Clin Chest Med 26 (2005) 167 – 182
Global Epidemiology of Tuberculosis
Dermot Maher, BM, BCh, DM, Mario Raviglione, MD*
Stop TB Department, World Health Organization, Avenue Appia, CH1211 Geneva 27, Switzerland
In 1993, the World Health Organization (WHO)
declared tuberculosis a global emergency because of
the scale of the epidemic and the urgent need to
improve global tuberculosis control [1,1a]. Since
then, WHO has promoted the strategy for global
tuberculosis control known as DOTS (a name derived
originally from directly observed treatment, short-
course) [2,3] and its adaptations (eg, as part of a
strategy of expanded scope where HIV prevalence
is high [4] and as DOTS-Plus in areas where the
prevalence of multidrug-resistant [MDR] tuberculosis
is high) [5]. This article provides an overview of the
current scale of the global tuberculosis epidemic. It
describes the global tuberculosis situation as mea-
sured by reported and estimated cases and deaths.
The increasing threats of HIV-related tuberculosis
and drug-resistant tuberculosis receive particular
attention. There is a brief review of the extent of im-
plementation of effective tuberculosis control using
the DOTS strategy. The article ends with a summary
of the approaches needed to accelerate progress in
global tuberculosis control.
Review of the global tuberculosis epidemic
As part of the description of the global tuber-
culosis epidemic, the size of the burden of tuber-
culosis indicates progress in tuberculosis control and
draws attention to the scale of the problem, thereby
helping to mobilize resources for tuberculosis control.
* Corresponding author.
E-mail address: raviglionem@who.ch (M. Raviglione).
0272-5231/05/$ – see front matter D 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.ccm.2005.02.009
The size of the burden of tuberculosis
Tuberculosis case notifications and reported deaths
Tuberculosis notification data are important and
are routinely reported by WHO [6]. At the country
level, a system of recording and reporting tuber-
culosis cases and their treatment outcomes (including
death) is an intrinsic part of the DOTS strategy
(Box 1). Therefore as the number of countries
implementing the DOTS strategy increases, routine
national tuberculosis program (NTP) data on tuber-
culosis cases and deaths are becoming more widely
available [6]. Notification data reflect health ser-
vice coverage and the efficiency of case-finding and
reporting activities of NTPs. Thus, in the developing
countries where tuberculosis incidence is generally
high, where access to health services may be limited,
and where NTP performance may be suboptimal,
notification data often represent only a fraction of
the true incident cases. In addition, because case
definitions vary among countries (eg, when some
countries’ notification data include all cases, both
new and re-treatment cases), comparisons of case
notification data from different countries are difficult.
In industrialized countries, however, where tuber-
culosis incidence is generally low, where health ser-
vice coverage is generally universal, and where NTPs
are effective, notifications of cases often closely ap-
proximate to the true incidence of tuberculosis. In
any country, under stable program conditions, case
notifications may provide useful data on the trend of
incidence and a means for obtaining rates by age, sex,
and risk group.
Despite the limitations of tuberculosis case noti-
fications, WHO has since 1997 published worldwide
data provided by its member states, most recently
referring to the 4.1 million cases reported in 2002 [6].
chestmed.theclinics.com
168 maher
Box 1. The five elements of the directly
observed treatment, short-course strategy
for tuberculosis control
 Sustained government commitment
to tuberculosis control
 Diagnosis based on quality-assured
sputum-smear microscopy mainly
among symptomatic patients
presenting to health services
 Standardized short-course
chemotherapy for all cases of
tuberculosis, under proper case-
management conditions including
direct observation of treatment
 Uninterrupted supply of quality-
assured drugs
 A standard recording and reporting
system enabling program monitoring
by systematic assessment of
treatment outcomes of all
patients registered
Data from Refs. [2,3].
Table 1 shows tuberculosis case notifications and
rates by WHO region. Three regions dominate the
worldwide distribution of notified cases: the South-
East Asian Region (36% of cases), the African
Region (24% of cases), and the Western Pacific
Region (20% of cases). The three other regions have
much smaller proportions of the cases notified
worldwide: the Region of the Americas (9%), the
Eastern Mediterranean Region (6%), and the Euro-
pean Region (5%). Fig. 1 shows tuberculosis case
notification rates by country in 2002 [6].
In industrialized countries, case notifications gen-
erally approximate the true incidence of tuberculosis
more closely than in developing countries. Tuber-
culosis case notifications steadily declined through-
out most of the twentieth century in industrialized
countries, beginning before the introduction of anti-
tuberculosis chemotherapy, largely because of socio-
economic improvements and possibly also because of
the isolation of infectious cases in sanatoria. The
effective application of chemotherapy in the latter
half of the twentieth century further accelerated the
decline. From the mid-1980s onwards, however,
several countries saw a failure of the expected con-
tinued decline, and others saw the trend reversed,
with case notifications increasing for the first time in
many years. For example, in the United States, after
& raviglione
30 years of previous steady decline, tuberculosis
incidence increased regularly between 1985 and 1992
[7]. Factors responsible for the reversal of the
previous trend included increased poverty among
marginalized groups in inner city areas, immigration
from countries with high tuberculosis prevalence, the
impact of HIV, and, most importantly, the failure to
maintain the necessary public health infrastructure
under the mistaken belief that tuberculosis was a
problem of the past.
Many countries in Europe, including Denmark,
the Netherlands, Sweden, and the United Kingdom,
also reported a failure of the expected continued de-
cline or even a steady rise in tuberculosis cases [8].
The high proportion of cases in the foreign-born (eg,
24% in France, 51% in the Netherlands, 54% in
Sweden, 68% in Switzerland) indicated immigration
as the main cause of this change in trend [9]. Annual
case rates in foreign-born populations often exceed
50 per 100,000 and may even exceed 100 per
100,000 (eg, in the Netherlands), in contrast to
annual case rates usually below 15 per 100,000 in
indigenous populations [9]. In Western Europe, the
impact of HIV on tuberculosis has been largely
limited to certain countries (eg, Spain, Portugal) and
cities (eg, Paris, Amsterdam) [10]. In most countries
in Western Europe, the proportion of AIDS cases
diagnosed with tuberculosis is low; two notable
exceptions are Spain and Portugal [11], where the
overlap between the population infected with HIV
and the population infected with Mycobacterium
tuberculosis is greater than in the other countries of
Western Europe. Tuberculosis incidence rates in
Japan are still high, at about 40 per 100,000, but
Table 1
Tuberculosis case notifications and rates by World Health
Organization region in 2002
No. of Proportion Rate
cases notified of global (per 100,000
WHO region (all forms) total (%) population)
African 992,054 24 148
Americas 233,648 9 27
Eastern 188,458 6 37
Mediterranean
European 373,497 5 43
Southeast Asia 1,487,985 36 94
Western Pacific 806,112 20 47
Global 4,081,754 — 66
Data from World Health Organization. Global tuberculosis
control: surveillance, planning, financing. WHO report
2004. Document WHO/HTM/TB/2004.331. Geneva (Swit-
zerland): World Health Organization; 2004. p. 21.
 global epidemiology of tuberculosis 169

