Extrapulmonary tuberculosis in Poland in the years 1974 – 2010

Introduction: The incidence of tuberculosis in Poland decreased from 128.5 in 100 000 in 1970 to 19.1 in 100 000 in 2010. In many countries, but not in Poland, according to the improvement of the epidemiological situation of tuberculosis (TB), the proportion of the extrapulmonary form of this disease is increasing. The aim of this study was to describe changes in extrapulmonary TB epidemiology in Poland from 1974 to 2010. Material and methods: Retrospective analysis of data from National TB Register on tuberculosis in Poland in the years 1974–2010. The percentage of extrapulmonary tuberculosis among all cases of tuberculosis, the differences in the proportion of extrapulmonary tuberculosis, and differences in various locations of lesions in this form of disease in relation to sex and age groups were assessed. Information was collected from about 626,093 cases of tuberculosis reported to the Register during the period 1972–2010. In 62,251 cases extrapulmonary tuberculosis was the only form of the disease (9.9% of all tuberculosis cases). The study material consisted of 396,344 male and 196,184 female cases; 30,885 subjects were 0–19 years of age, 191,542 were 20–39 years old, 237,256 were 40–59 years old, and 166,410 subjects were ≥ 60 years old. We compared data from the years 1974–1982 with more recent data (2002–2010). The test of proportions for two independent samples was used to assess the significance of differences in proportions. Results: The proportion of extrapulmonary tuberculosis (EPTB) among all TB cases was 11.2% in the years 1974–1982 and only 8.2% in the years 2002–2010. This difference was significant. The proportion of EPTB among all TB cases was higher in women than in men and was higher in people aged 0–19 years than in other age groups. The location of extrapulmonary tuberculosis was different in women and in men. Pleural TB was the most common form of extrapulmonary tuberculosis in both sexes with a predominance of males. Peripheral lymph nodes, bones and joints, urinary, genital, and skin TB were more common in women (these differences were significant). In the youngest age group intrathoracic lymph node TB dominated, and in the older age groups it was pleural TB. In accordance with the increase in age, the proportion of urinary tract, peripheral node, and pericardium TB increased. Central nervous system TB showed no predilection for a particular age group. Conclusions: The proportion of EPTB to all cases of TB is lower in Poland than in other countries. In addition, the proportion of EPTB had significantly decreased from 1974–1982 to 2002–2010. It may be due to difficulties in diagnosis of those forms of TB in Poland. Alternatively it is possible that those cases diagnosed in non-respiratory centres are not reported to the National TB Register.


Introduction
Extrapulmonary tuberculosis certainly arouses less interest than pulmonary tuberculosis, due to its lower infectiousness and thereby smaller epidemiological importance.However, it poses a serious clinical problem because of difficulties in diagnosis and the potential threat to life [1,2].
The Institute of Tuberculosis and Lung Diseases in Warsaw constantly monitors incidence of tuberculosis in Poland in relation to age, sex, infectiousness and location of lesions.Relevant data are reported by Regional Outpatients Clinics of Tuberculosis and Lung Diseases and by Regional Administration Units for Epidemics and Hygiene Control.
In 2010 extrapulmonary TB was reported to the register of patients with tuberculosis only in 517 cases, which constituted 6.9% of all reports of tuberculosis [3].Data from other countries show considerably higher contributions of extrapulmonary location, i.e. 15-45 % of all TB cases [4][5][6].
The reasons for this may be various.The occurrence of extrapulmonary TB is to certain degree genetically determined and is connected with the ethnic origin of patients.It is known that extrapulmonary TB often occurs in African Americans and in Asians [4][5][6][7][8].In some developed countries a large proportion of extrapulmonary TB depends on its occurrence among immigrants [4][5][6][7].It is also known that extrapulmonary changes more often occur in immunosuppressed patients, among others during epidemics of HIV infection, particularly in periods prior to the introduction of antiretroviral treatment [9][10][11][12][13][14].In this respect Poland is a unique country due to its relatively small contribution of emigrants and HIV infection to the incidence of tuberculosis.
In the majority of epidemiological data from numerous countries it has been shown that over the years, along with the improvement in the epidemiological situation of tuberculosis, the proportion of extrapulmonary forms of the disease is growing, even in the periods when it might not have been caused by an epidemic of HIV infections [4,[11][12][13][14][15].
The incidence of tuberculosis has considerably decreased in Poland during recent years.The incidence rate decreased from 128.5 in 100,000 persons in 1970 to 19.1 in 100,000 persons in 2010.
The aim of the present study was to assess whether during the decrease in the prevalence of TB in Poland, the proportion of extrapulmonary TB increased.Another issue was whether, in Poland, the type of location of this form of TB and its occurrence depend on sex and age.

