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Tuberculosis: the role of risk factors and social determinants

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Series
1814
www.thelancet.com Vol 375 May 22, 2010
Lancet 2010; 375: 1814–29
Published Online
May 19, 2010
DOI:10.1016/S0140-
6736(10)60483-7
See
Comment page 1755
See Perspectives page 1773
This is the fi rst in a
Series of
eight papers about tuberculosis
Stop TB Department, WHO,
Geneva, Switzerland
(K Lönnroth PhD, K Floyd PhD,
P Glaziou MD,
M C Raviglione MD); Division of
TB Elimination National Center
for HIV, Viral Hepatitis, STD
and TB Prevention, Centers for
Disease Control and
Prevention, Atlanta, GA, USA
(K G Castro MD); National
Leprosy and TB Programme,
and Kenya Medical
Research Institute, Nairobi,
Kenya (J M Chakaya MD); and
Tuberculosis 1
Tuberculosis control and elimination 2010–50: cure, care,
and social development
Knut Lönnroth, Kenneth G Castro, Jeremiah Muhwa Chakaya, Lakhbir Singh Chauhan, Katherine Floyd, Philippe Glaziou, Mario C Raviglione
Rapid expansion of the standardised approach to tuberculosis diagnosis and treatment that is recommended by WHO
allowed more than 36 million people to be cured between 1995 and 2008, averting up to 6 million deaths. Yet
tuberculosis remains a severe global public health threat. There are more than 9 million new cases every year
worldwide, and the incidence rate is falling at less than 1% per year. Although the overall target related to the
Millennium Development Goals of halting and beginning to reverse the epidemic might have already been reached in
2004, the more important long-term elimination target set for 2050 will not be met with present strategies and
instruments. Several key challenges persist. Many vulnerable people do not have access to aff ordable services of
suffi cient quality. Technologies for diagnosis, treatment, and prevention are old and inadequate. Multidrug-resistant
tuberculosis is a serious threat in many settings. HIV/AIDS continues to fuel the tuberculosis epidemic, especially in
Africa. Furthermore, other risk factors and underlying social determinants help to maintain tuberculosis in the
community. Acceleration of the decline towards elimination of this disease will need invigorated actions in four broad
areas: continued scale-up of early diagnosis and proper treatment for all forms of tuberculosis in line with the Stop
TB Strategy; development and enforcement of bold health-system policies; establishment of links with the broader
development agenda; and promotion and intensifi cation of research towards innovations.
Introduction
Global control of tuberculosis is far from complete. There
were 9·4 million estimated new cases of tuberculosis in
2008;1,2 multidrug-resistant (MDR) tuberculosis remains
a severe threat;3,4 and HIV continues to fuel the epidemic,
especially in Africa.1,5 With 1·8 million estimated deaths
every year, tuberculosis still takes a huge toll, especially
for the poorest people. It is a leading cause of death in
people in the most economically productive age-groups.6
People who are cured from this disease can be left with
lifetime sequelae that substantially reduce their quality of
life.7 The direct and indirect costs of tuberculosis, and the
social consequences, are often catastrophic for the
individual patient, the family, and the wider community.8
Fortunately, available drug regimens can cure most
patients,1 and tuberculosis treatment is among the most
cost-eff ective health interventions.9 If applied early in the
disease course it can eff ectively cut transmission and
prevent the disease from spreading. It can also yield
economic benefi ts that are ten times the cost of the
investment.10 Therefore, concerted action to ensure
universal access to high-quality tuberculosis diagnosis
and treatment is being pursued by almost all countries,
in line with WHO’s Stop TB Strategy (panel 1)11 and the
Stop TB Partnership’s Global Plan to Stop TB.12,13 The
medium-term target of these actions, set for 2015 in the
Search strategy and selection criteria
We searched PubMed, the Cochrane library, and the email
send-list TB-Related News and Journal Items Weekly Update
(prepared by the Centers for Disease Control and Prevention,
Atlanta, GA, USA). No predefi ned inclusion or exclusion
criteria were used. We purposively selected the publications
that were judged most relevant for the review, with a
preference for high-quality systematic reviews. We favoured
publications in the past 5 years, but did not exclude highly
regarded older publications.
Key messages
Rapid expansion of a standardised approach to tuberculosis diagnosis and treatment
cured more than 36 million people between 1995 and 2008, averting up to 6 million
deaths. However, tuberculosis remains a huge global public health concern, with more
than 9 million new cases occurring every year.
The Millennium Development Goal target to halt and begin to reverse tuberculosis
incidence by 2015 is estimated to have been reached in 2004 globally. However, the
decline is less than 1% per year.
With present eff orts, the targets to halve prevalence and death rates by 2015, compared
with 1990 rates, will probably be met in most regions, but might not be met worldwide.
The long-term elimination target, to reduce incidence to less than one case per million
by 2050, will not be reached with existing technologies and approaches.
• Intensifi ed case detection approaches are needed, linked to general health-system
strengthening, ensuring universal access to high-quality early diagnosis, treatment,
and care for all forms of this disease, including people infected with HIV and those
aff ected by multidrug-resistant tuberculosis.
Emphasis should be put on preventions, including preventive therapy, development
of better vaccines, and actions to address direct tuberculosis risk factors (eg, HIV,
undernutrition, diabetes, smoking, and drug and alcohol misuse), and underlying
social determinants (eg, poverty, and poor living and working conditions).
Acceleration of the present decline towards tuberculosis elimination will need
invigorated actions in four broad areas: continued scale-up of early diagnosis and
proper treatment in line with the Stop TB Strategy; development and enforcement of
bold health-system policies; establishment of links with the broader development
agenda; and promotion and intensifi cation of research.
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www.thelancet.com Vol 375 May 22, 2010
1815
context of the Millennium Development Goals (MDGs),
is to halt and to begin to reverse incidence of this disease.
Additional 2015 targets set by the Stop TB Partnership
are to halve tuberculosis prevalence and death rates
compared with 1990. A more long-term goal is to
eliminate the disease as a public health concern by
reducing incidence to less than one case per 1 million of
the population by 2050.14
In the fi rst paper in the Series, we assess progress
towards reaching these targets, with particular focus on
the 22 countries with a high burden of tuberculosis that
together have more than 80% of the world’s cases. We
then scrutinise the present model for global tuberculosis
control, and review the main challenges related to weak
health systems, inadequate medical technologies, MDR
tuberculosis, the HIV epidemic, other tuberculosis risk
factors, and social determinants. Finally, we identify
additional entry points for interventions and describe a
way forward towards more eff ective tuberculosis control.
Methods
This paper draws on three categories of data: a review of
published work; routine data submitted to WHO from
member states; and epidemiological estimates produced
by WHO based on data from routine surveillance,
surveys, and systematic literature reviews. Methods used
by WHO to estimate prevalence, rates of death, and
incidence, and related data limitations, are described in
detail elsewhere.1,2
Tuberculosis programme implementation and sur-
veillance data for 2008 were submitted to WHO by
member states in 2009. Of 204 countries and territories
from which data were requested, 198 responded,
representing more than 99% of the world’s total
population. In most countries, the reported data were
obtained from a standardised recording and reporting
system.15 To supplement this information, we undertook
a survey of present control policies and health systems,
as reported by the managers of the national tuberculosis
programmes (NTPs) in the 22 high-burden countries.
Table 1 and table 2 summarise key indicators of data
sources for burden estimates, progress towards targets,
NTP performance, and health-system context for the
22 countries with high tuberculosis burden.
The country data presented in this paper largely rely
on self-reported programme implementation and
surveillance data. Doubts have been raised about the
reliability of such data, which could be aff ected by political
pressure and confl icts of interest.17 WHO has put in place
a transparent process of data validation, which includes
close scrutiny of data at various levels by national and
international surveillance experts before submission,
and frequent external NTP reviews and data validation
missions. The methods used to derive estimates for every
country are available to the public.1,2,18
Nevertheless, the availability and quality of the required
surveillance data are often unsatisfactory because of
general health information defi ciencies,19 and trends
might therefore be diffi cult to interpret.17,18,20 Although in
most countries tuberculosis is a notifi able disease by law,
including in 15 of the 22 high-burden countries (table 2),
the compliance with such laws varies greatly. Cases
diagnosed outside NTPs—eg, in the private sector—are
not systematically notifi ed.21 Cause-of-death registration
is often non-existent or incomplete, and has been used as
a means to improve estimates of tuberculosis burden for
only four of the high-burden countries (table 1). The
indirect method to estimate incidence, through an
assumed fi xed relation between the annual risk of
tuberculosis infection and the incidence of new sputum-
smear-positive disease, is too uncertain and no longer
recommended.22 At the same time, only few population-
based epidemiological studies, such as surveys to
establish the prevalence of disease, have been undertaken.
Between 1990 and mid-2009, only six of the 22 high-
burden countries had completed national surveys, and
only two had done repeated surveys to assess trends
(table 1). Finally, although a unique global initiative for
drug-resistance surveillance has been in place since 1994,
several countries still have insuffi cient information about
drug resistance. 12 of the 22 countries had national data
for drug-resistance surveillance by 2009. Another six had
subnational information (table 1).
Substantial uncertainties thus surround estimates of
tuberculosis incidence, prevalence, and mortality.
Additionally, one of the traditional NTP performance
indicators, the case detection rate, is diffi cult to estimate
because of limitations with accuracy of both the numerator
(number of new cases of smear-positive tuberculosis
notifi ed in the country in a year) and the denominator
(estimated national incidence of new smear-positive
tuberculosis).23 The other traditional NTP performance
indicator, the treatment success rate in new sputum-
smear-positive cases treated in NTPs, can be correctly
assessed through cohort analysis on the basis of
standardised treatment registers. However, such data are
not routinely analysed for sputum-smear-negative cases or
for the large proportion of patients who are treated outside
NTPs—eg, in the private sector.21
Ultimately, comprehensive and reliable vital registration
and notifi cation systems are needed to generate valid
estimates.24 Although most countries are far from such a
situation,25 much work is being done to improve
estimates, including prevalence surveys and validation
mechanisms for notifi cation systems.1
Scale-up of diagnosis and treatment
Treatment and case detection rates
In 2008, 180 countries (91% of total countries reporting)
and all 22 high-burden countries reported that they were
implementing at least the essential directly observed
therapy, short course (DOTS) component of the Stop TB
Strategy (panel 1) through NTP or equivalent structures.
In all high-burden countries apart from one (Brazil),
Ministry of Health and Family
Welfare, New Delhi, India
(L S Chauhan MD)
Correspondence to:
Dr Knut Lönnroth,
Stop TB Department, WHO,
20, Avenue Appia, Geneva 27,
GE 1211, Switzerland
lonnrothk@who.int
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www.thelancet.com Vol 375 May 22, 2010
more than 90% of the population lived in areas in which
DOTS was the offi cial strategy (table 1).
The target of a treatment success rate of at least 85%
for new smear-positive cases treated in NTPs was reached
globally for the fi rst time in the 2007 cohort.2 However,
there were large variations across regions and countries.
The WHO eastern Mediterranean region (88%), the
southeast Asian region (88%), and the western Pacifi c
region (92%) surpassed the target. The region of the
Americas was close at 82%. The African region (79%)
and the European region (67%) both reported high death
and default rates, whereas the treatment failure rate was
also high in the European region.2 Nine of the 22 high-
burden countries did not reach the treatment success
target in 2007 (table 1). High prevalence of HIV and
MDR tuberculosis constitute specifi c challenges
impeding high success rates in Africa and Europe,
respectively. Health-system weaknesses, poor health-
care access, and several patient-related factors, including
nancial barriers, create challenges for treatment
adherence in many countries.1,26
The global case detection rate increased six-fold
between 1995 and 2008. However, after a period of
acceleration between 2001 and 2005, the rate stabilised
around 60% between 2006 and 2008.2 The target of 70%,
which was originally set for 2000 and then postponed for
2005, has thus not yet been reached globally. Estimated
case detection rates vary widely between countries and
regions (fi gure 1). Only six of 22 high-burden countries
had reached the 70% target for smear-positive tuberculosis
in 2008 according to the best estimate (table 1).
The combination of increased case detection rates
and improved rates of treatment success has resulted in
more than 43 million patients having been treated
under the DOTS and Stop TB Strategy principles
worldwide, with 36 million patients cured between 1995
and 2008.2 The case fatality rate halved from 8% to 4%
in this time. Up to 6 million deaths are estimated to
have been averted through scaling up DOTS, compared
with a scenario in which the situation before 1995 would
have continued.2 Nevertheless, the scope is huge to
further reduce burden, death, and transmission of
tuberculosis, especially by closing the case detection
gap of nearly 40% and reducing diagnostic delay.
Globally, the margin of possible improvement is less
for treatment success rates within NTPs, although
eff orts to reduce treatment inter ruption, treatment
failure, and case fatality are crucial in many settings.
Programmatic management of MDR tuberculosis
Globally there were an estimated 440 000 new cases of
MDR tuberculosis in 2008 (95% CI 390 000–510 000).
