APRECIT-BIS

Context

Tuberculosis (TB) is a respiratory disease caused by Mycobacterium tuberculosis (Mtb) bacteria. It is one of the main causes of death from an infectious disease worldwide and remains a major public health problem in Madagascar and Cameroon.

There are two main forms of TB:

• Tuberculosis infection (TBI) (formerly known as latent tuberculosis) is an asymptomatic or silent form of the disease. It is estimated that a quarter of the world’s population is infected. People with TBI are not contagious. TB preventive therapy (TBPT) may be offered to people with TBI.
• TB disease is the active, typically symptomatic and contagious form developing in 5 to 10% of persons with TBI. This is referred to as a progression from TBI to TB disease. A person with TB disease can infect between one and ten people they come into contact with, who will then become new cases of TBI. TB disease is curable through long-term antibiotic treatment (four to nine months), defined according to the antibiotic resistance profile of Mycobacterium tuberculosis.

To achieve the major objectives of the END TB strategy to eradicate TB by 2035, the World Health Organization (WHO) advocates the prevention, screening/diagnosis and treatment of both forms of tuberculosis: TBI and TB disease.

While finding and treating those with TB disease remains a priority for national programs for dealing with TB, finding and treating those with TBI presents a number of considerable obstacles in terms of organization, social and cultural issues, technology and logistics. The WHO guidelines for dealing with TBI recommend preventive treatment for all household contacts of a case of TB disease, and especially those who are aged under five or living with HIV (PLHIV). According to this strategy, only a minority of persons at risk of TB can benefit from this prevention measure.

The objective of the APRECIT-BIS project is to help national programs for dealing with TB to improve screening for TBI in populations at risk and to identify the people who may benefit from TBPT. To achieve this, three innovative TBI tests will be transferred and evaluated in Madagascar and Cameroon.

Funded by the ANRS-MIE (Emerging Infectious Diseases) agency, APRECIT-BIS includes a component to strengthen TB research capacity, led by a group of scientists from the Institut Pasteur in Madagascar, the Pasteur Center in Cameroon, the South African Tuberculosis Vaccine Initiative (University of Cape Town, South Africa), Hospices Civils de Lyon and the Mérieux Foundation.

Si identifier et traiter les personnes atteintes d’une TB maladie reste à ce jour la priorité des programmes nationaux de lutte contre la TB, identifier et traiter ceux atteints d’une ITB présente de nombreux obstacles organisationnels, socio-culturels, technologiques et logistiques. Sur le volet de l’ITB, l’OMS préconise un traitement préventif pour tous les contacts intradomiciliaires d’un cas de tuberculose maladie, en particulier ceux âgés de moins de 5 ans et les personnes vivant avec le VIH (PVVIH). Selon cette stratégie, seule une minorité de personnes à risque peuvent bénéficier de cette mesure de prévention.

L’objectif du projet APRECIT-BIS est de soutenir les PNLT (Programme National de Lutte contre la Tuberculose) à améliorer le dépistage de l’ITB chez les populations à risque, l’identification des personnes bénéficiaires du TPT. Pour cela, 3 tests innovants de l’ITB seront transférés et évalués à Madagascar et au Cameroun.

Financé par l’ANRS-MIE, APRECIT-BIS inclut un volet de renforcement des capacités en recherche sur la TB, animé par un groupe des scientifiques de l’Institut Pasteur de Madagascar, du Centre Pasteur du Cameroun, de la South-African Tuberculosis VaccineInitiative (Université de Cape Town, Afrique du Sud), des Hospices Civils de Lyon et de la Fondation Mérieux.

Objectives

The objectives of the APRECIT-BIS project are:

• To transfer and evaluate three innovative solutions for screening TB infection, which are also useful for identifying the beneficiaries of TB preventive treatment.
• To define a cost-effective screening strategy that is easy to operate in the field to support the national programs in dealing with TB.

In both Madagascar and Cameroon, many communities are vulnerable to TB. These include children under five and PLHIV living in the same household as a patient with TB disease who present an elevated risk of developing TB disease.

To address the TB problem at its source and limit the spread of the disease on a broad scale, the WHO recommends that people at risk are identified and provided with education and support for the preventive treatment of TB. This requires the development of a community intervention model combining the identification of people at risk with cost-effective and easy-to-use technological innovations to improve the screening and treatment of TBI.

Activities

The Mérieux Foundation has been coordinating the APRECIT operational research project, funded by L’Initiative (Expertise France) and operated in partnership with the Institut Pasteur in Madagascar and the Pasteur Center in Cameroon, since 2020. This project aims to support national programs for dealing with TB in Madagascar and Cameroon as they define a cost-effective strategy for testing and treating TBI at community level. As part of this project, TB household contacts agreed to participate in a TBI screening campaign and to be monitored by medical staff over an 18-month period. In accordance with WHO guidelines, household contacts aged under five and PLHIV were offered TB preventive treatment. Study participants identified with TBI who progressed to TB disease during the monitoring period were also given treatment. Biobanks of biological samples from each participant in the study were established and maintained in the two countries.

In 2023, as part of the APRECIT-BIS project funded by the ANRS-MIE agency, these biological samples will be analyzed using three innovative approaches to TBI screening. While these three approaches are currently still in research and development, they all present interesting and promising characteristics for large-scale deployment in the field to help health authorities identify the beneficiaries of TB preventive therapy more effectively and more precisely.

The analyses and studies carried out aim to determine the analytical performance of these three blood tests (TASA, RISK6 and protein signature) in preventing the progression of TB infection to TB disease, as well as defining their cost-effectiveness ratio, benefits and limits for large-scale deployment in the field.

Les analyses et études menées visent à déterminer les performances analytiques de ces trois tests sanguins (TASA, RISK6 et signature protéique) pour identifier les principaux bénéficiaires du TPT afin de prévenir l’évolution d’une ITB vers une TB maladie, ainsi qu’à définir leurs rapport cout-efficacité, leur avantages et limites pour une implémentation à large échelle sur le terrain.