W O R L D H E A L T H ORGANIZATION
EXECUTIVE BOARD Thirty-third Session
Provisional agenda item 2.6
ORGANISATION MONDIALE DE LA SANTÉ
EB33/13 Z 25 November 1963 ORIGINAL: ENGLISH
PROGRAMME REVIEW - TUBERCULOSIS
The attached document EB)2/2 was originally submitted to the thirty-seсond session of the Executive Board but the Board, at that time, decided to postpone consideration of this item until the thirty-third session.
W O R L D H E A L T H
ORGANIZATION ORGANISATION MONDIALE
DE LA SANT E
EXECUTIVE BOARD
Thirty-second Session
Provisional agenda item 3,7
EB52/2 .、 1 May 1963
ORIGINAL: ENGLISH
PROGRAMME REVIEW - TUBERCULOSIS
At the thirty-first session of the Executive Board1 a suggestion was made by several members that it would be of value for a regular and comprehensive review of one of the Organization's programme activities to be undertaken at each future session of the Executive Board.
The Director-General has considered it appropriate for the programme review at the thirty-second session of the Executive Board to be on the subject of
"Tuberculosis", which was amongst the subjects suggested during the discussion.
Accordingly, there is attached an outline document, which will be amplified when it is introduced to the Executive Board.
1 EB3l/Min/l5 Rev.l
EB32/2
page 2
OUTLINE OF WHO'S TUBERCULOSIS PROGRAMME 1 . INTRODUCTION
A conservative estimate of today's,global tuberculosis problem would be:
a pool of 10-15 million infectious cases, which is augmented each year by 2-3 million new cases and depleted by 1-2 million deaths together with an unknown number of
spontaneous and induced cures. The overwhelming part of this problem is faced in the developing countries, as illustrated by the fact that, in some of these
countries more than 70 per cent, of children are infected at the age of 14 years^
as against less than two per cent, in certain economically more favoured countries.
These figures express the problem of tuberculosis symbolically but the social aim of any tuberculosis control programme is obviously to lessen the real problem of human suffering and economic losses caused by the disease. It is often maintained that such economic losses are negligible in countries where there is unemployment. This argument stems from a static concept of the economies of disease. In a dynamic
concept of cumulative economic growth, the main purpose of neutralizing and preventing infectious sources of tuberculosis today is to contribute towards making the new
generations fit to meet the demand for efficient manpower when the economic take- off accelerates. Por this purpose, as well as for that of creating confidence in developing health services through the alleviation of present suffering, the diminution of tuberculosis as a public health problem has been allotted a high priority by
public health administrators in most of the developing countries• r
2 , W H O。R E S E A R C H PROGRAMME IN TUBERCULOSIS
The apparent excess of knowledge over its application has sometimes encouraged the view that there is no need for WHO to spend time and money on research in
tuberculosis. However, an analysis of the logistics of tuberculosis programmes in the developing countries over the last decade demonstrates the difficulties inherent in applying a knowledge originally developed for affluent socio-economic conditions, e.g,, the fragility of liquid BCG vaccine and the cost of individualized chemotherapy.
WHO'S assistance in the field of research takes various forms. A number of high-quality research programmes have arisen out of WHO-assisted service projects.
In other instances, Ш0 fs assistance has been directly aimed at setting up permanent
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national research centres. Finally, much of WHO'S research is carried out on a contractual basis by a large number of existing research institutes and laboratories;
here^ W H Ofs role is mainly confined to suggesting technical problems for investigation^
and co-ordinating and analysing results, in addition to making modest financial grants to the institutes concerned. A few examples of this research - arising out of which more than 125 papers have been published during the last five years - are mentioned below.
Standardization and simplification of products and techniques
WHO-directed research has proved that the diversity of testing/reading
techniques and tuberculin products used has been impeding inter- and intra-coimtry epidemiological comparisons of infection levels. It has also proved that, if a standard tuberculin is given in a standard dose and if the reaction is read according to a standardized technique, such a test is probably the most significant instrument available in tuberculosis epidemiology. This finding made WHO stimulate the
production and standardization of a batch of PPD tuberculin large enough to satisfy world needs for several decades. By this means it is possible not only to avoid repetition of extensive costly assays in animals and human beings, but to facilitate comparison of data from different areas and for different periods. This research also demonstrated large variations in potency between PPD dilutions due to variable adsorption of tuberculin to the inner surface of the container. A stabilizing diluent was therefore introduced together with the above mentioned international PPD batch, leading to tuberculin dilutions of accurate potency and high stability.