Fig. 1. Tuberculosis case notification rates by country in 2002. The designations employed and the presentation of material on
this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the
legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries.
White lines on maps represent approximate border lines for which there may not yet be full agreement. [From World Health
Organization. Global tuberculosis control: surveillance, planning, financing. WHO report 2004. Document WHO/HTM/TB/
2004.331. Geneva (Switzerland): World Health Organization; 2004. p. 218, fig. 4; with permission.]

are declining [12]. In other industrialized countries,
including Australia, New Zealand, and Canada, rates
have leveled off during the past few years below
10 per 100,000. The proportion of cases in the
foreign-born is about 70% in Australia and about
50% in Canada [12]. The implication of the high
proportion of cases in the foreign-born in most indus-
trialized countries is that tuberculosis control in these
settings depends on tuberculosis control globally.
Tuberculosis case notification rates are still high
in the countries of the former Soviet Union [6]. In
many countries the previous continued decline in case
notifications stopped or reversed from the early 1990s
onwards. For example, annual notification rates
doubled in Russia from 1990 to 2002, with an in-
creased proportion of cases in young adults [6].
Dramatic social changes following the end of the
Soviet Union engendered a combination of factors
responsible for the reversal of the previous trend,
probably through increased susceptibility to infection
and increased breakdown to disease after infection.
These factors include increased poverty and poor
living conditions (resulting in malnutrition, crowding,
and stress) and in some cases civil conflicts and
wars, deteriorating health services, and lack of drugs,
resulting in decreased rates of cure of tuberculosis
patients and continued transmission in the commu-
nity. The spread of HIV in some countries, particu-
larly the Russian Federation and Ukraine, has the
potential, if unchecked, to fuel the tuberculosis epi-
demic further.
Data on tuberculosis deaths are reported through
national vital registration systems and through the
routine standard NTP recording and reporting system.
Few developing countries have comprehensive vital
registration systems for the accurate reporting of
deaths. Routine NTP data on tuberculosis deaths are
becoming more widely available in developing
countries [6]. NTPs report these tuberculosis-cohort
deaths (the number and proportion of tuberculosis
patients dying during treatment) without specifying
cause, because the cause of death can rarely be
determined in countries where income is low and the
prevalence of tuberculosis is high [13]. Inaccurate
170 maher & raviglione

routine NTP reporting of cohort deaths and incom-
plete NTP coverage of all incident cases in many
countries limit the extent to which tuberculosis cohort
deaths reflect tuberculosis mortality.
Estimated tuberculosis cases and deaths
Because of the limitations of tuberculosis notifi-
cations and the difficulties in directly measuring the
numbers of cases and deaths, the size of the tuber-
culosis disease burden must be estimated. WHO esti-
mates of tuberculosis incidence and deaths are based
on a variety of inputs, including surveys of preva-
lence of tuberculosis infection and disease, vital
registration data, and independent assessments of
quality of surveillance systems [14,15]. In 2002 there
were an estimated 8.8 million new cases of tuber-
culosis worldwide, with an incidence rate of 141 per
100,000 population [6]. The global incidence rate of
tuberculosis is growing at approximately 1.1% per
year, although this overall global trend is fueled by
and hides much faster increases in sub-Saharan
Africa and in countries of the former Soviet Union
[6]. Table 2 summarizes tuberculosis incidence and
mortality estimates in 2002 by WHO regions [6,14].
Fig. 2 shows estimated tuberculosis incidence by
country for 2002 [6]. The ranking of countries by
number of tuberculosis cases draws attention to the
22 countries that account for roughly 80% of the
world’s tuberculosis burden (Table 3). Developing
countries suffer the brunt of the tuberculosis epi-
demic. Overall, it is estimated that 95% of the world’s
tuberculosis cases and 98% of the tuberculosis deaths
occur in the developing world [12], and that tuber-
culosis causes more than 25% of avoidable adult
deaths in the developing world [16]. The importance
of the tuberculosis problem for individual countries is
expressed as the annual incidence (absolute number
of cases occurring yearly) and as the incidence rate
(cases per 100,000 population). Fig. 3 shows esti-
mated tuberculosis incidence rates by country in 2002
[6]. Tuberculosis incidence rates are generally much
lower in industrialized countries than in developing
countries. Among the 15 countries with the highest
estimated tuberculosis incidence rates, 13 are in sub-
Saharan Africa, and in most of these countries the

