Background

Brain infections are common in low- and middle-income countries and are often fatal. Doctors are currently hamstrung by inadequate laboratory tests, especially in poorer parts of the world, and often don’t know what caused the infection and can’t give effective treatment. The situation is exacerbated by the emergence of new, previously unrecognized infections and infections resistant to antibiotics.

Better tests, which quickly tell doctors the cause of the infection and which antibiotics can treat it, will help patients with brain infections worldwide.

Aims

Central nervous system (CNS) infections are devastating conditions, especially in low and middle-income counties (LMIC). Clinical outcomes depend upon the rapid identification of the causative agent and instituting effective antimicrobial therapy, although the causative agent is only identified in <50% of patients. Furthermore, Southeast Asia is highly susceptible to the emergence of novel and drug-resistant pathogens. New diagnostic techniques are urgently required to respond rapidly to future outbreaks and improve patient outcomes.

This study will focus on the translational potential of mass spectrometry and next-generation sequencing (NGS) in clinical diagnostics of CNS infections in Viet Nam, and has three key goals:

1. To determine whether mass spectrometry of cerebrospinal fluid (CSF) will identify protein/peptide signatures associated with different infectious aetiologies;
2. To determine whether NGS-based metagenomic analysis will identify a broad range of known/unknown pathogens in the CSF and improve current standard laboratory assays.
3. To determine whether NGS can provide rapid, whole genome sequence-based prediction of antimicrobial susceptibility for Mycobacterium tuberculosis and Streptococcus pneumoniae.

The study aims to provide proof of principle that CSF proteomics- and NGS-based methods can improve upon the diagnostic assays currently available in hospital settings, especially in LMIC, and thereby potentially improve patient outcomes.

Approach

The study will recruit 750 patients with brain infections over three years at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. An analysis of the brain fluids from these patients will:

1. Discover whether the proteins in the fluid can tell us what is causing the infection;
2. Determine if finding the complete genetic code of the bug causing the infection is better than current conventional tests;
3. Determine if the genetic code can rapidly predict antibiotic resistance and guide effective treatment.