Tuberculosis: New treatments, new challenges

The fight against multidrug-resistant tuberculosis is gaining a new arsenal. But international migration - including the influx of refugees from Ukraine - poses new challenges.



In 2019, 1.4 million people died of TB. In 2015, it became the world's most deadly infectious disease, ahead of HIV, and is one of the top ten causes of death worldwide. Every year, around 10 million people develop an active form of TB. More than a third of these people are reportedly undiagnosed or untreated. 

Multidrug-resistant forms of tuberculosis (MDR-TB) are on the rise and account for up to 10% of cases in some countries. The treatments currently used, which are long, heavy and sometimes toxic for the patient, are a real challenge in terms of compliance. They are sometimes spread over two years, with the patient having to take up to 20 tablets a day. These treatments also rely on particularly painful injections. The side effects observed can be serious (deafness, psychosis).

A new treatment for multidrug-resistant tuberculosis

Bedaquiline and delamanid, registered by the European Medicines Agency in 2014, are the first anti-tuberculosis treatments to be developed in 50 years. The challenge was how to integrate them with existing MDR-TB treatments.

The endTB (Expand new drug markets for TB) consortium, which includes Médecins Sans Frontières (MSF), has been conducting a randomised controlled phase III trial since 2017. The aim is to find a short, effective and safe treatment for MDR-TB. Five new treatment regimens are being tested, combining bedaquiline and delamanid with other existing oral anti-TB drugs.

Final results will be known in 2023, but efficacy is estimated to be 85% in the first six months of treatment, compared to 56% for the standard protocol. Few side effects were observed. 

Another remarkable point is the study population. It included women, adolescents and people with comorbidities (HIV, hepatitis C, diabetes). Although often affected by tuberculosis, the latter rarely participate in such trials.

The situation in Ukraine

In 2018, Ukraine recorded 36,000 cases of TB, of which more than a third were MDR-TB. It is one of the 30 most affected countries in the world. As the prison population is particularly at risk, Médecins Sans Frontières has been carrying out activities to combat MDR-TB in detention centres in Mariupol and Bakhmut, as well as in the penitentiary colony of Dnipro since 2011.

A treatment programme has also been offered since 2018 in the hospital in Zhytomyr (north-western Ukraine). In addition to the new treatments tested in endTB, MSF offered therapeutic education sessions to improve adherence. In addition, the construction of a high-level biosafety laboratory was underway in the TB clinic. All these actions were suspended at the beginning of the Russian invasion.

The difficulty of monitoring refugees

The large number of Ukrainian refugees who are and will be received in European countries calls for increased vigilance on the part of European health professionals. In countries with a low incidence of tuberculosis, international migrants represent the most affected population (in 2016, 74% of cases in the UK and 90% in Sweden).

This is explained by the incidence in the countries of origin but also by the living conditions of migrants, during and after the journey. They increase the risk of infection (exposure to infected people, overcrowding in transit accommodation), delay diagnosis and may interrupt treatment previously started. Access to care in the host country is then hampered by language and cultural differences and the issue of financial support.

These particular conditions are all obstacles to the usual strategy for fighting tuberculosis, which is based on the rapid identification of contagious people in order to break the chain of transmission.



References:

- Expand new drug markets for TB (endTB)
- Evaluating Newly Approved Drugs for Multidrug-resistant TB (endTB)
- Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial
- MSF – «Tuberculose multirésistante : 750 patients recrutés à l’échelle mondiale pour un essai clinique inédit» Article from MSF, only available in French (translated title: "Multidrug-resistant tuberculosis: 750 patients recruited worldwide for a first-of-its-kind clinical trial")
- «Tuberculose et migrants» – La Lettre du Pneumologue (December 2018) Scientific paper, only available in French (translated title: "Tuberculosis and migrants")