Material and methods
The study material was data concerning tuberculosis in Poland in the years 1974-2010 collected by the National TB Register, kept by the Institute of Tuberculosis and Lung Diseases.
All cases in which changes in the lung occurred were registered as pulmonary tuberculosis, irrespective of whether extrapulmonary changes were also present.Until 2001 tuberculosis of intrathoracic lymph nodes and pleura were also registered as pulmonary TB.According to the guidelines of the World Health Organization (WHO), since 2002 these two forms of TB have been distinguished as extrapulmonary TB.
Therefore, in the analysis of the material up to 2001, data were corrected and the cases of pleural TB were transferred to the group of extrapulmonary TB.Such corrections could not have been made for tuberculosis of intrathoracic lymph nodes since this group was not distinguished in the material of the years 1974-2001.
Finally, the study material consisted of 626,093 TB cases reported to the Register in the study period.In 62,251 patients (9.9%) extrapulmonary TB was diagnosed as the only form of the disease.
In the study material 30,885 persons were 0-19 years of age, 191,542 were 20-39 years of age, 237,256 were 40-59 years of age and 166,410 persons were over 60.
The material consisted of 396,344 male and 196,184 female cases.In the documents of 33,565 cases observed in the years 1988 and 1996 there was no information on the patients' sex.
An analysis of prevalence of individual forms of extrapulmonary TB depending on age and sex was carried out.
In order to evaluate the frequency of occurrence (or diagnosis, or reporting) of extrapulmonary TB during the period of observation, recent data (2002-2010) were compared to data registered in the years 1974-1982.These periods were chosen for two reasons.First, there was a distinctive difference in incidence of TB between them (71.2 per 100,000 persons in 1975 and 19.7 per 100,000 persons in 2010).Secondly, according to the guidelines of the WHO, since 2002 extrapulmonary changes have been qualified more precisely.
The significance was examined using the test of proportions for two independent samples.

The results of the study
Extrapulmonary TB was noted significantly more often in persons 0-19 years of age than in the remaining age groups (Table 1).
Extrapulmonary TB most frequently concerned the pleura, peripheral lymph nodes, bones and urinary system.TB seldom occurred in the remaining locations (Table 2).
All forms of TB in the study period in Poland occurred more than twice more frequently in men than in women.Extrapulmonary TB was also observed in a larger number of men than women but this difference was slight.It was caused by the fact that extrapulmonary TB as the main location of the disease occurred significantly more often in women with tuberculosis than in men with tuberculosis (Table 3).
Women with TB not only demonstrated extrapulmonary TB significantly more often but also its location was different than in men.The most frequent form of TB in both sexes was pleural TB, which more often occurred in men; in women peripheral lymph node TB occurred significantly more often as well as bone, genital system and skin tuberculosis (Table 4, 5).
The comparison of the prevalence of extrapulmonary TB in the two chosen time intervals showed that it was significantly less often diagnosed in the years 2002-2010 than in the years 1974-1982.It did not depend on precision of diagnosis since the proportion of cases confirmed bacteriologically, although low, was in recent years close to that of the past (Table 6).
In the two study periods extrapulmonary TB was diagnosed more frequently in the group 0-19 years of age than in the remaining groups; proportions of patients with extrapulmonary TB in all TB patients differed significantly in the study periods in all age groups (Table 7).
Although recently pleural TB has been diagnosed more rarely, it has been still the most commonly diagnosed location of extrapulmonary TB.Peripheral lymph nodes and central nervous system TB have been more often diagnosed recently, whereas bone, urinary system TB and tuberculosis of the genitals have been diagnosed more seldom.Differences in the proportion of the mentioned forms of tuberculosis in all cases of extrapulmonary TB in the study periods were statistically significant (Table 8).
In order to define reasons for the higher prevalence of extrapulmonary TB in younger age groups, the analysis of the occurrence of separate locations of TB depending on age was carried out.This analysis was restricted to the period 2002-2010 due to the precisely defined extrapulmonary changes during this time (Table 9).
In the youngest age group the location within the intrathoracic lymph nodes predominated.At the age of 20-39 the most commmon were changes in the pleura.Along with the increased age there was a rise in the number of TB in the urinary system, peripheral nodes and pericardium.The occurrence of changes in the central nervous system did not show a predilection for any specific age group.

