Sputum Smear-positive Tuberculosis Cases Research Articles

The burden of drug resistance tuberculosis in Ghana; results of the First National Survey

Resistance to Tuberculosis drugs has become a major threat to the control of tuberculosis (TB) globally. We conducted the first nation-wide drug resistance survey to investigate the level and pattern of resistance to first-line TB drugs among newly and previously treated sputum smear-positive TB cases. We also evaluated associations between potential risk factors and TB drug resistance. Using the World Health Organization (WHO) guidelines on conducting national TB surveys, we selected study participants from 33 health facilities from across the country, grouped into 29 clusters, and included them into the survey. Between April 2016 and June 2017, a total of 927 patients (859 new and 68 previously treated) were enrolled in the survey. Mycobacterium tuberculosis complex (MTBC) isolates were successfully cultured from 598 (65.5%) patient samples and underwent DST, 550 from newly diagnosed and 48 from previously treated patients. The proportion of patients who showed resistance to any of the TB drugs tested was 25.2% (95% CI; 21.8–28.9). The most frequent resistance was to Streptomycin (STR) (12.3%), followed by Isoniazid (INH) (10.4%), with Rifampicin (RIF), showing the least resistance of 2.4%. Resistance to Isoniazid and Rifampicin (multi-drug resistance) was found in 19 (3.2%; 95% CI: 1.9–4.9) isolates. Prevalence of multidrug resistance was 7 (1.3%; 95% CI: 0.5–2.6) among newly diagnosed and 12 (25.0%; 95% CI: 13.6–39.6) among previously treated patients. At both univariate and multivariate analysis, MDR-TB was positively associated with previous history of TB treatment (OR = 5.09, 95% CI: 1.75–14.75, p = 0.003); (OR = 5.41, 95% CI: 1.69–17.30, p = 0.004). The higher levels of MDR-TB and overall resistance to any TB drug among previously treated patients raises concerns about adherence to treatment. This calls for strengthening existing TB programme measures to ensure a system for adequately testing and monitoring TB drug resistance.

Early Clearance of Mycobacterium Tuberculosis: The Infect Case Contact Cohort Study in Indonesia

Introduction: Early clearance of M. tuberculosis is the eradication of infection before an adaptive immune response develops. We studied highly exposed Tuberculosis (TB) case contacts to identify host factors associated with early clearance. Methods: Indonesian household contacts of sputum smear positive TB cases were recruited. An Interferon Gamma Release Assay (IGRA) was performed at baseline and 14 weeks. Early clearance was defined as a persistently negative IGRA. Contacts were characterised with respect to demographic and clinical characteristics, index case exposure, and disease phenotype. Associations with a positive IGRA at each time point were estimated. Results: From 462 TB patients, 1347 households contacts (median age 27·9 years) were recruited. At baseline, 780 (57·9%) had a positive IGRA and 490 (36·3%) were IGRA negative. After 14 weeks, 116/445 (26·1%) initially IGRA negative contacts were IGRA converters and 317 (71·2%; 25·0% of all contacts) remained persistently IGRA negative. After accounting for measures of exposure and possible confounders, BCG vaccination was associated with reduced risk of a positive IGRA at baseline (relative risk [RR]=0·90; 95% CI 0·83 - 0.99; p=0·03), and a strongly reduced risk of IGRA conversion (RR=0·55; 95% CI 0·40 - 0·76; P<0·001). IGRA conversion was associated with diabetes mellitus (RR=1·90; 95% CI 1·02 - 3·51; p=0·04) and smoking (RR=1·66; 95% CI 1·10 - 2·49; p=0·02). Conclusions: Early clearance, defined as two negative IGRA tests 14 weeks apart, is found in a quarter of TB case contacts and is strongly associated with BCG vaccination. Further studies of the underlying immune mechanisms will inform strategies for enhanced protection against M. tuberculosis infection. Funding: AV was supported by a New Zealand Health Research Council Clinical Training Research Fellowship. Cohort recruitment was funded by the University of Otago and Mercy Hospital, Dunedin, New Zealand. Qiagen donated the QuantiFERON® test materials used in the study. Enrollment clinical management and laboratory examination of index cases was conducted in the TANDEM project, which is supported by the European Union’s Seventh Framework Programme (FP7/2007–2013) under Grant Agreement Number 305279. MGN was supported by a Spinoza grant from the Netherlands Organisation for Scientific Research. Declaration of Interest: The authors have no conflict of interests to declare Ethical Approval: The study was approved by the Health Research Ethics Committee Universitas Padjadjaran (14/UN6.C2.1.2/KEPK/PN/2014) and the Southern Health and Disability Ethics Committee New Zealand (13/STH/132).

