Trends and Patterns of Tuberculosis: Interpretations and Prospects of Tuberculosis Control in Vojvodina, Yugoslavia, 1987–2000

Trends and patterns of tuberculosis: interpretations and prospects of tuberculosis control in Vojvodina, Yugoslavia, 1987–2000

M. Ilic,* M. I. Khan,† V. Kuruc,* S. Pavlovic,‡ M. Kristoforovic-Ilic,‡ U. Laaser† * Section of International Public Health, Sremska Kamenica, Yugoslavia; † Section of International Public Health, Bielefeld School of Public Health, Bielefeld, Germany; ‡ University of Novi Sad, Sremska Kamenica, Yugoslavia

SUMMARY

AIM: To assess the trends and pattern of tuberculosis in exhaustion were common. With the increasing trend of Vojvodina, Yugoslavia. alcoholism from 1987 to 2000, delays in reporting were METHODS: Using a retrospective design, data on 393 noticed. TB-related mortality was 1.4% in 1987 and diagnosed TB cases were investigated for the years 4.1% in 2000. Resistance to TB drugs among previously 1987, 1993 and 2000. treated cases was 2.7% in 1987, 0.9% in 1993 and RESULTS: TB case notiﬁcation has been increasing in 2.7% in 2000. With respect to the increasing resistance, Vojvodina. The number of reported TB cases was 146 in the levels of detection and surveillance were poor. The 1987, 101 in 1993 and 146 in 2000; cases were predom- implementation of the DOTS strategy remained fairly inantly in the age group 20–39 years (44.5%) in 1987, low. compared to the 40–59 year age group in 1993 and CONCLUSION: TB is a chronic problem in Vojvodina. 2000 (38.6% and 45.9%, respectively). The majority of Prompt community-oriented actions need to be taken to patients belonged to lower socio-economic groups. improve case detection and cure rates through DOTS. Manifestations of TB such as cough, weight loss and KEY WORDS: tuberculosis; trends; DOTS; Vojvodina

IN 1993, tuberculosis (TB) was declared a global emer- vision and monitoring of outcomes under the directly gency by the World Health Organization (WHO).1,2 observed treatment, short course (DOTS) strategy is The WHO has estimated that between 2000 and not applied routinely.1,3,12–20 2020 nearly one billion (1000 million) people will be According to the WHO classification, Yugoslavia newly infected, 200 million will become sick, and 35 comes under category 3, where progress in DOTS im- million will die from TB worldwide.1–5 Due to large plementation has remained static.1,3–5 Human immuno- diversities in the quality of care, TB trends and patterns deficiency virus and the acquired immune-deficiency are constantly changing in Europe.3 The collapse of syndrome (HIV/AIDS) and emerging multidrug resis- communism in the late 1980s and the difficult transi- tance are additional threats to TB control.1,3–7,11–14 tion from controlled to free market economies in the From 1993–1995, reported TB incidence in Yugosla- 1990s have taken a toll on the health status in the 17 via, particularly in the province of Vojvodina, countries of the Central and Eastern European (CEE) increased to 13.5%.4,12 During 1995–2000, no signif- Region.6–12 The 2003 World Health Report revealed icant progress was reported on DOTS expansion. In that TB treatment failure rates in the European 2001, the detection rate under DOTS was 25%, and Region (7%) and in the former Soviet (9%) countries supervision and monitoring of TB control activities were conspicuously high.1 In Yugoslavia alone, TB were poor.1 National data are poor, especially in areas cases notified in 1995 (n 2798) almost doubled such as Kosovo and Metohija, and the available fig- to 4556 in 2001.4,13 TB is endemic and is leading to ures do not allow precise distinction to be made increased mortality and morbidity.12–20 Prolonged between smear and culture results among bacterio- periods of war and war-induced socio-economic dif- logically-confirmed cases.1,3–5 Vigorous effort is still ficulties have added significantly to the poor perfor- needed to make DOTS a priority intervention for TB mance of the health systems.9,12–20 Treatment super- control in the country.1,3–7,11–15

Correspondence to: Dr Ibrahim Khan, Section of International Public Health, Bielefeld School of Public Health, pf. 100131 (IBS), Uni-Bielefeld, Bielefeld, 33501 Germany. Tel: (49) 521 106 5166. Fax: (49) 521 106 6009. e-mail: ibrahim. [email protected] or [email protected] Article submitted 22 August 2002. Final version accepted 29 April 2003. Tuberculosis in Yugoslavia 1065

