E D I T O R I A L C O M M E N TA R Y
Failure of Directly Observed Treatment for Tuberculosis
in Africa: A Call for New Approaches
Christopher C. Whalen
Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio
(See the article by Lawn et al. on pages 1040–7)
The tuberculosis pandemic continues to
evolve. In some parts of the world, tu-
berculosis case rates have decreased to his-
torically low levels, whereas, in other parts
of the world, the incidence of tuberculosis
is increasing. In sub-Saharan Africa, tu-
berculosis continues to be a major threat
to individual and public health as inci-
dence rates surpass 1000 cases per 100,000
population in some regions. In 1994, the
World Health Organization (WHO) de-
clared tuberculosis a global emergency and
introduced the directly observed treat-
ment, short course (DOTS), strategy for
global tuberculosis control, but the plan
has produced variable success. In the face
of this intensified effort to diagnose and
treat tuberculosis, the rates in sub-Saharan
Africa continue to climb. Various experts
have argued that the failure of the DOTS
strategy to control tuberculosis results
from failed implementation, poor public
health infrastructure, poverty, the lack of
interventions that are sensitive to personal
preferences, and the HIV epidemic. Al-
though each of these reasons may con-
Received 5 December 2005; accepted 6 December 2005;
electronically published 16 February 2006.
Reprints or correspondence: Dr. Christopher C. Whalen,
Dept. of Epidemiology and Biostatistics, WG-37, Case
Western Reserve University, School of Medicine, 10900 Euclid
Ave., Cleveland, OH 44106-4945 (ccw@case.edu).
Clinical Infectious Diseases 2006; 42:1048–50
 2006 by the Infectious Diseases Society of America. All
rights reserved.
1058-4838/2006/4207-0026$15.00
1048 • CID 2006:42 (1 April) • EDITORIAL COMMENTARY
tribute, the problem with the DOTS strat-
egy may be even more fundamental. What
is the rationale for the DOTS strategy? Is
it a public health intervention designed to
curb the spread of tuberculosis, or is it a
treatment guideline for tuberculosis?
The DOTS strategy was introduced in
1994 as a comprehensive plan for tuber-
culosis control built around 5 strategic ac-
tivities [1]. First, governments must com-
mit to control tuberculosis and provide
the human resources and infrastructural
capacity to deliver care for persons with
tuberculosis. Second, case detection is per-
formed through passive case-finding, with
microscopic examination of sputum sam-
ples used as the diagnostic standard.
Third, treatment consists of the standard
short-course regimen and must be given
using directly observed therapy. Fourth,
there must be a regular supply of medi-
cation to the national tuberculosis-control
program. Fifth, a system must be in place
for monitoring and tracking cases
throughout the country. As part of the
strategy, the WHO also proposed a per-
formance target of identifying 70% of tu-
berculosis cases and curing 85% of them.
The article by Lawn et al. [2] is an eco-
logic study that describes coincident tu-
berculosis and HIV epidemics in a town-
ship near Cape Town, South Africa. The
study is unique because it examines a pop-
ulation in a well-defined geographic re-
gion that was characterized by 2 popula-
tion census surveys 8 years apart, so
disease rates could be adjusted for de-
mographic changes. The community is
served by a single community health
clinic, making it likely that the means of
diagnosing and reporting cases of tuber-
culosis and HIV infection were uniform,
thereby avoiding detection and reporting
biases. The most striking feature of the
design is that DOTS was implemented in
an optimal way in the district, and the
program achieved cures rates of ⭓80% in
smear-positive cases of tuberculosis.
In this setting, the authors were able to
show that the tuberculosis rates increased
2.5-fold during the study period and con-
tinued to increase even after the preva-
lence of HIV infection had leveled off. Tu-
berculosis rates increased most among
adolescents and individuals aged 20–39
years—the age groups most likely to be
affected by HIV infection in this popu-
lation. The authors conclude that the
DOTS strategy alone was ineffective in this
community because of the population ef-
fects of HIV infection on tuberculosis.
Although it is important to herald the
successes of the DOTS strategy around the
world [3, 4] and to acknowledge its role
in preventing the emergence of multidrug-
resistant stains of Mycobacterium tuber-
culosis [5], we may learn more about tu-
berculosis control from examining where
the DOTS strategy has failed. By under-
standing the reasons for failure, we may
be able to modify and improve current
approaches and to design new strategies.