The major difficulty in culturing Myco, tubérculosis in simple laboratories such as are found in most developing countries is the complicated technique of preparing the culture media. Preliminary results from a co-opcrative study of a liquid medium prepared, transported, and stored in freeze-dried form show that this medium is as sensitive as the routinely employed solid medium and does not have a higher contamination rate.
In order to identify the underlying etiological causes for the so-called non- specific allergy commonly encountered in tropical countries, a co-operative project has worked on the development of standard methods for the classification of myco-
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b a c t e r i a a n d , at t h e s a m e t i m e , o n p r o v i d i n g i n f o r m a t i o n c o n c e r n i n g t h e g e o g r a p h i c a l d i s t r i b u t i o n o f d i f f e r e n t t y p e s o f m y c o b a c t e r i a c a u s i n g i n f e c t i o n a n d d i s e a s e i n m a n . P r o m t h e a v a i l a b l e d a t a i t a p p e a r s t h a t t h e o c c u r r e n c e o f a t y p i c a l s t r a i n s i s c o n c e n t r a t e d i n c e r t a i n g e o g r a p h i c a l r e g i o n s .
I n v i e w o f t h e a l a r m i n g l y h i g h p r e v a l e n c e s o f a c q u i r e d a n d p r i m a r y d r u g r e s i s t a n c e of M y c o . t u b é r c u l o s i s t h a t a r e b e i n g r e p o r t e d , t h e r e i s a n u r g e n t n e e d t o i n t r o d u c e i n t e r n a t i o n a l s t a n d a r d s i n t h i s f i e l d . T h r e e f u l l y q u a n t i t a t i v e m e t h o d s d e v e l o p e d b y d i f f e r e n t e x p e r i e n c e d l a b o r a t o r i e s a r e n o w b e i n g s t u d i e d b y W H O i n c o n s u l t a t i o n w i t h a n u m b e r of n a t i o n a l r e s e a r c h i n s t i t u t i o n s .
M a n y d i f f e r e n t B C G s t r a i n s a r e u s e d f o r t h e m a s s p r o d u c t i o n o f B C G v a c c i n e s b y v a r i o u s m e t h o d s . I n t e r n a t i o n a l l y r e - c o g n i z e d r e q u i r e m e n t s f o r B C G v a c c i n e s w o u l d t h e r e f o r e s e e m m o s t d e s i r a b l e . T h r e e s e r i e s of c o - o p e r a t i v e s t u d i e s c o m p l e t e d s o f a r h a v e p r o v i d e d t h e f o u n d a t i o n f o r t h e e l a b o r a t i o n of m i n i m u m r e q u i r e m e n t s f o r B C G v a c c i n e .
E p i d e m i o l o g y
A g r e a t a m o u n t o f e p i d e m i o l o g i c a l m a t e r i a l c o l l e c t e d w i t h u n i f o r m m e t h o d s a n d t e c h n i q u e s i n a b o u t 3 0 s a m p l e s u r v e y s i n d e v e l o p i n g c o u n t r i e s h a s y i e l d e d i m p o r t a n t i n f o r m a t i o n o n t h e s c o p e a n d l i m i t a t i o n s o f c u r r e n t s u r v e y m e t h o d o l o g y . F o r i n s t a n c e , t h e s t r i k i n g l a c k o f c o r r e l a t i o n b e t w e e n a s u b s t a n t i a l p r o p o r t i o n o f X - r a y shadows., o n t h e o n e h a n d , a n d p o s i t i v e b a c t e r i o l o g i c a l f i n d i n g s a n d t u b e r c u l i n r e a c t i o n s , o n t h e o t h e r , h a s m a d e i t c l e a r t h a t m a n y s u c h s h a d o w s a r e p r o b a b l y , o f a n o n - t u b e r c u l o u s n a t u r e .
I n s e v e r a l l o n g i t u d i n a l s t u d i e s l a r g e p o p u l a t i o n s u n d e r t h e i n f l u e n c e o f v a r i o u s t y p e s a n d i n t e n s i t i e s o f a n t i t u b e r c u l o s i s m e a s u r e s a r e f o l l o w e d - u p a t s h o r t i n t e r v a l s t o m e a s u r e t h e p a r a m e t e r s n e c e s s a r y f o r p e r f e c t i n g e p i d e m e t r i c m o d e l s t h a t c a n b e u s e d f o r c a l c u l a t i n g r e a l i s t i c f o r e c a s t s o f l o n g - t e r m c o n t r o l a n d e r a d i c a t i o n i n t e r - v e n t i o n s . I m p o r t a n t f i n d i n g s a r e : t h e l o n g i n t e r v a l b e t w e e n p r i m a r y i n f e c t i o n a n d t h e a p p e a r a n c e o f t h e d i s e a s e ; t h a t t h e g r e a t m a j o r i t y o f n e w c a s e s a r i s e i n p r e v i o u s l y i n f e c t e d a d u l t s； a n d t h a t it is p o s s i b l e a m o n g t h e l a t t e r t o p i c k o u t s m a l l h i g h - r i s k g r o u p s o n v^iich p r e v e n t i v e e f f o r t s c a n b e c o n c e n t r a t e d .