However, in that year less than 30 000 cases (7% of the
estimated global cases) were notifi ed to WHO, and only
around 6000 of them were treated in programmes
approved by the Green Light Committee (a body that
aims to increase access to high-quality, low-cost, second-
Panel 1: The Stop TB Strategy
The Stop TB Strategy
Vision
A tuberculosis-free world
Goal
To substantially reduce the global burden of tuberculosis by 2015 in line with the MDGs
and the Stop TB Partnership targets
Objective
Achieve universal access to quality diagnosis and patient-centred treatment
Reduce the human and socioeconomic burden associated with tuberculosis
Protect vulnerable populations from tuberculosis, tuberculosis and HIV, and drug-
resistant tuberculosis
Support development of new methods and enable their timely and eff ective use
Protect and promote human rights in tuberculosis prevention, care, and control
Targets
MDG 6, target 8: halt and begin to reverse the incidence of tuberculosis by 2015
Targets linked to the MDGs and endorsed by Stop TB Partnership:
2015: reduce prevalence of and deaths due to tuberculosis by 50% relative to 1990
2050: eliminate tuberculosis as a public health problem (less than one case per
million population)
Components of the strategy and implementation approaches
Pursue high-quality DOTS expansion and enhancement
Secure political commitment, with adequate and sustained fi nancing
Ensure early case detection and diagnosis through quality-assured bacteriology
Provide standardised treatment with supervision, and patient support
• Ensure eff ective drug supply and management
Monitor and assess performance and eff ect
Address tuberculosis/HIV, MDR tuberculosis, and the needs of poor and vulnerable populations
Scale up collaborative tuberculosis/HIV activities
Scale up prevention and management of MDR tuberculosis
Address the needs of tuberculosis contacts and of poor and vulnerable populations
Contribute to health-system strengthening based on primary health care
Help to improve health policies, human resource development, fi nancing, supplies,
service delivery, and information
Strengthen infection control in health services, other congregate settings, and
households
Upgrade laboratory networks, and implement the practical approach to lung health
Adapt successful approaches from other areas and sectors, and foster action on the
social determinants of health
Engage all care providers
Involve all public, voluntary, corporate, and private providers through public-private
mix approaches
Promote use of the international standards for tuberculosis care
Empower people with tuberculosis and communities through partnership
Pursue advocacy, communication, and social mobilisation
Foster community participation in tuberculosis care, prevention, and health promotion
Promote use of the Patients’ Charter for Tuberculosis Care
Enable and promote research
Undertake programme-based operational research
Advocate for and participate in research to develop new diagnostics, drugs, and vaccines
MDG=Millennium Development Goal. DOTS=directly observed therapy, short course. MDR=multidrug resistant.
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Sources for TB burden estimates Progress towards epidemiological targets* Diagnosis and treatment within national TB programmes*
National
prevalence
survey
since
1990
(year)
In-depth
analysis of
routine
surveillance
data in past
3 years
Analysis of
vital
registration
data in past
3 years
Drug-
resistance
surveillance
(most
recent year)
Estimated
incidence,
all forms,
per
100 000,
2008†
Yearly
change in
estimated
incidence,
all forms,
1990–
2008 (%)‡
Estimated
preval-
ence in
2008 vs
1990
(%)§
Estimated
death rate
in 2008 vs
1990
(%)¶
MDR-TB
prevalence
in new
cases (year
of DRS, %)
Pop
living in
districts
with
DOTS,
2007
(%)
Notifi ed
under
NTP, of
estimated
new ss+
cases,
2008 (%)||
Yearly
change
1998–2008
in proportion
notifi ed in
NTP, new ss+
(%)**
NTP
treatment
success
rate, new
ss+, 2007
cohort
(%)††
Notifi ed
TB
patients
tested
for HIV,
2008
(%)
HIV-
positive
notifi ed
TB cases
receiving
ART,
2008 (%)
MDR-TB
cases
notifi ed/
estimated
number,
2008 (%)
Treated
under GLC/
estimated
MDR-TB
cases,
2008 (%)
Afghanistan N Y N N 190 0·0% 96% 100% ·· 97% 61% 21% 87% ·· ·· ·· 0·0%
Bangladesh 2008 Y N N 220 0·0% 75% 79% ·· 100% 61% 13% 92% ·· ·· ·· 1·1%
Brazil N Y Y 1996 46 –3·3% 30% 47% 0·9% 75% 75% 3·1% 72% 49% 91% 25% 0·0%
Burma N Y N 2007 400 0·0% 43% 57% 4·2% 95% 43% 21% 79% 3% 28% 5·4% 0·0%
Cambodia 2002 N N 2001 490 –1·0% 48% 60% 0·0% 100% 56% 8·0% 94% 54% 22% 1·4% 1·9%
China 1990,
2000
Y N 2007 97 –1·0% 34% 42% 5·7% 100% 72% 12% 87% 8% 20% ·· 0·0%
DR Congo N Y N 1999‡‡ 380 4·7% 240% 240% 5·8% 100% 66% 5·4% 84% 19% 20% 2·3% 2·6%
Ethiopia N Y N 2005 370 4·7% 960% 570% 1·6% 95% 32% 13% 91% 23% 44% 2·5% 0·0%
India N Y N 2006‡‡ 170 0·0% 54% 69% 2·8% 100% 70% 9·6% 87% 2% ·· 0·3% 0·0%
Indonesia 2004 Y N 2004‡‡ 190 0·0% 46% 56% 2·0% 100% 80% 17% 85% ·· ·· 4·8% 0·0%
Kenya N Y N 1995‡‡ 330 6·0% 99% 270% 0·0% 100% 68% 5·6% 94% 83% 30% 3·1% 0·8%
Mozambique N Y N 2006 420 4·7% 240% 440% 3·5% 100% 47% 5·9% 85% 81% 30% 5·1% 0·0%
Nigeria N Y N N 300 4·7% 190% 260% ·· 91% 24% 20% 82% 62% 45% 0·21% 0·0%
Pakistan N Y N N 230 0·0% 47% 54% ·· 99% 58% 22% 91% 3% 100% 0·26% 0·0%
Philippines 1997,
2007
N Y 2004 280 –1·8% 55% 170% 4·0% 100% 67% 5·5% 89% 1% ·· 7·2% 4·0%
Russia N Y Y 2006‡‡ 110 0·0% 30% 60% 13·0% 100% 73% 0·3% 58% 100% 23% 18% 4·0%
South Africa N Y Y 2002 960 6·4% 200% 590% 1·8% 100% 68% 0·97% 83% 39% 25% 48% 0·0%
Thailand N Y N 2006 140 0·0% 92% 100% 1·7% 100% 64% 16% 88% 96% 38% 12% 0·0%
Uganda N N N 1997 310 3·6% 270% 200% 0·5% 100% 54% 5·0% 75% 63% 19% 3·6% 0·0%
Tanzania N Y N 2007 190 –1·0% 41% 64% 1·1% 100% 70% 2·5% 92% 77% 30% 2% 0·0%
Vietnam 2007 Y N 2006 200 –0·1% 73% 81% 2·7% 100% 62% 2·9% 74% 11% 32% ·· 0·0%
Zimbabwe N Y N 1995‡‡ 760 4·7% 170% 230% 1·9% 100% 24% 6·0% 78% 9% 23% ·· 0·0%
TB=tuberculosis. MDR-TB=multidrug-resistant tuberculosis. DRS=drug-resistant surveillance. Pop=population. DOTS=directly observed therapy, short course. NTP=national tuberculosis programme. ss+=sputum-smear positive. ART=antiretroviral
treatment. GLC=Green Light Committee. N=no. Y=yes. DR=Democratic Republic.*Only best estimates are reported here. Ranges for several of these indicators are reported in WHO’s Global Tuberculosis Control Report.2 †Stop TB Partnership tuberculosis
elimination target: to reduce incidence to less than 0·1 case per 100 000 population and per year by 2050. ‡Incidence is assumed to follow a linear trend on the log scale during 1990–2008. Millennium Development Goal (MDG) 6, target 8, is to have
halted and begun to reverse the incidence of tuberculosis by 2015. §Expressed as the ratio of estimated prevalence in 2008 over 1990, as a percentage. MDG indicator 23a. The related Stop TB Partnership target is to halve prevalence in 2015 compared
with 1990.12 ¶Expressed as the ratio of estimated mortality (excluding HIV-positive individuals) in 2008 over 1990. MDG indicator 23b. The related Stop TB Partnership target is to halve death rate in 2015 compared with 1990.12 ||Also called the case
detection rate. MDG indicator 24a. The related Stop TB Partnership target set for 2005 was 70%.12 **The ratio of notifi ed over estimated incident cases is assumed to follow a linear trend on the log scale during 1990–2008. ††MDG indicator 24b. The
related Stop TB Partnership target set for 2005 was 85%.12 ‡‡Subnational. §§Countries that together have 80% of the estimated global number of tuberculosis cases.
Table 1: Epidemiological situation and tuberculosis programme implementation in 22 countries with high tuberculosis burden§§
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Free TB
diagnosis,
2009*
Sputum-
smear
microscopy
availability
≥1 per
100 000
pop, 2008†
CDS test
lab
availability
≥1 per
5 million
pop,
2008†
Free
rst-
line
drugs
in NTP,
2009
Free
second-
line
drugs in
NTP,
2009
Stock-
outs of
rst-line
drugs
peri-
pheral
level,
2008
Paediatric
formulation
available,
2009
NTP
expenditure
per head,
2010 (US$)
Government
health
expenditure
per head,
2006 (US$)‡
NTP
expenditure
of total
government
health
expenditure,
2010 (%)
NTP
funding
gap (%
of
budget)
Private
health
expenditure
of total
health
expenditure,
2006 (%)‡
Proportion
of listed
private
providers
engaged
by NTP,
2008 (%)
TB drugs
available in
private
pharmacies,
2009
TB drugs
available
without
prescription,
2009
TB is a
notifi able
disease by
law, 2009
Afghanistan N Y N Y N N N 0·36 9 4·0% 3% 68% 1% Y Y N
Bangladesh N N N Y Y N N 0·10 4 2·5% 1% 68% 20% Y Y Y
Brazil Y Y N Y Y N Y 0·27 204 0·1% 24% 52% NA§NN Y
Burma N N N Y Y N Y 0·08 1 8·1% 75% 87% 7% Y Y Y
Cambodia N Y N Y Y N Y 0·70 8 8·7% 36% 74% 23% N N N
China NN N Y Y N N 0·16 38 0·4% 13% 59% NA§YY Y
DR Congo Y Y N Y Y .. Y 0·23 2 11·7% 77% 81% 65% N N Y
Ethiopia N Y N Y .. N N 0·19 4 4·6% 50% 41% .. Y N N
India Y Y N Y Y N Y 0·08 7 1·2% 17% 75% 17%|| Y Y N
Indonesia N Y N Y Y N Y 0·22 20 1·1% 31% 50% 2% Y Y Y
Kenya N Y N Y Y N Y 0·34 14 2·4% 61% 52% ·· Y Y Y
Mozambique Y Y N Y Y N Y 0·67 11 6·1% 56% 29% ·· N N Y
Nigeria N N N Y N Y Y 0·17 10 1·7% 59% 70% ·· Y Y N
Pakistan Y N N Y N N Y 0·11 3 3·8% 69% 84% 6% Y Y N
Philippines N Y N Y Y Y Y 0·49 17 2·9% 0% 67% 13% Y Y Y
Russia Y Y Y Y Y Y Y 8·68 232 3·7% 2% 37% NA§YY Y
South Africa Y N Y Y Y N Y 7·30 160 4·6% 0% 62% 20% Y N Y
Thailand Y Y Y Y Y N Y 0·72 73 1·0% 6% 36% 19% Y N Y
Uganda Y Y N Y N N N 0·25 6 4·2% 67% 75% .. N N N
Tanzania N Y N Y Y N Y 0·48 13 3·7% 32% 42% 8%** N N Y
Vietnam N N N Y Y N N 0·14 15 0·9% 0% 68% 30% Y Y Y
Zimbabwe N N N Y .. Y Y 0·48 35 1·4% 35% 51% .. N N Y
TB=tuberculosis. pop=population. CDS=culture and drug susceptibility. lab=laboratory. NTP=national tuberculosis programme. N=no. Y=yes. NA=not appliable. DR=Democratic Republic. *Smear, radiography, and culture free for all people suspected of
tuberculosis, as needed. †Benchmark for population coverage of diagnostic facilities as defi ned in Global Plan to Stop TB, 2006–2015.12 ‡Data from World Health Statistics, 2009.16 §Not applicable. In these countries, private sector is small and/or not
involved in tuberculosis diagnosis or treatment. ¶Diagnostic smear microscopy and radiography are free if suspects present to a tuberculosis dispensary, but not in general hospitals or tuberculosis hospitals. Free culture in a few selected sites only.
||Refers to proportion of private doctors registered with the medical association. The proportion would be much lower if the denominator also included other types of private providers, but the number is unknown. **Refers to private hospitals only.
††Countries that together have 80% of the estimated global number of tuberculosis cases.
Table 2: Health-systems context in 22 countries with high tuberculosis burden††
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1819
line antituberculosis drugs for the treatment of MDR
tuberculosis among providers who comply with WHO’s
guidelines).1 16 of the 22 high-burden countries had no
cases of MDR tuberculosis treated in programmes
approved by the Green Light Committee in 2007, whereas
ve did not report any notifi ed MDR tuberculosis cases
(table 1). Further scale-up of programmatic management
of MDR tuberculosis is thus crucial, and is discussed by
Gandhi and colleagues in this Series.27
Tuberculosis and HIV collaboration
In 2008, HIV status was known for 22% of all notifi ed
cases of tuberculosis globally. However, the worldwide
total of about 357 000 HIV-positive patients with
tuberculosis who were identifi ed in 2008 represent only
25% of the estimated 1·4 million incident HIV-infected
tuberculosis cases. About 254 000 of them received co-
trimoxazole prophylaxis, and about 114 000 were enrolled
on antiretroviral treatment (ART). This proportion
represents only about a third of the targets for 2008 in the
Global Plan to Stop TB, 2006–2015.2,12 Screening for
tuberculosis in HIV-positive individuals more than
doubled from 0·6 million to 1·4 million people between
2007 and 2008, but still represents only 4% of the estimated
35 million people with HIV infection worldwide. Only
about 50 000 of those screened negative for active
tuberculosis were provided with isoniazid preventive
therapy in 2008.2 Thus, despite progress in the
implementation of tuberculosis and HIV interventions,
greatly increased collaboration between programmes and
services is needed for these diseases, and is discussed by
Harries and colleagues in this Series.28
Epidemiological eff ect
Estimated global tuberculosis prevalence and death have
decreased during most of the past decade (fi gure 2).
However, with the present rate of decline, the targets for
prevalence and death rate set for 2015 might not be met
globally, mainly because of the rapid increase in
prevalence and death rate in Africa during the 1990s,
which only recently reverted to a modest fall.2
The estimated number of incident cases in the world
increased from 9·3 million to 9·4 million between 2007
and 2008, and the number of deaths associated with
tuberculosis increased from 1·77 million to 1·82 million.2
These increases are the net eff ect of a growing world
population, off setting modest reductions in global
incidence and death rates per head. Global incidence
was estimated at 139 cases (range 131–148) per
100 000 popul ation in 2008, which had decreased from
143 cases (136–151) per 100 000 population in the apparent
peak year of 2004 (fi gure 2). Incidence seems to be falling
in all six WHO regions (fi gure 3) and in eight of nine
epidemio logical subregions (fi gure 4). If these trends are
sustained, the world as a whole and most regions are on
track to achieve the MDG target to begin to reverse the
trend in incidence. Even if that is the case, the estimated
global decline between 2004 and 2008 is very modest at
–0·7% per year, and will need to be substantially
accelerated to get even close to the elimination target
that is set for 2050.
