Tuberkuloos Eestis rõhuasetusega ravimresistentsusele: koguhaigestumus, korduvhaigestumus ja suremus

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Tuberkuloos (TB) on nakkushaigus, mille tekitaja on peamiselt õhu kaudu leviv bakter Mycobacterium tuberculosis. TB ja eeskätt multiresistentne TB (MDR-TB) on jätkuvalt Eestis üheks peamiseks probleemiks nii patsientide kui riiklikul tasandil. MDR-TB on TB vorm, mille puhul tavalised TB-vastased ravimid ei ole efektiivsed. MDR-TB ekstreemset vormi nimetatakse eriti resistentseks TB-ks (XDR-TB). M/XDR-TB ravi eeldab madalama efektiivsusega, rohkemate kõrvaltoimetega ja ligikaudu kümme korda kallimate nn. reservrea ravimite kasutamist. Eesti kuulub maailma 27 kõrgeima M/XDR-TB-ga osakaaluga riigi hulka. Pärast 1990. aastate teravaid sotsiaalmajanduslikke muutusi kahekordistus TB-haigestumus Eestis 1998. aastaks. Alates 2000. aastast hakkas kasvama ka HIV-nakatunud TB-haigete osakaal. On teada, et HIV ja TB võimendavad teineteist vastastikku. Nii haigestub kogu nakatumisele järgnenud elu jooksul TB-sse ligikaudu 10% M. tuberculosis’ega nakatunud isikutest. HIV-infektsiooni lisandumisel on aga TB-sse haigestumuse risk tunduvalt kõrgem, ulatudes 5-10%-ni aastas. Tõhustamaks TB-alast tööd ning pidurdamaks kasvavat TB ja MDR-TB epideemiat moodustati 1998 aastal Riiklik Tuberkuloositõrje programm. Seoses kõrge M/XDR-TB- haigestumuse ja kallite reservrea ravimite puudumisega taotles Eesti 2000. aastal ühena viiest esimesest riigist Maailma Terviseorganisatsiooni MDR-TB komitee luba osta kõrgekvaliteedilisi reservrea ravimeid alandatud hindadega. Nii Eestis kui ülemaailmselt on olemas oht, et kahe samaaegselt laieneva ning teineteist õhutava epideemia, M/XDR-TB ja HIV koosmõju tulemusena väljub TB ja M/XDR-TB epideemia kontrolli alt. Pärast rohkem kui 10-aastast TB-programmi tegutsemist on oluline analüüsida TB- ja M/XDR-TB-haigestumust ning suremust ning neid mõjutavaid tegureid, et tagasiside kaudu tõhustada TB-vastast tööd ning võimaldada patsientidele tulemusrikkamat ravi. Alates 1998 aastast, samaaegselt Eesti Tuberkuloositõrje programmi kehtestamisega ning käsikäes üleriigilise M/XDR-TB raviks vajalike reservreapreparaatide olemasoluga ning sisemajanduse koguprodukt suurenemisega, on TB- ja M/XDR-TB-haigestumus Eestis vähenenud. Samas on HIV-infitseeritus viimase kümnendi jooksul tõusnud ning eelduste kohaselt jätkab tõusu veel mõne aja jooksul. Vältimaks kahe epideemia, HIV ja TB, eriti aga HIV ja M/XDR-TB koosmõju on oluline senisest kiiremas tempos alandada TB- ja M/XDR-TB-haigestumust. Alandamaks TB-haigestumust on oluline lühendada nakkusohtlikkuse perioodi pikkust, mis tähendab, et TB-d tuleb haigestunud isikul viivitamatult diagnoosida ja ravida. Me leidsime oma uurimistöös, et esimese MDR-TB komitee soovituste kohaselt ravitud M/XDR-TB-haigete ravi edukus oli vaid 61,1%, kusjuures nakkuse leviku efektiivseks piiramiseks ühiskonnas soovitab Maailma Terviseorganisatsioon 75%-list ravi efektiivsust. Järeldasime, et Eestis oli ravi efektiivsus nii madal peamiselt lubamatult kõrge ravikatkestajate osakaalu (22,3%) tõttu. Samuti tõdesime, et TB- ja M/XDR-TB-haigete kogusuremus oli kõrgem võrreldes kogurahvastiku suremusega. Eriti väljendunud oli suremus põhjustesse, mis on tingitud suitsetamisest, alkoholi liigtarbimisest ja HIV-nakkusest. Kõige haavatavamad olid vanemad ja mitte-Eesti rahvusest inimesed ning madalama haridustasemega isikud. Samas peale edukat ravi oli TB- ja M/XDR-TB-haigete kogusuremus ülalpool loetletud põhjustesse jätkuvalt kõrgem kogurahvastiku omast, kuid polnud seotud ravimresistentsuse esinemisega. Kokkuvõtteks, Eestis on TB ja M/XDR-TB kõrge haigestumus tihedalt seotud HIV-infektsiooniga ning mõjutatud sellistest faktoritest nagu suitsetamine, alkoholi liigtarvitamine, madalam haridustase ja sotsiaalne tõrjutus, mis on omakorda seotud vaesusega. Selleks, et tõsta Eestis M/XDR-TB ravi edukust ja tõhustada TB, MXDR-TB leviku vastast tööd üldisemalt, peavad TB-ga seotud raviteenused olema suunatud kõikide eelmainitud kitsaskohtade vastu.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

