Harmonisation of TB control in the WHO European region: the history of the Wolfheze Workshops.

In 1990 a workshop was organised in the village of Wolfheze (the Netherlands), where experts discussed the critical interventions that would foster elimination of TB in Europe. This event has been followed by several more over the following two decades to become known as the "Wolfheze Workshops". This article provides a brief overview of the history and the impact the Wolfheze Workshops have had on the commitment of European governments to standardise definitions, recording and reporting systems and, thus, permitted comparison of interventions and improving TB control across borders. The Wolfheze Workshops have been and still are an essential platform for this exchange of experiences, promoting common approaches.

Tuberculosis contact investigation and short-course preventive therapy among young children in Africa.

SETTING: The largest cities in Benin, Burkina Faso, Cameroon and Central African Republic.OBJECTIVE: To demonstrate the feasibility and document the effectiveness of household contact investigation and preventive therapy in resource-limited settings.DESIGN: Children under 5 years living at home with adults with bacteriologically confirmed pulmonary tuberculosis (TB) were screened using questionnaire, clinical examination, tuberculin skin test and chest X-ray. Children free of active TB were offered preventive treatment with a 3-month rifampicin-isoniazid (3RH) or 6-month isoniazid (6H) regimen in Benin. Children were followed-up monthly during treatment, then quarterly over 1 year. Costs of transportation, phone contacts and chest X-rays were covered.RESULTS: A total of 1965 children were enrolled, of whom 56 (2.8%) had prevalent TB at inclusion. Among the 1909 children free of TB, 1745 (91%) started preventive therapy, 1642 (94%) of whom completed treatment. Mild adverse reactions, mostly gastrointestinal, were reported in 2% of children. One case of incident TB, possibly due to a late TB infection, was reported after completing the 3RH regimen.CONCLUSION: Contact investigation and preventive therapy were successfully implemented in these resource-limited urban settings in programmatic conditions with few additional resources. The 3RH regimen is a valuable alternative to 6H for preventing TB.

Outbreak of influenza A(H1N1)v without travel history in a school in the Toulouse district, France, June 2009.

In June 2009, for the first time in France, a confirmed outbreak of influenza A(H1N1)v without history of travel occurred in a secondary school in Toulouse district. A total of 15 cases were confirmed among students of which three were asymptomatic. This report describes the outbreak and its public health implications.

Outcome definitions for multidrug-resistant tuberculosis treated with shorter treatment regimens.

To assess whether the revised 2013 World Health Organization (WHO) definitions for multidrug-resistant tuberculosis (MDR-TB) treatment outcomes apply to shorter treatment regimens in low- and middle-income countries and to propose modified criteria. Criteria for 'failure' and 'cure' outcomes were assessed using data on 1006 patients enrolled in an observational study on the standardised 9-11 month shorter MDR-TB regimen in Africa. Absence of conversion in the intensive phase, a WHO criteria for failure, was the worst performing criterion; reversion had low sensitivity and other criteria provided limited added value. Based on our study results, we propose new definitions for 'treatment failure' as treatment termination or the permanent discontinuation of 2 anti-tuberculosis drugs due to 1) positive culture after 6 months of treatment (except for one isolated positive culture) or 2) at least two consecutive grade 2+ positive sputum smears after 6 months of treatment if culture is not available; and for 'cure' as treatment completion without proof of failure AND two consecutive negative cultures taken 30 days apart, one of which should be after 6 months of treatment. The proposed new definitions are applicable to shorter regimens in low- and middle-income countries, and should also work for the newly recommended longer regimens. .

Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries.

SETTING: Nine countries in West and Central Africa. OBJECTIVE: To assess outcomes and adverse drug events of a standardised 9-month treatment regimen for multidrug-resistant tuberculosis (MDR-TB) among patients never previously treated with second-line drugs. DESIGN: Prospective observational study of MDR-TB patients treated with a standardised 9-month regimen including moxifloxacin, clofazimine, ethambutol (EMB) and pyrazinamide (PZA) throughout, supplemented by kanamycin, prothionamide and high-dose isoniazid during an intensive phase of a minimum of 4 to a maximum of 6 months. RESULTS: Among the 1006 MDR-TB patients included in the study, 200 (19.9%) were infected with the human immunodeficiency virus (HIV). Outcomes were as follows: 728 (72.4%) cured, 93 (9.2%) treatment completed (81.6% success), 59 (5.9%) failures, 78 (7.8%) deaths, 48 (4.8%) lost to follow-up. The proportion of deaths was much higher among HIV-infected patients (19.0% vs. 5.0%). Treatment success did not differ by HIV status among survivors. Fluoroquinolone resistance was the main cause of failure, while resistance to PZA, ethionamide or EMB did not influence bacteriological outcome. The most important adverse drug event was hearing impairment (11.4% severe deterioration after 4 months). CONCLUSIONS: The study results support the use of the short regimen recently recommended by the World Health Organization. Its high level of success even among HIV-positive patients promises substantial improvements in TB control.

