The devil we know: is the use of injectable agents for the treatment of MDR-TB justified?

For decades, second-line injectable agents (IAs) have been the cornerstone of treatment for multidrug-resistant tuberculosis (MDR-TB). Although evidence on the efficacy of IAs is limited, there is an expanding body of evidence on the serious adverse events caused by these drugs. Here, we present the results of a structured literature review of the safety and efficacy of IAs. We review the continued widespread use of these agents in the context of therapeutic alternatives-most notably the newer TB drugs, bedaquiline and delamanid-and from the context of human rights, ethics and patient-centered care. We conclude that there is limited evidence of the efficacy of IAs, clear evidence of the risks of these drugs, and that persons living with MDR-TB should be informed about these risks and provided with access to alternative therapeutic options.

Reversing the tuberculosis upwards trend: a success story in Romania.

At present, no published evidence is available on the effectiveness of the DOTS (directly observed treatment, short-course) strategy in reducing the incidence of tuberculosis (TB) within a country in the European "hot spots". The present study aimed to demonstrate the effectiveness of the strategy implementation in reversing the epidemiological TB trend in Romania based on programmatic data analysis. Key programme indicators were analysed from 1998 to 2007, and included DOTS coverage, case-detection rate, treatment success and overall incidence of notified cases. Internationally agreed definitions were used. The key programme indicators began declining and the World Health Assembly targets were reached (79% case-detection of new sputum-smear positive cases and 85.5% success rate in new culture-positive TB cases), 7 yrs after initiation of the DOTS expansion. The success story in Romania suggests that other middle-income, high-incidence countries (i.e. those belonging to the former Soviet Union) might be able to reach the World Health Assembly Targets and curb the burden of tuberculosis.

Diagnosis and treatment of tuberculosis in undocumented migrants in low- or intermediate-incidence countries.

SETTING: Countries with low or intermediate tuberculosis (TB) incidence. OBJECTIVES: 1) To gather information on individuals and TB patients who are undocumented migrants and their access to TB diagnostic and treatment services; 2)to discuss interventions to strengthen diagnosis and treatment and 3) to formulate recommendations on how to ensure adequate TB prevention and control. DESIGN: Questionnaires sent to members of the Working Group (WG) on Transborder Migration and TB, managers of national TB programmes and EuroTB correspondents; literature research and development of a paper by a writing committee through consultation. RESULTS: Undocumented migrants represent 5-30% of immigrants and 5-10% of TB cases. Most countries reported full access to diagnosis and treatment, but in practice there were limitations. Most countries also reported that they could and did deport cases who were on TB treatment. A variety of activities to ensure access were reported from different countries. CONCLUSION: The WG recommends that 1) health authorities and/or health staff should ensure easy access to low-threshold facilities where undocumented migrants who are TB suspects can be diagnosed and treated without giving their names and without fear of being reported to the police or migration officials. Health authorities should remind health staff that they have an obligation of confidentiality; 2) each country should ensure that undocumented migrants with TB are not deported until completion of treatment; and 3) authorities and non-governmental sectors should raise awareness among undocumented migrants about TB, emphasising that diagnosis and treatment should be free of charge and wholly independent of migratory status.

Active case finding of tuberculosis in Europe: a Tuberculosis Network European Trials Group (TBNET) survey.

Tuberculosis control depends on successful case finding and treatment of individuals infected with Mycobacterium tuberculosis. Passive case finding is widely practised: the present study aims to ascertain the consensus and possible improvements in active case finding across Europe. Recommendations from national guidelines were collected from 50 countries of the World Health Organization European region using a standard questionnaire. Contacts are universally screened for active tuberculosis and latent tuberculosis infection (LTBI). Most countries (>70%) screen those with HIV infection, prisoners and in-patient contacts. Screening of immigrants is related to their contribution to national rates of tuberculosis. Only 25 (50%) out of 50 advise a request for symptoms in their guidelines. A total of 36 (72%) out of 50 countries recommend sputum examination for those with a persistent cough; 13 countries do not, even if the chest radiograph suggests tuberculosis. Nearly all countries (49 out of 50) use tuberculin skin testing (TST); 27 (54%) out of 50 countries also perform chest radiography irrespective of the TST result. Interpretation of the TST varies widely. All countries use 6-9 months of isoniazid for treatment of LTBI, with an estimated median (range) uptake of 55% (5-92.5%). Symptoms and sputum examination could be used more widely when screening for active tuberculosis. Treatment of latent tuberculosis infection might be better focused by targeted use of interferon-gamma release assays.

