Clin Chest Med 26 (2005) 183 – 195

Epidemiology of Tuberculosis in the United States

Eileen Schneider, MD, MPHa,*, Marisa Moore, MD, MPHa,b,
Kenneth G. Castro, MDa
a
Division of Tuberculosis and Elimination, Centers for Disease Control and Prevention, 1600 Clifton Road, MS E-10,
Atlanta, GA 30333, USA
b
TB Control Program, San Diego County Health and Human Services, Department of Public Health Services,
3851 Rosecrans Street, MS P511D, San Diego, CA 92110, USA

Historical background
The epidemiology of tuberculosis (TB) in the
United States has changed remarkably over the last
2 centuries. In the nineteenth century, TB was the
leading cause of death. As the nineteenth century prog-
ressed, TB mortality decreased, partly because of
improved socioeconomic conditions [1,2], especially
in urban settings, and partly owing to the natural
behavior of epidemics [3]. After the tubercle bacillus
was identified as the causative agent of TB by Robert
Koch in 1882, the approach to TB control changed
greatly, and the concepts of public health, prevention,
and segregation of TB patients gained more accep-
tance. As a result, in industrialized countries, the
prescribed treatment of rest, isolation, nutrition, and
fresh air for TB patients was achieved with long stays
in sanatoria [1,2].
By the late 1800s, TB was more than ever con-
sidered a public health issue, even though there were
few well established local or state public health
departments [1,2,4]. More resources became avail-
able, and public health programs dedicated to TB con-
trol were established. In 1904, the first voluntary
health agency dedicated to TB, the National Tuber-
culosis Association (now the American Lung Asso-
ciation), was organized [1,5]. TB surveillance and
This work was funded by the Division of Tuberculosis
and Elimination, Centers for Disease Control and Prevention.
* Corresponding author.
E-mail address: ees2@cdc.gov (E. Schneider).
data collection was a priority for the National Tu-
berculosis Association. As the mortality rate con-
tinued to decrease, attention focused on TB case
finding. Armed with a new diagnostic tool, the chest
roentgenogram, mass chest radiograph screenings
were conducted beginning in the early 1930s and
continuing into the 1950s, enabling the diagnosis of
TB patients before they became symptomatic [2].
The need to expand data collection to include TB
morbidity in addition to TB mortality was acknowl-
edged [1,2]. Reliable and complete morbidity data
would allow TB experts to measure more accurately
the magnitude of the TB problem and the effec-
tiveness of control efforts. In 1920, the National Tu-
berculosis Association published its first Diagnostic
Standards and Classifications of TB to assist health
care providers and standardize diagnostic criteria
[5,6]. National TB mortality and morbidity data,
coordinated by the National Tuberculosis Associa-
tion, became available in 1933. In 1944, a United
States Public Health Service Act mandated the crea-
tion of a national TB control program [1]. With
the introduction of the therapeutic agents streptomy-
cin (1947), p-aminosalicylic acid (1949), isoniazid
(1952), and pyrazinamide (1952) TB mortality rates
decreased dramatically. Between 1930 and 1960, the
mortality rate decreased by 92%, from 71 to 6 deaths
per 100,000 population.
Because of the widespread use of chemotherapy,
long hospitalizations for TB were no longer needed,
and TB sanatoria and hospitals began to close [1,2,5].
Having a standard definition for a reportable case of
TB for surveillance purposes became paramount [7],