Estimated trends in incidence vary widely between
regions (fi gures 3 and 4), and these trends are not clearly
correlated with trends in NTP performance indicators.
Eastern European and former Soviet Union countries had
an increase in incidence in the 1990s (fi gure 4).29 The
recent stabilisation of this trend is associated with
improved NTP performance, but other factors have
contributed, such as general socioeconomic improve-
ments.30 The rapid increase and subsequent stabilisation
and then decrease in incidence from 2004 in sub-Saharan
African countries (fi gures 3 and 4) is strongly correlated
with trends in HIV prevalence,5,31 whereas NTP
performance indicators have improved only marginally in
these countries since 2003.1,2
The eastern Mediterranean, southeast Asian, and
western Pacifi c WHO regions improved average NTP
performance substantially between the end of the 1990s
and 2008. Case detection rates increased (fi gure 1), and
treatment success rates were greater than 80% in the past
10 years. Yet, comparing 1995–99 and 2006–08, the rates
of decrease in incidence have remained stable at low
levels in these regions (fi gure 4).1 In the 22 high-burden
100
80
60
40
Year Year Year
20
0
Estimated case detection rate (%)
AFR
1996
1998
2000
2002
2004
2006
2008
AMR
1996
1998
2000
2002
2004
2006
2008
EMR
100
80
60
40
20
0
Estimated case detection rate (%)
EUR SEA WPR
1996
1998
2000
2002
2004
2006
2008
Figure 1: Estimated case detection rate (new smear-positive tuberculosis), by WHO region, 1995–2008
Vertical segments represent 95% Cls. The horizontal line shows the 70% target set for 2005. AFR=African region.
AMR=American region. EMR=eastern Mediterranean region. EUR=European region. SEA=southeast Asian region.
WPR=western Pacifi c region.
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countries, the estimated incidence decreased between
1990 and 2008 in only six countries, and only two had an
average yearly decrease of more than 1%.
Two studies32,33 suggest that changes in estimated
national tuberculosis incidence are more strongly
associated with changes in national socioeconomic indices
and the general health status of the population than with
NTP performance. Several examples of epidemiological
eff ect associated with DOTS implementation exist,
including in China,34 Cuba,35 parts of south India,36 Peru,37
Chile,38 and Uruguay.39 However, distinguishing the eff ects
of DOTS from those of social and economic improvements
has been diffi cult.33,40 Other countries—including
Vietnam,41 Morocco,42 Burma, some states in India, and
Sri Lanka43—have not yet had the expected eff ect despite
apparent long-term good programme performance. Many
of the high-burden countries that achieved substantial
improvements in programme performance over the past
10 years have recorded very modest decreases in estimated
incidence (table 1).
Expansion of the control model
The apparent modest eff ect on tuberculosis incidence
contrasts with mathematical modelling studies, suggesting
that detecting at least 70% of the incident cases of highly
infectious tuberculosis and curing at least 85% of them
would lead to a 5–10% reduction per year in incidence, and
that the rate of decline would be substantial also at lower
case detection rates.44–46 However, recent analyses suggest
that reaching these targets leads to a rapid decline in
incidence over a short period only.47,48 For sustained rapid
decline, both targets need to be exceeded, and combined
with additional interventions.40,47 In this section we discuss
how the present tuberculosis control model could be
further expanded to achieve the acceleration in tuberculosis
incidence decline that is needed to approach the elimination
target set for 2050.
Eff ective reduction of transmission
To cut transmission eff ectively, the duration of
infectiousness has to be kept to a minimum through
early diagnosis and treatment.49–51 There are no targets for
reduction of treatment delay, nor is delay routinely
measured and reported.1,50 However, much research has
shown that long treatment delays are a common problem,
which relate to insuffi cient knowledge about tuberculosis
in the population, stigma, poor access to health care,
missed diagnosis by health-care workers, and inadequate
diagnostic instruments.52 Addressing these factors is
essential to ensure early diagnosis and cure.
Findings from three population-based tuberculosis
prevalence surveys draw attention to additional
challenges for early case detection. In these surveys, in
which all participants were tested for tuberculosis
irrespective of symptoms, 47%, 57%, and 61% of those
with bacteriologically confi rmed pulmonary tuberculosis
did not report symptoms that corresponded to the
commonly used criteria (such as cough for more than
3 weeks) for suspecting disease and prompting
diagnostic investigation.53–55 Most were not previously
diagnosed, and thus constituted a large proportion of
untreated patients with infectious tuberculosis who
could be detected early only through more active
screening approaches than by screening for chronic
cough in people who actively seek health care.
Much attention has been given to smear-positive
tuberculosis, because it is the most infectious form of
this disease. However, the risk of transmission from
sputum-smear-negative cases is not negligible,56 and
smear-negative tuberculosis could become smear-positive
as the disease progresses. Early case detection of all types
of tuberculosis might further reduce transmission.
The rate of transmission is also determined by the
environment in which transmission takes place. Infection-
control measures aff ect the risk of transmission in
health-care facilities and congregate settings.57 Poverty,
urbanisation, crowded living conditions, increased
population density, and migration constitute societal forces
Rate per 100 000
Incidence (all forms, including HIV)A
Prevalence (all forms, including HIV)
B
Rate per 100 000
0
0
120
110
100
15
20
30
35
40
45
25
150
200
250
300
350
130
140
150
160
0
Mortality (excluding HIV)
C
Rate per 100 000
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
Year
2000
2001
2002
2003
2004
2005
2006
2007
2008
Figure 2: Estimated global rates of tuberculosis incidence (A), prevalence (B), and mortality (C), 1990–2008
Vertical segments represent 95% Cls.
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1821
that favour transmission, and changes in these factors can
have a substantial eff ect on tuberculosis trends.40,58,59
Reduction in the risk of progression from infection to
active disease
Preventive therapy with isoniazid is recommended by
WHO for people with HIV who are at risk of tuberculosis,
and for young children who have had contact with a person
with infectious disease.60 This intervention needs to be
urgently scaled up.1,28,60 Potentially, preventive therapy can
be expanded to additional risk groups, but further research
is needed to establish cost-eff ectiveness and feasibility,
especially in low-income and middle-income countries.
Modelling studies suggest that interventions to stop
progression from latent infection to active disease might
be of particular importance for future tuberculosis
control. If tuberculosis transmission can be eff ectively
reduced, the number of tuberculosis cases arising from
recent infections will be kept to a minimum, while an
increasing proportion of incident cases will be generated
from the huge number of people with latent tuberculosis
infection.47,61 The 2 billion individuals who are estimated
to be already latently infected will continue to generate
tuberculosis for decades, unless reactivation to active
disease can be prevented. Therefore, even with the most
optimistic scenario of a substantially reduced transmission
through full scale-up of early diagnosis and treatment,
the projected incidence in 2050 may still be 100 times
higher than the elimination target.47,62
A crucial question for global tuberculosis control is
therefore how immune competence can be improved
within populations. One approach would be to develop
improved medical technologies for prevention. For
example, the combination of a new highly eff ective pre-
exposure vaccine,63 combined with a more eff ective
preventive therapy,64 would potentially have a dramatic
eff ect on incidence.47 A highly eff ective vaccine63 after
exposure would in principle have the same eff ect as would
preventive treatment. Unfortunately, these methods are
not yet available, and the funding for innovative research
in this area is far behind what is needed.65
A second approach consists of preventive actions that
are aimed at reducing the prevalence of factors that
increase the risk of progression from infection to
disease. HIV is the most potent risk factor within
individuals,66 with a relative risk of more than 20.2 HIV
is an important factor within populations in countries
where HIV prevalence is moderate to high, such as
those in sub-Saharan Africa. Less potent but more
common risk factors might also have an important and
underappreciated role.62 Systematic reviews have shown
that undernutrition,67,68 smoking,69,70 diabetes,71–73 and
alcohol misuse74,75 are individual risk factors that can
double or triple the risk of development of active
tuberculosis (table 3). Indoor air pollution is a possible
causal factor, but the evidence base is still incomplete.70
Mathematical modelling studies have shown the
potential importance of these factors; fi ndings have
suggested that a large part of the tuberculosis burden in
India can be attributed to smoking (40%)82 and diabetes
(15%),83 and that gradual reductions in the prevalence of
smoking and exposure to indoor air pollution in China
could reduce incidence by an additional 14–52% by
2033, which is in excess of the expected eff ect of
sustained good NTP performance.84
A wide range of comparatively uncommon medical
disorders (eg, silicosis, malignant diseases, and chronic
systemic illnesses), and immunosuppressive treatments,
are established risk factors for tuberculosis.59,85 These risk
factors have important implications for individuals, but
are of less public health relevance. Furthermore, a set of
common factors, such as chronic helminth infections,
depression or mental illness, pregnancy and the post-
partum period, and outdoor air pollution have been
postulated as risk factors for tuberculosis, but very little
research has been done to test these hypotheses.
Table 3 shows the estimated relative risk, prevalence,
and corresponding population attributable fractions of
selected risk factors for tuberculosis in high-burden
countries. Table 3 includes only factors that are common,
can be changed, have a strong or growing evidence base
for a causal relation with tuberculosis, and for which there
are quantitative data for the strength of the association. In
400
300
200
Year
100
0
10
20
30
40
50
60
70
0
0
50
100
150
200
250
0
50
100
150
Rate per 100
000 populationRate per 100
000 population
AFR
1990 1995 2000 2005
AMR EMR
0
50
100
150
Year
1990 1995 2000 2005
Year
1990 1995 2000 2005
50
60
40
30
20
10
0
EUR SEA WPR
Tuberculosis incidence
Notification rates
Figure 3: Estimates of tuberculosis incidence (all forms) and notifi cation rates, by WHO region, 1990–2008
Vertical segments represent 95% Cls. Accidents in notifi cation time series are generally the result of errors and
inconsistencies in reporting from national tuberculosis programmes. AFR=African region. AMR=American region.
EMR=eastern Mediterranean region. EUR=European region. SEA=southeast Asian region. WPR=western Pacifi c region.
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the high-burden countries, undernutrition and smoking
seem to contribute the highest proportion of cases, but the
variation in relative importance of diff erent risk factors is
large across countries. Indoor air pollution has a high
population attributable fraction, but a causal relation is
not yet proven. HIV, alcohol misuse, and diabetes are
important factors, especially in adults. In most African
high-burden countries, HIV is a leading attributable factor.
Alcohol misuse and diabetes are predicted to increase in
low-income and middle-income countries and might be
crucial factors in coming decades.73,86
Genetic factors are also important determinants of host
defence. Natural selection might be part of the explanation
of a decrease in tuberculosis burden in industrialised
countries.87 Furthermore, some populations in present
high-burden countries might have, on average, weaker
host defences because of genetic predisposition,
possibly linked to shorter history of exposure to
Mycobacterium tuberculosis. Age and sex are strong
determinants, with highest risks in elderly people, those
who are very young, and in men older than 20 years.59
Although not possible to change, increased understanding
of genetic and age-related factors is important to develop
case detection strategies, to interpret and predict future
tuberculosis trends,47,61 and to advance the basic knowledge
of immunity against this disease that is needed for the
development of improved vaccines and treatments.
The way forward: action on four fronts
Continued scale-up of early diagnosis and treatment in
line with the Stop TB Strategy
Countries should aim to diagnose and treat successfully
as close as possible to 100% of all estimated tuberculosis
cases—ie, all forms of the disease and all age-groups.
Most high-burden countries have far to go to close the
case detection gap. In 2008, 39% of all estimated new
cases and 97% of the estimated incident cases of MDR
tuberculosis were not detected by NTPs,2 and many were
detected after long delays.52
Some of the missing cases are already being managed,
but not notifi ed. Many people with tuberculosis seek and
receive care in the private sector and in public facilities
that are not linked to NTPs.21 These providers, who rarely
follow the International Standards for Tuberculosis Care
(ISTC)88 or notify cases to health authorities, should be
actively encouraged to collaborate with NTPs through
public-private mix approaches.89
Others access health services, but are not diagnosed.
The WHO recommendation to test all individuals with
chronic cough (2–3 weeks) who seek health care60 is not
followed consistently throughout the health-care system.26
Improvement of basic laboratory and radiography
services is the fi rst essential step.60 Actively asking all
patients about chronic cough, particularly those at
increased risk for tuberculosis, can yield additional
cases.90,91 Further more, use of a duration of cough shorter
than 3 weeks as a cutoff point for active tuberculosis
investigations increases yield.92 Cough screening can be
strengthened through the practical approach to lung
health, which promotes screening for tuberculosis in all
patients with respiratory diseases.93,94 Screening of all
people with HIV for tuberculosis yields a substantial
number of additional tuberculosis cases.1 Active screening
in health facilities of other high-risk groups—such as
people aff ected by diabetes,95 smoking-related diseases,69
alcohol misuse,75 and undernutrition67—could further
increase the yield, but more research is needed to
examine feasibility and cost-eff ectiveness.
To help with increased detection, the defi nition of
smear-positive tuberculosis has been changed, such that
one positive sputum smear of two is suffi cient for the
diagnosis of smear-positive tuberculosis.96 The two
smears can be done on the same day to simplify diagnosis
for the patient and to reduce costs.97 To simplify the
15
10
5
0
–5
6
4
2
–2
0
–4
0
–5
–10
–20
–15
–25
–100
–50
0
Rate of change in incidence per year (%) Rate of change in incidence per year (%)Rate of change in incidence per year (%)
Africa: high HIV burden Africa: low HIV burden Central Europe
5
10
0
–5
–10
Eastern Europe High-income countries Eastern Mediterranean
Year
–6
–4
–2
–1
0
1995–99 2006–08
–7
–5
–3
–100
–50
0
Year
1995–99 2006–08
Year
1995–99 2006–08
5
0
–5
–10
Latin America Southeast Asia Western Pacific
5
10
0
–5
–10
Figure 4: Rates of change in estimated tuberculosis incidence during 1995–99 and 2006–08, in nine
epidemiological subregions
The open red diamonds denote group mean rates of change.