Multidrug resistant tuberculosis in Iceland - case series and review of the literature

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenBACKGROUND: Multidrug resistant tuberculosis (MDR-TB) is a growing health problem in the world. Treatment outcomes are poorer, duration longer and costs higher. We report three cases of MDR-TB diagnosed in Iceland in a six year period, 2003-8. CASE DESCRIPTIONS: The first case was a 23-year-old immigrant with a prior history of latent TB infection treated with isoniazid. He was admitted two years later with peritoneal MDR-TB. He was treated for 18 months and improved. The second case was a 23-year-old immigrant diagnosed with pulmonary MDR-TB after having dropped out of treatment in his country of origin. Clinical and microbiological response was achieved and two years of treatment were planned. The third case involved a 27-year-old asymptomatic woman diagnosed with MDR-TB on contact tracing, because of her brother's MDR-TB. 18 months of treatment were planned. CONCLUSIONS: Clustering of cases of MDR-TB in the last six years, accounting for almost 5% of all Icelandic TB cases in the period, suggests that an increase in incidence might be seen in Iceland in coming years. The infection poses a health risk to the patients and the general public as well as a financial burden on the health care system. Emphasis should be put on rapid diagnosis and correct treatment, together with appropriate immigration screening and contact tracing.Inngangur: Fjölónæmir berklar eru vaxandi vandamál í heiminum. Árangur meðferðar er verri, sjúkrahúslegur lengri og kostnaður hærri en við lyfnæma berkla. Hér er lýst þremur tilfellum fjölónæmra berkla sem greinst hafa á Íslandi síðastliðin sex ár, 2003-2008. Sjúkratilfelli: Fyrsta tilfellið var 23 ára innflytjandi frá Asíu sem lokið hafði fyrirbyggjandi meðferð vegna jákvæðs berklaprófs. Tveimur árum síðar lagðist hann inn með berkla í kviðarholi sem reyndust vera fjölónæmir. Hann lauk 18 mánaða meðferð og læknaðist. Annað tilfellið var 23 ára maður sem lagðist inn vegna fjölónæmra lungnaberkla. Hann hafði áður fengið meðferð í heimalandi sínu í A-Evrópu en ekki lokið henni. Hann lá inni í sjö mánuði og náði bata en gert var ráð fyrir tveggja ára meðferð. Þriðja tilfellið var 27 ára einkennalaus kona sem greindist með fjölónæma lungnaberkla við rakningu smits vegna fjölónæmra berkla bróður. Fyrirhuguð var 18 mánaða meðferð. Ályktun: Á síðustu sex árum greindust þrjú tilfelli fjölónæmra berkla hér á landi sem er nálægt 5% allra berklatilfella á tímabilinu. Á 12 árum þar á undan greindist eitt tilfelli og gæti þetta bent til yfirvofandi fjölgunar. Fjölónæmir berklar eru alvarlegir, erfiðir og kostnaðarsamir í meðhöndlun. Mikilvægt er að standa vel að berklavörnum, sérstaklega skimun innflytjenda

Multidrug-resistant Tuberculosis Management in Resource-limited Settings

Managing MDRTB through national programs can yield results similar to those seen in wealthier settings

Barriers to reaching the targets for tuberculosis control: multidrug-resistant tuberculosis

The development and expansion of WHO’s DOTS strategy was successful, with 83% of the world’s population living in countries or parts of countries covered by this strategy by the end of 2004. Treatment success in the 2003 DOTS cohort of 1.7 million patients was 82% on average, close to the 85% target. Treatment success was below average in the African Region (72%), which can be partly attributed to occurrence of HIV co-infection, and in the European Region (75%), partly due to drug resistance. Drug resistance, specifically multidrug resistance and extensive drug resistance, is a serious threat to public health in all countries, especially in the Russian Federation, where the highest rates of multidrug resistance are presently accompanied by a rapid increase in HIV infection. Based on the experience of the first projects approved by the Green Light Committee, the treatment success of patients with multidrug-resistant tuberculosis (MDR-TB) is lower than that of drug-susceptible cases, but nevertheless reaches 70%. The collaborative effort of different organizations, professionals and communities is needed to address the development and spread of multidrug resistance and extensive drug resistance, which combined with the epidemic of HIV infection is one of the barriers to dealing effectively with TB. This effort should be directed towards facilitating the diagnosis and treatment of TB patients, in particular by improving access to drug susceptibility testing and strengthening treatment delivery by rigorous adherence to DOTS as outlined by the Stop TB Partnership