The sixth Nationwide Tuberculosis Prevalence Survey in Korea, 1990

The sixth Nationwide Tuberculosis Prevalence Survey in Korea, 1990 Y. P. Hong, S. J. Kim, D. W. Kwon. S. C. Chang, W. J. Lew. Y. C. Han Km-em National Tuherculo.sis Association,

Seoul, Korea

IS U M M A R Y. Setting: Nationwide random sample survey for tuberculosis in 1990. Objective: To investigate the prevalence of tuberculosis infection, morbidity and drug resistance

and BCG coverage, and to compare the findings with those of the previous 5 surveys. Design: The following investigations were performed: tuberculin test, BCG scar screening, chest miniature radiography (70 mm x 70 mm) for those aged over 5 years, sputum direct smear, culture and drug susceptibility test, and a questionnaire to obtain history of chemotherapy and symptoms. Results: The coverage of the investigation has been of more than 95% in each survey. The main findings are as follows: BCG coverage of those aged under 30 and of infants (aged under 1 year) has increased from 24% to 86% and from 1% to 79% respectively. The observed tuberculin positivity (2 10 mm in diameter) of subjects aged under 30 has decreased from 45% to 27%. The reduction of positivity was significant in children aged 59 years, from 34% to 8%. The annual risk of infection has dropped by over 6% annually. The prevalence of pulmonary tuberculosis per 100 000 has decreased: direct smear-positive from 690-143, smear and/or culture positive from 940-241 and active cases from 5065-1842 respectively. The drug resistance rate had increased to the peak of 47% in 1980, but had decreased to 27% in the last survey. Conclusion: The tuberculosis situation has improved significantly in every aspect in the last 25 years. R &?S U M &-.Cadre: Enquete nationale d’echantillons randomises pour depister la tuberculose en 1990. Objet: Evaluer la prevalence de I’infection tuberculeuse, la morbidite et la resistance aux drogues, ainsi que la couverture vaccinale par le BCG. Comparaison avec les 5 enquetes precedentes. Sche’ma: Les investigations suivantes ont CtC faites: test tuberculinique, depistage des cicatrices vaccinales, radiophotographie thoracique (70 mm x 70 mm) chez les sujets ages de plus de 5 ans, examen bacteriologique des crachats, culture et test de sensibilite aux drogues, questionnaire pour obtenir des details sur les antecedents de chimiotherapie et les symptomes. Re’sultats: La couverture de I’investigation a depasse 95% pour chaque enquete. Les principales constatations sont les suivantes: la couverture vaccinale des sujets ages de moins de 30 ans et des nouveaux-nes (ages de moins d’un an) a augmente de 24% a 86% et de 1% a 79% respectivement. La positivite tuberculinique observee (> 10 mm de diametre) chez les sujets ages de moms de 30 ans a diminue de 45% a 27%. La diminution de la positivite Ctait significative chez les enfants ages de 5 a 9 ans, passant de 34% a 8%. Le risque annuel d’infection a diminue de 6% par an. La prevalence de la tuberculose pulmonaire pour 100 000 habitants a diminue : pour les positifs a I’examen direct de 690 a 143, pour les frottis positifs etiou les positifs a la culture de 940 a 214, et les cas actifs sont passes de 5065 a 1842. Le taux d’antibioresistance avait augmente a un pit de 47% en 1980, alors que lors de la derniere enquete il s’etait abaisse a 27%. Conclusion: La situation de la tuberculose s’est amelioree de fagon significative dans tous ses aspects depuis 25 ans. R E S Cl M E N. Marco de referencia:

Estudio aleatorio por muestreo a nivel national para la investigation de la tuberculosis en 1990. Objetivo: Investigar la prevalencia de la infection tuberculosa, la morbilidad, la resistencia a 10s medicamentos y la cobertura BCG, comparando 10s resultados con 10s de cinco estudios anteriores.

Correspondence to: Dr. Youngpyo Hong. Director, Korean Institute of Tuberculosis/Korean National Tuberculosis Association. 14 Woomyundong, Sochogu, Seoul 137-140. Korea. Paper r-cc~eiwd 23 A~qust 1992. Final ~wxion ac,cepted 10 F~~Iw~~ / 993.