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1823
diagnostic algorithm for sputum-smear-negative cases,
diagnosis based on initial radiography has been
recommended for people with HIV.98
The sensitivity of conventional sputum-smear micro-
scopy is low,99 but can be improved through various
sputum processing techniques, fl uorescent microscopy,
and new techniques such as light-emitting-diode (LED)
uorescent microscopy.100 Replacement of solid with
liquid cultures increases sensitivity and reduces delay.45
New diagnostics are available or under development, but
most need to be further assessed and fi eld tested.101 A
rapid and simple point-of-care test would improve early
case detection substantially.100 These approaches do not
help people who do not access health services. The
poorest and most vulnerable groups are well known to
face the largest access barriers,8,40 and in many settings
this includes women because of disempower ment,
stigma, and few fi nancial resources.102,103 These problems
need specifi c actions to improve access for poor people.104
Health-care seeking behaviour can also be improved
through engagement of various partners, including
community organisations, in awareness campaigns.105
Active case fi nding outside health facilities might also be
warranted. Since contacts of cases are at substantially
increased risk of contracting tuberculosis,106 contact
investigation is a logical fi rst step. A systematic review of
the eff ects of investigations in tuberculosis contacts in low-
income and middle-income countries showed that 4·5% of
HIV* Undernutrition† Diabetes‡ Alcohol misuse§ Smoking¶ Indoor air
pollution||
P >15 y
(%)
PAF
>15 y
(%)
PAF
total
pop (%)
P total
pop (%)
PAF total
pop (%)
P >15 y
(%)
PAF
>15 y
(%)
PAF
total
pop (%)
P >15 y
(%)
PAF
>15 y
(%)
PAF
total
pop (%)
P >15 y
(%)
PAF
>15 y
(%)
PAF total
pop
(%)
P total
pop (%)
PAF
total
pop (%)
Afghanistan 0·1% 2·5% 1·5% 23·0% 33·6% 6·6% 12·2% 6·8% 0·1% 0·2% 0·1% 21·0% 17·4% 10·0% 95·0% 27·5%
Bangladesh 0·1% 2·5% 0·2% 27·0% 37·3% 3·5% 6·8% 4·6% 0·9% 1·7% 1·1% 26·0% 20·6% 14·5% 88·0% 26·0%
Brazil 0·6% 13·4% 8·9% 6·0% 11·7% 6·0% 11·2% 8·3% 11·1% 17·4% 13·2% 16·0% 13·8% 10·3% 12·0% 4·6%
Burma 0·7% 15·2% 11·2% 19·0% 29·5% 2·8% 5·6% 4·1% 1·2% 2·2% 1·6% 29·0% 22·5% 17·5% 95·0% 27·5%
Cambodia 0·8% 17·0% 11·8% 26·0% 36·4% 3·5% 6·8% 4·4% 4·1% 7·2% 4·7% 28·0% 21·9% 15·0% 95·0% 27·5%
China 0·1% 2·5% 1·3% 9·0% 16·5% 4·5% 8·6% 6·9% 8·3% 13·6% 11·1% 34·5% 25·7% 21·4% 80·0% 24·2%
DR Congo 1·4% 20·9% 12·3% 76·0% 62·6% 2·6% 5·2% 2·8% 5·3% 9·1% 5·1% 8·0% 7·4% 4·1% 95·0% 27·5%
Ethiopia 2·1% 29·2% 18·8% 46·0% 50·3% 2·0% 4·0% 2·3% 5·3% 9·1% 5·3% 5·0% 4·8% 2·7% 95·0% 27·5%
India 0·3% 7·2% 5·0% 21·0% 31·6% 7·1% 13·0% 9·1% 5·8% 9·9% 6·9% 19·0% 16·0% 11·3% 74·0% 22·8%
Indonesia 0·2% 4·9% 2·9% 17·0% 27·2% 4·6% 8·8% 6·5% 1·2% 2·2% 1·6% 34·0% 25·4% 19·7% 72·0% 22·4%
Kenya 8·6% 62·8% 47·7% 32·0% 41·3% 2·8% 5·6% 3·2% 5·3% 9·1% 5·4% 14·0% 12·3% 7·4% 81·0% 24·5%
Mozambique 12·5% 71·0% 57·9% 38·0% 45·5% 3·3% 6·5% 3·7% 5·3% 9·1% 5·3% 12·0% 10·7% 6·3% 80·0% 24·2%
Nigeria 3·9% 43·3% 25·6% 9·0% 16·5% 3·5% 6·8% 4·0% 26·1% 33·2% 21·7% 7·0% 6·5% 3·8% 67·0% 21·1%
Pakistan 0·1% 2·5% 1·5% 23·0% 33·6% 7·6% 13·8% 9·3% 0·1% 0·2% 0·2% 21·0% 17·4% 11·8% 72·0% 22·4%
Philippines 0·1% 2·5% 0·2% 16·0% 26·0% 6·7% 12·3% 8·3% 4·1% 7·2% 4·7% 33·0% 24·8% 17·4% 47·0% 15·8%
Russia 1·1% 17·7% 11·4% 3·0% 6·2% 9·0% 15·9% 13·8% 33·3% 38·8% 35·0% 49·0% 32·9% 29·4% 7·0% 2·7%
South Africa 18·1% 78·0% 69·7% 2·5% 5·2% 4·5% 8·6% 6·0% 15·2% 22·4% 16·4% 19·0% 16·0% 11·4% 18·0% 6·7%
Thailand 1·4% 21·5% 15·8% 17·0% 27·2% 7·7% 13·9% 11·3% 18·6% 26·1% 21·8% 23·0% 18·7% 15·4% 72·0% 22·4%
Uganda 5·4% 51·4% 37·4% 15·0% 24·8% 1·7% 3·4% 1·8% 5·3% 9·1% 4·9% 12·0% 10·7% 5·8% 95·0% 27·5%
Tanzania 6·2% 54·9% 40·4% 35·0% 43·5% 2·6% 5·2% 3·0% 5·3% 9·1% 5·3% 14·0% 12·3% 7·3% 95·0% 27·5%
Vietnam 0·5% 11·4% 7·9% 14·0% 23·5% 2·9% 5·7% 4·1% 4·1% 7·2% 5·2% 23·0% 18·7% 14·0% 70·0% 21·9%
Zimbabwe 15·3% 75·0% 65·6% 40·0% 46·8% 4·1% 7·9% 5·0% 5·3% 9·1% 5·8% 19·0% 16·0% 10·4% 73·0% 22·6%
Weighted
average
0·8% 16·0% 11·0% 16·7% 26·9% 5·4% 10·2% 7·5% 8·1% 13·4% 9·8% 26·5% 20·9% 15·8% 71·2% 22·2%
Point estimate of relative risk was used. When prevalence was available only for adults, the prevalence in adults was adjusted for proportion of population younger than 15 years to estimate the total population PAF.
PAF estimates presented here do not account for interaction between risk factors, nor for prevention of secondary cases. Uncertainty limits for PAF (not shown) are large, since they are determined by the confi dence
limits for the relative risk estimate, as well as the confi dence limits for prevalence estimates. P=prevalence. y=years. PAF=population attributable fraction, which is equal to [prevalence×(relative risk–1)]/
[prevalence×(relative risk–1)+1]. pop=population. DR=Democratic Republic. *HIV: relative risk=26·7, 95% CI 20–35. Point estimate is for low HIV prevalence settings (0·1–1%), lower bound is for high HIV prevalence
setting (>1%), and upper bound is for very low HIV prevalence settings (<0·1%). Relative risk estimates are from WHO, 2009.1,2 Diff erent estimates have been applied according to HIV prevalence in respective country.
Prevalence data are from UNAIDS, 2008.76 †Undernutrition: relative risk=3·2, 95% CI 3·1–3·3 for body-mass index 16 kg/m² versus 25 kg/m², based on average reduction in tuberculosis incidence of 13·8% (95% CI
13·4–14·2) per unit increase in body-mass index, as reported in a meta-analysis by Lönnroth and colleagues.68 Prevalence data are from prevalence of undernourishment as reported in: The State of Food Insecurity in the
World 2008.77 ‡Diabetes: relative risk=3·1, 95% CI 2·3–4·3. Point estimate and 95% CI are from pooled estimate in meta-analysis by Jeon and Murray (2008).72 Prevalence data are from IDF, 2010.78 §Alcohol misuse:
relative risk=2·9, 95% CI 1·9–4·6. Point estimate and 95% CI are from pooled estimate in meta-analysis by Lönnroth and colleagues (2008).74 Prevalence data are from average of prevalence of heavy drinking in men and
women (>40 g alcohol per day for men and >20 g per day for women). China, Brazil, India, Nigeria, Pakistan, Russia, South Africa, and Thailand data from Rehm and colleagues.75 Other data are based on regional estimates
reported in WHO, 2004.79 ¶Smoking: relative risk=2·0, 95% CI 1·6–2·5. Point estimate and 95% CI are from pooled estimate comparing risk of pulmonary tuberculosis in current versus never smokers, in meta-analysis by
Lin and colleagues (2007).70 Prevalence data are from WHO, 2008.80 ||Indoor air pollution: relative risk=1·4, 95% CI 0·6–3·4. Point estimate and 95% CI from pooled estimate comparing risk of pulmonary tuberculosis in
studies controlling for smoking, in meta-analysis by Lin and colleagues (2007).70 Prevalence data are from WHO, 2006.81
Table 3: Prevalence and population attributable fractions of selected tuberculosis risk factors, in 22 high-burden countries
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identifi ed household contacts had active tuberculosis at the
time of screening, and additional contacts subsequently
developed disease.107 Mass radiography screening was
historically a standard element of control programmes in
industrialised countries,108 but was later strongly dis-
couraged because of low cost-eff ectiveness.109,110 None-
theless, several alternatives to mass screening are available,
which are more targeted and potentially more cost eff ective,
although rigorous analysis is still necessary. These options
include screening of subpopulations with a particularly
high risk of exposure, such as health-care workers,111
prisoners,112 drug addicts,113 homeless people,114 slum
dwellers, refugees, migrants, displaced populations,115 or
other high-risk groups.116
Strategies to improve treatment outcomes should be
tailored to local situations, but ensuring that internationally
recommended treatment regimens and quality-assured
drug formulations are being consistently used is
essential,117 and avoiding drug stockouts is crucial. Drug
management in NTPs has improved over the past two
decades, but improvements can still be made. In 2008,
four of the 22 high-burden countries had drug stockouts.
Poor treatment adherence should be addressed through
patient-friendly service delivery models and intensifi ed
patient support that addresses social and economic factors
hindering treatment adherence,8,104,118 while respecting
human rights and ethical principles.119 When case fatality
is high, common causes need to be identifi ed and
addressed, including the possible eff ect of comorbidities.
In the absence of ART, HIV increases the risk of death
during tuberculosis treatment.120 Both diabetes and
smoking have been associated with increased tuberculosis
case fatality, but the eff ect on mortality, failure, and
relapse of these and other risk factors needs further
study.67,69,73,75 High rates of treatment failure should trigger
careful assessment of treatment adherence and drug-
resistance patterns.
Development and enforcement of bold health-system
policies
An important reason for slow scale-up of quality
tuberculosis diagnosis and treatment is that most NTPs
operate within weak and underfunded health systems
with generally poor infrastructure, an insuffi cient
workforce, limited capacity to enforce policies, and poor
governance functions.18,121,122
Funding for tuberculosis control in high-burden
countries more than doubled between 2002 and 2009
(fi gure 5).2 Nevertheless, large funding gaps remain. The
funding shortfall expected in these countries in 2010 is
US$0·5 billion, and in all countries the defi cit in 2010
compared with the Global Plan to Stop TB is $2·1 billion.2,12
Many countries are struggling to sustain basic diagnostic
and treatment services. At the same time, they are trying
to scale up management of MDR tuberculosis and
collaborative tuberculosis and HIV activities, and to
introduce new methods and strategies that increase
complexity and cost. Therefore, despite increased
resources, the gap between what is needed and what can
be funded with available resources is increasing. Eight of
the high-burden countries had funding gaps of more
than 50% of the required NTP budget in 2009 (table 2).
Although most high-burden countries have managed to
increase national funding for tuberculosis control over
recent years, many still rely heavily on international
support.2 With government health expenditure of $20 per
head or less in 16 of the 22 countries, and on average
3·6% of government health expenditure used for NTPs
(table 2), this fi nding is not surprising. International
funding for tuberculosis control has increased over the
past decade, especially from the Global Fund to Fight
AIDS, Tuberculosis and Malaria (fi gure 5),1,2 which
contributed more than 60% of the external funding for
tuberculosis control and provided treatment for 6 million
people with this disease up to 2009.123 However, the
increasing acknowledgment of huge unmet needs in
other health areas, combined with a global fi nancial
crisis, means that competition for scarce resources has
intensifi ed both nationally and internationally. This risks
increased inequality, with the poorest and most aff ected
people having potentially reduced access to preventive
and treatment services, especially in areas in which social
protection mechanisms are weak or non-existent.124
Within existing constraints, NTPs try to provide services
that are free of charge or highly subsidised, with mixed
success. Although NTPs in most high-burden countries
provide free sputum-smear microscopy for all patients
with suspected pulmonary tuberculosis, only nine of 22 also
provide other diagnostic tests free of charge (table 2). Most
US$ millions
Year
2002 2003 2004
1491
2005 2006
1612
1842
2159
2345 2415
2637
2007 2008 2009 2010
1500
1000
500
0
3000
2500
2000
Unknown*
Global Fund to Fight AIDS, Tuberculosis and Malaria
Grants (excluding Global Fund)
Loans
Government, general health-care services (excluding loans)
Government, NTP budget (excluding loans)
1151 1241
Figure 5: Funding for tuberculosis control by source of funding in
22 high-burden countries, 2002–10
NTP=national treatment programme. *Unknown source applies only to a
proportion of the budget for multidrug-resistant tuberculosis hospitals in
South Africa.
