Current medical treatment for tuberculosis
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7375.1282 (Published 30 November 2002) Cite this as: BMJ 2002;325:1282All rapid responses
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Mutidrug resistant tuberculosis is one of the most important emerging
infectious diseases in the world. Its incidence may further rise due to
the increasing incidence of both HIV infection and diabetes. Both of these
infections cause immunosuppression in an individual increasing the
susceptbility to tuberculosis.
In diabetes polymorpho leucocyte action is impaired and there is
impaired phagocytosis and impaired intra cellular antioxidant bactericidal
activity. This is vital for the defences against the tuberculosis bacilli
which lives in the intracellular environment of the macrophage. The
effectiveness of intracellular killing mechanisms improve with better
glycaemic control.
Therefore, patinets newly diagnosed to have tuberculosis should also
be screened for diabetes apart from screening them for HIV infection.
Competing interests:
None declared
Competing interests: No competing interests
In Chan and Iseman's clinical review (1), some comments are made on
aspects of chemotherapy and management with which we take issue. The
points at issue have already been covered in the evidence-based guidelines
on both the chemotherapy and management (2) and the control and prevention
of tuberculosis (3) by the Joint Tuberculosis Committee of the British
Thoracic Society, but we feel that they bear re-statement.
a) Pyridoxine supplementation, of up to 50mg/day as routine:
Isoniazid peripheral neuropathy is very uncommon. Pyridoxine is
appropriate for those at increased risk of peripheral neuropathy (2).
However pyridoxine antagonises isoniazid on a milligramme for milligramme
basis. Studies have shown that only 6mg/day prevent peripheral neuropathy,
so only 10mg (the smallest tablet size available) should be used, if
indicated.
b) Routine liver function monitoring: Detailed advice has been given
(4) and is incorporated in the 1998 Code of Practice (2), but regular
liver function is not required in those with normal pretreatment liver
function, unless symptoms, in an informed patient, suggest hepatic upset.
c) Monthly visual acuity checks on ethambutol: In patients with
normal visual acuity (Snellen chart), normal renal function, and with an
ethambutol dose of 15mg/kg, ocular toxicity is ectremely rare, and there
is no evidence that regular ocular checks prevent events (5). Detailed
advice is again incorporated into the 1998 treatment guidelines (2).
d) The recommendation that all suspected/confirmed cases of
tuberculosis admitted to hospital should be in negative pressure
isolation: Of the 7300 tuberculosis patients in England and Wales,
approximately 4000 are culture confirmed, of these 1.3% have Multi-Drug
Resistant (MDR) TB (Scotland 0.3%, Northern Ireland O%). A detailed
algorithm is given in the 2000 Code of Practice (3), with risk
stratification for the patient, type of ward/room used and for risk of MDR
-TB.
Professor L.P.ormerod, Professor of Respiratory Medicine, Blackburn
Royal Infirmary, Blackburn Lancs, UK.
Dr I.A.Campbell (Chairman), Consultant Respiratory Physician, Llandough
Hospital, Cardiff, Wales.
Dr P.D.O.Davies, Consultant Respiratory Physician, Aintree University
Hospital, Liverpool, UK.
For the Joint Tuberculosis Committee of the British Thoracic Society.
1. Chan EC, Iseman MD. Current medical treatment for tuberculosis. Br
Med J 20002; 325: 1282-86.
2. Joint Tuberculosis Committee of the British Thoracic Society.
Chemotherapy and management of tuberculosis in the United Kingdom:
recommendations 1998. Thorax 1998; 53: 536-548.
3. Joint Tuberculosis Committee of the British Thoracic Society.
Control and prevention of tuberculosis in the United Kingdom: Code of
Practice 2000. Thorax 2000; 55: 887-901.
4. Ormerod LP, Skinner C, Wales JM. Hepatotoxicity of
antituberculosis drugs. Thorax 1996; 51: 111-3.
5. Citron KM, Thomas GO. Ocular toxicity from ethambutol. Thorax
1986; 41: 737-9.
Competing interests:
None declared
Competing interests: No competing interests
In their recent Clinical Review entitled Current Medical Treatment
for Tuberculosis[1], Chan and Iseman referred to the global resurgence of
tuberculosis and the increase in case rates seen in North America and
Western Europe over the last 10 years. Two of the causes mentioned for
these increased case rates are immigration and co-infection with HIV.
In Croydon, as in many other parts of London, we have seen changing
patterns of immigration with large numbers of refugees and asylum seekers
arriving from parts of the world with very high incidence of tuberculosis.
