Tubercle and Lung Disease

Item

Title: Tubercle and
Lung Disease
extracted text: rub. nlc andt-unx
74 I45-146
.
Longman Group UK Lui

Tubercle and
Lung Disease

Editorial

Drugs are not enough
Failure of short-course chemotherapy in a district in India

II

undertaken in Beijing. China, where twice-weekly, com
The world owes a debt of gratitude to India for its research
pletely supervised treatment resulted in the cure ol many
in the field of tuberculosis. It is India that taught us about
new patients2 and later of many chronic patients/ In the
the supreme importance of bacteriology in the diagnosis
IUATLD supported programmes in Africa and Central
and control of tuberculosis; it is the research conducted in
America.4-' Styhlo introduced hospitalization during the
India that has shown that hospitalization is not essential; it
initial phase of chemotherapy for patients unable to attend
has provided us with principles of chemotherapy, includ
treatment centres daily, with gratifying results.
ing the increasingly important knowledge that intermittent^
It is to be hoped that India will not only solve the
treatment is as good as daily treatment. *
problems presented in Datta's report, but that it will again
During the Jubilee celebrations of the National Tuber
assume scientific leadership in this area. Perhaps the way
culosis Institute (NTI) in Bangalore. Halfdan Mahler, the
to proceed is not to try to add minor improvements to the
then Director General of the WHO and a former researcher
exiting programme, but to start from ’the other end . as it
of the NTI. was quoted as saying; All countries benefit
were, by organizing perfect, completely supervised treat
from the fruits of Indian research - all countries except
ment ,(this is possible due to the excellence of the
India/ The study reported by Dr Manjula Dana and her
epidemiological teams working in the Tuberculosis Re
colleagues in this issue constitutes both a powerful and a
search Centre in Madras) and then start removing
rather sad confirmation of Dr Mahler s assessment.
individual, more costly components of such an experimen
In this study a fully intennittent 6 month regimen with
tal programme, while retaining excellent results. Even a
twice weekly rifampicin, isoniazid and pyrazinamide was
wealthy country would be loo poor to allow treatment
offered to almost 4000 smear-positive patients with pul
programmes of the kind described by Dr Manjula Datta to
monary tuberculosis in North Arcot district; those who
continue; possibly even expensive hospitalization would
could not attend twice weekly (about one third of the
prove more cost effective in terms of epidemiological
patients) were offered a -standard- regimen of isoniazid
impact.
and thiacetazone.
The way this study was conducted and the results n
Stefan Grzybowski
obtained constitute an unmitigated disaster^ there weie
University of British Colombia
apparently 416 registrations with 2 or more treatment
Vancouver General Hospital
cards ( we are not told if such patients received double or
Respiratory Division
triple dosage). Only a little more than 40% of patients
Vancouver
completed 80% or more of treatment while a slightly larger
Canada
group took less than 50% of chemotherapy. The fatality
rate was extremely high/with over one quarter of the is >• -■'
References
patients dying, while another quarter remained bacten1 Grzybowski S. Enarson D E. Fate of cases of pulmonary
ologicallv positive when examined 6-36 months after
tuberculosis under various treatment programmes. Bull Im Union
startinc treatment. Resistance to antimicrobial agents was
Tuberc 1978; 53 (2): 70-75.
common among such cases, with 60-80% of them show-^
■> G Q. Kan. L. X. Zhang. J. C. Wu. Z. L. Ma. C. W. Liu. F. Z. Sun.
Supervised intermittent chemotherapy for pulmonary tuberculosis^
ing resistance to INH and 12% to rifampicin.
in a rural area of China. Tubercle 1985; 66: 1-7
7
These results are no better than would have been the
3 L. X. Zhang. G. Q. Kan. J C. Wu. C. W. Liu. V. S Dai. F. Z Sun.
case if no treatment whatsoever had been given.1 The
The control of chronic infectious patients with pulmonary
tuberculosis in a rural area of China. Tubercle 1989; 70: 21--5. _
causes of this disaster are multiple, but most likely relate
4 Stvblo K. IL'AT Paris. Chum H J. Treatment results of smearto non-compliance of the health staff with regulations
positive tuberculosis in the Tanzania National Tuberculosis and
governing treatment, and non-compliance ot patient^with
Leprosv Programme: standard and shon-course chemotherapy.
XXVIth IL'AT World Conference on Tuberculosis and Respiratory
taking their medication.
Diseases 1986: 122-126.
__ There have been numerous attempts to improve pa
5. Nuyangulu D S. Nkhoma W N. Salampom F M L. Factors
successful
being
those
tients’ compliance, among the more
145

A

Journal of the Royal Society of Medicine Volume 85 April 1992

c
relevance to the pathology. It was recommended that
Salazopyrin be taken life-long, but the runner
withdrew this after 6 months and has had no further
episodes. It is obvious that since that time there has
been an increased awareness of lower gastrointestinal
problems in runners. I would suggest that the
runner described by myself had a milder version of
inflammatory' bowel disease to that described in your
Journal.
Wendy N Dodds
St Luke's Hospital
Bradford. West Yorkshire BD5 ONA

