2025-26 Project (Harrison & Molloy & Jarvis)

The epidemiology and dynamics of antifungal resistant Candida acquisition and transmission within ICU settings in high burden Southern African countries

SUPERVISORY TEAM

Supervisor

Professor Tom Harrison at City St George’s
Email: tharriso@sgul.ac.uk

Co-Supervisor

Dr Síle Molloy at City St George’s
Email: smolloy@sgul.ac.uk

Co-Supervisor

Professor Joe Jarvis at LSHTM
Email: joseph.jarvis@lshtm.ac.uk

PROJECT SUMMARY

Project Summary

Candida species make up 5 of the 11 WHO-listed high/critical priority fungal pathogens due to rising incidence, mortality and antifungal resistance. South Africa has the largest documented epidemic of antifungal-resistant Candida infections; around a third of bloodstream infections caused by C. auris. Neighbouring countries are probably similarly affected, although surveillance data is limited. Through the Fungal Surv project, Candida auris has been detected for the first time in Botswana and Mozambique.   This project will use established datasets from around a thousand adults admitted to ICUs in South Africa and Mozambique, including Candida species distribution and phenotypic/genomic resistance profiles in invasive/commensal and environmental samples alongside antifungal consumption data. Advanced statistical and modelling techniques examine the dynamics of antifungal resistance colonisation, acquisition and transmission, in relation to antifungal exposure and preventative interventions. This unique dataset presents an opportunity to acquire a wide range of skills, whilst generating globally important AMR research.

Project Key Words

AMR (antimicrobial resistance), Candida, Candida auris

MRC LID Themes

  1. Infectious Disease
  2. Global Health
  3. Health Data Science
  4. Translational and Implementation Research

Skills

MRC Core Skills

  1. Quantitative skills
  2. Interdisciplinary skills
  3. Whole organism physiology

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

– Research protocol development 
– Statistical analysis planning 
– Dataset management 
– Multidisciplinary team-work 
– Epidemiology and statistical modelling 
– Genomic epidemiology 
– Scientific writing and presentation of research findings

Routes

Which route/s are available with this project?

  • 1+4 = Yes
  • +4 = Yes

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

  • City St George’s – MSc Genomic Medicine
  • 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

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution, meeting – at the minimum – the institutional research degree regulations and expectations. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training (for research degree study). Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Primary location for duration of this research degree: City St George’s, London

Travel requirements for this project: Visits to study and collaborating sites would be beneficial, including up to 3 months’ placement at the NICD which has a core sequencing facility.

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • Minimum City St George’s institutional eligibility criteria for doctoral study.
  • MSc or equivalent training in epidemiology

Other useful information

  • Potential Industrial CASE (iCASE) conversion? = No
  • Following upgrading, the project supervisory team will change (pending approval from City St George’s RD Committee). It is envisaged that at that time Dr Molloy will become Primary Supervisor, with the other two named supervisors as Co-Supervisors.

PROJECT IN MORE DETAIL

Scientific description of this research project

Antifungal resistant Candida infections are a rising global health threat, disproportionately affecting resource-limited settings. South Africa has the largest documented epidemic of antifungal-resistant Candida infections driven by WHO critical/ high priority pathogens Candida auris and Candida parapsilosis. Candida auris has recently been detected in Mozambique. This project aims to build understanding of drivers and potential solutions to this problem. 

1. Project objectives 
– To describe the epidemiology of Candida colonisation and invasive infection among adults admitted to ICUs in South Africa and Mozambique. 
– To describe antifungal medicine consumption within facilities 
– To examine the dynamics of Candida antifungal resistance acquisition, emergence and transmission in relation to antifungal exposure and environmental contamination.  
– To assess the impact of antifungal stewardship (AFS) and infection prevention and control (IPC) interventions on antifungal resistant Candida colonisation and infection.   

2. Techniques to be used 
Advanced statistical and mathematical modelling methods will be used to analyse epidemiological data from a large multicentre prospective cohort study among adults in ICUs across 6 hospitals in South Africa and Mozambique. During this study, data and samples will be collected from around 1000 participants, including comorbidities, antimicrobial prescriptions, incidence of invasive Candida infections and outcomes. Invasive and colonising isolates of Candida grown from serial swabs of commonly-colonised body will be analysed for species identity and phenotypic/ genotypic resistance profiles using minimum inhibitory concentrations (MIC) and whole genome sequencing. Point prevalence surveys of environmental contamination by Candida and antifungal consumption will also be performed within the participating ICUs and at facility level. During the cohort study, AFS and IPC practices will be audited alongside implementation of training, and the provision of AFS/IPC ‘champion’ pharmacist and nursing staff. 

The analysis of these large and unique datasets will build understanding of the drivers of particularly high rates of antifungal resistant Candida infections observed in these settings. 

3. Confirmed availability of any required databases or specialist materials 
The data will be available following the conduct of observational studies funded by:
1) the Wellcome Trust (‘COMBAT Candida’ 316549/Z/24/Z), and a GAMRIF FAILSAFE award (https://cmm-failsafe.com, University of Exeter) as part of a larger programme of work in South Africa and
2) by a CDC-funded surveillance project (‘Fungal Surv’) for the work in Mozambique.

The protocol for these studies are in development and will be submitted for approval by the relevant ethical committees and facility research committees. We expect that data collection will start in early 2025, with the majority of data available by the date of PhD commencement. 

4. Potential risks to the project and plans for their mitigation.
Since the studies are funded and planned with collaborators (Prof Nelesh Govender, Dr Rae Wake, Prof Tihana Bicanic) who have extensive experience in the delivery of clinical mycology research, including at the study sites, we are confident that the data for this PhD project will be available and of high quality. If there is any delayed or missing data, analysis could be augmented by a similar dataset from a prospective cohort study (‘CandiRes UK’: (https://www.isrctn.com/ISRCTN14165977), which is ongoing and has already recruited >300 adults from UK ICUs.

Further reading

Relevant preprints and/or open access articles:
(DOI = Digital Object Identifier)

Additional pre-application materials:

  • Allebone-Salt P, Davidson H, Wake R, Logan C, Caswall, B, Mazzella A, et al. Colonising Candida in the ICU: the impact of antifungal exposure on epidemiology and resistance. Poster presented at: ESCMID Global; 2024 Apr 27; Barcelona. Abstract P2811

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.

MRC LID LINKS

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