Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs. To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites. Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB). The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance.
Comment In: Eur Respir J. 2008 Nov;32(5):1413-518978145
Ivanovo Oblast, Russian Federation, 300 km north-east of Moscow, where a pilot DOTS TB control programme was implemented in October 1995.
To determine the frequency of TB recurrence among MDR (multidrug-resistant) patients who achieved treatment 'success' on standard short-course chemotherapy.
All patients with MDR tuberculosis, defined as resistance to at least isoniazid and rifampicin, who were declared 'cured' or 'treatment completed', were identified using the district register and traced whenever possible. Eligible patients underwent medical examination and, if necessary, chest radiography, sputum smear examination, culture and susceptibility testing. If the patient had died, the relatives were interviewed to try to determine the reasons for death.
Of 18 patients eligible for analysis, five (27.8%) were documented to have recurrence (two of seven patients resistant to HRSE, one of five patients resistant to HRS and two of six patients resistant to HR). Patients receiving the Category I regimen were more likely to relapse than those receiving the Category II regimen (40% vs. 12.5%). The median time to relapse was 8 months; 2.46 recurrences were observed in 100 person-months (3.17 in category I and 1.3 in Category II patients).
The frequency of TB recurrence among MDR-TB patients declared 'cured' after short-course chemotherapy is high. Improvements in treatment success, after removal of programme-related pitfalls in the treatment delivery process, must incorporate methods for early detection of MDR, along with adequate treatment regimens including second-line drugs. Culture-based bacteriological confirmation at the end of treatment is recommended.
Global trends in resistance to antituberculosis drugs. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance.
BACKGROUND: Data on global trends in resistance to antituberculosis drugs are lacking. METHODS: We expanded the survey conducted by the World Health Organization and the International Union against Tuberculosis and Lung Disease to assess trends in resistance to antituberculosis drugs in countries on six continents. We obtained data using standard protocols from ongoing surveillance or from surveys of representative samples of all patients with tuberculosis. The standard sampling techniques distinguished between new and previously treated patients, and laboratory performance was checked by means of an international program of quality assurance. RESULTS: Between 1996 and 1999, patients in 58 geographic sites were surveyed; 28 sites provided data for at least two years. For patients with newly diagnosed tuberculosis, the frequency of resistance to at least one antituberculosis drug ranged from 1.7 percent in Uruguay to 36.9 percent in Estonia (median, 10.7 percent). The prevalence increased in Estonia, from 28.2 percent in 1994 to 36.9 percent in 1998 (P=0.01), and in Denmark, from 9.9 percent in 1995 to 13.1 percent in 1998 (P=0.04). The median prevalence of multidrug resistance among new cases of tuberculosis was only 1.0 percent, but the prevalence was much higherin Estonia (14.1 percent), Henan Province in China (10.8 percent), Latvia (9.0 percent), the Russian oblasts of Ivanovo (9.0 percent) and Tomsk (6.5 percent), Iran (5.0 percent), and Zhejiang Province in China (4.5 percent). There were significant decreases in multidrug resistance in France and the United States. In Estonia, the prevalence in all cases increased from 11.7 percent in 1994 to 18.1 percent in 1998 (P
Deaths due to tuberculosis have decreased uniformly in all countries in Western Europe, and most have occurred among those aged > or = 65 years. In recent years, tuberculosis case notifications have continued to decline in Belgium, Finland, France, Germany, and Spain, and have levelled off in Sweden and the United Kingdom; increases have, however, been recorded in Austria, Denmark, Ireland, Italy, Netherlands, Norway, and Switzerland. In Denmark, Netherlands, Norway, Sweden, and Switzerland an increasing number of cases of tuberculosis among foreign-born residents has resulted in a change from the expected downward trend. Human immunodeficiency virus (HIV) infection appears to contribute only marginally to the overall tuberculosis morbidity; however, it appears to be important in Paris and its surrounding areas, and tuberculosis is very common among HIV-infected persons in Italy and Spain. Despite these recent changes in the incidence of tuberculosis, there is currently no evidence of its increased transmission among the youngest age groups of the indigenous populations. Properly designed disease surveillance systems are critical for monitoring the tuberculosis trends so that each country can identify its own high-risk groups and target interventions to prevent, diagnose, and treat the disease. Tuberculosis remains a global disease and because of increasing human migrations, its elimination in Western Europe cannot be envisaged without concomitant improvements in its control in high-incidence, resource-poor countries.
The aim of this paper is to assess trends in tuberculosis morbidity and mortality in the countries of Eastern Europe and the former USSR. Data on morbidity and mortality were obtained from reports of the Ministries of Health, a 1992 WHO questionnaire, national tuberculosis associations, and other sources. The quality of surveillance of tuberculosis cases differs widely between countries. Ranging from 19 to 80 per 100,000 population in 1990-1992, tuberculosis notification rates of most Eastern European and former USSR countries are higher than those of Western European countries. The lowest tuberculosis notification rate is reported in the Czech Republic, while the highest are reported in Romania and Kazakhstan. While in Albania, Croatia and Slovenia notification rates have continued to decline, in the remaining countries of Eastern Europe the declining trend has recently stopped. Nevertheless, countries such as the Czech Republic, Hungary, Poland and the Slovak Republic have experienced a distinct rate decrease when the 3-year average rate around 1985 is compared to that around 1990, despite the very recent levelling-off or increase. In Romania, the previous decline in notification rate ended in 1985 and in the period 1986-1992 an average 5.4% annual increase was observed. In this country, two-thirds of all cases still occur among young adults. Among the Baltic countries of the former USSR, the declining trend continues in Estonia, whereas in Latvia and Lithuania notification rates decreased less markedly from 1985 to 1990 than in the first half of the 1980s. Among the other European countries of the former USSR, Russia and Ukraine had a slow decline in the first half of the 1980s and a more pronounced one from 1985 to 1990. During the latter period of time, in Belarus and Moldova the decrease has been steeper. In the Caucasian countries of the former USSR, where underreporting and low case-finding are recognized, case rates have stabilized in Armenia, while in Azerbaijan and Georgia there was a decrease from 1985 to 1990. Among the Asian countries of the former USSR, Kazakhastan and Tajikistan reported a lower decline in case rates from 1985 to 1990 than from 1980 to 1985. Kyrgyzstan, Turkmenistan, and Uzbekistan reported increases in notification rates from 1985 to 1990: in Turkmenistan an average 5.5% annual increase in rate was observed between 1987 and 1991. Tuberculosis mortality is steadily increasing in Romania, Armenia, Kyrgyzstan, Latvia, Lithuania, Moldova, and Turkmenistan, while no decline is seen in most of the other countries of Eastern Europe and the former USSR.(ABSTRACT TRUNCATED AT 400 WORDS)