Given the escalating burden of TB, this article aims Table 1 Features of TB cases in Vojvodina to assess the trends and pattern of TB, and the impact Patient characteristics 1987 1993 2000 of control interventions in Vojvodina, Yugoslavia. Number of patients 146 101 146 Age (average,) years 47 50 55 SUBJECTS AND METHODS Sex (M/F), % 66/34 67/33 71/29 Proportion refugee population, % — 16 12 The Institute of Lung Diseases in Sremska Kamenica, Proportion employed, % 18 76 72 Previous interruption of treatment, % 13 19 31 Vojvodina, was selected for a retrospective sentinel BCG vaccination status, % NA 68 73 review of the medical records of 393 TB patients Reported TB-associated mortality, % 1.4 1.9 4.1 diagnosed and treated between 1987 and 2000 in the TB history in close contacts/family, % NA 18 34 Institute. Vojvodina is one of the semi-autonomous BCG bacille Calmette-Guérin; NA not available. provinces of the Former Republic of Yugoslavia, with high population density (10 538 000) and demographic variety. Novi Sad is the administrative, economic and decline (Figure 1).1 More males were affected than cultural seat of the province.3,4 females in each of the three years 1987, 1993 and Based on data availability, a comparison of TB 2000 (Table 1). TB-related mortality increased from trends was carried out by reviewing cases from three 1.4% 1993 to 4.1% in 2000. History of TB in close selected major categories, 1987, 1993 and 2000. contacts, previous interruption of treatment and the Cases were selected on the basis of full record avail- number of refugees were fairly high. The age of the TB ability for the previous 6 to 8 months and confirma- cases varied between the three years studied (Figure 2): tory reports of sputum smear for 1987, 1993 and the majority of TB cases in 1987 were in the age group 2000, respectively. Cases with incomplete and miss- 20–39 years (44.5%), while they were mainly in the ing data on treatment outcome, laboratory confirma- age group 40–59 years in 1996 and 2002 (respectively tion and sputum conversion were excluded. TB cards 38.6% and 45.9%), i.e., in the most economically pro- in the TB facility were also cross-checked against the ductive age groups. The number of patients aged TB register. In order to ascertain long-term yearly TB under 20 years was 6.2% in 1987 and 5.9% in 1993, trends and patterns, case detection data were col- while the number of patients aged 60 years was 13% lected starting from the year of treatment from 1987 in 1987 and 19.9% in 1993. By 2000, the number of to 2000. Along with other sample characteristics, TB cases in the economically productive age had delays in reporting and comparisons of trends in diag- fallen from 80.8% to 70.3% and the number of nosis were depicted graphically. TB cases were grouped patients aged 60 years had increased to 25.4%. in terms of age, sex, socio-economic status, pattern of Stratifying patients on the basis of socio-economic manifestations, diagnosis, reporting delays and treat- parameters, 89.1% of patients in 1987 had no perma- ment outcome. Three local TB experts and two from nent income source or job, and 10.9% were pension- the University of Bielefeld, Germany, were involved in ers, while in 1993, 76% of the patients were employed, the review. To increase the quality and breadth of the although there was no information on income levels. study, published literature was retrieved through The number of TB cases among the unemployed com- Medline with multiple key words, TB in FR Yugosla- munity increased from 9.9% to more than 20%. In via, tuberculosis in Vojvodina, TB drug resistance in 2000, however, 28.1% of cases were unemployed. Yugoslavia, and infectious diseases in Yugoslavia, With respect to frequency of TB in the employed or and were included in the review. income earning groups in 1987, the pattern appeared to change in 1993 and again in 2000. RESULTS TB case notification rates have been unsteady in Voj- dovina, showing an increase in 2001 after a short

Figure 1 TB case notiﬁcation rate in the former Republic of Figure 2 Age of TB patients, 1987, 1993 and 2000, Vojvodina Yugoslavia.1 Province. 1066 The International Journal of Tuberculosis and Lung Disease