323

324

Tubercle and Lung Disease

M&do:

Se efectuaron las siguientes investigaciones : prueba de tuberculina, busqueda de cicatriz BCG, radiografia miniaturizada de t&ax (70 mm x 70 mm) para 10s sujetos de mas de cinco adios de edad, baciloscopia, cultivo y pruebas de sensibilidad y un cuestionario con respect0 a 10s antecedentes de quimioterapia y a 10s sintomas. Resultados: La cobertura de las investigaciones fue de mas del 95% en todos 10s estudios. Los principales resultados son 10s siguientes : la cobertura de BCG de 10s sujetos de menos de 30 anos de edad y la de 10s lactantes (menos de 1 atio de edad) ha aumentado de 24% a 86% y de 1% a 79%, respectivamente ; la observation de una prueba de tuberculina positiva (2 10 mm de diametro) en 10s sujetos de menos de 30 aiios de edad ha disminuido de 45% a 27%; la reducci6n de la positividad fue importante en 10s sujetos de 5 a 9 anos de edad (de 34% a 8%) ; el riesgo anual de infection se redujo en mas de 6% por aiio ; la prevalencia de la tuberculosis pulmonar por 100 000 habia disminuido : con baciloscopia positiva de 690 a 143, con baciloscopia y/o cultivo positivos de 940 a 241 y 10s cases activos de 5065 a 1842. La resistencia a 10s medicamentos aument6 con un maxim0 de 47% en 1980 y disminuy6 a 27% en el ultimo estudio. Conchsidn: La situation de la tuberculosis ha mejorado significativamente en todos 10s aspectos en 10s ultimos 25 aiios.

INTRODUCTION The first nationwide tuberculosis prevalence survey was conducted in 1965. Since then the survey has been repeated at 5 year intervals.’ The surveys were designed to investigate the size and trend of the tuberculosis problem and to collect relevant information for the National Tuberculosis Programme (NTP). The Korean Institute of Tuberculosis of the Korean National Tuberculosis Association (KIT/KNTA) planned and executed the surveys under the auspices of the Ministry of Health and Social Affairs (MOHSA). The procedures have been essentially identical throughout the 6 surveys, except for some changes to the eligible age group of the subjects for skin tests. The last survey was conducted from April to September 1990.

dified enumerating district (ED) defined according to the 1985 census: 134 from the urban stratum and 56 from the rural stratum, each with an equal sampling fraction. EDs with special mass accommodation facilities, such as armed forces bases or various dormitories and hospitals, were excluded from the sampling.

Census of eligible subjects In each area the Census Unit paid home visits to every household to confirm the eligible subjects on the name list of the registry prepared by the local authority. A final census was taken as of 5.00 am on the first day of the examination and the list of eligible subjects was finalized, including those temporarily staying in the area and excluding temporary absentees, thus the de facto population for the survey.

PROCEDURES Skin testing and screening of BCG scar Organization and budget The survey was executed with six mobile teams in Metropolitan Seoul and four mobile teams in the other areas in 1990. Each team consisted of (1) the Census Unit, (2) the Mass Miniature Radiography (MMR) and Sensitin-injection Unit and (3) the Bacteriology and Skin-test Reading Unit. The budgets required were: US$13 250 in 1965, $32 250 in 1970, $89 500 in 1975, $106 200 in 1980, $385 000 in 1985 and $466 400 in 1990. Costs per capita examined were US$O.81, $1.53, $2.89, $4.03, $8.73 and $8.50 respectively.

Tuberculin test was performed for the eligibles with 1TU of RT 23 with Tween 80 (Statens Seruminstitut, Copenhagen). The transverse diameter of induration was read approximately 72 hours after intracutaneous injection. The tests were performed among all age groups in 1965 and 1990, and among those aged under 30 years in the other surveys. Those eligible for tuberculin skin test had their shoulders and arms inspected for any scar or lesion due to previous BCG vaccination. The number of scars, if any, and the types of morphology were recorded.

Chest X-ray examination Sampling The sample size was determined by the KIT in consideration of the estimated prevalences, the degree of desired precision and the budget. The Economic Planning Bureau (EPB) performed a sampling using a multistage stratified cluster sampling procedure. A total of 190 clusters were finally sampled, using as a sample unit a mo-

A chest miniature radiograph (70 mm x 70 mm) was taken for those aged 5 years and over. Field reading of films was done by the end of the workday for each area. All persons with any possible abnormality were eligible for detailed investigation of past history of tuberculosis and for bacteriological examinations; all these radiographs were sent to the KIT and read by

The 6th Nationwide

three central readers. Readers were not informed of the bacteriological findings or of chemotherapy history. Radiological classifications were performed according to the old American Thoracic Society (ATS) standards’ for reasons of consistency.

Tuberculosis

examinations

Those with any abnormal radiological findings were eligible for bacteriological examination. Three spot specimens were collected: two laryngeal swabs and one sputum expectorated after swabbing. Direct smears were made on the spot and at provincial laboratories. The specimens were inoculated onto culture media at provincial laboratories. Two smear slides and four inoculated culture tubes were sent to the Central Laboratory for further processing. In order to be compatible with the previous surveys, the culture examination was performed by the same method using Loewenstein-Jensen medium (treated with 5% oxalic acid and neutralized with 5% sodium citrate). Additional culture has been done by the Petroff method using Ogawa medium from 1970 onward. However, the culture positives found by the latter and their drug resistance are excluded in this report. The ZiehlNeelsen stained smears were read by light microscope; the results of the microscopy were recorded according to the ATS standard.’ All mycobacterial isolates were submitted to drug susceptibility tests’ and identification tests. Mycobacteria other than tuberculosis (MOTT) are excluded from the data presentation.

