB in the neonatal period, BCG vaccination
should be deferred until six months of preventive isoniazid therapy have been administered to the infant (so that
isoniazid does not inactivate the live organisms in the BCG vaccine).
Developed countries In the United states (and other developed countries), BCG vaccination may be
considered in infants and children 5 years in the following circumstances [5,90].
The child is exposed continually to an untreated or ineffectively treated patient who has infectious pulmonary TB,
and neither separation from infectious patient nor long-term primary preventive therapy is feasible.
The child is exposed continually to a patient who has infectious pulmonary TB caused by M. tuberculosis strains
resistant to isoniazid and rifampin, and separation from the infectious patient is not feasible.
Exposure to MDR-TB The efficacy of BCG vaccination for healthcare workers, travelers, and individuals in the
community with expected exposure to drug-resistant tuberculosis is uncertain. However, given the potentially significant
risk of multidrug-resistant TB treatment failure, together with the relatively low rate of complications related to BCG
vaccination in immunocompetent individuals, some favor administering BCG vaccination to unvaccinated, tuberculinnegative individuals exposed to multidrug-resistant TB [88]. Further study is needed to reconcile the protective efficacy
of BCG vaccination in the setting of multidrug-resistant TB exposure among older children and adults.
Healthcare workers The protective efficacy of BCG vaccination in healthcare workers is not certain [91]. In
settings with low risk of M. tuberculosis transmission, BCG vaccination for healthcare workers is not warranted [91]. In
regions with high risk for TB transmission, careful adherence to TB infection control practices should be emphasized.
Despite data demonstrating the limited efficacy of BCG in adults, consideration of BCG vaccination may be
appropriate for healthcare workers from low-risk countries caring for patients or refugees in tuberculosis-endemic
countries [92,93]. (See "Tuberculosis transmission and control".)
In the setting of substantial risk for exposure to multidrug-resistant TB strains, BCG vaccination for healthcare workers

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should be considered on an individual basis [88]. In such circumstances, counseling should be offered regarding the
variable data for BCG vaccination efficacy, including discussion of risks and benefits associated with BCG vaccination.
GROUPS NOT TO VACCINATE
Immunocompromised patients Safety of Bacille Calmette-Gurin (BCG) administration in immunocompromised
individuals is an important concern given that it is a live vaccine. BCG vaccination should not be administered to
individuals with immune compromise due to HIV infection, congenital immunodeficiency, malignancy, or
immunosuppressive drugs such as corticosteroids and tumor necrosis factor-alpha blockers. (See 'Safety and adverse
effects' above.)
In addition, caution should be observed among immunocompromised patients with household or other close contact
with individuals recently been immunized with BCG; drainage from the injection site contains live organisms and should
be covered to avoid transmission.
Adults with HIV infection and individuals with HIV infection in areas of low tuberculosis prevalence should NOT receive
BCG vaccination [80]. The role of BCG vaccination for HIV-infected children in areas with endemic tuberculosis is
discussed in the preceding section. (See 'Children' above.)
Pregnant women Although BCG vaccination has not been associated with harmful fetal effects, it should not be
administered in pregnancy since it is a live vaccine [5].
SUMMARY AND RECOMMENDATIONS
Bacille Calmette-Gurin (BCG) is a live strain of Mycobacterium bovis developed by Calmette and Gurin for use
as an attenuated vaccine (intradermal or multiple percutaneous puncture) to prevent tuberculosis (TB) and other
mycobacterial infections. The magnitude of protection appears to be in the range of 80 percent in the first 15
years of life but is much lower subsequently. (See 'Mycobacteria and host immunity' above.)
The greatest benefit of BCG appears to be diminished risk of TB, including tuberculous meningitis and
disseminated disease in children. Vaccination of mycobacteria-nave newborns and infants appears to confer
greater benefit than vaccination of older children and adults who have often had mycobacteria exposure. (See
'Active disease' above.)
Injection site reactions are common following BCG vaccination. Management of local reactions consists of
attentive wound care; the efficacy of antimycobacterial therapy is uncertain, and indolent lesions are best
managed with observation alone. Since viable organisms can be recovered from ulcer drainage, vaccination sites
should be covered to reduce transmission of the vaccine strain. (See 'Safety and adverse effects' above.)
Serious adverse effects include osteitis, osteomyelitis, and disseminated infection. Disseminated BCG infection
following BCG vaccination occurs most commonly in the setting of HIV infection and other forms of
immunosuppression. (See 'Safety and adverse effects' above.)
Most individuals who have received BCG vaccine have a tuberculin reaction of 3 to 19 mm in size at two to three
months following vaccination. The reaction wanes with time; at more than 10 years after vaccination, it is
generally <10 mm. Therefore, previous BCG vaccination should not influence decisions regarding tuberculin skin
testing or interpretation of results in individuals vaccinated more than 10 years earlier. Testing with an
interferon-gamma release assay may permit distinction between positive tuberculin reactions due to BCG versus
tuberculosis. (See 'Tuberculin test interpretation' above.)
In areas where the prevalence of TB is high, we recommend that a single dose of BCG be administered to
healthy neonates as soon as possible after birth (Grade 1A). This includes administration of BCG vaccination to
neonates born to mothers with unknown HIV status. (See 'Children' above.)
BCG should NOT be administered to individuals with immune compromise due to HIV infection, congenital
immunodeficiency, malignancy, or immunosuppressive drugs. For asymptomatic infants with unknown HIV status
born to mothers known to be HIV infected, the optimal approach to BCG vaccination is uncertain and should be

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considered in conjunction with local factors. (See 'Immunocompromised patients' above and 'Children' above.)
We suggest NOT administering BCG in the setting of pregnancy (Grade 2C). (See 'Groups not to vaccinate'
above.)
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GRAPHICS
Bacille Calmette-Gurin vaccination scarification

Bacille Calmette-Gurin scarification (arrow) on deltoid.


Graphic 91059 Version 1.0

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Disclosures
Disclosures: C Fordham von Reyn, MD Nothing to disclose. Daniel J Sexton, MD Grant/Research/Clinical Trail Support: Cubist [C. difficile
infection (Fidaxomycin)]. Consultant/Advisory Boards: Johnson & Johnson [Pelvic mesh-related infection]; Sterilis [Medical waste disposal
systems]; Magnolia Medical Technologies [Intravenous devices]. Other Financial Interest: National Football League [Infection control program].
Equity Ownership/Stock Options: Magnolia Medical Technologies [Intravenous devices]. Elinor L Baron, MD, DTMH Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a
multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is
required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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