Table 2
Summary of tuberculosis estimates by World Health Organization region in 2002
WHO region
AFRa AMR EMR EUR SEAR WPR Global
Population (millions) 672 857 507 877 1591 1718 6222
New cases of TB (all forms)
No. of incident cases (thousands) 2354 370 622 472 2890 2090 8798
Incidence rate (per 100,000) 350 43 123 54 182 122 141
Change in incidence rate 1997 – 2000 (%/y) 5.9 3.6 0.7 1.9 2.1 0.2 1.1
HIV prevalence in new adult cases (%) 37.0 5.5 2.8 3.6 3.5 1.2 12.0
Attributable to HIV (thousands) 506.0 11.0 9.8 10.0 56.0 14.0 656.0
Attributable to HIV (% of adult cases) 31.0 5.0 2.5 3.3 2.9 1.1 11.0
New SS+ cases of TB
No. of incident cases (thousands) 1000 165 279 211 1294 939 3888
Prevalence rate of SS+ TB (per 100,000) 224 25 102 34 166 104 112
Prevalent SS+ cases HIV+ (%) 6.9 1.0 0.4 0.7 0.5 0.2 1.8
Deaths from TB
No. of deaths from TB (thousands) 556 53 143 73 625 373 1823
Deaths from TB (per 100,000) 83.0 6.2 28.0 8.3 39.0 22.0 29.0
Deaths from TB in HIV-positive adults (thousands) 208.0 3.7 4.8 3.0 26.0 5.5 251.0
Adult AIDS deaths caused by TB (%) 15.0 5.4 20.0 13.0 7.6 14.0 13.0
TB deaths attributable to HIV (%) 34.0 6.5 3.2 3.9 3.8 1.4 13.0
Abbreviations: adult, 15 – 49 years old; AFR, African; AMR, Americas; EMR, Eastern Mediterranean; EUR, European; SEAR,
Southeast Asia; SS+, sputum smear-positive; TB, tuberculosis; WPR, Western Pacific.
a
WHO African region comprises sub-Saharan Africa and Algeria. The remaining North African countries are included in
the WHO Eastern Mediterranean region.
Data from World Health Organization. Global tuberculosis control: surveillance, planning, financing. WHO report 2004.
Document WHO/HTM/TB/2004.331. Geneva (Switzerland): World Health Organization; 2004; and Corbett EL, Watt CJ,
Walker N, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med
2003;163:1009 – 21.
 global epidemiology of tuberculosis 171

Fig. 2. Estimated tuberculosis incidence by country in 2002. The designations employed and the presentation of material on this
map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal
status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries.
White lines on maps represent approximate border lines for which there may not yet be full agreement. [From World Health
Organization. Global tuberculosis control: surveillance, planning, financing. WHO report 2004. Document WHO/HTM/TB/
2004.331. Geneva (Switzerland): World Health Organization; 2004; with permission.]

prevalence of HIV infection among tuberculosis
patients is high [6].
In conclusion, worldwide notification data and
estimates suggest a steady decline in the tuberculosis
burden in many regions except in sub-Saharan Africa
and the former Soviet Union. The reasons for the
persisting global tuberculosis burden include (1) pov-
erty and the widening gap between rich and poor
in various populations (eg, developing countries,
inner city populations in developed countries);
(2) previous neglect of tuberculosis control (inad-
equate case detection, diagnosis, and cure); (3)
changing demography (increasing world population
and changing age structure); and (4) the impact of the
HIV pandemic [17].
HIV-related tuberculosis
Through potent immunocompromise of infected
hosts, HIV has emerged as the most important risk
factor for progression of dormant M. tuberculosis
infection to clinical tuberculosis disease [18]. A short
overview of HIV epidemiology is useful because HIV
is such an important force driving the tuberculosis
epidemic in sub-Saharan Africa and has the potential
to drive the tuberculosis epidemic in other regions
wherever HIV transmission spreads unchecked. HIV
surveillance systems in most countries with gener-
alized epidemics rely on tracking HIV prevalence
among pregnant women attending antenatal clinics.
These antenatal clinic data, supplemented by data
from other sources such as blood donors and sex
workers, are used to obtain national estimates of HIV
prevalence among men and women and to assess
trends. By the end of 2003, an estimated 38 million
adults and children worldwide had HIV infection or
AIDS [19]. Of these, 25 million (66%) were in sub-
Saharan Africa, and 6.5 million (17%) were in South
and South-East Asia. In 2003, 4.8 million adults and
children were newly infected with HIV. An estimated
2.9 million adults and children died from HIV/AIDS
172 maher & raviglione

Table 3
Ranking of countries by estimated number of tuberculosis cases
Number estimated
All cases Smear-positive cases
Rate Rate
Population No. (per 100,000 No. (per 100,000 Cumulative
Rank Country (thousands) (thousands) population) (thousands) population) incidence (%)
1 India 1,049,549 1761 168 787 75 20
2 China 1,294,867 1459 113 656 51 37
3 Indonesia 217,131 557 256 250 115 43
4 Nigeria 120,911 368 304 159 132 47
5 Bangladesh 143,809 318 221 143 99 51
6 Pakistan 149,911 272 181 122 81 54
7 Ethiopia 68,961 255 370 110 159 57
8 Philippines 78,580 251 320 113 144 60
9 South Africa 44,759 250 558 102 227 62
10 Democratic Republic 51,201 196 383 85 167 65
of the Congo
11 Russian Federation 144,082 182 126 81 56 67
12 Kenya 31,540 170 540 70 223 69
13 Vietnam 80,278 155 192 69 86 70
14 United Republic 36,276 132 363 56 155 72
of Tanzania
15 Brazil 176,257 110 62 49 28 73
16 Uganda 25,004 94 377 41 164 74
17 Zimbabwe 12,835 88 683 35 271 75
18 Mozambique 18,537 81 436 34 182 76
19 Thailand 62,193 80 128 35 57 77
20 Afghanistan 22,930 76 333 34 150 78
21 Cambodia 13,810 76 549 33 242 79
22 Myanmar 48,852 75 154 33 68 80
High-burden countries 3,892,274 7005 180 3100 80 80

