Singh B
Lipunga GD
Thangavelu P
Dhar S
Ferreira Cronemberger L
Abhilash KPP
Abraham AM
de Brito CAA
Brito Ferreira ML
Chandrashekar N
Duarte R
Fajardo Modol A
Ghale BC
Kang G
Gowda VK
Kuriakose K
Lant S
Mallewa M
Mbale E
Moore SC
Mwangalika G
Kamath PBT
Navvuga P
Nyondo-Mipando AL
Phiri TJ
Pimentel Lopes de Melo C
Pradeep BS
Rawlinson R
Sheha I
Thomas PT
Newton CR
de Sequeira PC
Sejvar JJ
Dua T
Turtle L
Verghese VP
Arraes Lwms
Desmond N
Easton A
Jones JA
Lilford RJ
Netravathi M
McGill F
Michael BD
Mwapasa V
Griffiths MJ
Parry CM
Ravi V
Burnside G
Brain Infections Global Intervention Study Group
Cornick J
Franca RFO
Desai AS
Rupali P
Solomon T
Lancet. 2025;405991-1003
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. FUNDING: UK National Institute for Health and Care Research.
