Tài liệu The Role of BCG Vaccine in the Prevention and Control of Tuberculosis in the United States: A Joint Statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices docx

LINK DOWNLOAD MIỄN PHÍ TÀI LIỆU "Tài liệu The Role of BCG Vaccine in the Prevention and Control of Tuberculosis in the United States: A Joint Statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices docx": http://123doc.vn/document/1037707-tai-lieu-the-role-of-bcg-vaccine-in-the-prevention-and-control-of-tuberculosis-in-the-united-states-a-joint-statement-by-the-advisory-council-for-the-.htm

EX OFFICIO MEMBERS — Continued
Georgia S. Buggs
Office of Minority Health
Public Health Service
Rockville, MD
Carole A. Heilman, Ph.D.
National Institutes of Health
Bethesda, MD
Warren Hewitt, Jr.
Substance Abuse and Mental Health
Services Administration
Rockville, MD
J. Terrell Hoffeld, D.D.S.
Agency for Health Care Policy
and Research
Rockville, MD
Gary A. Roselle, M.D.
Department of Veterans Affairs
VA Medical Center
Cincinnati, OH
Bruce D. Tempest, M.D., F.A.C.P.
Indian Health Service
Gallup, NM
Basil P. Vareldzis, M.D.
Agency for International Development
Washington, DC
LIAISON REPRESENTATIVES
John B. Bass, Jr., M.D.
American Thoracic Society
University of South Alabama
Mobile, AL
Nancy E. Dunlap, M.D.
American College of Chest Physicians
University of Alabama at Birmingham
Birmingham, AL
Wafaa M. El-Sadr, M.D., M.P.H.
Infectious Disease Society of America
New York, NY
Alice Y. McIntosh
American Lung Association
New York, NY
Norbert P. Rapoza, Ph.D.
American Medical Association
Chicago, IL
Michael L. Tapper, M.D.
Society for Healthcare Epidemiology
of America
New York, NY
COMMITTEE REPRESENTATIVES
Advisory Committee on the
Prevention of HIV Infection
Walter F. Schlech, M.D.
Victoria General Hospital
Halifax, Nova Scotia, Canada
Hospital Infection Control Practices
Advisory Committee
Susan W. Forlenza, M.D.
New York City Department of Health
New York, NY
Hospital Infection Control Practices
Advisory Committee
Mary J. Gilchrist, Ph.D.
Veterans Administration Medical Center
Cincinnati, OH
National TB Controllers Association
Bruce Davidson, M.D., M.P.H.
Philadelphia Department of
Public Health
Philadelphia, PA
Vol. 45 / No. RR-4 MMWR iii
Advisory Committee on Immunization Practices (ACIP)
1995
CHAIRPERSON
Jeffrey P. Davis, M.D.
Chief Medical Officer
Wisconsin Department of Health and
Social Services
Madison, WI
EXECUTIVE SECRETARY
Dixie E. Snider, M.D., M.P.H.
Associate Director for Science
Centers for Disease Control and
Prevention
Atlanta, GA
MEMBERS
Barbara A. DeBuono, M.D., M.P.H.
New York State Department of Health
Albany, NY
Kathryn M. Edwards, M.D.*
Vanderbilt University
Nashville, TN
Fernando A. Guerra, M.D.
San Antonio Metro Health District
San Antonio, TX
Neal A. Halsey, M.D.*
Johns Hopkins University
Baltimore, MD
Rudolph E. Jackson, M.D.*
Morehouse School of Medicine
Atlanta, GA
Stephen C. Schoenbaum, M.D.
Harvard Community Health Plan
of New England
Providence, RI
Fred E. Thompson, Jr., M.D.
Mississippi State Department of Health
Jackson, MS
Joel I. Ward, M.D.
UCLA Center for Vaccine Research
Harbor-UCLA Medical Center
Torrance, CA
EX OFFICIO MEMBERS
M. Carolyn Hardegree, M.D.
Food and Drug Administration
Bethesda, MD
John R. La Montagne, Ph.D.
