Tuberculosis Trends in Serbia at the Beginning of the 21st Century

Dragica P. Pesut MD, PhD

Institute of Lung Diseases and Tuberculosis, Clinical Centre of Serbia

Research and Epidemiology

Belgrade, Serbia and Montenegro

e-mail: dppesut@Verat.Net

Abstract

SETTING: Serbia, a state of Serbia and Montenegro confederation (former Yugoslavia), an intermediate TB burden European Balkan country with previous constant decline of TB incidence rate (IR).The last decade of the 20th century has brought socio-economic crisis, civil war, bombing campaign and mass migration of population with disintegration of Yugoslavia.

OBJECTIVE: To examine TB epidemiological features in Serbia in period 1991-2002.

METHODS: National referral   institution notification data analysis.

RESULTS: TB IR is stable with 37.6 per 100000 population in 2002 (sputum smear positive pulmonary TB IR is 22 per 100,000). IR is the highest in male’s age group 40 – 44. Number of newly diagnosed cases in groups aged 15-24 years declines. Treatment was successful in 84-89% and treatment failure found in 2.89% of cases. Mortality rate achieved 3.6 per 100000 population in 2000 and relapses account for 7.93%.

BCG vaccination is still mandatory with coverage of newborns of 96%.  

CONCLUSION: There is potential risk of increasing TB trend in the future. There is need of HCWs continual medical education and increasing people’s awareness towards TB.

INTRODUCTION

Expected eradication of tuberculosis (TB) in the mid last century was not achieved in spite of development of potent anti-tuberculosis drugs. Now, at the beginning of the 21st century, the problem of TB is still present due to the increasing number of immunodeficient persons in the world. In 1993, WHO expressed its great concern due to the epidemiological situation with this disease and declared TB as global problem (1).

Serbia&Montenegro (formerly Yugoslavia) is a Balkan - European intermediate TB burden country (1,2). Serbian national tuberculosis surveillance system was founded in 1952 and organized on pyramidal basis. The number of patients affected with TB in the last half of the 20th century was constantly declining by its last decade. Since 1956 TB incidence rate (IR) dropped down ten fold from 324/100,000 population in 35-year period and thus Serbia entered 1990s with IR of 41/100,000 population (3). The average IR at Balkan was 45/100,000 population, while in Europe it was 27/100,000, which was significantly below the world average (4,5). Serbian National TB Programme (NTP) developed in 1966 and adapted in 1998 and 2003 already had included all five crucial elements of Directly Observed Treatment Short Course strategy (DOTS), which may facilitate full application of the recommended strategy. DOTS  was newly implemented in 2001.

The subject of the present study is epidemiological situation with TB in Serbia at the beginning of the 21st century. The analyzed period from 1991 to 2002 is  characterized with economic crisis and mass migration of population from war-affected regions of neighboring Bosnia&Herzegovina with previously highest TB IR in the former Yugoslavia  - 81/100,000 population (Chart 1)

Nowadays, about 10% of Serbian population comprises refugees and internally displaced persons. Due to worsening of the economic crisis the average monthly pension dropped from US$100 in 1996 to US$38 in 1999 and per capita health expenditures have fallen from US$ 200 in 1996 to US$ 60 in 1999. The unemployment has reached 40% at the end of the century (5). In spring 1999, Serbia was faced with bombing campaign of more than two months duration. Some of TB patients postponed their presenting to medical institutions, spending time indoors, in crowded cellars and shelters, with healthy and exhausted people and small children, which might influenced TB transmission incidence (6,7).

METHODS

The annual summaries of the national referral institution - the Institute of Lung Diseases and TB, Clinical Centre of Serbia in Belgrade - have been used for estimation of TB incidence and mortality and the other relevant epidemiological features (8). The official mortality data of the Republic Institute of Statistics have been used, too. To allow comparison by sex and age and to facilitate comparisons, age groups were defined as follows: < 15, 15-24, 25-34, 35-44, 45-54, 55-64 and ≥65 years.