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1825
high-burden countries charge for radiography, culture, and
drug-susceptibility testing (DST). Suffi cient coverage of
sputum-smear microscopy (≥one per 100 000 population)
has been achieved in 14 of these countries, but the
benchmark coverage (≥one per 5 million population) for
culture and DST has been reached in only three (table 2).
These defi ciencies are an indicator of generally weak
laboratory diagnostic services.
All high-burden countries report provision of free fi rst-
line tuberculosis drugs within NTPs (table 2). Second-line
drugs for patients with MDR tuberculosis treated by the
NTP are also, in principle, free of charge in most of these
countries. However, since programmatic management of
MDR tuberculosis has so far been implemented on a
small scale, a very small proportion of patients have access
to the drugs (table 2). Furthermore, NTPs in six high-
burden countries have no paediatric formulations
(table 2). Many patients purchase drugs in private
pharmacies. Tuberculosis drugs can be bought in private
pharmacies in 15 high-burden countries, and without a
prescription in 12 of them (table 2), creating the conditions
for uncontrolled and irrational use of drugs,125 which are
seldom produced by manufacturers that have been
prequalifi ed or quality assured.126 It is estimated that half
of the market for fi rst-line drugs is in the private sector
and that the private sector dominates the market for
second-line drugs.127 Irrational and expensive drug use in
the private sector contributes to the development of drug
resistance and to huge expenditure for patients.21
This situation stems from a wider health-system
challenge, in which the gap created by small amounts of
government investment in health is fi lled with largely
unregulated private care. In high-burden countries, on
average 60% of overall health expenditure is in the
private sector; the fi gure is 50% or more in 17 of these
countries (table 2), and much of this amount is out-of-
pocket expenditure by patients. In many countries,
especially in Asia, the private sector is the dominant
health provider, and the fi rst port of call for most people
with tuberculosis. The quality of diagnostic and
treatment services is often substandard. Diagnostic
algorithms and drug regimens are not in line with
international standards, tuberculosis drugs are often
sold over the counter, patient support and supervision
mechanisms are often absent, and treatment success
rates are consequently low.21 Active engagement of the
private sector and promotion of care in line with the
ISTC (including free, quality-assured drugs) can improve
quality of care, achieve high cure rates, and substantially
reduce costs to patients.89 Even so, most high-burden
countries have not actively and systematically engaged
private providers (table 2). An underlying diffi culty is
weak regulatory framework for private health care,
rendering NTPs powerless to impose standards on
providers who are unwilling to collaborate. The necessary
solution will have to include strengthened government
stewardship of the private sector.128
Tuberculosis is associated with a wide range of
comorbidities. Globally, about 15% of people with this
disease are infected with HIV.2 From the data in table 3 we
can deduce that about 50% of patients with tuberculosis in
high-burden countries are undernourished; in adults,
about 50% are smokers, about 20% misuse alcohol, and
about 15% have diabetes, with much higher numbers in
some countries than in others. Services for these diseases
are often underdeveloped in low-income and middle-
income countries and, as a result, they are often not
diagnosed.95 Meeting the medical-care needs of patients
with tuberculosis therefore requires access to basic primary
health-care services, beyond good tuberculosis care. Within
national health plans, NTPs should strengthen
collaboration with other public health programmes to
contribute to the prevention, treatment, and management
of these conditions. Frameworks for such work are already
well established for HIV, and are being developed for
smoking-related diseases.129
Finally, the challenge of inadequate information about
tuberculosis morbidity and mortality needs to be
addressed in the context of broad eff orts to tackle general
defi ciencies in health-information systems. Experience
in China has shown how improvements in the general
disease-notifi cation system, combined with increased
public health funding and regulatory interventions,
improved both the quality of tuberculosis statistics and
programme performance.130
Establishment of links with the broader development
agenda
The positive eff ects of improved living conditions and
nutritional status in industrialised countries over the past
century,131 the negative eff ects of the economic downturn in
countries of eastern Europe and the former Soviet Union
in the 1990s,29,30 and the clear association between broad
development indicators and tuberculosis incidence trends
in the past century and in recent years32,33,40 are examples of
how socioeconomic factors can aff ect tuberculosis
epidemics. Most of the proximate risk factors for
tuberculosis are associated with social conditions. People
from low socioeconomic status groups typically have more
frequent contact with people with active disease, a higher
likelihood of crowded living and working conditions,
greater food insecurity, lower levels of health awareness or
less power to act on existing knowledge concerning healthy
behaviour, and less access to quality health care than do
those from high socioeconomic groups.40 Malnutrition,
crowding, and exposure to indoor air pollution are direct
markers of poverty. The prevalence of smoking is
consistently highest in low socioeconomic groups in all
regions worldwide. For HIV, alcohol misuse, and diabetes,
the trend is not straightforward, but in middle-income and
high-income countries these factors are more prevalent in
low socioeconomic groups.132
Improved wealth, education, and social protection would
greatly benefi t tuberculosis control.133 However, some
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aspects of economic development might have a negative
eff ect. Rapid industrialisation, urbanisation, and migra-
tion—dominant occurrences in most developing
countries—can create ideal conditions for tuberculosis
epidemics to fl ourish, unless accompanied by good urban
planning, social reforms, environmental protection, and a
strong and well coordinated health system. The incidence
in urban areas is generally higher than in rural areas,134
possibly because of a combination of high population
density and lifestyle changes associated with urban living.
Exposure to some tuberculosis risk factors such as smoking,
alcohol misuse, and unhealthy diet can increase when
absolute poverty falls at the same time as rapid sociocultural
transition leads to changed patterns in health behaviour.135
What clearly emerges is a need for both public health
interventions to tackle specifi c tuberculosis risk factors,
and high-level political decisions to reduce poverty and
promote social protection, education, and empowerment.
The more upstream the intervention is implemented, the
more widespread the eff ect for public health. Tuberculosis
shares many social determinants with other key public
health conditions, including the diseases that are direct
risk factors for tuberculosis.132 The Commission on Social
Determinants of Health developed frameworks for action
to address a wide range of social determinants.136 Although
the main responsibility to pursue health in all policies rests
with the ministry of health and other ministries, the NTP
and its international technical partners should lend support
to the implementation of these frameworks, both through
advocacy and by helping to address the social conditions of
patients and their families.
First and foremost this approach entails ensuring that
the costs of care for patients are kept to a minimum to
minimise risk of further impoverishment (panel 2). The
combined direct and indirect costs to patients during
tuberculosis treatment in NTPs can range from
$50 to $300, even when tuberculosis tests and drugs are
provided free of charge.8 Costs before treatment, for
seeking care, are often even greater, and the total cost
often constitutes more than 50% of the yearly income of
patients with tuberculosis in developing countries. Out-
of-pocket expenditure can be substantially reduced
through elimination of user fees (eg, link to universal
health coverage and the establishment of social
insurance schemes), decentralisation of services, and
community-based care.8,137,138 Additionally, NTPs can
provide support in the form of travel vouchers, food
packages, conditional cash transfers, microcredit
schemes, and vocational training, while advocating to
employers and trade unions to protect the rights of
workers aff ected by tuberculosis.
Political commitment—the fi rst element of the Stop TB
Strategy—should not only include commitment from
governments to invest in and support tuberculosis
diagnosis and treatment programmes, but also recognition
by all political contributors, including civil society and
health activists, that this disease is an expression of a
development crisis that will be ultimately addressed by
removal of the upstream drivers of the epidemic.
Promotion and intensifi cation of research
An intensive eff ort is needed to develop new medical
technologies for prevention, diagnosis, and treatment.101,139,140
Further basic epidemiological research will be needed into
risk factors and social determinants. Eff ectiveness and
cost-eff ectiveness of new strategies for improved early
case detection, treatment, and prevention need to be
assessed. Operational research into how to rapidly transfer,
introduce, and adapt new methods and strategies to local
contexts is also needed. Finally, the data and methods used
to assess tuberculosis burden and trends need to be
further improved.25 Tuberculosis research investments
have increased in recent years, but from very low amounts.
The present investments of about $0·5 billion per year are
insuffi cient to accelerate research that is needed to pursue
tuberculosis elimination.141
Conclusions
Proper tuberculosis care and control averted up to
6 million deaths and cured 36 million people between
1995 and 2008. However, this disease is still causing
considerable burden and loss of productivity. Much
intensifi ed action is needed to control and ultimately
eliminate the disease. Every country should now focus
Panel 2: Possible strategies to reduce costs for patients
with tuberculosis and their families
Provision of all tuberculosis services free of charge
• Sputum-smear microscopy
Culture, radiography, and other tests
Drugs (including second-line drugs)
Consultation and registration fees
Reduction of diagnostic delay and health-care spending
• Decentralise diagnosis
Improve referral routines
Address access barriers
Reduce stigma and discrimination
Further treatment decentralisation and patient
supportive care
• Community-based treatment
Engage all care providers
Introduction of enabling supportive packages
Travel vouchers, cash transfer
• Food support
Promotion of continued work, compensation for lost
earnings, and social welfare support
• Health education
Livelihood support, vocational training
Dialogues with employers and sickness insurance systems
Enrolment in appropriate social welfare programmes
Series
www.thelancet.com Vol 375 May 22, 2010
1827
action in the four areas of continued scale-up of early
diagnosis and proper treatment, development and
enforcement of bold health-system policies, establish-
ment of links with the broad development agenda, and
promotion and intensifi cation of research eff orts.
Monitoring of key indicators, such as those presented in
tables 1 and 2, and continuous assessment of determinants,
such as those listed in table 3, will prove crucial for the
understanding of the challenges, needs, and the progress
towards achievement of the global targets.
Contributors
KL did the initial literature search, undertook the survey of tuberculosis
control policies and health-systems context, did the analysis of
population attributable fractions, wrote the fi rst draft of the report, and
coordinated its completion. KGC, JMC, and LSC undertook additional
literature searches, and contributed to signifi cant parts of the text. KF
and PG coordinated the data collection, did the analysis, and produced
the graphs of tuberculosis epidemiology and tuberculosis programme
performance and funding. MCR conceptualised the paper, wrote parts of
it, revised regularly, and guided its development and completion,
including that of the tables. All authors reviewed drafts of the paper and
approved the fi nal report.
Steering committee
This article is part of The Lancet Series on tuberculosis, which was
developed and coordinated by Alimuddin Zumla (University College
London Medical School, London, UK); Mario C Raviglione (Stop TB
Department, WHO, Geneva, Switzerland); and Ben Marais
(University of Stellenbosch, Stellenbosch, South Africa).
Confl icts of interest
We declare that we have no confl icts of interest.
Acknowledgments
No external funding was provided for this research. KL, KF, PG, and
MCR are staff members of WHO. The authors alone are responsible for
the views expressed in this publication and they do not necessarily
represent the decisions or policies of WHO.
References
1 WHO. Global tuberculosis control 2009. WHO/HTM/TB/2009.411.
Geneva: World Health Organization, 2009.
2 WHO. Global tuberculosis control—a short update to the 2009 report.
WHO/HTM/TB/2009.426. Geneva: World Health Organization, 2009.
3 Wright A, Zignol M, Van Deun A, et al, for the Global Project on
Anti-Tuberculosis Drug Resistance Surveillance. Epidemiology of
antituberculosis drug resistance 2002–07: an updated analysis of the
Global Project on Anti-Tuberculosis Drug Resistance Surveillance.
Lancet 2009; 373: 1861–73.
4 Cheng MH. Ministerial meeting agrees plan for tuberculosis
control. Lancet 2009; 373: 1328.
5 Corbett EL, Watt CJ, Walker N, et al. The growing burden of
tuberculosis: global trends and interactions with the HIV epidemic.
Arch Int Med 2003; 163: 1009–21.
6 Lopez AD, Mathers CD, Ezzati M, Murray CJL, Jamison DT. Global
burden of disease and risk factors. New York: Oxford University
Press and The World Bank, 2006.
7 Miller TL, McNabb SJN, Hilsenrath P, et al. Personal and societal
health quality lost to tuberculosis. PLoS One 2009; 4 :e5080.
8 Hanson C, Floyd K, Weil D. Tuberculosis in the poverty alleviation
agenda. In: Raviglione M, ed. TB: a comprehensive international
approach. New York: Informa Healthcare, 2006: 1097–114.
9 Jamison DT, Breman JG, Measham AR, et al, eds. Disease control
priorities in developing countries, 2nd edn. New York: Oxford
University Press and The World Bank, 2006.
10 Laxminarayan R, Klein EY, Darley S, Adeyi O. Global investments
in TB control: Economic benefi ts. Health Aff 2009; 28: w730–42.
11 Raviglione MC, Uplekar M. WHO’s new Stop TB Strategy. Lancet
2006; 367: 952–55.
12 Stop TB Partnership. The global plan to stop TB 2006–2015. WHO/
HTM/STB/2006.35. Geneva: World Health Organization, 2006.
13 Maher D, Dye C, Floyd K, et al. Planning to improve global health:
the next decade of tuberculosis control. Bull World Health Organ
2007; 85: 341–47.
14 Dye C, Maher D, Weil D, Espinal M, Raviglione M. Targets for
global tuberculosis control. Int J Tuberc Lung Dis 2006; 10: 460–62.
15 WHO. Revised TB recording and reporting forms and registers—
version 2006. WHO/HTM/TB/2006.373. Geneva: World Health
Organization, 2006.
16 WHO. World health statistics 2009. Geneva: World Health
Organization, 2009.
17 Murray CJL, Lopez AD, Wibulpolprasert S. Monitoring global
health: time for new solutions. BMJ 2004: 329: 1096–100.
18 Dye C, Raviglione M. Monitoring global health: WHO has mandate
and expertise. BMJ 2004; 330: 195.
19 Atun R, Weil DEC, Tan Eang M, Mwakyusa D. Health-system
strengthening and tuberculosis control. Lancet 2010; published
online May 19. DOI:10.1016/S0140-6736(10)60493-X.
20 Obermeyer Z, Abbott-Klafter J, Murray CJL. Has the DOTS strategy
improved case fi nding or treatment success? An empirical
assessment. PLoS ONE 2008; 3: e1721.
21 Uplekar M, Pathania V, Raviglione M. Private practitioners and public
health: weak links in tuberculosis control. Lancet 2001; 358: 912–16.
