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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Encephalitis; Meningitis; Abscess Brain
• Intervention / Treatment: Other: Pragmatic, multi-component package

• Study Type: Observational
• Enrollment (Estimated): 2230

Contacts and Locations

• Study Contact: Name: Bhagteshwar Singh, MBChB; Phone Number: +441517957577; Email: bsingh@liverpool.ac.uk

Study Locations

• Brazil
  • Recife, Brazil
    • FIOCRUZ
• India
  • Bangalore, India
    • National Institute of Mental Health and Neurosciences
  • Vellore, India
    • Christian Medical College
• Malawi
  • Blantyre, Malawi
    • Malawi Liverpool Wellcome Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients presenting to a study hospital with symptoms and/or signs suggestive of an acute brain infection.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Liverpool
• Collaborators: Oswaldo Cruz Foundation; University of Warwick; National Institute for Health Research, United Kingdom; Liverpool School of Tropical Medicine; Kamuzu University of Health Sciences; Christian Medical College, Vellore, India; National Institute of Mental Health and Neuro Sciences, India; Malawi-Liverpool-Wellcome Trust Clinical Research Programme
• Investigators: Principal Investigator: Tom Solomon, PhD, Institute of Infection & Global Health, University of Liverpool

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2021
• Primary Completion (Actual): December 31, 2022
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 1, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 9, 2019

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases; Encephalitis; Meningitis
• Other Study ID Numbers: UoL001430 - 4069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No