Inquiries Subjects eligible for radiological examination were asked, at the time of chest X-ray, whether they had any history of chemotherapy for tuberculosis. Further confirmatory inquiries were made for the drugs taken previously. duration and place of treatment, at the time of sputum collection. and all eligible subjects were asked for symptoms.

Survey

in Korea.

325

IYYO

people move to the urban areas. The coverage of the 1990 survey was of more than 95% in every examination.

BCG vaccination Bacteriological

Prevalence

coverage

Scar screening has been available to more than 95% throughout the surveys. BCG vaccination coverage among those aged under 30 has increased from 24.3% in 1965 to 86.0% in 1990 (Table 1). The age specific coverage curve reaches a peak at 15-l 9 years at a level of 94% (figure not shown). The coverage has increased considerably. from 1.1 c/c in 1965 to 78.8% in 1990, among those under 1 year of age. and has increased from 16.7% in 1965 to 73.8% in 1990 among those of school entrance age (6 years). Over 90% of those aged 12-13 were shown as vaccinated in the 1990 survey. Subjects having normal scar(s) were 91 .O%, hypertrophic 5.5%. keloid 3.5% and mixed types 0.05%.

Tuberculosis

infection

The coverage of skin tests has ranged from 95% to 99% throughout the surveys. The frequency distribution of indurations in the 7974 subjects of 1965 and the 3908 subjects of 1990 aged O-29 years with no BCG scars are shown in Figure 1. The curves show bimodal distribution with one mode at 0 mm and another between 18 mm and 20 mm in 1965 and 14 mm and 16 mm in 1990, and antimode at 8-10 mm in 1965 and 6-8 mm in 1990. A distinct mode ( 18-20 mm) and antimode ( IO- 12 mm) were seen in 4282 children aged O-9 years in 1965. however no distinct antimode was noted in 2021 children of the same age in 1990. The modes (other than 0 mm) of the tuberculin reactors without BCG scars have changed over the period of the surveys. For the O-29 year population. the mode lay in an induration of 18-20 mm from 1965 through to 1975, 16-18 mm in 1980. 16-20 mm in 1985 and 14-16 mm in 1990. For the O-9 year population. the mode remained unchanged from 1965 through to 1975, at 18-20 mm. However, it became flat ( 14-20 mm) in

RESULTS Sample areas and eligible subjects The number of ED increased from 54 (urban 28/rural 26) in 1965 to 190 in 1990. The number of eligible subjects within the population increased from 16 317 in 1965 to 54870 in 1990 (21 027 in 1970, 31 018 in 1975. 26 343 in 1980 and 44 108 in 1985). Age distribution of the 1990 population counts a definitely smaller proportion of those aged 20-24 years than the census population. as has been the case in the previous surveys. This is attributable to the exclusion from sampling of areas with mass accommodation facilities, amongst other reasons. Older age groups become preponderant in rural areas in later years. as the younger

Table 1. BCG years of age

vaccinntion

coverage

by age youp.

‘; under

30

IY65

I Y70

IY75

IYXO

19x5

I 001)

observed adjusted

24.3 25.7

13.4 12.6

60.6 59.4

6Y.Y hY.6

80. I X0.3

x.5.x

04 s-9 IO-I4 IS-19 20-24 25-29

6.1 2x.1 4Y.i 32.6 72.0 5.5

38.X 53.3 52.6 37.3 28.3 70.5

4X.2 72.8 77.1 62.9 1Y.2 2Y.3

,49.X 71.2 XX.X Xi.1 60.0 4Y.Y

h5.Y 75.7 ‘12.7 93.1 83.0 65.X

78.4 77.0 XY.3 94.3 Y7.0 8.3.Y

Total

Age

‘adjusted

to 1975 ccncus population.

Xh.0

326

Tubercle and Lung Disease

%

O-29

% 65

years

O-9

-1990

1f

o+-T?i” Fig. 1 -

______

__a-e-l965

!.8

Frequency

L?

12

16

distributions

71

20

years

24

of tuberculin

28

reactions

1

32mm by induration

1980, 14-18 mm in 1985, and then the distinct mode became indiscernible in 1990. The observed tuberculin positive (2 10 mm in diameter) rates are shown in Table 2. In every survey, the age-specific reactivity showed a roughly sigmoid curve with a steep rise around 10-14 years (figure not shown). The observed prevalence of infection in those aged O-29 years has decreased from 44.5% in the first survey to 27.3% in the last survey. The adjusted infection rates according to the population distribution ratio of

0

,

L-3

-1_.

