BioMed Central Page 1 of 9 (page number not for citation purposes) BMC Public Health Open Access Research article Risk factors for poor tuberculosis treatment outcome in Finland: a cohort study Tuula Vasankari*1,2, Pekka Holmstr��m1, Jukka Ollgren1, Kari Liippo2, Maarit Kokki1 and Petri Ruutu1 Address: 1Department of Infectious Disease Epidemiology, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland and 2Department of Respiratory Medicine, Turku University Hospital, Paimio Hospital, Alvar Aallon tie 275, 21540 Preitil��, Finland Email: Tuula Vasankari* - tuula.vasankari@utu.fi Pekka Holmstr��m - Pekka.Holmstrom@welho.com Jukka Ollgren - jukka.ollgren@ktl.fi Kari Liippo - Kari.Liippo@tyks.fi Maarit Kokki - Maarit.KOKKI@ec.europa.eu Petri Ruutu - petri.ruutu@ktl.fi * Corresponding author Abstract Background: We investigated the patient- and treatment-system dependent factors affecting treatment outcome in a two-year cohort of all treated culture-verified pulmonary tuberculosis (TB) cases to establish a basis for improving outcomes. Methods: Medical records of all cases in 1995 ��� 1996 were abstracted to assess outcome of treatment. Outcome was divided into three groups: favourable, death and other unfavourable. Predictors of unfavourable outcome were assessed in univariate and multivariate analysis. Results: Among 629 cases a favourable outcome was achieved in 441 (70.1%), 17.2% (108) died and other unfavourable outcome took place in 12.7% (80). Significant independent risk factors for death were male sex, high age, non-HIV -related immunosuppression and any other than a pulmonary specialty being responsible for stopping treatment. History of previous tuberculosis was inversely associated with the risk of death. For other unfavourable treatment outcomes, significant risk factors were pause(s) in treatment, treatment with INH+RIF+EMB/SM, and internal medicine specialty being responsible at the end of the treatment. Conclusion: We observed a significant association with unfavourable outcome for the specialty responsible for treatment being other than pulmonary, but not for the volume of cases, which has implications for system arrangements. Poor outcomes associated with immunosuppression and advanced age, with frequent comorbidity, stress a low threshold of suspicion, availability of rapid diagnostics, and early empiric treatment as probable approaches in attempting to improve treatment outcomes in countries with very low incidence of TB. Background Early diagnosis of tuberculosis and effective treatment are the key elements in reduction of transmission of infection and finally achieving elimination of TB [1]. World Health Organization (WHO) has set the international target value for a favourable treatment outcome at 85% [2]. Treatment outcome monitoring is a core part of surveil- lance necessary to succeed in tuberculosis elimination [3]. The WHO has published a recommendations for assessing Published: 14 October 2007 BMC Public Health 2007, 7:291 doi:10.1186/1471-2458-7-291 Received: 18 December 2006 Accepted: 14 October 2007 This article is available from: http://www.biomedcentral.com/1471-2458/7/291 �� 2007 Vasankari et al. licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

BMC Public Health 2007, 7:291 http://www.biomedcentral.com/1471-2458/7/291 Page 2 of 9 (page number not for citation purposes) the outcome of tuberculosis treatment in 1990's [4], revised recently [5,6]. In many industrialized countries with good treatment facilities and a secured supply of drugs free of charge for patients, treatment results have not reached the targets set by WHO [7-18]. The main reason for this is the high rate of death as an unfavourable outcome, frequently with much comorbidity from other diseases. Incomplete treat- ment carries a risk of development of resistance, increased disease transmission, and increased morbidity and mor- tality [19]. In our earlier report from Finland, a favourable outcome was reached in only 65%, death being the out- come in as much as 19%, and defaulting, transferring out or physician's decision to stop treatment early being rea- sons for other unfavourable outcomes in 12% of the cases [20]. The specific reasons for unsuccessful outcomes are impor- tant in order to improve treatment systems. In a recent outcome analysis from Norway, where the large majority of TB cases are in immigrants, only high age and isoniazid (INH) resistance were significant risk factors for non-suc- cessful outcome [21]. In earlier studies, high age, alcohol- ism, HIV-infection, male sex and immigration have been associated with unfavourable outcomes [7,12,22]. In low incidence countries, many of the clinical units treating tuberculosis patients have small and decreasing numbers of patients. This necessitates an assessment of the need to concentrate patients in fewer units to retain the level of experience sufficient for successful outcomes. There is varying evidence from assessments made in other areas of complex treatments, such as leukaemia, AIDS, demanding surgery and myocardial infarction, that the volume of treatments has an effect on the outcome [23,24]. It is possible that treatment organisation and implementation in bigger hospitals are more effective and up to date [25]. However, there is little data available on whether the volume of tuberculosis patients treated would associate with favourable outcomes. We assessed the patient and treatment system dependent factors affecting treatment outcome in a national, popula- tion-based two-year cohort of all culture-verified pulmo- nary tuberculosis cases in Finland, with a TB incidence of 12,5 per 100 000 per year during the study period, to establish a basis for improving the proportion of favoura- ble outcomes. Methods Study cohort, case definitions and data collection The method of identifying all culture-confirmed tubercu- losis cases in Finland, with the first positive culture sam- ple date between January 1st, 1995, to December 31st, 1996 (N = 1059), present in either the National Infectious Disease Register (NIDR) or through a separate query to all microbiological laboratories has been described else- where [26]. A case of tuberculosis was defined for the study as pulmo- nary using the case definition of NIDR, i.e. as a culture finding for M. tuberculosis in sputum or bronchoalveolar lavage (BAL), or as a culture finding for M. tuberculosis from another sample type in a case with sputum smear positive for acid fast bacilli. With this definition, 737 (70 % of the whole cohort) cases with pulmonary tuberculosis were identified. Species identification for Mycobacterium tuberculosis was carried out in every case. There were alto- gether 660 isolations of mycobacteria other than M. tuberculosis during the study period. Only culture posi- tive cases were taken into the study in order to be able to study only the fully confirmed cases. Out of the 737 pulmonary tuberculosis cases, complete medical records were available from 711 (96%). Among these 711 cases, twenty-two (3.1%) had previously been treated for tuberculosis after the year 1970, and were excluded from the outcome analysis as re-treatment cases. Of the 689 cases, 33 were still on treatment at 12 months, and were also excluded from the analysis. Of the remain- ing 656 cases, 27 were not treated, among them 19 (70.4%) were men and 8 (29.6%) women. Of this group, with a median age of 82.0 years, 24 died before treatment and 3 were left untreated. Those without treatment were excluded from the main analysis of 629 actually treated cases (Figure 1). Definitions of treatment Tuberculosis treatment was initiated in and supervised by the pulmonary departments of public hospitals in the great majority of cases. Chemotherapy actually given to each patient, according to record review, was grouped into six categories (Table 1). Definitions for the grouping were based on the national recommendations in Finland fol- lowing the recommendations by WHO, ATS and BTS [27- 32]. We have previously described the treatment grouping in detail [20]. Duration of treatment was assessed only for standard treatment groups (A ��� D). In the combination of isoniazid, rifampicin and pyrazinamide (HRZ) with or without an extra drug, the recommended duration of treatment was defined as 167 ��� 213 days. For the combi- nation isoniazid, rifampicin and ethambutol (HRE) or isoniazid, rifampicin and streptomycin (HRS) �� extra drug, the recommended duration of treatment was defined as 243 ��� 304 days. Pauses of chemotherapy were recorded only when lasting at least one week, and calcu- lated only for standard treatments.