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184 schneider et al
and in 1951, a committee consisting of state TB con-
trol officers and sanatoria directors published recom-
mendations for TB case reporting and counting
procedures [8]. In 1952, the United States Public
Health Service (USPHS) Tuberculosis Control Pro-
gram instituted procedures to report new cases of
TB. Not until 1953, through the cooperation of the
states, did the USPHS receive reports from the entire
United States, heralding the birth of the national TB
surveillance system [1,2].
National tuberculosis surveillance system
Since 1953, the national TB surveillance system
has been modified several times to monitor and re-
spond better to changes in TB morbidity. Data are
collected on TB cases that have been verified and
have met the Centers for Disease Control and Pre-
vention (CDC) public health surveillance case defi-
nition for TB [9,10]. TB is a reportable disease in
each state [11]. In 1985, the national TB surveillance
system changed: originally collecting aggregate data,
the CDC began collecting individual case reports
on a form called the Report of Verified Case of
Tuberculosis (RVCT). Currently, data are collected
by reporting areas (the 50 states, the District of Co-
lumbia, New York City, Puerto Rico, and jurisdic-
tions in the Pacific and Caribbean) using the RVCT.
An RVCT is completed for each reported new TB
disease case and contains patient demographic, clini-
cal, and laboratory information. An RVCT is com-
pleted by the health department for each confirmed
TB case and transmitted to the CDC to be included
in the national TB surveillance database. The CDC
annually publishes a report summarizing national
TB statistics [10]. Also included in this annual report
are the ‘‘Recommendations for Counting Reported
TB Cases,’’ which were last revised in 1997.
The CDC has maintained a computer database
on TB surveillance data since 1985. State and local
TB programs have been able to collect, manage, and
transfer TB surveillance data (i.e., RVCT) electroni-
cally to the CDC first through software for expanded
TB surveillance (SURVS-TB, 1993 – 1997) and cur-
rently through the Tuberculosis Information Manage-
ment System (TIMS, 1998 – present). In 1993, the
RVCT was expanded to collect additional information
(eg, drug resistance, HIV infection) in response to the
TB epidemic of the mid-to-late 1980s and early
1990s. The most recent modification was imple-
mented in January 2003 to meet federal standards for
the classification of race and ethnicity. Additional
changes for the national TB surveillance system are
on the horizon with a revision of the RVCT.
Reporting of RVCT data to the CDC also will
be modified with the transitioning of the TIMS to
the Web-based National Electronic Disease Surveil-
lance System.
Tuberculosis resurgence
Noting that extraordinary strides against TB have
been made both in treatment and surveillance since
the 1950s, many TB experts have believed that TB
elimination in the United States is within reach [1,2].
In 1959, the historic Arden House Conference, spon-
sored by the National Tuberculosis Association and
the USPHS Tuberculosis Control Program, brought
together TB experts to formulate a plan on how to
eliminate TB; this plan served as a basis for future TB
control efforts [12]. TB incidence continued to
decrease. From 1953 through 1985, TB case numbers
decreased by 74%, from 84,304 to 22,201 cases,
and the case rate decreased by 82%, from 53.0 to
9.3 cases per 100,000 population. As a result, many
no longer considered TB to be a major problem.
In the early 1970s, federal funding allocated for
TB control began to decrease, and, as a result, many
TB control services were dismantled [13,14]. Al-
though TB funds were decreasing, the cost of treating
TB was increasing. In 1981, only $3.7 million was
appropriated to the CDC to fight TB nationally.
In 1987, the Advisory Committee (now Council)
for Elimination of Tuberculosis (ACET) was estab-
lished, and its membership was directed to develop a
strategic plan for TB elimination [15]. The ACET and
the CDC published this plan, proposing a TB in-
cidence interim goal for the year 2000 of 3.5 or fewer
TB cases per 100,000 population and an elimination
target of less than 1 TB case per million population
by 2010. In the mid-to-late 1980s, however, the
longstanding downward trend in TB incidence was
interrupted. In 1986, a 2.6% annual increase in the
case number was documented, signaling the begin-
ning of the TB resurgence (Fig. 1). In the late 1980s,
after decades of decreasing TB incidence, TB once
again became a major threat.
The resurgence had a significant impact on TB
control strategies in the United States. Because of
newly identified risk groups, the focus of many TB
control strategies had to be shifted, and many pro-
grams needed to be overhauled. CDC researchers
concluded that the resurgence had resulted in an es-
timated 52,100 excess TB cases from 1985 through
1992 [16]. Several factors have been linked to the
resurgence, including the deterioration of the TB
program infrastructure, the HIV/AIDS epidemic,
 epidemiology of tuberculosis in the united states
28,000
Number of TB Cases
26,000
24,000
22,000
20,000
18,000
16,000
14,000
12,000
1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003
Year
Fig. 1. Reported tuberculosis cases in the United States from 1981 to 2003.
drug-resistant TB, TB among foreign-born persons,
and an increase in transmission, especially in con-
gregate and institutional settings [16 – 19].
The degree to which each of these factors affected
TB control at the local level varied, but two of these
factors, the HIV/AIDS epidemic and TB among
foreign-born persons, strongly influenced the TB re-
surgence in the United States. HIV infection is con-
sidered to be the greatest risk factor known today
for TB. Several large outbreaks of multidrug-resistant
TB (MDR-TB) (ie, TB resistant to at least isoniazid
and rifampin) among persons infected with HIV were
documented in Florida and New York City [20 – 22].
In 1991, 41% of culture-positive TB patients in New
York City were also infected with HIV, and 19% had
MDR-TB [23]. Early diagnosis of TB among persons
infected with HIV was difficult because of the lack of
specific clinical findings, such as a positive tuberculin
skin test result and an abnormal chest radiograph.
Ineffective isolation precautions also contributed to
nosocomial transmission of MDR-TB among patients
and health care providers [24 – 26]. HIV-related TB
outbreaks were also documented in other congregate
settings [27] such as correctional facilities [28] and
homeless shelters [29,30]. Another important factor
fueling the TB resurgence was the immigration of
persons from countries that have high rates of TB
[19]. The proportion of reported TB cases among
foreign-born persons increased from 22% in 1986
(the first year birthplace data were collected by the
national TB surveillance system) to 30% in 1993.