National Institutes of Health
Bethesda, MD
*These ACIP members rotated off the committee; however, they made substantive contributions
to this report.
iv MMWR April 26, 1996
LIAISON REPRESENTATIVES
American Academy of Family
Physicians
Richard K. Zimmerman, M.D.
University of Pittsburgh
Pittsburgh, PA
American Academy of Pediatrics
Georges Peter, M.D.
Rhode Island Hospital
Providence, RI
American Academy of Pediatrics
Caroline B. Hall, M.D.
University of Rochester
Rochester, NY
American College of Obstetricians
and Gynecologists
Marvin S. Amstey, M.D.
Highland Hospital
Rochester, NY
American College of Physicians
Pierce Gardner, M.D.
State University of New York
at Stonybrook
Stonybrook, NY
American Hospital Association
William Schaffner, M.D.
Vanderbilt University
Nashville, TN
American Medical Association
Edward A. Mortimer, Jr., M.D.
Case Western Reserve University
Cleveland, OH
Canadian National Advisory Committee
on Immunization
David W. Scheifele, M.D.
Vaccine Evaluation Center
Vancouver, British Columbia, Canada
Hospital Infections Control
Practices Advisory Committee
David W. Fleming, M.D.
Oregon Health Division
Portland, OR
Infectious Diseases Society of America
William P. Glezen, M.D.
Baylor College of Medicine
Houston, TX
National Association of State Public
Health Veterinarians
Keith A. Clark, D.V.M., Ph.D.
Texas Department of Health
Austin, TX
National Vaccine Program
Anthony Robbins, M.D.
Office of the Assistant Secretary for
Health
Washington, DC
U.S. Department of Defense
Michael Peterson, D.V.M., Dr.P.H.
Office of the Surgeon General
Department of the Army
Falls Church, VA
U.S. Department of Veterans Affairs
Kristin L. Nichol, M.D., M.P.H.
Veterans Administration Medical Center
Minneapolis, MN
Vol. 45 / No. RR-4 MMWR v
The following CDC staff members prepared this report:
Margarita E. Villarino, M.D., M.P.H.
Robin E. Huebner, Ph.D., M.P.H.
Ann H. Lanner
Lawrence J. Geiter, M.P.H.
Division of Tuberculosis Elimination
National Center for HIV, STD and TB Prevention (Proposed)
in collaboration with the
Advisory Council for the Elimination of Tuberculosis
and the
Advisory Committee on Immunization Practices
vi MMWR April 26, 1996
The Role of BCG Vaccine in the Prevention and
Control of Tuberculosis in the United States
A Joint Statement by the
Advisory Council for the Elimination of Tuberculosis
and the Advisory Committee on Immunization Practices
Summary
This report updates and replaces previous recommendations regarding the
use of Bacillus of Calmette and Guérin (BCG) vaccine for controlling tuberculosis
(TB) in the United States (
MMWR
1988;37:663–4, 669–75). Since the previous
recommendations were published, the number of TB cases have increased
among adults and children, and outbreaks of multidrug-resistant TB have oc-
curred in institutions. In addition, new information about the protective efficacy
of BCG has become available. For example, two meta-analyses of the published
results of BCG vaccine clinical trials and case-control studies confirmed that the
protective efficacy of BCG for preventing serious forms of TB in children is high
(i.e., >80%). These analyses, however, did not clarify the protective efficacy of
BCG for preventing pulmonary TB in adolescents and adults; this protective effi-
cacy is variable and equivocal. The concern of the public health community
about the resurgence and changing nature of TB in the United States prompted
a re-evaluation of the role of BCG vaccination in the prevention and control of
TB. This updated report is being issued by CDC, the Advisory Committee for the
Elimination of Tuberculosis, and the Advisory Committee on Immunization Prac-
tices, in consultation with the Hospital Infection Control Practices Advisory
Committee, to summarize current considerations and recommendations regard-
ing the use of BCG vaccine in the United States.