Global total 6,219,011 8797 141 3887 63 100

The top 22 countries account for roughly 80% of the world’s tuberculosis burden.
Data from World Health Organization. Global tuberculosis control: surveillance, planning, financing. WHO report 2004.
Document WHO/HTM/TB/2004.331. Geneva (Switzerland): World Health Organization; 2004. p. 22.

during 2003. Roughly 2.2 million (76%) of these
deaths occurred in sub-Saharan Africa. Sub-Saharan
Africa is the region with the highest overall HIV
prevalence rate in the general adult (15 – 49 years)
population, 7.5% at the end of 2003.
Of 20 countries in the world with an adult HIV
prevalence rate in 2003 above 5%, 19 are in sub-
Saharan Africa (the other is Haiti). In seven countries
in southern Africa, adult HIV prevalence is 15% or
above. Although the countries that have the highest
rates of HIV infection are in Africa, certain countries
in South-East Asia and Latin America are also badly
affected, with an adult HIV prevalence of 1% to 5%.
Although the rise in HIV prevalence seems now to be
decelerating or even decreasing in parts of Eastern
and Southern Africa, it is still increasing rapidly in
some other large populations, for example in the
Russian Federation.
Tuberculosis cases
The HIV pandemic has dramatically fuelled
tuberculosis in populations where there is overlap
between those infected with M. tuberculosis and
those infected with HIV. Table 4 shows the number
of M. tuberculosis- and HIV-coinfected adults (15 –
49 years) in WHO regions and globally by the end of
2000 [14]. Of the 11.4 million adults coinfected with
M. tuberculosis and HIV worldwide by the end of
2000, 70% were in sub-Saharan Africa (Table 4) [14].
The estimated national HIV prevalence in tuber-
culosis patients reflects the extent of the overlap
 global epidemiology of tuberculosis 173

Fig. 3. Estimated tuberculosis incidence rates by country in 2002. The designations employed and the presentation of material on
this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the
legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries.
White lines on maps represent approximate border lines for which there may not yet be full agreement. [From World Health
Organization. Global tuberculosis control: surveillance, planning, financing. WHO report 2004. Document WHO/HTM/TB/
2004.331. Geneva (Switzerland): World Health Organization; 2004. p. 215, fig. 1; with permission.]

Table 4 between the population infected with M. tuberculosis

Number and global percentage of Mycobacterium tuber- and the population infected with HIV in that country.
culosis- and HIV-coinfected adults (15 – 49 years) in World
Fig. 4 shows the estimated HIV prevalence in
Health Organization regions by the end of 2000
tuberculosis patients by country in 2002. The esti-
No. of people mated HIV prevalence in tuberculosis patients is
coinfected with greater than 20% in nearly all of the countries of sub-
M. tuberculosis Proportion
Saharan Africa and is greater than 50% in most of the
and HIV of global
WHO region (thousands) total (%)
countries of the southern cone. Haiti is the only
country outside sub-Saharan Africa where the esti-
African 7979 70 mated HIV prevalence in tuberculosis patients is
Americas 468 4
greater than 20%. The largest share of the global
Eastern Mediterranean 163 1
European 133 1
burden of HIV-related tuberculosis falls on sub-
Southeast Asia 2269 20 Saharan Africa, where 31% of new cases of tuber-
Western Pacific 427 4 culosis (all forms) and 34% of tuberculosis deaths are
attributable to HIV, and where HIV is now the most
Total 11,440 100 important single predictor of tuberculosis incidence
Data from Corbett EL, Watt CJ, Walker N, et al. The grow- (Fig. 5) [14].
ing burden of tuberculosis: global trends and interac- The increasing spread of HIV, especially in
tions with the HIV epidemic. Arch Intern Med 2003;163: Eastern and Southern Africa, resulting in an increased
1009 – 21. population of M. tuberculosis- and HIV-coinfected
174 maher & raviglione

Fig. 4. Estimated HIV prevalence in tuberculosis cases by country in 2002. The designations employed and the presentation of
material on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization
concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers
or boundaries. White lines on maps represent approximate border lines for which there may not yet be full agreement. [From
World Health Organization. Global tuberculosis control: surveillance, planning, financing. WHO report 2004. Document WHO/
HTM/TB/2004.331. Geneva (Switzerland): World Health Organization; 2004. p. 216, fig. 2; with permission.]

people, has driven the incidence of tuberculosis

1000
upwards in sub-Saharan Africa [6]. From 1997 to
2002, the tuberculosis incidence rate in the WHO
(per 100,000 population)
Estimated TB incidence