In the early 1990s, the newly established Federal
Tuberculosis Task Force revaluated existing TB
strategies and formulated the National Action Plan
to Combat MDR-TB [31]. In the United States, a
monumental public health effort to control TB was
initiated [32,33]. Federal funding was increased and
used to rebuild the TB infrastructure, strengthen sur-
185
veillance, augment case finding and contact inves-
tigations, advance laboratory capacity (eg, drug-
susceptibility testing and new diagnostic tools), and
ensure each patient completed therapy through the
use of directly observed therapy (DOT).
After the tuberculosis resurgence, 1993 – 2003
During the resurgence, the national TB incidence
peaked in 1992 at 26,673 cases (10.5 cases per
100,000 population). The aggressive attack on TB in
the United States resulted in the annual TB case num-
ber and case rate decreasing in 1993 to 25,108 cases,
9.7 cases per 100,000 population. Tuberculosis be-
came more localized to well-defined risk groups and
geographic areas [34,35]. In response, strategic plans
were revised to help prioritize efforts and outline
updated recommendations for TB elimination in the
United States [36,37].
From 1993 to 2002, the average year-to-year de-
crease in TB rate was 6.9%. In 2003, however, the
CDC reported the smallest annual decrease in the TB
rate (1.9%) and TB case numbers (184) since the re-
surgence, raising concern about a possible slowing
of the progress against TB. For 2003, 14,874 TB
cases were reported in the United States, with a rate
of 5.1 per 100,000 population that remains higher
than the national interim goal of 3.5 cases per
100,000 population set for 2000. Moreover, despite
the decline in TB nationwide, rates have increased
in certain states, and elevated TB rates continue to be
reported in certain populations (eg, foreign-born per-
sons and racial/ethnic minorities). In 2003, 12 states
and the District of Columbia reported case rates
above the national average, and 20 states reported
increases in case number compared with 2002 [10].
186 schneider et al
Age
The distribution of TB cases and case rates
among age groups remained relatively stable. In
2003, 34.2% of TB patients were 25 to 44 years old,
28.9% were 45 to 64, 20.2% were 65 years and
older, 10.6% were 15 to 24 years, and 6.2% were
children under 15 years. In contrast, 2003 TB case
rates (cases per 100,000 population) were highest
(8.4) among persons 65 years and older, followed by
a rate of 6.3 for those 45 to 64, 6.0 for those 25 to
44 years, 3.8 for those 15 to 24 years, and 1.5 for
children under 15. Although TB case rates among
children under 15 are low, certain groups of children
(eg, younger children, racial and ethnic minorities,
and foreign-born children) are at higher risk for TB
[38]. Children pose unique challenges to TB control:
1. TB in children is considered a sentinel event,
usually indicating recent transmission.
2. TB diagnosis in children, especially in children
under 5 years of age, can be more difficult be-
cause they often have nonspecific signs and
symptoms and fewer positive bacteriologic
tests because of the paucity of mycobacteria.
3. Children, especially infants, are at an increased
risk for progressing from latent TB infection
(LTBI) to active and sometimes severe TB dis-
ease [38].
Race/ethnicity
Disparities in TB rates persist among racial and
ethnic minority populations (Table 1). Overall, the
highest TB rates are seen among Asian/Pacific
Islanders, in large part because of the high proportion
of foreign-born persons in this population. Among
foreign-born persons, non-Hispanic blacks had the
highest case rate in 2003 and were the only group
with an increase in case rate from 1998 to 2003. In
2003, among TB patients born in the United States,
case rates for non-Hispanic blacks and for American
Indian/Alaska Natives were 7.7 and 6.8 times, respec-
tively, that of non-Hispanic whites. Local, state, and
federal public health partners, including the CDC
and the ACET, are collaborating to develop effective
strategies to reduce racial disparities in TB [39].
Foreign-born tuberculosis patients
National TB surveillance for patient country of
birth began in 1986, when 4925 (21.8%) new cases
were reported among foreign-born persons. The pro-
portion of foreign-born TB patients remained rela-
tively stable at 22% to 23% until 1990, when the
proportion and number of cases among foreign-born
persons began to increase (Fig. 2). Since then, the
proportion has increased steadily, with foreign-born
persons accounting for 53.4% of the national case
total in 2003. This trend results from the relatively
stable case count in foreign-born persons since the
mid 1990s, with 7902 cases reported in 2003,
coupled with the significant decrease in cases among
US-born persons (Fig. 3). In 1992, 19,225 cases
among US-born persons were reported in the United
States; this number decreased to 6903 in 2003.
TB case rates among foreign-born persons have
been consistently higher than among US-born per-
sons [40]. The 2003 TB rate among all foreign-born
persons (23.6 cases per 100,000 population) was
8.8 times greater than that among US-born persons
(2.7 cases per 100,000 population). Six birth coun-
tries of foreign-born TB patients have consistently
accounted for approximately 60% of the foreign-
born TB cases reported in the United States annually.
In 2003, Mexico accounted for 25.6% of foreign-
born patients; the Philippines, 11.5%; Viet Nam,
8.4%; India, 7.6%; China 4.8%; and Haiti 3.3%. The
number of states reporting 50% or more of their
TB cases among foreign-born persons has also been
increasing, from two states in 1986, to 14 states in
1998, and to 25 states in 2003 (Fig. 4). Five states
have consistently reported the most foreign-born
TB patients: California, New York, Texas, Florida,
and New Jersey. In 2003, these states combined re-
ported almost two thirds of the total cases in foreign-
born TB persons (California, 30.6%; New York,
12.4%; Texas, 9.0%; Florida, 5.9%; and New Jersey,
4.4%). Within each state, the birth-country composi-
tion often varies. In 2003, the most common birth
country for reported foreign-born TB patients from
California and Texas was Mexico; for New York, it
was China; for Florida, it was Haiti; and for New
Jersey, it was India. In addition, TB patients from
certain countries were concentrated in certain states.
For example, in 2003, New York reported 63.5% of
the national total of TB patients born in the Do-
minican Republic and 55.7% of those born in Ecua-
dor. Florida reported 60.0% of the TB patients born
in Cuba and 49.2% of those born in Haiti; Califor-
nia reported 52.0% of the TB patients born in the
Philippines and 48.6% of the patients born in Laos;
and Minnesota reported 55.2% of TB patients born
in Somalia. This diversity poses unique challenges to
state and local TB control programs and must be
addressed to facilitate case finding and contact in-
vestigations and to ensure completion of therapy.
Table 1