Gut fermentation

Eaton’s paper on gut fermentation (November JRSM
1991, p669) drew my memory back many years.
I think it was believed1 that the condition - intestinal
carbohydrate dyspepsia - was due to colonization
of the small gut by coliforms following a bout of
gastroenteritis. A high starch diet maintained the
abnormal bacterial population leading to abdominal
distension, the production of excess flatus and, as
months passed, increasing introspection, frustration
and polysymptomatology' in the patient.
When I was serving in the RCAF in the mid-fifties
a fighter pilot saw me with symptoms of intestinal
carbohydrate dyspepsia to such an extent that he
could not tolerate high altitude flying. He gave a
typical history. I took him off bread and other cereal
based food, potatoes, and pulses for 3 days - he was
then to fly again; he did so and was very much better.
I kept him on the same regimen for 2 weeks and
then added firstly bread, then other cereals and finally
potatoes over a further fortnight. He did not consult
me again.
I have seen many patients with similar symptoms
since then and they all did well. Patients were always
told the reasons for the low starch regimen.
I see fewer patients now, being partially retired
and working in a different field, but if I saw a
patient tomorrow with a bubbly distended gut
following, even remotely, an attack of diarrhoea,
I would ask for a stool culture and microscopy and
if these were normal I would advise the low starch
regimen. Only if symptoms continued would I ask for
further investigation.
G Matthews
47 Melbury Road
Holland Park. London W14 SAD

References
1 Scott RB. Price’s textbook of the practice of medicine,
10th edn. London: Oxford University Press, 1966:524-5

What is the best dosage schedule for patients?

Peter Keen (November 1991 JRSM, p640i states
‘non-compliance by patients is not a new discovery . . .’
quoting a perceptive and witty Stephen Leacock
reference. However, Hippocrates wrote that ‘the
physician should keep aware of the fact that the
patients often lie when they state they have taken
certain medicines’. In 1710, during a plague outbreak,
a judicial edict was read from pulpits in a district of
east Prussia that ‘all those would be regarded as
suicides and their corpses would be publicly hanged
who refused to take the prescribed medicines even if
these proved to be of no avail’.1 Keen states ‘It was
only about 20 years ago that compliance was formally

identified as an important factor in therapeutic
evaluation . . .’ referring to a valuable 1979
publication2.
Tuberculosis physicians were well aware, in the
mid-1950s, of non-compliance of patients taking bulky,
unpleasant PAS. In 1958 and 1962 I documented the
general, problem of self-administration of drugs, quoting
qpcarnples from other diseases and chemoprophylaxis
and summarized our findings from the Tuberculosis
Research Unit, Madras, that the problem applied notf
only to PAS but to isoniazid, a drug given in small
dosage, and even a placebo*'. Compliance led the
two MRC tuberculosis units to develop intermittent
regimens, making fully supervised chemotherapy
possibly then to shortening the duration of chemo-F
therapy and then to short duration fully intermittent/

regimens. We have moved far beyond once daily
dosage, discussed by Keen, to intermittency as
infrequent as once weekly in the continuation phase
of treatment and MRC colleagues5 have studied in
depth the mechanisms of action of pulses of anti-y
tuberculosis drugs.|Physician compliance6 remains
another essential issue.
Our MRC view is problems of patient compliance
are best solved by the development of intermittent

and depot regimens
Wallace Fox

28 Mount Ararat Road
Richmond. Surrey TW10 SPG

References
1 Nohl J. In: Clarke CH, transl. The black death.
A chronicle of the plague. London: George Allen & Unwin
Ltd. 1926:78
2 Hayes RB. Taylor DW, Sackett DL, eds. Compliance in
health care. Baltimore: Johns Hopkins University Press,
1979
3 Fox W. The problem of self-administration of drugs; with
particular reference to pulmonary tuberculosis. Tubercle
1958:39:269-74
4 Fox W. Self-administration of medicaments: a review of
published work and a study of the problems. Bull Int
Union Tuberc 1962;32:307-31
5 Mitchison DA, Dickinson JM. Laboratory' aspects of
intermittent drug therapy. Postgrad Med J 1971;
47:737-41
6 Fox W. Compliance of patients and physicians: experience
and lessons from tuberculosis - I and II. BMJ 1983;
287:33-5, 101-5

Crohn’s disease of the vulva

The letter from Hossain and Bazaz (November
1991 JRSM, p 693) suggests that if medical therapy
fails for Crohn’s disease of the vulva, vulvectomy or
debridement therapy may be required. I suggest
before resorting to surgery try local injection of
triamcinolone as a suspension into the vulval areas
both intradermally and below any ulcerated areas.
I discussed this in 1985 at my Presidential Address
to the Section of Coloproctology and I use this
technique for perianal, peristomal Crohn's disease
and pyodermal gangrenosum. I have only seen one
mild Crohn’s disease involvement of the vulva which
did not require this therapy but I would very strongly
recommend that it be tried before radical surgery. It
does require general anaesthetic and up to 40 mg can
be given at one time.
Douglas Millar
Senior Consultant Surgeon.
Colchester District General Hospital,
Essex

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