Leptospirosis is a zoonotic bacterial infection occurring worldwide caused by Leptospira interrogans. Although sporadically reported in high income countries, low-and-middle income countries bear a high burden of cases - particularly in the South East Asian, Pacific, and Central and South American geographical areas. More frequent climate catastrophes, poor infrastructure and social deprivation in these areas often precipitate outbreaks and epidemics.
The evidence for the management of leptospirosis in adults, particularly in severe disease, is limited by methodological inconsistency and a lack of established outcome measures. A 2012 Cochrane review of antimicrobial treatment included seven randomized trials spanning 1988-2007. The outcome measures used varied from mortality, length of hospital stay, urinary culture clearance, resolution of biochemical changes, and defervescence. Despite four trials including individuals with severe disease, no definitions of severity were provided. Duration of symptoms varied at presentation in each study. The review concluded there was insufficient evidence to advocate for, or against, the use of antimicrobials due to poor methodological quality or underpowered studies. Similarly, when considering immunosuppressive therapies for severe leptospirosis disease, the last systematic review conducted in 2014 concluded there was insufficient data to establish efficacy. Outcomes measures included death, duration of ventilation, and duration of bleeding.
The establishment of core outcome sets (COS) to define outcome measures is increasingly vital to improve relevance of clinical trials to health service users and policy makers.9 Standardization of measures would add consistency and lead to harmonization of leptospirosis therapeutic trials, thereby reducing waste in production and reporting of research. There are currently no established primary efficacy or safety outcomes for a definitive clinical trial of leptospirosis treatments, a significant contributing factor to current inconclusive systematic reviews regarding treatment and which represents a neglected research area.
Dr Nathaniel Lee (Principal Investigator) - London School of Hygiene & Tropical Medicine, School of Tropical Medicine and Global Health Nagasaki University
Dr Chris Smith (Supervisor) - London School of Hygiene & Tropical Medicine, School of Tropical Medicine and Global Health Nagasaki University
Professor Robin Bailey (Supervisor) - London School of Hygiene & Tropical Medicine
Professor Koya Ariyoshi (Supervisor) - School of Tropical Medicine and Global Health Nagasaki University
Dr Tansy Edwards (Lead Supervisor) - London School of Hygiene & Tropical Medicine
Disease Category: Infectious disease
Disease Name: Leptospirosis
Age Range: 16 - 99
Sex: Either
Nature of Intervention: Any
- Clinical experts
- Consumers (caregivers)
- Consumers (patients)
- Epidemiologists
- Governmental agencies
- Methodologists
- Policy makers
- Regulatory agency representatives
- Researchers
- Statisticians
- COS for clinical trials or clinical research
- COS for practice
- Consensus meeting
- Delphi process
- Focus group(s)
- Interview
- Literature review
- Nominal group technique (NGT)
- Semi structured discussion
- Survey
- Systematic review
The project will be carried out in three phases. Phase 1 will establish existing knowledge about outcomes, and consist of a systematic review of the literature from ongoing Cochrane Reviews to determine efficacy and safety outcomes reported to date, for evaluation of therapeutic interventions for Leptospirosis. An additional systematic search of non-randomised studies and grey literature will be conducted to identify other relevant data for inclusion. This will update current information for any existing knowledge gaps, and enable updating of global distribution of morbidity/mortality burden for Leptospirosis diseases which will allow the screening and identification of suitable proposed trial centres
Phase 2 will consist of exploring outcomes of interest with healthcare providers and end-users directly affected by Leptospirosis, to identify outcomes important to these groups, through the use of qualitative methods. This will, in addition, identify target population groups, explore acceptability of therapeutic interventions, and assess feasibility of conducting trial activities. Early identification and partnership with end-user groups will allow enhancement of Patient and Public Involvement activities throughout the COMET process as well as beyond into active clinial trial research periods.
Phase 3 will consist of employing the Delphi technique targeted at experts and other stakeholders through the use a questionnaire and consensus meetings. Outcomes and acceptability identified in Phase 1 and Phase 2 can be brought to a larger plenary at this point. Multiple panels formed of homogenous stakeholder groups will be used in order to harmonize opinions. We will include as many stakeholders as possible in a worldwide geographic spread across at least two rounds in order to deal with feedback