epidemiology of tuberculosis in the united states

Number and rate per 100,000 population of tuberculosis cases in the United States in 1998 and 2003
US-born Foreign-born Totalb
1998 2003 1998 2003 1998 2003
% change % change % change
Race/ethnicitya No. Rate No. Rate 1998 – 2003 No. Rate No. Rate 1998 – 2003 No. Rate No. Rate 1998 – 2003
Hispanic 1282 6.6 1015 4.3 33.8 2785 26.0 3073 19.6 24.7 4091 13.5 4115 10.5 22.2
Non-Hispanic
Black 4968 16.0 3086 9.2 42.6 841 48.5 1048 52.0 7.2 5816 17.8 4145 11.7 34.4
Asian/Pacific Islanderc 213 5.8 204 5.4 6.9 3411 55.4 3288 41.2 25.6 3637 36.9 3510 29.8 19.3
Asian ... ... 155 4.4 ... ... ... 3252 41.1 ... ... ... 3425 30.0 ...
Native Hawaiian and Other ... ... 49 15.7 ... ... ... 36 48.6 ... ... ... 85 22.1 ...
Pacific Islander
White 3914 2.1 2358 1.2 40.6 550 8.5 427 6.1 27.7 4473 2.3 2790 1.4 38.6
American Indian/Alaska Native 248 12.6 173 8.1 36.3 ... ... ... ... ... 254 12.7 176 8.1 36.2
Totald 10,633 4.3 6903 2.7 38.2 7598 30.2 7902 23.6 21.8 18,287 6.8 14,874 5.1 24.4
a
In 2003, two modifications were made to the tuberculosis report form: (1) multiple race entries were allowed, with 0.3% selecting more than one race, and (2) the previous category of
Asian/Pacific Islander was divided into ‘‘Asian’’ and ‘‘Native Hawaiian or Other Pacific Islander.’’
b
Persons included for whom country of birth was unknown: 56 in 1998 and 69 in 2003.
c
For comparison with 1998, data for 2003 Asian/Pacific Islander = Asian plus Native Hawaiian and Other Pacific Islander.
d
Persons included for whom race/ethnicity was unknown: 16 for all, 8 for US-born, and 5 for foreign-born persons in 1998; 101 for all, 58 for US-born, and 35 for foreign-born
persons in 2003. In 2003, persons included who selected multiple races: 37 for all, 9 for US-born, 28 for foreign-born persons.