In the United States, the prevalence of
M. tuberculosis
infection and active
TB disease varies for different segments of the population; however, the risk for
M. tuberculosis
infection in the overall population is low. The primary strategy
for preventing and controlling TB in the United States is to minimize the risk for
transmission by the early identification and treatment of patients who have ac-
tive infectious TB. The second most important strategy is the identification of
persons who have latent
M. tuberculosis
infection and, if indicated, the use of
preventive therapy with isoniazid to prevent the latent infection from progress-
ing to active TB disease. Rifampin is used for preventive therapy for persons
who are infected with isoniazid-resistant strains of
M. tuberculosis.
The use of
BCG vaccine has been limited because a) its effectiveness in preventing infec-
tious forms of TB is uncertain and b) the reactivity to tuberculin that occurs after
vaccination interferes with the management of persons who are possibly in-
fected with
M. tuberculosis.
In the United States, the use of BCG vaccination as a TB prevention strategy
is reserved for selected persons who meet specific criteria. BCG vaccination
should be considered for infants and children who reside in settings in which the
likelihood of
M. tuberculosis
transmission and subsequent infection is high,
Vol. 45 / No. RR-4 MMWR 1
provided no other measures can be implemented (e.g., removing the child from
the source of infection). In addition, BCG vaccination may be considered for
health-care workers (HCWs) who are employed in settings in which the likeli-
hood of transmission and subsequent infection with
M. tuberculosis
strains
resistant to isoniazid and rifampin is high, provided comprehensive TB infection-
control precautions have been implemented in the workplace and have not been
successful. BCG vaccination is not recommended for children and adults who
are infected with human immunodeficiency virus because of the potential ad-
verse reactions associated with the use of the vaccine in these persons.
In the United States, the use of BCG vaccination is rarely indicated. BCG
vaccination is not recommended for inclusion in immunization or TB control
programs, and it is not recommended for most HCWs. Physicians considering
the use of BCG vaccine for their patients are encouraged to consult the TB con-
trol programs in their area.
INTRODUCTION
Because the overall risk for acquiring
Mycobacterium tuberculosis
infection is low
for the total U.S. population, a national policy is not indicated for vaccination with
Bacillus of Calmette and Guérin (BCG) vaccine. Instead, tuberculosis (TB) prevention
and control efforts in the United States are focused on a) interrupting transmission
from patients who have active infectious TB and b) skin testing children and adults
who are at high risk for TB and, if indicated, administering preventive therapy to those
persons who have positive tuberculin skin-test results. The preferred method of skin
testing is the Mantoux tuberculin skin test using 0.1 mL of 5 tuberculin units (TU) of
purified protein derivative (PPD) (
1
).
BCG vaccination contributes to the prevention and control of TB in limited situ-
ations when other strategies are inadequate. The severity of active TB disease during
childhood warrants special efforts to protect children, particularly those <5 years of
age. In addition, TB is recognized as an occupational hazard for health-care workers
(HCWs) in certain settings. In 1988, the Immunization Practices Advisory Committee
and the Advisory Committee for Elimination of Tuberculosis published a joint state-
ment on the use of BCG vaccine for the control of TB (
2
). Based on available
information concerning the effectiveness of BCG vaccine for preventing serious forms
of TB in children, this statement recommended BCG vaccination of children who are
not infected with
M. tuberculosis
but are at high risk for infection and for whom
other public health measures cannot be implemented. The statement recommended
against BCG vaccination for HCWs at risk for occupationally acquired
M. tuberculosis
infection because a) BCG vaccination interferes with the identification of HCWs who
have latent
M. tuberculosis
infection and the implementation of preventive-therapy
programs in health-care facilities and b) the protective efficacy of BCG for pulmonary
TB in adults is uncertain.
