- Email: [email protected]
Follow-up tuberculosis prevalence survey of Transkei
Tuber&e 61 (1980)
71-79
?’ Longman
Ltd
Group
FOLLOW-UP
0041-3879/80/00100071$02.00
TUBERCULOSIS
P. B. Fourie”,
PREVALENCE
SURVEY
OF TRANSKEI
E. M. S. Gatner, E. Glatthaar and H. H. Kleeberg
Tuberculosis Research Institute
of the South African Medical
Research
Council, Pretoria, R.S.A.
Summary After 5 years a follow-up prevalence survey was conducted in Transkei on a randomly selected sample of the rural population. The parameters investigated were bacteriological prevalence of tubercle bacilli in sputum, radiological prevalence of chest abnormalities associated with tuberculosis in adults, and hypersensitivity to tuberculin in children. Bacteriological positivity was 2.1 % on smear microscopy and 4.3 % on culture. Radiological evidence of tuberculosis was demonstrable in 12.5 % of subjects, of whom 8.7 % were considered active and 3.8 % inactive. The mean prevalence of tuberculin positivity according to the Mantoux test was 30.1 %. An annual risk of infection of 4 % was calculated, showing a continuous decrease of 5 % per year on the 7 % risk of infection encountered in 1972. Compared with the first survey, a general reduction in prevalence of tuberculosis is evident. R&urn6 Cinq ans apres une premiere enquete de prevalence, une nouvelle enqu&e a et6 menee au Transkei sur un echantillon choisi au hasard de la population rurale. Les parametres etudies etaient la prevalence de la presence des bacilles tuberculeux a I’examen bacteriologique des crachats, la prevalence d’anomalies du thorax decelees a I’examen radiologique et evocatrices de tuberculose, et la prevalence de la sensibilite a la tuberculine chez I’enfant. La positivite bacteriologique etait de 2.1 % a I’examen du frottis et de 4.3 % a la culture. Des images radiologiques de tuberculose existaient chez 12.5 % des sujets; 8.7 % ont et6 considerees actives et 3.8 % inactives. La prevalence moyenne de la positivite a la tuberculine d’apres le test de Mantoux Btait de 30.1 %. On a calcule que le risque annuel d’infection etait de 4 %, montrant une diminution continue de 5 % par an du risque de 7 % qui existait en 1972. Si I’on compare les resultats actuels a ceux, de la premiere enquete, il existe une reduction dvidente dans la prevalence de la tuberculose. Resumen En Transkei se realizd una segunda encuestra, 5 arias despues de la primera, en una muestra de la poblaci6n rural tomada al azar. Los parlmetros estudiados fueron la prevalencia de la presencia del bacilo tuberculoso en el examen bacteriologico de expectoraci&t, la prevalencia de anomalias en el examen radioldgico de t&ax, que podian evocar una tuberculosis y la hipersensibilidad a la tuberculina en 10s nir’ios. *Requests for reprints should be directed 0001 Republic of South Africa.
to Mr P. B. Fourie, Tuberculosis
Research
Institute,
Private
Bag X385,
Pretoria,
72
Fourie and others La positividad bacteriologica fue de 2.1 por ciento a la microcopia directa y de 4,3 por ciento al cultivo. En 12,5 por ciento de 10s sujetos se observaron imagenes radiologicas de tuberculosis, de las cuales 8,7 por ciento fueron consideradas activas y 3,8 por ciento inactivas. La prevalencia promedio de la positividad a la tuberculina segun el test de Mantoux due de 30,l por ciento. Se calculo que el risego anual de infection era de 4 por ciento, con una disminucidn regular de 5 por ciento por aiio a partir del riesgo de infection de 7 por ciento encontrado en 1972. Si se comparan 10s resultados actuales a 10s de la primera encuesta, se observa una reducidn evidente en la prevalencia de la tuberculosis. Introduction
The Tuberculosis Research Unit of the MRC has reported on a tuberculosis survey conducted in Transkei in 1972 [I 1. Mantoux testing showed 38.8 % of children aged between 3 months and 14 years to be positive reactors. Based on this tuberculin testing data the annual risk of tuberculous infection in Transkei in 1972 was calculated at 7 % with an expected downward trend of 2 % per year [2]. Whilst an 8 % prevalence of tuberculosis was found on the chest x-rays of adults, poor quality films and significant reader disagreement combine to suggest that this figure was an underestimate. In a separate study in 1972 of the prevalence of bacteriologically positive disease conducted in 16 randomly selected sites a case yield of 6.5 % culture positives was obtained. [3]. After a 5-year interval the Transkei Health Department invited the TBRI to undertake a follow-up survey in order to determine the prevalence of tuberculous infection and disease in the state. The South African National Tuberculosis Association’s former Transkei branch assisted. The epidemiological parameters investigated were the tuberculin status in children, sputum status by smear and cultural examination, and radiographic lung lesions in adults. Transkei has a population of approximately 2 million, 3 % of whom live in urban areas. Xhosa constitute the main tribe (95 % of total population) with mainly Zulu and South Sotho making up the rest. Topographically Transkei is a broken landscape characterised by mountain ranges and deeply eroded valleys. Three-quarters of the surface is very hilly or mountainous and only 11 % is flat or undulating. Health services are rendered at 3 levels: clinics, mission hospitals and reference hospitals. The number of hospitals and clinics totalled 30 and 110 respectively on 1 January 1976. Beds numbered 6312 in 1976 and some 3500 nursing posts had been created by that time. However, health services are hampered by poor roads and mountainous terrain, a general lack of confidence in modern medicine by a large proportion of the population and financial shortages. Subjects and methods Study population The random sample consisted of 4187 registered Xhosas from 12 selected sites in 11 districts (Figure I), and was representative of the rural population. The sampling methods are described elsewhere [l, 41 and follow the procedures outlined by the World Health Organization [5]. A total of 3459 registered persons (83 %) completed the tests. Co-operation of the sample subjects was very good. Default can mainly be ascribed to problems with travelling over rough terrain to the screening site. Many of the males also worked far away from home and could not attend. Sputum specimens were collected from 94 % and X-rays were taken of 75 % of the 1789 adults attending. Tuberculin tests were performed on 1816 children of whom 96 % returned for reading. In addition to the registered sample, 1290 volunteers were investigated for the same parameters. Because of adult males predominantly making use of migrant labour
Tuberculosis
in Transkei
73
SOUTH AFRICA
TRANSKEI
Figure I.