Monitoring tuberculosis contact tracing outcomes in Western Sydney, Australia

Treatment of latent tuberculosis infection (LTBI) is an important component of strategies to achieve global tuberculosis (TB) elimination, but implementation is rarely monitored. This is a retrospective review of TB...

Risk Factors Associated with Tuberculosis Infection Among Household Children Contacts of Sputum Smear Positive Tuberculosis Cases

Background: India has highest burden of tuberculosis (TB) globally. The source of infection for children is usually an adult in their household with active TB. Only few studies have been carried out among household children contacts of active TB patients in India to assess the risk factors of infection among children. Aim and Objective: To study the risk factors of TB infection among household children contacts of sputum positive patients. Material and Methods: We conducted study on 200 household children contacts (1-15 years) of sputum positive patients registered at DOTS centers in Lucknow district, Uttar Pradesh. Stratified sampling was done. A semi structured questionnaire was administered to collect the information. Infection in children was assessed by TST (Mantoux test). Results: TST positivity in children of TST positivity was associated with female index case (p=0.027), lower socioeconomic status (p=0.011), overcrowding (0.008) and duration of symptoms before treatment (p&lt;0.001). Among the factors of children, age &gt;6 years, duration of stay with index case &gt;10 hours/day and malnutrition were significantly associated. Conclusion: The study concludes that TB infection among children is significantly associated with various factors related to index case, susceptible host and environment, which can be intervened to prevent TB infection in children.

Under-reporting of sputum smear-positive tuberculosis cases in Kenya

Although an estimated three million tuberculosis (TB) cases worldwide are missed by national TB programs annually, the level of under-reporting of diagnosed cases in high TB burden settings is largely unknown. To quantify and describe under-reporting of sputum smear-positive TB cases in Kenya. A national-level retrospective TB inventory study was conducted. All sputum smear-positive TB cases diagnosed by public or private laboratories during 1 April-30 June 2013 were extracted from laboratory registers in 73 randomly sampled subcounties and matched to TB cases in the national TB surveillance system (TIBU). Bivariate and multivariate analyses were conducted. In the subcounties sampled, 715 of 3409 smear-positive TB cases in laboratory registers were not found in TIBU. The estimated level of under-reporting of smear-positive TB cases in Kenya was 20.7% (95%CI 18.4-23.0). Under-reporting was greatest in subcounties with a high TB burden. Unreported cases were more likely to be patients aged ⩾55 years, have scanty smear results, and be diagnosed at large facilities, private facilities, and facilities in high TB burden regions. In Kenya, one fifth of smear-positive TB cases diagnosed during the study period went unreported, suggesting that the true TB burden is higher than reported. TB surveillance in Kenya should be strengthened to ensure all diagnosed TB cases are reported.

Prevalence of pulmonary tuberculosis in adult population of Tanzania: a national survey, 2012.

Tanzania is classified as one of the 22 high tuberculosis (TB) burden countries; however, the true burden of TB disease in the country remains unknown. To assess the prevalence of bacteriologically confirmed pulmonary TB (PTB) in the adult population. This was a community-based cluster randomised survey with proportional-to-population-size selection of primary sampling units (districts). Participants were screened for TB using a symptom questionnaire and chest X-ray (CXR). Those with abnormal CXR and/or at least one symptom suggestive of TB were classified as individuals with presumptive TB, and asked to submit three sputum specimens for smear microscopy and culture. The weighted prevalence for sputum smear-positive TB cases was 249 per 100 000 adult population (95%CI 192-305) and that for bacteriologically confirmed TB cases was 293/100 000 (95%CI 228-358). Individuals aged ⩾45 years comprised 55% (71/129) of the identified smear-positive cases, but just 28% (6793/24 648) of the notified TB cases. CXR screening identified more TB cases than symptom screening. When weighted for human immunodeficiency virus prevalence among notified new smear-positive cases, the overall case detection of incident TB cases in 2012 was between 37% and 48%. The prevalence of sputum smear-positive PTB and bacteriologically confirmed PTB in the adult population was higher than previous World Health Organization estimates. There is a potential underestimation of the number of bacteriologically confirmed PTB cases in the adult population. The age distribution of prevalent cases suggests an epidemiological shift towards the older generations, which has been a sign of successful TB control activities in the past. However, the survey shows that many infectious TB cases are currently missed by the National Tuberculosis Programme.