Do active case-finding projects increase the number of tuberculosis cases notified at national level?

OBJECTIVE: To analyse the impact of active tuberculosis case finding (ACF) projects on the number of sputum smear-positive (SS+) tuberculosis (TB) cases notified at national level. METHODS: Case-finding results of the 16 countries that participated in the first wave of the TB REACH project were analysed. Information on the number of SS+ TB cases at national level were taken from the 2014 World Health Organization global tuberculosis report. A segmented linear regression model was used to analyse trends in notification. RESULTS: An increase in SS+ TB cases from 3% to 334% was observed in the areas of intervention of the TB REACH project in almost all countries. There were no significant increases in the number of SS+ TB cases notified at the national level in most countries, except in two countries during the intervention period (Benin and Kenya), and in one country after the intervention period (Somalia). CONCLUSIONS: The TB REACH project had no impact on SS+ TB cases notified at national level in almost all countries during and after the intervention. ACF projects are pilot studies that are often difficult to reproduce at national level due to their high cost and the lack of human resources.

Numbers of tuberculosis cases: dreams and reality.

BACKGROUND: Use of estimated numbers of tuberculosis (TB) cases for planning purposes in some sub-Saharan countries. OBJECTIVE: To document the uncertainties of official World Health Organization estimates and problems encountered in using them for planning. DESIGN: Brief review of the methods used in estimation, using different sub-Saharan countries to illustrate problems. RESULTS: The annual risk of tuberculous infection, used for many years to calculate estimates, is no longer considered a valid method. New methods are based on an assessment of the completeness of TB notification data (the Onion Model) and prevalence surveys of bacteriologically proven pulmonary TB cases; however, these are subject to bias and are very imprecise. Examples from sub-Saharan countries reflect these difficulties and show that official estimates vary substantially, by up to a quarter of the initial values. Donors, particularly the Global Fund, rely on these estimates and push countries to arbitrarily increase planned numbers of notified cases to improve 'case detection rates'. CONCLUSION: Use of estimated numbers to monitor progress in TB control may be counterproductive, costly and risky. It would be much more realistic to accept that low-income countries plan their strategies based on TB notifications rather than on case detection rates that are more dream than reality.

Implementation of isoniazid preventive therapy in children aged under 5 years exposed to tuberculosis in Benin.

SETTINGS: Two large tuberculosis (TB) centres under a well-functioning National TB Programme (NTP) in Benin, West Africa. OBJECTIVE: To assess the feasibility and results of integrating a programme of isoniazid preventive therapy (IPT) in children aged <5 years exposed to TB as part of the existing routine activities of the NTP. METHOD: All children aged <5 years living in the household of a patient with smear-positive pulmonary TB were examined by a doctor and received IPT if no evidence of TB was detected. The children were followed clinically by a nurse for 6 months. RESULTS: From January 2013 to June 2014, 496 children were examined and prescribed IPT among 499 notified contacts; 86% adhered to IPT for at least 6 months. There were six deaths and three cases of active TB among the children, all during the first 3 months of follow-up. CONCLUSIONS: In an African country with moderate TB incidence and a well-functioning NTP, the integration of IPT into the NTP for children aged <5 years exposed to TB in the family was feasible based on simple tools associated with the follow-up of index cases. The rate of adherence to IPT was high.

Factors associated with tuberculosis at AIDS diagnosis in France.