187
188 schneider et al

Number of Foreign-born Percentage of Foreign-born

TB Cases TB Cases
10,000 60

8,000 50

40
6,000
30
4,000
20
2,000 10

0 0
1986 1988 1990 1992 1994 1996 1998 2000 2002
Year
Number of Foreign-born TB Cases Percentage of Foreign-born TB Cases

Fig. 2. Trends in tuberculosis cases in foreign-born persons in the United States from 1986 to 2003.

Most TB cases among foreign-born persons are
caused by Mycobacterium tuberculosis complex in-
fections acquired abroad [41]. Among foreign-born
children, aged younger than 15 years, who had TB,
60% were diagnosed within 18 months of arrival in
the United States [38]. Prompt evaluation of foreign-
born persons for TB following their arrival in the
United States can help identify persons who have
LTBI and are eligible for preventive therapy; prompt
evaluation can prevent development of active TB
disease [41,42]. Foreign-born TB patients are also
more likely to have drug resistance and are less likely
to be HIV infected than US-born TB patients [40].
The lower proportion of foreign-born TB patients
infected with HIV results in part from HIV screening
requirements for persons seeking permanent resi-
dency in the United States [43].
TB among foreign-born persons is a major com-
ponent of TB morbidity in the United States [40]
and reflects the global TB situation, defined in 1993
by the World Health Organization (WHO) as a
global emergency [44,45]. The WHO estimated that
in 2002 there were 8.8 million new cases of TB
(141 cases per 100,000 population) [46]. Among the
22 high-burden countries, India and China ac-
counted for 46% of the total. Among the 15 coun-
tries that have the highest TB rates (>400 cases per
100,000 population), 13 are in Africa, and 12 of
these had high TB/HIV incidence rates (>100 cases
per 100,000 population) among adults 15 to 49 years

Number of US-born Percentage of US-born

TB Cases TB Cases
20,000 100
90
80
15,000
70
60
10,000 50
40
30
5,000
20
10
0 0
1986 1988 1990 1992 1994 1996 1998 2000 2002
Year
Number of US-born TB Cases Percentage of US-born TB Cases

Fig. 3. Trends in tuberculosis cases in persons born in the United States from 1986 to 2003.
 epidemiology of tuberculosis in the united states 189

Number of states with ≥50% TB cases

30

in foreign-born persons
25
23
22 22
20
15 15
14

10
10 9
6
5
4 4
3 3
2 2 2
0
1986 1988 1990 1992 1994 1996 1998 2000 2002
Year

Fig. 4. Number of states with 50% or more of tuberculosis cases in foreign-born persons in the United States from 1986 to 2003.