E B 3 2 / 2
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Public health
Studies on simultaneous BCG and smallpox vaccination have been undertaken to examine the possible interaction in terms of immunity and frequency of local complications. Preliminary data indicate that this is a safe public health procedure which may reduce cost and increase coverage.
Considerable gains in terms of cost, training, integration, and coverage, could be achieved in many developing countries through indiscriminate BCG vaccination, that is, dispensing with the tuberculin test prior to BCG vaccination. The first results from pilot studies indicate that this vaccination procedure will not give rise to an intolerable frequency or gravity of local complications.
As there are indications that persons with non-specific sensitivity have some degree of acquired immunity to tuberculosis, a trial has been designed to assess the protective effect of BCG vaccination in one of the many tropical and sub-tropical countries in which low-grade sensitivity has been found to be highly prevalent.
Several research centres are investigating the clinical efficiency and
applicability of domiciliary/ambulatory chemotherapy of tuberculosis in populations living in adverse socio-economic conditions. The first basic finding was that one year1 s well supervised domiciliary chemotherapy is as effective as one year's
hospital treatment with the same combination of drugs, and that it does not expose the patient's contacts to any special risk. Further trials are under way to find the cheapest possible - yet efficient and non-toxic - regimens. A most delicate problem for controlling tuberculosis is the indispensable long-term co-operation of patients. The alarming increase in cases with bacilli that have acquired resistance to the standard drugs is the consequence of inadequate co-operation. Directly supervised, intermittent chemotherapy could go a long way towards improving this situation; the first results were promising enough to prompt a complete series of investigations to determine patients1 response to various frequencies of adminis- tration of both first- and second-line drugs.
In sociological investigations, attempts have been made to disclose the main reasons for treatment default• This problem is being approached through the analysis of inter- and intra-individual differences in the regularity of self-
E B 3 2 / 2 page 6
medication with varying intensities and systems of motivation。 No clear-cut
correlation has been found between regularity and such apparently important factors as education, living standards, personality, etc. But in a controlled study of awareness of symptoms in villagers, it was found, contrary to expectations, that more than three-quarters of all persons with highly infectious tuberculosis not only are aware of symptoms indicative of tuberculosis, but have already taken some action to seek help - a finding of great potential importance for treatment motivation.
Another project has studied, in a community, the usefulness of isoniazid chemoprophylaxis in preventing infection from developing into disease. Whereas patients with infectious tuberculosis living in the same area took the prescribed drugs with reasonable regularity, less than one-fifth of the group receiving chemoprophylaxis did so. This finding may explain why the distribution of
isoniazid did not significantly prevent infection from developing into disease in this study population.
The utility of operations research methodology in tuberculosis control is being tested in several field projects. Because this "science of common sense" deals
with the total - ecological and sociological - system in a country, it promises better results in developing public health strategies in tuberculosis control than the
conventional pragmatic, and, by necessity, often biased, approach, 3 . WHO'S CONTROL PROGRAMME IN TUBERCULOSIS
WHO-assisted activities in the past
BCG vaccination was the obvious first choice when the need for some international measure to reduce the tuberculosis problem was realized more than a decade ago.
To date, approximately 400 million people have been tuberculin-tested and of these approximately 15〇 million have been BCG-vaccinated, in internationally-assisted programmes covering 6l countries and territories. Twelve WHO/uNICEF-assisted programmes are still in progress with a monthly output of about 2#5 million tests and one million vaccinations. However impressive these figures may b e , certain technical and operational observations must be considered in assessing the influence of these campaigns on the tuberculosis problem in the countries concerned. Special
EBJ2/.2 page 7
assessment surveys h a v e shown that less t h a n satisfactory levels of allergy have been found in several tropical countries owing to difficulties in ensuring adequate protection of the fragile vaccine against heat and l i g h t . There are also
indications that in some programmes the vaccination coverage of the susceptible population has b e e n insufficient. Increasing emphasis has therefore b e e n placed on the integration of B C G vaccination into a more comprehensive control programme and on the use of h e a t - s t a b l e , f r e e z e - d r i e d , BCG vaccine。
Demonstrat ion and training centres were designed to demonstrate and teach m o d e r n diagnostic and curative m e t h o d s . Initially these h i g h l y specialized centres could not serve the needs of a gradually expanding control service as the methods demonstrated - copied from clinical tuberculosis services in the economically advanced countries: s u r g e r y , collapse t h e r a p y , isolation - were out of tune w i t h local needs and r e s o u r c e s . T h e advent of inexpensive oral chemotherapy h a s now made possible a gradual evolution of the purpose of these centres towards referral and evaluation functions w i t h i n the framework of the n a t i o n a l tuberculosis p r o g r a m m e .