The study by Lawn et al. [2] offers some
insight into why the DOTS strategy failed,
at least in this small, well-studied African
community. Some experts have stated that
the main reason for the DOTS strategy’s
failure is lack of proper implementation
[6–8]. But that is not likely here, because
all tuberculosis care was offered through
a single clinic that achieved WHO treat-
ment goals. Lawn and colleagues argue
that the HIV epidemic fueled the tuber-
culosis epidemic in the township, citing
the temporal association between the 2 ep-
idemics and its biologic plausibility as evi-
dence. As an ecologic study, however, it is
possible that an unmeasured factor, such
as population migration, has produced the
results we observe. In the United States,
for example, we witnessed a resurgence of
tuberculosis from 1986 to 1993 that was
initially attributed to the “new” AIDS ep-
idemic but was later attributed to tuber-
culosis in foreign-born individuals, with
HIV infection playing a lesser role [9]. In
this township, we find ourselves confront-
ing a similar interpretation. Detailed mo-
lecular epidemiology of tuberculosis cases
and HIV serostatus of individuals would
help to clarify the transmission dynamics
among individuals in this population.
So where does the DOTS strategy falter?
DOTS is not optimally designed to inter-
rupt the spread of tuberculosis. Epidemics
result from the transmission of a micro-
organism from infectious persons to ⭓1
susceptible individual. The force of this
transmission is captured in the basic re-
productive rate of an epidemic, a param-
eter that can be understood as the number
of new infections among susceptible in-
dividuals during the infectious period of
a case. Only 3 determinants underlie this
important parameter: (1) the number of
contacts (per unit time) between an in-
fectious patient and susceptible contacts;
(2) the probability of infection (or dis-
ease), given adequate contact for trans-
mission from the patient to a susceptible
individual; and (3) the duration of infec-
tiousness of the index case.
When one examines the elements of
DOTS, only the treatment of disease di-
rectly alters one of these key epidemic pa-
rameters by reducing the duration of in-
fectiousness. The DOTS strategy does not
address the number and frequency of con-
tacts or the likelihood of disease after in-
fection. For tuberculosis, it is estimated
that a single patient may infect ∼10 con-
tacts before receiving treatment [10]. With
a lifetime risk of tuberculosis of ∼10%
[11], then each case of tuberculosis will be
replaced by another, at some point in the
future. In the presence of HIV infection,
however, the dynamics are altered, because
HIV infection is associated with a high risk
for progressive primary tuberculosis [12]
and reactivation of disease [13]. A single
tuberculosis case will likely yield 11 sub-
sequent case, thereby accentuating an
epidemic.
Our experience with DOTS teaches us
that treatment of tuberculosis alone is in-
effective in containing its spread in some
communities, particularly where HIV in-
fection is endemic. New approaches
should be developed that interrupt the
spread of M. tuberculosis in the commu-
nity. These public health interventions
may aim to alter contact patterns of in-
fectious patients through real-time geo-
graphic mapping of disease incidence or
through social development programs.
Other interventions might aim to reduce
the risk of disease after infection, either by
treating latent tuberculosis infection in
high-risk groups (e.g., HIV-infected per-
sons and household contacts), or by the
systematic treatment of HIV infection
with antiretroviral therapy [14]. As sug-
gested by Lawn et al. [2], age-specific, ac-
tive case finding in high-risk populations
might also preempt tuberculosis spread by
reducing the duration of infectiousness.
The common theme for these approaches
is to target transmission as the main goal
of the intervention.
In summary, a framework for tuber-
culosis control requires clearly defined
EDITORIAL COMMENTARY • CID 2006:42 (1 April) • 1049
goals—that is, whether an intervention
targets primarily transmission or treat-
ment. The DOTS strategy is an excellent
and well-orchestrated set of treatment
guidelines that provide governments,
ministries of health, and health care pro-
fessionals unambiguous advice on how to
treat patients with tuberculosis. And for
this reason, it should remain a centerpiece
in our efforts to treat tuberculosis disease.
The study from Cape Town illustrates the
urgent need to develop novel strategies to
act as companions to DOTS. These novel
public health strategies should have as
their primary goal to interrupt the spread
of tuberculosis. Because of the potential
effect of HIV infection on tuberculosis
control, these strategies must also integrate
with the HIV prevention and treatment
programs.
Acknowledgments
Financial support. Tuberculosis Research
Unit (AI-45244-95383) and an investigator-initi-
ated grant (AI51219) from the National Institutes
of Allergy and Infectious Diseases, and the AIDS
International Training and Research Program
(TW-00011) of the Fogarty International Center,
National Institutes of Health.
Potential conflicts of interest. C.C.W.: no
conflicts.
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