old, highlighting the magnitude of the TB/HIV epi- Drug-resistant tuberculosis

demic and the influence of HIV/AIDS on TB [46].
Therefore, immigration from regions that have high Drug-resistant TB, especially MDR-TB, places
rates of drug-resistant TB (eg, Eastern Europe) as an increased burden on all aspects of TB control,
well as from regions that have high rates of HIV in- including diagnosis, case management, treatment,
fection (eg, sub-Saharan Africa) substantially affect the and cost [52 – 54]. MDR-TB is defined as resistance
epidemiology of TB in the United States. The CDC to at least isoniazid and rifampin, two of the most
is collaborating with partners such as the US Agency effective antituberculosis agents in the TB arsenal.
for International Development, the International When used in conjunction with other antitubercu-
Union Against TB and Lung Disease (IUATLD), the losis agents, rifampin can significantly shorten the
KNCV TB Foundation (formerly the Royal Nether- treatment course of TB. Although many factors
lands Tuberculosis Association), and WHO to assist have been associated with the development of drug
countries that have high burdens of TB. Collabora- resistance, including naturally occurring spontaneous
tions have focused on building program capacity, mutations, two of the most commonly encountered
operational research, and programmatic evaluation to and preventable factors are nonadherence to therapy
address problems such as TB/HIV and drug resis- and inappropriate use of antituberculosis drugs. Poor
tance in TB patients. TB screening among immigrant infection-control practices within hospitals caring
and refugee visa applicants is being improved through for patients who have drug-resistant TB have also
the development of new diagnostic tools [47] and played an important role in the nosocomial trans-
updated medical screening guidelines [43]. In addi- mission of MDR-TB [20 – 22].
tion, because Mexico contributes the largest number Collection of drug-susceptibility results became
of foreign-born TB patients in the United States, part of routine national TB surveillance in 1993, in
the CDC has been collaborating with partners in the part because of the recommendations outlined by
United States and Mexico to help control TB along the National Action Plan to Combat MDR-TB [31].
the United States – Mexico border. These efforts in- Before 1993, several regional and national drug sus-
clude an innovative new initiative that uses a bina- ceptibility surveys on TB patients were conducted
tional health card to track and manage binational [52]. In 1991, findings of a nationwide survey re-
TB patients who cross the border to ensure continuity vealed 14.2% of cases were resistant to at least one
of TB care and completion of treatment [48,49]. drug and 3.5% were resistant to at least isoniazid
Worldwide, TB is a recognized cause of morbidity and rifampin (MDR-TB) [55]. The strongest risk
and mortality in children. A renewed interest by factor for drug resistance was geographic location.
domestic and international health agencies has New York City had the highest MDR-TB rate (13%)
focused on mobilizing and strengthening global and accounted for 61% of the total MDR-TB cases
efforts to improve surveillance, and to promote reported in the United States.
program and research initiatives to reduce the bur- Analysis of national TB surveillance data col-
den of TB on children [50,51]. lected from 1993 through 1996 revealed a 13.5%,
190 schneider et al
incidence of resistance to at least one drug, and the
incidence of MDR-TB was 2.2% [56]. Higher drug-
resistance rates were seen among TB patients who
have had a previous episode of TB, foreign-born
persons, HIV-infected persons, and persons residing
in specific geographic areas (eg, New York City).
In the mid-to-late 1990s, several outbreaks involv-
ing highly drug-resistant strains of M. tuberculosis
(ie, strain W) were investigated [57 – 59]. These
strains share a common drug resistance to first-line
antituberculosis medications (eg, isoniazid, rifampin,
ethambutol, and, at that time, streptomycin) as well
as resistance to some second-line medications, mak-
ing treatment difficult and costly. The majority of
strain W TB cases were reported by New York City
[57,59], although outbreaks have occurred elsewhere,
including one that was attributed to bronchoscope
contamination in South Carolina [58]. To facilitate
early detection of strain W isolates, the CDC began
recommending that health departments notify the
CDC of all M. tuberculosis isolates that have
strain W – resistance patterns [59].
Since 1998, overall multidrug resistance among
culture-positive TB patients, who do not have a prior
history of TB, has been relatively stable (~1%)
(Fig. 5), although outbreaks and regional differ-
ences continue to occur. Historically, overall drug-
resistance rates among those who have a previous
history of TB have been higher than for those who
do not have a previous history of TB. In 2003,
among TB patients who had a prior history of TB,
12.6% had resistance to at least isoniazid and 3.6%
had MDR-TB, whereas 7.9% of TB patients who
did not have a prior history of TB had resistance to
Number of MDR TB Cases
450
400
350
300
250
200
150
100
50
0 0.0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
Year
Number of MDR TB Cases
Fig. 5. MDR-TB among persons without a history of tuberculosis in the United States from 1993 to 2003. MDR-TB is defined
as resistance to at least isoniazid and rifampin.
at least isoniazid and 0.9% had MDR-TB. Addition-
ally, drug resistance (MDR-TB and resistance to at
