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

Completed

• Conditions: Meningitis; Abscess Brain; Encephalitis
• Interventions: Other: Pragmatic, multi-component package

• Registration Number: NCT04190303
• Lead Sponsor: University of Liverpool

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-01
• Study First Submitted QC: 2019-12-04
• Study First Posted: 2019-12-09
• Study Start: 2021-02-17
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2233

Inclusion Criteria

1. 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.
2. Symptom duration of less than 4 weeks.

Exclusion Criteria

1. Neonates, i.e. children under the age of 28 days.
2. 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).
3. People without an indwelling device, having undergone neurosurgical procedures within the preceding 12 months.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Post-intervention	Pragmatic, multi-component package	Care following development and delivery of the system-level intervention

Primary Outcome Measures

Name	Time	Method
Microbiological diagnosis	During hospital admission, or at 30 days if participant still in hospital	Proportion of patients achieving microbiological diagnosis
Syndromic diagnosis	During hospital admission, or at 30 days if participant still in hospital	Proportion of patients achieving syndromic diagnosis

Secondary Outcome Measures

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

Trial Locations

Locations (4)

National Institute of Mental Health and Neurosciences; 🇮🇳 Bangalore, India

Christian Medical College; 🇮🇳 Vellore, India

Malawi Liverpool Wellcome Trust; 🇲🇼 Blantyre, Malawi

FioCruz; 🇧🇷 Recife, Brazil