Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries
Authors: 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
Journal: JAMA Network Open (2024)

Importance The 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. Objective To 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 Participants This 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 Measures Descriptive 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). Results Of 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 Relevance In 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.