Development of a TB vaccine trial site in Africa and lessons from the Ebola experience.

Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.

Optimizing the efficiency of tuberculosis active case-finding in health facilities and communities.

SETTING: Efficient tuberculosis (TB) active case-finding strategies are important in settings with high TB burdens and limited resources, such as those in western Kenya.OBJECTIVE: To guide efforts to optimize screening efficiency, we identified the predictors of TB among people screened in health facilities and communities.DESIGN: During February 2015-June 2016, adults aged ≥15 years reporting any TB symptom were identified in health facilities and community mobile screening units, and evaluated for TB. We assessed the predictors of TB using a modified Poisson regression with generalized estimating equations to account for clustering according to screening site.RESULTS: TB was diagnosed in 484 (20.3%) of 2394 symptomatic adults in health facilities and 39 (3.4%) of 1424 in communities. In health facilities, >10% of symptomatic adults in all demographic groups had TB, and no predictors were associated with a ≥2-fold increased risk. In communities, the independent predictors of TB were male sex (adjusted prevalence ratio [aPR] = 4.26, 95%CI 2.43-7.45), HIV infection (aPR 2.37, 95%CI 1.18-4.77), and household TB contact in the last 2 years (aPR 2.84, 95%CI 1.62-4.96).CONCLUSION: Our findings support the notion of general TB screening in health facilities and evaluation of the adult household contacts of TB patients.

Lessons learned from community-based tuberculosis case-finding in western Kenya.

SETTING: Although Kenya has a high burden of tuberculosis (TB), only 46% of cases were diagnosed in 2016. OBJECTIVE: To identify strategies for increasing attendance at community-based mobile screening units. DESIGN: We analysed operational data from a cluster-randomised trial, which included community-based mobile screening implemented during February 2015-April 2016. Community health volunteers (CHVs) recruited individuals with symptoms from the community, who were offered testing for human immunodeficiency virus (HIV) and sputum collection for Xpert® MTB/RIF testing. We compared attendance across different mobile unit sites using Wilcoxon rank-sum test. RESULTS: A total of 1424 adults with symptoms were screened at 25 mobile unit sites. The median total attendance among sites was 54 (range 6-134, interquartile range [IQR] 24-84). The median yields of TB diagnoses and new HIV diagnoses were respectively 2.4% (range 0.0-16.7, IQR 0.0-5.3) and 2.5% (range 0.0-33.3, IQR 1.2-4.2). Attendance at urban sites was variable; attendance at rural sites where CHVs were paid a daily minimum wage was significantly higher than at rural sites where CHVs were paid a nominal monthly stipend (P < 0.001). CONCLUSION: Mobile units were most effective and efficient when implemented as a single event with community health workers who are paid a daily wage.

Pilot implementation of a contact tracing intervention for tuberculosis case detection in Kisumu County, Kenya.

Leveraging an existing community health strategy, a contact tracing intervention was piloted under routine programmatic conditions at three facilities in Kisumu County, Kenya. Data collected during a 6-month period were compared to existing programmatic data. After implementation of the intervention, we found enhanced programmatic contact tracing practices, noting an increase in the proportions of index cases traced, symptomatic contacts referred, referred contacts presenting to a facility for tuberculosis screening, and eligible contacts started on isoniazid preventive therapy. As contact tracing is scaled up, health ministries should consider the adoption of similar contact tracing interventions to improve contact tracing practices.

En s'appuyant sur la stratégie de santé communautaire existante, une intervention de recherche des contacts a été pilotée dans des conditions de routine des programmes dans trois structures du comté de Kisumu, Kenya. Les données recueillies sur une période de 6 mois ont été comparées aux données de programme existantes. Après la mise en œuvre de l'intervention, nous avons trouvé des pratiques améliorées de recherche des contacts dans les programmes, notant une augmentation des proportions de recherche des cas index, de référence des contacts symptomatiques, de présentation des contacts référés vers une structure de dépistage de la tuberculose et de mise en route des contacts éligibles sous traitement préventif par isoniazide. A mesure que la recherche des contacts est accrue, les ministres de la santé devraient envisager l'adoption d'interventions similaires de recherche des contacts afin d'améliorer les pratiques de recherche des contacts.

A partir de una estrategia de salud comunitaria existente, se puso a prueba una intervención de investigación de contactos de los pacientes tuberculosos (TB) en las condiciones programáticas corrientes, en tres establecimientos del condado de Kisumu en Kenia. Los datos recogidos durante un período de 6 meses se compararon con los datos existentes del programa. Después de la ejecución de la intervención se observó una intensificación de las prácticas programáticas de seguimiento de los contactos, con un aumento de la proporción de casos iniciales localizados, la remisión de los contactos sintomáticos, la remisión de los contactos que acudían a un centro con el fin de practicar la detección de la TB y un aumento del número de pacientes idóneos que comenzaban el tratamiento preventivo con isoniazida. Al ampliar la escala del seguimiento de los contactos, los ministerios de salud deberían considerar la adopción de intervenciones de investigación de contactos semejantes a la que se ensayó en el presente estudio, con el fin de mejorar las prácticas de localización de contactos.