Theme 1: Current practice in diagnosis and management of patients with suspected brain infection. 

Key to understanding difficulties in the hospital management of patients with brain infections is an exploration of the attitudes of patients, families and health-care workers, and of the social and structural contexts shaping their behaviour. For example, in some cultures, patients may be thought “possessed by spirits”; and even a blood test can be considered as a loss of self, let alone a more invasive investigation, such as lumbar puncture (LP) – the critical investigation to examine the cerebrospinal fluid and identify the causative organism.

In addition to structural constraints with overburdened systems, health care workers may also have concerns around procedures to manage brain infections; for example, they may fear performing the LP, or lack the skills to perform it; laboratory staff may be unsure of the diagnostic approaches to use for different samples.

This theme built on previous and ongoing work on understanding structural and social barriers in pathways to care for brain infections, as well as previous ethnographic work on risk and response to severe illness [1]. We used interviews and focus groups to help us understand current beliefs, knowledge, attitudes and practice, and these guided training as well as development of the intervention. 

Theme 2: Improving diagnosis and early management through development of a compound intervention.

Based on our assessment of current practice in Theme 1, our aim was to work with service users and providers to develop a sustainable multi-component intervention, tailored to each hospital’s needs. The service improvement intervention would be designed to tackle challenges and barriers to optimal care, and would comprise a number of components, including a staged approach to improved diagnostics, clinical and laboratory training, access to equipment and consumables, clinical algorithms, and logistical improvements.

One challenge was the underuse of LP procedures to obtain cerebrospinal fluid, which is critical for confirming and identifying causes of brain infection. In the UK, we have shown that the introduction of a simple LP pack, containing appropriate equipment and guidance, greatly improved the uptake and performance of this investigation, e.g. increasing the percentage of patients with a PCR diagnosis from 17% to 50% [2]. We proposed to pilot its use in resource-limited settings within the intervention.

Theme 3: Strengthening diagnosis through pathogen discovery and host genomic approaches.

Newer diagnostic approaches, including those we have been developing in Liverpool, offer prospects for improving diagnostic yield. These include multiplex PCR of CSF for common pathogens, next-generation sequencing, and characterising host response genes through mRNA microarray [3,4,5]. This latter approach, for example our TRIM test (patent filed, in partnership with Fast Track Diagnostics) is proving especially useful distinguishing bacterial from viral infections, thus supporting appropriate use of antibiotics and helping to combat antimicrobial resistance. Automated molecular diagnostic approaches are reducing in price, and becoming especially suitable for settings where traditional microbiological skill sets are limited.

Theme 4: Policy, health economics and implementation

To ensure our work and its outcomes make a real difference, we worked closely with policymakers and our patient and public involvement (PPI) panel throughout the programme. This was vital to ensure the intervention was context-appropriate, feasible, and sustainable beyond the programme itself.

The intervention and diagnostics were subjected to a cost effectiveness evaluation to investigate their cost-benefit balance.

Theme 5: Training, capacity building and long-term sustainability

Training and capacity building was an integral part of the GHRG, to ensure long term sustainability. It included MRes places for both UK and overseas students, who joined the cohort supported through UoL’s extensive global health training programmes. We offered short course training, extending our annual Liverpool Neurological Infectious Diseases course, which has trained more than 500 doctors from the UK, Europe, Africa, Asia, and America, since 2007. We offered generic, and brain infections-specific online training through our partner, the Global Health Research Network. We extended the reach of our GHRG, developing a web-based Brain Infection Network and Registry, to allow other institutions to join the community and begin capturing information about patients in their settings.


1. Desmond NA, Nyirenda D, Dube Q, et al. Recognising and treatment seeking for acute bacterial meningitis in adults and children in resource-poor settings: a qualitative study. PLoS One 2013; 8: e68163.

2. Michael BD, Powell G, Curtis S, et al. Improving the diagnosis of central nervous system infections in adults through introduction of a simple lumbar puncture pack. Emerg Med J 2013; 30: 402-5.

3. Mallewa M, Vallely P, Faragher B, et al. Viral central nervous system infections in children from a malaria-endemic area of Malawi: a prospective cohort study Lancet Global Health 2013; 1:e153–e60.

4. Benjamin LA, Lewthwaite P, Vasanthapuram R, et al. Human parvovirus 4 as potential cause of encephalitis in children, India. Emerg Infect Dis 2011; 17: 1484-7.

5. Sweeney TE, Wong HR, Khatri P. Robust classification of bacterial and viral infections via integrated host gene expression diagnostics. Sci Transl Med 2016; 8: 346ra91.