High prevalence of drug-resistant tuberculosis, Republic of Lithuania, 2002.

BACKGROUND: Nations of the former Soviet Union have the world's highest reported levels of resistance to anti-tuberculosis drugs. We conducted the first national survey of anti-tuberculosis drug resistance in the Republic of Lithuania. METHODS: We tested Mycobacterium tuberculosis isolates from all incident culture-positive pulmonary TB patients registered in 2002. New patients were those treated for <1 month with any first-line anti-tuberculosis drug (isoniazid [INH], rifampin [RMP], ethambutol, or streptomycin); previously treated patients were those treated for > or =1 month. RESULTS: Of 1163 isolates, 475 (41%) were resistant to at least one first-line drug, and 263 (23%) were resistant to at least INH and RMP (MDR); this included 76/818 (9.3%) from new patients and 187/345 (54%) from previously treated patients. Of 52 MDR isolates randomly selected for extended testing at an international reference laboratory, 27 (51%, 95%CI 38-66) had resistance to pyrazinamide, 21 (40%, 95%CI 27-55) to kanamycin, and 9 (17%, 95%CI 8-30) to ofloxacin. CONCLUSIONS: The prevalence of MDR-TB in Lithuania is among the world's highest. Among MDR-TB isolates, aminoglycoside and fluoroquinolone resistance were common. To combat drug-resistant TB, Lithuania has implemented the WHO global TB control strategy (DOTS), and is developing an MDR-TB treatment program (DOTS-Plus).     

Drug resistance among smear-positive tuberculosis patients in Ho Chi Minh City, Vietnam.

OBJECTIVES: To assess the pattern of drug resistance among smear-positive tuberculosis (TB) patients in an inner city area in Vietnam. METHODS: A random sample of patients diagnosed by the national TB programme (NTP) were offered HIV testing and submitted sputum for Mycobacterium tuberculosis drug sensitivity testing. RESULTS: Of 1433 isolates from new patients, 360 (25%) were resistant to isoniazid (INH), 57 (4.0%) to rifampicin (RMP), 421 (29%) to streptomycin (SM) and 28 (2.0%) to ethambutol. Among 401 previously treated patients, this was 218 (54%), 109 (27%), 217 (54%) and 26 (7%), respectively. Multidrug resistance (MDR) was observed in 55 (3.8%) new and 102 (25%) previously treated patients. RMP resistance was strongly associated with resistance to INH (OR 46) and INH plus SM (OR 91, P = 0.004). Prevalence of drug resistance tended to decrease with age. Neither any resistance nor MDR was significantly associated with HIV infection. CONCLUSIONS: In this inner city area, levels of drug resistance, in particular of MDR among previously treated patients, are high. This may be related to the use of NTP regimens in the context of highly prevalent combined SM and INH resistance which may favour acquisition of RMP resistance.     

Drug resistance of Mycobacterium tuberculosis in the Sunamganj District of Bangladesh

Spread of drug-resistant tuberculosis (TB) threatens TB-control programmes, and all countries need to monitor the patterns and trends of anti-TB drug resistance. Such data assess the quality of control programmes and help forecast future trends of drug resistance. It will also help to establish guidelines for TB therapy. The aim of the current study was to describe the rate of drug-resistant Mycobacterium tuberculosis in the Sunamganj District of Bangladesh. Bacterial isolates were collected from sputum smear positive (ss+) patients who attended the National TB Programme from November 2003 to December 2004. A total of 95 isolates was tested for susceptibility to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) at the National Reference Laboratory for Mycobacteria at the Norwegian Institute of Public Health (NIPH), Oslo. The total resistance among new cases to any drug was 31%. For SM it was 18%, INH 23%, RMP 2%, EMB 10% and 2% were multidrug-resistant (MDR). The National Tuberculosis Programme (NTP) in Sunamganj is still effective, although the high resistance to INH is alarming. An increased risk of treatment failure has been demonstrated in areas with high levels of INH resistance, and a high proportion of INH resistant cases may develop resistance to RMP during treatment.     