An interesting finding of the study was the pattern Table 2 List of frequently reported manifestations of alcoholism among cases in 1993 and 2000. Alco- of tuberculosis in Vojvodina hol consumption was measured based on units; severe 1987 1993 2000 alcoholism among TB cases was defined as more than Symptoms % % % two units or glasses per day.* The percentage of moder- Dry cough 65.7 69.3 64.4 ate alcoholics was 16.8% in 1993 and 19.8% in 2000, Weight loss 22.6 51.5 65.7 while severe alcoholism rose from 20.8% in 1993 to Exhaustion 45.9 53.4 58.9 High temperature (fever) 46.5 40.6 43.2 34.3% in 2000. Loss of appetite 31.5 52.5 55.5 The pattern of care seeking among patients was Chest pain 27.4 31.6 36.9 also reviewed. The time to reporting to the doctor Perspiration 31.5 28.7 33.6 General weakness 12.3 26.7 29.5 after the appearance of manifestations varied widely Breathlessness 10.3 16.8 27.4 among the different categories; 41.4% of patients in Haemoptysis 14.4 19.8 19.1 1987 consulted a physician after 15 days, compared Hoarseness 0 4.9 6.1 Headache 0 0.9 2.1 to 31.2% in 1993 and 12.8% in 2000. The delay in reporting was increased by 1 to 3 months in both 1993 and 2000. Delays in diagnosis due to the physician could not be evaluated. In 1987, more than half localised changes increased from 26.8% to 52.7% of the patients (54.6%) were hospitalised immedi- between 1993 and 2000. The number of patients with ately, while in 2000 this number fell significantly to cavitary TB was of concern: 35.6% of patients in 1987 29.3%. The number of patients for whom hospitalisa- and 65.7% in 2000 had cavities in the lungs. In a tion was clearly delayed from 15 to 30 days increased comparison of age with advanced TB state (bilateral from 35.2% to 50% in 1987 and from 8.6% to 15.7% cavitary form), an increasing trend of patients with in 2000. Similarly, the number of patients hospitalised advanced cavitary TB (from 8.9% in 1987 to 13.7% after a more significant delay of 1–3 months rose to in 2000) was noticed, particularly among patients 5% in 2000 from 1.6% in 1987. aged 40–59 years. A similar increase (from 1.4% in Disease detection was based mainly on clinical 1987 to 11.6% in 2000) was also noticed in the age symptoms. Among the list of manifestations, cough group 60 years. was the most frequently reported complaint among The chemotherapy regimens prescribed were eval- TB patients (Table 2). A unique pattern of manifesta- uated. Regimens containing three TB drugs were tion was observed among various categories depend- most common in all three years. Isoniazid was the key ing upon the site of involvement. Weight loss, exhaus- component of the anti-tuberculosis regimen, given in tion, fever, loss of appetite, chest pain, and increased 89% of cases, followed by rifampicin and pyrazina- perspiration were the main symptoms reported. Fig- mide. In 1993, shortages of ethambutol and strepto- ure 3 illustrates the trends of the various methods mycin on the market excluded them from the treat- used for screening, detection and confirmation of TB. ment regimens. Direct sputum microscopy was used to diagnose the Physicians’ approaches in prescribing treatment disease in almost a third of patients (30.1%) in 1987. were variable. Prescription of a standardised regimen By 1993 this had risen to 36.7%, and by 2000 almost and adjustment to the patient’s weight and age were 71.9% of cases were declared positive by direct poorly followed. In several cases, TB treatment was microscopy, while 10.2% were diagnosed by histo- interrupted due to shortages of drugs on the market. logical or cytological examination. The use of sensi- Overall, more than 21% of patients had a history of tivity testing was extremely limited. Coupled with the interruption of treatment, while 12% were relapse cases use of conventional diagnostics, in 1987 the diagnosis and 7% did not return after diagnosis. No actions were in 33.6% of patients was supported by histological taken by TB caregivers to enhance patients’ adherence screening and cytology. The frequency of using culture declined from 61% in 1987 to 21.7% in 2000.19 Research is needed to evaluate whether this is due to lack of resources or errors in practice. X-ray is still a widely favoured method of diagnosis. Chest X-rays of the pulmonary TB cases were meticulously examined for infiltration and involvement of lungs in the different years of the study. In 1987, the majority of patients (71.2%) had localised unilateral radiological changes, compared to 61% in 1993 and 46.6% in 2000. The percentage of bilaterally

