Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries

Author:

Ajanovic Sara123,Madewell Zachary J.4,El Arifeen Shams5,Gurley Emily S.56,Hossain Mohammad Zahid5,Islam Kazi Munisul5,Rahman Afruna5,Assefa Nega7,Madrid Lola78,Abdulahi Mohammednur7910,Igunza Kitiezo Aggrey11,Murila Florence11,Revathi Gunturu1213,Christopher Mugah11,Sow Samba O.1415,Kotloff Karen L.15,Tapia Milagritos D.15,Traor Cheik Bougadari14,Mandomando Inacio1316,Xerinda Elisio316,Varo Rosauro13,Kincardett Milton316,Ogbuanu Ikechukwu U.1718,Nwajiobi-Princewill Phillip19,Swarray-Deen Alim20,Luke Ronita21,Madhi Shabir A.22,Mahtab Sana2223,Dangor Ziyaad22,du Toit Jeanie22,Akelo Victor24,Mutevedzi Portia2223,Tippett Barr Beth A.2425,Blau Dianna M.4,Whitney Cynthia G.21,Bassat Quique1232627, ,Solomon Fatima28,Sorour Gillian28,Lombaard Hennie28,Wadula Jeannette28,Petersen Karen28,Hale Martin28,P. Govender Nelesh28,J. Swart Peter28,G. Lala Sanjay28,Velaphi Sithembiso28,Chawana Richard28,Adam Yasmin28,Wise Amy28,Myburgh Nellie28,Bari Sanwarul28,Parveen Shahana28,Kamal Mohammed28,Uddin Ahmed A.S.M. Nawshad28,Hoque Mahbubul28,Tasnim Saria28,Islam Ferdousi28,Ariuman Farida28,Mosiur Rahman Mohammad28,Begum Ferdousi28,Zaman K. Zaman28,Rahman Mustafizur28,Ahmed Dilruba28,Sabrina Flora Meerjady28,Shirin Tahmina28,Rahman Mahbubur28,Oundo Joseph28,Ibrahim Alexander M.28,Temesgen Fikremelekot28,Gure Tadesse28,Alemu Addisu28,Mulatu Yeshi Melisachew28,Abayneh Gizaw Mahlet28,MS Orlien Stian28,Ali Solomon28,Aggrey Igunza Kitiezo28,Otieno Peter28,Nyamthimba Onyango Peter28,Agaya Janet28,Oliech Richard28,Akinyi Were Joyce28,Gethi Dickson28,Aol George28,Misore Thomas28,Owuor Harun28,Muga Christopher28,Oluoch Bernard28,Ochola Christine28,M. Tennant Sharon28,L. Greene Carol28,Mehta Ashka28,Johnson J. Kristie28,Gaume Brigitte28,Mamby Keita Adama28,Koka Rima28,D. Fairchild Karen28,Kone Diakaridia28,Sidibe Diakaridia28,Sanogo Doh28,Onwuchekwa Uma U.28,Kourouma Nana28,Sissoko Seydou28,Bougadari Traore Cheick28,Juma Jane28,Diarra Kounandji28,Traore Awa28,Diarra Tiéman28,Chawla Kiranpreet28,Nhampossa Tacilta28,Manhique Zara28,Mocumbi Sibone28,Menéndez Clara28,Munguambe Khátia28,Nhacolo Ariel28,Maixenchs Maria28,Moseray Andrew28,Bintu Tarawally Fatmata28,Seppeh Martin28,Mash Ronald28,Ojulong Julius28,Duduyemi Babatunde28,Bunn James28,Swaray-Deen Alim28,Bangura Joseph28,Jambai Amara28,Mannah Margaret28,Ita Okokon28,Chukwuegbo Cornell28,Sannoh Sulaiman28,Nwajiobi Princewill28,Kowuor Dickens28,Kaluma Erick28,Balogun Oluseyi28,Jo Cain Carrie28,Samura Solomon28,Pratt Samuel28,Moses Francis28,Sesay Tom28,Squire James28,Kamanda Sesay Joseph28,Kaykay Osman28,Halu Binyam28,Legesse Hailemariam28,Smart Francis28,Kenneh Sartie28,Ameh Soter28,Ritter Jana28,Wilson Tais28,Winchell Jonas28,Witherbee Jakob28,Garel Mischka28,T. Salzberg Navit28,P. Koplan Jeffrey28,Han Lee Kyu28,Martines Roosecelis28,Warang Shamta28,Diaz Maureen28,Waller Jessica28,Nair Shailesh28,Liu Lucy28,Liu Courtney Bursuc28,LaHatte Kristin28,Raymer Sarah28,Blevins John28,Argeseanu Solveig28,Vyas Kurt28,Bhandari Manu28

Affiliation:

1. Barcelona Institute for Global Health, Barcelona, Spain

2. University of Barcelona, Barcelona, Spain

3. Centro de Investigaçao em Saúde de Manhiça, Manhiça, Mozambique

4. Global Health Center, US Centers for Disease Control and Prevention, Atlanta, Georgia

5. International Center for Diarrhoeal Diseases Research, Dhaka, Bangladesh

6. Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

7. College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia

8. Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom

9. Ayder Specialized Comprehensive Hospital, Mekelle University, Mekelle, Ethiopia

10. Addis Ababa University, Addis Ababa, Ethiopia

11. Kenya Medical Research Institute, Kisumu, Kenya

12. Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya

13. Kisumu County of Department of Health, Kisumu, Kenya

14. Centre pour le Développement des Vaccins, Ministère de la Santé, Bamako, Mali

15. Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore

16. Instituto Nacional de Saude, Maputo, Mozambique

17. Crown Agents, Freetown, Sierra Leone

18. World Hope International, Freetown, Sierra Leone

19. Department of Medical Microbiology, National Hospital Abuja, Abuja, Nigeria

20. Department of Obstetrics and Gynaecology, University of Ghana Medical School, Accra, Ghana

21. Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia

22. South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

23. Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

24. US Centers for Disease Control and Prevention, Nairobi and Kisumu, Kenya

25. Nyanja Health Research Institute, Salima, Malawi

26. Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain

27. Pediatrics Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

28. for the Child Health and Mortality Prevention Surveillance (CHAMPS) Consortium

Abstract

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.

Publisher

American Medical Association (AMA)

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