Paediatric and adolescent infections

Infections are a very important reason why children get sick. In many parts of the world, large numbers of children still die from infectious diseases, like HIV, tuberculosis, malaria and blood infections. This programme of research uses different kinds of studies to answer questions about how we can best manage and treat infections in children and young people, both to reduce their chance of dying and being sick for longer, but also to increase their quality of life. This includes studies to work out what are the best drugs to use, thinking not just about controlling infections like HIV or curing infections like tuberculosis, but also what side-effects the drugs might have or how easy or hard families find it to take different numbers and types of pills every day. Other studies are working out what aspects of living with a long-term infection like HIV have the biggest impact on children and young people’s lives, including how they manage school and friends. The goal is to provide evidence so that national and international guidelines for managing children and young people with infections recommend the best options for them.

This integrated programme of complementary randomised trials, cohorts and pharmacovigilance studies aims to address questions about medicines and other interventions relevant to the most frequent and serious infectious diseases affecting children worldwide, in particular HIV, tuberculosis, malaria and sepsis. This is important because infectious diseases still dominate as causes of childhood mortality and morbidity and disproportionately affect children in sub-Saharan Africa. The programme has a large international component in Europe, North and South America, Thailand and Africa, and is at the forefront of both national and international research in paediatric infectious diseases.
The most appropriate research study designs are used for each specific question, not repeating all studies done in adults but using research in adults to identify where questions may be different or likely have different answers in children. Recognising the relative paucity of research in children, multiple complementary questions are addressed in factorial trials wherever possible to increase the evidence base for clinical management, and add value to the original investment in setting up and running the trial. Substudies investigating aspects such as pharmacokinetics, immunology, virology, and adherence are also included alongside trials wherever possible, as are additional analyses of trial data in an observational framework. High quality additional long-term data can also be collected in trial extensions by linking to cohorts. However, not all questions regarding the optimal management and treatment of HIV-infected children can be answered by randomised trials, because many cannot be framed as an implementable intervention. Data from cohort studies are used to answer these population-level questions of major relevance to children, adolescents and their families.
Our future plans are
• to continue to address clinically relevant questions in paediatric infectious diseases through appropriate research designs, and
• to ensure that results are incorporated into national and international management guidelines and policy, and then into clinical practice, including through additional operational research if relevant.
Several randomised trials in HIV and tuberculosis are funded and in advanced planning phases. Ongoing analyses within cohorts and cohort collaborations led by the group are addressing a wide range of contextual topics that can be generalised to the treatment and care of the wider population of HIV-infected children and young people. A large programme of pharmacovigilance studies continues to provide important long-term safety data to the European Medicines Agency on newly licensed antiretroviral drugs for children.