Figure 3 Methods used to diagnose TB, 1987, 1993 and * One unit contains approximately 10 g alcohol. 2000, Vojvodina Province. Tuberculosis in Yugoslavia 1067 or health education. Detailed information on treat- Although the majority of cases in the present study ment outcome, such as cure, relapse, transfer and were employed in 2000, in monetary terms purchas- default were not available for the majority of cases. ing power remains weak, and people do not have suf- Surveillance of multidrug resistance is not widely ficient resources. High inflation rates have further practised, and little information was documented. influenced patients’ care seeking patterns and adher- Reported resistance among previously treated cases ence.9,12,15,17,20 The majority of patients depend on was 2.7% in 1987 (mostly to isoniazid and rifampi- public health facilities for treatment, but these facili- cin), while it was 0.9% in 1993 and 2.7% (to strep- ties themselves have insufficient resources to satisfy tomycin only) in 2000. the expectations and needs of TB patients. An increasing tendency towards alcohol consumption among advanced TB cases was frequently re- DISCUSSION ported.17 The tendency towards excessive alcohol The present study provides significant information consumption among TB patients may be associated about the increasing burden of TB cases in various with socio-economic or disease-related mental insta- age groups, delays in reporting, patterns of manifes- bility. Hazardous drinking patterns were found in a tation and treatment outcome in Vojdovina. Current Croatian AUDIT study (Alcohol Use Disorders Iden- TB control interventions have had little impact on tification Test) among hospitalised TB patients.8 Our reducing the burden of TB or changing the TB pat- study therefore highlights the need for more explana- tern. Although cases have been detected, the follow- tory research on related behavioural issues and on- up system for supervised treatment is weak. Poor going trends in the community. Delays in diagnosis and treatment outcome, delays in reporting, increasing commencement of treatment can have fatal conse- mortality and acquired drug resistance in Vojvodina quences, not only for the patient but also for the indicate poor TB control. The current situation health system.1,2,5,7,13,16,17,21 The fact that patients urgently needs DOTS and fine tuning of TB interven- were more likely to delay treatment may be related to tions in accordance with WHO recommendations. a poor awareness of the TB problem or an inability of A periodic shift of TB trends among the more the system to detect and treat in time. Delays in seek- socio-economically productive ages was evident. As ing care in the initial 15 days after the appearance of shown in the age categories, the majority of the TB symptoms were common in the lower income group. cases were in the economically productive age Reported resistance and complications are a clear groups. An increasingly aged population, along indication of the need for rapid action. Complications with deteriorating socio-economic conditions and such as cavitary TB increased dramatically when care lack of access to competent care, are important fac- seeking was delayed, followed by late admission and tors of this increase in the number of TB cases.1,3,4,7 ultimately late commencement of proper treatment. Prompt diagnosis and case management play a cru- According to Zafran et al., delays in detection and cial role in the effective eradication of TB.1,2,5 Cou- associated complications were the main factors con- pled with the results of our study, an increasing tributing to the death of the majority of TB cases stud- number of TB cases have been widely documented ied retrospectively at the Institute for Lung Diseases from the war-affected zones.4,12–16,19–21 Similar TB and Tuberculosis, Sremska Kamenica.17 The Institute trends have also been re-ported in neighbouring has its own approach to TB control: treatment out- countries.1,6,8,10–20,22 In Bucharest, Romania, when come monitoring is not routinely done, and most TB cases were compared from 1989 to 1994, an patients were given unsupervised treatment. Currently, increasing occurrence of advanced TB (bilateral only 16% of the infected population have access to localisation with cavities from 28% to 36%) and DOTS, leaving a significant proportion of cases out of mortality was traced in the population aged 60 its reach.1,3,6,7,12,14,15 The diagnostic and screening meth- years.22 Acimovic et al., in 1996, supported the ods applied varied significantly between the years notion that pulmonary tuberculosis in the war areas studied, with increasing use of direct microscopy in of Yugoslavia from 1991–1995 was characterised 2000. This review is a stimulus for further research by a greater frequency of severe clinical forms (cav- into the related issues. itary, bilateral and extensive) and by high bacillary The TB scenario in the region overall could not be counts.12 The incidence of TB was examined in described due to the limitations of the study; however, native residents from 1985 to 1994 and displaced the study does raise questions about the quality of TB persons from 1992 to 1994 in the pre-war and war interventions. Yearly comparisons were not possible periods from 1985–1994 in Zagreb, Croatia. The due to the incompleteness of the available data. Com- most significant predictors of the TB incidence rate mitment to improving case detection, expansion of were the period (year) and residence status. The supervised care, adequate drug supplies, regular follow- results did not, however, indicate a potential change up and monitoring are integral components of the in the natural decline of the incidence of tuberculo- DOTS strategy,1 which has proved the most cost- sis in the resident population.9,19 effective method of TB control. DOTS not only saves 1068 The International Journal of Tuberculosis and Lung Disease patients’ lives and reduces the cost of treatment, it gently needed. WHO Press release EURO/11/02, Copenhagen also lessens the risk of complications. Launching a and The Hague, 6 June 2002. nationwide surveillance system to measure the exact 11 Raviglione M C, Rieder H L, Styblo K, Khomenko A G, Es- teves K, Kochi A. Tuberculosis trends in eastern Europe and magnitude of TB and putting more focus on health the former USSR. Tubercle Lung Dis 1994; 75: 400–416. promotion and behavioural issues will significantly 12 Acimovic S, Sikimic S, Ponomarev D, et al. 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RÉSUMÉ