Map of Transkei and the distribution of survey sites.
opportunities, a heavy imbalance existed in the sex distribution of the population over 15 years of age. Males represented 19.3 % and females 80.7 % of the sample. However, in both sex groups an even distribution of ages occurred. Tuberculin
testing
All children from 3 months RT23 (Statens Seruminstitut, nursing sisters performed the injected a forearm selected by the presence or absence of a
to 18 years old were Mantoux tested with 2TU of human PPD Copenhagen) and with 2TU of avian PPD. Two experienced tests. To avoid bias, both sisters handled both tuberculins and means of a list of random binary numbers. On the day of injection BCG scar was recorded.
Mantoux tests were read independently by the sisters after 72 hours. Reactions to intradermal injections were recorded by measuring the transverse diameter of the induration using metric calipers. Each test was read independently by readers having no knowledge of which PPD had been injected into each arm. Radiological
examinations
Persons 15 years of age and older were eligible for a 100 mm chest roentgenogram. X-rays were read independently by 3 experienced tuberculous clinicians who classified them according to the categories presented in Table I. The minimal requirement for classification of an X-ray was agreement between 2 readers. For the purposes of this paper, X-rays are assigned to the categories tuberculosis active, tuberculosis inactive and no tuberculous pathology (Table I). Miliary tuberculosis was not encountered.
74
Fourie and others
Table I.
Classification
of X-ray films
No tuberculous pathology No radiological abnormality Abnormalities,
judged to be unrelated to TB
Abnormalities of thoracic cage or spine possibly related to TB, e.g. hunchback, Parenchymal abnormality, aetiology uncertain
etc.
Active tuberculosis Minimal shadow(s), judged to be TB Moderately advanced shadows, judged to be TB, without cavity Moderately advanced shadow(s), judged to be TB, with suspected or obvious cavity Far advanced shadow(s), judged to be TB, without cavity Far advanced shadow(s), judged to be TB, with suspected or obvious cavity Inactive tuberculosis Pleural effusion, thickening or calcification possibly of TB origin without other signs of TB Fibrotic and/or calcified shadows radiologically inactive and judged to be of TB origin (excluding sma!l calcifications) Miliary tuberculosis Technical
fault: unreadable
plate
Technical difficulties of plates taken. Bacteriological
experienced
with
the mobile X-ray unit resulted
in a loss of 25 %
investigations
Sputum specimens were obtained using the saline aerosol inhalation technique described by Gatner, Gartig and Kleeberg [6] and air freighted to the Tuberculosis Research Institute laboratories in Pretoria. After grading for quality and quantity, sputa were digested or decontaminated using a modified Petroff technique and 2 smears and 3 cultures (2 LowensteinJensen (LJ) and 1 LJ plus pyruvate) were prepared from each treated specimen. Smears were stained with auramine-phenol and examined The simplified smear grading scheme was as follows : 0 to 3 bacilli seen in whole smear:
negative
4 bacilli per smear to 1 in each field :
scanty
More than 1 per field to 10 per field :
moderate
More than 10 per field :
numerous.
by fluorescence
microscopy.
Cultures were incubated aerobically at 35-36”C, examined after one week for contamination, examined weekly up to 4 weeks for Mycobacterium tuberculosis and examined finally at 10 weeks. On the appearance of colonies resembling M. tuberculosis the degree of culture positivity was noted and identity confirmed by the niacin and nitrate reduction tests. Mycobacteria other than tubercle bacilli were recovered and provisionally identified by growth rate, pigment production, temperature relationships and the niacin, nitrate reduction, tween hydrolysis, arylsulfatase (for rapid growers) and urease (for scotochromogens) tests. All isolates of /1/11.tuberculosis were subjected to drug sensitivity testing using an absolute concentration method. Calculation
of the annual risk of infection
and its trend
The method employed in the calculation of the risk of infection was developed by Styblo, Meijer and Sutherland [7] and is based on the prevalence of tuberculosis infection in a population as determined by tuberculin testing. To estimate the trend, data from at least 2 surveys are
Tuberculosis
in Transkei
75
necessary. The exponential rate of decrease or increase wrth time of the annual risk of infection is derived by comparing any pair of prevalence figures. Results The prevalence of tuberculosis in Transkei is summarized in Table II. The yield of positive cases from sputum smear microscopy was 2.1 % and from sputum culture 4.3 %. Based on tworeader-agreement 8.7 % of the plates showed active pulmonary tuberculosis. Thus the culture case yield was twice that of smear microscopy, and the yield of active cases as found on X-ray was twice that found on culture. The correlation coefficient between smear microscopy and culture rates is 0.7 which makes the postulation of a 1 :2 relationship acceptable. However, a low correlation exists between X-ray positivity (active) and both smear microscopy and culture positivity, the respective coefficients being -0.1 and 0.3. Prevalence
rates based on tuberculin
sensitivity
The prevalence of tuberculous infection is based on the criterion of positive reactors showing 10 mm or more induration to 2TU RT23 human PPD. Figure 2 illustrates the prevalence rates in children according to age. An almost linear increase in the number of infected with age can be seen. This phenomenon indicates high and continuous exposure to infectious cases. Striking differences between the prevalence in different survey sites are evident, which range from 12.7 % to 52.3 % (Figure 3). As was found in the 1972 survey [I 1, no obvious correlation exists between tuberculin positivity rates and physiographic regions (i.e. highveld, hinterland and coast). This observation also applies to the other parameters investigated. By defining a positive reactor to avian tuberculin as a person showing an induration measuring 6 mm or more but at least 2 mm more than the reaction to human PPD [I ] a prevalence of 6.7 % can be calculated. Strong reactors may be defined as persons with avian reactions measuring more than 10 mm and at least 6 mm more than human reactions. Applying this criterion the prevalence is 2.3 %. There is little difference between the strong reactor rates of the various age groups, the mean rate of the under-l 5-year-olds being 2.1 % (range 1.7 % to 2.4 %). Table II. site *
Site prevalence of tuberculosus Prevalence rates (%) Smear positive
Culture positive
1 .J
4.3 5.0 5.3 4.4 1.3 1.7 5.0 4.2 6.5 6.7 2.9 5.3 4.3
1 .J
8 9 10 11
12 All
disease in Transkei adults.