From 1985 through 1992, a resurgence in the incidence of TB occurred in the United
States and included increases in the number of TB cases among adults and children
and outbreaks of multidrug-resistant TB (MDR-TB) involving patients, HCWs, and cor-
rectional-facility employees. In addition, meta-analyses have been conducted recently
using previously published data from clinical trials and case-control studies of BCG
2 MMWR April 26, 1996
vaccination. These developments have prompted a re-evaluation of the role of BCG
vaccination in the prevention and control of TB in the United States. CDC, the Advisory
Council for the Elimination of Tuberculosis (ACET), and the Advisory Committee on
Immunization Practices (ACIP), in consultation with the Hospital Infection Control
Practices Advisory Committee, are issuing the following report to summarize current
considerations and recommendations regarding the use of BCG vaccine in the United
States.
BACKGROUND
Transmission and Pathogenesis of
M. tuberculosis
Most persons infected with
M. tuberculosis
have latent infection. Among immuno-
competent adults who have latent
M. tuberculosis
infection, active TB disease will
develop in 5%–15% during their lifetimes (
3–5
). The likelihood that latent infection will
progress to active TB disease in infants and children is substantially greater than for
most other age groups (
6
). Active TB disease can be severe in young children. With-
out appropriate therapy, infants <2 years of age are at particularly high risk for
developing life-threatening tuberculous meningitis or miliary TB (
7
).
The greatest known risk factor that increases the likelihood that a person infected
with
M. tuberculosis
will develop active TB disease is immunodeficiency, especially
that caused by coinfection with human immunodeficiency virus (HIV) (
8–10
). Other
immunocompromising conditions (e.g., diabetes mellitus, renal failure, and treatment
with immunosuppressive medications) also increase the risk for progression to active
TB disease, but the risk is not as high as the risk attributed to HIV infection (
8,11
). In
addition, recency of infection with
M. tuberculosis
contributes to the risk for develop-
ing active TB disease. Among immunocompetent persons, the risk for active TB
disease is greatest during the first 2 years after infection occurs; after this time period,
the risk declines markedly (
8
). However, the risk for active TB disease among HIV-
infected persons, who have a progressive decline in immunity, may remain high for an
indefinite period of time or may even increase as the immunosuppression progresses.
Furthermore, persons who have impaired immunity are more likely than immuno-
competent persons to have a weakened response to the tuberculin skin test; this
weakened response makes both the identification of persons who have latent
M. tu-
berculosis
infection and the decisions regarding whether to initiate TB preventive
therapy more difficult.
Epidemiology of TB in the United States
From 1953, when national surveillance for TB began, through 1984, TB incidence
rates in the United States declined approximately 6% per year. However, during 1985,
the morbidity rate for TB decreased by only 1.1%, and during 1986, it increased by
1.1% over the 1985 rate (
12
). This upward trend continued through 1992, when the
incidence was 10.5 cases per 100,000 population. For 1993, the reported incidence of
TB was 9.8 cases per 100,000 population, representing a 5.2% decrease from 1992;
however, this decline was still 14% greater than the 1985 rate (
13
). For 1994, the
Vol. 45 / No. RR-4 MMWR 3
number of cases decreased 3.7% from 1993, but this number still represented a 9.7%
increase over the rate for 1985 (
14
).
In general, active TB disease is fatal for as many as 50% of persons who have not
been treated (
15
). Anti-TB therapy has helped to reduce the number of deaths caused
by TB; since 1953, the TB fatality rate has declined by 94%. According to 1993 provi-
sional data for the United States, 1,670 deaths were attributed to TB, representing a
mortality rate of 0.6 deaths per 100,000 population. The mortality rate for 1953 was
12.4 deaths per 100,000 population (
16
).
The prevalence of
M. tuberculosis
infection and active TB disease varies for differ-
ent segments of the U.S. population. For example, during 1994, 57% of the total
number of TB cases were reported by five states (i.e., California, Florida, Illinois, New
York, and Texas), and overall incidence rates were twice as high for men as for women
(
16
). For children, disease rates were highest among children ages ≤4 years, were low
among children ages 5–12 years, and, beginning in the early teenage years, increased
sharply with age for both sexes and all races. Cases of TB among children <15 years
of age accounted for 7% of all TB cases reported for 1994.