Surveillance of Mycobacterium tuberculosis drug resistance in Hong Kong, 1986-1999, after the implementation of directly observed treatment.

OBJECTIVE: To study changing trends in TB epidemiology with emphasis on drug resistance rates in various age groups from 1986-1999. DESIGN: Laboratory-based data on drug susceptibility testing against streptomycin (SM), isoniazid (NH), rifampicin (RMP) and ethambutol (EMB) had been collected continuously in a centralised TB laboratory in Hong Kong. Epidemiological parameters such as sex, age and drug resistance rates in new and retreatment cases were measured and analysed for longitudinal trends. RESULTS: Of 48 924 non-duplicate isolates from new TB cases, 7045 (14.4%) were resistant to one or more drugs, 5773 (11.8%) were resistant to SM and/or INH while 881 (1.8%) were multidrug-resistant (MDR-TB). Of 3857 isolates from retreatment patients, 1176 (30.5%) were resistant to one or more drugs, 616 (16.0%) were resistant to SM and/or [NH, and 467 (12.1%) were MDR-TB. For isolates from new cases, significant declines were observed in the resistance rates against any drug, SM alone, INH alone, SM+INH and INH+RMP. For retreatment isolates, significant declines were also observed in resistance to any drug and INH+RMP. In both new and retreatment cases, isolates from patients aged over 65 years showed significantly lower drug resistance (any drug and INH+RMP) compared with other age groups (16-34 years and 35-65 years). CONCLUSION: With successful implementation of DOTS over a 14-year period, laboratory-based surveillance data showed significant declines in drug resistance, including MDR-TB. This has occurred amidst demographic changes associated with a generally ageing population as well as highly mobile sectors that are in constant exchange with highly endemic areas.     

Secular trends in susceptibility patterns of Mycobacterium tuberculosis isolates in Kuwait, 1996-2005

OBJECTIVE: To determine the incidence and trends of drug resistance among all Mycobacterium tuberculosis strains isolated during a 10-year period in Kuwait. DESIGN: Drug susceptibility data for M. tuberculosis isolates recovered from all pulmonary and extra-pulmonary tuberculosis (TB) patients in Kuwait from January 1996 to December 2005 were collected and analysed. Patients were divided into Kuwaiti nationals and expatriates. Prior treatment status was not recorded. RESULTS: From 1996 to 2005, 5399 non-repetitive culture-positive TB cases (56% from pulmonary sites and 44% from extra-pulmonary sites) among 917 (17%) Kuwaiti nationals and 4482 (83%) expatriates were identified throughout Kuwait. Overall resistance rates were as follows: any drug 12.5%, isoniazid (INH) 9.1%; rifampicin (RMP) 1.1%, ethambutol (EMB) 2.0%, streptomycin 4.3% and multidrug resistance (MDR) 0.9%. The resistance rates over the 10-year period remained nearly same. However, significant differences were noted in resistance rates for RMP and MDR among pulmonary vs. extra-pulmonary cases and for any drug, INH and EMB among isolates from Kuwaiti vs. expatriate patients. CONCLUSIONS: Moderate and stable single drug resistance (<10%) and low MDR rates (<1%) were found among TB cases in Kuwait. These findings highlight the importance of ongoing control measures to limit the development and spread of drug-resistant M. tuberculosis in Kuwait.     

Resistance of Mycobacterium tuberculosis isolates in different populations in Greece during 1993-2002.

