E-drug: Major infectious diseases in the world
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[I thought the below editorial is of particular importance to all
involved in management of TB. The Journal has an additional article
on the management of multi-drug resistant TB in Turkey. Thanks to
Valeria Frighi for alerting me. Copied as fair use. HH]
The Major Infectious Diseases in the World
To Treat or Not to Treat?
NEJM, Vol 345:208-210, No 3, 19 July 2001
Paul Farmer
In this issue of the Journal, Tahaolu and coworkers report on their
experience in treating a cohort of patients infected with strains of
Mycobacterium tuberculosis that are resistant to powerful
antituberculosis drugs. Tuberculosis caused by strains that are
resistant to at least isoniazid and rifampin is, by convention, termed
"multidrug-resistant tuberculosis."1 The authors of this report work
in a referral center in Turkey that has available a full complement of
clinical, laboratory, and surgical services, including multidrug
treatment regimens given for 18 to 24 months, resources for the
management of side effects, adjuvant surgery when necessary, and
full financial and nutritional support. Tahaolu et al. show that with a
high standard of care, the treatment of multidrug-resistant
tuberculosis can have excellent results, especially among younger
patients without serious coexisting conditions.
This study is important for several reasons. It has already been
documented that multidrug-resistant tuberculosis is a pandemic.
Drug-resistant cases of tuberculosis have been reported in every
country surveyed.2,3,4 M. tuberculosis is an airborne pathogen,
and persons with active, pulmonary tuberculosis caused by a
multidrug-resistant strain can transmit the disease to others as long
as they are alive and coughing. For the hundreds of thousands who
are sick with multidrug-resistant tuberculosis, the report by Tahaolu
et al. should come as welcome news. Throughout the world, most
patients with multidrug-resistant tuberculosis are like the majority of
those in the Turkish study: young and middle-aged adults who are
not infected with the human immunodeficiency virus (HIV) and who
do not have serious coexisting conditions. Almost none of these
patients, however, are receiving effective therapy, and most remain
infectious.
Some Journal readers may be surprised to learn that the great
majority of patients with multidrug-resistant tuberculosis throughout
the world are not receiving effective therapy. The need for such
therapy in "resource-poor settings" the latest euphemism for
poverty is disputed in international tuberculosis-control circles, and
it is argued that multidrug-resistant tuberculosis is too expensive
and too difficult to treat. The authors of the current study take note
of the debate about "whether to consider multidrug-resistant
tuberculosis treatable or untreatable, given the often limited
resources available." Some have claimed that multidrug-resistant
tuberculosis can be treated with a short course of chemotherapy
(i.e., treatment based on isoniazid and rifampin, the very drugs to
which multidrug-resistant strains of M. tuberculosis are, by
definition, resistant). It was not until last year that this
misconception was put to rest. In a six-country study, the cure
rates among patients with laboratory-documented,
multidrug-resistant tuberculosis were well under 50 percent in most
settings.5 In a study in Ivanovo Oblast, Russia, only 5 percent of
patients with multidrug-resistant tuberculosis were cured by
short-course chemotherapy.6
It is not surprising that patients infected with multidrug-resistant
strains of M. tuberculosis are not cured by treatment with the drugs
to which the strains are resistant. Moreover, delays in establishing
the diagnosis and initiating effective therapy are associated with
poor outcomes, even when patients do finally receive effective
therapy. In accordance with the current public health convention, all
patients in Turkey who have smear-positive pulmonary tuberculosis
receive empirical short-course chemotherapy based on isoniazid and
rifampin. In the study by Tahaolu et al., drug-susceptibility testing
was performed on specimens obtained from patients at the outset
of therapy, and the results were then ignored. The delay in initiating
effective therapy might have been reduced if the results of these
tests had been taken into account.
It is not standard practice in North America or in Europe to perform
such laboratory tests and then disregard the results. Why would
such a procedure be followed? In most resource-poor settings, all
patients receive empirical, standardized short-course chemotherapy,
and it is assumed that drug-susceptibility testing is not available.
Turkey is not a resource-poor country but geopolitically a part of
Europe. At the facility described in this report, although it is
perhaps not as handsomely equipped as a referral center in the
United States, doctors have far more resources at hand than do the
beleaguered doctors trying to battle tuberculosis in Latin America,
the former Soviet Union, and other regions where
multidrug-resistant tuberculosis is a major problem. The report by
Tahaolu et al. shows that multidrug-resistant tuberculosis is
treatable, at least where there are centers of excellence to deal with
the problem.