During the 1950s, TB was identified as an occupational hazard for HCWs in certain
settings (
17
). In the United States, the risk for acquiring
M. tuberculosis
infection di-
minished for most HCWs as the disease became less prevalent; however, the risk is
still high for HCWs who work in settings in which the incidence of TB among patients
is high. The precise risk for TB among HCWs in the United States cannot be deter-
mined because tuberculin skin-test conversions and active TB disease among HCWs
are not systematically reported. However, recent outbreaks of TB in health-care set-
tings indicate a substantial risk for TB among HCWs in some geographic areas.
Since 1990, CDC has provided epidemiologic assistance during investigations
of several MDR-TB outbreaks that occurred in institutional settings. These outbreaks
involved a total of approximately 300 cases of MDR-TB and included transmission of
M. tuberculosis
to patients, HCWs, and correctional-facility inmates and employees in
Florida, New Jersey, and New York (
18–23
). These outbreaks were characterized by
the transmission of
M. tuberculosis
strains resistant to isoniazid and, in most cases,
rifampin; several strains also were resistant to other drugs (e.g., ethambutol, strepto-
mycin, ethionamide, kanamycin, and rifabutin). In addition, most of the initial cases of
MDR-TB identified in these outbreaks occurred among HIV-infected persons, for
whom the diagnosis of TB was difficult or delayed. The fatality rate among persons
who had active MDR-TB was >70% in most of the outbreaks.
TB Prevention and Control in the United States
The fundamental strategies for the prevention and control of TB include:
• Early detection and treatment of patients who have active TB disease. The most
important strategy for minimizing the risk for
M. tuberculosis
transmission is the
early detection and effective treatment of persons who have infectious TB (
24
).
• Preventive therapy for infected persons. Identifying and treating persons who
are infected with
M. tuberculosis
can prevent the progression of latent infection
to active infectious disease (
25
).
4 MMWR April 26, 1996
• Prevention of institutional transmission. The transmission of
M. tuberculosis
is
a recognized risk in health-care settings and is a particular concern in settings
where HIV-infected persons work, volunteer, visit, or receive care (
26
). Effective
TB infection-control programs should be implemented in health-care facilities
and other institutional settings (e.g., homeless shelters and correctional facilities)
(
27,28
).
BCG vaccination is not recommended as a routine strategy for TB control in the
United States (see Recommendations). The following sections discuss BCG vaccines,
the protective efficacy and side effects associated with BCG vaccination, considera-
tions and recommendations for the use of BCG vaccine in selected persons, and
implementation and surveillance of BCG vaccination.
BCG VACCINES
BCG vaccines are live vaccines derived from a strain of
Mycobacterium bovis
that
was attenuated by Calmette and Guérin at the Pasteur Institute in Lille, France (
29
).
BCG was first administered to humans in 1921. Many different BCG vaccines are avail-
able worldwide. Although all currently used vaccines were derived from the original
M. bovis
strain, they differ in their characteristics when grown in culture and in their
ability to induce an immune response to tuberculin. These variations may be caused
by genetic changes that occurred in the bacterial strains during the passage of time
and by differences in production techniques. The vaccine currently available for im-
munization in the United States, the Tice strain, was developed at the University of
Illinois (Chicago, Illinois) from a strain originated at the Pasteur Institute. The Food and
Drug Administration is considering another vaccine, which is produced by Connaught
Laboratories, Inc., for licensure in the United States. This vaccine was transferred from
a strain that was maintained at the University of Montreal (Montreal, Canada).