OBJECTIVE: To identify factors associated with tuberculosis (TB) at AIDS diagnosis in France. DESIGN: Analysis of surveillance data. METHODS: Among all adult AIDS cases diagnosed since January 1988 and reported by December 1993 in France, the proportion diagnosed with AIDS-defining TB (extrapulmonary TB among cases diagnosed between 1988 and 1992, all forms of TB among cases diagnosed in 1993) was analysed by year of diagnosis, sex, age, nationality, profession, HIV transmission group and region of residence by multiple logistic regression. RESULTS: Between 1988 and 1992, 5.7% (1134 out of 19,968) of AIDS patients were diagnosed with AIDS-defining extrapulmonary TB. Presence of extrapulmonary TB was associated with male sex [adjusted odds ratio (AOR), 1.7], nationality from a sub-Saharan country (AOR, 4.8), heterosexual contact or injecting drug use (AOR, 2.4 and 2.7, respectively), residence in the Paris area (AOR, 1.7), and unemployment or factory work (AOR, 2.5 and 2.4, respectively). In 1993, 10.6% (393 out of 3721) of AIDS patients were diagnosed with TB (all forms). In multivariate analysis, three factors were independently associated with the risk of presenting TB at AIDS diagnosis: transmission category, nationality, and region of residence. CONCLUSIONS: Some factors associated with TB at AIDS diagnosis in France are known to be related to a high incidence of TB in industrialized countries (nationality, from a developing country, male sex, low socioeconomic status). The independent association with injecting drug use or residence in Paris suggests a contribution of recent TB infection in specific groups of HIV-infected persons. This contribution should be evaluated to implement appropriate preventive measures.

Determinants of delayed diagnosis of HIV infection in France, 1993-1995.

OBJECTIVE: To describe the circumstances of the first HIV-positive test and to study the determinants of a delayed diagnosis of HIV infection. METHODS: In a retrospective study among adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts, data on socioeconomic characteristics, circumstances of first HIV-positive test and attitudes and behaviours regarding medical care were collected in a confidential interview and analysed for potential association with a late test, defined as a first HIV-positive test within 6 months of AIDS diagnosis. RESULTS: Of the 359 AIDS patients studied, 69 (19.2%) had a late test. Late testers were more likely than other patients to have had an HIV-positive test because of clinical symptoms (89.7 versus 38.9%, P < 0.001) and not to perceive themselves as being at risk of infection with HIV (53.6 versus 39.3%, P < 0.05). The proportion of late testers was 34.6% among heterosexually infected patients, 12.7% among homo-/ bisexual men and 9.6% among injecting drug users. Factors independently associated with a late test were male gender [adjusted odds ratio (aOR), 5.6; 95% confidence interval (CI), 1.7-18.9] and absence of earned income (aOR, 5.2; 95% CI, 1.4-19) among heterosexually infected patients; high education (aOR, 3.1; 95% CI, 1.0-9.6) and having consulted a person practising alternative medicine (aOR, 3.4; 95% CI, 1.2-10) in homo-/bisexual men. CONCLUSIONS: Despite incentives to be tested for HIV, many individuals in France are still tested too late, even if they are in known high-risk groups. Efforts to test HIV-infected people as early as possible should be made by increasing the perception of HIV risk and decreasing the level of missed opportunities for testing. Current case management approaches make this recommendation critically important from both public health and an individual perspective.

Epidemiology and control of tuberculosis in Western European cities.

SETTING: Major cities of Western Europe. OBJECTIVE: To describe major variations in the epidemiology and control of tuberculosis in large Western European Cities. DESIGN: Postal survey using contacts identified through the EURO-TB surveillance network. RESULTS: Twenty cities responded. In most cities, notification rates were substantially higher than national rates. Rates ranged from less than 10 per 100,000 in Reykjavik and Belfast to over 70 per 100,000 in Lisbon. MDR-TB ranged from less than 1% of cases in many cities to over 5% in Rome and Milan. The proportion of patients estimated to be HIV-positive ranged from less than 5% in many countries to over 20% in Milan. These variations in epidemiology were accompanied by major variations in control policy, particularly in approaches to new entrant screening and BCG vaccination. CONCLUSION: In Western Europe, tuberculosis is primarily a problem of large cities. Some of these cities have very high rates of tuberculosis. There is little consensus about the best approaches to control. The evidence base for the effectiveness of different aspects of TB control needs to be strengthened.

Feasibility of surveillance resistance to antituberculosis drugs :Europe, 1997.

Between 28% and 100% of isolates from ten countries from the EuroTB network in 1997 were reported with data on antituberculosis drug susceptibility. Drug resistance was commoner among foreign-born patients and in general among patients who had been treate

Surveillance of tuberculosis in the WHO European region in 1995 : results of the feasibility study.