The analysis does not include data from Southern Serbian province Kosovo and Metohia (separated territory) for they were not reported to Serbian TB referral institution since 1997. TB epidemiological situation in this territory has been  compared to the other parts of Serbia owing to WHO official data (1).

RESULTS

A total of 2828 newly diagnosed TB cases in Serbia were reported to the Institute of Lung Diseases and Tuberculosis in Belgrade in 2002. TB IR over 1991-2002 period shows stable condition, fluctuating and ranging from 31.4 to 37.9 per 100,000 population. It varies with respect to the studied region (Chart 1) and ranges from 20 to 74/100,000 population. This latter refers to Macva region, which is close to a neighboring TB high incidence country on the West. The mortality rate achieved its highest value of 3.6/100,000 in 1996 and 2000 (Figure 1). Figure 2 shows female/male ratio among the affected individuals and Figure 3 TB incidence, by sex and age. Clear increase of newly diagnosed cases from year-to-year during the decade is evidenced in the group above the age of 70 years, both females and males and group aged 45-49 years. As for groups aged 15-19 years and 20-24 years, the number of newly diagnosed cases declines.

Out of total number of TB cases, according to the available classification, pulmonary and extra-pulmonary tuberculosis account for 93.6% and 6.4%, respectively. The ratio is stable and has not been significantly changed with respect to previous period (Some of the cases of TB pleural disease might be reported as pulmonary TB in central Serbia and in Vojvodina province (20% of total population) classification to respiratory and extra-respiratory TB used to be present.

Analysis of the clinical forms of the most frequent fibro-caseous pulmonary tuberculosis (PTB), has evidenced 51% of extensive, predominantly multi-cavernous and bilateral forms of PTB of the particularly epidemiological significance. Sputum-smear positive PTB IR is about 20 per 100000 population and has stabile trend ( Figure 4).

Mycobacterium sputum smear positivity was recorded in more than 60% and less than 70% of the cases of pulmonary TB (PTB), 64% on average in the analyzed period (Figure 5). The district/regional differences are evident and range from only 23% to 70.5%. The latter refers to the hospitalized patients of the City of Belgrade, Clinical Centre of Serbia, predominantly. The percentage of PTB culture positive cases has not been distinguished in the annual summaries and estimated to be up to 89% by individual data obtained last few years for central Serbia and studies at hospitalized patients. (9,10) At the national referral institution, the number was significantly higher in the course of individual one-year analysis and in direct connection with extensiveness of the disease (80% extensive forms) (10).

In 84% to 89% of newly detected cases annually, treatment outcome was successful (cured + completed, by WHO/IUATLD definition) (11). Treatment failure was recorded in 2.89% of cases. With respect to the total number of the newly recorded cases of the disease, relapses account for 7.93%, at the average.

The available notification data have enabled analysis of M. tuberculosis resistance to anti-tuberculosis drugs, predominantly “isoniazide”, “isoniazide and rifampicin” and “others”. The average incidence in the total primary resistance during analyzed period was 6.9%, being the highest in 1996 – 11.44%. Acquired resistance rate ranged between 3.28 and 8.34% with the average value of 5.29%. Decreasing tendency of total resistance, both primary and acquired, and monoresistance to isoniazide is observed in 12-year period. Total MDR TB in Serbia at the beginning of the 21st century is considered to be 1.8% and primary MDR TB alone – 0.8%.

BCG vaccination is mandatory, once at birth, with high coverage of newborns (96%). Active TB case-finding by contact tracing has lead to 1.14% (1056) of new TB cases detected among the examined contacts (pooled data).