Vaccine Efficacy
Reported rates of the protective efficacy of BCG vaccines might have been affected
by the methods and routes of vaccine administration and by the environments and
characteristics of the populations in which BCG vaccines have been studied. Different
preparations of liquid BCG were used in controlled prospective community trials con-
ducted before 1955; the results of these trials indicated that estimated rates of
protective efficacy ranged from 56% to 80% (
30
). In 1947 and 1950, two controlled
trials that used the Tice vaccine demonstrated rates of protective efficacy ranging from
zero to 75% (
31,32
). Since 1975, case-control studies using different BCG strains indi-
cated that vaccine efficacies ranged from zero to 80% (
33
). In young children, the
estimated protective efficacy rates of the vaccine have ranged from 52% to 100% for
prevention of tuberculous meningitis and miliary TB and from 2% to 80% for preven-
tion of pulmonary TB (
34–39
). Most vaccine studies have been restricted to newborns
and young children; few studies have assessed vaccine efficacy in persons who re-
ceived initial vaccination as adults. The largest community-based controlled trial of
BCG vaccination was conducted from 1968 to 1971 in southern India. Although two
different vaccine strains that were considered the most potent available were used in
this study, no protective efficacy in either adults or children was demonstrated 5 years
Vol. 45 / No. RR-4 MMWR 5
after vaccination. These vaccine recipients were re-evaluated 15 years after BCG vac-
cination, at which time the protective efficacy in persons who had been vaccinated as
children was 17%; no protective effect was demonstrated in persons who had been
vaccinated as adolescents or adults (
39
).
The renewed interest in examining the indications for BCG vaccination in the
United States included consideration of the wide range of vaccine efficacies deter-
mined by clinical trials and estimated in case-control studies. Two recent meta-
analyses of the published literature concerning the efficacy of BCG vaccination for
preventing TB attempted to calculate summary estimates of the vaccine’s protective
efficacy. The first of these meta-analyses included data from 10 randomized clinical
trials and eight case-control studies published since 1950 (
40
). The results of this
analysis indicated an 86% protective effect of BCG against meningeal and miliary TB
in children in clinical trials (95% confidence interval [CI]=65%–95%) and a 75% protec-
tive effect in case-control studies (95% CI=61%–84%). The meta-analyst conducting
this study determined that the variability in the rates of protective efficacy of BCG
against pulmonary TB differed significantly enough between these 18 studies to pre-
clude the estimation of a summary protective efficacy rate.
The second meta-analysis reviewed the results of 14 clinical trials and 12 case-
control studies (
41
). The meta-analysts used a random-effects regression model to
explore the sources of the heterogeneity in the efficacy of the BCG vaccine reported in
the individual studies. Using a model that included the geographic latitude of the
study site and the data validity score as covariates, they estimated the overall protec-
tive effect of BCG vaccine to be 51% in the clinical trials (95% CI=30%–66%) and 50%
in the case-control studies (95% CI=36%–61%). The scarcity of available data concern-
ing the protective efficacy afforded by both BCG vaccination of adults and the type of
vaccine strain administered precluded the inclusion of these factors as covariates in
the random-effects regression model. However, these researchers determined that
vaccine efficacy rates were higher in studies conducted of populations in which per-
sons were vaccinated during childhood compared with populations in which persons
were vaccinated at older ages. Furthermore, they determined that higher BCG vaccine
efficacy rates were not associated with the use of particular vaccine strains.
Eight studies of the efficacy of BCG vaccination in HCWs also were reviewed by the
investigators conducting the second meta-analysis. In these eight studies, which were
conducted during the 1940s and 1950s, the meta-analysts identified the following
methodologic problems: small study population sizes; inadequate data defining the
susceptibility status of study populations; uncertain comparability of control pop-
ulations; incomplete assessment of ongoing exposure to contagious TB patients;
inadequate follow-up of study populations; lack of rigorous case definitions; and dif-
ferences in either BCG dose, vaccine strain, or method of vaccine administration.
These methodologic weaknesses and the heterogeneity of the results were suffi-
ciently substantial to preclude analysis of the data for the use of BCG vaccine in HCWs.
In summary, the recently conducted meta-analyses of BCG protective efficacy have
confirmed that the vaccine efficacy for preventing serious forms of TB in children is
high (i.e., >80%). These analyses, however, were not useful in clarifying the variable
information concerning the vaccine’s efficacy for preventing pulmonary TB in adoles-
cents and adults. These studies also were not useful in determining a) the efficacy of
BCG vaccine in HCWs or b) the effects on efficacy of the vaccine strain administered
6 MMWR April 26, 1996