This has co-incided with a 100% increase in notifications in Croydon over
the last 11 years. HIV seroprevalence in new entrants in Croydon has been
surveyed by anonymous salivary testing with 5/115 (4.3%) positive[2]. To
try to address the issue of high rates of TB in new entrants to the UK,
the Joint Tuberculosis Committee of the British Thoracic Society
recommends new entrant screening for all immigrants, refugees and asylum
seekers from countries of high TB incidence[3]. In our view there is no
conclusive evidence that such screening is effective in areas with a very
mobile new entrant population.
We have set up a clinic for new entrants known to be living in
Croydon, many of whom are not notified through the Port of Arrival system.
This is a holistic clinic attended by Refugee Health Visitors who offer
help with wider needs such as housing issues, finding schools, registering
with General Practitioners etc. and screening for TB takes place at the
same time. We have diagnosed only 3 cases of active TB over a period of
47 months (see table). These had mild or absent symptoms and were not
infectious. Over the same period of time, approximately 110 cases of
active TB were diagnosed in symptomatic new entrants presenting either
through A/E, or referred by General Practitioners. Many of these were not
known to the appropriate official authorities and had therefore not been
contacted for screening prior to their diagnosis of tuberculosis.
Croydon new entrants screened Jan. 1999 - Nov. 2002 Total no. screened in New Entrant Screening Clinic 2855 TB diagnosed 3 BCG given 93 Chemoprophylaxis given 58 New entrants with TB diagnosed via A/E or GPs 110
It could be argued that the considerable resources required for new
entrant screening would be better spent on ensuring that all new entrants
have rapid and easy access to Primary Care for assessment of all health
needs. This is not the case at present. There should be a fast track
referral system to local Chest Clinics for early diagnosis of tuberculosis
and referral to HIV Clinics as appropriate. Chest Clinics should continue
to screen the children of new entrant families as children and teenagers
make up the group most likely to benefit from BCG or anti-tuberculous
chemoprophylaxis as appropriate.
1 Edward D Chan, Michael D Iseman. Current medical treatment for
tuberculosis. BMJ 2002;325:1282-6
2 Bowen EF, Rice PS, Cooke NT, Whitfield RJ, Rayner CF. HIV
seroprevalence by anonymous testing in patients with Mycobacterium
tuberculosis and in tuberculosis contacts. Lancet 2000;356(9240):1488-9
3 Control and prevention of tuberculosis n the United Kingdom:Code of
practice 2000.Thorax;55:887-901
Competing interests:
None declared
Competing interests: Croydon new entrants screened Jan. 1999 - Nov. 2002 Total no. screened in NewEntrant Screening Clinic 2855TB diagnosed 3BCG given 93Chemoprophylaxis given 58New entrants with TB diagnosedvia A/E or GPs 110
Dear Sirs,
Chan and Iseman have written an interesting overview on several
aspects of the treatment of tuberculosis.1
However, I was surprised by their claim that directly observed
therapy (DOT) is an effective means of ensuring completion of treatment.
They even illustrate this assertion in a figure where they compare
completion rates for patients on DOT and non-supervised therapy. What they
fail to inform the reader of is that this is based purely on observational
data.2 Although the review from which these figures were taken included
several randomised controlled trials, none of these trials evaluated the
relative effectiveness of DOT to non-supervised treatment - they compared
various types of DOT.
Now, a few years after that review was published, randomised
controlled trials of DOT versus non-supervised treatment have been done
and have even been assessed in a systematic review.3 The conclusion is not
in favour of believing in DOT’s effectiveness. Clearly, this evidence must
be taken seriously into consideration when making a statement on whether
or not DOT is effective.
Interestingly to some of us, perhaps, this seems to be yet another
example of the tendency to overestimate the effectiveness of an
intervention when relying on non-randomised studies.4
1. Chan ED, Iseman MD. Current medical treatment for tuberculosis.
BMJ 2002;325:1282-1286.
2. Chaulk CP, Kazandjian VA. Directly observed therapy for treatment
completion of pulmonary tuberculosis: consensus statement of the Public
Health Tuberculosis Guidelines Panel. JAMA 1998;279:943-8.
3. Volmink J, Garner P. Directly observed therapy for treating
tuberculosis (Cochrane Review). In: The Cochrane Library, Issue 4, 2002.
Oxford: Update Software.
4. Kunz R, Vist G, Oxman AD. Randomisation to protect against selection
bias in healthcare trials (Cochrane Methodology Review). In: The Cochrane
Library, Issue 4, 2002. Oxford: Update Software.