OBJECTIVE: To document the prevalence of resistance of Mycobacterium tuberculosis to isoniazid (INH), rifampicin (RMP) and both combined (multidrug resistance [MDR]) in Greece from 1993 to 2002. DESIGN: We studied a single sputum sample per patient from 4108 patients referred to the Greek National Referral Centre for Mycobacteria. Patients were divided into native Greeks, immigrants and repatriated Greeks originating from the former Soviet Union. Prior treatment status was not recorded. RESULTS: A statistically significant increase in resistance to INH and RMP and MDR was noted comparing the years 1993-1997 to 1998-2002 (P < 0.0001). Resistance to INH and RMP and MDR rose from 5.6% to 7.71%, from 1.57% to 4.49% and from 1.23% to 3.98%, respectively, among native Greeks and from 23.63% to 32.91%, from 6.36% to 15.19% and from 6.36% to 13.92% among repatriated Greeks. Smaller changes were seen among immigrants (from 15.43% to 9.57% for INH, from 5.51% to 6.12% for RMP and from 5.71% to 5.32% for MDR). CONCLUSION: We documented an increase in M. tuberculosis resistance to INH and RMP, and MDR. This was mainly limited to native and repatriated Greeks. Although this is likely the result of immigration and of mismanagement of index cases in Greece, molecular methods are needed to better describe the situation.     

The national tuberculosis drug resistance survey in Cambodia, 2000-2001.

SETTING: Cambodia has a high incidence of tuberculosis (TB). Hospital-based DOTS was predominant throughout the country from 1994 to 2002. OBJECTIVES: To determine the prevalence of resistance to four major anti-tuberculosis drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin (SM), among new cases as a baseline before a new National Tuberculosis Programme strategy with decentralised ambulatory DOTS was widely implemented. DESIGN: A cluster sampling of TB diagnostic centres with probability proportional to the number of new cases in a diagnostic centre in 1999 was used. Intake of cases took place from October 2000 to April 2001. RESULTS: From 734 isolates collected, drug susceptibility test results were obtained for 638 new cases. The prevalence of resistance to any of four drugs was 10.1% (95%CI 7.7-13). Resistance to INH was 6.1% (95%CI 4.3-8.4) and resistance to RMP 0.6% (95%CI 0.2-1.6). No multidrug-resistant (MDR) case was found among the new cases (95%CI 0.0-0.6). Three of 96 previously treated cases had MDR (3.1%, 95%CI 1.0-9.0). CONCLUSION: The first survey indicates that the current prevalence of MDR is low. It is necessary to track resistance trends when restructuring a DOTS-based programme.     

Evaluation of the resazurin assay for the detection of multidrug-resistant Mycobacterium tuberculosis in Madagascar.

SETTING: Multidrug-resistant (MDR) tuberculosis (TB) can jeopardise the success of national TB control programmes. Rapid, simple drug susceptibility tests applicable in developing countries would allow earlier treatment of patients with MDR infections. OBJECTIVE: To test the feasibility and performance of the resazurin microtitre assay (REMA) as an indirect test for detecting isoniazid (INH) and rifampicin (RMP) resistance of Mycobacterium tuberculosis strains in Madagascar. DESIGN: Study comparing the sensitivity and specificity of the REMA plate test with the L?wenstein-Jensen proportion method for determining the resistance of M. tuberculosis strains to INH and RMP. RESULTS: The sensitivity and specificity of the resazurin test were studied in 77 strains and were respectively 95% and 97.3% for the detection of INH resistance, and 95% and 100% for the detection of RMP resistance. The sensitivity and specificity for the identification of MDR strains were respectively 89% and 100%. CONCLUSION: The resazurin test is sensitive and specific enough for the detection of INH- and RMP-resistant strains. It is also easy to use, rapid and inexpensive, making it suitable for developing countries. Its usefulness for national drug resistance surveys should be assessed.     

Characterization of clinical isolates of Mycobacterium tuberculosis resistant to drugs and detection of RpoB mutation in multidrug-resistant tuberculosis in the Philippines.