Prevalence surveys have b e e n an invaluable aid in overcoming a difficulty
encountered in many of the countries that request international assistance for their tuberculosis programmes: the lack of precise information o n the extent and nature of the tuberculosis p r o b l e m . Specially trained W H O teams were therefore set up to assist countries in carrying out sample surveys of the prevalence of tuberculosis and simultaneously to study a n d develop practical and reliable survey methods and t e c h n i q u e s . A vast amount of epidemiological data has b e e n accumulated from more than 30 such s u r v e y s , and relatively precise estimates of the prevalence of tuber- culosis in many c o u n t r i e s , particularly on the A f r i c a n c o n t i n e n t , have b e e n o b t a i n e d .
Summing up past W H O assistance in the field of tuberculosis c o n t r o l , two
features stand outs the feasibility of applying control measures on a country-wide s c a l e , and the limitations in transposing specialized services from economically advanced countries to those with limited financial and medical r e s o u r c e s •
E B 3 2 / 2 page 8
W H O - a s s i s t e d control activities today; national tuberculosis programmes
T h e objective of a n a t i o n a l tuberculosis programme is the control of t u b e r c u l o s i s , that i s， the gradual reduction of the number of infectious and infected persons -
in the context o f , and in consonance w i t h , the developmental process in the country as a w h o l e . Inexpensive means exist for putting such a control programme into effect partly through a direct attack with drugs upon the tubercle bacilli in the reservoir of h u m a n infectors and partly through increasing the specific resistance of the susceptible population w i t h B C G vaccination against the consequences of unavoidable exposure to tubercle b a c i l l i .
B u t the character of tuberculosis epidemiology is such that there is little prospect of lessening the problem rapidly• T o control t u b e r c u l o s i s , t h e r e f o r e , services must have the character of permanent programmes and not of emergency campaigns: even i f , for i n s t a n c e , a very substantial diminution in the present infectious pool were t o be brought about by a single case-finding and treatment c a m p a i g n , there is every likelihood that almost the same size of infectious pool w o u l d b u i l d up again in a few y e a r s1 time because most n e w infectious cases seem to result from the breakdown of an infection that took place several years a g o .
F u r t h e r m o r e , owing to the ubiquity of t u b e r c u l o s i s , only such control measures as lend themselves to application throughout the national territory can make an epidemiological i m p a c t . In this c o n n e x i o n , it is worth n o t i n g that mass B C G
v a c c i n a t i o n of "susceptibles" h a s proved to be a comparatively cheap a n d operationally simple measure- and that a considerable part of the infectious case-load can be
dealt w i t h by a basic h e a l t h unit - after very little specialized training - through simple microscopy diagnosis and ambulatory t r e a t m e n t . A t this j u n c t u r e , and taking a l l other priorities into c o n s i d e r a t i o n , a minimum national programme relying on these two elements w o u l d seem to be within the reach of all c o u n t r i e s .
If control measures are to be applicable n a t i o n a l l y , they must be socially
acceptable• For instance, the long-term success of the essential preventive services in tuberculosis depends on the amount of curative activities t h a t are linked with t h e m . In t u r n , the felt need for curative services depends on the general public's awareness of the d i s e a s e . I t has b e e n shown that this awareness is much greater
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than previously s u s p e c t e d , and curative services must therefore be made available to all persons whose symptoms prompt them to report for assistance and in whom tuberculosis is d i a g n o s e d . This can be achieved if all non-specialized health agencies are guided and assisted in diagnosing and curing the disease in the course of their routine f u n c t i o n s .
