BIGlobal Intervention Study: Improving Diagnosis and Management of Suspected Brain Infections Globally

Study Overview
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Brief Summary
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Background: Patients with suspected brain infections pose major challenges to low and middle income countries, including their disproportionately high burden, diverse causes with inadequate surveillance, requirement for invasive and expensive tests, and the difficulty of management without a clear diagnosis. This is all compounded by resource and system constraints. Few studies have attempted to improve the care of these people in resource-limited settings. Aim: This study sets out to improve the diagnosis and early management of people with suspected acute (<28 days of symptoms) brain infections in low and middle income countries, using a coordinated thematic approach. Outcomes: The primary outcome will be proportion of people with suspected acute brain infection receiving a diagnosis. Secondary outcomes will include mortality, length of stay in hospital, quality of life, degree of disability, and proportion having a lumbar puncture test. Participants: Children and adults with features consistent with an acute brain infection, including meningitis and encephalitis, will be recruited at a variety of hospitals in Brazil, India and Malawi. Study procedures: An assessment of current practice and capabilities at each hospital, including patient and sample journey observations and interviews with healthcare staff, will identify barriers to optimal care. Using this, a sustainable pragmatic multi-component intervention will be produced, with components modifiable to each hospital's needs. Outcomes will be reassessed post-intervention.

Official Title
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NIHR Global Health Research Group on Brain Infections Study: Establishing a Standard Care Package to Improve Diagnosis and Early Hospital Management of Patients With Suspected Acute Brain Infections in Low and Middle Income Countries

Conditions
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Meningitis, Encephalitis, Abscess Brain

Intervention / Treatment
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* Other: Pragmatic, multi-component package


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults, infants and children presenting to a study hospital with symptoms and/or signs suggestive of acute brain infection, which could be suspected encephalitis, suspected meningitis, or alternative features raising suspicion of brain infection. Symptom duration of less than 4 weeks. Exclusion Criteria: Neonates, i.e. children under the age of 28 days. People with pre-existing indwelling ventricular devices (e.g. extra-ventricular drains, ventriculo-peritoneal shunts) or other implants in contact with the meninges or brain (e.g. deep brain stimulators). People without an indwelling device, having undergone neurosurgical procedures within the preceding 12 months.

Ages Eligible for Study
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Minimum Age: 4 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Baseline (pre-intervention)<br>Current routine care | |
| Post-intervention<br>Care following development and delivery of the system-level intervention | Other: Pragmatic, multi-component package<br>* This system-level intervention will be tailored to the needs and capacity of each hospital site, co-developed with policymakers and hospital staff<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological diagnosis | Proportion of patients achieving microbiological diagnosis | During hospital admission, or at 30 days if participant still in hospital | 
| Syndromic diagnosis | Proportion of patients achieving syndromic diagnosis | During hospital admission, or at 30 days if participant still in hospital | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion receiving, and time to lumbar puncture | Proportion of study participants receiving a lumbar puncture, and time to lumbar puncture | During hospital admission, or at 30 days if participant still in hospital | 
| Proportion having appropriate cerebrospinal fluid investigations | All of: cell count, total and differential; CSF protein concentration; CSF glucose concentration; paired serum/blood glucose concentration; microscopy and culture for bacteria | During hospital admission, or at 30 days if participant still in hospital | 
| Mortality | All-cause | At 30 days | 
| Length of stay in hospital | Duration of hospital admission | During hospital admission, or at 30 days if participant still in hospital | 
| Time to appropriate empirical therapy | Time to appropriate empirical anti-infective therapy | During hospital admission, or at 30 days if participant still in hospital | 
| Time to appropriate definitive therapy | Time to appropriate definitive anti-infective therapy | During hospital admission, or at 30 days if participant still in hospital | 
| Quality of life score | Using EuroQol EQ-5D questionnaires scoring 5 domains at levels 1-3 each, and an overall health state from 0 to 100. | At hospital discharge, or at 30 days if participant still in hospital | 
| Quality of life score | Using EuroQol EQ-5D questionnaires scoring 5 domains at levels 1-3 each, and an overall health state from 0 to 100. | At 30 days after presentation to hospital | 
| Liverpool Outcome Score | Score measuring neurological function after brain infection, reporting a lowest score of 15 domains between 2 and 5, and a total score with range 33-75. | At hospital discharge, or at 30 days if participant still in hospital | 
| Liverpool Outcome Score | Score measuring neurological function after brain infection, reporting a lowest score of 15 domains between 2 and 5, and a total score with range 33-75. | At 30 days after presentation to hospital |