Bacillus Calmette-Guérin (BCG Live Systemic )


Note: This monograph is specific for the Bacillus Calmette-Guérin (BCG) live vaccine, intended for immunization of uninfected (tuberculin negative) persons to induce tuberculin sensitivity as a protection against tuberculosis infection. Only BCG live vaccine labeled for use against tuberculosis infection should be used for immunization, or where labeled for use both against tuberculosis infection and bladder cancer (for bladder cancer see Bacillus Calmette-Guérin (BCG) Live, Mucosal-Local ). {01} {03} {04} {38} The efficacy of the BCG vaccines currently available has not been demonstrated directly and can only be inferred. {03} {15} {16} {18}


VA CLASSIFICATION
Primary: IM100

Commonly used brand name(s): TICE BCG.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Immunizing agent (active)—

Indications

Accepted

Tuberculosis (prophylaxis)—BCG live vaccine is recommended for protection against tuberculosis in the following persons if tuberculin skin test (purified protein derivative [PPD]) result is negative.
—   • Infants and children who   —Are at high risk of intimate and prolonged exposure to persistently untreated or ineffectively treated patients with infectious pulmonary tuberculosis and who cannot be removed from the source of exposure, and cannot be placed on long-term preventive therapy;
   —Are continuously exposed to persons with tuberculosis who have bacilli resistant to isoniazid and rifampin; {01} {03} {04} {05} {16} {18} {21} {35} {36} {37} {38}
   —Are in groups in which the rate of new infections exceeds 1% per year and for whom the usual surveillance and treatment programs have been attempted but are not operatively feasible. {01} {03} {04} {05} {16} {18} {20} {21} {27} {30} {35} {36} {37} {38}

   • Household contacts of untreated or insufficiently treated tuberculosis patients, especially patients with a positive sputum culture, when the contacts cannot be effectively shielded from prolonged exposure to the patients. {01} {03} {04} {05} {16} {18} {32} {35} {36} {37} {38}


—Selective vaccination is indicated for international travelers with a negative or weakly positive PPD who may be in a high-risk environment for prolonged periods without access to tuberculin testing surveillance. {01} {03} {04} {32} {37} {38}

—Health care workers who are likely to be exposed continuously to multidrug-resistant tuberculosis may benefit from vaccination with BCG live. {44} {45} {47} {48} {49}

Unaccepted
Routine BCG vaccination is no longer recommended in the U.S. since the risk of infection is very low. Also, routine vaccination of health care workers repeatedly exposed to tuberculosis infection is not recommended; tuberculin testing surveillance and prophylactic isoniazid are preferable. {01} {03} {04} {05} {18} {32} {35} {36} {37} {38}

BCG live vaccine labeled for use only as an immunizing agent for the prevention of tuberculosis is not intended for use in the treatment of bladder carcinoma. BCG live vaccine labeled for use against tuberculosis infection and bladder cancer can be used for both. BCG vaccine has no value in the treatment of tuberculosis disease. {03} {38}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    A live culture of attenuated organisms of bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis . {07} The original attenuated strain was distributed by Calmette and Guérin widely throughout the world for preparation of BCG vaccine. Until the development of lyophilization techniques, by which the seed culture is preserved currently, the strain was continued by repeated subculturing. This has resulted in the appearance of a number of seed strains with differing characteristics in various countries. {02} {03} {15} {16} {42} {43}
    In the U.S., approved BCG live vaccine is prepared from an acceptable seed lot shown to produce vaccines that meet all the prescribed requirements for the product and that have been evaluated in clinical trials for their ability to induce tuberculin sensitivity. {03} {07} {15} {16} No data are available concerning the clinical efficacy of this strain. {03} {15} {16} {18}
    The efficacy of any of the currently available BCG vaccines has not been demonstrated directly and can only be inferred. {03} {15} {16} {18}

Mechanism of action/Effect:

BCG live vaccine induces cell-mediated immunity against tuberculosis. {03} However, its mechanism of action is unknown, and it is unclear whether BCG induces antitubercular antibodies. {03} {37}


Other actions/effects:

BCG live vaccine induces antibodies that bind to Mycobacterium leprae and may be effective in providing protection against leprosy. {10} {11} {12} {13} {34} {37} {39} {43}