4.4 1.5 0.6 1 .J 2.5 0.0 4.2 3.0 1 .J 1.5 2.1
*See Figure 1.
X-ray positive 7.4 4.4 4.7 7.0 9.6 3.1 3.8 12.0 12.4 15.4 9.4 13.3 8.7
76
Fourie and others
PREVALENCE 30.1 f ‘1. 1
,1
AGE GROUP (
1 to 3
L to 6
7to
9
10 to 12
13 to 15
I6 to 18
ALL
in years 1
Figure 2. Prevalence of tuberculous infection human PPD in children without BCG scars.
by age according
to positive
reactions
of 10 mm or more to 2TU of RT23
PREVALENCE
SITE
1
2
3
4
5
6
7
8
9
10
II
12 I
Figure 3. Prevalence of tuberculous infection by site according to 2TU of RT23 human PPD in children without BCG scars.
to the percentage
positive
reactions
ALL
of 10 mm or more
Bacteriological investigations Of the 2230 sputum specimens obtained, 1681 from registered persons and 549 from volunteers, 1759 were subjected to grading for quality. Of these, 86 % were satisfactory in that they contained traces of mucus or mucopurulent material while 76 % of specimens of satisfactory quality had a volume of at least 3 ml. Of 47 sputa which were positive by microscopy 77 % were confirmed by culture of M. tuberculosis, 12.8 % by the isolation of non-tuberculous mycobacteria and 10.6 % were designated false positive. Microscopic positivity is correlated with culture positivity in Table III. Sputum culture was twice as effective as smear microscopy in detecting tubercle bacilli. Of the 27 strongly culture positive sputa (+ to + + + +) 92.6 % would have been detected by microscopy alone. However, only 19 % of the 1 to 50 colony sputa would have been detected had smear microscopy been the sole diagnostic criterion. The 150 isolates of species of non-tuberculous mycobacteria will be reported on elsewhere on completion of serotyping. The overall culture contamination rates were 4.2 % for LJ medium and 5.8 % for LJ supplemented with pyruvate. Thirty-four specimens were written off because of contamination of all
Tuberculosis Table III. Culture positivity specimens cu:ture
Smear
,;olal
2129 31 19 1 1 2 2183 -
examination
77
of 2230 paired
Total
Negative Negative 1 colony 2-20 colonies 21 50 colonies
compared with results of microscopic
in Transkei
Scanty 8 2 3 5 1 4 3 26 -
Moderate 3
Numerous -
2 1 6 1 13
5 3 8
2140 33 22 8 2 5 16 4 2230
3 culture tubes. There was no significant difference in either positivity attributable to the incorporation of pyruvate in the LJ medium.
or degree of positivity
Drug sensitivity testing of 71 M. tuberculosis strains isolated from the sputum of registered persons indicates an isoniazid resistance rate of 17 % amongst the Transkei Xhosas. The overall isoniazid resistance was found to be 28 % in the 1972 survey (unpublished data). Radiological
investigations
A total of 1332 X-ray films was taken of registered persons. Of these films, 8.0 % were unreadable due to poor quality. Agreement between two readers on the interpretation of lung abnormalities was high (93.1 %). Of the films adjudged to denote tuberculous pathology, 70 % were considered active. Table IV summarizes the findings of the X-ray readers. Culture positivity is compared with X-ray findings in Table V. Of the 90 culture positive individuals, 38 were classified as tuberculosis on X-ray, of which 34 were being considered to be active. Twenty-one culture positives were described as negative on X-ray and no films were available for the remaining 31 culture positive individuals. The annual risk of infection
and its trend
De Ville de Goyet (1974) determined a 7 % risk of infection in Transkei in 1972 and predicted a 2 % annual decrease. The annual risk based on the 1977 survey data was 4 % which indicates a 10 % decrease annually in the risk of infection if compared with the 1974 calculation. However, by applying all tuberculin test data from both of these surveys to the mathematical model used inthecalculationof therisk,acontinuousdecreaseof 5%perannumispredicted (Figure4).
Table IV.
