Supervisor: professor Alan Altraja (TÜ kopsukliinik) ja Mati Rahu (TAI)
Opponent: professor Peter F.O. Davies, MD, PhD (Liverpool Heart and Chest Hospital, Suurbritannia)
Tuberculosis (TB) is an infectious disease caused by airborne bacillus Mucobacterium tuberculosis. TB and particularly the multidrug-resistant TB (MDR-TB) continues to be a major problem in Estonia, both at the level of individual patients, as well as at the national level. MDR-TB is a form of TB, where the usual anti-TB drugs are not effective. The extreme form of MDR-TB has been labeled extensively drug-resistant TB (XDR-TB). For treatment of M/XDR-TB, the use of so called second-line anti-TB drugs is necessary. Second-line anti-TB drugs are less effective than usual ant-TB drugs; they have more side effects and are approximately ten times more expensive. Due to the high proportion of M/XDR-TB among the TB cases, Estonia belongs to the group of 27 high-M/XDR-TB-burden countries in the world. By 1998, after the sharp socio-economic changes in 1990's, the TB notification rate almost doubled in Estonia. Furthermore, from 2000, the number of HIV-infected cases is increasing. This is particularly alarming because TB and HIV are known to fuel each other. Following an infection with TB bacilli, there is approximately 10% lifetime risk of developing TB disease among non-HIV-infected persons, whereas the risk of developing TB among HIV-positive persons is up to 510% annually. In 1998, the National TB Programme was established in Estonia to manage the rising TB and M/XDR-TB epidemic. In 2000, due to the high proportion of M/XDR-TB cases and the lack of expensive second-line anti-TB drugs, the National TB Programme applied to the Green Light Committee of the Stop TB Partnership for concessionally-priced high-quality drugs for treatment of M/XDR-TB. There is a concern that as the result of two colliding epidemics of TB and M/XDR-TB and HIV, the TB and M/XDR-TB epidemic will go out of control in Estonia, as well as internationally. After more than 10 years of implementation of the National TB Programme, it is important to evaluate the trend of TB and M/XDR-TB notification rate, disease recurrence and mortality, as well as the factors influencing them. This is necessary to further improve the management of TB and to provide better care to the patients. We found that from 1998, the TB and M/XDR-TB incidence has decreased in Estonia and that the decrease was in a close time relation to the establishment of the National TB Programme, growth of the wealth of the population and assuring the countrywide availability of the second-line anti-TB drugs. Meanwhile, the rising proportion of TB and HIV co-infected persons has increased during the last decade and this increase is anticipated to continue in the future. To avoid colliding TB and HIV and even worse, M/XDR-TB and HIV co-epidemic, it is crucial to decrease the TB incidence faster than it is currently done. Furthermore, to decrease TB incidence the time of infectiousness has to be decreased, which means that the patients have to be diagnosed earlier and treated promptly. We found that in Estonia, the treatment success of M/XDR-TB patients was 61.1%, which is lower than the World Health Organization recommended 75%. We concluded that the main reason for the low treatment success and therefore continuous spread of M/XDR-TB infection was an unacceptably high proportion (22.3%) of patients defaulting treatment. Furthermore, we found that the all-cause mortality among TB and M/XDR-TB patients was higher than that in the overall population. Particularly pronounced were deaths due to smoking and alcohol abuse, as well as due to HIV. The most vulnerable were foreign-born persons and persons with lower education. After the TB and M/XDR-TB patients had successfully completed the treatment, the mortality remains still higher In conclusion, in Estonia, the TB and M/XDR-TB epidemic is closely connected to the HIV epidemic and interlinked with the higher mortality due to the life-style factors, such as tobacco smoking and alcohol abuse, as well as social aspects, such as lower educational level, social marginalization and poverty. To improve the management of TB and M/XDR-TB in general and the treatment outcome of M/XDR-TB in particular, the TB-related service package should cover all the mentioned challenges.