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
Authors: Bhagteshwar Singh, Gareth D Lipunga, Premkumar Thangavelu, Shalley Dhar, Lorena Ferreira Cronemberger, Kundavaram Paul Prabhakar Abhilash, Asha Mary Abraham, Carlos Alexandre Antunes de Brito, Maria Lúcia Brito Ferreira, Nagarathna Chandrashekar, Rui Duarte, Anna Fajardo Modol, Ben Chirag Ghale, Gagandeep Kang, Vykuntaraju K Gowda, Kevin Kuriakose, Suzannah Lant, Macpherson Mallewa, Emmie Mbale, Shona C Moore, Gloria Mwangalika, Prasanna B T Kamath, Patricia Navvuga, Alinane Linda Nyondo-Mipando, Tamara J Phiri, Camila Pimentel Lopes de Melo, B S Pradeep, Rebecca Rawlinson, Irene Sheha, Priya Treesa Thomas, Charles R Newton, Patricia Carvalho de Sequeira, James J Sejvar, Tarun Dua, Lance Turtle, Valsan Philip Verghese, Luciano Wagner de Melo Santiago Arraes, Nicola Desmond, Ava Easton, Jessica Anne Jones, Richard J Lilford, M Netravathi, Fiona McGill, Benedict D Michael, Victor Mwapasa, Michael J Griffiths, Christopher M Parry, Vasanthapuram Ravi, Girvan Burnside, Jennifer Cornick, Rafael Freitas de Oliveira França, Anita S Desai, Priscilla Rupali, Tom Solomon
Journal: The Lancet (2025)

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.