800 African region grew at approximately 4% per year,

and at 6% per year in Eastern and Southern Africa,
600 faster than on any other continent and considerably
faster than the 1% per year global increase. In several
400
African countries, including those with well-organ-
200 ized control programs [20,21], annual tuberculosis
case notification rates have risen more than fivefold
0 since the mid 1980s, reaching more than 400 cases
0 10 20 30 40
per 100,000 population [6]. Because HIV infection
Estimated HIV prevalence, adults 15-49 yrs (%)
rates are higher in women than men, more tuber-
culosis cases are also being reported among women,
Fig. 5. Estimated tuberculosis incidence in relation to
estimated HIV prevalence for 42 countries in the WHO especially those aged 15 to 24 years. Although
African Region. (From Corbett EL, Watt CJ, Walker N, et al. tuberculosis case notifications typically show a male
The growing burden of tuberculosis: global trends and gender predominance, in several African countries
interactions with the HIV epidemic. Arch Intern Med 2003; with high rates of HIV infection, the majority of
163:1018; with permission.) notified tuberculosis cases are now women [6].
 global epidemiology of tuberculosis
Tuberculosis deaths
The aims of tuberculosis control are to reduce
tuberculosis mortality, morbidity, and disease trans-
mission while preventing the development of drug
resistance [13]. Tuberculosis deaths are not related to
the public health objective of cutting the cycle of
disease transmission, but, as an adverse outcome for
tuberculosis patients and their families, they are an
important indicator of NTP performance and of
progress toward reaching the global health targets
agreed as part of the United Nations Millennium
Development Goals (MDGs) [22]. These consider-
ations are particularly important in countries with
high HIV prevalence where the advent of the HIV
epidemic has dramatically increased both the inci-
dence of tuberculosis and tuberculosis deaths.
It is useful to consider briefly tuberculosis case
fatality (the proportion of tuberculosis cases that die
within a specified time) in the pre-HIV era (before
and after the introduction of effective antituberculosis
chemotherapy) before turning to the HIV era (ie, from
the 1980s onwards). Tuberculosis case fatality was
high before the introduction of effective antitubercu-
losis chemotherapy. For example, survival analysis of
confirmed pulmonary tuberculosis patients diagnosed
between 1925 and 1934 in a large town in Denmark
showed that the probability of dying ranged between
17% and 29%, 32% and 43%, and 42% and 55%
1 year, 3 years, and 5 years after tuberculosis diag-
nosis, respectively [23]. In an observational study
of sputum-positive tuberculosis patients diagnosed
between 1928 and 1938 in the United Kingdom, 40%
of patients died in the first year after they were
diagnosed with tuberculosis [24]. A reduction in
tuberculosis deaths usually quickly followed the
introduction of antituberculosis chemotherapy. Data
on tuberculosis case fatality in the prechemotherapy
era in sub-Saharan Africa are lacking, but data
from clinical trials of combination chemotherapy in
Eastern Africa in the 1970s showed a low case fatal-
ity [25].
HIV has dramatically increased tuberculosis case
fatality as measured in clinical trials and as reflected
by tuberculosis cohort deaths reported by NTPs. Risk
of death during and after tuberculosis treatment is
higher among HIV-positive than among HIV-negative
patients who have smear-positive pulmonary tuber-
culosis and is higher still among HIV-positive
patients who have smear-negative tuberculosis (prob-
ably reflecting their greater degree of immunosup-
pression) [26]. In sub-Saharan Africa, up to 30%
of HIV-infected tuberculosis patients die within
12 months of starting treatment [27]. Even with
treatment regimens that are highly effective in HIV-
175
negative pulmonary tuberculosis patients, cohort
deaths for HIV-positive pulmonary tuberculosis
patients in some sub-Saharan African countries are
now as high as 20% for sputum smear – positive cases
and 50% for sputum smear – negative cases [26].
Tuberculosis cohort deaths are linked closely to
HIV prevalence, both within countries (ie, in many
countries tuberculosis cohort deaths have increased as
adult HIV seroprevalence has increased) and in wider
areas (tuberculosis cohort deaths and national HIV
seroprevalence in sub-Saharan Africa are strongly
correlated) [26]. The increase in tuberculosis deaths
in populations with high HIV prevalence in sub-
Saharan Africa may change the popular perception of
tuberculosis as a curable disease and threaten the
reputation of NTPs. This experience may have an
adverse influence on the willingness of tuberculosis
suspects to come forward for diagnosis and on the
ability of the NTPs to ensure that tuberculosis pa-
tients complete treatment.
Measures to prevent tuberculosis deaths in coun-
tries with high HIV prevalence include [27]
1. Antiretroviral therapy (likely to have the great-
est impact)
2. Tuberculosis treatment regimens of proven ef-
fectiveness
3. Preventive therapy for HIV-related diseases
other than tuberculosis (eg, co-trimoxazole to
prevent common bacterial infections)
4. Improved tuberculosis and HIV control services
5. Improved general health services with better
diagnosis and treatment of HIV-related diseases
Implementing these measures will need increased
financial and human resources for the general health
services and for tuberculosis and HIV programs and
more effective collaboration between tuberculosis
and HIV/AIDS programs [4].
Drug-resistant tuberculosis
Drug resistance and eventually MDR (ie, resis-
tance to at least isoniazid and rifampicin) are ex-
pected to occur wherever there is inadequate
application of antituberculosis chemotherapy [28].
An assessment of the number and distribution of
drug-resistant tuberculosis cases is important for
planning tuberculosis control, because the treatment
of resistant cases is more costly and more complex
when second-line drugs are used, with more fre-
quent failures and deaths. The distinction between
resistance among new cases (previously known as
176 maher & raviglione

primary resistance) and resistance among previ-
ously treated cases (previously known as acquired
resistance) is important because of their different im-
plications for NTPs. Three rounds of surveys coor-
dinated by WHO and the International Union Against
Tuberculosis and Lung Disease (IUATLD) between
1996 and 2002 have yielded data on antituberculosis
drug resistance among new and previously treated
cases. The third round of surveys included new data
from 77 settings or countries collected between 1999
and 2002 and gave the following results for resistance
among new and previously treated cases [29].
New cases
Data on new cases were available for 75 settings.
In total, 55,779 patients were surveyed. The preva-
lence of resistance to at least one antituberculosis
drug (any resistance) ranged from 0% in some
Western European countries to 57.1% in Kazakhstan
(median, 10.2%). Median prevalences of resistance to
specific drugs were as follows: streptomycin, 6.3%;
isoniazid, 5.9%; rifampicin, 1.4%; and ethambutol,
0.8%. Prevalence of MDR ranged from 0% in eight
countries to 14.2% in Kazakhstan (51/359) and Israel
(36/253) (median, 1.1%). Fig. 6 shows by participat-
ing country the prevalence of MDR-tuberculosis
among new tuberculosis cases. Other high prevalen-
ces of MDR were observed in Tomsk Oblast (Russian
Federation) (13.7%), Karakalpakstan (Uzbekistan)
(13.2%), Estonia (12.2%), Liaoning Province (China)
(10.4%), Lithuania (9.4%), Latvia (9.3%), Henan
Province (China) (7.8%), and Ecuador (6.6% on
preliminary data).
Trends in drug resistance in new cases were
determined in 46 settings (20 with two data points
and 26 with at least three). Significant increases in
prevalence of any resistance were found in Peru,
Botswana, New Zealand, Poland, and Tomsk Oblast,
(Russian Federation). Cuba, Hong Kong SAR, and
Thailand reported significant decreases over time.
Tomsk Oblast (Russian Federation) and Poland
showed significantly increased prevalences of MDR.
Decreasing trends in MDR were observed in Hong
Kong SAR, Thailand, and the USA.

