A multifaceted intervention to improve diagnosis and early management of hospitalised patients with suspected acute brain infections in Brazil, India, and Malawi: an international multicentre intervention study.

Journal: Lancet (London, England)

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Affiliated Institutions:  Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; Tropical and Infectious Diseases Unit, Royal Liverpool University Hospital, Liverpool, UK; Christian Medical College, Vellore, Tamil Nadu, India; Liverpool School of Tropical Medicine, Liverpool, UK. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. Christian Medical College, Vellore, Tamil Nadu, India. National Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India. Department of Sociology, Federal University of Pernambuco, Recife, Brazil; Oswaldo Cruz Foundation Pernambuco, Recife, Brazil. Department of Clinical Medicine, Federal University of Pernambuco, Recife, Brazil; Hospital das Clinicas, Recife, Brazil; Autoimmune Research Institute, Recife, Brazil. Department of Neurology, Hospital da Restauração, Recife, Brazil. Institute of Population Health, University of Liverpool, Liverpool, UK. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK. Department of Neurology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; National Institute of Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK. Kamuzu University of Health Sciences, Blantyre, Malawi. Kamuzu University of Health Sciences, Blantyre, Malawi; Queen Elizabeth Central Hospital, Blantyre, Malawi. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; National Institute of Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; The Pandemic Institute, Liverpool, UK. Sri Devaraj Urs Academy of Higher Education and Research, Kolar, India; Sri Devaraj Urs Medical College, Kolar, India; R L Jalappa Hospital, Kolar, India. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Kamuzu University of Health Sciences, Blantyre, Malawi. Oswaldo Cruz Foundation Pernambuco, Recife, Brazil. Department of Psychiatry, University of Oxford, Oxford, UK; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya. Laboratory of Arboviruses and Haemorrhagic Viruses, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, US Centers for Disease Control and Prevention, Atlanta, GA, USA. Brain Health Unit, World Health Organization, Geneva, Switzerland. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; National Institute of Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Tropical and Infectious Diseases Unit, Royal Liverpool University Hospital, Liverpool, UK. Hospital Correia Picanço, Recife, Brazil. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, UK. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; Encephalitis International, Malton, UK. Liverpool School of Tropical Medicine, Liverpool, UK; Alder Hey Children's Hospital, Liverpool, UK; Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, Bangor, UK. University of Birmingham, Birmingham, UK. Leeds Teaching Hospitals NHS Trust, Leeds, UK. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; National Institute of Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; The Walton Centre NHS Foundation Trust, Liverpool, UK. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; National Institute of Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Centre for Child and Adolescent Health Research, University of Sydney, Sydney, NSW, Australia. Liverpool School of Tropical Medicine, Liverpool, UK. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; National Institute of Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; The Walton Centre NHS Foundation Trust, Liverpool, UK; The Pandemic Institute, Liverpool, UK. Electronic address: tsolomon@liverpool.ac.uk.

Abstract summary 

Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi.With hospital stakeholders, policy makers, and patient and public representatives, we co-designed a multifaceted clinical and laboratory intervention, informed by an evaluation of routine practice. The intervention, tailored for each setting, included a diagnostic and management algorithm, a lumbar puncture pack, a testing panel, and staff training. We used multivariable logistic regression and interrupted time series analysis to compare the coprimary outcomes-the percentage of patients achieving a syndromic diagnosis and the percentage achieving a microbiological diagnosis before and after the intervention. The study was registered at ClinicalTrials.gov (NCT04190303) and is complete.Between Jan 5, 2021, and Nov 30, 2022, we screened 10 462 patients and enrolled a total of 2233 patients at 13 hospital sites connected to the four study centres in Brazil, India, and Malawi. 1376 (62%) were recruited before the intervention and 857 (38%) were recruited after the intervention. 2154 patients (96%) had assessment of the primary outcome (1330 [62%] patients recruited pre-intervention and 824 [38%] recruited post-intervention). The median age across centres was 23 years (IQR 6-44), with 1276 (59%) being adults aged 16 years or older and 888 (41%) children aged between 29 days and 15 years; 1264 (59%) patients were male and 890 (41%) were female. Data on race and ethnicity were not recorded. 1020 (77%) of 1320 patients received a syndromic diagnosis before the intervention, rising to 701 (86%) of 813 after the intervention (adjusted odds ratio [aOR] 1·81 [95% CI 1·40-2·34]; p<0·0001). A microbiological diagnosis was made in 294 (22%) of 1330 patients pre-intervention, increasing to 250 (30%) of 824 patients post-intervention (aOR 1·46 [95% CI 1·18-1·79]; p=0·00040). Interrupted time series analysis confirmed that these increases exceeded a modest underlying trend of improvement over time. The percentage receiving a lumbar puncture, time to appropriate therapy, and functional outcome also improved.Diagnosis and management of patients with suspected acute brain infections improved following introduction of a simple intervention package across a diverse range of hospitals on three continents. The intervention is now being implemented in other settings as part of the WHO Meningitis Roadmap and encephalitis control initiatives.UK National Institute for Health and Care Research.

Authors & Co-authors:  Singh Bhagteshwar B Lipunga Gareth D GD Thangavelu Premkumar P Dhar Shalley S Ferreira Cronemberger Lorena L Abhilash Kundavaram Paul Prabhakar KPP Abraham Asha Mary AM de Brito Carlos Alexandre Antunes CAA Brito Ferreira Maria Lúcia ML Chandrashekar Nagarathna N Duarte Rui R Fajardo Modol Anna A Ghale Ben Chirag BC Kang Gagandeep G Gowda Vykuntaraju K VK Kuriakose Kevin K Lant Suzannah S Mallewa Macpherson M Mbale Emmie E Moore Shona C SC Mwangalika Gloria G Kamath Prasanna B T PBT Navvuga Patricia P Nyondo-Mipando Alinane Linda AL Phiri Tamara J TJ Pimentel Lopes de Melo Camila C Pradeep B S BS Rawlinson Rebecca R Sheha Irene I Thomas Priya Treesa PT Newton Charles R CR de Sequeira Patricia Carvalho PC Sejvar James J JJ Dua Tarun T Turtle Lance L Verghese Valsan Philip VP Arraes Luciano Wagner de Melo Santiago LWMS Desmond Nicola N Easton Ava A Jones Jessica Anne JA Lilford Richard J RJ Netravathi M M McGill Fiona F Michael Benedict D BD Mwapasa Victor V Griffiths Michael J MJ Parry Christopher M CM Ravi Vasanthapuram V Burnside Girvan G Cornick Jennifer J França Rafael Freitas de Oliveira RFO Desai Anita S AS Rupali Priscilla P Solomon Tom T

Study Outcome 

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Authors :  55
Identifiers
Doi : S0140-6736(25)00263-6
SSN : 1474-547X
Study Population
Male
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England