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.

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.

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.

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.

Predictors of symptoms of post-traumatic stress disorder after the AZF chemical factory explosion on 21 September 2001, in Toulouse, France.

OBJECTIVE: To analyse in the general population the prevalence and predictors of symptomatology consistent with post-traumatic stress disorder (S-PTSD) 18 months after an industrial explosion. DESIGN: Cross-sectional survey. PARTICIPANTS AND OUTCOME MEASURES: A random sample of 1191 city inhabitants, including an oversample of the immediate area (<3 km). S-PTSD was measured by the self-administered Impact of Event Scale-Revised. The relation between S-PTSD and individual vulnerability factors, immediate exposure and post-trauma factors was analysed by gender. RESULTS: S-PTSD was more prevalent in the immediate area than in the peripheral area (women 19% vs 8%; men 8% vs 2%, p<0.01). In the immediate area, S-PTSD was independently associated with birth outside France (men: OR(a) = 13.9, 95% CI 3.7 to 52.8; women: OR(a) = 2.1, 95% CI 1.0 to 4.2), age more than 40 years (men: OR(a) = 4.3, 95% CI 1.01 to 18.2; women: OR(a) = 2.3, 95% CI 1.1 to 4.5), previous psychotropic treatment (men: OR(a) = 11.5, 95% CI 2.4 to 53.6), proximity to the explosion (less educated men only) (OR(a) = 9.3, 95% CI 1.9 to 44.7), rescue efforts (men: OR(a) = 5.2, 95% CI 1.5 to 18.2), temporarily uninhabitable home (men: OR(a) = 5.8, 95% CI 1.9 to 18.1), personal injury (women: OR(a) = 3.7, 95% CI 1.7 to 8.4), financial difficulties (men: OR(a) = 17.4, 95% CI 4.2 to 72.1; women: OR(a) = 3.4, 95% CI 1.7 to 7.1) and inconvenience due to closure of public services (women: OR(a) = 4.1, 95% CI 1.6 to 9.9). CONCLUSIONS: Individual vulnerability, exposure and post-trauma factors were associated with S-PTSD. Vulnerable subgroups, defined by low socioeconomic characteristics may warrant focused screening after such disasters.

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.

Standardization of antituberculosis drug resistance surveillance in Europe. Recommendations of a World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) Working Group.

Surveillance of antituberculosis drug resistance is an essential tool for evaluating the quality of tuberculosis control programmes. Consensus-based recommendations on uniform reporting of antituberculosis drug resistance surveillance data in Europe have been developed by a Working Group of the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD). Laboratories should use standardized methods for testing drug susceptibility with a quality assurance programme including national and international proficiency testing. The proportion of drug resistance, particularly resistance to isoniazid, rifampicin or both (multidrug resistance) among all definite, i.e. culture-positive, tuberculosis cases at the start of treatment is the major indicator of interest. It should be calculated separately among patients treated previously and among those who have never been treated with > or = 1 month of combined antituberculosis drugs. The Working Group recommends that, in countries in which resources allow, laboratories report drug susceptibility test results on all isolates of the Mycobacterium tuberculosis complex. Test results of the specimen at the start of treatment and clinical data from the notification should be linked using a suitable identifier. Results should be presented by calendar year and analysed by age, sex, place of birth, site of disease and sputum smear results. In countries in which a routine system cannot be organized, representative surveys or sentinel systems are possible alternatives. In some countries, the annual prevalence of multidrug-resistant tuberculosis may be estimated through a national laboratory reporting system.

[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.

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

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

Surveillance of tuberculosis in Europe.

In 1995, countries of the WHO European Region approved WHO/IUATLD recommendations for the standardisation of tuberculosis in Europe including a common case definition, the notification of cases by both clinicians and laboratories, the computerisation of individual data and a common list of essential variables. Since 1996, the Euro TB programme started collecting data from European countries based on these recommendations. Data on tuberculosis cases, both definite (culture confirmed) and other cases, reported in 1995, 1996 and 1997 have been collected in the 51 countries of the WHO European Region. Close to 350,000 tuberculosis cases were reported each year, of which almost 2/3 were in countries of the former USSR. Most countries located in the eastern part of Europe, Portugal and Spain, reported 20 cases per 100,000 or over. Conversely, most countries situated in the western part of Europe, the Czech Republic and Israel, reported cases per 100,000. Notification rates were highest above 64 years of age in countries reporting cases per 100,000 and peaked in the 35-54 years old age group in other countries. Since 1995, notification rate declined or stabilised in most countries with cases per 100,000, but increased in several other countries, particularly in most republics of ex USSR. Tuberculosis surveillance systems are still heterogeneous among European countries. Regarding the case definition, a few countries notify only new cases, some countries notify only new and relapse cases and some also include other categories of recurrent cases in the notification. Only a few countries have a national reporting system of M. tuberculosis isolated which can be linked to clinical data. In 1997, 20 of the 51 countries had individual computerised data. The availability of essential variables differs between countries but is increasing over time. The standardisation and quality of epidemiological information on tuberculosis in Europe has clearly improved since the beginning of the Euro TB programme. It is hoped that this will help tuberculosis control efforts in the European Region.