Clinical Advancement

A key strength of the RCDD stems from the expertise that it possesses along the entire translational research continuum from discovery to development through to implementation and policy.  This transdisciplinary research environment is unique in an academic setting and is critical towards the successful generation of new drugs and diagnostics that have an impact on target patient populations.

Current activities in infection therapeutics include those of the Malaria in Pregnancy (MiP) Consortium, led by Prof Feiko ter Kuile which has conducted major trials of the prevention of malaria in pregnant women and children and safety of antimalarials in first trimester pregnancy.  Malaria in pregnancy clinical trials expanded with EDCTP and MRC/DFID/WT Joint Global Health Trials grants to evaluate the safety and efficacy of intermittent preventive treatment with dihydroartemisinin-piperaquine in Kenya, Tanzania, and Malawi, as an alternative to the current policy which is under increasing threat due to drug resistance.  MiP is also nearing the completion of a large 3-year trial of preventive treatment in pregnant women in Indonesia with nested studies on acceptability, feasibility and cost effectiveness. In addition, the MiP Consortium secretariat initiated a new collaboration with the Oxford-led Worldwide Antimalarial Resistance Network (WWARN) to develop a module on malaria in pregnancy and to support the curation of clinical data from across all known trials and studies to enable pooled analyses to create an evidence base for policy. WHO and its Evidence Review Group (ERG) on malaria in pregnancy recommended to review its malaria policy for treatment of pregnant women as a result of a meta-analysis on the safety of artemisinins in the first trimester of pregnancy.

Professor David Lalloo is presently conducting major trials of treatment strategies for cryptococcal meningitis,  assessing safety of antimalarials in real-life deployment and is involved in the development/evaluation of new snakebite diagnostics and treatments (with Dr Rob Harrison).

Professor Shabbar Jaffar is conducting trials for the treatment of cryptococcal meningitis, pre-emptive treatment of HIV-infected cryptococcal antigen (CrAg) positives to prevent development of meningitis, a trial of scale up of CrAg screening and trials of models of HIV care/treatment.   Professor Bertie Squire is currently involved in Health economic evaluation of the STREAM trial of shortened regimens for the management of MDR-TB.

RCDD is also involved in clinical studies to evaluate new diagnostics for TB in Nigeria, Ethiopia and Moldova (led by Professor Luis Cuevas) and to develop health system approaches that facilitate population access to diagnostics and treatment. These studies led to the up-scale of approaches to reach communities in rural Ethiopia and urban slums of Nigeria. The EU funded IMPACT TB led by Dr Maxine Caws will aim to increase case finding in Vietnam and Nepal. IMPACT TB will assess the potential long-term effects of sustained active case-finding on the TB epidemic and document barriers to access diagnostics and health system costs using different service provision models. Professor Bertie Squire is leading an Operational modeling study to inform scale up and deployment of TB diagnostics for MDR-TB in The Philippines (MRC Newton Fund). 

The Evidence Synthesis for Global Health Group Cochrane editorial base expanded its scope to include HIV/AIDS. HIV/AIDS synthesis asks different questions to standard trial effectiveness research, requires a greater range of methods, including systems, observational and qualitative data and needs to be nimble. Professor Paul Garner was the methodologist on the WHO HIV/AIDS Operational Guidelines Group and the group contributed substantively to the production of the India National Guidelines for Extra-pulmonary TB released 2016.

Dr Miriam Taegtmeyer co-ordinates the Qualitative Research Network of the UNITAID/ Population Services International (PSI) HIV Self-Testing Africa (STAR) Project.  Activities include clinical trials on scale up of oral fluid tests for HIV self testing in Africa, a clinical performance study of Oraquick in Zambia and laboratory work on visual stability of HIV self test diagnostics for use in EQA systems. 

Typhoid fever is a re-emerging problem in sub-Saharan Africa and a persistent problem in Asia. Whilst there is considerable optimism about the role that conjugate vaccines will play in the future of typhoid control, it is likely that we will need a combination of vaccination and Water, Sanitation and Hygiene (WASH). With funding from the Bill and Melinda Gates Foundation, Dr Nick Feasey and collaborators will support the control of typhoid fever by vaccination through identifying the environmental reservoirs of Salmonella Typhi associated with human infection to target interventions to interrupt transmission. The identification of S. Typhi from food, water and the environment has previously been challenging, but a number of novel or repurposed methods should change this and the group will develop methods to identify environmental reservoirs of S. Typhi and use these findings to inform targeted interventions through spatial modeling.

The Respiratory Infection group completed a large vaccine trial for the experimental human pneumococcal carriage and continues recruiting volunteers (led by Dr Daniela Ferreira and Professor Stephen Gordon).   Further intervention trials have included The Cooking and Pneumonia (CAPS) trial (led by Dr Kevin Mortimer), which completed a large randomised trial of 150 villages in Malawi. Households with a child up to the age of 4.5 years received fan-assisted stoves to replace traditional cooking methods (mainly open fires) to test whether reducing exposure to biomass in the household reduces the incidence of pneumonia in children.  The trial was published in the Lancet in 2016.