least isoniazid) has been seen more commonly in
foreign-born TB patients (2003: MDR-TB, 1.2%;
isoniazid, 10.6%) than in US-born TB patients (2003:
MDR-TB, 0.6%; isoniazid, 4.6%).
Knowledge of drug-resistance rates worldwide
is critical to controlling the global epidemic and has
direct implications for TB control in the United States
[60,61]. A more comprehensive understanding of
global drug resistance was made possible with the
formation of the Supranational Reference Labora-
tory Network in 1994 and the WHO/IUATLD Global
Project on Anti-Tuberculosis Drug Resistance Sur-
veillance. Newly released data reveal that TB patients
in parts of Eastern Europe and Central Asia are
10 times more likely to have MDR-TB than patients
in the rest of the world, with some MDR-TB inci-
dence rates higher than 10% (Israel, 14.2%; Kazakh-
stan,14.2%; Tomsk Oblast [Russian Federation],
13.7%; Uzbekistan, 13.2%; Estonia, 12.2%; and
Liaoning [China], 10.4%) [61].
Tuberculosis/HIV coinfection
Today, any discussion about TB is incomplete
without a discussion about HIV/AIDS. Knowing a
TB patient’s HIV status is critical to management,
treatment, contact investigation, and prevention
[62 – 67]. The CDC recommends that all TB patients,
independent of risk factors, should undergo voluntary
HIV counseling, testing, and referral [64,65,67].
Nonetheless, HIV status is not reported nationally
for many TB patients in the United States. This in-
Percentage of MDR TB Cases
3.0
2.0
1.0
Percentage of MDR TB Cases
 epidemiology of tuberculosis in the united states
complete reporting of HIV status probably reflects
several factors including concerns about confiden-
tiality, interpretation of laws and regulations in cer-
tain states and local jurisdictions, and reluctance by
health care providers to report HIV test results to the
TB surveillance program staff [10]. Information on
HIV status was added to the national TB surveillance
system in 1993, in response to the TB resurgence.
HIV test results (ie, negative, positive, or indeter-
minate) were reported for 45.7% of TB patients aged
25 to 44 years in 1993 and for 65.3% in 2002. In
this group, positive HIV test results were reported for
29.1% in 1993 and for 15.9% in 2002. Historically,
reported TB/HIV coinfection rates and case numbers
have been relatively high in a few states and urban
areas. In 2002, 60% of the positive HIV test results
among TB patients aged 25 to 44 years were reported
from five areas: California, Florida, Georgia, New
York City, and Texas. Crossmatching of state TB
registries and HIV/AIDS registries in 1993 and 1994
revealed that 14% (range, 0% – 31%) of persons
reported to have TB in the United States were also
listed in HIV/AIDS registries [68]. TB-AIDS cases
were more likely to be in persons aged 25 to 44 years,
male, culture-positive for M. tuberculosis, and US-
born. In geographic areas where the prevalence rates
of HIV-infected persons were high, drug resistance,
especially MDR-TB (6%) and rifampin monoresis-
tance (3%), was reported among TB-AIDS patients.
HIV coinfection has several key implications for
the overall treatment and management of TB. HIV
infection increases the risk of (1) TB disease pro-
gression among persons who have LTBI, (2) rapid
progression of those newly infected with M. tuber-
culosis to active TB disease, and (3) reinfection with
M. tuberculosis [67,69]. Many of the TB outbreaks
among persons infected with HIV that occurred
during the resurgence were complicated by high
drug-resistance rates and resulted in mortality rates
reaching 70% [21 – 23]. TB outbreaks among HIV-
infected persons have illustrated the continued need
for appropriate treatment and monitoring of this
population [70 – 73]. The use of antiretroviral ther-
apy has significantly decreased mortality and mor-
bidity, including the development of opportunistic
infections (eg, TB) among HIV-infected persons.
New concerns have developed, however, concern-
ing the potential for drug – drug interactions, develop-
ment of resistance to rifamycin, and paradoxical
reactions. Drug – drug interactions, primarily between
rifamycin and protease inhibitors and nonnucleoside
reverse transcriptase inhibitors, have resulted in new
treatment guidelines and recommendations [66,66a].
Acquired rifampin monoresistance has been docu-
191
mented in HIV-infected patients who have low CD4+
T-lymphocyte counts, extrapulmonary disease, and
concomitant antifungal therapy [74,75]. Clinicians
treating TB-HIV – coinfected persons should be fa-
miliar with current diagnostic, management (eg, DOT),
and treatment modalities to maximize therapeutic
success and minimize TB transmission, drug resis-
tance, adverse effects, and treatment failures [64,67].
Globally, the HIV/AIDS epidemic has had an
immense impact on TB control, especially in sub-
Saharan Africa, where an estimated two thirds of
persons who have HIV/AIDS live, and has contrib-
uted significantly to TB morbidity and mortality
[76 – 78]. In these countries, TB incidence and case
fatality are strongly associated with HIV prevalence.
The prevalence of drug-resistant TB is expected to
increase greatly as the HIV epidemic spreads to areas
of the world where drug-resistant TB is more
prevalent (eg, Asia, Eastern Europe) [61,76]. The
scaling up of treatment programs providing anti-
retroviral therapy will require patient and health care
provider education and close monitoring to opti-
mize therapy, reduce transmission, and reduce drug-
resistant TB [79].
Development of new tools
An important component of disease control is the
development of new diagnostic tests, pharmacologic
agents, and vaccines. The resurgence of TB in the