Fig. 6. Prevalence of MDR-tuberculosis among new tuberculosis cases, 1994 – 2002. The designations employed and the
presentation of material on this map do not imply the expression of any opinion whatsoever on the part of the World Health
Organization concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation
of its frontiers or boundaries. Dashed lines represent approximate border lines for which there may not yet be full agreement.
[From World Health Organization. Anti-tuberculosis drug resistance in the world. Report no. 3. The WHO/IUATLD Global
Project on Anti-tuberculosis Drug Resistance Surveillance 1999 – 2002. Document WHO/HTM/TB/2004.343. Geneva
(Switzerland): World Health Organization; 2004. p. 47; with permission.]
 global epidemiology of tuberculosis 177

Previously treated cases
Data on previously treated cases were available
for 66 settings. In total, 8405 patients were surveyed.
The median prevalence of resistance to at least one
drug (any resistance) was 18.4%, with the highest
prevalence, 82.1%, in Kazakhstan (262/319). Median
prevalences of resistance to specific drugs were as
follows: isoniazid, 14.4%; streptomycin, 11.4%;
rifampicin, 8.7%; and ethambutol, 3.5%. The median
prevalence of MDR was 7.0%. Fig. 7 shows by par-
ticipating country the prevalence of MDR tuber-
culosis among previously treated tuberculosis cases.
The highest prevalences of MDR were reported in
Oman (58.3%; 7/12) and Kazakhstan (56.4%; 180/
319). Among countries of the former Soviet Union,
the median prevalence of resistance to the four drugs
was 30%, compared with a median of 1.3% in all
other settings. Given the small number of subjects
tested in some settings, prevalence of resistance
among previously treated cases should be interpreted
with caution.
Drug-resistance trends in previously treated cases
were determined in 43 settings (19 with two data
points and 24 with at least three data points). A
significant increase in the prevalence of any resis-
tance was observed in Botswana. Cuba, Switzerland,
and the United States showed significant decreases.
The prevalence of MDR significantly increased in
Estonia, Lithuania, and Tomsk Oblast (Russian
Federation). Decreasing trends were significant in
Slovakia and the United States. More representative
geographic coverage of global antituberculosis drug
resistance surveillance, with further data from longi-
tudinal studies, will enable more accurate and com-
prehensive monitoring of global trends in the spread
of MDR tuberculosis. Increases in prevalence of
resistance can be caused by poor or worsening tuber-
culosis control, immigration of patients from areas of
higher resistance, outbreaks of drug-resistant disease,
and variations in surveillance methodologies.
In conclusion, although drug-resistant tuberculosis
is present in all settings surveyed, the prevalence of
MDR is high only in certain settings. Because good
tuberculosis control practices are generally associ-
ated with lower or decreasing levels of resistance,
the findings of the WHO/IUATLD Global Project