Competing interests:
None declared
Competing interests: No competing interests
Dear Sirs,
Though Tuberculosis has faded out and again staged a renaissance in the
minds of many western health care professionals,it has remained THE killer
in developing countries such as Nepal.
Agressive use of DOTS and its variants will only work if adequate access
to healthcare were coupled with a strong political and socio-economic
backing(Its an uphill struggle even then).That,however,is lacking as
political sloganeering gets mixed up with aid grants and a decidedly poor
population - who would rather till their fields rather than walk 2-3
hrs(sometimes upto 1-2 days)to the nearest healthcare facility in Nepal
for upto nine months.
I do appreciate the benefit of anti-tubercular medication and particularly
DOTS.However,the message that any therapy,however good,will not be truly
beneficial unless something can be done for the health and lives of people
as a whole rather than just a disease should perhaps be emphasized.
Competing interests:
None declared
Competing interests: No competing interests
The global epidemic of tuberculosis is getting worse every year. We
have no new diagnostic tests for tuberculosis, no new drugs, no magic
cures. Even in the high-tech medical centers of the United States and
other industrialized countries, doctors use nineteenth-century diagnostic
methods and 30-to 50-year old treatments—because there are no others—for a
disease that is running way ahead of us. Until very recently, there was no
interest in this crisis from anybody except the few physicians, nurses,
and health-care workers who treat tuberculosis daily. But things are
beginning to change.
India is one of few ‘hot spots’ of the world where multidrug
resistant tuberculosis has increased beyond control. Though World Bank
aided DOTS-therapy has been implemented and covered more than 50% of the
country but still things are not under control. As more than 60% of
tubercular cases are being treated by GPs of which most of them are
unqualified doctors things are getting out of control. Thus treatable TB
cases land up with MDR-TB.
Competing interests:
None declared
Competing interests: No competing interests
Drs Chan and Iseman have made an important contribution to the debate
on control of tuberculosis with their paper on medical treatment. The
authors highlight the importance of the DOT component of the DOTS strategy
and argue that improvements in patient adherence are critical if control
of this global pandemic is to be achieved. We wholeheartedly agree that
ensuring adherence is important but believe that the evidence that DOT is
the most effective way to ensure adherence to treatment in all settings is
not as clear-cut as the authors suggest (1,2,3). Indeed in their figure on
the effectiveness of different adherence models drawn from Chaulk and
Kazandjian’s consensus statement the confidence intervals are wide and
cross, underlining something of this uncertainty.(4) Having said this,
however, it seems clear that in some settings the DOT component of DOTS
does improve adherence. Programmes in such diverse settings as New York
City, Peru, Tanzania, and parts of India and China, for example, lend
support to this contention.
What is interesting is how the terminology of DOTS is evolving,
perhaps as it attempts to capture something of the diverse approaches that
might be demanded of the DOT component in different settings. We now have
straight DOT, ‘modified’ DOT, and ‘enhanced’ DOT, not to mention clinic-
based DOT, community-based DOT, and DOTS-Plus for multidrug resistant
tuberculosis. The emerging diversity reinforces our belief that DOT
programmes need to be context sensitive. Therefore, we would argue that
what is needed is a more nuanced understanding of the contextual factors
that support or weaken different models used to encourage treatment
adherence. Indeed, all components of the DOTS strategy should, we believe,
be analysed and evaluated using a framework that captures the complexity
of the wider health and socio-political system in which these components
are embedded.(5) Only by capturing in our analysis and evaluation tools
something of the complex environment in which tuberculosis programmes sit
can we hope to draw lessons (from both successes and failures) that might
be applicable to other settings.
1. Zwarenstein M, Schoeman JH, Vundule C, Lombard CJ, Tatley M.
Randomised controlled trial of self-supervised and directly observed
treatment of tuberculosis. Lancet. 1998 Oct 24;352(9137):1340-3.
2. Kamolratanakul P, Sawert H, Lertmaharit S, Kasetjaroen Y, Akksilp S,
Tulaporn C, Punnachest K, Na-Songkhla S, Payanandana V. Randomized
controlled trial of directly observed treatment (DOT) for patients with
pulmonary tuberculosis in Thailand. Trans R Soc Trop Med Hyg. 1999 Sep-
Oct;93(5):552-7.
3. Volmink J, Garner P. Directly observed therapy for treating
tuberculosis. Cochrane Database Syst Rev. 2001;(4):CD003343. Review.