mid-to-late 1980s to 1992 was associated with delays
in the diagnosis and identification of drug resistance.
This situation generated renewed interest in the de-
velopment of several new diagnostic tools and the
subsequent genomic sequencing of M. tuberculosis.
During the past few years, TB diagnostic capabili-
ties have improved through new techniques for
the rapid detection of M. tuberculosis complex (eg,
nucleic acid amplification tests) [80], identification
of M. tuberculosis (eg, nucleic acid probe), rapid de-
tection of latent TB infection (eg, whole-blood inter-
feron gamma assay [QuantiFERON (Cellestis Inc.,
Valencia, California)]) [81,82], the investigational
enzyme-linked immunospot test (ELISPOT) [83],
and differentiation of M. tuberculosis strains (eg,
DNA fingerprinting) [84,85].
In the 1990s, molecular genetic typing (genotyp-
ing) of M. tuberculosis strains became a commonly
used tool to understand outbreaks and transmission
dynamics. In 1996, the CDC established the National
TB Genotyping and Surveillance Network to deter-
mine the usefulness of molecular genotyping in more
routine TB control settings using the IS6110-based
restriction fragment length polymorphism (RFLP)
192 schneider et al
technique supplemented with spacer oligonucleotide
typing (spoligotyping) on M. tuberculosis isolates
[86,87]. Genotyping, in conjunction with epidemio-
logic investigation, has proven a useful adjunct to
epidemiologic investigations in tracing the chain of
transmission [88]. The techniques are particularly
useful in outbreaks and institutional settings, identi-
fying groups at risk for TB (eg, homeless persons),
identifying contacts and social networks, under-
standing exogenous reinfection, and confirming labo-
ratory cross-contamination [89,90]. To refine the
understanding of TB transmission and epidemiol-
ogy and to advance TB control, the CDC has
launched the National TB Genotyping Program,
which provides the capacity to genotype M. tuber-
culosis isolates from all culture-positive TB patients
in the United States. Two polymerase chain reaction –
based genotyping tests (spoligotyping, mycobacterial
interspersed repetitive units analysis) will be supple-
mented with IS6110 RFLP testing for selected speci-
mens [91]. The goal of this program is to improve
the characterization of TB transmission dynamics and
to use the results to improve the efficiency of public
health interventions.
In 1995, following a several-year hiatus in the
USPHS-sponsored clinical trials, the CDC reinstated
clinical TB research, creating the TB Trials Con-
sortium (TBTC). The TBTC currently is coordinat-
ing several studies, including efficacy trials for the
use of moxifloxcin as a first-line drug in the treat-
ment of TB disease. Information gained from the
earliest of these studies contributed to the Food and
Drug Administration licensure of rifapentine, a long-
acting rifampin and the first anti-TB drug approved
in 25 years [92]. Additional studies include a com-
parison of several generations of QuantiFERON
with the tuberculin skin test in the diagnosis of LTBI
[81]. In 2001, the CDC established the TB Epide-
miologic Studies Consortium to conduct multicenter
epidemiologic, behavioral, and operational research
studies. Furthermore, recognizing the need for TB
prevention globally, a renewed interest, fueled by
generous funding has resulted in actively revisiting
vaccine development [93,94]. Numerous organiza-
tions, both in the public and private sectors, are con-
ducting major research efforts to develop a safe and
effective TB vaccine.
Elimination of tuberculosis in the United States:
remaining challenges
After decades of decline, an unprecedented re-
surgence in TB began in 1986 and continued through
1992, with case numbers increasing by 20%. Follow-
ing an intensive campaign and mobilization of new
resources, TB cases once again began to decline.
Remarkable gains have been made since the early
1990s, with efforts being concentrated on maintain-
ing control of TB, speeding the decline of TB, and
developing new tools [37]. Key TB epidemiologic
features that have been identified include an increas-
ing proportion of TB cases among persons born in
countries where TB is endemic, racial and ethnic
disparities, and localized unique epidemiologic pro-
files in areas throughout the United States. Develop-
ment of new tools, such as vaccines, antituberculosis
drugs, and rapid diagnostic tests have also been
identified as vital measures needed to eliminate TB
in the United States.
The smallest decline since the resurgence was
seen in 2003, raising the concern about a possible
slowing of the progress against TB or even a reversal
of the decline. Despite increasing health care costs
and demands for increased programmatic and opera-
tional efforts, funding for TB control has not in-
creased [95]. The elimination of TB in the United
States will require sustained efforts such as identify-
ing and targeting populations at high risk for TB,
remaining actively involved in the global effort
against TB, and maintaining adequate resources.
Acknowledgments
The authors thank the state and local tuberculosis
control officials in health departments throughout
the United States who collected and reported the
national surveillance data presented in this article,
the surveillance staff at the Division of TB Elimi-
nation, Centers for Disease Control and Prevention,
who maintain the database, Ann H. Lanner for her
editorial review of the manuscript, and Dr. Thomas
Navin and Dr. Michael Iademarco for their critical
review of the manuscript.
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