Private practitioners' contributions to the Revised National Tuberculosis Control Programme in a South Indian district.

Tumkur District, South India. To assess the participation of for-profit, formal private practitioners (PPs) under the Revised National Tuberculosis Control Programme's (RNTCP's) public-private mix (PPM) schemes and document their contribution to RNTCP pulmonary tuberculosis (TB) case finding. RNTCP reports at district TB centre were reviewed. PPs were mapped and their referrals of presumptive TB cases to the RNTCP during 2011 were assessed using laboratory registers at designated microscopy centres (DMCs). None of the 424 PPs had signed up for any PPM scheme. However, 22% made at least one referral to a DMC in 2011. PP referrals constituted 15% of the presumptive TB cases examined at the DMCs, and PPs contributed to 23% of the sputum smear-positive TB cases detected. Among PP referrals, the proportion of confirmed smear-positive cases was high (24%). Fifteen years after the start of PPM, formal engagement of PPs with RNTCP was non-existent. However, PPs do refer cases to the RNTCP and contribute to a fraction of TB case detection. The high proportion of confirmed sputum smear-positive cases suggests that PPs tend to make selective referrals. More efforts are needed to promote the engagement of PPs in the RNTCP.

Intensified tuberculosis case finding amongst vulnerable communities in southern India.

India mainly uses passive case finding to detect tuberculosis (TB) patients through the Revised National Tuberculosis Control Programme (RNTCP). An intensified case finding (ICF) intervention was conducted among vulnerable communities in two districts of Karnataka during July-December 2013; 658 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 8.8% relative to the pre-intervention period (July-December 2012) in intervention communities as compared to an 8.6% decrease in communities without the ICF intervention. ICF activities brought TB services closer to vulnerable communities, moderately increasing TB case detection rates.

Evaluation of TB Case Finding through Systematic Contact Investigation, Chhattisgarh, India.

Rationale. Contact investigation is an established tool for early case detection of tuberculosis (TB). In India, contact investigation is not often conducted, despite national policy, and the yield of contact investigation is not well described. Objective. To determine the yield of evaluating household contacts of sputum smear-positive TB cases in Rajnandgaon district, Chhattisgarh, India. Methods. Among 14 public health care facilities with sputum smear microscopy services, home visits were conducted to identify household contacts of all registered sputum smear-positive TB cases. We used a standardized protocol to screen for clinical symptoms suggestive of active TB with additional referral for chest radiograph and sputa collection. Results. From December 2010 to May 2011, 1,556 household contacts of 312 sputum smear-positive TB cases were identified, of which 148 (9.5%) were symptomatic. Among these, 109 (73.6%) were evaluated by sputum examination resulting in 11 cases (10.1%) of sputum smear-positive TB and 4 cases (3.6%) of smear-negative TB. Household visits contributed additional 63% TB cases compared to passive case detection alone. Conclusion. A standard procedure for conducting household contact investigation identified additional TB cases in the community and offered an opportunity to initiate isoniazid chemoprophylaxis among children.

Impact of awareness drives and community-based active tuberculosis case finding in Odisha, India.

India's Revised National Tuberculosis Control programme employs passive case detection. The new sputum smear-positive case detection rate is less than 70% in Odisha State. During April-June 2012, active case finding (ACF) was conducted through awareness drives and field-based tuberculosis (TB) screening in select communities with the lowest case detection rates. During the campaign, 240 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 11% relative to April-June 2011 in intervention communities compared to an 0.8% increase in non-intervention communities. ACF brought TB services closer to the community and increased TB case detection.