Protective effect

BCG live vaccination induces tuberculin sensitivity in more than 90% of vaccinated individuals. The protection afforded by BCG live vaccination has been reported from different field trials ranging from 0 to 80%, 50% in meta-analysis. However, there is poor correlation between tuberculin skin test conversion rates or size of induration and protective immunity. {24} {50} Protection, while prolonged, has not been judged to be permanent. In some clinical trials, protection has been negligible. {16} {41} The level of protection against meningitis or miliary tuberculosis in children has been found to be 64 to 86% in clinical trials and 75 to 83% in case control studies. {23} {28} {50}


Precautions to Consider

Pregnancy/Reproduction
Fertility—
Studies have not been done.

Pregnancy—
Studies have not been done in humans. It is not known whether BCG vaccine can cause harm to the fetus when administered to a pregnant woman. BCG vaccine should be given to a pregnant woman or a woman of childbearing age only if the potential benefits outweigh the possible risks. {06} {18} {33} {37} {38}

Studies have not been done in animals.

FDA Pregnancy Category C. {06}

Breast-feeding

It is not known whether BCG vaccine is distributed into breast milk. However, problems in humans have not been documented. {37}

Pediatrics

Infants less than 1 month of age should be given one-half of the usual dose. If a vaccinated infant remains tuberculin negative and the vaccine is still indicated, the vaccination should be repeated at full dose after the infant reaches 1 year of age. {37} The World Health Organization (WHO) does not recommend tuberculin skin testing prior to BCG vaccination for infants and children, who are the largest group of individuals receiving BCG in the world. The WHO has recommended that, in populations where the risk of tuberculosis is high, human immunodeficiency virus (HIV)-infected children who are asymptomatic should receive BCG vaccine at birth or as soon as possible thereafter. {18} However, in populations where the incidence of tuberculosis is low, the risk of disseminated BCG infection outweighs the potential benefit from BCG live vaccination. {44} {46} {47} {48} {49} For unvaccinated infants, the Expanded Programme on Immunization (EPI) at WHO recommends simultaneous administration of BCG, measles, DTP, and polio vaccines. EPI, however, does not recommend mixing different vaccines in one syringe, and if vaccines cannot be given on the same day, then live vaccines should be separated by at least 4 weeks. These recommendations of the WHO are based on the fact that the separate administration of live vaccines is not practical or feasible in many developing countries where BCG usage is greatest. {50}


Geriatrics


Appropriate studies on the relationship of age to the effects of BCG vaccine have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Antitubercular agents    (antitubercular agents, such as isoniazid, rifampin, and streptomycin, inhibit multiplication of BCG; therefore, BCG vaccine may not be effective if administered during treatment with these medications {05})


» Corticosteroids    (possibility of the vaccine establishing a systemic infection {18})


» Immunosuppressant agents    (immunosuppressant agents may interfere with the development of the immune response and should be used only under medical supervision {03})


» Vaccines, killed or live virus    (concurrent administration with BCG is not recommended; it is recommended that live virus vaccines be given 6 to 8 weeks after BCG; and that killed virus vaccines be given 7 days before or 10 days after BCG {03} {37})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Tuberculin, purified protein derivative (PPD)    (a positive reaction is produced in most patients, usually 6 to 12 weeks after BCG vaccination; however, administration of a tuberculin test a few years after BCG vaccination may result in either positive or negative reaction {03} {37})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Fever    (BCG should not be administered until the cause of the fever has been determined; if the fever is caused by infection, BCG should be withheld until the patient is afebrile and off all therapy {37} {38})


» Impaired immune response, including that associated with{46} HIV infection    (BCG vaccine is less effective in patients with decreased natural immunity; in addition, the risk of disseminated BCG infection may be increased {05} {17} {18} {19} {22} {26} {31} {33} {37} {38})


Risk-benefit should be considered when the following medical problems exist
Extensive skin infections{37}{38}
Sensitivity to BCG live or any of its component substances{03}{37}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Tuberculin, PPD skin test    (it is usually impossible to distinguish between tuberculin sensitivity caused by M. tuberculosis infection and tuberculin sensitivity resulting from the vaccine; therefore, caution should be exercised in interpreting tuberculin skin test reactions {03} {29} {38} {40})