22 van Leth F, van der Werf MJ, Borgdorff MW. Prevalence of
tuberculous infection and incidence of tuberculosis: a re-assessment
of the Styblo rule. Bull World Health Organ 2008; 86: 20–26.
23 Borgdorff MW. New measurable indicator for tuberculosis case
detection. Emerg Infect Dis 2004; 10: 1523–28.
24 Dye C, Bassili A, Bierrenbach A, et al. Measuring tuberculosis
burden, trends, and the impact of control programmes.
Lancet Infect Dis 2008; 8: 233–43.
25 van der Werf MJ, Borgdorff MW. Targets for tuberculosis control:
how confi dent can we be about the data? Bull World Health Organ
2007; 85: 370–76.
26 Lönnroth K, Uplekar M, Ottmani S, Blanc L. Achieving higher case
detection and cure rates: national programmes and beyond.
In: Raviglione M, ed. Tuberculosis: the essentials. New York:
Informa Healthcare, 2009.
27 Gandhi NR, Nunn P, Dheda K, et al. Multidrug-resistant and
extensively drug-resistant tuberculosis: a threat to global control of
tuberculosis. Lancet 2010; published online May 19. DOI:10.1016/
S0140-6736(10)60410-2.
28 Harries AD, Zachariah R, Corbett EL, et al. The HIV-associated
tuberculosis epidemic—when will we act? Lancet 2010; published
online May 19. DOI:10.1016/S0140-6736(10)60409-6.
29 Shilova MV, Dye C. The resurgence of tuberculosis in Russia.
Philos Trans R Soc Lond B Biol Sci 2001; 356: 1069–75.
30 WHO. Global tuberculosis control. WHO/HTM/TB/2008.393.
Geneva: World Health Organization, 2008.
31 UNAIDS. 2008 report on the global AIDS epidemic. UNAIDS/08.25E/
JC1510E. Geneva: Joint United Nation Programme on HIV/AIDS, 2008.
32 Dye C, Lönnroth K, Jaramillo E, Williams BG, Raviglione M.
Trends in tuberculosis and their determinants: an overview of
134 countries. Bull World Health Organ 2009; 87: 683–91.
33 Oxlade O, Schwartzman K, Behr MA, et al. Global tuberculosis
trends: a refl ection of changes in tuberculosis control or in
population health? Int J Tuberc Lung Dis 2009; 13: 1238–46.
34 China Tuberculosis Control Collaboration. The eff ect of tuberculosis
control in China. Lancet 2004; 364: 417–22.
35 Gonzalez E, Armas L, Llanes MJ. Progress towards tuberculosis
elimination in Cuba. Int J Tuberc Lung Dis 2007; 11: 405–11.
36 Subramani R, Santha T, Frieden TR, et al. Active community
surveillance of the impact of diff erent tuberculosis control measures,
Tiruvallur, south India, 1968–2001. Int J Epidemiol 2007; 36: 387–93.
37 Suarez PG, Watt CJ, Alarcon E, et al. The dynamics of tuberculosis
in response to 10 years of intensive control eff ort in Peru.
J Infect Dis 2001; 184: 473–78.
38 Zuniga M, Rojas M. Programa Nacional de Control de la
Tuberculosis año 2000: avances hacia la eliminación.
Rev Chil Enferm Resp 2002; 18: 55–63.
39 Rodriguez De Marco J, Sanches D, Alvarez Goya. El control de la
tuberculosis en Uruguay: 25 años de la implantación del Programa
Nacional de Control de la Tuberculosis. Washington DC,
Pan American Health Organization, 2007.
Series
1828
www.thelancet.com Vol 375 May 22, 2010
40 Lönnroth K, Jaramillo E, Williams BG, Dye C, Raviglione M.
Drivers of tuberculosis epidemics: the role of risk factors and social
determinants. Soc Sci Med 2009; 68: 2240–46
41 Vree M, Duong BD, Sy DN, Co NV, Borgdorff MW, Cobelens FGJ.
Tuberculosis trends, Vietnam. Emerg Infect Dis 2007; 13: 796–97.
42 Dye C, Ottmani S, Laasri L, Benchelkh N. The decline of
tuberculosis epidemics under chemotherapy: a case study in
Morocco. Int J Tuberc Lung Dis 2001; 11: 1225–31.
43 Watt C, Hosseini M, Lönnroth, K, Williams B, Dye C. The global
epidemiology of tuberculosis. In: Schaaf HS, Zumla AI, eds.
Tuberculosis. London: Global Medicine, Elsevier, 2009.
44 Styblo K, Bumgarner JR. Tuberculosis can be controlled with
existing technologies: evidence. The Hague: Tuberculosis
Surveillance Research Unit, 1991.
45 Dye C, Garnett GP, Sleeman K, Williams BG. Prospects for
worldwide tuberculosis control under the WHO DOTS strategy.
Lancet 1998; 352: 1886–91.
46 Borgdorff M, Floyd K, Broekmans JF. Interventions to reduce
tuberculosis mortality and transmission in low- and middle-income
countries. Bull World Health Organ 2002; 80: 217–27.
47 Dye C, Williams B. Eliminating human tuberculosis in the
twenty-fi rst century. J R Soc Interface 2008; 5: 653–62.
48 Dowdy DW, Chaisson RE. The persistence of tuberculosis in the
age of DOTS: reassessing the eff ect of case detection.
Bull World Health Organ 2009; 87: 296–304.
49 Dye C. Tuberculosis 2000-2010: control, but not elimination.
Int J Tuberc Lung Dis 2000; 4: s146–52.
50 Lin X, Chongsuvivatwong V, Lin L, Geater A, Lijuan R. Dose–response
relationship between treatment delay of smear-positive tuberculosis
patients and intra-household transmission: a cross-sectional study.
Trans R Soc Trop Med Hyg 2008; 102: 797–804.
51 John TJ, John SM. Paradigm shift for tuberculosis control in high
prevalence countries. Trop Med Int Health 2009; 14: 1428–30.
52 Storla DG, Yimer S, Bjune GA. A systematic review of delay in the
diagnosis and treatment of tuberculosis. BMC Public Health 2008; 8: 15.
53 Hoa NB, Sy DN, Nhung NV, Tiemersma EW, Borgdorff MW,
Cobelens FGJ. A national survey of tuberculosis prevalence in
Vietnam. Bull World Health Organ 2010: 88: 273–80.
54 National TB Prevalence Survey, 2002, Cambodia. Phnom Penh:
Ministry of Health, 2002.
55 Ayles H, Schaap A, Nota A, et al. Prevalence of tuberculosis,
HIV and respiratory symptoms in two Zambian communities:
implications for tuberculosis control in the era of HIV. PLoS One
2009; 4: e5602.
56 Behr MA, Warren SA, Salamon H, et al. Transmission of
Mycobacterium tuberculosis from patients smear-negative for
acid-fast bacilli. Lancet 1999; 353: 444–49.
57 Bock NN, Jensen PA, Miller B, Nardell E. Tuberculosis infection
control in resource-limited settings in the era of expanding HIV
care and treatment. J Infect Dis 2007; 196: S108–13.
58 Vynnycky E, Fine P. Interpreting the decline in tuerculosis: the role
of secular trend in eff ective contact. Int J Epidemiol 1999; 28: 327–34.
59 Rieder H. Epidemiologic basis of tuberculosis control. Paris:
International Union Against Tuberculosis and Lung Disease, 1999.
60 WHO. Implementing the WHO Stop TB Strategy—a handbook for
national tuberculosis programmes. WHO/HTM/TB/2008.401.
Geneva: World Health Organization, 2008.
61 Vynnycky E, Borgdorff MW, Leung CC, Tam CM. Limited impact
of tuberculosis control in Hong Kong: attributable to high risks of
reactivation disease. Epidemiol Infect 2008; 136: 943–52.
62 Lönnroth K, Raviglione M. Global epidemiology of tuberculosis:
prospects for control. Semin Respir Crit Care Med 2008; 29: 481–91.
63 Hoft DF. Tuberculosis vaccine development: goals, immunological
design, and evaluation. Lancet 2008; 372: 164–75.
64 Ginsberg AM, Spigelman M. Challenges in tuberculosis drug
research and development. Nat Med 2007; 13: 290–94.
65 Chaisson RE, Harrington M. How research can help control
tuberculosis. Int J Tuberc Lung Dis 2009; 13: 558–68.
66 Havlir DV, Barnes PF. Tuberculosis in patients with human
immunodefi ciency virus infection. N Engl J Med 1999; 340: 367–73.
67 Cegielski P, McMurray DN. The relationship between malnutrition
and tuberculosis: evidence from studies in humans and
experimental animals. Int J Tuberc Lung Dis 2004; 8: 286–98.
68 Lönnroth K, Williams BG, Cegielski P, Dye C. A homogeneous
dose-response relationship between body-mass index and
tuberculosis incidence. Int J Epidemiol 2010; 9: 149–55.
69 Slama K, Chiang CY, Enarson D, et al. Tobacco and tuberculosis:
a qualitative systematic review and meta analysis.
Int J Tuberc Lung Dis 2007; 11: 1049–61.
70 Lin H, Ezzati M, Murray M. Tobacco smoke, indoor air pollution
and tuberculosis: a systematic review and meta-analysis.
PLoS Med 2007; 4: e142.
71 Stevenson C, Critchley JA, Forouhi NG, et al. Diabetes and the risk
of tuberculosis: a neglected threat to public health. Chronic Illn 207;
3: 228–245.
72 Jeon CY, Murray MB. Diabetes mellitus increases the risk of active
tuberculosis: a systematic review of 13 observational studies.
PLoS Med 2008; 5: e152.
73 Dooley KE, Chaisson RE. Tuberculosis and diabetes mellitus:
convergence of two epidemics. Lancet Infect Dis 2009; 9: 737–46.
74 Lönnroth K, Williams BG, Stadlin S, Jaramillo E, Dye C.
Alcohol use as a risk factor for tuberculosis—a systematic review.
BMC Public Health 2008; 8: 289.
75 Rehm J, Samokhvalov AV, Neuman M, et al. The association
between alcohol use, alcohol use disorders and tuberculosis (TB).
A systematic review. BMC Public Health 2009; 9: 450.
76 UNAIDS. 2008 report on the global AIDS epidemic.
UNAIDS/08.25E/JC1510E. Geneva: UNAIDS, 2008.
77 Food and Agriculture Organization of the United Nations. The State
of Food Insecurity in the World 2008. Rome: Food and Agriculture
Organization of the United Nations, 2008.
78 IDF. International Diabetes Federation Diabetes Atlas, 2010
estimates. http://www.eatlas.idf.org (accessed Dec 15, 2009).
79 WHO. Global Status Report on Alcohol 2004. Geneva: World Health
Organization, 2004.
80 WHO. Tobacco atlas. Geneva: World Health Organization, 2008.
81 WHO. Fuel for life—household energy and health. Geneva: World
Health Organization, 2006.
82 Hassmiller K. The impact of smoking on population level tuberculosis
outcomes. TSRU progress report 2007. The Hague: KNCV, 2007.
83 Stevenson CR, Forouhi NG, Roglic G, et al. Diabetes and tuberculosis:
the impact of the diabetes epidemic on tuberculosis incidence.
BMC Public Health 2007; 7: 234.
84 Lin HH, Murray M, Cohen T, Colijn C, Ezzati M. Eff ects of smoking
and solid-fuel use on COPD, lung cancer, and tuberculosis in China:
a time-based, multiple risk factor, modelling study. Lancet 2008;
372: 1473–83.
85 Barboza CEG, Winter DH, Seiscento M, Santos UP, Filho MT.
Tuberculosis and silicosis: epidemiology, diagnosis and chemotherapy.
J Bras Pneumol 2008; 34: 961–68.
86 WHO. Global Status Report on Alcohol 2004. Geneva: World Health
Organization, 2004.
87 Davies RPO, Tocque K, Bellis MA, Remmington T, Davies PDO.
Historical declines in tuberculosis in England and Wales:
improving social conditions or natural selection?
Int J Tuberc Lung Dis 1999; 3: 1051–54.
88 Hopewell PC, Pai M, Maher D, Uplekar M, Raviglione MC.
International standards for tuberculosis care. Lancet Infect Dis 2006;
6: 710–25.
89 Lönnroth K, Uplekar M, Blanc L. Hard gains through soft contracts—
productive engagement of private providers in tuberculosis control.
Bull World Health Organ 2006; 84: 876–83.
90 Aluoch JA, Swai OB, Edwards EA, et al. Study of case-fi nding for
pulmonary tuberculosis in outpatients complaining of a chronic cough
at a district hospital in Kenya. Am Rev Respir Dis 1984; 129: 915–20.
91 Sanchez-Perez HJ, Hernan MA, Hernandez-Diaz S, Jansa JM,
Halperin D, Ascherio A. Detection of pulmonary tuberculosis
in Chiapas, Mexico. Ann Epidemiol 2002; 12: 166–72.
92 Thomas A, Chandrasekaran V, Joseph P, et al. Increased yield of
smear positive pulmonary TB cases by screening patients with
≥2 weeks cough, compared to ≥3 weeks and adequacy of 2 sputum
smear examinations for diagnosis. Indian J Tuberc 2008; 55: 77–83.
93 Camacho M, Nogales M, Manjon R, Del Granado M, Pio A,
Ottmani S. Results of PAL feasibility test in primary health care
facilities in four regions of Bolivia. Int J Tuberc Lung Dis 2007;
11: 1246–52.
Series
www.thelancet.com Vol 375 May 22, 2010
1829
94 Fairall LR, Zwarenstein M, Bateman ED, et al. Eff ect of educational
outreach to nurses on tuberculosis case detection and primary care
of respiratory illness: pragmatic cluster randomized controlled trial.
BMJ 2005; 331: 750–54.
95 Harries AD, Billo N, Kapur A. Links between diabetes mellitus and
tuberculosis: should we integrate screening and care?
Trans R Soc Trop Med Hyg 2009; 103: 1–2.
96 WHO. Revision of the case defi nition for sputum smear positive
tuberculosis: Background document. Geneva: World Health
Organization, 2008.