Prevalence of radiological
X-ray category
Prevalence
No tuberculous pathology Active tuberculosis Inactive tuberculosis Miliary tuberculosis
87.5 8.7 3.8 0.0
*At least 2 readers agreeing. Overall between readers was 93.1 %.
(%) *
agreement
chest abnormalities
in Xhosa adults
78
Fourie and others
Table V.
Comparison
Culture
of culture positivitv
Total
x-ray No tuberculosus pathology
1 colony Z-20 colonies 21-50 colonies
Active tuberculosis
2 1
:~
1_ - +_ +_ Total
21
*Unreadable
plates/no
7
agreement
(% 1
tuberculosis
I -
1
17 7 3 1 1 2
4
31
2 1 -
between
,uRKY -.
Other*
Inactive
5 5 5 1 2 12 4 34
9 9 -
I~--
t
with X-rav result for 90 culture positive cases
readers/no
films available.
I FCRWiFXI FROJXTED
-.
33 22 8 2 5 16 4 90
-.
-.
RISK TREND I: 2% COWNMRD
ANNUALLY
-_
-...-.-. 1 BETWEEN SURVEYS= ‘r?., “n”“““.“~
5
ANNU&LY
YJRVEY II ’
I
72
I
I
73
7L
I
75
,
76
,
77
CALENDAR YEARS Figure 4.
Estimates
of the trend in the annual
risk of infection
in Transkei
Discussion Although there is an evident decrease in the estimated annual risk of infection for Transkei, the calculated figure for 1977 still represents the highest in rural Southern Africa. Unpublished data from 5 other rural surveys indicate infection risks varying between 1 .I5 % and 2 % for 4 while the Xhosas of Ciskei when surveyed in 1975 were observed to have a 4 % annual risk of infection with no demonstrable downward trend. There is no evidence that non-tuberculous mycobacterial infections present any health threat to the Xhosa of Transkei despite appreciable exposure, as evidenced by skin testing with avian PPD and by the finding of organisms in 8 % of sputa. However, 79 % of nontuberculous mycobacteria cultured were manifested as 1 -colony isolates. Sputum culture is a more effective case-finding tool than either X-ray or microscopy since 23 % of culture positive cases were missed by X-ray and 53.5 % were missed by microscopy. For tuberculosis control case-finding by sputum culture is recommended because the use of
Tuberculosis
in Transkei
79
smear microscopy as the sole case-finding tool is likely to be unrewarding. The mass indiscriminate use of mobile X-ray units, apart from the misgivings voiced by Toman [8] would precipitate an impossible case-load, a portion of which would not require chemotherapy. Mobile X-ray units could, however, be used to give a boost to a sputum culture campaign by providing a filter for symptomatic individuals. As for any high prevalence tuberculosis area, appropriate control measures are tuberculosis health education, intensive case-finding supported by an established treatment infrastructure, extensive BCG campaigns and controlled treatment schemes. Based on the results of the 1977surveysputum culture programmeweestimate,conservatively, that there are 44 000 open pulmonary tuberculosis cases in Transkei distributed amongst an adult population of 1 .2 million. Whilst Styblo [9] has suggested that for estimating the number of open cases in a population a 1 % annual risk is equivalent to 60 smear positive cases per 100 000 population, the observation is made that in Transkei a more meaningful relationship is that a 4 % annual risk is equivalent to 4 % culture positivity amongst the adult population. The 1972 surveys [I, 21 demonstrated the same relationship with risk of infection having been 7 % and culture positivity 6.6 %. However, it should be stressed that Styblo’s index refers to populations not medically interfered with. In the light of the drawbacks faced by health services as mentioned earlier, tuberculosis prevalence has diminished dramatically since 1972, and the continued downward trend predicted by the risk of infection model is encouraging. Acknowledgements We thank the South African National Tuberculosis Association and the Transkei Health Department for their support and co-operation during the survey, and the survey team for their loyal efforts, Dr W. Lukas led the field team for two weeks. Dr T. F. B. Collins and Dr D. Theofanidis kindly assisted one of us (E. Glatthaar) in X-ray reading. Thanks are also due to Mrs Delna Stander and her laboratory team for the sputum investigations, and to Mrs Karin Depken and Miss Dori Mowbray for the tuberculin tests which they performed so expertly. References South
African Tuberculosis Study Group (1974). Tuberculosis in the Transkei. An epidemiological survey. South African Medical Journal, 48, 149. De Ville de Goyet, C. (1974). Annual risk of tuberculosis infection in the Transkei. Problems connected with Its estimation from the data of a tuberculin survey. South African Medical Journal, 48, 957. De Ville de Goyet, C., Et Kleeberg, H. H. (1 S74). Comparison of tuberculosis case-finding in a high prevalence area. South African Medical Journal, 48, 2582. Arabin, G., Gartig, D., Et Kleeberg, H. H. First tuberculosis prevalence survey in KwaZulu. South African Medical Journai (in press). World Health Organization (1958). Technical guide for tuberculosis survey teams. World Health Organization Tuberculosis Research Office Technical Guide No. 1. Gatner, E. M. S., Gartig, D., Et Kleeberg, H. H. (1977). Sputum induction by saline aerosol. South African Medical Journal, 51, 279. Styblo, K., Meijer, J.. Et Sutherland, I. (1969). The transmission of tubercle bacilli. Its trend in a human population. Tuberculosis Surveillance Research Unit Report No. 1. Bulletin of the /nternationa/tJnion against Tuberculosis 42. 5. Toman, K. (1976). Mass radiography in tuberculosis control. World Health Organization Chronicle, 30, 51. Styblo, K. (1976). Surveillance of tuberculosis. international Journal of Epidemiology, 5, 63.