Side/Adverse Effects

Note: The initial skin lesions, which are small red papules, appear in 10 to 14 days and reach a maximum diameter of 3 mm each after 4 to 6 weeks, which may scale and slowly subside. {38} If not an abscess forms, which usually softens and tends to open spontaneously. {38} The abscess heals within a few weeks, and, in such instances, a scar may form. {18} {38} The intensity and duration of the local reaction depend on the depth of penetration achieved in administration and the individual variation in tissue reaction. {01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Abscesses (accumulation of pus)
    
dermatologic reactions (peeling or scaling of the skin)
    
granulomas (aggregation of inflammatory cells)
    
lymphadenitis (inflammation of 1 or more lymph nodes)
    
ulceration at site of injection (sores at place of injection){08}{14}{18}{20}{33}

Incidence rare
    
Allergic reaction or erythema nodosum (skin rash)
    
BCG infection, disseminated (fever; cough)
    
osteomyelitis (increase in bone pain){09}{18}{20}{33}


Note: Symptoms of disseminated BCG infection may be difficult to distinguish from those of gram-negative sepsis or severe hypersensitivity reactions. Disseminated BCG infection is usually diagnosed based on the presence of fever and chills. Disseminated infection following BCG administration has occurred in individuals with impaired immune responses, especially children. {05} {19} It has also occurred following administration of BCG vaccine in patients with acquired immune deficiency syndrome (AIDS) and symptomatic HIV infection, and, rarely, in patients with asymptomatic HIV infection. If disseminated BCG infection is suspected in an individual who has received BCG live, appropriate antitubercular therapy should be initiated. {01} {03}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Bacillus Calmette-Guérin (BCG) Live (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before receiving this vaccine
»   Conditions affecting use, especially:
Sensitivity to BCG live {03}
Other medications, especially antitubercular agents, corticosteroids, immunosuppressant agents, or killed or live virus vaccines {01} {03} {04} {38}
Other medical problems, especially fever, or impaired immune response, including symptomatic HIV infection {01} {03} {04} {38}

Proper use of this vaccine
» Importance of telling the patient that the vaccine contains live organisms

» Proper dosing


Side/adverse effects
Signs of potential side effects, especially abscesses, allergic reaction or erythema nodosum, dermatologic reactions, disseminated BCG infection, granulomas, lymphadenitis, oseteomyelitis, and ulceration at site of injection. {01} {04} {05} {18} {26} {38}


General Dosing Information
The potency of BCG vaccines varies markedly and is related to several factors. These factors include the intrinsic immunogenicity of the particular strain, as well as other properties conferred by the method of preparation of the vaccine. {03} {15} {16} {20} {25} {34} In each country, the use of a particular vaccine depends on what is permitted by the national control authority and is based on the results of controlled field trials, which may not have included the particular national vaccine. {03} {15} {16} The results have shown considerable variations, depending on the particular vaccines included, and may also be related to the immunity status of the subject population. {03} {15} {16} {20} {26}

BCG live vaccine for immunization against tuberculosis should be administered according to the manufacturer's instructions. {01} {38}

Before the vaccine is administered, the risks and benefits of the vaccination should be fully explained to the patient, parent, or guardian. {01}

The patient should be advised that the vaccine contains live organisms. {01} {04} {05} {38}

BCG live vaccine should be used with caution in individuals with asymptomatic HIV infection and in individuals known to be at high risk for HIV infection. {01} {04} {05} {19} {20} {31} {33} {35}

BCG live vaccine should be administered only to individuals with a negative tuberculin skin test. The tuberculin skin test (preferably done by Mantoux method) should be performed within 6 weeks prior to administration of BCG live vaccine. In persons highly sensitive to tuberculosis antigens, severe reactions may occur. {01} {03} {04} {37} {38} However, the WHO does not recommend tuberculin skin testing prior to BCG vaccination for infants and children, who are the largest group of individuals receiving BCG in the world. {50}