In s h o r t , the national tuberculosis p r o g r a m m e , if it is to exert an impact
on the problem of t u b e r c u l o s i s , must take into account the epidemiological efficiency of the t o o l s , and their applicability and a c c e p t a b i l i t y . T h e methods recommended b y W H O for developing national tuberculosis programmes are derived from the analysis of k e y variables in this system of e p i d e m i o l o g i c a l , m e d i c a l , o p e r a t i o n a l , and
sociological f a c t o r s . The functional relationships of these methods may be illustrated as follows:
W H O ' s assistance to national tuberculosis programmes is most often g i v e n through a team comprising a medical o f f i c e r , a s t a t i s t i c i a n , an X - r a y t e c h n i c i a n , a
laboratory t e c h n i c i a n , and a public h e a l t h n u r s e . This team n o r m a l l y stays in the country for two to four years until a nationally applicable programme has b e e n defined and t e s t e d , training of all types of personnel c o n s o l i d a t e d , and national
E B 3 2 / 2 page 10
expansion b e g u n . In some of the R e g i o n s , inter-country teams assist governments
in assessing the epidemiological magnitude- of the tuberculosis p r o b l e m , the potentiality of developing tuberculosis c o n t r o l , and the operational performance of the national tuberculosis programme。 S e v e r a l of the R e g i o n s h a v e found it u s e f u l to co-ordinate all W H O assistance in tuberculosis through a R e g i o n a l Epidemiological and Training Centre which permits the immediate pooling of experience; inservice training of n a t i o n a l and international personnel; and centralization of complex statistical w o r k .
T o meet the shortage of key planners and organizers for n a t i o n a l tuberculosis p r o g r a m m e s , inter-regional training courses in the epidemiology and control of tuberculosis have been organized: 35 W H O fellows from 29 countries attended these courses in I 9 6 5 . A substantial number of fellowships are also awarded for
individually arranged training•
A very important function of WHO is to propound uniform methods and techniques through technical g u i d e s , m a n u a l s , f o r m s , e t c ” developed on the basis of all the field experience a c q u i r e d . R e p o r t s of expert committees play a n important role in shaping and lending authority to technical p o l i c i e s . R e g i o n a l and inter-regional m e e t i n g s of tuberculosis workers are useful for d i s s e m i n a t i r : new technical k n o w l e d g e .
Considerable efforts are made by W H O to induce manufacturers to produce equipment and supplies particularly suitable for use in the developing c o u n t r i e s , e . g . X - r a y u n i t s , built according to radically n e w c o n c e p t s , that combine versatility of a p p l i c a t i o n , with ease of o p e r a t i o n , simplicity of m a i n t e n a n c e , and safety from r a d i a t i o n •
4 . CO-OPERATION W I T H UNICEF A N D THE INTERNATIONAL UNION AGAINST TUBERCULOSIS
Throughout the existence of W H Ofs tuberculosis p r o g r a m m e , UNICEF has given very important material assistance to the activities recommended b y W H O . In the p a s t , the m a i n support w a s g i v e n to the B C G programmes but^ since the review and report made by the Thirteenth UNICEF/WH〇 Joint Committee o n H e a l t h P o l i c y , the scope for UNICEF aid has b e e n considerably broadened to include support for comprehensive n a t i o n a l tuberculosis control p r o g r a m m e s .
EB)2/2 page 11
The International Union against Tuberculosis supports W H O ' s efforts in many important w a y s , e . g . , through developing standard terminology for tuberculosis, disseminating information about WHO-assisted a c t i v i t i e s , and encouraging n a t i o n a l tuberculosis associations to support governmental e f f o r t s .
5 . SUMMARY A№) CONCLUSIONS
1 . Tuberculosis is a serious public h e a l t h problem in almost a l l the developing c o u n t r i e s , where one-half t o one p e r c e n t , of the adult population excrete tubercle b a c i l l i .
2 . W H Ofs research programme in tuberculosis h a s made important contributions to:
the standardization of diagnostic techniques; an understanding of the epidemiological behaviour of tuberculosis; control measures applicable u n d e r adverse socio-economic conditions; methodology for public h e a l t h practice research in tuberculosis.
WHO-assisted projects in tuberculosis control have evolved w i t h increasing knowledge from specialized application of independent measures towards integration of all specific antituberculosis measures into one programme w i t h i n the operational framework of the general h e a l t h services.
4 . The expanding basic h e a l t h service of almost any developing country h a s sufficient technical and economic means a t its disposal to vaccinate the total susceptible population systematically w i t h B C G a t least once every 5 - 1 0 y e a r s . In a d d i t i o n , i t should be able to operate simplified b u t reasonably efficient case- finding and ambulatory treatment throughout the country w i t h a minimum of specialized s u p p o r t . M a n y serious difficulties, such as traditional b u d g e t i n g , w a n i n g interest in t u b e r c u l o s i s , inadequately functioning h e a l t h infra-s tructure s , treatment d e f a u l t s , and drug r e s i s t a n c e , need to be o v e r c o m e , b u t if application and research are closely geared to these d i f f i c u l t i e s , global tuberculosis control is b o u n d to make impressive progress d u r i n g the n e x t d e c a d e s .