Estimating the tuberculosis burden in resource-limited countries: a capture-recapture study in Yemen

The lack of applicable population-based methods to measure tuberculosis (TB) incidence rates directly at country level emphasises the global need to generate robust TB surveillance data to ascertain trends in disease burden and to assess the performance of TB control programmes in the context of the United Nations Millenium Development Goals and World Health Organization targets for TB control. To estimate the incidence of TB cases (all forms) and sputum smear-positive disease, and the level of under-reporting of TB in Yemen in 2010. Record-linkage and three-source capture-recapture analysis of data collected through active prospective longitudinal surveillance within the public and private non-National Tuberculosis Programme sector in twelve Yemeni governorates, selected by stratified cluster random sampling. For all TB cases, the estimated ratio of notified to incident cases and completeness of case ascertainment after record linkage, i.e., the ratio of detected to incident cases, was respectively 71% (95%CI 64-80) and 75% (95%CI 68-85). For sputum smear-positive TB cases, these ratios were respectively 67% (95%CI 58-75) and 76% (95%CI 66-84). We estimate that there were 13 082 (95%CI 11 610-14 513) TB cases in Yemen in 2010. Under-reporting of TB in Yemen is estimated at 29% (95%CI 20-36).

Tuberculosis epidemiology trends in Armenia

Background: Tuberculosis (TB) in Armenia is one of the most serious public health problems. The Ministry of Health has the overall responsibility for TB control in the country. TB control interventions in Armenia are guided by the National TB Control Program for 2007 – 2015 years. Methods: The article is based on the TB epidemiological data from National TB Control Office register. Results: In 2010 incidence of new TB cases in general population (per 100 000) was 41.3 and decreased by 9.2% compared to the incidence of 2009. Out of all registered TB cases 75% were new cases and 25% were re-treatment cases. In 2010 1329 new TB cases were notified and out of whose 339 were new sputum smear-positive TB cases. The incidence of sputum smear-positive pulmonary TB in 2010 in general population was about 10.4 per 100 000. In 2010 incidence of new TB cases among children was 10.7 per 100 000 population compared to 12.2 per 100 000 in 2009. The notification rate was 43.4 per 100 000 in urban population and 37.5 per 100 000 in rural population. In 2010 TB mortality rate was 2.9 per 100,000 population and decreased by about 25% compared to 2009. Among those who died from TB in 2010 57% were primary TB cases and 18% were diagnosed after autopsy. Treatment success rate for new smear positive cases equals to 73.3% for 2008 cohort and 72.5% for 2009 cohort. The Drug Resistant TB treatment in the country was start in 2010. Percent of treatment failures was increasing since 2005 till 2007 and majority of those failed treatment due to DR TB and now they are enrolled on second line treatment. Conclusion: Armenia now is one of the 18 high priority countries for TB control in the WHO European Region and also among the 27 multi-drug resistant TB burden countries in the world. The National TB Control Program of Armenia now is in process of strengthening essential DOTS elements for prevention drug resistant TB forms, rising TB case detection rate, providing comprehensive social support and psychological assistance to the patients in order to ensure treatment adherence.

Adherence to isoniazid preventive therapy in Indonesian children: A quantitative and qualitative investigation.

BackgroundIt is recommended that young child contacts of sputum smear positive tuberculosis cases receive isoniazid preventive therapy (IPT) but reported adherence is low and risk factors for poor adherence in children are largely unknown.MethodsWe prospectively determined rates of IPT adherence in children < 5 yrs in an Indonesian lung clinic. Possible risk factors for poor adherence, defined as ≤3 months prescription collection, were calculated using logistic regression. To further investigate adherence barriers in-depth interviews were conducted with caregivers of children with good and poor adherence.ResultsEighty-two children eligible for IPT were included, 61 (74.4%) of which had poor adherence. High transport costs (OR 3.3, 95% CI 1.1-10.2) and medication costs (OR 20.0, 95% CI 2.7-414.5) were significantly associated with poor adherence in univariate analysis. Access, medication barriers, disease and health service experience and caregiver TB and IPT knowledge and beliefs were found to be important determinants of adherence in qualitative analysis.ConclusionAdherence to IPT in this setting in Indonesia is extremely low and may result from a combination of financial, knowledge, health service and medication related barriers. Successful reduction of childhood TB urgently requires evidence-based interventions that address poor adherence to IPT.