For BCG vaccine (Tice strain)
BCG vaccine (Tice strain) is administered percutaneously, using a sterile multiple-puncture disk. The multiple-puncture disk is a thin wafer-like stainless steel plate from which 36 points protrude. The disk is held by magnet type holder. In this method of administration a drop of vaccine is placed on the patient's arm and spread with the wide edge of the disk. The disk is placed gently over the vaccine and the magnet is centered. The arm is grasped firmly from underneath, tensing the skin appreciably. Downward pressure is applied on the magnet so the points of the disk are well buried in the skin. With pressure still exerted, the disk is rocked forward and backward and from side to side several times. Pressure underneath the arm is then released and the magnet is slid off the disk. In a successful procedure, the points of the disk remain in the skin. If the points are on top of the skin, the procedure must be repeated. After a successful puncture, the disk is removed and the vaccine is spread evenly over the puncture area with the wide edge of the disk. Each disk should be used only once and discarded after autoclaving. The magnet should be sterilized after each individual vaccination. {01} {04} {27} {37}

For BCG vaccine (Connaught strain)
BCG vaccine (Connaught strain) is administered intracutaneously into the outer surface of the upper arm. Repeat vaccination is advisable for individuals remaining tuberculin negative to the Mantoux test more than 3 months after the initial vaccination. {38}

For BCG vaccine (Montreal strain)
BCG vaccine (Montreal strain) is administered intradermally into the deltoid region of the arm or the upper external part of the thigh. Any unused portion of BCG vaccine and all material used for reconstituting the vaccine must be sterilized prior to disposal. {38}

For treatment of adverse effects
Recommended treatment consists of the following:

   • Triple-drug antituberculosis therapy or
   • Appropriate 3- or 4-drug antitubercular therapy.


Parenteral Dosage Forms

BCG VACCINE (TICE STRAIN) USP

Usual adult and adolescent dose
Tuberculosis (prophylaxis)
Percutaneous, 0.02 to 0.03 mL of the reconstituted vaccine. {01} {04} {05}


Usual pediatric dose
See Usual adult and adolescent dose . {01} {04}

Note: If BCG live is indicated in neonates younger than 1 month of age, the dosage should be decreased by 50%. If indications persist and the tuberculin skin test is negative, a full dose of BCG live should be given after 1 year of age. {01} {04}


Size(s) usually available:
U.S.—


1 to 8 × 10 8 CFU, or approximately 50 mg (wet weight) per vial (Rx) [TICE BCG{01}]

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (35.6 and 46.4 °F). Protect from light. {01} {04} {07}

Preparation of dosage form:
Reconstituted by adding 1 mL (2 mL for neonates younger than 1 month of age) of sterile water for injection should be added to the vial using a sterile syringe. The mixture should then be drawn back into the syringe, and expelled again into the vial 3 times to mix it thoroughly. {01} {04}


BCG VACCINE(CONNAUGHT STRAIN)

Usual adult and adolescent dose
Tuberculosis (prophylaxis)
Intracutaneous, 0.1 mL of the reconstituted vaccine.


Usual pediatric dose
Tuberculosis (prophylaxis)
Children 1 year of age and over: See Usual adult and adolescent dose.

Children up to 1 year of age: Intracutaneous, 0.05 mL of the reconstituted vaccine.


Size(s) usually available:
U.S.—
Not commercially available.

Canada—


Multi-dose vial (Rx)[Generic]

Packaging and storage:
Store between 2 and 8 °C (35.6 and 46.4 °F). Protect from light.

Stability:
Reconstituted vaccine should be used immediately and any that is unused by the end of the day should be destroyed. The reconstituted vaccine should be stored at 4 °C during the day of reconstitution. {38}


BCG VACCINE(MONTREAL STRAIN)

Usual adult and adolescent dose
Tuberculosis (prophylaxis)
Intradermal, 0.1 mL (0.075 mg of BCG) of the reconstituted vaccine.


Usual pediatric dose
Tuberculosis (prophylaxis)
Children 2 years of age and over: See Usual adult and adolescent dose .

Children up to 2 years of age: Intradermal, 0.1 mL (0.0375 mg of BCG) of the reconstituted vaccine.


Size(s) usually available:
U.S.—
Not commercially available.

Canada—


0.75 mg of freeze-dried vaccine per ampule (Rx)[Generic]

Packaging and storage:
Store between 2 and 8 °C (35.6 and 46.4 °F). Protect from light.

