Evidence map›Paper›PMID 40081400›Full record

Observational studyLancet (London, England)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.

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 and 45 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
In one paragraph

Observational study in Lancet (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04190303 (NIHR Global Health Research Group on Brain Infections Study), which is not on this map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04190303 completednot on this map

NIHR Global Health Research Group on Brain Infections Study: Establishing a Standard Care Package to Improve Diagnosis and Early Hospital Management of Patients With Suspected Acute Brain Infections in Low and Middle Income Countries

TypeobservationalSponsorUniversity of LiverpoolRan2021 to 2022Enrolled2,233ConditionsMeningitis, Encephalitis, Abscess BrainArmsPragmatic, multi-component package
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Guideline
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

55 authors.

Bhagteshwar SinghInstitute 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.
Gareth D LipungaMalawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Premkumar ThangaveluChristian Medical College, Vellore, Tamil Nadu, India.
Shalley DharNational Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
Lorena Ferreira CronembergerDepartment of Sociology, Federal University of Pernambuco, Recife, Brazil; Oswaldo Cruz Foundation Pernambuco, Recife, Brazil.
Kundavaram Paul Prabhakar AbhilashChristian Medical College, Vellore, Tamil Nadu, India.
Asha Mary AbrahamChristian Medical College, Vellore, Tamil Nadu, India.
Carlos Alexandre Antunes de BritoDepartment of Clinical Medicine, Federal University of Pernambuco, Recife, Brazil; Hospital das Clinicas, Recife, Brazil; Autoimmune Research Institute, Recife, Brazil.
Maria Lúcia Brito FerreiraDepartment of Neurology, Hospital da Restauração, Recife, Brazil.
Nagarathna ChandrashekarNational Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
Rui DuarteInstitute of Population Health, University of Liverpool, Liverpool, UK.
Anna Fajardo ModolInstitute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK.
Ben Chirag GhaleChristian Medical College, Vellore, Tamil Nadu, India.
Gagandeep KangChristian Medical College, Vellore, Tamil Nadu, India.
Vykuntaraju K GowdaDepartment of Neurology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India.
Kevin KuriakoseInstitute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK.
Suzannah LantInstitute 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.
Macpherson MallewaKamuzu University of Health Sciences, Blantyre, Malawi.
Emmie MbaleKamuzu University of Health Sciences, Blantyre, Malawi; Queen Elizabeth Central Hospital, Blantyre, Malawi.
Shona C MooreInstitute 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.
Gloria MwangalikaMalawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Prasanna B T KamathSri Devaraj Urs Academy of Higher Education and Research, Kolar, India; Sri Devaraj Urs Medical College, Kolar, India; R L Jalappa Hospital, Kolar, India.
Patricia NavvugaInstitute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK.
Alinane Linda Nyondo-MipandoMalawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Kamuzu University of Health Sciences, Blantyre, Malawi.
Tamara J PhiriKamuzu University of Health Sciences, Blantyre, Malawi; Queen Elizabeth Central Hospital, Blantyre, Malawi.
Camila Pimentel Lopes de MeloOswaldo Cruz Foundation Pernambuco, Recife, Brazil.
B S PradeepNational Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
Rebecca RawlinsonInstitute 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.
Irene ShehaMalawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Priya Treesa ThomasNational Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
Charles R NewtonDepartment of Psychiatry, University of Oxford, Oxford, UK; KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
Patricia Carvalho de SequeiraLaboratory of Arboviruses and Haemorrhagic Viruses, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
James J SejvarDivision of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, US Centers for Disease Control and Prevention, Atlanta, GA, USA.
Tarun DuaBrain Health Unit, World Health Organization, Geneva, Switzerland.
Lance TurtleInstitute 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.
Valsan Philip VergheseChristian Medical College, Vellore, Tamil Nadu, India.
Luciano Wagner de Melo Santiago ArraesHospital Correia Picanço, Recife, Brazil.
Nicola DesmondMalawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, UK.
Ava EastonInstitute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; Encephalitis International, Malton, UK.
Jessica Anne JonesLiverpool School of Tropical Medicine, Liverpool, UK; Alder Hey Children's Hospital, Liverpool, UK; Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, Bangor, UK.
Richard J LilfordUniversity of Birmingham, Birmingham, UK.
M NetravathiNational Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
Fiona McGillLeeds Teaching Hospitals NHS Trust, Leeds, UK.
Benedict D MichaelInstitute 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.
Victor MwapasaKamuzu University of Health Sciences, Blantyre, Malawi.
Michael J GriffithsInstitute 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.
Christopher M ParryLiverpool School of Tropical Medicine, Liverpool, UK.
Vasanthapuram RaviNational Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
Girvan BurnsideInstitute of Population Health, University of Liverpool, Liverpool, UK.
Brain Infections Global Intervention Study Group
Jennifer CornickInstitute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Rafael Freitas de Oliveira FrançaOswaldo Cruz Foundation Pernambuco, Recife, Brazil.
Anita S DesaiNational Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
Priscilla RupaliChristian Medical College, Vellore, Tamil Nadu, India.
Tom SolomonInstitute 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.

Funding

Department of Health NIHR200134Wellcome TrustWorld Health Organization 001
6 · The paper itself

Abstract

backgroundBrain 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.

methodsWith 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.

findingsBetween 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.

interpretationDiagnosis 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.

fundingUK National Institute for Health and Care Research.

Indexed as

Brain DiseasesAcute DiseaseAdolescentAdultBrazilChildChild, PreschoolFemaleHospitalizationHumansIndiaInfantInterrupted Time Series AnalysisLogistic ModelsMalawiMale

Identifiers

PMID40081400
PMCPMC7618301

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.