Ii I

1990 1965

I

4

I

8

I

12

sizes in mm among examinees

16

I

20

24

28

I

32mm

without BCG scar.

age groups of the 1975 census showed 53.8% in 1965 and 32.3% in 1990. Higher infection rates have been observed in urban than rural areas, while no constant differences have been noted between the sexes. The downward trend of the positive rate for 5-9 years of age is almost straight, while that for O-4 years showed no downward trend between 1975 and 1985. The percentage prevalences of tuberculosis infection in cohorts born from 1960 to 1990 are shown in Figure 2. 17.5% of the children born in 1960 were infected

Table 2. Indurations of 10 mm or more to 1 TU of PPD RT 23 with Tween 80 among persons without BCG scar. % under 30 years of age Year Total Observed adjusted* Area Urban Rural Sex Male Female

1965

1970

1975

1980

1985

1990

44.5 53.8

46.9 49.2

46.9 45.9

41.7 41.1

38.7 38.8

27.3 32.3

51.8 41.4

58.0 39.9

50.3 44.2

43.6 38.9

39.4 37.3

28.8 23.0

46.2 43.0

46.3 47.5

46.4 47.4

42.4 41.0

37.3 39.8

26.9 27.8

10.2 33.7 69.5 69.4 77.3 80.0

8.5 26.1 54.1 72.0 73.4 81.8

4.8 15.9 49.6 69.6 78.8 81.3

4.9 12.6 32.1 71.1 73.2 79.7

5.4 8.9 29.2 63.1 74.5 80.5

3.1 8.1 23.5 58.4 56.4 67.5

Age o-4 5-9 lo-14 15-19 20-24 25-29

*adjusted to 1975 census population.

Fig. 2 - Percentage prevalence born from 1960 to 1985.

of tuberculosis

infection in cohorts

The 6th Nationwide Tuberculosis Prevalence Survey in Korea, IYYO

childhood, less remarkable during nearly flat after 25 years of age.

Risk of tuberculosis

'55

adolescence

327 _

and

infection

The 5-9 (7.5) year age group has been adopted to assess the trend of tuberculosis infection, because the infection rates have been biased by the presence of those BCG scars no longer observable in the vaccinated and by MOTT infection in younger children, and the high coverage of BCG in older children and adolescents. Observed prevalences of infection in the 5-9 year group have decreased from 33.7% in 1965 to 8.1% in 1990 (Tables 2 and 3). A comparison has been made between the prevalence based on the regression line and the prevalences observed in surveys. Observed prevalences of tuberculosis infection conform well to the calculated prevalences (31.5%~, 23.X%, 17.7%. 13.0%, 9.5% and 6.9%) in the respective surveys. Average annual risks of infection in cohorts of the 5-9 year age group have been calculated on the basis of infection prevalences observed in the six surveys. The risk has decreased successively, from 5.3% in 1965 to 1.1% in 1990 (Table 3). A linear regression was obtained by the equation of the annual infection risk based on the observed infection prevalence: according to this line, the risk of infection for each year shows a 6.44% reduction. Another attempt has been made to assess the changing trend of tuberculosis infection in the S-9 year group by adopting the method of the WHO Tuberculosis Research Office.’ The method assumes that in all age groups, the specific reactions are distributed normally with a mode lying between 14 mm and 18 mm induration. The 17 mm mode (17 mm x 2, mirror image distribution) has been adopted. The modified infection rates were 46.7% in 1965 and 4.1% in 1990, and the annual risks of infection were 8.1% in 1965 and 0.55% in 1990 (Table 3). The annual reduction rate thus far assessed is 10.2%.

I~_ _I_ I ?__~~_ _._~,

'65

'75

'65

'95

20'05

2015

2025

Fig. 3 - Estimated percentage prevalence of tuberculosis infection in cohort? born from 1935 to 1985, according to age.

when they had reached 4 years of age in 1965, a prevalence which had increased to 68% by the age of 14 in 1975. While the infection rates in the under 15-yearold age group of cohorts born in 1965, 1970, 1975, and 1980 showed decreasing trends, it remained unchanged in the over- 14-year-old age group. The prevalences of tuberculosis infection for the cohorts born from 193.5-1985 at 5-year intervals (including the 1957 and 1958 tuberculin surveys), have been estimated from the figures calculated on the basis of annual risk of infection derived from the observed infection prevalence of the 5-9 year age group; a figure was obtained simulating the method of Styblo et a1.4 The observed and estimated prevalences at 7.5 years of age conform well throughout the six surveys (Fig. 3). For the individual cohort, the rise of the curve is steep during

Prevalences

of pulmonary

The rates are classified into four categories: (1) smearpositives: smear-positive culture positive. (2) smear and/

Table 3. Estimates of prevalence of tuberculosis infection with M~~cohuc~terium annual risk of infection among children age 7.5 years (2 cut-off points) Tuberculin

tested

Year of survey

Total examined no.

No BCG scar no.