SETTING: Retrospective study of Mycobacterium tuberculosis isolates at the STD/AIDS Cooperative Central Laboratory, Philippines. OBJECTIVE: To describe patterns of M. tuberculosis resistance against first-line anti-tuberculosis drugs, and to analyze the rpoB gene codon mutation of rifampicin (RMP) resistant isolates and correlate genotypic and phenotypic patterns. DESIGN: One hundred and sixty-four M. tuberculosis complex isolates were retrieved for phenotypic analysis; 89 were resistant to any anti-tuberculosis drug and 50 were RMP-resistant, whereas 48 were multidrug-resistant (MDR). Of these 48, only 33 were available for genotypic analysis of the rpoB gene. RESULTS: Most drug-resistant isolates were phenotypically resistant to isoniazid (INH) (93%), and the probability of an RMP-resistant isolate becoming MDR was 96%. In 33 MDR isolates, 13 types of mutations in nine independent codons were identified; the most frequently mutated codons were S531L (61%) and G510H (15%), which were present in 76% (25/33) of the isolates. S531L was noted in 85.7% of the RMP + INH + SM resistant isolates, while only 80% of the isolates with INH + RMP, EMB + SM resistance showed this mutation. CONCLUSION: The high probability of RMP isolates being MDR suggests that genetic analysis of RMP resistance is useful in detecting MDR-TB. Worldwide accumulation of findings on circulating MDR-TB strains provides indispensable information about the re-emergence of TB.     

Nationwide study of drug resistance among acid-fast bacilli positive pulmonary tuberculosis cases in Lebanon.

OBJECTIVE: To assess the prevalence of drug resistance among smear-positive sputum specimens from pulmonary tuberculosis (TB) cases in Lebanon. DESIGN: Between July 2002 and April 2004, 224 newly diagnosed TB cases and 21 previously treated TB cases were collected nationwide. Mycobacterium tuberculosis isolates were tested against isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB) using the BACTEC-TB system. RESULTS: M. tuberculosis and non-tuberculous mycobacteria (NTM) isolates were recovered from 190 and 15 new cases, respectively, and from 16 and 1 previously treated cases, respectively. Overall drug resistance among new TB vs. previously treated TB cases was 19.5% and 75%, and for single drugs it was INH (12% vs. 63%), RMP (3% vs. 56%), SM (12% vs. 44%) and EMB (3% vs. 44%). The overall rate of multidrug resistance (MDR) was 5.8% (1% vs. 62.5%). The male:female ratio was 1.3:1; most were young adults. CONCLUSION: Relatively moderate single drug resistance and very low MDR rates were found among new TB cases, while among previously treated TB cases very high resistance and MDR resistance rates were detected. Such findings underline the need for ongoing stringent control measures to curb the spread of M. tuberculosis and its deleterious effects.     

Risk factors for drug-resistant tuberculosis among non-US-born persons in New York City.

SETTING: New York City (NYC). OBJECTIVES: To examine the extent to which prior tuberculosis (TB) treatment, length of residence in the United States and other factors are associated with the occurrence of drug resistance among non-US-born persons in NYC. DESIGN: Cases were non-US-born persons diagnosed with TB in NYC from 1998-1999 and from 2001-2002, with an initial Mycobacterium tuberculosis isolate resistant to any first-line anti-tuberculosis drug. Controls were randomly selected from non-US-born persons whose isolates were susceptible to all first-line anti-tuberculosis drugs. RESULTS: Overall, cases with multidrug-resistant (MDR) TB were more likely to have had prior TB treatment; other drug resistance was not associated with prior TB treatment. In a multivariate model, the relationship between MDR-TB and prior treatment remained significant for non-US-born persons regardless of length of time in the U.S. CONCLUSIONS: The findings underscore the utility of monitoring trends in drug resistance among the non-US-born by time in the US and prior treatment to determine where or when drug resistance may be occurring.     

Primary and acquired drug resistance in Polish tuberculosis patients: results of a study of the national drug resistance surveillance programme.