97 Hirao S, Yassin MA, Khamofu HG, et al. Same-day smears in the
diagnosis of tuberculosis. Trop Med Int Health 2007; 12: 1459–63.
98 WHO. Improving the diagnosis and treatment of smear-negative
pulmonary and extrapulmonary tuberculosis among adults and
adolescents—recommendations for HIV-prevalent and resource-
constrained settings. WHO/HTM/TB/2007.379. Geneva: World
Health Organization, 2007.
99 Harries A. What are the relative merits of chest radiography and
sputum examination (smear microscopy and culture) in case
detection among new outpatients with prolonged chest symptoms?
In: Frieden T, ed. Toman’s tuberculosis, second edition. Geneva:
World Health Organization, 2004.
100 Pai M, Ramsay A, O’Brien R. Evidence-based tuberculosis
diagnosis. PLoS Med 2008; 5: e156.
101 Wallis RS, Pai M, Menzies D, et al. Biomarkers and diagnostics for
tuberculosis: progress, needs, and translation into practice.
Lancet 2010; published online May 19. DOI:10.1016/S0140-
6736(10)60359-5.
102 Diwan V, Thorson A, Winkvist A. Gender and tuberculosis. NHV
Report 1998:3. Göteborg: Nordic School of Public Health, 1998.
103 TDR. Gender and tuberculosis: Cross-site analysis and implications
of a multi-country study in Bangladesh, India, Malawi, and
Colombia. TDR Report Series No.3. Geneva: World Health
Organization, Special Programme for Research and Training in
Tropical Diseases, 2006.
104 WHO. Addressing poverty in TB control - options for national
TB control programmes. WHO/HTM/TB/2005.352. Geneva:
World Health Organization, 2005.
105 Jaramillo E. The impact of media-based health education on
tuberculosis diagnosis in Cali, Colombia. Health Policy Plan 2001;
16: 68–73.
106 Grzybowski S, Barnett GD, Styblo K. Contacts of cases of active
pulmonary tuberculosis. Bull Int Union Tuberc 1975; 50: 90–106.
107 Morrison J, Pai M, Hopewell PC. Tuberculosis and latent tuberculosis
infection in close contacts of people with pulmonary tuberculosis in
low-income and middle-income countries: a systematic review and
meta-analysis. Lancet Infect Dis 2008; 8: 359–68.
109 Golub JE, Mohan CI, Comstock GW, Chaisson RE. Active case
nding of tuberculosis: historical perspective and future prospects.
Int J Tuberc Lung Dis 2005; 9: 1183–203.
108 WHO. WHO Expert Committee on Tuberculosis. Ninth report. WHO
Technical Series, No 552. Geneva: World Health Organization, 1974.
110 Borgdorff MW, Floyd K, Broekmans JF. Interventions to reduce
tuberculosis mortality and transmission in low- and middle-income
countries. Bull World Health Organ 2002; 80: 217–27.
111 Menzies D, Joshi R, Pai M. Risk of tuberculosis infection and
disease associated with work in health care settings.
Int J Tuberc Lung Dis 2007; 11: 593–605.
112 WHO. Guidelines for the Control of Tuberculosis in Prisons.
WHO/TB/98.250. Geneva: World Health Organization, 1998.
113 WHO. Policy guidelines for collaborative TB and HIV services for
injecting and other drug users: an integrated approach. WHO/
HTM/TB/2008.404. Geneva: World Health Organization, 2008.
114 de Vries G, van Hest RA, Richardus JH. Impact of mobile
radiographic screening on tuberculosis among drug users and
homeless persons. Am J Respir Crit Care Med 2007; 176: 201–07.
115 WHO. Tuberculosis care and control in refugee and displaced
populations. WHO/HTM/TB/2007.377. Geneva: World Health
Organization, 2007.
116 Gonzales-Ochoa E, Brooks JL, Matthys F, et al. Pulmonary
tuberculosis case detection through fortuitous cough screening
during home visits. Trop Med Intern Health 2009; 14: 131–35.
117 WHO. Treatment of tuberculosis—guidelines (4th edn).
Geneva: World Health Organization, 2009.
118 Volmink J, Garner P. Directly observed therapy for treating
tuberculosis. Cochrane Database Syst Rev 2006; 2: CD003343.
119 Boggio A, Zignol M, Jaramillo E, Nunn P, Pinet G, Raviglione M.
Limitations on human rights: are they justifi able to reduce the
burden of TB in the era of MDR- and XDR-TB? Health Hum Rights
2008; 10: 121–26.
120 Lawn SD, Churchyard G. Epidemiology of HIV-associated
tuberculosis. Curr Opin HIV AIDS 2009; 4: 325–33.
121 Travis P, Bennett S, Haines A, et al. Overcoming health-systems
constraints to achieve the Millennium Development Goals.
Lancet 2004; 364: 900–06.
122 WHO. Contributing to health system strengthening—guiding
principles for national tuberculosis programmes. WHO/HTM/
TB/2008.400. Geneva: World Health Organization, 2008.
123 The Global Fund. The Global Fund 2009: innovation and impact.
Geneva: The Global Fund, 2010.
124 Garrett L, Chowdhury AMR, Pablos-Méndez A. All for universal
coverage. Lancet 2009; 374: 1294–99.
125 Kobaidze K, Salakaia A, Blumberg HM. Over the counter availability of
antituberculosis drugs in Tbilisi, Georgia in the setting of a high
prevalence of MDR-TB. Interdiscip Perspect Infect Dis 2009; published
online June 11. doi:10.1155/2009/513609.
126 Caudron JM, Ford N, Henkens M, Macé C, Kiddle-Monroe R,
Pinel J. Substandard medicines in resource-poor settings:
a problem that can no longer be ignored. Trop Med Int Health 2008;
13: 1062–72.
127 The TB Alliance. Pathway to patients—charting the dynamics of the
global TB drug market. New York: The TB Alliance, 2007.
128 Lagomarsino G, Nachuk S, Kundra SS. Public stewardship of
private providers in mixed health systems. Washington: Research
for Development Institute, 2009.
129 WHO and International Union against Tuberculosis and Lung
Disease. A WHO/The Union monograph on TB and tobacco control.
WHO/TB/2007.390. Geneva: World Health Organization, 2008.
130 Wang L, Liu J, Chin DP. Progress in tuberculosis control and
evolving public-health system in China. Lancet 2007; 369: 691–96.
131 McKeown T, Record RG. Reasons for the decline of mortality in
England and Wales during the nineteenth century. Popul Stud 1962;
16: 94–122.
132 Blas E, Sivasankara AK, eds. Priority public health conditions: from
learning to action on social determinants of health. Geneva: World
Health Organization, 2010.
133 Jaramillo E. Encompassing treatment with prevention: the path for
a lasting control of tuberculosis. Soc Sci Med 1999; 49: 393–404.
134 Lönnroth K, Zignol M, Uplekar M. Controlling TB in large
metropolitan settings. In: Raviglione M, ed. TB: a comprehensive
international approach. New York: Informa Healthcare, 2006.
135 Kjellström T, Mercado S, Sattherhwaite D, McGranaham G, Friel S,
Havemann K. Our cities, our health, our future: acting on social
determinants for health equity in urban settings. Report to the
WHO Commission on Social Determinants of Health from the
Knowledge Network on Urban Settings. Kobe: World Health
Organization Kobe Centre, 2007.
136 Commission on Social Determinants of Health. Achieving health
equity: from root causes to fair outcomes—Commission on Social
Determinants of Health interim statement. Geneva: World Health
Organization, 2007.
137 Islam MA, Wakai S, Ishikawa N, et al. Cost-eff ectiveness of
community health workers in tuberculosis control in Bangladesh.
Bull World Health Organ 2002; 80: 445–50.
138 Nganda B, Wang’ombe J, Floyd K. Cost and cost-eff ectiveness of
increased community and primary care facility involvement in
tuberculosis care in Machakos District, Kenya. Int J Tuberc Lung Dis
2003; 7: S14–20.
139 Abu-Raddad LJ, Sabatelli L, Achterberg JT, et al. Epidemiological
benefi ts of more-eff ective tuberculosis vaccines, drugs, and
diagnostics. Proc Natl Acad Sci USA 2009; 106: 13980–85.
140 Ma Z, Lienhardt C, McIlleron H, Nunn AJ, Wang X. Global
tuberculosis drug development pipeline: the need and the reality.
Lancet 2010; published online May 19. DOI:10.1016/S0140-
6736(10)60359-9.
141 Treatment Action Group. 2009 report on tuberculosis research
funding trends, 2005–2008. New York: Treatment Action Group,
2009.
... The community's socioeconomic status can affect all stages of the pathogenesis of TB (Duarte et al., 2018). Economic growth and poverty reduction will be essential elements in reducing TB cases (Lönnroth et al., 2010). Therefore, in order for economic growth to contribute effectively in controlling TB cases, it is necessary to have the right combination of health and public policies. ...
... It can lead to a higher incidence of TB in areas with high population growth and urbanization in slum areas. Occurred in the 19th century on the European continent, there was a significant relationship that high levels of urbanization had resulted in population densities that tended to be vulnerable to the incidence of TB (Lönnroth et al., 2010). Another population problem from the study by Austin et al. (2016) investigated empirically 99 third world countries for the period 1995-2010 regarding TB, which has become a global health problem and a threat to development in third world countries and the results of this study indicate that high population growth rates have contributed to the high prevalence of tuberculosis among the poor. ...
... Apolinario et al. (2017), in their research conducted in Portugal, found that the physical condition of a densely populated house would facilitate the incidence of TBtransmission, which would be more comfortable and faster through the air if in the house residents were suffering from TB or acid-resistant bacteria positive who accidentally cough. Mycobacterium tuberculosis that settles in the house will last up to 2 hours so that it has the possibility of transmitting TB to other family members who live in the home environment (Dotulong et al., 2015).TB cases in urban areas are closely related to high population density (Lönnroth et al., 2010;Bhunu et al., 2012). Because in densely populated urban areas, many people exposed to TB have low socioeconomic status conditions, such as malnutrition, anemia, poverty, inadequate sanitation, humid physical conditions, air ventilation, and low lighting (Janssens & Rieder, 2008). ...
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The threat of TB continues to occur in the world. In 2018, 10 million people suffered from TB, and 1.5 million people die from this infectious disease. Referring to target 3 of Sustainable Development Goals (SDGs) goals 03 regarding good health and well-being, by 2030, end the epidemic of AIDS, TB, malaria, and neglected tropical diseases and combat hepatitis, water-borne diseases, and other communicable diseases. Based on data from the WHO, Indonesia ranks 3rd for TB cases globally. The estimated population suffering from TB is 845,000 cases; only 68 percent of cases were found and treated in 2018. The high number of TB cases in Indonesia could threaten the golden generation's opportunity in the next 2025 demographic bonus, where the number of productive age population is higher than the population non-productive age. This study found that population factors such as population, population density, and the number of poor people had a positive and significant effect on TB cases. In contrast, the GRDP per capita, the number of health workers, and literacy rates negatively affected the TB cases. Furthermore, environmental factors from the availability of proper sanitation and toilet facilities show a negative but insignificant effect on TB cases.
... Such tobacco and alcohol misuse further weakens the immune system and increases the risk of TB treatment failure, relapse and death. 21,22 In addition, there are concerns that the use of one substance, for example, alcohol, can serve as a gateway toward the use of tobacco or other substances. 23 Frequent risky drinkers smoked more cigarettes per day and had greater temptations to smoke in positive affective/social situations. ...
... This could be important in making a new policy to prevent and control TB and may, therefore, help reduce the global TB burden. 21,27 ...
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This study aimed to assess the prevalence and patterns of tobacco and alcohol use and the associations with socio-demographic variables among presumptive TB patients. A cross-sectional study was conducted among 397 presumptive TB patients in a tertiary hospital in Myanmar. Global Adult Tobacco Survey (GATS) questionnaire and AUDIT-C were used to measure daily tobacco use (single, any or dual use of smoked and smokeless tobacco) and harmful alcohol use, respectively. Multiple and multinomial logistic regression were used to examine the associations with socio-demographic factors. The prevalence of daily use of dual tobacco and any tobacco was 28.2% and 65.7%, respectively. Harmful alcohol use was also high (44.8%). While single use of daily tobacco and harmful alcohol was 28.2% and 7.3%, respectively, concurrent tobacco and alcohol use was 37.5%. While being male and having low education were associated with tobacco use, concurrent tobacco and harmful alcohol use were associated with male gender, low education, and occupation with the government or a company. Due to the high prevalence of tobacco and alcohol misuse, identifying those at risk of tobacco and alcohol misuse and providing integrated care services in a health facility should be considered as a joint activity in national TB and tobacco control programmes.
... Some of the factors that have traditionally been associated with TB include poverty, crowding, undernutrition, inadequate access to medical care, low literacy, unemployment, public assistance, social protection, and indoor air pollution. [20][21][22]. The United Nations included that no TB-affected household should experience catastrophic costs due to the disease by 2020 as one of the three Sustainable Development Goals (2016-2030) [23][24][25]. ...
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Introduction Pulmonary tuberculosis (TB) is a major source of global mortality and morbidity, particularly in the developing world. Latent infection has enabled it to spread to approximately a quarter of the world's population. The late 1980s and early 1990s saw an increase in the number of reported TB cases related to the HIV epidemic and immigration, as well as the spread of multidrug-resistant TB (MDR TB). Few studies have reported pulmonary TB mortality trends. Our study reports and compares trends in pulmonary TB mortality between 1985 and 2018 in countries throughout the world. Methods We utilized the World Health Organization (WHO) mortality database to extract TB mortality data based on the International Classification of Diseases (ICD) 10 system. Based on the availability and quality of data, we included Canada and the United States (US) from the Americas; Austria, Belgium, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Latvia, Lithuania, Netherlands, Poland, Portugal, Republic of Moldova, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, and United Kingdom from Europe; Australia, New Zealand, and Japan from the Western Pacific region. Crude mortality rates were dichotomized by sex and reported by year. We computed age standardized death rates (ASRDs) per 100,000 population using the world standard population. Pulmonary TB mortality trends were examined using Joinpoint regression analysis and reported using estimated annual percentage changes (EAPCs). Results We observed a decrease in mortality in males and females in all countries except the Republic of Moldova, which showed an increase in female mortality (+0.12%). Among all countries, Lithuania had the greatest reduction in male mortality (-12.01%) between 1993-2018, and Hungary had the greatest reduction in female mortality (-1.57%) between 1985-2017. Male mortality declined at a steady rate across the study period. Slovenia had the most rapid recent declining trend for males with an EAPC of -47% (2003-2016), followed by Australia (-33.6%, 2014-2017), whereas Croatia and Austria showed an increase in EAPC of +25.0% (2015-2017) and +17.8% (2010-2014), respectively. For females, New Zealand had the most rapid recent declining trend (-47.2%, 1985-2015), followed by Hungary (-35.1%, 2004-2007), whereas Croatia showed an increase in EAPC (+24.9%, 2014-2017). Conclusion Pulmonary TB mortality is disproportionately higher among Central and Eastern European countries. This communicable disease cannot be eliminated from any one region without a global approach. Priority action areas include ensuring early diagnosis and appropriate treatment to the most vulnerable groups. In low- and middle-income countries with high TB incidence, attenuation of socioeconomic determinants including extreme poverty, inadequate living conditions, and malnutrition remains crucial.
