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Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries
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ImportanceThe emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies.ObjectiveTo characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival.Design, Setting, and ParticipantsThis cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023.Main Outcomes and MeasuresDescriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies).ResultsOf the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to death were considered preventable.Conclusions and RelevanceIn this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death. However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses. The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms. Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.
American Medical Association (AMA)
Sara Ajanovic
Zachary J. Madewell
Shams El Arifeen
Emily S. Gurley
Mohammad Zahid Hossain
Kazi Munisul Islam
Afruna Rahman
Nega Assefa
Lola Madrid
Mohammednur Abdulahi
Kitiezo Aggrey Igunza
Florence Murila
Gunturu Revathi
Mugah Christopher
Samba O. Sow
Karen L. Kotloff
Milagritos D. Tapia
Cheik Bougadari Traor
Inacio Mandomando
Elisio Xerinda
Rosauro Varo
Milton Kincardett
Ikechukwu U. Ogbuanu
Phillip Nwajiobi-Princewill
Alim Swarray-Deen
Ronita Luke
Shabir A. Madhi
Sana Mahtab
Ziyaad Dangor
Jeanie du Toit
Victor Akelo
Portia Mutevedzi
Beth A. Tippett Barr
Dianna M. Blau
Cynthia G. Whitney
Quique Bassat
Fatima Solomon
Gillian Sorour
Hennie Lombaard
Jeannette Wadula
Karen Petersen
Martin Hale
Nelesh P. Govender
Peter J. Swart
Sanjay G. Lala
Sithembiso Velaphi
Richard Chawana
Yasmin Adam
Amy Wise
Nellie Myburgh
Sanwarul Bari
Shahana Parveen
Mohammed Kamal
A.S.M. Nawshad Uddin Ahmed
Mahbubul Hoque
Saria Tasnim
Ferdousi Islam
Farida Ariuman
Mohammad Mosiur Rahman
Ferdousi Begum
K. Zaman Zaman
Mustafizur Rahman
Dilruba Ahmed
Meerjady Sabrina Flora
Tahmina Shirin
Mahbubur Rahman
Joseph Oundo
Alexander M. Ibrahim
Fikremelekot Temesgen
Tadesse Gure
Addisu Alemu
Melisachew Mulatu Yeshi
Mahlet Abayneh Gizaw
Stian MS Orlien
Solomon Ali
Kitiezo Aggrey Igunza
Peter Otieno
Peter Nyamthimba Onyango
Janet Agaya
Richard Oliech
Joyce Akinyi Were
Dickson Gethi
George Aol
Thomas Misore
Harun Owuor
Christopher Muga
Bernard Oluoch
Christine Ochola
Sharon M. Tennant
Carol L. Greene
Ashka Mehta
J. Kristie Johnson
Brigitte Gaume
Adama Mamby Keita
Rima Koka
Karen D. Fairchild
Diakaridia Kone
Diakaridia Sidibe
Doh Sanogo
Uma U. Onwuchekwa
Nana Kourouma
Seydou Sissoko
Cheick Bougadari Traore
Jane Juma
Kounandji Diarra
Awa Traore
Tiéman Diarra
Kiranpreet Chawla
Tacilta Nhampossa
Zara Manhique
Sibone Mocumbi
Clara Menéndez
Khátia Munguambe
Ariel Nhacolo
Maria Maixenchs
Andrew Moseray
Fatmata Bintu Tarawally
Martin Seppeh
Ronald Mash
Julius Ojulong
Babatunde Duduyemi
James Bunn
Alim Swaray-Deen
Joseph Bangura
Amara Jambai
Margaret Mannah
Okokon Ita
Cornell Chukwuegbo
Sulaiman Sannoh
Princewill Nwajiobi
Dickens Kowuor
Erick Kaluma
Oluseyi Balogun
Carrie Jo Cain
Solomon Samura
Samuel Pratt
Francis Moses
Tom Sesay
James Squire
Joseph Kamanda Sesay
Osman Kaykay
Binyam Halu
Hailemariam Legesse
Francis Smart
Sartie Kenneh
Soter Ameh
Jana Ritter
Tais Wilson
Jonas Winchell
Jakob Witherbee
Mischka Garel
Navit T. Salzberg
Jeffrey P. Koplan
Kyu Han Lee
Roosecelis Martines
Shamta Warang
Maureen Diaz
Jessica Waller
Shailesh Nair
Lucy Liu
Courtney Bursuc Liu
Kristin LaHatte
Sarah Raymer
John Blevins
Solveig Argeseanu
Kurt Vyas
Manu Bhandari
Title: Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries
Description:
ImportanceThe emergence of acute neurological symptoms in children necessitates immediate intervention.
Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources.
Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies.
ObjectiveTo characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival.
Design, Setting, and ParticipantsThis cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa).
Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years.
This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death.
Data analysis was performed between July 22, 2022, and January 15, 2023.
Main Outcomes and MeasuresDescriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies).
ResultsOf the 2127 deaths of children codified during the study period, 1330 (62.
5%) had neurological evaluations recorded and were included in this analysis.
The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.
0%) were male and 727 (54.
7%) presented with neurological symptoms during illness before death.
The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.
2%]), meningoencephalitis (135 [10.
2%]), and cerebral malaria (68 [5.
1%]).
There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria.
Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools.
However, only 25 children (18.
5%) with meningitis had a lumbar puncture performed before death.
Nearly 90% of deaths (442 of 511 [86.
5%]) with neurological diagnoses in the chain of events leading to death were considered preventable.
Conclusions and RelevanceIn this cross-sectional study of children aged younger than 5 years, neurological symptoms were frequent before death.
However, clinical phenotypes were insufficient to differentiate the most common underlying neurological diagnoses.
The low rate of lumbar punctures performed was especially worrying, suggesting a challenge in quality of care of children presenting with neurological symptoms.
Improved diagnostic management of neurological emergencies is necessary to ultimately reduce mortality in this vulnerable population.
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