High risk of tuberculosis in health care workers in Romania.

SETTING: The main university hospital in Iasi, Romania. OBJECTIVE: To assess whether health care workers (HCWs) have a higher risk of acquiring tuberculosis (TB) than the general population, and if TB incidence varies between departments, to develop adequate infection control measures. DESIGN: All records of TB cases among HCWs were reviewed by cross-checking laboratory and medical records (retrospectively, 1971--1996; prospectively 1997--2003, following the implementation of the first World Health Organization pilot project in Romania). Annual TB incidence rates among HCWs were calculated and compared with those of the general population; relative and attributable risk with 95% confidence intervals (CI) were calculated. RESULTS: Fifty TB cases were diagnosed in HCWs; 42% were nurses, 24% ancillary staff, 12% physicians, 10% laboratory staff, 10% administrative staff and 2% radiology technicians. The mean incidence of TB in Romania during the study period was 96.8 per 100,000 persons/year (95%CI 83.5-110.1); the mean incidence among HCWs was 942.8/100,000 persons/year (95%CI 726.3-1159.3, P < 0.001); comparing the two previous absolute risks, the mean relative risk was 11 (95%CI 8-14) and the attributable risk 846. CONCLUSION: TB is a major occupational hazard in Iasi, Romania, where a great potential exists for further development of an effective infection control plan.

Tuberculosis-HIV co-infection: policy and epidemiology in 25 countries in the WHO European region.

OBJECTIVES: The aims of this study were to collect and review tuberculosis (TB)-HIV data for Europe and to provide an overview of current health policies addressing co-infection. METHODS: We collected reported cases of TB-HIV from the 25 most affected member states of the World Health Organization (WHO) European region. Countries were also asked whether they had implemented health policies covering collaborative TB-HIV activities and what their main achievements, obstacles and needs were in addressing TB-HIV. RESULTS: Twenty countries reported registering a total of 6925 TB-HIV cases in 2005. Among TB patients tested, 3.3% were found to be HIV-positive, up from 2.1% in 2004. The male-to-female ratio was 2.7:1. The largest percentage of co-infections were reported in people aged 25-34 years (47.8%). Recommended TB-HIV policies have been implemented in many of the countries. CONCLUSIONS: Case-finding has improved in many countries and the reported incidence of TB-HIV is increasing in the European region, particularly among young adults, although it remains low compared to other parts of the world. Strengthened coordination of existing TB and HIV services is still needed.

National Tuberculosis Programme in Romania 1997-2000: how it works.

Romania displays one of the highest epidemiological parameters of tuberculosis among European countries: the incidence reached 113.3 per 100,000 in 1998, the prevalence of chronic cases was 18.9 and mortality 11.5 per 100,000 in 1996. A National Tuberculosis Programme aimed at decreasing the present burden of the disease has been elaborated according to the WHO strategy in 1997 and for its implementing. The National Committee on Pneumophtisiology and the Central Unit of the National Institute of Pneumophtisiology were made responsible. Tuberculosis managers and supervisors were nominated in each of the 48 counties and a total of 18,000 family doctors were involved in this programme at the primary health care level. Tuberculosis has been declared the second health priority in Romania and the following budget providers for its effective control were acquired: Ministry of Health, World Bank, Open Society Foundation, Funds of Romania and World Health Organization. The following achievements can be mentioned so far: A technical manual on the National Programme has been published, WHO modules on DOTS strategy were translated into Romanian, a training course on the WHO-DOTS strategy was organized for tuberculosis managers and laboratory chiefs, a pilot project on the WHO-DOTS strategy started in lasi, first control visits in counties and pneumophtisiologists were implemented, training for family doctors was organized and a project for health education with video shots was presented on the national TV channel.