71-79
?’ Longman
Ltd
Group
FOLLOW-UP
0041-3879/80/00100071$02.00
TUBERCULOSIS
P. B. Fourie”,
PREVALENCE
SURVEY
OF TRANSKEI
E. M. S. Gatner, E. Glatthaar and H. H. Kleeberg
Tuberculosis Research Institute
of the South African Medical
Research
Council, Pretoria, R.S.A.
Summary After 5 years a follow-up prevalence survey was conducted in Transkei on a randomly selected sample of the rural population. The parameters investigated were bacteriological prevalence of tubercle bacilli in sputum, radiological prevalence of chest abnormalities associated with tuberculosis in adults, and hypersensitivity to tuberculin in children. Bacteriological positivity was 2.1 % on smear microscopy and 4.3 % on culture. Radiological evidence of tuberculosis was demonstrable in 12.5 % of subjects, of whom 8.7 % were considered active and 3.8 % inactive. The mean prevalence of tuberculin positivity according to the Mantoux test was 30.1 %. An annual risk of infection of 4 % was calculated, showing a continuous decrease of 5 % per year on the 7 % risk of infection encountered in 1972. Compared with the first survey, a general reduction in prevalence of tuberculosis is evident. R&urn6 Cinq ans apres une premiere enquete de prevalence, une nouvelle enqu&e a et6 menee au Transkei sur un echantillon choisi au hasard de la population rurale. Les parametres etudies etaient la prevalence de la presence des bacilles tuberculeux a I’examen bacteriologique des crachats, la prevalence d’anomalies du thorax decelees a I’examen radiologique et evocatrices de tuberculose, et la prevalence de la sensibilite a la tuberculine chez I’enfant. La positivite bacteriologique etait de 2.1 % a I’examen du frottis et de 4.3 % a la culture. Des images radiologiques de tuberculose existaient chez 12.5 % des sujets; 8.7 % ont et6 considerees actives et 3.8 % inactives. La prevalence moyenne de la positivite a la tuberculine d’apres le test de Mantoux Btait de 30.1 %. On a calcule que le risque annuel d’infection etait de 4 %, montrant une diminution continue de 5 % par an du risque de 7 % qui existait en 1972. Si I’on compare les resultats actuels a ceux, de la premiere enquete, il existe une reduction dvidente dans la prevalence de la tuberculose. Resumen En Transkei se realizd una segunda encuestra, 5 arias despues de la primera, en una muestra de la poblaci6n rural tomada al azar. Los parlmetros estudiados fueron la prevalencia de la presencia del bacilo tuberculoso en el examen bacteriologico de expectoraci&t, la prevalencia de anomalias en el examen radioldgico de t&ax, que podian evocar una tuberculosis y la hipersensibilidad a la tuberculina en 10s nir’ios. *Requests for reprints should be directed 0001 Republic of South Africa.
to Mr P. B. Fourie, Tuberculosis
Research
Institute,
Private
Bag X385,
Pretoria,
72
Fourie and others La positividad bacteriologica fue de 2.1 por ciento a la microcopia directa y de 4,3 por ciento al cultivo. En 12,5 por ciento de 10s sujetos se observaron imagenes radiologicas de tuberculosis, de las cuales 8,7 por ciento fueron consideradas activas y 3,8 por ciento inactivas. La prevalencia promedio de la positividad a la tuberculina segun el test de Mantoux due de 30,l por ciento. Se calculo que el risego anual de infection era de 4 por ciento, con una disminucidn regular de 5 por ciento por aiio a partir del riesgo de infection de 7 por ciento encontrado en 1972. Si se comparan 10s resultados actuales a 10s de la primera encuesta, se observa una reducidn evidente en la prevalencia de la tuberculosis. Introduction
The Tuberculosis Research Unit of the MRC has reported on a tuberculosis survey conducted in Transkei in 1972 [I 1. Mantoux testing showed 38.8 % of children aged between 3 months and 14 years to be positive reactors. Based on this tuberculin testing data the annual risk of tuberculous infection in Transkei in 1972 was calculated at 7 % with an expected downward trend of 2 % per year [2]. Whilst an 8 % prevalence of tuberculosis was found on the chest x-rays of adults, poor quality films and significant reader disagreement combine to suggest that this figure was an underestimate. In a separate study in 1972 of the prevalence of bacteriologically positive disease conducted in 16 randomly selected sites a case yield of 6.5 % culture positives was obtained. [3]. After a 5-year interval the Transkei Health Department invited the TBRI to undertake a follow-up survey in order to determine the prevalence of tuberculous infection and disease in the state. The South African National Tuberculosis Association’s former Transkei branch assisted. The epidemiological parameters investigated were the tuberculin status in children, sputum status by smear and cultural examination, and radiographic lung lesions in adults. Transkei has a population of approximately 2 million, 3 % of whom live in urban areas. Xhosa constitute the main tribe (95 % of total population) with mainly Zulu and South Sotho making up the rest. Topographically Transkei is a broken landscape characterised by mountain ranges and deeply eroded valleys. Three-quarters of the surface is very hilly or mountainous and only 11 % is flat or undulating. Health services are rendered at 3 levels: clinics, mission hospitals and reference hospitals. The number of hospitals and clinics totalled 30 and 110 respectively on 1 January 1976. Beds numbered 6312 in 1976 and some 3500 nursing posts had been created by that time. However, health services are hampered by poor roads and mountainous terrain, a general lack of confidence in modern medicine by a large proportion of the population and financial shortages. Subjects and methods Study population The random sample consisted of 4187 registered Xhosas from 12 selected sites in 11 districts (Figure I), and was representative of the rural population. The sampling methods are described elsewhere [l, 41 and follow the procedures outlined by the World Health Organization [5]. A total of 3459 registered persons (83 %) completed the tests. Co-operation of the sample subjects was very good. Default can mainly be ascribed to problems with travelling over rough terrain to the screening site. Many of the males also worked far away from home and could not attend. Sputum specimens were collected from 94 % and X-rays were taken of 75 % of the 1789 adults attending. Tuberculin tests were performed on 1816 children of whom 96 % returned for reading. In addition to the registered sample, 1290 volunteers were investigated for the same parameters. Because of adult males predominantly making use of migrant labour
Tuberculosis
in Transkei
73
SOUTH AFRICA
TRANSKEI
Figure I.