What about countries where there are no centers of excellence? In
a squatter settlement in Haiti and in a slum in Peru, my colleagues
and I have obtained similar cure rates in treating patients with
chronic multidrug-resistant tuberculosis.7,8 Many communicable
diseases can now be cured. Others, although still uncurable, can be
suppressed effectively with therapy. That patients with
multidrug-resistant tuberculosis are going untreated raises the
general question of the standards of care for patients with chronic
infectious diseases who have the misfortune to live in impoverished
countries. The assumption that these diseases are treatable in some
places and not in others is widely accepted. A lack of infrastructure
is commonly cited as the justification for lower standards of care in
some countries, but the real issue is cost. It has been argued that
the high cost of "second-line" antituberculosis medications makes
the treatment of multidrug-resistant tuberculosis problematic in poor
countries. However, the prices of these medications, which have
long been off patent, are exorbitant because there has not been a
concerted effort to treat patients who have tuberculosis and who
live in poverty.9 The destitute sick generate no perceptible demand
in the medical marketplace.
The most important question facing modern medicine involves
human rights. We are witnessing a growing "outcome gap." Some
populations have access to increasingly effective interventions;
others are left out in the cold. The more effective the treatment, the
greater the injustice meted out to those who do not have access to
care.
The question of global injustice applies directly to AIDS, which has
recently overtaken tuberculosis as the world's leading infectious
cause of death among adults. Over the past five years, deaths from
AIDS in the United States have dropped sharply, as have
admissions related to HIV infection in U.S. hospitals, because of
widespread use of highly active therapy against the virus. But these
advances, like those in the treatment of multidrug-resistant
tuberculosis, have served only a tiny minority of persons throughout
the world who could benefit from them. For most HIV-infected
persons, these lifesaving drugs are unavailable. We hear all kinds of
excuses. Efforts to treat AIDS and multidrug-resistant tuberculosis
in areas such as Africa and Haiti, which lack a health care
infrastructure, are dismissed as "unsustainable" or "not appropriate
technology." Antiviral therapy and complex antituberculosis
therapies are not considered cost effective in an era in which
money is worshipped so ardently that it is difficult to attack market
logic without being called misguided or irresponsible.
In too many policy discussions, the argument that treatment is not
cost effective is largely a means of ending unwelcome discussions
about the destitute sick. A high-ranking official in the U.S.
Department of the Treasury recently objected to a strategy that
would make anti-HIV drugs available on the continent where they
are most needed. He is quoted as saying that Africans lack the
necessary "concept of time," implying that the drugs would be
ineffective because of the required schedule of administration.10
Despite the absence of data that support these claims and much
experience to the contrary they are persuasive within the elite
circles where decisions are made that affect the health and fates of
millions of the world's sick.
Prevention is, of course, always preferable to treatment. But
epidemics of treatable infectious diseases should remind us that
although science has revolutionized medicine, we still need a plan
for ensuring equal access to care. As study after study shows the
power of effective therapies to alter the course of infectious
disease, we should be increasingly reluctant to reserve these
therapies for the affluent, low-incidence regions of the world where
most medical resources are concentrated. Excellence without equity
looms as the chief human-rights dilemma of health care in the 21st
century.
Paul Farmer, M.D., Ph.D.
Harvard Medical School
Boston, MA 02115
References
1. Tahaolu K, T�r�n T, Sevim T, et al. The treatment of
multidrug-resistant tuberculosis in Turkey. N Engl J Med
2001;345:170-174.
2. Pablos-M�ndez A, Raviglione MC, Laszlo A, et al. Global
surveillance for antituberculosis-drug resistance, 1994-1997. N
Engl J Med 1998;338:1641-1649. [Erratum, N Engl J Med
1998;339:139.]
3. Program in Infectious Disease and Social Change. The global
impact of drug-resistant tuberculosis. Boston: Harvard Medical
School, 1999.
4. Espinal MA, Laszlo A, Simonsen L, et al. Global trends in
resistance to antituberculosis drugs. N Engl J Med
2001;344:1294-1303.
5. Espinal MA, Kim SJ, Suarez PG, et al. Standard short-course
chemotherapy for drug-resistant tuberculosis: treatment
outcomes in 6 countries. JAMA 2000;283:2537-2545.
6. Primary multidrug-resistant tuberculosis -- Ivanovo Oblast,
Russia, 1999. MMWR Morb Mortal Wkly Rep
1999;48:661-664.
7. Farmer PE, Bayona J, Shin S, et al. Preliminary results of
community-based MDR-TB treatment in Lima, Peru. Int J Tuberc
Lung Dis 1998;2:Suppl:S371-S371.
8 Farmer PE, Furin JJ, Shin SS. The clinical management of
multidrug-resistant tuberculosis. J Respir Dis 2000;21:53-6.
9. Kim JY, Furin JJ, Shakow AD, et al. Treatment of
multidrug-resistant tuberculosis (MDR-TB): new strategies for
procuring second- and third-line drugs. Int J Tuberc Lung Dis
1999;3:Suppl 1:S81-S81.
10.Kahn J. Rich nations consider fund of billions to fight AIDS.
New York Times. April 29, 2001:6.
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