Fig. 7. Prevalence of MDR-tuberculosis among previously treated tuberculosis cases, 1994 – 2002. The designations employed
and the presentation of material on this map do not imply the expression of any opinion whatsoever on the part of the World
Health Organization concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the
delimitation of its frontiers or boundaries. Dashed lines represent approximate border lines for which there may not yet be full
agreement. [From World Health Organization. Anti-tuberculosis drug resistance in the world. Report no. 3. The WHO/IUATLD
Global Project on Anti-tuberculosis Drug Resistance Surveillance 1999 – 2002. Document WHO/HTM/TB/2004.343. Geneva
(Switzerland): World Health Organization; 2004. p. 53; with permission.]
178 maher
emphasize the vital importance of strengthening
tuberculosis control worldwide, by expanding and
improving the quality of implementation of the
DOTS strategy, to prevent the emergence of further
drug resistance. National programs need to manage
MDR tuberculosis cases, regardless of prevalence,
through application of the DOTS-Plus strategy [30].
Status of global tuberculosis control
The scale of the tuberculosis epidemic, as de-
scribed previously, and the human rights approach
to tuberculosis demand effective and urgent action
[31]. WHO has promoted the DOTS strategy to
control tuberculosis primarily by the interruption of
transmission through the rapid identification and cure
of infectious cases. By 2002, the number of countries
and territories implementing the DOTS strategy was
180 (of 210), with an estimated 69% of the world’s
population living in administrative areas of countries
where the DOTS strategy was being implemented [6].
In practice, however, the proportion of the population
with access to the DOTS strategy is less than this
administrative figure because of several possible
barriers to access, including geographic, financial,
and cultural impediments, within the administrative
area. Relying on currently available methods of diag-
nosis and treatment, the DOTS strategy is effective,
affordable, and adaptable in different settings (eg, as
part of a strategy of expanded scope where HIV
prevalence is high [4], as DOTS-Plus in areas where
the prevalence of MDR tuberculosis is high [5], and
as public-private mix [PPM] DOTS where the ma-
jority of tuberculosis suspects consult private practi-
tioners) [32].
WHO coordinates a global tuberculosis monitor-
ing and evaluation project in which countries report
annual progress in implementation of the DOTS
strategy [33]. The World Health Assembly (WHA)
has set global targets for tuberculosis control through
the implementation of the DOTS strategy [34]. The
choice of these global targets reflected the need to
achieve a significant epidemiologic impact by reach-
ing targets that field experience had demonstrated
were feasible in countries with a high incidence of
tuberculosis. These targets are to detect at least 70%
of all new infectious cases and to cure at least 85% of
those detected by 2005 [35]. A 70% case detection
rate and an 85% cure rate eventually would reduce
both the prevalence of infectious tuberculosis cases
and the number of infected contacts by about 40%
[36] and would lead to an expected decline in annual
& raviglione
tuberculosis incidence rate of 6% to 7% per year [37].
The epidemiologic impact on the global tuberculosis
epidemic of sustained achievement of these targets is
expressed in the MDG relevant to tuberculosis (Goal
6, Target 8), ‘‘to have halted and begun to reverse
incidence by 2015’’ [22]. The epidemiologic inter-
pretation of this goal set by politicians is to decrease
tuberculosis prevalence and deaths by half by 2015.
The following section summarizes the most recent
assessment of progress in implementation of the
DOTS strategy toward achieving the cure rate and
case detection targets as set out in the 2004 WHO
Report, which reports on the cases detected in 2002
and the outcomes of treatment of patients detected in
2001 [6].
Cases detected and notified
Through the global tuberculosis monitoring and
evaluation project coordinated by WHO, countries
report annually the number and type of tuberculosis
cases detected, reported, and treated under DOTS and
non-DOTS programs [6]. In 2002, approximately
3 million patients who were newly diagnosed with
tuberculosis, 1.4 million of whom were smear-
positive, were reported in DOTS programs. A total
of 13.3 million tuberculosis patients and 6.8 million
smear-positive patients were treated in DOTS pro-
grams between 1995 and 2002. Regarding new cases
of sputum smear – positive pulmonary tuberculosis,
for the calculation of case detection rate in each
country, the numerator is the number of annual cases
detected and reported under the DOTS strategy, and
the denominator is the estimated annual incidence
of cases in that country. The numerator is derived
annually from country reports of registered cases (ie,
cases detected and reported under the DOTS strat-
egy). The denominator is an estimate based on a
variety of inputs, as outlined earlier. One of the
challenges in improving the accuracy of measurement
of the case detection rate is ensuring that all cases
detected by different care providers (eg, private
practitioners) and treated in line with the DOTS strat-
egy are reported through the NTP. The 1.4 million
smear-positive cases reported globally by DOTS
programs in 2002 represent 37% of the estimated
incidence, a little more than half of the 70% target.
Treatment success
The cure rate is reported by each country through
cohort analysis of standard treatment outcomes of
registered patients (Table 5) [13]. Because practice
varies considerably among countries in documenting
 global epidemiology of tuberculosis
Table 5
Standard treatment outcomes in patients who have sputum
smear-positive pulmonary tuberculosis
Outcome Patient characteristics
Cure Patient who is sputum smear-negative
in the last month of treatment and at
least on one previous occasion
Treatment Patient who has completed treatment
completeda but who does not meet the criteria to
be classified as a cure or a failure
Treatment Patient who is sputum smear-positive
failure at 5 months or later during treatmentb
Died Patient who dies for any reason during
the course of treatment
Default Patient whose treatment was interrupted
for 2 consecutive months or more
Transfer out Patient who has been transferred to
another recording and reporting unit
and for whom the treatment outcome
is not known
a
Treatment success is defined as the sum of patients
cured and those who have completed treatment.
b
Also a patient who was initially smear-negative before
starting treatment and became smear-positive after complet-
ing the initial phase of treatment.
Data from World Health Organization. Treatment of tuber-
culosis: guidelines for national programmes. 3rd edition.
Document WHO/CDS/TB/2003.313. Geneva (Switzerland):
World Health Organization; 2003. p. 55.
negative sputum smears on completion of treatment,
for practical purposes the treatment success rate (cure
plus treatment completion) is used as a proxy for cure
rate. Treatment success under DOTS for the 2001
cohort was 82% on average. As in previous years,
treatment success was substantially below average in
the WHO African Region (71%) and in the former
Soviet Union (70%). Low treatment success in these
two regions is attributable, in part, to NTPs failing to
cope with the increased caseload fuelled by HIV and
the problem of drug resistance, respectively. All in-
dicators of treatment outcome were much worse in
non-DOTS areas, although the true outcome of treat-
ment is unknown for a high proportion of patients
in non-DOTS areas because of the lack of use of
standardized definitions and lack of systematic
reporting when programs are weak. Fatal outcomes
were most common in Africa (7.2%), where a higher
percentage of cases is HIV-positive, and in Europe
(5.9%), where a higher percentage of cases occurs
among the elderly. Treatment interruption (default)
was most frequent in the WHO African Region
(10.3%), Eastern Mediterranean Region (7.2%), and
South-East Asia Region (6.7%). Transfer without
follow-up was also especially high in Africa (6.6%).
179
Treatment failure was conspicuously high in the Euro-