Map of Transkei and the distribution of survey sites.
opportunities, a heavy imbalance existed in the sex distribution of the population over 15 years of age. Males represented 19.3 % and females 80.7 % of the sample. However, in both sex groups an even distribution of ages occurred. Tuberculin
testing
All children from 3 months RT23 (Statens Seruminstitut, nursing sisters performed the injected a forearm selected by the presence or absence of a
to 18 years old were Mantoux tested with 2TU of human PPD Copenhagen) and with 2TU of avian PPD. Two experienced tests. To avoid bias, both sisters handled both tuberculins and means of a list of random binary numbers. On the day of injection BCG scar was recorded.
Mantoux tests were read independently by the sisters after 72 hours. Reactions to intradermal injections were recorded by measuring the transverse diameter of the induration using metric calipers. Each test was read independently by readers having no knowledge of which PPD had been injected into each arm. Radiological
examinations
Persons 15 years of age and older were eligible for a 100 mm chest roentgenogram. X-rays were read independently by 3 experienced tuberculous clinicians who classified them according to the categories presented in Table I. The minimal requirement for classification of an X-ray was agreement between 2 readers. For the purposes of this paper, X-rays are assigned to the categories tuberculosis active, tuberculosis inactive and no tuberculous pathology (Table I). Miliary tuberculosis was not encountered.
74
Fourie and others
Table I.
Classification
of X-ray films
No tuberculous pathology No radiological abnormality Abnormalities,
judged to be unrelated to TB
Abnormalities of thoracic cage or spine possibly related to TB, e.g. hunchback, Parenchymal abnormality, aetiology uncertain
etc.
Active tuberculosis Minimal shadow(s), judged to be TB Moderately advanced shadows, judged to be TB, without cavity Moderately advanced shadow(s), judged to be TB, with suspected or obvious cavity Far advanced shadow(s), judged to be TB, without cavity Far advanced shadow(s), judged to be TB, with suspected or obvious cavity Inactive tuberculosis Pleural effusion, thickening or calcification possibly of TB origin without other signs of TB Fibrotic and/or calcified shadows radiologically inactive and judged to be of TB origin (excluding sma!l calcifications) Miliary tuberculosis Technical
fault: unreadable
plate
Technical difficulties of plates taken. Bacteriological
experienced
with
the mobile X-ray unit resulted
in a loss of 25 %
investigations
Sputum specimens were obtained using the saline aerosol inhalation technique described by Gatner, Gartig and Kleeberg [6] and air freighted to the Tuberculosis Research Institute laboratories in Pretoria. After grading for quality and quantity, sputa were digested or decontaminated using a modified Petroff technique and 2 smears and 3 cultures (2 LowensteinJensen (LJ) and 1 LJ plus pyruvate) were prepared from each treated specimen. Smears were stained with auramine-phenol and examined The simplified smear grading scheme was as follows : 0 to 3 bacilli seen in whole smear:
negative
4 bacilli per smear to 1 in each field :
scanty
More than 1 per field to 10 per field :
moderate
More than 10 per field :
numerous.
by fluorescence
microscopy.
Cultures were incubated aerobically at 35-36”C, examined after one week for contamination, examined weekly up to 4 weeks for Mycobacterium tuberculosis and examined finally at 10 weeks. On the appearance of colonies resembling M. tuberculosis the degree of culture positivity was noted and identity confirmed by the niacin and nitrate reduction tests. Mycobacteria other than tubercle bacilli were recovered and provisionally identified by growth rate, pigment production, temperature relationships and the niacin, nitrate reduction, tween hydrolysis, arylsulfatase (for rapid growers) and urease (for scotochromogens) tests. All isolates of /1/11.tuberculosis were subjected to drug sensitivity testing using an absolute concentration method. Calculation
of the annual risk of infection
and its trend
The method employed in the calculation of the risk of infection was developed by Styblo, Meijer and Sutherland [7] and is based on the prevalence of tuberculosis infection in a population as determined by tuberculin testing. To estimate the trend, data from at least 2 surveys are
Tuberculosis
in Transkei
75
necessary. The exponential rate of decrease or increase wrth time of the annual risk of infection is derived by comparing any pair of prevalence figures. Results The prevalence of tuberculosis in Transkei is summarized in Table II. The yield of positive cases from sputum smear microscopy was 2.1 % and from sputum culture 4.3 %. Based on tworeader-agreement 8.7 % of the plates showed active pulmonary tuberculosis. Thus the culture case yield was twice that of smear microscopy, and the yield of active cases as found on X-ray was twice that found on culture. The correlation coefficient between smear microscopy and culture rates is 0.7 which makes the postulation of a 1 :2 relationship acceptable. However, a low correlation exists between X-ray positivity (active) and both smear microscopy and culture positivity, the respective coefficients being -0.1 and 0.3. Prevalence
rates based on tuberculin
sensitivity
The prevalence of tuberculous infection is based on the criterion of positive reactors showing 10 mm or more induration to 2TU RT23 human PPD. Figure 2 illustrates the prevalence rates in children according to age. An almost linear increase in the number of infected with age can be seen. This phenomenon indicates high and continuous exposure to infectious cases. Striking differences between the prevalence in different survey sites are evident, which range from 12.7 % to 52.3 % (Figure 3). As was found in the 1972 survey [I 1, no obvious correlation exists between tuberculin positivity rates and physiographic regions (i.e. highveld, hinterland and coast). This observation also applies to the other parameters investigated. By defining a positive reactor to avian tuberculin as a person showing an induration measuring 6 mm or more but at least 2 mm more than the reaction to human PPD [I ] a prevalence of 6.7 % can be calculated. Strong reactors may be defined as persons with avian reactions measuring more than 10 mm and at least 6 mm more than human reactions. Applying this criterion the prevalence is 2.3 %. There is little difference between the strong reactor rates of the various age groups, the mean rate of the under-l 5-year-olds being 2.1 % (range 1.7 % to 2.4 %). Table II. site *
Site prevalence of tuberculosus Prevalence rates (%) Smear positive
Culture positive
1 .J
4.3 5.0 5.3 4.4 1.3 1.7 5.0 4.2 6.5 6.7 2.9 5.3 4.3
1 .J
8 9 10 11
12 All
disease in Transkei adults.