OBJECTIVE: To determine the prevalence and patterns of primary and acquired drug resistance among Mycobacterium tuberculosis isolates recovered from tuberculosis patients in Poland. DESIGN: In a prospective survey, M. tuberculosis strains were collected from 3970 tuberculosis patients (2976 newly diagnosed cases and 994 previously treated patients) bacteriologically confirmed by culture between November 1996 and October 1997. METHODS: Drug susceptibility testing to isoniazid (INH), streptomycin, ethambutol and rifampicin (RMP) was performed on L?wenstein-Jensen medium according to the proportion method and/or using the radiometric Bactec 460 TB system. RESULTS AND CONCLUSION: The male to female ratio was 2.61:1. The patients were aged between 6 and 82 years, with 86% of males and 77% of females aged over 35 years. Primary resistance to any drug was found in 3.6% of new patients; any INH resistance was 2.6%, any RMP resistance was 0.7%, and multidrug resistance (to INH and RMP [MDR]) was 0.6%. In previously treated cases, resistance to any drug was 17.0%, any INH resistance 14.1%, any RMP resistance 7.8%, and MDR 7.0%. Drug-resistant tuberculosis does not present a big problem in Poland; primary drug resistance has been monitored since 1960 with decreasing frequency, and rates remain at the same level as 20 years ago. Studies such as this should be conducted regularly to monitor drug resistance in Poland in order to effectively manage national tuberculosis control efforts.     

Pattern of mycobacterial resistance to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the state of Qatar after the implementation of DOTS and a limited expatriate screening programme.

OBJECTIVE: To determine the resistance pattern of Mycobacterium tuberculosis to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the State of Qatar after the implementation of DOTS and an expatriate screening programme on arrival. METHOD: A state-wide, population-based, retrospective analysis of all cases of pulmonary tuberculosis with positive M. tuberculosis culture reported to the Division of Public Health TB Unit from January 1996 to December 1998. M. tuberculosis sensitivity testing was done by the Bactec method for isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB). The results were interpreted as a daily change of the growth index of test vials (with drug) compared with controls. RESULTS: There were 406 isolates with positive M. tuberculosis culture. Sixty-one (15%) were resistant to one or more of the four anti-tuberculosis drugs, of which 58 (95%) were from newly diagnosed cases (primary) and three (5%) were from previously treated cases (acquired). Primary resistance was as follows: any resistance 15%, INH 12.4%, RMP 2%, SM 5.2%, EMB 0.8% and multidrug resistance (MDR, resistance to INH and RMP at least) was found in 0.8%. Acquired resistance was as follows: any resistance 15%, INH 15%, RMP 5%, SM 5% and MDR 5%. CONCLUSION: The prevalence of resistance to four anti-tuberculosis drugs is strikingly low due to the limited expatriate screening programme (chest radiography) and implementation of DOTS. The four-drug regimen is recommended for the initial phase of therapy until the results of sensitivity testing are known.     

Impact of drug-resistant tuberculosis on the survival of HIV-infected patients.

OBJECTIVE: To determine the effect of drug-resistant tuberculosis (TB) on the survival of human immunodeficiency virus (HIV) infected patients in an area with a high prevalence of TB. DESIGN: Retrospective cohort study. RESULTS: Of 225 HIV-TB patients with a mean age of 35.8 years, 72.4% were male. The median CD4 cell count at TB diagnosis was 44 cells/mm3. Sixty per cent presented with extra-pulmonary TB (EPTB). Sixty-three (28%) patients were infected with Mycobacterium tuberculosis resistant to at least one drug; respectively 16.4%, 9.3%, 5.3% and 12.9% were resistant to isoniazid (INH), rifampicin (RMP), ethambutol and streptomycin, and 14 (6.2%) had multidrug-resistant TB (MDR-TB). During a median follow-up of 11.5 months, 4% died. From Kaplan-Meier analysis, INH resistance, RMP resistance and MDR-TB were associated with shorter survival (log-rank test, P < 0.005). Cox's proportional hazard model showed that MDR-TB (hazard ratio [HR] 11.7; 95% CI 2.1-64.9), not receiving antiretroviral therapy (ART) (HR 7.9; 95% CI 1.5-43.1) and EPTB (HR 5.1; 95% CI 1.9-25.9) were significant risk factors for death. CONCLUSION: MDR-TB and EPTB substantially reduce survival among patients co-infected with HIV and TB. Early detection and optimal treatment of MDR-TB are crucial. ART significantly prolongs survival and should be initiated in HIV-TB co-infected patients.     