Discussion
In Poland extrapulmonary TB occurred more frequently in younger age groups.It concerned the whole material and all study groups.
Similar observations were made by other authors [6,7,[14][15][16][17].The more frequent occurrence of extrapulmonary TB in younger age groups in the Polish material was caused first of all by involvement of lymph nodes of the mediastinum, whereas pleural TB predominated in the group of young adults.Taking into consideration that both these forms of TB may be a symptom of primary tuberculosis, it may be the evidence of infection with Myobacterium tuberculosis in Poland late in life.
The most frequent form of extrapulmonary TB in Poland was tuberculosis of the pleura.This was in accordance with observations from Estonia [17] and of men in Hong Kong [18]; however, in all remaining countries the most frequently observed form was TB of the peripheral lymph nodes [5][6][7][8].The relatively rare occurrence of TB of the central nervous system, which does not show a predilection for a specific age group, points to the good effects of obligatory BCG vaccination of all newborns in Poland in the prevention of this disease.
Apart from the comparatively low prevalence of extrapulmonary TB in Poland, it was shown, similarly as in other publications, that women are more prone to this form of the disease than men [6,7,12,15,18,20].It was also shown that in Poland location of extrapulmonary TB is different in women than in men.Although in Poland the pleura is the most frequent place of location in both sexes, tuberculosis of peripheral lymph nodes occurred in women twice as frequently as in men.The majority of publications emphasize a predilection for involvement of the peripheral lymph nodes in Asians.Only two publications show a prevalence of this form of TB in women [15,19].
The comparison of the proportion of extrapulmonary TB cases to all TB cases during the two chosen periods has shown that in Poland, along with the decrease of TB incidence, the proportion of extrapulmonary TB also decreased.The only study in which, along with the decrease in the frequency of TB cases, a parallel decrease in the frequency of extrapulmonary TB was observed, comes from Estonia [17].In all other reports it was shown that according to the improvement of the epidemiological situation of TB, the proportional prevalence of the extrapulmonary form does not decrease but, on the contrary, it increases [3,[11][12][13][14].
There may be many reasons for such discrepancies.Some publications come from the countries where a large proportion of patients with tuberculosis constitute immigrants from regions of higher prevalence of extrapulmonary TB [4][5][6][7][8].In other reports the growth in the number of extrapulmonary TB cases is connected with an epidemic of HIV infection [9,10].It is known that a tendency towards extrapulmonary changes and even to their specific location is of genetic origin [21,22].Therefore, it is possible that a typical feature of the Polish population is a low tendency towards extrapulmonary changes.On the other hand, according to publications from Germany and the Netherlands [2,7], the estimated prevalence of these forms of TB in our region amounts to 15% of all TB cases, so it is distinctly higher than the number currently registered in Poland.However, it should be remembered that many TB patients in Western Europe are born in these countries as descendants of immigrants, who belong to ethnic groups in which extrapulmonary TB occurs more frequently.

Conclusions
To sum up, it should be noted that we have not managed to define why extrapulmonary TB is relatively seldom diagnosed in Poland, and why the frequency of diagnosis thereof decreases.It may depend on lower incidence of this form of the disease, which is possible in the country where TB concentrates in older age groups, with the predominance of men (incidence of men at the age of 50-54 is four times higher than that of their peers -women), and where HIV infection and immigration do not significantly influence the epidemiology of tuberculosis [3].It may depend on difficulties in diagnosing of these forms of tuberculosis.Significant decrease of TB incidence in Poland may cause a diminished experience in diagnosis extrapulmonary TB.A more optimistic version may assume that these cases are diagnosed by physicians of another speciality than pulmonary but that they are not reported to the Register.It is difficult to assess how many cases is reported to the Register, and according to the WHO, different deficiencies in this field are common [23].

Table 3 . Incidence of extrapulmonary tuberculosis (EPTB) in Poland in the years 1974-2010 according to the sex of patients
p < 0,01; *number of cases is lower than in Table1becuse no information about the sex of the patients in the years 1988 and 1996 was available

Table 9 . Localization of extrapulmonary tuberculosis (EPTB) according to age of patients in Poland in the years 2002-2010 Localization of EPTB Age (years) Total 0-19 20-39 40-59 > 60 No of patients (%)Table 7 . Comparison of the frequency of extrapulmonary tuberculosis (EPTB) in Poland according to age in the years 1974- -1982 and 2002-2010 Age groups Years 1974-1982 Years 2002-2010 P-value No of TB No of EPTB % of EPTB Standard deviation No of TB No of EPTB % of EPTB Standard deviation
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