OBJECTIF : Déterminer les tendances et le type de la de poids et la fatigue, étaient fréquentes. Avec la tendance tuberculose (TB) en Vojvodina, Yougoslavie. croissant de l’alcoolisme de 1987 à 2000, on a remarqué MÉTHODES : Dans une étude rétrospective, les données des retards de notification. Le taux de fatalité liée à la de 393 patients diagnostiqués comme tuberculeux (dos- tuberculose était de 1,4% en 1987 et 4,1% en 2000. La siers de cas) en 1987, en 1993 et 2000 ont été évaluées. résistance aux antituberculeux chez les cas déjà traités RÉSULTATS : Le taux de notification des cas TB est en était de 2,7% en 1987, 0,9% et 1993 et 2,7% en 2000. augmentation en Vojvodina. Le nombre de patients TB Par rapport à ce taux croissant de résistance, le dépistage était de 146 en 1987, 101 en 1993 et 146 en 2000 ; la et la surveillance des cas sont inefficaces. L’application plupart appartenaient au groupe d’âge de 40 à 59 ans en de la stratégie DOTS reste faible. 1993 et 2000 (respectivement de 39% et 46%) comparé CONCLUSION : La tuberculose est un problème très à 20–39 ans en 1987. La majorité des sujets provenaient importante en Vojvodina. Des actions rapides orientées sur des groupes socio-économiques les plus démunis. Des la collectivité doivent être prises pour améliorer les taux de manifestations de la tuberculose, telles la toux, la perte dépistage et de guérison utilisant la stratégie DOTS.

RESUMEN

OBJETIVO : Determinar las tendencias y el tipo de tuber- datos de 393 pacientes (informes de casos) diagnostica- culosis (TP) en Vojvodina. dos como TB en 1987, 1993 y 2000. MÉTODO : De manera retrospectiva se analizaron los RESULTADOS : Hay una tasa creciente de notificación de Tuberculosis in Yugoslavia 1069 casos en Vojvodina, de 146 en 1987, hasta 101 en 1993 la tuberculosis fue de 1,4% en 1987 y de 4,1% en 2000. y 146 en 2000. La mayoria pertenecía al grupo de edad La resistencia a los antituberculosos en los casos ya tra- de 40 a 59 años en 1993 y 2000 (respectivamente de tados fue de 2,7% en 1987, 0,9% en 1993 y 2,7% en 39% y 46%) comparado con 20–39 años en 1987. La 2000. Dada este tasa creciente de resistencia, la detec- mayoria fueron personas con nivel socioeconómico más ción y la vigilancia de los casos son ineficaces. La apli- bajo. Las manifestaciones tales la tos, la pérdida de peso cación de la strategia DOTS queda muy pobre. y la fatiga fueron muy frecuentes. Con la tendencia cre- CONCLUSIÓN : Se necesita emprender acciones rápidas ciente del alcoholismo de 1987 a 2000, se observaron orientadas hacia la comunidad para mejorar las tasas de retrasos de notificación. La tasa de fatalidad asociada a detección y curación utilisando la strategia DOTS.