Surveillance of Mycobacterium tuberculosis drug resistance in France, 1995-1997. AZAY Mycobacteria Study Group.

OBJECTIVE: To measure the rate of primary and secondary drug resistance of Mycobacterium tuberculosis on an ongoing basis. DESIGN: Data on all culture-positive tuberculosis were collected prospectively from 1995 through 1997 from a microbiological laboratory network of 19 university hospitals throughout France, and submitted quarterly to the National Reference Centre for Surveillance of Mycobacterial Diseases. RESULTS: A total of 2998 patients were included in the study. Among the 2333 (78%) previously untreated patients, 8.6% had isolates resistant to any drug, 4.8% to streptomycin (SM) alone, 1.2% to isoniazid (INH) alone, 1.8% to SM + INH, and 0.3% to INH + rifampicin (RMP) or multidrug resistance (MDR). Foreign birth was independently associated with a higher risk of primary resistance to any drug (odds ratio [OR] 1.5). Among the 268 (9%) previously treated patients, 20.9% had isolates resistant to any drug, 6.3% to SM alone, 3.4% to INH alone, 4.1% to SM + INH, and 3.7% to INH + RMP. Foreign birth (OR = 2.3), and human immunodeficiency virus positive status (OR = 4.4) were independently associated with a higher risk of secondary resistance to any drug. CONCLUSION: During the last 30 years there has been no increase in resistance to any drug among previously untreated patients. As expected, secondary resistance was highly associated with foreign birth. MDR-TB remains a rare event in France.     

Anti-tuberculosis drug resistance in patients with HIV and tuberculosis in South India.

SETTING: Tuberculosis Research Centre clinics at Chennai and Madurai, Tamil Nadu, South India. OBJECTIVES: To investigate the prevalence and pattern of drug resistance among patients with HIV and pulmonary tuberculosis (PTB). DESIGN: Prospective cohort study of HIV-positive patients with PTB between January 2001 and May 2003. Sputum mycobacterial culture and drug susceptibility testing were performed. RESULTS: A total of 204 patients with positive sputum cultures for Mycobacterium tuberculosis were included; 167 of them were new cases, and 37 had a history of previous anti-tuberculosis treatment for > 1 month. Among the former, resistance to isoniazid (INH) was observed in 22 (13%) and MDR-TB in 7 (4.2%). Reported resistance rates in this geographic area among new cases ranged from 15% to 28% for INH and 2.8% to 3.4% for MDR (INH + rifampicin [RMP]). In contrast, among HIV-positive patients with a history of previous treatment, resistance was found to INH in 10 (27%) and to RMP in 7 (18.9%), while MDR-TB was seen in 5 (13.5%) patients. CONCLUSION: Among new TB patients, MDR-TB is marginally higher in HIV-positive patients than in the non-HIV-infected population in this region. Standard treatment guidelines should be followed. Higher rates of drug resistance are observed among previously treated patients.     

Primary drug-resistant tuberculosis in children.

