Effective early detection of tuberculosis in young children
The TB-Speed consortium, led by the University of Bordeaux, hypothesized that screening young children admitted for severe pneumonia for tuberculosis, followed by prompt treatment for those who screen positive, could reduce the lethality of severe tuberculosis-related pneumonia. These results have just been published in The Lancet Infectious Diseases international journal.
Tuberculosis affects one million children each year, of which less than half are diagnosed and treated, resulting in more than 200,000 deaths yearly.
In a new study, researchers and clinicians from the TB-Speed consortium led by the University of Bordeaux, in collaboration with the French National Research Institute for Sustainable Development (IRD) and MU-JHU (research collaboration between Makerere University and John Hopkins University in Uganda), have shown that admission screening for tuberculosis in children with severe pneumonia is feasible and could improve the diagnosis of tuberculosis in children in countries with a high incidence of the disease.
Although this screening did not reduce all-cause mortality at 12 weeks of follow-up compared to the standard of care, it increased the number of children diagnosed with tuberculosis, in particular those with microbiological confirmation, and reduced the delay for the initiation of treatment.
In addition, lethality and tuberculosis detection rates were four to five times higher in the subgroup of children with severe acute malnutrition compared to other children.
The study also showed that collecting and testing nasopharyngeal and stool samples with a rapid molecular diagnostic test (Xpert MTB/RIF Ultra) was feasible in very vulnerable children and was well tolerated. The results of the study plead in favor of a more systematic use of this test for these children, especially those suffering from severe acute malnutrition, and confirm the importance of tuberculosis as a cause of severe pneumonia in children. These results were published in The Lancet Infectious Diseases international journal.
The TB-Speed project
TB-Speed is a research program funded by Unitaid and L’Initiative, aimed at reducing infant mortality from tuberculosis (TB) by developing, testing and delivering an innovative, decentralized, cost-effective and feasible childhood tuberculosis diagnostic strategy to increase case detection in children.
This research project is implemented in seven countries in sub-Saharan Africa and Southeast Asia. It includes several studies testing different diagnostic approaches in specific pediatric populations at risk of tuberculosis or in specific contexts.
TB-Speed team in Mozambique to test for tuberculosis © TB-Speed
The context of the study
In countries with a high incidence of tuberculosis, the disease can be a cause of severe pneumonia in children and contribute to infantile mortality in the youngest of them. Usually, the diagnosis of tuberculosis is considered only in children with prolonged symptoms, in those who have failed one or more antibiotic treatments for community-acquired pneumonia, or in those with a history of contact with a sick person. Thus, many cases of tuberculosis are not identified or are diagnosed late, increasing the risk of poor evolution and death. Children with tuberculosis-related pneumonia very often have acute symptoms and are not considered presumptive cases of tuberculosis. It is in this context that the TB-Speed consortium hypothesized that early detection could reduce the lethality of severe tuberculosis-related pneumonia.
TB-Speed Pneumonia is a large-scale, international trial to evaluate the effect of molecular tuberculosis testing in addition to standard World Health Organization (WHO) treatment in children admitted for severe pneumonia. The study, funded by Unitaid and l’Initiative, led by the University of Bordeaux and promoted by Inserm, was conducted in 16 tertiary hospitals in six countries with a high incidence of tuberculosis (Côte d’Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia). It evaluated the impact on severe pneumonia mortality of systematic molecular detection of tuberculosis using the Xpert MTB/ RIF Ultra (ultra) rapid molecular diagnostic test performed on a nasopharyngeal aspiration sample and a stool sample added to the WHO recommended standard of care for severe pneumonia, which includes broad-spectrum antibiotic treatment, oxygen if indicated and treatment of co-morbidities such as HIV infection and severe malnutrition. A total of 2,570 children were enrolled in the study between March 2019 and March 2021.
Impact of systematic tuberculosis detection on mortality in young children with severe pneumonia in high tuberculosis incidence countries – a stepped wedge cluster randomized trial (2022). Olivier Marcy and al. The Lancet of infectious diseases.