4.4 1.5 0.6 1 .J 2.5 0.0 4.2 3.0 1 .J 1.5 2.1
*See Figure 1.
X-ray positive 7.4 4.4 4.7 7.0 9.6 3.1 3.8 12.0 12.4 15.4 9.4 13.3 8.7
76
Fourie and others
PREVALENCE 30.1 f ‘1. 1
,1
AGE GROUP (
1 to 3
L to 6
7to
9
10 to 12
13 to 15
I6 to 18
ALL
in years 1
Figure 2. Prevalence of tuberculous infection human PPD in children without BCG scars.
by age according
to positive
reactions
of 10 mm or more to 2TU of RT23
PREVALENCE
SITE
1
2
3
4
5
6
7
8
9
10
II
12 I
Figure 3. Prevalence of tuberculous infection by site according to 2TU of RT23 human PPD in children without BCG scars.
to the percentage
positive
reactions
ALL
of 10 mm or more
Bacteriological investigations Of the 2230 sputum specimens obtained, 1681 from registered persons and 549 from volunteers, 1759 were subjected to grading for quality. Of these, 86 % were satisfactory in that they contained traces of mucus or mucopurulent material while 76 % of specimens of satisfactory quality had a volume of at least 3 ml. Of 47 sputa which were positive by microscopy 77 % were confirmed by culture of M. tuberculosis, 12.8 % by the isolation of non-tuberculous mycobacteria and 10.6 % were designated false positive. Microscopic positivity is correlated with culture positivity in Table III. Sputum culture was twice as effective as smear microscopy in detecting tubercle bacilli. Of the 27 strongly culture positive sputa (+ to + + + +) 92.6 % would have been detected by microscopy alone. However, only 19 % of the 1 to 50 colony sputa would have been detected had smear microscopy been the sole diagnostic criterion. The 150 isolates of species of non-tuberculous mycobacteria will be reported on elsewhere on completion of serotyping. The overall culture contamination rates were 4.2 % for LJ medium and 5.8 % for LJ supplemented with pyruvate. Thirty-four specimens were written off because of contamination of all
Tuberculosis Table III. Culture positivity specimens cu:ture
Smear
,;olal
2129 31 19 1 1 2 2183 -
examination
77
of 2230 paired
Total
Negative Negative 1 colony 2-20 colonies 21 50 colonies
compared with results of microscopic
in Transkei
Scanty 8 2 3 5 1 4 3 26 -
Moderate 3
Numerous -
2 1 6 1 13
5 3 8
2140 33 22 8 2 5 16 4 2230
3 culture tubes. There was no significant difference in either positivity attributable to the incorporation of pyruvate in the LJ medium.
or degree of positivity
Drug sensitivity testing of 71 M. tuberculosis strains isolated from the sputum of registered persons indicates an isoniazid resistance rate of 17 % amongst the Transkei Xhosas. The overall isoniazid resistance was found to be 28 % in the 1972 survey (unpublished data). Radiological
investigations
A total of 1332 X-ray films was taken of registered persons. Of these films, 8.0 % were unreadable due to poor quality. Agreement between two readers on the interpretation of lung abnormalities was high (93.1 %). Of the films adjudged to denote tuberculous pathology, 70 % were considered active. Table IV summarizes the findings of the X-ray readers. Culture positivity is compared with X-ray findings in Table V. Of the 90 culture positive individuals, 38 were classified as tuberculosis on X-ray, of which 34 were being considered to be active. Twenty-one culture positives were described as negative on X-ray and no films were available for the remaining 31 culture positive individuals. The annual risk of infection
and its trend
De Ville de Goyet (1974) determined a 7 % risk of infection in Transkei in 1972 and predicted a 2 % annual decrease. The annual risk based on the 1977 survey data was 4 % which indicates a 10 % decrease annually in the risk of infection if compared with the 1974 calculation. However, by applying all tuberculin test data from both of these surveys to the mathematical model used inthecalculationof therisk,acontinuousdecreaseof 5%perannumispredicted (Figure4).
Table IV.
