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.

Singh, Bhagteshwar, Lipunga, Gareth D, Thangavelu, Premkumar, Dhar, Shalley, Ferreira Cronemberger, Lorena, Abhilash, Kundavaram Paul Prabhakar, Abraham, Asha Mary, de Brito, Carlos Alexandre Antunes, Brito Ferreira, Maria Lúcia, Chandrashekar, Nagarathna, Duarte, Rui, Fajardo Modol, Anna, Ghale, Ben Chirag, Kang, Gagandeep, Gowda, Vykuntaraju K, Kuriakose, Kevin, Lant, Suzannah, Mallewa, Macpherson, Mbale, Emmie, Moore, Shona C, Mwangalika, Gloria, Kamath, Prasanna B T, Navvuga, Patricia, Nyondo-Mipando, Alinane Linda, Phiri, Tamara J, Pimentel Lopes de Melo, Camila, Pradeep, B S, Rawlinson, Rebecca, Sheha, Irene, Thomas, Priya Treesa, Newton, Charles R, de Sequeira, Patricia Carvalho, Sejvar, James J, Dua, Tarun, Turtle, Lance, Verghese, Valsan Philip, Arraes, Luciano Wagner de Melo Santiago, Desmond, Nicola ORCID: https://orcid.org/0000-0002-2874-8569, Easton, Ava, Jones, Jessica, Lilford, Richard J, Netravathi, M, McGill, Fiona, Michael, Benedict D, Mwapasa, Victor, Griffiths, Michael J, Parry, Christopher, Ravi, Vasanthapuram, Burnside, Girvan, Cornick, Jennifer, França, Rafael Freitas de Oliveira, Desai, Anita S, Rupali, Priscilla and Solomon, Tom (2025) '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.'. The Lancet, Vol 405, Issue 10483, pp. 991-1003.

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Abstract

Background
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.

Methods
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.

Findings
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.

Interpretation
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.

Item Type:	Article
Corporate Authors:	Brain Infections Global Intervention Study Group
Subjects:	WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 245 Meningococcal infections WL Nervous System > WL 200 Meninges. Blood-brain barrier
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):	https://doi.org/10.1016/S0140-6736(25)00263-6
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	11 Apr 2025 09:29
Last Modified:	11 Apr 2025 09:29
URI:	https://archive.lstmed.ac.uk/id/eprint/26456

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