Improving survival in HIV-infected adults at risk of cryptococcal meningitis

Investigating the causes of severe illness and death in HIV-infected cryptococcal positive patients

Dr Rachel Wake, Professor Tom Harrison, Dr Joseph Jarvis, Associate Professor Nelesh Govender
Start Date
01 Feb 2017
Diagnosis and treatment
St George's University of London, London, UK, National Institution for Communicable Diseases, Johannesburg, South Africa

What is this study about? 

Cryptococcal meningitis is a potentially fatal fungal infection and a leading cause of death in HIV-infected adults.

Current estimates suggest there are 214,000 cases of cryptococcal meningitis per year, with up to 70% of cases occurring in HIV prevalent areas of Sub-Saharan Africa.

Part of the cryptococcal fungus (called CrAg) can be detected in the blood of some HIV-infected patients even when there are no symptoms of cryptococcal meningitis.

These CrAg positive patients are more likely to die than CrAg negative patients, irrespective of whether they go on to develop meningitis or how advanced their HIV is.

The aim of this project is to investigate the causes of severe illness and death in HIV-infected CrAg positive patients.

The project is divided into two studies:

  • Study 1 will investigate the proportion of HIV-infected CrAg positive patients that have ‘subclinical’ cryptococcal meningitis; cryptococcal infection of the meninges which is not currently causing symptoms or signs. As part of this study, the team will evaluate the accuracy of using a newly developed test for diagnosing subclinical cryptococcal meningitis by measuring levels of CrAg in the patient’s blood. If this test works, it would be much quicker and cheaper than existing tests, and could be used to diagnose and treat cases early, before full blown disease develops
  • Study 2 will look at the causes of death in HIV-infected CrAg positive patients compared to HIV-infected CrAg negative patients. This will help doctors understand whether CrAg positive patients are more vulnerable to other infections, such as tuberculosis (TB), due to an underlying problem with their immune system. 

Potential outcomes

This research will answer fundamental questions about the increased risk of death in HIV-infected CrAg positive patients. Gaining a better understanding of the relationship between CrAg levels in the blood and subclinical cryptococcal meningitis could help doctors identify patients at risk of developing full blown disease and prescribe antifungal treatment at an earlier stage. Similarly, if CrAg positive patients are found to be more susceptible to other infections, such as TB, this could lead to extra screening, earlier treatment and/or the use of medications to stop such infections from developing. Ultimately, this research could increase the chances of survival of HIV-infected CrAg positive patients in the future.

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Liz Rodgers
Research Officer

Hi, I’m Liz and I’m MRF's Research Officer.

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