Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Mar 22;405(10483):991-1003.
doi: 10.1016/S0140-6736(25)00263-6. Epub 2025 Mar 10.

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

Bhagteshwar Singh  1 , Gareth D Lipunga  2 , Premkumar Thangavelu  3 , Shalley Dhar  4 , Lorena Ferreira Cronemberger  5 , Kundavaram Paul Prabhakar Abhilash  3 , Asha Mary Abraham  3 , Carlos Alexandre Antunes de Brito  6 , Maria Lúcia Brito Ferreira  7 , Nagarathna Chandrashekar  4 , Rui Duarte  8 , Anna Fajardo Modol  9 , Ben Chirag Ghale  3 , Gagandeep Kang  3 , Vykuntaraju K Gowda  10 , Kevin Kuriakose  9 , Suzannah Lant  11 , Macpherson Mallewa  12 , Emmie Mbale  13 , Shona C Moore  14 , Gloria Mwangalika  2 , Prasanna B T Kamath  15 , Patricia Navvuga  9 , Alinane Linda Nyondo-Mipando  16 , Tamara J Phiri  13 , Camila Pimentel Lopes de Melo  17 , B S Pradeep  4 , Rebecca Rawlinson  11 , Irene Sheha  2 , Priya Treesa Thomas  4 , Charles R Newton  18 , Patricia Carvalho de Sequeira  19 , James J Sejvar  20 , Tarun Dua  21 , Lance Turtle  22 , Valsan Philip Verghese  3 , Luciano Wagner de Melo Santiago Arraes  23 , Nicola Desmond  24 , Ava Easton  25 , Jessica Anne Jones  26 , Richard J Lilford  27 , M Netravathi  4 , Fiona McGill  28 , Benedict D Michael  29 , Victor Mwapasa  12 , Michael J Griffiths  30 , Christopher M Parry  31 , Vasanthapuram Ravi  4 , Girvan Burnside  8 ; Brain Infections Global Intervention Study Group; Jennifer Cornick  63 , Rafael Freitas de Oliveira França  17 , Anita S Desai  4 , Priscilla Rupali  3 , Tom Solomon  64
Collaborators, Affiliations
Observational Study

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

Bhagteshwar Singh et al. Lancet. .

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.

Funding: UK National Institute for Health and Care Research.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests BS reports grant funding from the Medical Research Council ([MRC], grant MR/V033441/1), which also supported GDL, PT, CAAdB, GM, TJP, RR, IS, AE, VM, GB, JC, RFdOF, PR, and TS. LT reports grant funding from MRC, the UK Coronavirus Immunology Consortium, the UK National Institute for Health and Care Research (NIHR), the Wellcome Trust, the US Food and Drug Administration, and UK Department of Health and Social Care; consulting fees paid to his institution by the Medicines and Healthcare products Regulatory Agency (MHRA), AstraZeneca, and Synairgen; speaker fees paid to his institution by Eisai; and has a patent filed on a Zika vaccine (GB2318495·5). AE is the Chief Executive of Encephalitis International, reports royalties from her book Life After Encephalitis (Routledge Psychology Press, London, UK), and consults on infectious diseases for the Wellcome Trust. RJL reports grant funding from NIHR (Applied Research Collaboration West Midlands). BDM reports speaker fees from University of Massachusetts (Boston, MA, USA) and Beth Israel Deaconess Medical Center (Boston, MA, USA), and payment for medicolegal expert work. CMP reports grant funding from the Joint Global Health Trials Scheme (MR/TOO5033/1). TS reports grant funding from NIHR (IS-HPU-1112-10117); royalties from Oxford University Press, Elsevier, Liverpool University Press, and Cambridge University Press; consulting fees from GSK, Siemens, and the MHRA; and has a patent filed for a test for bacterial meningitis (GB1606537.7). JJS reports support for travel from WHO. MJG reports honoraria and support for conference attendance and speaker fees paid to his institution by Siemens Healthineers; a patent for a novel test for bacterial meningitis; grant income from an MRC DPFS research award; and collaboration with MedTechtoMarket as part of the MRC Developmental Pathway Funding Scheme award. All other authors declare no competing interests.

Figures

Figure 1
Figure 1. Study profile
*A further ten patients who were enrolled pre-intervention and 11 patients who were enrolled post-intervention had inadequate data for assessment of syndromic diagnosis, resulting in 1320 pre-intervention patients and 813 post-intervention patients being included in the analysis for that outcome.
Figure 2
Figure 2. Achievement of the co-primary outcomes of syndromic diagnosis and microbiological diagnosis
(A) Percentage of patients achieving a syndromic diagnosis, per month, pooled across all centres. (B) Percentage of patients achieving a microbiological diagnosis, per month, pooled across all centres. Dots represent percentages of patients achieving a diagnosis in each month of recruitment. The blue line represents the observed trend across these points. The shaded blue around this line represents the 95% CI around these percentages. The dashed red line represents the counterfactual situation: a predicted trend assuming no intervention was delivered, based on pre-intervention data. The shaded red around this line represents the 95% CI around these percentages. The vertical dashed black line represents the timepoint at which the intervention was implemented.
See this image and copyright information in PMC

Comment in

References

    1. Hay SI, Abajobir AA, Abate KH, et al. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1260–344. doi: 10.1016/S0140-6736(17)32130-X. - DOI - PMC - PubMed
    1. WHO. Why encephalitis matters? Report of the virtual meeting, 28–29 June 2022. 2023. [accessed June 14, 2024]. https://www.who.int/publications/i/item/9789240069176 .
    1. WHO. Defeating meningitis by 2030: a global road map. 2021. [accessed June 14, 2024]. https://www.who.int/publications/i/item/9789240026407 .
    1. Michael B, Menezes BF, Cunniffe J, et al. Effect of delayed lumbar punctures on the diagnosis of acute bacterial meningitis in adults. Emerg Med J. 2010;27:433–38. - PubMed
    1. Salazar L, Hasbun R. Cranial imaging before lumbar puncture in adults with community-acquired meningitis: clinical utility and adherence to the infectious diseases Society of America guidelines. Clin Infect Dis. 2017;64:1657–62. doi: 10.1093/cid/cix240. - DOI - PMC - PubMed

Publication types

Associated data