pean region (8.1%), mainly because of high failure
rates in the former Soviet Union, most likely resulting
from the high prevalence of MDR tuberculosis.
In summary, the global case detection rate for pa-
tients who had sputum smear – positive tuberculosis
was 37% in 2002, half of the 70% target, whereas
treatment success under the DOTS strategy for the
2001 cohort was 82% on average, close to the 85%
target. Although this progress toward the WHA 2005
targets of 70% case detection and 85% treatment
success represents a considerable gain, making an
impact on the global tuberculosis burden as expressed
in the 2015 MDGs will require speeding prog-
ress toward meeting and then sustaining the 2005
WHA targets.
Approaches needed to accelerate progress in
global tuberculosis control
A global alliance named the Stop TB Partnership
provides the means for international partners and the
governments of countries with high tuberculosis
incidence to intensify efforts to accelerate progress
in global tuberculosis control [38]. The development
of new tools for tuberculosis control (eg, a more
effective vaccine [39], better diagnostic tests [40], and
improved preventive [41] and therapeutic [42] ap-
proaches) holds out the prospect of rapid progress in
tuberculosis control in the future. In the meantime,
the challenge in maximizing the impact of currently
available methods of diagnosis and treatment lies in
implementing the DOTS strategy and its adaptations
as effectively and as widely as possible.
In coordination with a global network of partners
known as the DOTS Expansion Working Group
(DEWG), WHO is committed to implementing the
DOTS strategy as effectively and as widely as pos-
sible [43]. WHO published the Global DOTS
Expansion Plan (GDEP) in 2001 [44]. The GDEP is
based on two pillars: the preparation in each country
of a mid-term (at least 5-year) DOTS expansion plan,
and the establishment of a mechanism for interagency
coordination ensuring that all relevant partners
contribute to the implementation of the national plan.
Effective development and implementation of the
national plan depends on the engagement of the full
range of health providers under NTP stewardship:
government services, whether Ministry of Health
(nationally and locally administrated services) or not
(eg, social security schemes, prisons, military), and
nongovernment services (eg, NGOs, community
180 maher
groups [45], private practitioners [32], and employers
[46]). In practice, all health providers should refer
patients to public health facilities delivering tuber-
culosis care under the DOTS strategy or deliver
tuberculosis care consistent with the DOTS strategy
in collaboration with the NTP. The failure of
providers to deliver care consistent with the DOTS
strategy compromises the achievements of NTPs and
the chances of successful tuberculosis control. Gov-
ernments should consider reform of legislative and
regulatory frameworks to engage the full range of
health providers and will need to invest in developing
human resource capacity (for strengthened NTP
stewardship and service delivery) [47].
Three of the main adaptations of the DOTS
strategy are as part of a strategy of expanded scope
where HIV prevalence is high [4], as DOTS-Plus in
areas where the prevalence of MDR tuberculosis is
high [5], and as PPM DOTS where the majority of
tuberculosis suspects consult private practitioners
[32]. Until recently, the efforts to control tuberculosis
among HIV-infected people have focused mainly on
identifying and curing infectious tuberculosis cases
among patients presenting to general health services.
This approach targets the final step in the sequence of
events by which HIV fuels tuberculosis, namely the
transmission of M. tuberculosis infection by infec-
tious tuberculosis cases. The strategy of expanded
scope for tuberculosis control in populations with
high HIV prevalence comprises interventions against
tuberculosis (the DOTS strategy and tuberculosis
preventive treatment) and interventions against HIV
(and therefore indirectly against tuberculosis) (eg,
condoms, treatment of sexually transmitted infec-
tions, safe injecting drug use, and highly active
antiretroviral treatment) [4].
DOTS-Plus is the programmatic approach to the
diagnosis and treatment of MDR tuberculosis within
the context of DOTS programs. Management
involves the diagnosis of MDR tuberculosis through
quality-assured culture and drug-susceptibility testing
and treatment with second-line drugs under proper
case management conditions. In response to the
seriousness of MDR tuberculosis as a global public
health problem, the DOTS-Plus Working Group was
established in 1999 to promote improved manage-
ment of MDR tuberculosis in resource-limited
countries. The Working Group aims to assess the
feasibility and cost effectiveness of the use of second-
line antituberculosis drugs in DOTS-Plus projects.
Since 2000, the Working Group’s Green Light
Committee has successfully negotiated with the
pharmaceutical industry to obtain substantial conces-
sionary prices for second-line drugs that otherwise
& raviglione
were unaffordable in poor settings. As a result, prices
of the most expensive regimens have dropped
by 95%.
PPM-DOTS is the means of engaging private
practitioners in collaboration with the NTP in the
delivery of tuberculosis care consistent with the
DOTS strategy. This approach is necessary where
large numbers of tuberculosis suspects seek care from
private practitioners rather than from public health
services. Recent studies indicate the success of the
PPM approach in achieving high rates of case detec-
tion, notification, and cure [48]. A global subgroup of
the DEWG concerned with PPM-DOTS is promoting
the scaling up of this approach, accompanied by the
necessary strengthening of the NTP stewardship and
leadership roles. Lessons learned from PPM-DOTS
are applicable to engaging the contributions of a wide
range of public providers who in many countries are
providing tuberculosis care independently of the NTP
(eg, in prisons and social security programs).
Accelerating progress in global tuberculosis con-
trol depends on developments in the specific field of
tuberculosis control and on strengthening health
systems. In 2003, the Stop TB Partnership convened
a second ad hoc committee on the tuberculosis epi-
demic to seek solutions to the health system con-
straints to more rapid progress in global tuberculosis
control and to make recommendations to overcome
those constraints [49,50]. The committee made
recommendations under seven headings (many of
which cut across the different aspects of tuberculosis
control) [49]:
1. Consolidate, sustain, and advance achievements
2. Enhance political commitment (and its trans-
lation into policy and action)
3. Address the health workforce crisis
4. Strengthen health care systems, particularly
primary care delivery
5. Accelerate the response to the TB/HIV emergency
6. Mobilize communities and the corporate sector
7. Invest in research and development to shape
the future.
Implementation of these recommendations de-
pends on coordination between the health care sector
and other sectors to deliver effective tuberculosis
control covering all populations in need.
Summary
In 2002 there were an estimated 8.8 million new
cases of tuberculosis worldwide, and the global
 global epidemiology of tuberculosis
incidence rate was growing at approximately 1.1%
per year. The scale of the global tuberculosis epi-
demic indicates the huge challenge for tuberculosis
control, which is complicated by the impact of HIV
and drug-resistant tuberculosis. Global efforts to
implement the DOTS strategy widely and effectively
have resulted in a global case detection rate of 37%
in 2002, more than half of the target of 70%, and
treatment success for the 2001 cohort of 82%, on
average, close to the target of 85%. Faster progress
toward global targets depends on future development
of new drugs, diagnostics, and vaccines, meanwhile
overcoming health system constraints to intensified
implementation of the DOTS strategy and to its
adaptations in areas with high prevalence of HIV or
MDR tuberculosis or where not all care providers
deliver the internationally recommended standard
of care.
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