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The World Health Organization has developed target product profiles containing minimum and optimum targets for key characteristics for tests for tuberculosis treatment monitoring and optimization. Tuberculosis treatment optimization refers to initiating or switching to an effective tuberculosis treatment regimen that results in a high likelihood of a good treatment outcome. The target product profiles also cover tests of cure conducted at the end of treatment. The development of the target product profiles was informed by a stakeholder survey, a cost-effectiveness analysis and a patient-care pathway analysis. Additional feedback from stakeholders was obtained by means of a Delphi-like process, a technical consultation and a call for public comment on a draft document. A scientific development group agreed on the final targets in a consensus meeting. For characteristics rated of highest importance, the document lists: (i) high diagnostic accuracy (sensitivity and specificity); (ii) time to result of optimally [less than or equal to] 2 hours and no more than 1 day; (iii) required sample type to be minimally invasive, easily obtainable, such as urine, breath, or capillary blood, or a respiratory sample that goes beyond sputum; (iv) ideally the test could be placed at a peripheral-level health facility without a laboratory; and (v) the test should be affordable to low- and middle-income countries, and allow wide and equitable access and scale-up. Use of these target product profiles should facilitate the development of new tuberculosis treatment monitoring and optimization tests that are accurate and accessible for all people being treated for tuberculosis. L'Organisation mondiale de la sante a elabore des profils de produits cibles contenant des cibles minimales et optimales pour les caracteristiques principales des essais destines au suivi et a l'optimisation du traitement de la tuberculose. L'optimisation du traitement de la tuberculose fait reference a l'instauration d'un regime de traitement efficace de la tuberculose ou a l'adoption d'un tel regime, avec une probabilite elevee d'obtenir de bons resultats therapeutiques. Les profils de produits cibles couvrent egalement les essais de guerison effectues a l'issue du traitement. Les profils de produits cibles ont ete elabores sur la base d'un sondage aupres des parties prenantes, d'une analyse cout-efficacite et d'une analyse du parcours de soins du patient. Des retours supplementaires des parties prenantes ont ete obtenus au moyen d'un processus cree selon la methode Delphi, d'une consultation technique et d'un appel a commentaires publics sur un projet de document. Un groupe d'elaboration scientifique s'est mis d'accord sur les objectifs finaux lors d'une reunion de concertation. En ce qui concerne les caracteristiques jugees les plus importantes, le document enumere ce qui suit: (i) une grande precision diagnostique (sensibilite et specificite); (ii) un delai ideal d'obtention des resultats [less than or equal to] 2 heures et au maximum de 1 jour; (iii) le type d'echantillon requis doit etre peu invasif et facile a obtenir, comme l'urine, l'haleine ou le sang capillaire, ou bien un echantillon respiratoire au-dela des expectorations; (iv) idealement, l'essai pourrait avoir lieu dans un etablissement de sante peripherique sans laboratoire ; et (v) l'essai devrait etre abordable pour les pays a revenu faible et intermediaire et permettre un acces large et equitable ainsi qu'une mise a l'echelle. L'utilisation de ces profils de produits cibles devrait faciliter la mise au point de nouveaux essais de surveillance et d'optimisation du traitement de la tuberculose qui soient precis et accessibles a toutes les personnes suivant un traitement pour la tuberculose. La Organizacion Mundial de la Salud ha elaborado perfiles de productos objetivo que contienen objetivos minimos y optimos para las caracteristicas principales de las pruebas de seguimiento y optimizacion del tratamiento de la tuberculosis. La optimizacion del tratamiento de la tuberculosis consiste en iniciar o cambiar a un regimen eficaz de tratamiento de la tuberculosis que ofrezca una alta probabilidad de un buen resultado terapeutico. Los perfiles de productos objetivo tambien abarcan las pruebas de curacion realizadas al final del tratamiento. La elaboracion de los perfiles de los productos objetivo se baso en una encuesta a las partes interesadas, un analisis de rentabilidad y un analisis de la via de atencion al paciente. Se obtuvo informacion adicional de las partes interesadas mediante un proceso tipo Delphi, una consulta tecnica y una convocatoria de comentarios publicos sobre un borrador del documento. Un grupo de desarrollo cientifico acordo los objetivos finales en una reunion de consenso. Para las caracteristicas clasificadas de mayor importancia, el documento enumera: (i) alta precision diagnostica (sensibilidad y especificidad); (ii) tiempo hasta el resultado de optimamente [less than or equal to] 2 horas y no mas de 1 dia; (iii) el tipo de muestra requerida debe ser minimamente invasiva, facil de obtener, como orina, aliento o sangre capilar, o una muestra respiratoria que vaya mas alla del esputo; (iv) idealmente la prueba podria realizarse en un centro sanitario periferico sin laboratorio; y (v) la prueba debe ser asequible para los paises de ingresos bajos y medios y permitir un acceso amplio y equitativo y su expansion. El uso de estos perfiles de producto objetivo deberia facilitar el desarrollo de pruebas nuevas de seguimiento y optimizacion del tratamiento de la tuberculosis que sean precisas y accesibles para todas las personas que reciben tratamiento antituberculoso. [phrase omitted], Introduction Tuberculosis continues to be a major cause of morbidity and mortality globally, despite being curable and preventable. In 2021, an estimated 10.6 million people had tuberculosis disease and 1.6 [...]