Effectiveness of involving the private medical sector in the National TB Control Programme in Bangladesh: evidence from mixed methods

ObjectivesIn Bangladesh, private healthcare is common and popular, regardless of income or area of residence, making the private sector an important player in health service provision. Although the private sector...

Engaging hospitals to meet tuberculosis control targets in China: using the Internet as a tool to put policy into practice

Tuberculosis (TB) services in China are provided through a large network of TB dispensaries. Even though hospitals are not as well placed to follow recommended standards of TB care, a significant proportion of people with TB symptoms seek care from hospitals. In spite of having a policy and mandate in place, the Ministry of Health had little success in encouraging hospitals to refer suspected TB cases to dispensaries. Following the epidemic of severe acute respiratory syndrome in 2003, the government set up a nationwide Internet-based communicable diseases reporting system. This achieved productive collaboration between hospitals and TB dispensaries. From 2004 to 2007, the percentage of TB suspects and patients needing referral from hospitals who arrived in TB dispensaries increased substantially from 58.7% to 77.8% and the contribution of hospitals to diagnosing sputum smear-positive TB cases doubled from 16.3% to 32.9%. Using the Internet-based reporting system, hospitals in China contributed to finding about one third of all sputum smear-positive TB cases and helped meet the global TB control target of detecting 70% of such cases. Based on the data available from routine surveillance facilitated by this Internet-based system, this paper details the process and outcomes of strengthening collaboration between hospitals and TB dispensaries using the Internet as a tool and its potential application to other country settings.

Decay Kinetics of an Interferon Gamma Release Assay with Anti-Tuberculosis Therapy in Newly Diagnosed Tuberculosis Cases

BackgroundQualitative and quantitative changes in IGRA response offer promise as biomarkers to monitor Tuberculosis (TB) drug therapy, and for the comparison of new interventions. We studied the decay kinetics of TB-specific antigen T-cell responses measured with an in-house ELISPOT assay during the course of therapy.MethodsNewly diagnosed sputum smear positive TB cases with typical TB chest radiographs were recruited. All patients were given standard anti-TB treatment. Each subject was followed up for 6 months and treatment outcomes were documented. Blood samples were obtained for the ESAT-6 and CFP-10 (EC) ELISPOT at diagnosis, 1-, 2-, 4- and 6-months. Qualitative and quantitative reversion of the ELISPOT results were assessed with McNemar test, conditional logistic regression and mixed-effects hierarchical Poisson models.ResultsA total of 116 cases were recruited and EC ELISPOT was positive for 87% (95 of 109) at recruitment. There was a significant decrease in the proportion of EC ELISPOT positive cases over the treatment period (p<0.001). Most of the reversion occurred between the start and first month of treatment and at completion at 6 months. ESAT-6 had higher median counts compared to CFP-10 at all time points. Counts for each antigen declined significantly with therapy (p<0.001). Reverters had lower median SFUs at the start of treatment compared to non-Reverters for both antigens. Apart from the higher median counts for non-Reverters, no other risk factors for non-reversion were found.ConclusionsTB treatment induces qualitative and quantitative reversion of a positive in-house IGRA in newly diagnosed cases of active TB disease. As this does not occur reliably in the majority of cured individuals, qualitative and quantitative reversion of an IGRA ELISPOT has limited clinical utility as a surrogate marker of treatment efficacy.