IYSX I Y63 lY6X

1965 1970 I975

4169 4992 427’)

1973 1978

1980

19x3

1990

3415 3834 5484

2998 22X I II66 880 1177 1210

Cohort born on average on January I

I985

tuberculosis

ruhrrc~ulosis

Prevalence ot infection >I0 mm >I7 mm X 2 Q c/ 33.7 26. I IS.9 12.6 X.Y 8.1

46.7 32.2 20.7 9.2 5.X 4.1

and average

Annual rish of infection 210 mm 217 mm x 2 % 4 5.3 3.9 ?..3 1.X I .2 I.1

X. I 5.1 3.0

I -3 0.X 0.5 __~~~___

328

Tubercle and Lung Disease

Table 4. Prevalence of pulmonary of the population aged over 5 Year Smear positive cases Total observed adjusted’ Area Urban Rural Sex Male Female 5-19 Age 20-34 35-49 5@64 +65

tuberculosis.

Rates per 100 000

1965

1970

1975

1980

1985

1990

690 709 385 838 996 401 194 958 1454 939 914

560 617 522 _

480 480 526 446 703 272 83 522 862 1280 846

309 280 242 384 500 126 53 250 567 723 938

239 220 197 311 408 86 20 212 476 550 461

143 110 96 245 229 66 12 55 260 327 432

-

Smear and/or culture positive cases Total observed 935 741 adjusted 970 770 Area Urban 695 793 Rural 1063 708 Sex Male 1422 1023 Female 496 478 5-19 280 128 Age 20-34 1257 734 3549 1891 1363 50-64 1670 2016 +65 914 2227

765 750 763 765 1061 486 215 718 1191 1955 2030

544 510 387 723 825 277 14 401 908 1276 2439

443 400 385 541 709 202 60 396 681 980 1537

241 190 188 355 363 132 30 118 340 549 897

Active cases Total observed adjusted* Area Urban Rural Sex Male Female 5-19 Age 20-34 3549 5C-64 +65

3326 3300 3164 3444 4207 2501 1777 2856 4168 6825 9814

2509 2400 2380 2655 3282 1770 842 2171 3472 5697 8255

2158 2000 2072 2305 2827 15.52 690 2008 2610 4422 7582

1842 1600 1580 2406 2494 1258 795 1200 1898 3607 6148

5065 4222 5000 4400 5252 4161 497 1 4261 6372 5113 3864 3389 2397 2370 4665 3467 7737 6099 10 752 7852 13708 14134

*adjusted to 1975 census population - not available

or culture positives (sputum positive): smear positive culture positive plus smear-negative culture positive, (3) active pulmonary tuberculosis patients (smear and/or culture positives plus smear-negative culture negative radiologically active cases) and (4) inactive cases. Rates are shown per 100 000 population aged over 5 years (Table 4). The coverage of radiological examinations has been of over 95% and bacteriological examinations of over 97% (except for 1975 when it was 93%), throughout the surveys.

Smear andlor culture positive cases The rates observed have decreased from 935 in 1965 to 241 in 1990, showing 5.3% of annual reduction (2.0% from 1965 through 1975, 7.4% from 1975 onward). They have been higher in rural areas in the last 3 surveys, and high in males and those aged over 35. The proportions of advanced cases in the sputum-positive cases showed a trend of reduction: 45%, 32%, 28%, 30%, 23% and 22% in the respective surveys. The estimated numbers of patients were 226 000 in 1965 and 95 000 in 1990. Active cases The rates decreased from 5065 in 1965 to 1842 in 1990, with an annual reduction rate of 3.97%. The urban/rural ratio has been much the same except for that of the last survey, when the rate was higher in the rural area. Sex and age distributions are similar in the sputum-positives. The estimated number of patients was 1 240 000 in 1965 and 728 000 in 1990. Inactive cases The rates of inactive cases were 1417 (1965), 1691 (1970), 2569 (1975), 1244 (1980), 3342 (1985) and 3851 (1990) respectively, increasing by 4.1% per annum. The estimated number of cases was 350 000 in 1965 and 1 520 000 in 1990.

History of chemotherapy The proportions of those reported to have present or past chemotherapy (old cases) among sputum positive cases

Nww(unknown)

200

100

Smear-positive cases The prevalences observed have decreased from 690 in 1965 to 143 in 1990, with an annual reduction rate (1965-1990) of 6.10% (3.56% from 1965 through 1975, 7.76% from 1975 onward). The rates have been preponderant in rural areas in the last three surveys. They have been distinctly higher in males (ratio about 4:1), and in those aged over 35. The estimated number of patients was 170 000 in 1965 and 56 000 in 1990. The proportion of smear-positive patients among the smear and/ or culture patients has changed: 73% in 1965 and 76% in 1970, 63% in 1975, and 57%, 54% and 59% respectively from 1980 onward.

0

100

200

Md(knovml

Fig. &-Old/new case rates and drug resistance cases per 100 000.

in sputum positive

The 6th Nationwide Table 5.

