2024-25 Project (Warren-Gash & Mansfield)

How do infections affect trajectories of frailty across settings?



Professor Charlotte Warren-Gash at LSHTM
Email: charlotte.warren-gash1@lshtm.ac.uk


Dr Kathryn Mansfield at LSHTM
Email: kathryn.mansfield@lshtm.ac.uk


Project Summary

Frailty affects older populations worldwide and is associated with reduced quality of life, disability and mortality. Acute infections may lead to short-term complications in vulnerable groups. It is less clear whether and how infections influence longer-term trajectories of ageing including frailty development in different populations. This PhD project aims to use harmonised data from population-based longitudinal studies in the UK, US, Mexico and India to investigate associations between diagnosed infections and frailty trajectories across settings. Findings will be triangulated with linked electronic health record and biological data on serum antibodies to infection from UK Biobank. This is important to inform global strategies for frailty prevention.

Project Key Words

Frailty; Infections; Harmonised cohorts; Electronic health records

MRC LID Themes

  • Global Health = Yes
  • Health Data Science = Yes
  • Infectious Disease = No
  • Translational and Implementation Research = No


MRC Core Skills

  • Quantitative skills = Yes
  • Interdisciplinary skills = No
  • Whole organism physiology = No

Skills we expect a student to develop/acquire whilst pursuing this project

Systematic reviews and meta-analysis. Experience of cleaning, harmonising and analysing longitudinal survey data from across settings. In depth knowledge of frailty indices and phenotypes. Manipulation of large linked health datasets from UK Biobank. Conducting cohort studies using various multivariable regression techniques. Advanced skills in statistical packages such as Stata or R.


Which route/s is this project available for?

  • 1+4 = Yes
  • +4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

  • LSHTM – MSc Epidemiology
  • LSHTM – MSc Health Data Science
  • LSHTM – MSc Medical Statistics

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? Yes


Particular prior educational requirements for a student undertaking this project

  • LSHTM’s standard institutional eligibility criteria for doctoral study.
  • Applicants must hold, or expect to obtain before the start of the PhD, a relevant MSc (Epidemiology, Health Data Science or Medical Statistics) awarded with good grades, or have a combination of relevant qualifications and experience which demonstrates equivalent ability and attainment.  
  • This project can also be awarded as 1+4 (1-year MSc programme + 4-year PhD candidature). Through this route, a relevant BSc awarded with good grades is required.

Other useful information

  • Potential CASE conversion? = No


Scientific description of this research project

Frailty is an important condition characterised by reduced physiological reserve. Typically affecting older adults, it is associated with reduced quality of life, disability and mortality. The burden and severity of frailty varies across populations worldwide. While common, acute infections can be detrimental to short-term physical and cognitive function, it is unclear how infections influence frailty trajectories.

Understanding the relationship between infections and trends and trajectories of frailty in different groups will inform strategies for frailty prevention.   

Project objectives 
1. To conduct a systematic review of literature assessing any association between acute infections and development of frailty in older adults 
2. To investigate associations between diagnosed infections and frailty trajectories using harmonised data from population-based longitudinal studies in the UK, US, Mexico and India 
3. To investigate whether infectious burden measured by
a) linked electronic health record diagnoses,
b) serum antibodies to multiple pathogens is associated with frailty trajectories using UK Biobank data    

Techniques to be used 
A systematic review will first be carried out to assess and appraise existing evidence for any association between different infections and incident or worsening frailty in older adults worldwide.   

Informed by findings from the systematic review, the PhD student will design studies to investigate the association between recent diagnosed infections and frailty trajectories using a combination of harmonised longitudinal cohorts available through the Gateway to Global Aging platform. These will include datasets from the US Health and Retirement Study (HRS), the English Longitudinal Study on Ageing (ELSA), the Mexico Health and Aging Study (MHAS) and the Longitudinal study on Aging in India (LASI). Frailty will be measured using validated frailty indices based on a cumulative deficit model. Data will be analysed using linear mixed effect models and potentially meta-analysed across settings.    

Linked electronic health record and biological data from UK Biobank will be used to investigate the same association with specific infection phenotypes in a high income setting. Triangulation across datasets and populations will help to increase confidence in the findings. These will inform approaches to frailty prevention through tackling infections.   

Confirmed availability of any required databases or specialist materials 
Data from the harmonised longitudinal studies are available to download free of charge through the Gateway to Global Aging website after registration by the student and obtaining appropriate permissions. Detailed codebooks for each study are available to inform the analyses. The supervisory team has extensive experience of accessing and using UK Biobank data for research studies into infections and conditions of older age.    

Potential risks to the project and plans for their mitigation 
Data from UK Biobank on antibodies to infections for 60,000 participants are estimated to be available in 2025. Should this timeline be delayed, the student will be able to work with UK Biobank infection pilot data on around 10,000 participants, which is currently available

Further reading

(Relevant preprints and/or open access articles)

Additional information from the supervisory team

  • The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.
    Warren-Gash-Mansfield Recording


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