Preparation of dosage form:
1 mL (2 mL for children under 2 years of age) of the diluent supplied with the vaccine is added to the ampule via a sterile syringe. The suspension is then drawn into the syringe, and expelled again into the ampule, 2 times to ensure homogenicity. The ampule should not be shaken, to avoid frothing of the solution. The reconstituted solution should be allowed to stand for one minute before use.



Revised: 07/20/1995



References
  1. TICE BCG package insert (Organon—US), Rev 3/94, Rec 8/94.
  1. Brewer TF, Colditz GA. Relationship between Bacille Calmette-Guérin (BCG) strains and the efficacy of BCG vaccine in the prevention of tuberculosis. Clin Infect Dis 1995; 20: 126-35.
  1. McEvoy GK, editor. AHFS Drug information 94. Bethesda, MD: American Society of Hospital Pharmacists, 1994: 2184-6.
  1. PDR Physicians' desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data Production Company, 1994: 1638-40.
  1. Drug evaluations annual 1994. Chicago: American Medical Association, 1994: 1627-30, 1955-6.
  1. Briggs GG, Freeman RK, Yaffe SJ. A reference guide to fetal and neonatal risk. Drugs in pregnancy and lactation. 3rd ed. Baltimore: Williams & Wilkins, 1990: 627/v.
  1. The United States pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 166.
  1. Brewer AM, Edwards KM, Palmer PS, Hinson HP. Bacille Calmette-Guérin immunization in normal healthy adults. J Infect Dis 1994; 170: 476-9.
  1. Hoppe JE, Orlikowsky T, Klingebiel T, Niethammer D. Costal BCG osteomyelitis presenting as a tumor. Infection 1992; 20(2): 94-6.
  1. Ponnighaus JM, Fine PEM, Sterne JAC, Wilson RJ, Msosa E, Gruer PJK, et al. Efficacy of BCG vaccine against leprosy and tuberculosis in northern Malawi. Lancet 1992; 339: 636-9.
  1. Lwin K, Sundaresan T, Gyi MM, Bechelli LM, Tamondong C, Garbajosa PG, et al. BCG vaccination of children against leprosy: fourteen-year findings of the trial in Burma. Bull World Health Organ 1985; 63(6): 1069-78.
  1. Muliyil J, Nelson KE, Diamond EL. Effect of BCG on the risk of leprosy in an endemic area: a case control study. Int J Lepr 1991; 59(2): 229-36.
  1. Bagshawe A, Scott GC, Russell DA, Wigley SC, Merianos A, Berry G. BCG vaccination in leprosy: final results of the trial in Karimui, Papua New Guinea, 1963-79. Bull World Health Organ 1989; 67(4): 389-99.
  1. Baki A, Oncü M, Usta S, Yildiz K, Karagüzel A. Therapy of regional lymphadenitis following BCG vaccination. Infection 1991; 19(6): 414-6.
  1. Fine PEM, Rodriguez LC. Mycobacterial diseases. Lancet 1990; 335: 1016-20.
  1. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 1994; 271(9): 698-702.
  1. Ryder RW, Oxtoby MJ, Mvula M, Batter V, Baende E, Nsa W, et al. Safety and immunogenicity of bacille Calmette-Guérin, diphtheria-tetanus-pertussis, and oral polio vaccines in newborn children in Zaire infected with human immunodeficiency virus type 1. J Pediatr 1993; 122(5 pt 1): 697-702.
  1. Centers for Disease Control. Use of BCG vaccines in the control of tuberculosis: a joint statement by the ACIP and the Advisory Committee for Elimination of Tuberculosis. MMWR. Morb Mortal Wkly Rep 1988; 37(43): 663-75.
  1. Guidelines on the management of tuberculosis and HIV infection in the United Kingdom. Subcommittee of the Joint Tuberculosis Committee of the British Thoracic Society. BMJ 1992; 304: 1231-3.
  1. Centers for Disease control. International notes. BCG vaccination and pediatric HIV infection—Rwanda, 1988-1990. MMWR. Morb Mortal Wkly Rep 1991; 40(48): 833-6.
  1. Joseph CA, Watson JM, Fern KJ. BCG immunization in England and Wales: a survey of policy and practice in schoolchildren and neonates. BMJ 1992; 305: 495-8.