Missed opportunity for standardized diagnosis and treatment among adult Tuberculosis patients in hospitals involved in Public-Private Mix for Directly Observed Treatment Short-Course strategy in Indonesia: a cross-sectional study

BackgroundThe engagement of hospitals in Public-Private Mix (PPM) for Directly Observed Treatment Short-Course (DOTS) strategy has increased rapidly internationally - including in Indonesia. In view of the rapid global scaling-up of hospital engagement, we aimed to estimate the proportion of outpatient adult Tuberculosis patients who received standardized diagnosis and treatment at outpatients units of hospitals involved in the PPM-DOTS strategy.MethodsA cross-sectional study using morbidity reports for outpatients, laboratory registers and Tuberculosis patient registers from 1 January 2005 to 31 December 2005. By quota sampling, 62 hospitals were selected. Post-stratification analysis was conducted to estimate the proportion of Tuberculosis cases receiving standardized management according to the DOTS strategy.ResultNineteen to 53% of Tuberculosis cases and 4-18% of sputum smear positive Tuberculosis cases in hospitals that participated in the PPM-DOTS strategy were not treated with standardized diagnosis and treatment as in DOTS.ConclusionThis study found that a substantial proportion of TB patients cared for at PPM-DOTS hospitals are not managed under the DOTS strategy. This represents a missed opportunity for standardized diagnoses and treatment. A combination of strong individual commitment of health professionals, organizational supports, leadership, and relevant policy in hospital and National Tuberculosis Programme may be required to strengthen DOTS implementation in hospitals.

An analysis of the costs and treatment success of collaborative arrangements among public and private providers for tuberculosis control in Indonesia

To identify the cost-effectiveness of collaborative arrangements among public and private providers to employ the Directly Observed Treatment short-course (DOTS) strategy for tuberculosis (TB) control in Indonesia. Three strategies were assessed: hospital out-patient diagnosis with referral to public health centres (PHCs) for treatment, hospital out-patient diagnosis and treatment, and private practitioner referral of suspects to PHCs. The outcome was the number of sputum smear positive TB cases successfully treated. Costs include direct costs to providers and patients. Uncertainty analysis was done for both costs and effectiveness data. The average cost per case successfully treated ranged from US$169 to $567 for different strategies. The cost per additional case successfully treated incremental to existing TB programmes ranged from US$152 to $982. In three of four provinces assessed, there was a clearly preferred strategy or strategies, although the preferred strategy differed by province; in one province a preferred strategy could not be identified. All strategies increased TB case finding, although attribution is tentative because of the study design. Neither collaboration among private practitioners nor among hospitals is clearly preferred based on cost-effectiveness. For hospitals, this study suggests that having hospitals refer patients to health centres is preferable over hospitals administering treatment.

Incidence of Tuberculosis and the Predictive Value of ELISPOT and Mantoux Tests in Gambian Case Contacts

BackgroundStudies of Tuberculosis (TB) case contacts are increasingly being utilised for understanding the relationship between M. tuberculosis and the human host and for assessing new interventions and diagnostic tests. We aimed to identify the incidence rate of new TB cases among TB contacts and to relate this to their initial Mantoux and ELISPOT test results.Methods and FindingsAfter initial Mantoux and ELISPOT tests and exclusion of co-prevalent TB cases, we followed 2348 household contacts of sputum smear positive TB cases. We visited them at 3 months, 6 months, 12 months, 18 months and 24 months, and investigated those with symptoms consistent with TB. Those who were diagnosed separately at a government clinic had a chest x-ray. Twenty six contacts were diagnosed with definite TB over 4312 person years of follow-up (Incidence rate 603/100,000 person years; 95% Confidence Interval, 370–830). Nine index and secondary case pairs had cultured isolates available for genotyping. Of these, 6 pairs were concordant and 3 were discordant. 2.5% of non-progressors were HIV positive compared to 12% of progressors (HR 6.2; 95% CI 1.7–22.5; p = 0.010). 25 secondary cases had initial Mantoux results, 14 (56%) were positive ; 21 had initial ELISPOT results, 11 (52%) were positive; 15 (71%) of 21 tested were positive by one or the other test. Of the 6 contacts who had concordant isolates with their respective index case, 4 (67%) were Mantoux positive at recruitment, 3 (50%) were ELISPOT positive; 5 (83%) were positive by one or other of the two tests. ELISPOT positive contacts, and those with discordant results, had a similar rate of progression to those who were Mantoux positive. Those negative on either or both tests had the lowest rate of progression.ConclusionsThe incidence rate of TB disease in Gambian TB case contacts, after screening for co-prevalent cases, was 603/100,000 person years. Since initial ELISPOT test and Mantoux tests were each positive in only just over half of cases, but 71% were positive by one or other test, positivity by either might be the best indication for preventive treatment. These data do not support the replacement of the Mantoux test by an ELISPOT test in The Gambia or similar settings.