DISCUSSION

We assume the data are a good approximation of all active TB cases in Serbia without Kosovo and Metohia. The notification, based on pyramidal system, has long-time routine in Serbia. (12) At Kosovo and Metohia, southern Serbian province, TB IR has always been much higher than in central Serbia and Vojvodina province.  WHO reports of still double worse TB IR there (78/100,000 population) in 2001. (13)

The evidenced TB incidence by the end of the analyzed decade was similar to that from its beginning without previous continual decreasing trend. Numerous obstacles have made complex  Serbian pulmonary service work (lack of the basic working materials, intermittent drug supply interruption) and the numerous factors lead to prolonged emotional stress and malnutrition of the population (economical crisis with low incomes and increasing unemployment, the war and mass migration of population). Stable instead of previous decreasing TB trend in Serbia in 1991 - 2002 period is not unexpected but the situation is not that dramatic as in the former Soviet Union Republics.(13,14,15) The majority of risk factors are still present and it seems they could not be solved soon despite of the economical and health care reforms done and the plannes for their progress.

HIV infection does not significantly influence TB incidence in Serbia yet, although there is no systemic testing of TB patients for HIV status. Serbia and Montenegro ranks among HIV/AIDS low incidence countries, but the situation with TB (and HIV/AIDS) in the neighboring countries might make Serbia&Montenegro country with potential risk of worsening of TB epidemiological situation.(13,16,17) The former Soviet Union republics experienced similar transformation/crisis at the end of the 20th century. TB epidemiological situation was worsening from year-to-year together with drug resistance TB problem, which was presented with 37% of all TB cases in Estonia.(15,18) Drug-resistance TB cases number in Serbia is of decreasing tendency according to notification data and 5.4% in 2001 includes both initial and acquired one, which is similar to data from the neiborough Hungary and significantly lower than those in Romania.(17,19,20)

Multi-Drug-Resistant (MDR) TB, which includes 20% of all TB patients among affected inmates in some Russian prisons complicates situation in the region of Balkan, too, particularly in Romania. (17,21) According to notification data, MDR TB in Serbia does not still seem to be a major problem. Central TB register further development and individual data make it possible to analyze drug resistance in previously treated and new TB cases. The second-line drugs are almost completely unavailable and the measures of prevention of TB transmission both for hospitalized and outpatients are not fully applied.(22, 23) There is a need for further improvement of the notification and laboratory quality control as well as health care workers education in prevention (the priority), recognizing and management of MDR-TB.  Since 2000 National mycobacterial laboratory is under supervision of supranational laboratory in Borstel, Germany. Since 2003 its staff is less exposed to the professional hazard of infection. (24, 25)

Inclusion of computerized information system would improve and make more efficient reporting system that has been fully harmonized with WHO/EuroTB recommendations. Education of HCWs is of an enormous importance, especially in active case-finding in new risk groups (refugees) and prevention of MDR-TB (26,27).

CONCLUSION

The end of the 20th century in Serbia was characterized by complex socio-economic and political situation enriched with a wide spectrum of TB risk factors, formation of vulnerable populations and especially refugees, internally displaced people, prisoners and Roma in slams. Tuberculosis and HIV incidence in the neighboring countries of Balkan region together with local setting characteristics might make Serbia at the beginning of the 21st century a state with potential risk of worsening of TB epidemiological situation.

Acknowledgements

The author would like to thank all those health care workers in Serbia, who have made efforts to obtain TB notification data and especially the staff of pulmonary facilities network, the Research and Epidemiology Department of the Institute of Lung Diseases and Tuberculosis, Clinical Centre of Serbia in Belgrade and National Reference Laboratory.  

Biographical Sketch

Dragica P. Pesut MD, PhD is associate professor at the School of Medicine University of Belgrade, Serbia and Montenegro (formerly Yugoslavia). She is a specialist in lung diseases and tuberculosis with twenty-year clinical experience. Completed postgraduate studies in Medical genetics, doctoral thesis in tuberculosis and lung cancer susceptibility. Current position: Head of Research and Epidemiology Department of the Institute of Lung Diseases and Tuberculosis, Clinical Centre of Serbia, Belgrade, Serbia and Montenegro. Research interest: Tuberculosis epidemiology and interventions.

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