SETTING: The Western Cape Province of South Africa, an area with a high tuberculosis (TB) incidence where initial isoniazid (INH) resistance and multidrug resistance (MDR) among adults was 3.9% and 1.1%, respectively, during 1992-1993. OBJECTIVE: To determine the drug resistance incidence among children as compared to adults, to compare the clinical features of drug-resistant and drug-susceptible TB, and the degree of INH resistance in isoniazid-resistant isolates. METHODS: All Mycobacterium tuberculosis cultures obtained from children (0-13 years) at a regional hospital were prospectively collected from August 1994 to April 1998 and susceptibility testing done on each child's specimens. Degree of INH resistance was determined in available resistant isolates. The children's clinical records were reviewed. RESULTS: Susceptibility results were available in 306/338 children with cultures of M. tuberculosis; 21 isolates (6.9%) were INH-resistant, and seven were MDR. Taking into account study limitations, the incidence of INH resistance was 5.6% and MDR 1% in children aged <5 years. Clinical features were similar in children with drug-susceptible and drug-resistant TB. CONCLUSION: The incidence of drug resistance in childhood tuberculosis in Western Cape is low, and probably reflects the level of primary drug resistance amongst organisms currently circulating in the community.     

Evaluation of drug resistance in pulmonary tuberculosis patients at Sureyyapasa Chest Diseases Hospital, Istanbul, Turkey.

SETTING: Sureyyapasa Chest Diseases and Thoracic Surgery Training Hospital, Istanbul, Turkey. OBJECTIVE: To determine levels of Mycobacterium tuberculosis resistance to first-line drugs in patients with pulmonary tuberculosis (PTB). DESIGN: Between 1 January and 31 December 2005, all hospitalised PTB patients with culture-positive M. tuberculosis specimens and corresponding drug susceptibility tests (DST) for isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol, routinely performed for every tuberculosis (TB) case at our centre, were included. RESULTS: Of a total of 1513 cases, 1277 (84.4%) were new and 236 (15.6%) were previously treated cases. Of the 1513 isolates, 290 (19%) isolates were resistant to at least one of the drugs tested. Resistance among new and previously treated cases was respectively 16.3% (209 of 1277) and 34.3% (81/236). Any SM resistance and any INH resistance were the most common drug resistance in new cases, while any RMP resistance was the most common drug resistance in previously treated cases. Multidrug resistance was detected in 3.2% (n = 41) of new cases and in 13.5% (n = 32) of previously treated cases. CONCLUSION: Planning for TB control requires an assessment of the number and distribution of drug-resistant cases, with laboratories providing accurate and reliable results.     

Molecular genetics of drug-resistant Mycobacterium tuberculosis isolates in Finland, 1995-2004

SETTING: Modern molecular methods help us to understand the transmission and epidemiology of Mycobacterium tuberculosis. OBJECTIVE: To analyse the molecular epidemiology of drug-resistant tuberculosis (TB), and to characterise isoniazid (INH) and rifampicin (RMP) resistance conferring mutations in Finland during 1995-2004. DESIGN: A total of 3959 new M. tuberculosis isolates underwent drug susceptibility testing; all phenotypically resistant isolates were genotyped by IS6110 restriction fragment length polymorphism and spoligotyping if necessary. INH- and/or RMP-resistant isolates were sequenced for their resistance associated genes, katG locus 315 and rpoB, respectively. RESULT: Of the 3959 isolates tested (92.4% of culture-positive cases), 183 (4.6%) were resistant to at least one first-line anti-tuberculosis drug; 14 (0.4%) isolates were multidrug-resistant. Thirty-seven (20.4%) resistant isolates belonged to 17 clusters, and the largest cluster included four isolates. The Beijing family genotype accounted for 8.8% (16 isolates) of all drug-resistant isolates. A Ser315Thr mutation in katG was found in 46.7% (56 isolates) of the INH-resistant isolates and rpoB was mutated in 85.7% (18 isolates) of the isolates resistant to RMP. CONCLUSION: Transmission of drug-resistant TB is rare in Finland, especially between indigenous and immigrant populations. Screening of mutations that confer INH and RMP resistance seems to be feasible if risk factors for multidrug resistance exist.