Introduction: Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally. Discussion: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary. Conclusions: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potentia drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV. Keywords: TB; HIV care continuum; differentiated care; public health; co-infection; treatment, 1 INTRODUCTION Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). This population contributes substantially to the global TB burden, with a higher risk of [...]

Fewer than 20% of patients with multidrug-resistant (MDR) tuberculosis are receiving treatment and there is an urgent need to scale up treatment programmes. One of the biggest barriers to scale-up is the treatment regimen, which is lengthy, complex, ineffective, poorly tolerated and expensive. For the first time in over 50 years, new drugs have been developed specifically to treat tuberculosis, with bedaquiline and potentially delamanid expected to be available soon for treatment of MDR cases. However, if the new drugs are merely added to the current treatment regimen, the new regimen will be at least as lengthy, cumbersome and toxic as the existing one. There is an urgent need for strategy and evidence on how to maximize the potential of the new drugs to improve outcomes and shorten treatment. We devised eight key principles for designing future treatment regimens to ensure that, once they are proven safe in clinical trials, they will be clinically effective and programmatically practicable. Regimens should contain at least one new class of drug; be broadly applicable for use against MDR and extensively drug-resistant Mycobacterium tuberculosis complex strains; contain three to five effective drugs, each from a different drug class; be delivered orally; have a simple dosing schedule; have a good side-effect profile that allows limited monitoring; last a maximum of 6 months; and have minimal interaction with antiretrovirals. Following these principles will maximize the potential of new compounds and help to overcome the clinical and programmatic disadvantages and scale-up constraints that plague the current regimen.

Author(s): Grania Brigden 1,*, Nguyen Viet Nhung 2, Alena Skrahina 3, Norbert Ndjeka 4, Dennis Falzon 5, Matteo Zignol 5 Summary points The World Health Organization (WHO) plays an important [...]

Tuberculosis is a disease that needs more investment in research and development. More people--1.4 million in 2015--die from tuberculosis every year than from human immunodeficiency virus (1.1 million deaths; 400 [...]

Introduction: There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey. Methods: Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings. Results: Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR−TB patients were also top priorities in their respective categories. Results were internally consistent and robust. Discussion: Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data. Conclusion: There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB. [ABSTRACT FROM AUTHOR]

Simpler, shorter, safer and more effective treatments for tuberculosis that are easily accessible to all people with tuberculosis are desperately needed. In 2016, the World Health Organization (WHO) developed target regimen profiles for the treatment of tuberculosis to make drug developers aware of both the important features of treatment regimens, and patient and programmatic needs at the country level. In view of recent ground-breaking advances in tuberculosis treatment, WHO has revised and updated these regimen profiles. We used a similar process as for the 2016 profiles, including a baseline treatment landscape analysis, an initial stakeholder survey, modelling studies estimating the impact and cost-effectiveness of novel tuberculosis treatment regimens, and an extensive stakeholder consultation. We developed target regimen profiles for the treatment of rifampicin-susceptible and rifampicin-resistant tuberculosis, as well as a pantuberculosis regimen that would be appropriate for patients with any type of tuberculosis. We describe the revised target regimen profile characteristics, with specific minimal and optimal targets to be met, rationale and justification, and aspects relevant to all target regimen profiles (drug susceptibility testing, adherence and forgiveness, treatment strategies, post-tuberculosis lung disease, and cost and access considerations). We discuss the trade-offs of proposed characteristics for decision-making at developmental or operational levels. We expect that, following these target regimen profile revisions, tuberculosis treatment developers will produce regimens that are quality-assured, affordable and widely available, and that meet the needs of affected populations. [ABSTRACT FROM AUTHOR]