Tuberculosis

Prevalence

Survey in Korea. 1090

Drug resistance 1965

1970

1975

No. (o/C)

No. (c/c)

No. (%)

19x0 No. (%)

1085 No. (%)

I YYO No. (‘ir I

All cases Te\ted Rerihtant

71 27 (3X.(~)

107 42 (39.3)

188 7’7 (3X.3)

11x S6 (47.5)

I70

I I.3 31(17.1)

New case\ Te\ted

42

I I (26.2)

72 IY (16.4)

143 39 (27.3)

63 IS (23.X)

2Y 16 (55.2)

3s 23 (65.7)

45 33 (73.3)

SS 41 (74.5)

Year

Re\i\tant Old ca\es Te\ted ReAant

319

were: 41.0% (1965), 29.7% (1970), 24.2% (1975), 47.2% (1980), 42.6% (1985) and 33.9% (1990) respectively. The rates (per 100 000) of the sputum-positive old and new (found during the surveys) cases in the POpulations surveyed are shown in Figure 4. The old case rate dropped initially from 1965 to 1970, and stayed much the same, at around 200, in 1970. 1975 and 198.5, with an intervening increase to around 250 in 1980; it then decreased to 80 in 1990. The new case rates remained unchanged at around 550 from 1965 through to 1975, followed by a sudden drop to 280 in 1980. with a stepwise reduction to 150 by 1990. The annual reduction rate of new case rates throughout the six surveys was 4.9% (8.3% from 1975 onward).

Drug resistance The overall drug resistance rates to one or more antituberculosis drugs remained unchanged (38%-39%) from 1965 through to 1975, increased to the peak of 47% in 1980 and then decreased to 27% in 1990 (Table 5). The drug resistance rates (initial) in new cases were much the same (around 27%) from 1965 through to 1975, but decreased to 15% in 1990. Drug resistance in old patients increased steadily to a peak of 75% in 1980, and then decreased to 54% by 1990. The drug resistant case rates per 100 000 have decreased considerably (Fig. 4), from 145 to 26 in initial drug resistance and in drug resistance in old patients from 2 11 to 4 I. The total drug resistant case rates have decreased to less than one-fifth (from 356 to 67) in the last 25 years. A detailed analysis is omitted, as it has been reported separately.”

DISCUSSION The Republic of Korea has a population of 42.8 million (1990 estimate) in a territory of 99 000 square kilometers. National income per capita was US$93 in 1965 and US$4313 in 1990. The NTP was launched in 1962 and has been implemented through the network of health centres. In 1990, 259 health centres with more than 1300 subcentres were administratively supervised by the city/provincial governments and technically sup-

60 (35.3) IO0 I’) (lY.01

7x lZ(l5.J)

70 31 (5X.61

35 I’) (53.31

ported by KNTA. There are private sectors as well, sharing around 50% of the patients. The first nationwide tuberculosis survey in Korea was performed in 1965, with subsequent surveys conducted at 5 year intervals up to 1990. The findings of the prevalence surveys are believed to be closely related with the NTP efforts. thus. the discussion will take the NTP performances into account. Systematic BCG vaccination covering the entire country through the NTP has been performed since 1962. Preschool children and first graders (6 years of age) at primary school are eligible for direct vaccination. School leavers (12 years of age) who show a negative tuberculin test (under 10 mm in diameter) are given BCG regardless of the previous vaccination. Roughly 1.5-2.5 million children have been vaccinated annually. The coverage found in the prevalence surveys has increased successively in every age group. The infant coverage has significantly increased from 1% to 79%. A drawback of this increased coverage is the reduction in the number of eligible children to measure the infection rate. Thus, the reliability of the rate of tuberculosis infection and the annual risk of infection would have decreased. A shift to the left was observed in the modes of the induration size of the tuberculin reactions (Fig. I). The same phenomenon was reported by Broekmans, observed in Ho-Chi-Minh City in Vietnam.’ One (SJK) of the authors presumed that this might be due to the reduction of the infecting doses. Another possible cause is the strength of the tuberculin used. However. the latter could be ruled out, as the source of the tuberculin has been identical (Copenhagen) in every survey. The most probable explanation would be the reduction of density of exposure. supported by the fact that the prevalence of infectious cases has decreased. It seems that the ‘usual’ 10 mm cut-off point would give a reasonable distinction between subjects infected and those non-infected with tubercle bacilli according to the induration histogram of tuberculin reactions in the O-29 year-old population. However. there are several confounding factors to be considered. The frequency distribution of indurations in non-vaccinated subjects aged 13 and over is influenced by the selective BCG vaccination scheme for sixth graders aged 12-13 years. BCG vaccinations is offered to those children

