World TB Day: new collaborative projects to tackle tuberculosis

The research awards have been made possible by a new scheme that is funded by one of the oldest gifts we hold, the Dorothy Temple Cross Fund, which was originally set up by Florence Temple Cross in 1929 to support Fellows undertaking research or teaching in TB overseas. The new scheme was launched as the Dorothy Temple Cross International TB Collaboration Grant in September 2020 to support international collaborations between researchers in the UK and Africa.

TB meningitis (TMB) is one of the most severe forms of TB in children, occurring when the bacterial infection manifests in the central nervous system. Up to 50 per cent of children that develop the condition will lose their lives, and not all of those that survive respond well to treatment, with many children developing long-term neurological conditions. Despite this, current diagnostic tests only identify up to 60 per cent of TMB cases, missing many others and delaying treatment.

Dr Sabrina Bakeera-Kitaka from Makerere University in Uganda and Dr Robindra Basu Roy from the London School of Hygiene and Tropical Medicine (LSHTM) are evaluating whether new diagnostic tests can differentiate between samples from children with TMB, and samples from children with other similar illnesses at Mulago National Referral Hospital, Kampala, Uganda. This research will provide the foundations for larger studies to ensure that diagnostic tests do not miss cases of TMB in the future.

During treatment for TMB, increased pressure on the brain is relieved by draining excess fluid, which may contain molecules to help us understand the progression of the disease. Dr Tariq A. Ganief from the University of Cape Town and Dr Karl Burgess from the University of Edinburgh are investigating these molecules to try and guide diagnosis of TMB and develop effective treatment strategies.

Approximately one-quarter of the world's population has a TB infection, but the majority of people never develop disease as different immune cells control the infection. However, in some people, the infection becomes active, resulting in tuberculosis disease, lung damage, and spreading to new individuals. To help control TB and develop a vaccine, researchers need to be able to identify which people are at risk of disease development and identify the immune responses that are protective, in order to prevent disease progression.

Dr Fatoumatta Darboe from the Medical Research Council Unit, The Gambia at LSHTM and Dr Jackie Cliff from the LSHTM are collaborating on a research project investigating the role of certain immune cells known as ‘unconventional T cells’ in protecting the body against the progression of TB.

Dr Robert Krause from the African Health Research Institute, South Africa and Professor Paul Elkington from the University of Southampton, are looking at the effect of different types of immune cells on TB progression, known as ‘B cells’. Previous research has found that these ‘B cells’ stop bacterial growth in the lungs of people infected with TB, so this project will build on these findings to gain a deeper insight.

TB is treatable and curable, but treatment typically takes six months and involves four antimicrobial drugs. The effectiveness of these treatments is becoming compromised due to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of TB. Treatment options for people infected with resistant strains are severely limited, and there is a need to develop new drugs that are effective against these strains.

Dr Elizabeth V.M. Kigondu from the Kenya Medical Research Institute and Dr Paul Race from the University of Bristol are investigating new natural drug combinations for the treatment of drug-resistant TB. The researchers will investigate the potential of different drug combinations, including newly discovered natural product antibiotics with molecules that block common drug resistance mechanisms. It is hoped that this research will help to unlock new options for effective TB treatments in the future.

Dr Angela Hind, Chief Executive of the Medical Research Foundation, said: “We hope these new collaborative projects will not only help to increase our understanding of TB, but also act as a catalyst for new partnerships, future funding and ground-breaking research.

“Despite over 90 years passing since Dorothy Temple Cross died from TB and her mother set up a Fund in her memory, the need for ongoing research and investment in TB remains. While TB occurs all over the world, it is a particularly big problem in African countries, making international collaborations between researchers in Africa and those in the global north vital in battling this deadly infectious disease.”