Treatment and management of MDR-TB in Latvia

Background Latvia has consistently ranked among the countries with the highest rates of MDR-TB in the world. In the first Global Tuberculosis Drug Resistance Survey (1996), 14.4%, or 1 out of 7, of all newly diagnosed sputum smear-positive tuberculosis cases in Latvia were diagnosed as MDR-TB. (1) Data also show that the proportion of cases with additional resistance to second-line anti-tuberculosis drugs is high. In the meantime, HIV seroprevalence is increasing among TB patients. Latvia, with an estimated population of 2.35 million, joined the European Union on 1 May 2004. Latvian economy had been severely affected by the collapse of the Soviet Union, with gross domestic product (GDP) per capita falling by nearly 35% in real terms in 1992. GDP per capita in 1999 was US$ 4200, increasing to US$11 500 in 2004. Latvia concurrently experienced dramatic increases in TB morbidity and mortality peaking in 1998, together with the appearance of drug-resistant and MDR-TB. (2,3) Latvia adopted WHO's recommended DOTS strategy for TB control in 1996 and subsequently introduced MDR-TB management (4) in 1997. This relies on MDR-TB treatment with individualized regimens under the consilium or expert consultation process. The treatment is provided at four inpatient treatment centres (including a prison TB ward) followed by outpatient directly observed therapy. All funding for TB and MDR-TB control comes from the government. In 2000 Latvia's National Tuberculosis Program (NTP) sought MDR-TB management support from the Green Light Committee (GLC) and got approval to treat 350 more MDR-TB patients. The GLC enabled Latvia to treat all patients diagnosed with MDR-TB. Epidemiology In 1991, the incidence of TB was 29 cases per 100 000 population, (5) increasing to 74/100 000 in 1998 and then declining to 53.5/100 000 in 2005. Case finding shows 49% case detection by smear microscopy. Drug-resistant TB case detection strategy in Latvia is based on drug sensitivity tests (DST) on solid media. For high-risk MDR-TB cases, the BACTEC/MIGT system is used, as well as the INNO LiPA test to detect rifampicin resistance in 2-4 days. Extensive resistance to first- and second-line drugs among MDR-TB patients is well known in Latvia. One of the reasons is the country's long and extensive use of second-line drugs before implementing the DOTS strategy. Extensive resistance affects the MDR-TB treatment regimen and outcomes. For cohorts registered from 2000 to 2005, resistance to kanamycin was 49%; capreomycin, 39%; ofloxacine, 9%; protheonamide, 30%; para-aminosalycilic acid, 31%; and thiacethasone, 23%. In the first worldwide survey, published in May 2006, estimates for years 2000-2004 showed that 19% of MDR-TB patients have resistance to first-line drugs defined as MDR-TB plus resistance to three drugs of six classes of second-line drugs. (6) Using the new revised extensive drug resistance (XDR-TB) definition of resistance to at least rifampicin and isoniazid, additional resistance to any fluoroquinolone and to any of three second-line injectable drugs (capreomycin, kanamycin or amikacin), such extensively resistant TB was found in 39 cases, or 5.2% of all MDR-TB cases registered during the past six years. Two-thirds, or 67%, of MDR-TB patients out of 820 treated in the years 2000-2003 were cured; 6% were dead; 14% defaulted; and treatment failed in 13% of cases. (7,8) The treatment success rate for XDR-TB patients is low: out of all 48 patients treated from 2000 to 2005 (including MDR-TB retreatment cases with XDR-TB), only 18 (38%) were cured, while treatment failed for 22 (46%). Among all MDR-TB cases in the cohorts, 3% were co-infected with HIV; this proportion increased to 12% among XDR-TB cases. Treatment success for TB/HIV co-infected new patients, at 74%, is similar to overall treatment success for new TB patients, but the HIV-associated MDR-TB success rate is 56%. …