Prevalence of radiological
X-ray category
Prevalence
No tuberculous pathology Active tuberculosis Inactive tuberculosis Miliary tuberculosis
87.5 8.7 3.8 0.0
*At least 2 readers agreeing. Overall between readers was 93.1 %.
(%) *
agreement
chest abnormalities
in Xhosa adults
78
Fourie and others
Table V.
Comparison
Culture
of culture positivitv
Total
x-ray No tuberculosus pathology
1 colony Z-20 colonies 21-50 colonies
Active tuberculosis
2 1
:~
1_ - +_ +_ Total
21
*Unreadable
plates/no
7
agreement
(% 1
tuberculosis
I -
1
17 7 3 1 1 2
4
31
2 1 -
between
,uRKY -.
Other*
Inactive
5 5 5 1 2 12 4 34
9 9 -
I~--
t
with X-rav result for 90 culture positive cases
readers/no
films available.
I FCRWiFXI FROJXTED
-.
33 22 8 2 5 16 4 90
-.
-.
RISK TREND I: 2% COWNMRD
ANNUALLY
-_
-...-.-. 1 BETWEEN SURVEYS= ‘r?., “n”“““.“~
5
ANNU&LY
YJRVEY II ’
I
72
I
I
73
7L
I
75
,
76
,
77
CALENDAR YEARS Figure 4.
Estimates
of the trend in the annual
risk of infection
in Transkei
Discussion Although there is an evident decrease in the estimated annual risk of infection for Transkei, the calculated figure for 1977 still represents the highest in rural Southern Africa. Unpublished data from 5 other rural surveys indicate infection risks varying between 1 .I5 % and 2 % for 4 while the Xhosas of Ciskei when surveyed in 1975 were observed to have a 4 % annual risk of infection with no demonstrable downward trend. There is no evidence that non-tuberculous mycobacterial infections present any health threat to the Xhosa of Transkei despite appreciable exposure, as evidenced by skin testing with avian PPD and by the finding of organisms in 8 % of sputa. However, 79 % of nontuberculous mycobacteria cultured were manifested as 1 -colony isolates. Sputum culture is a more effective case-finding tool than either X-ray or microscopy since 23 % of culture positive cases were missed by X-ray and 53.5 % were missed by microscopy. For tuberculosis control case-finding by sputum culture is recommended because the use of
Tuberculosis
in Transkei
79
smear microscopy as the sole case-finding tool is likely to be unrewarding. The mass indiscriminate use of mobile X-ray units, apart from the misgivings voiced by Toman [8] would precipitate an impossible case-load, a portion of which would not require chemotherapy. Mobile X-ray units could, however, be used to give a boost to a sputum culture campaign by providing a filter for symptomatic individuals. As for any high prevalence tuberculosis area, appropriate control measures are tuberculosis health education, intensive case-finding supported by an established treatment infrastructure, extensive BCG campaigns and controlled treatment schemes. Based on the results of the 1977surveysputum culture programmeweestimate,conservatively, that there are 44 000 open pulmonary tuberculosis cases in Transkei distributed amongst an adult population of 1 .2 million. Whilst Styblo [9] has suggested that for estimating the number of open cases in a population a 1 % annual risk is equivalent to 60 smear positive cases per 100 000 population, the observation is made that in Transkei a more meaningful relationship is that a 4 % annual risk is equivalent to 4 % culture positivity amongst the adult population. The 1972 surveys [I, 21 demonstrated the same relationship with risk of infection having been 7 % and culture positivity 6.6 %. However, it should be stressed that Styblo’s index refers to populations not medically interfered with. In the light of the drawbacks faced by health services as mentioned earlier, tuberculosis prevalence has diminished dramatically since 1972, and the continued downward trend predicted by the risk of infection model is encouraging. Acknowledgements We thank the South African National Tuberculosis Association and the Transkei Health Department for their support and co-operation during the survey, and the survey team for their loyal efforts, Dr W. Lukas led the field team for two weeks. Dr T. F. B. Collins and Dr D. Theofanidis kindly assisted one of us (E. Glatthaar) in X-ray reading. Thanks are also due to Mrs Delna Stander and her laboratory team for the sputum investigations, and to Mrs Karin Depken and Miss Dori Mowbray for the tuberculin tests which they performed so expertly. References South
African Tuberculosis Study Group (1974). Tuberculosis in the Transkei. An epidemiological survey. South African Medical Journal, 48, 149. De Ville de Goyet, C. (1974). Annual risk of tuberculosis infection in the Transkei. Problems connected with Its estimation from the data of a tuberculin survey. South African Medical Journal, 48, 957. De Ville de Goyet, C., Et Kleeberg, H. H. (1 S74). Comparison of tuberculosis case-finding in a high prevalence area. South African Medical Journal, 48, 2582. Arabin, G., Gartig, D., Et Kleeberg, H. H. First tuberculosis prevalence survey in KwaZulu. South African Medical Journai (in press). World Health Organization (1958). Technical guide for tuberculosis survey teams. World Health Organization Tuberculosis Research Office Technical Guide No. 1. Gatner, E. M. S., Gartig, D., Et Kleeberg, H. H. (1977). Sputum induction by saline aerosol. South African Medical Journal, 51, 279. Styblo, K., Meijer, J.. Et Sutherland, I. (1969). The transmission of tubercle bacilli. Its trend in a human population. Tuberculosis Surveillance Research Unit Report No. 1. Bulletin of the /nternationa/tJnion against Tuberculosis 42. 5. Toman, K. (1976). Mass radiography in tuberculosis control. World Health Organization Chronicle, 30, 51. Styblo, K. (1976). Surveillance of tuberculosis. international Journal of Epidemiology, 5, 63.