4. Chaulk CP, Kazandjian VA. Directly observed therapy for treatment
completion of pulmonary tuberculosis: consensus statement of the Public
Health Tuberculosis Guidelines Panel. JAMA 1998;279:943-8.
5. Capturing health systems complexity: a conceptual framework for
development, implementation, evaluation, and monitoring of communicable
disease programmes. Atun R, Lennox-Chhugani N, Samyshkin YA, Coker RJ.
EJPH (in press).
Competing interests:
None declared
Competing interests: No competing interests
Dear colleagues,
first of all I wanted to say that last year I have been interpreting for
Dr. Michael Iseman in Tartu, Estonia, where he presented lectures about
multidrug resistant tuberculosis for TB professionals from many countries.
His lectures were really very usefull for all participants and they were
so enthusiastic and interesting! I also work in ordinary state hospital
for patients with TB. We have 200 beds (120 for adults, 50 for children
and 30 - for surgery department).
In Russia anti-TB drugs are absolutely free for patients. Still now many
of our patients stay in hospital for long period - 6 months or even more
and stay in hospital and all care is also free. If a patient is working,
during one year government pays full salary (average salary in my region
is 150 USD) from social insurance fund, and if he does'nt work - 20 USD.
We started to use DOTS three years ago, but DOTS programme was not a new
one for us - even in the Soviet Union in hospital patient should take
drugs under control.
But the situation is still bad. Why?
First - many patients in 1990-1999 have had uneffective treatment, because
sometimes we had only 1-2 drugs. And now we have many MDR cases
Second - we have many primary MDR cases from contact
Third - some people have no motivation. Typical situation and my typical
patient - a person form prison, without work, home and family. In the
hospital, when he has TB, he will obtain food and bed, and payment for
disability. If he will recover,no employer will give him job, because
people do not like ex-prisoners and they are afraid of tuberculosis. Many
of patients are alcoholic. In my region we have no cases of HIV-assotiated
TB.
Forth - in far-away rural areas patients have no possibility to come to TB
office every day.
And may be one of the most important reasons - lack of information in the
community - people do not know what is tuberculosis, they are afraid and
some patients are in isolation - even in the family.
I am agree with opinion, that in distant areas DOTS soulb be changed - in
my country we can place patient to the hospital to intensive phase of
treatment, and then he can take medications in TB office every 10 days for
continuation of treatment.
But at least in the first phase treatment should be under durect
observation, because some people do not want to take medications, some can
forget and in prisons patients sometimes sell rifampicine for treatment of
sexual-transmitted diseases. One of my patients - very nice person, he had
generalised TB with lung, pleural, peritoneal, renal and spinal
involvement, said "Nobody explained to me, what is happening. And during
stay in other hospital I put my drugs in the toilet (!!!)- that was for
one month". I spent much time, discussing with him during my duties in the
hospital. Fortunately he recovered without any problems, but he could die
without appropriate information. MDR patients should be treated in
hospital - because they are dangerous and second line drugs have
unpleasant side effects.
In these ways we can reduce number of infectious cases and at least
isolate MDRs. And after 3 years of DOTS implementation we see the results
- number of new cases in my region slightly decreased. I hope that we can
reduse number of patients. But we should do something and change DOTS
according to our circumstances.
Competing interests:
None declared
Competing interests: No competing interests
The authors claim that DOT is effective in enhancing adherence and
treatment completion. However a recent Cochrane review by Volmink and
Garner (not cited by the authors) concludes that "randomized trials
provide no evidence that directly observed therapy in low and middle
income country settings improves cure or treatment completion rates in
patients with tuberculsosi". Can the authors respond to this conclusion
and explain why this systematic review did not feature in their report.
Sincerely
Ross Upshur
Competing interests:
None declared
Competing interests: No competing interests
Current medical treatment for tuberculosis.:Extra Box (Patient Information)
"Although there are modest side effects from drugs used to treat
tuberculosis, serious toxicity is rare and is readily managed if reported
promptly." is quoted from the patient information. Good and practical
advice for patients, but what if the doctors involved in the case are not
aware of potential side effects? From personal experience I know patients
are being told episodes of optical neuropathy whilst taking
antituberculous chemotherapy cannot possibly be medication related but
signs of the disease. Perhaps the example of Blackburn Royal Infirmary
should be followed. Once the doctors have decided on the appropriate
medication the patient is shown and talked through each tablet, told of
possible side effects and told to report any adverse reactions.
As GP`s are not usually aware of medication side effects the patients
only recourse is the consultant. Consultants must be aware and also warn
patients of potential side effects.
Competing interests:
None declared
Competing interests: No competing interests