Efforts to assess the changing epidemiology of tuberculosis (TB) in Europe have been limited by differences in definitions and in the quality of tuberculosis surveillance systems between countries. In order to standardise the surveillance of TB among Euro.

Surveillance of tuberculosis in Europe.

This paper summarises recommendations for uniform reporting on tuberculosis cases made by a working group set up in 1994 following a meeting on tuberculosis control in low prevalence countries. The meeting had been organised jointly by the World Health Or

Surveillance of tuberculosis in the WHO European Region 1995-1996.

The EuroTB programme for the surveillance of tuberculosis in Europe was set up in 1996 to collect, analyse, and disseminate data on tuberculosis cases notified in the World Health Organization (WHO) European Region. Following a feasibility study performed

European recommendations on surveillance of antituberculosis drug resistance.

Antituberculosis drug resistance, whose extent in Europe is not well documented, is a serious threat to tuberculosis control. The aim of the recent European recommendations on antituberculosis drug resistance surveillance, issued by a working group compos

[European surveillance of infectious diseases: the case of AIDS and tuberculosis]. / Surveillance européenne des maladies infectieuses: les cas du SIDA et de la tuberculose.

In 1992, the Maastricht treaty gave specific responsibilities to the European Community in the field of research, information and health education. Several European surveillance systems for infectious diseases have been organised. The surveillance of AIDS was set up in 1984 after the emergence of this new disease. Seven western European countries participated initially. The system currently covers 48 of the 51 countries of the WHO European region. Based on a common case definition, it enables analysis of trends and comparisons which considerably facilitate the understanding of the epidemic and its determinants, and the evaluation of preventive actions. European countries have now decided to set up a reporting system for HIV infection. The surveillance of tuberculosis started in 1996 in response to the reversal of trends in reported cases observed in western Europe and to the threat of multi-drug resistant tuberculosis epidemics. Common recommendations on definitions and data collection procedures facilitated its establishment. Most countries of the WHO European region participated in the first year, revealing a very heterogeneous epidemiological situation. The next objective is to set up a surveillance system for antituberculosis drug resistance. The European surveillance of AIDS and tuberculosis are examples of systems adapted to the specific characteristics of Europe: similarities in diagnostic procedures, similarities in access to treatments, and common requirements regarding both the exchange of information and the coordinated response to public health threats. They are not simply looking for a common denominator. They are creating a real momentum among participating countries towards a better quality and a higher level of pertinence of the information.

[Factors associated with medical management of HIV infected persons in two French districts, 1993-1995]. / Facteurs associés à la prise en charge médicale des personnes infectées par le VIH dans deux départements français, 1993-1995.

BACKGROUND: The regularity of medical followup of HIVinfected patients greatly influences the effectiveness of antiretroviral treatments and of prophylaxis of opportunistic infections. METHODS: To identify potential barriers to a regular followup, a retrospective study was conducted among the adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts (Gironde and HautsdeSeine). Medical followup was described based on the frequency of CD4 counts in the medical file and on a confidential interview among patients whose HIV infection had been diagnosed at least 6 months before AIDS. Irregular followup (less than one CD4 count per year when CD4> 500/ mm(3), and per 6months when CD4< 500/ mm(3)) within the two years preceding AIDS diagnosis was analysed according to socioeconomic status and to social and behavioral factors. RESULTS: Among 290 patients, followup was irregular in 51% of the patients (injecting drug users: 66%, homo/bisexual men: 41%, patients infected through heterosexual contact: 49%, p<0.01). Factors independently associated with irregular followup were low income level (adjusted odds ratio (aOR)= 2.4; 95% confidence interval (CI), 1.44.1); absence of regular practitioner at HIV diagnosis (aOR= 1.9; 95% CI 1.13.3); imprisonment between HIV diagnosis and AIDS (aOR= 3.8; 95% CI 1.310. 9), and being non homo/bisexual male (aOR= 2.4; 95% CI 1.15.1) versus homo/bisexual male (aOR= 1.3; 95% CI 0.72.7) and female (reference). CONCLUSIONS: Results of this study show that several socioeconomic, psychological and cultural barriers to a regular preAIDS medical followup still exist. Impact of new antiretroviral therapy may only be optimal if these barriers are overcome.