Rapid tests for fungal infection in critical care

  • Laura Loughlin

Student thesis: Doctoral ThesisDoctor of Medicine


Invasive fungal infection, comprising invasive Candida infection and invasive Aspergillus infection present a diagnostic challenge in the critical care setting due to the poor accuracy and slow turnaround time associated with culture-based tests. While invasive Candida infection is a well-described condition with known high morbidity and mortality, Aspergillus infection is under-recognised with an unknown burden in the intensive care unit (ICU) patient cohort. Despite differences in their levels of recognition by clinicians, the management of both conditions would benefit from accurate, non-culture based tests to enable rapid diagnosis.

The aim of this project was to describe the epidemiology of Candida and Aspergillus infection in critically ill patients. Following on from this, for Candida infection, the aim was to develop a protocol for a large-scale, prospective multicentre study of the accuracy of non-culture based tests and assess feasibility through a pilot study. For Aspergillus infection, the aim was to assess the accuracy of non-culture tests using data from United Kingdom (UK) ICU patients with suspected ventilator associated pneumonia (VAP).

For invasive Candida infection, local epidemiology suggested worrying trends in resistance, which reflect the global pattern and highlight the need for accurate diagnostic tests in ICU patients. The feasibility of a protocol for a UK wide study (The A-STOP study) to assess the accuracy of 1,3-β-D-glucan (BDG) and two polymerase chain reaction (PCR) based tests for Candida was demonstrated through a one-year pilot. Additionally, the barriers and facilitators to recruitment in the A-STOP study were explored. The key barriers were addressed in a protocol change, the impact of which was evaluated.

The UK wide prevalence of Aspergillus infection in patients with suspected VAP was 12.4%, which was higher than expected and highlighted the need for new, rapid testing methods. Assessment of diagnostic accuracy of serum BDG and Aspergillus PCR in bronchoalveolar lavage fluid (BALF) and serum, using a galactomannan-based definition as a reference standard, suggestedthat BDG had the greatest sensitivity of these tests and serum PCR had the greatest specificity. Given its sensitivity, BDG may have a role in identifying those patients who warrant further investigation and a combination of BDG plus serum PCR has favourable characteristics for confirmation of infection.
Date of AwardJul 2021
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SponsorsPfizer Ltd
SupervisorRonan McMullan (Supervisor) & Cecilia O'Kane (Supervisor)


  • Candida
  • Aspergillus
  • rapid diagnostics
  • critical care
  • Galactomannan
  • PCR
  • Beta D Glucan
  • prevalence

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