330

Tubercle and Lung Disease

showing indurations of 9 mm or less regardless of previous vaccination. Thus, the proportion (rates) of those with a reaction of more than 10 mm among the nonBCG vaccinated were definitely different between the under 10 years and the over IO-years-of-age. Consequently, the observed indurations of 10 mm or more are grossly overestimated and do not indicate the true prevalence of tuberculosis infection at the respective ages. Therefore, the rates cannot be used for epidemiological purposes. On the other hand, BCG vaccination at school-entry age (6 years) is given only to those with no BCG scar. The age group O-9 years, therefore, would be more suitable for estimating the prevalence of tuberculosis infection than the older age groups. However there are other biases: one is the inclusion of BCG-induced tuberculin reactions, because the less than l-year-old infants are vaccinated with a half dose (0.05 ml), with which it has been reported elsewhere that nearly 40% of vaccinees do not possess a visible scar after 3 years. Secondly, the 1990 histogram of children aged O-9 suggests that infections with mycobacteria other than Mycohacteriurn tuberculosis are present. Findings supporting this were discovered in the surveys of skin sensitivity to the various mycobacterial sensitins, performed in 1985’ and 1990. These findings indicated that a considerable number of children might have been sensitized by M. avium-intracellularescrofulaceum complex or by M. fortuitum with or without tuberculosis infection. Thus, the ‘usual’ 10 mmor-more cut-off point will overestimate the prevalence of infection with tubercle bacilli in every age group. We used the group of 5-9 year-old children for the estimation of infection prevalences and annual risk of infection (ARI). However, the decreased numbers of eligible children due to high BCG coverage undermines the accuracy, apart from the above-mentioned confounding factors. Even in the 5-9 year age-group, the annual risk of infection thus obtained might be overestimated, and consequently the reduction rate of the AR1 (6.44% by regression line) might be underestimated. An estimation using the WHO Tuberculosis Research Office method was attempted to compensate for the confounding factors; the 17 mm mirror image estimation showed a steeper reduction of AR1 (10.2%). Treatment policy in the NTP should have influenced the prevalence of tuberculosis and drug resistance. The regimen was very poor up to the early 1960s and the application of long-term triple chemotherapy from 1962 did not improve treatment efficiency.’ However, the efficiency has improved significantly since the application of intensive short course chemotherapy from the early 1980s. The prevalence of pulmonary tuberculosis has decreased steadily: in the last 25 years smear-positive cases have decreased from 690 to 143, smear and/or culture positive cases from 940 to 241 and active cases from 5065 to 1842 per 100 000. The reduction rate has been higher in smear positive cases, the annual re-

duction rate being over 6%. The reduction rate seems to have accelerated since 1975. The proportion of smearpositives among all sputum-positive cases has decreased, as has the proportion of advanced cases among sputum positive cases. There seems to have been a trend toward milder and paucibacillary forms in the past quarter of a century. Case rates become concentrated in males in older age groups. The prevalence of active cases seems overestimated, as the ratios of actives to sputumpositives have ranged roughly between 3: 1 and 6:1, probably due to the policy that the readers should not be informed of the history of chemotherapy and the bacteriological findings. The inactive case rate and the number of cases have increased significantly. The magnitude of the tuberculosis problem is variable in the East-Asian countries. Several Asian countries other than Korea have performed nationwide tuberculosis prevalence surveys at 5 year intervals, namely: Japan from 1953, 5 times: ‘” Taiwan from 1957/58, 7 times;” China from 1979, twice;‘? and the Philippines 1981/83 once.‘j In Japan, the sputum-positive case rates per 100 000 in all age groups was 750 in 1953 and fell to 120 by 1973. The rate in Taiwan was 1020 among those over 20 years of age in the first survey (1957) and decreased to 110 by 1987/88. It was 205 for all age groups in China in 1984185; however, there were significant variations between the Provinces (Xinjiang 304, Beijing 75), since it is a vast country. In the Philippines, the rate was 1250 for those over 10 years of age in 1981/83. The proportions of old cases have been in the range of about 25%-45% of sputum-positive patients and around 15% to 40% of active patients. It is well known that many old cases conceal their history of tuberculosis; therefore, these proportions are biased: old cases are more or less underestimated and new cases overestimated. In fact a relatively large proportion of the alleged new patients in the survey were later disclosed to be old patients. Although some believe that these proportions show treatment coverage, they should reflect case finding/treatment efficiency as indicated and discussed by Mori.lJ The intervening factor to be considered in this context is the duration of sputum positivity (shorter in the current intensive short-course chemotherapy, and longer in the former long-term treatment) in the initially positive patients. Quite a number of initially positive patients on good chemotherapy should already have achieved negative conversions at the time of the survey. Only the recently found positive cases could be classified as old positives, which would consist of a very small fraction of old cases. In comparison, those who retained their positive status after several months of treatment and were found to be old cases in the surveys would probably be failing or failed cases with emerging or acquired drug resistance (Fig. 4). Therefore, the proportions of sputum-positive cases should not be considered as the treatment coverage rates. Instead, the old case rates should be interpreted rather as the reflection of treatment efficiency. As a result, the increased rate of old sputum-positive cases in 1980 would re-