  1. Centers for Disease Control. Vaccines and toxoids indicated or specifically contraindicated for situations involving special health status, United States. MMWR. Morb Mortal Wkly Rep 1991; 40(RR-12): 59.
  1. Clemens JD, Chuong JJH, Feinstein AR. The BCG controversy. A methodological and statistical reappraisal. JAMA 1983; 249(17): 2362-9.
  1. Simchen E, Zilber N, Wartski S, Shakaya GR. Incidence of tuberculosis among children born in Israel—1956 to 1979. Isr J Med Sci 1984; 20: 695-701.
  1. Simchen E, Zilber N, Wartski S, Shakaya GR, Marcus JH. Effect of mass BCG vaccination at birth on the incidence of tuberculosis among Jewish children in Israel. Isr J Med Sci 1984; 20: 1150-7.
  1. Desforges JF, Gardner P, Schaffner W. Current concepts. Immunization of adults. N Engl J Med 1993; 328(17): 1252-8.
  1. Cundall DB, Ashelford DJ, Pearson SB. BCG immunization of infants by percutaneous multiple puncture. BMJ 1988; 297: 1173-4.
  1. BCG vaccination against tuberculosis: international perspectives. Vaccinate the newborn in developing countries and those at risk in developed countries [editorial]. BMJ 1993; 306: 222-3.
  1. Bacille Calmette-Guérin vaccinations and tuberculin skin tests [commentary]. JAMA 1985; 253(23): 3438-9.
  1. Curtis HM, Leck I, Bamford FN. Incidence of childhood tuberculosis after neonatal BCG vaccination. Lancet 1984; 1: 145-8.
  1. De Cock KM, Soro B, Coulibaly IM, Lucas SB. Tuberculosis and HIV infection in sub-Saharan Africa. JAMA 1992; 268(12): 1581-7.
  1. Use of BCG Vaccines in the Control of Tuberculosis: A Joint Statement by the ACIP and the Advisory ACIP Committee for Elimination of Tuberculosis. JAMA 1988; 260(20): 2983-4, 2988, 2991.
  1. Tardieu M, Truffot-Pernot C, Carriere JP, Dupic Y, Landrieu P. Tuberculosis meningitis due to BCG in two previously healthy children. Lancet 1988; 1: 440-1.
  1. Fine PEM, Ponnighaus JM, Maine N, Clarkson JA, Bliss L. Protective efficacy of BCG against leprosy in Northern Malawi. Lancet 1986; 2: 499-502.
  1. Centers for Disease Control. Recommendations of the Advisory Committee on Immunization Practice (ACIP): Use of vaccines and immune globulins for persons with altered immunocompetence. MMWR. Morb Mortal Wkly Rep 1993; 42(RR-4): 6.
  1. Gennaro AR, editor. Remington's pharmaceutical sciences. 18th ed. Easton, PA: Mack Publishing Company, 1990: 1393.
  1. Grabenstein JD, editor. ImmunoFacts: Vaccines and immunologic drugs. St Louis: Facts and Comparisons, 1993: 36-42.
  1. Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 142-3.
  1. Fine PEM, Sterne JAC, Ponnighaus JM, Rees RJW. Delayed-type hypersensitivity, mycobacterial vaccines and protective immunity. Lancet 1994; 344: 1245-9.
  1. Roche PW, Triccas JA, Avery DT, Fifis T, Billman-Jacobe H, Britton WJ. Differential T cell responses to mycobacteria-secreted proteins distinguish vaccination with Baciile Calmette-Guérin from infection with mycobacterium tuberculosis. J Infect Dis 1994; 170: 1326-30.
  1. Menzies D, Fanning A, Yuan L, Fitzgerald M. Tuberculosis among health care workers. N Engl J Med 1995; 332(2): 92-8.
  1. Brewer TF, Colditz GA. Bacille Calmette-Guérin vaccination for the prevention of tuberculosis in health care workers. Clin Infect Dis 1995; 20: 136-42.
  1. Fine PEM. Bacille Calmette-Guérin vaccines: A rough guide. Clin Infect Dis 1995; 20: 11-4.
  1. Panel comment, 03/95.
  1. Panel comment, 03/95.
  1. Panel comment, 04/95.
  1. Panel comment, 03/95.
  1. Panel comment, 03/95.
  1. Panel comment, 04/95.
  1. Panel comment, 05/95.
Hide
(web5)