This is the first study of risk factors for pulmonary TB in Croatia. The social determinants of tuberculosis in the study population are related to unemployment, the lowest level of education and poor household equipment, and to some extent malnutrition. Poverty undoubtedly contributes to the incidence of tuberculosis through increased progression from infection to disease due to poor diet or stress, and greater difficulties in using health services .
Former and current smoking, as well as contact with tuberculosis, was significant among the behavioural factors. This merits attention because smoking is a highly prevalent hazardous habit, both in our population and in the world, and is also socially accepted. According to recently published data from the Croatian national follow-up cohort study, CroHort, 21% of respondents were smokers in 2008 .
Passive exposure to tobacco smoke in non-smokers in a bivariate analysis was also associated with tuberculosis. Those exposed to passive smoke inhaled similar toxic substances as active smokers, although in different concentrations. Passive smoking has a smaller effect on the morbidity of tuberculosis at the individual level, but it can have a much greater impact at the population level, because anyone who breathes the same air can be exposed, whether a smoker or non-smoker . This relationship is important because smoking is one of the habits on which influence may be exerted. In Croatia, this association may be emphasized as an integral part of the prevention of cancer and cardiovascular diseases that are more prevalent than tuberculosis. Anti-smoking campaigns, legislation, restrictions on smoking in public places and institutions, and high tobacco prices are likely to contribute to a decrease in the prevalence of smoking.
Various biological factors (chronic renal failure / dialysis, transplantation, HIV infection, immunosuppressive therapy) that were proven in other studies [23–26] were not confirmed here, probably due to the fact that these conditions are not highly prevalent in this population.
However, it was found that diabetes and malignant diseases were associated with the incidence of tuberculosis. All of them suppress the cellular immune function, a key defence mechanism against M. tuberculosis[27–29].
The association of diabetes and TB has been observed in several studies, regardless of the design and the geographic area in which the studies were conducted, and the incidence of tuberculosis. A recent systematic review showed that diabetes carried a relative risk of 3.11 in the cohort studies, while in the case–control studies the odds ratios were heterogeneous, ranging from 1.16 to 7.83 . This study shows that the likelihood of developing tuberculosis in patients with diabetes is 2.4 times higher than in the general population. Therefore, the national tuberculosis programme can benefit from the active search for and treatment of latent tuberculosis infection (LTBI) in diabetics, and from the appropriate diagnosis and treatment of diabetes .
The significant occurrence of TB in patients with malignant diseases is explained by a weakened immune system due to the primary disease and the influence of anticancer therapy [28, 31]. Similar symptoms and overlapping clinical features, association with previous fibro calcified lesions in the lungs, and unclear LTBI testing results make the diagnosis of TB and LTBI in cancer patients demanding. On the other hand, the increased risk of TB in patients with a malignant disease makes these patients a target group for LTBI treatment, particularly because the number of new cases of malignant disease is increasing in Croatia [30, 32]. High risk was observed in a low BMI, which was also found elsewhere [29, 33]. It was found that the incidence of TB decreased with an increase in the BMI. This trend was almost linear on a logarithmic scale, regardless of gender and age [7, 34]. It was calculated in one study that the relative risk of undernourished people developing TB was 6–10 . This study also shows that a low and, to a lesser extent, a normal BMI, carried a higher risk than a high BMI. Although the number of undernourished subjects in both study groups was not high, the frequency of overweight participants was almost three times higher among those in the control group than in the cases. Malnutrition is an important cause of acquired immune dysfunction that can be managed by appropriate interventions .
Unlike most other high income, low-incidence European countries, HIV-coinfection and TB among drug addicts and prisoners do not seem to play an important role in TB epidemiology in Croatia [11, 16, 17].
These results might be more significant today in terms of unemployment, diabetes and malignant diseases since their burden in Croatia is increasing, while smoking, which is decreasing, might be less relevant as a TB risk factor [21, 32, 35].
The results of this study should be interpreted in the light of some limitations. Data on height and weight were taken from the participants’ recall, and it is possible that the BMI data were not entirely accurate. The studies that have explored uncommon risk factors had a larger sample size, mostly based on data from a TB register, or a dialysis or transplantation register and the like. Therefore, it is possible that the sample size, when it comes to factors that are present in a population of less than 10%, is insufficient to detect association.
Unlike some studies, the control group sample was selected from the general population rather than from other hospital patients, friends or relatives of TB patients, thereby enabling the analysis of more potential risk factors. Control sampling allows us to believe that the control group represents the total Croatian population. Criteria for the inclusion of patients were strict and allowed only culture-confirmed pulmonary cases. The survey was conducted by skilled physicians who perform surveys and field work on a daily basis.