The 6th Nationwide

tlect the accumulation of chronic cases accompanied by the peak of drug resistance. The rates were the same in 1970, 1975 and 1985, but had decreased considerably in 1990. On the other hand, the new case rates might be a reflection of the case-finding activities. The new positive case rates were much the same from 1965 through to 1975. and then decreased stepwise up to 1990. On the whole it could be stated that treatment efficiency has improved recently and that case-finding activities may have improved from 1975 onward. The drug resistance rates per 100 000 have decreased to less than one-fifth. The reduction rate exceeded that of the sputum-positive case rate. This finding indicates a reduction in the treatment failure rates due to drug resistance. The advantages and disadvantages of the periodic prevalence surveys have been discussed by Shimao.‘” The validity or I-ea&rrhilifv of the prevalence of infection and/or the annual risk of infection might have been hampered by the high BCG vaccination coverage. Therefore, periodic prevalence surveys could be valuable in countries or regions where BCG coverage is high and notification is poor. It seems that the important and valuable findings from the surveys will certainly contribute to the tuberculosis programmes and add to the understanding of tuberculosis epidemiology. Acknowledgements We are greatly indebted to innumerable persons and organizations who cannot all be named. Our deepest and sincere gratitude goes to all the participants, advisers and reviewers who have been engaged in the past six surveys over the period of a quarter of a century: from village leaders, health workers, local officers, personnel of KNTA. Staffs of City/Provincial Tuberculosis Supervisory Teams, City/Provincial and Central governmental authorities, to the experts and the eminent scholars from international and domestic institutions, organizations and academic circles.

Tuberculosis

Prevalence

Survey m Korea. 1990

33 I

References 1. Ministry of Health & Social Affairs and the Korean National Tuberculosis Association. Report on the 6th Tuberculosis Prevalence Survey in Korea (in Korean). Seoul: Miniq of Health & Social Affairs and the Korean National Tuberculosl\ Association. 1990. 2. American Thoracic Society. Diagnostic standard and classification of tuberculosis and other mycohacterial disease\. New York: National Tuberculosis Association. 1961. 3. Canetti G. Fox W. Khomenko A et al. Adv~anccs in techniques of testmg mycobacterial drug sensitivity. and the use of sensitivq tests in tuberculosis control programme. Bull World Health Organ 1969; 41: 2143. 4. Styblo K. Meijer .I. Sutherland I. The transmission of tubercle bacilli. its trend in a human population. Bull Int Union Tuberc 1969; 42: 3639. 5. Bleiker M A. Sutherland I, Styblo K. ten Dam H G. Mialjenovic 0. Guidelines for estimating the risks of tuber-culous infection from tuberculin test results in a representative sample of children. Bull Int Union Tuberc Lung Dis 19X9: 64(2): 7-l 2. 6. Kim S J. Hong Y P. Drug resistance of M\‘c,oh~l[~tr,f.iltnf tzrhr~~xlosis in Korea. Tubercle Lung Dis 1992: 73: 2 19-224. 7. Broekmans J. The tuberculosis problem in Vietnam and its trend. Preliminary results of the WHO resurvey. Tuberculosis Surveillance Research Unit of the International Union against Tuberculosis and Lung Disease, Progress Report 1989. X. Ministry of Health & Social Affairs and the Korean National Tuberculosis Association. The Second Report on the 5th Tuberculosis Prevalence Survey in Korea (in Korean). Seoul: Ministry of Health & Social Affairs and the Korean National Tuberculosis Association. 1985. 9. Grzybowski S. Enarson D A. The fate of ca\es of pulmonary tuberculosis under various treatment programmcs. Bull Int Union Tuberc 1Y78: 53: 70-75. 10 Ministry of Health and Welfare. Tuberculosis Prevalence Survey ( 1973) (in Japanese). Tokyo: Japan Anti-Tuherculosi~ Association. 1975. II Chang C E. Report on the 7th tuberculosis prevalence survey m Taiwan (3987-19881. Proceedings of the First Congress of the Asia Pacific Society of Respirology. Tokyo. 19xX. pp 137-148. 12 Ministry of Public Health. Nationwide Random Survey for the Epidemiology of Tuberculosis in 198411985. Beijing: Ministry of Public Health of People’s Republic of China. 1985. 13 Cruz A Y. Evangelista R S. Lopez J S, Cabello J S, Pabillore R F, Sarmiento A G. Tuberculosis situation in the Philippines. Proceedings of the First Congress of the Asian Pacific Society of Respirology. Tokyo: 19X8: pp 129-132. 14. Mori T. Significance of tuberculosis survey. Proceedings of the First Congress of the Asian Pacific Society of Respirology. Tokyo: 1988; pp 15X-161. 15. Shimao T. Tuberculosis prevalence survey,. Bull Int Union Tuberc 1982; 57: 126-132.