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.

Progress in global rollout of new multidrug-resistant tuberculosis treatments.

SETTING: The global multidrug-resistant tuberculosis (MDR-TB) epidemic has grown over the past decade and continues to be difficult to manage. In response, new drugs and treatment regimens have been recommended.OBJECTIVE: In 2017 and again in 2018, the International Union Against Tuberculosis and Lung Disease (The Union) drug-resistant (DR) TB Working Group collaborated with RESIST-TB to implement an internet survey to members of The Union around the world to assess access to these new treatment strategies.DESIGN: A nine-question survey was developed using SurveyMonkey®. The survey was open for participation to all members of The Union registered under the TB Section. Two reminders were sent during each survey. The responses were analyzed taking into account the WHO Region to which the respondent belonged.RESULTS: The 2018 survey showed a global increase in implementation of the shorter (9-month) MDR-TB regimen (from 33% to 56% of respondents, P < 0.001) and an increase in the use of bedaquiline and/or delamanid (from 25% to 41% of respondents, P < 0.001) compared to 2017. There were substantial variations in roll-out between WHO regions.CONCLUSION: These results demonstrate improvement in global implementation of the new treatment strategies over a 1-year period.

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.

Insights into drug-resistant tuberculosis treatment: results of The Union DR-TB Working Group Survey, 2017.

The past 4 years have seen the introduction of new regimens and new drugs to treat multidrug-resistant tuberculosis (MDR-TB). To identify implementation trends over time, the DR-TB Working Group of the International Union Against Tuberculosis and Lung Disease (The Union), in collaboration with RESIST-TB, launched an online survey to Union members around the world. Survey results showed substantial diversity in treatment roll-out: 36% of respondents stated that their country is using the 9-month regimen for MDR-TB treatment; 41% are using bedaquiline and delamanid, but not the 9-month regimen; 28% are using both; and 22% of respondents indicated that their country does not currently offer either of these treatment options. Survey respondents also identified specific challenges to the introduction of shorter MDR-TB regimens and new drugs, including access to rapid diagnosis of fluoroquinolone resistance and case management. The results of this survey are intended to help identify research and implementation gaps while highlighting the importance of global implementation of scalable regimens for the treatment of MDR-TB.

Les quatre dernières années ont vu l'introduction de nouveaux protocoles et de nouveaux médicaments dans le traitement de la tuberculose multirésistante (TB-MDR). Dans le but d'identifier les tendances de la mise en œuvre dans le temps, le groupe de travail sur la TB résistante de l'Union Internationale contre la tuberculose et les maladies respiratoires (L'Union), en collaboration avec RESIST-TB, a lancé une enquête en ligne auprès des membres de l'Union autour du monde. Les résultats de l'enquête ont montré une grande diversité dans le lancement du traitement : 36% des répondants ont affirmé que leur pays utilisait le protocole de 9 mois pour le traitement de la TB-MDR ; 41% utilisent la bédaquiline et le délamanide, mais pas le protocole de 9 mois ; 28% utilisent les deux ; et 22% des répondants ont indiqué que leur pays n'offrait actuellement aucune de ces options de traitement. Les répondants ont également identifié les défis spécifiques à l'introduction de protocoles plus courts et de nouveaux médicaments de TB-MDR, notamment l'accès à un diagnostic rapide de la résistance aux fluoroquinolones et la prise en charge des cas. Les résultats de cette enquête sont destinés à contribuer à identifier les lacunes en matière de recherche et de mise en œuvre, tout en mettant en lumière l'importance de la mise en œuvre mondiale de protocoles évolutifs pour le traitement de la TB-MDR.

En los últimos 4 años ha tenido lugar la introducción de nuevos esquemas terapéuticos y nuevos fármacos para el tratamiento de la tuberculosis multirresistente (TB-MDR). Con el propósito de evaluar las tendencias de su aplicación en el transcurso del tiempo, el grupo de trabajo sobre TB farmacorresistente de la Unión Internacional Contra la Tuberculosis y Enfermedades Respiratorias (La Unión), en colaboración con la iniciativa RESIST-TB, emprendió una encuesta en línea dirigida a los miembros de La Unión en todo el mundo. Los resultados pusieron de manifiesto una gran diversidad del despliegue del tratamiento. El 36% de quienes respondieron afirmaba que en su país se utiliza el esquema de 9 meses para el tratamiento de la TB-MDR; el 41% utiliza bedaquilina y delamanid, pero no el esquema de 9 meses; el 28% utilizan ambos; y el 22% de quienes respondieron indicaba que en su país no se ofrece en la actualidad ninguna de estas opciones terapéuticas. Las respuestas a la encuesta revelan también dificultades específicas con la introducción de los esquemas más cortos de tratamiento de la TB-MDR y con los nuevos medicamentos, entre ellas el acceso al diagnóstico rápido de la resistencia a las fluoroquinolonas y el manejo de los casos. Los resultados de esta encuesta tienen por finalidad contribuir a reconocer las lagunas en la investigación y en la ejecución y al mismo tiempo destacar la importancia de la introducción mundial de esquemas ampliables de tratamiento de la TB-MDR.

QTc and anti-tuberculosis drugs: a perfect storm or a tempest in a teacup? Review of evidence and a risk assessment.

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.