... Some studies from China and India reported that smoking increases the severity and mortality rate of tuberculosis [2,3]. In 2010, the WHO suggested a stronger focus on preventing exposures to tuberculosis [4]. In addition to cancer and coronary heart disease, numerous studies have identified smoking as a risk factor in the development of TB [5,6]. ...
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Background: Smoking plays a key role in the development of tuberculosis (TB) infection and is also a predictor of poor TB treatment prognosis and outcomes. The current study was conducted to determine the prevalence of smoking and to assess the effects of smoking on treatment outcomes among TB patients. Methods: A multi-center retrospective study design was used to collect data from TB patients in four different states of Malaysia, namely Penang, Sabah, Sarawak, and Selangor. The study included medical records of TB patients admitted to the selected hospitals in the period from January 2006 to March 2009. Medical records with incomplete data were not included. Patient demographics and clinical data were collected using a validated data collection form. Results: Of all patients with TB (9337), the prevalence of smokers was 4313 (46.2%). Among smokers, 3584 (83.1%) were associated with pulmonary TB, while 729 (16.9%) were associated with extrapulmonary TB. Male gender (OR = 1.43, 95% CI 1.30-1.58), Chinese ethnicity (OR = 1.23, 95% CI 1.02-1.49), Sarawak indigenous ethnicity (OR = 0.74, 95% CI 0.58-0.95), urban residents (OR = 1.46, 95% CI 1.33-1.61), employed individuals (OR = 1.21, 95% CI 1.09-1.34), alcoholics (OR = 4.91, 95% CI 4.04-5.96), drug abusers (OR = 7.43, 95% CI 5.70-9.60) and presence of co-morbid condition (OR = 1.27, 95% CI 1.16-1.40) all showed significant association with smoking habits. This study found that 3236 (75.0%) patients were successfully treated in the smokers' group, while 4004 (79.7%) patients were non-smokers. The proportion of deaths (6.6%, n = 283), defaulters (6.6%, n = 284) and treatment interruptions (4.7%, n = 204) was higher in the smokers' group. Conclusions: Smoking has a strong influence on TB and is a major barrier towards treatment success (OR = 0.76, 95% CI 0.69-0.84, p < 0.001). Therefore, the findings indicate that smoking cessations are an effective way to decrease treatment failure and drug resistance.
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The COVID-19 pandemic has caused widespread disruptions to tuberculosis (TB) care and service delivery in 2020, setting back progress in the fight against TB by several years. As newer COVID-19 variants continue to devastate many low and middle-income countries in 2021, the extent of this setback is likely to increase. Despite these challenges, the TB community can draw on the comprehensive approaches used to manage COVID-19 to help restore progress and mitigate the impact of COVID-19 on TB. Our team developed the ‘Swiss Cheese Model for Ending TB’ to illustrate that it is only through multisectoral collaborations that address the personal, societal and health system layers of care that we will end TB. In this paper, we examine how COVID-19 has impacted the different layers of TB care presented in the model and explore how we can leverage some of the lessons and outcomes of the COVID-19 pandemic to strengthen the global TB response.
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The German pathologist and politician Rudolf Virchow proposed the concept of sociomedical causation, emphasising the role of social and environmental factors in the aetiology and prevention of diseases. Virchow's achievements are threefold: he was a founder of scientific biomedicine, he characterised medicine as a social science as much as a biological science and he promoted and improved public health. In his landmark report of a typhus epidemic in mid-19th century Germany, Virchow drew a connection between the epidemic and poverty and living conditions. He proposed radical social reform and stated that, “medicine is social science and politics nothing but medicine on a grand scale”. The task of medicine was therefore not merely to treat disease but also to contribute to the health of the entire population. Virchow realised that, in order to improve the health of the public, medicine must attend to both its biological and social underpinnings. His work has had far-reaching consequences for the development of public health and medical sociology. As in Virchow's times, poverty, deprived living conditions, malnutrition, crowding and economic insecurity determine to a high degree the prevalence of disease and life expectancy in low- and middle-income countries today. Sociomedical causation is not limited to infectious diseases but also extends to the contemporary pandemics of non-communicable diseases. Obesity and other non-communicable diseases cannot be addressed effectively without considering and acting on the social determinants of health. The concept of “health in all policies” has emerged with the goal of promoting political action addressing the social determinants of health. This concept concerns prevention of disease, promotion of a healthy lifestyle and improvement of factors potentially harmful to the health of entire populations. The current “health-in-all-policies” reforms in China may advance the global evidence base for the prevention of chronic disease in low-, middle- and high-income countries.
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Eighty-five percent of the world's new Tuberculosis cases are found in thirty high burdened countries, one of which is South Africa. South Africa is one of the eight countries that are said to account for the two thirds of the total new Tuberculosis cases. The Tuberculosis epidemic is driven by the following reasons: firstly, poor living conditions which are a result of the wide gap between the rich and the poverty stricken among some populations; and, secondly, late presentation to health facilities. Over the years, healthcare programs have made a meaningful impact in identifying patients presenting to Tuberculosis care. A global Tuberculosis report shows an estimated sixty million lives were saved through Tuberculosis treatment and diagnosis between the years 2000 and 2019. This progress has encouraged the United Nations to set the health target of eradicating the Tuberculosis epidemic by 2030. For this goal to be attained, strategies to modify risk behaviour need to remain a main priority. In the South African context, it would be important to note the diversity of the individuals experience which is rooted in South African socio-political history and has resulted in high levels of social inequality and disparate socio-economic status groups, as a significant factor when considering the well-being of Tuberculosis infected South Africans. The aim of this research was to understand health related well-being in South Africa, by noting and comparing the diversity of life satisfaction experience between participants from different sociodemographic status groups across South Africa. In this interview statistician Motladi Matatiele and Demographer Nancy Stiegler from the University of Western Cape discuss the possible factors of subjective well-being in the Tuberculosis infected South African population and provide an understanding of the behavioural aspects tied to Tuberculosis infection.
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Background While persons who receive immigrant and refugee visas are screened for active tuberculosis before admission into the United States, nonimmigrant visa applicants (NIVs) are not routinely screened and may enter the United States with infectious tuberculosis. Objectives We evaluated the costs and benefits of expanding pre-departure tuberculosis screening requirements to a subset of NIVs who arrive from a moderate (Mexico) or high (India) incidence tuberculosis country with temporary work visas. Methods We developed a decision tree model to evaluate the program costs and estimate the numbers of active tuberculosis cases that may be diagnosed in the United States in two scenarios: 1) “Screening”: screening and treatment for tuberculosis among NIVs in their home country with recommended U.S. follow-up for NIVs at elevated risk of active tuberculosis; and, 2) “No Screening” in their home country so that cases would be diagnosed passively and treatment occurs after entry into the United States. Costs were assessed from multiple perspectives, including multinational and U.S.-only perspectives. Results Under “Screening” versus “No Screening”, an estimated 179 active tuberculosis cases and 119 hospitalizations would be averted in the United States annually via predeparture treatment. From the U.S.-only perspective, this program would result in annual net cost savings of about $3.75 million. However, rom the multinational perspective, the screening program would cost $151,388 per U.S. case averted for Indian NIVs and $221,088 per U.S. case averted for Mexican NIVs. Conclusion From the U.S.-only perspective, the screening program would result in substantial cost savings in the form of reduced treatment and hospitalization costs. NIVs would incur increased pre-departure screening and treatment costs.
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Abstrak Tuberkulosis (TB) masih menjadi masalah utama kesehatan di Indonesia termasuk di Propinsi Sumatera Utara. Telah dilaporkan efikasi yang baik dari pengobatan TB di berbagai daerah, keberhasilan pengobatan TB dipengaruhi oleh banyak factor termasuk status nutrisi. Penelitian ini bertujuan untuk menemukan adanya hubungan indeks massa tubuh dan albumin dengan konversi sputum pasien tuberculosis, khususnya pasien tuberculosis paru positif kuman Basil Tahan Asam. Penelitian ini dilaksanakan di dua Pusat Kesehatan Masyarakat di Kota Medan antara bulan Oktober dan Nopember 2018. Seluruh subjek penelitian sejumlah 39 pasien TB dengan positif kuman Basil Tahan Asam ikut serta. Subjek penelitian menerima pengobatan TB sesuai panduan. Indeks masa tubuh, albumin, dan sputum diukur dengan menggunakan stature meter dan timbangan digital. Proporsi subjek penelitian di bawah normal, normal dan di atas normal adalah 13 (33.3%), 21 (53.9%) and 5 (12.8%), berturut-turut. Kadar albumin termasuk kadar normal ditemukan pada 25 subjek penelitian (64.1%), dan selebihnya termasuk kategori rendah. Indeks massa tubuh normal berhubungan bermakna dengan peningkatan kadar albumin (p
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OBJECTIVE: To determine whether differences in national trends in tuberculosis incidence are attributable to the variable success of control programmes or to biological, social and economic factors. METHODS: We used trends in case notifications as a measure of trends in incidence in 134 countries, from 1997 to 2006, and used regression analysis to explore the associations between these trends and 32 measures covering various aspects of development (1), the economy (6), the population (3), behavioural and biological risk factors (9), health services (6) and tuberculosis (TB) control (7). FINDINGS: The TB incidence rate changed annually within a range of ±10% over the study period in the 134 countries examined, and its average value declined in 93 countries. The rate was declining more quickly in countries that had a higher human development index, lower child mortality and access to improved sanitation. General development measures were also dominant explanatory variables within regions, though correlation with TB incidence trends varied geographically. The TB incidence rate was falling more quickly in countries with greater health expenditure (situated in central and eastern Europe and the eastern Mediterranean), high-income countries with lower immigration, and countries with lower child mortality and HIV infection rates (located in Latin America and the Caribbean). The intensity of TB control varied widely, and a possible causal link with TB incidence was found only in Latin America and the Caribbean, where the rate of detection of smear-positive cases showed a negative correlation with national incidence trends. CONCLUSION: Although TB control programmes have averted millions of deaths, their effects on transmission and incidence rates are not yet widely detectable.
Thesis
italic>Objective . In India, TB kills more smokers than all types of cancer combined. Substantial evidence links smoking and TB; smokers are more susceptible to, are spreading, and dying from an infectious disease. Research objectives are to: estimate individual-level increases in TB risks among smokers; understand the underlying mechanisms by which smoking impacts TB risks; estimate the impact of smoking on population-level TB outcomes, and to begin to investigate policy implications. Methods . A compartmental model is developed to represent key aspects of TB transmission and disease progression, and smoking is introduced based on a review of the impact of smoking on lung function, immune response, and social contact patterns. Individual-level effects of smoking are constrained by estimates of the unconditional relative risks of being infected, developing TB, and dying from TB for smokers compared to never-smokers estimated in a meta-analysis. The model is used to estimate the population-level impact of smoking on TB outcomes and the effect of tobacco- and TB-control policies on projected TB outcomes. Results . Ever-smokers are 1.7 (95%CI 1.3-2.0), 2.7 (2.0-3.9), and 2.4 (1.3-4.2) times more likely to be infected with M. tuberculosis, to develop TB, and to die from TB, respectively, than never-smokers. It seems unlikely that these values could be produced unless smokers are more likely to become infected given exposure to M. tuberculosis and to progress to disease given infection. Translating these individual-level effects to the population level when 29% of adults smoke (the average in developing countries), an estimated 60% of all incident TB disease (95%CI given uncertainty in TB dynamics 56-65%; expected range given uncertainty in the underlying mechanisms 59-72%) and 57% of TB deaths (52-62%; 55-69%) are attributable to smoking. Among never-smokers, 42% of incident TB (36-48%; 39-59%) and 42% of TB mortality (36-48%; 38-58%) is attributable to smoking. Conclusions . Considering both the direct effects of smoking on individuals' own health and the indirect effects of contagion, smoking impacts population-level TB outcomes substantially. Fortunately, smoking is an identifiable and modifiable risk factor. Neglecting to control tobacco use could significantly offset strides made in TB control.
Article
OBJECTIVE: To investigate whether short-term annual declines of 5-10% in the incidence of tuberculosis (TB) can be sustained over the long term by maintaining high case detection rates (CDRs). METHODS: We constructed a compartmental difference-equation model of a TB epidemic in a hypothetical population of constant size with a treatment success rate of 85%. The impact of CDR on TB incidence was then investigated by generating an equilibrium population with no TB case detection and increasing the smear-positive CDR under two scenarios: (i) rapid expansion by 10% per year to a CDR of 80% after 8 years, and (ii) gradual expansion by 1% per year to a CDR of 90% after 90 years. The model was applied in two hypothetical populations: one without HIV and the other with a stable HIV incidence representative of the African Region. The CDR for smear-negative TB was assumed to be a constant fraction of the smear-positive CDR. FINDINGS: In the absence of a TB control programme, the projected annual incidence of TB was 513 cases per 100 000 population, with a point prevalence of 1233 per 100 000 and an annual TB-specific mortality rate of 182 per 100 000. Immediately increasing the TB CDR from 0% to 70% caused a 74% reduction in TB incidence within 10 years. However, once case detection stabilized at any constant level