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
. 2024 Sep 3;7(9):e2431512.
doi: 10.1001/jamanetworkopen.2024.31512.

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

Sara Ajanovic  1   2   3 , Zachary J Madewell  4 , Shams El Arifeen  5 , Emily S Gurley  5   6 , Mohammad Zahid Hossain  5 , Kazi Munisul Islam  5 , Afruna Rahman  5 , Nega Assefa  7 , Lola Madrid  7   8 , Mohammednur Abdulahi  7   9   10 , Kitiezo Aggrey Igunza  11 , Florence Murila  11 , Gunturu Revathi  12   13 , Mugah Christopher  11 , Samba O Sow  14   15 , Karen L Kotloff  15 , Milagritos D Tapia  15 , Cheik Bougadari Traor  14 , Inacio Mandomando  1   3   16 , Elisio Xerinda  3   16 , Rosauro Varo  1   3 , Milton Kincardett  3   16 , Ikechukwu U Ogbuanu  17   18 , Phillip Nwajiobi-Princewill  19 , Alim Swarray-Deen  20 , Ronita Luke  21 , Shabir A Madhi  22 , Sana Mahtab  22   23 , Ziyaad Dangor  22 , Jeanie du Toit  22 , Victor Akelo  24 , Portia Mutevedzi  22   23 , Beth A Tippett Barr  24   25 , Dianna M Blau  4 , Cynthia G Whitney  21 , Quique Bassat  1   2   3   26   27   28 ; Child Health and Mortality Prevention Surveillance (CHAMPS) Consortium
Collaborators, Affiliations

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

Sara Ajanovic et al. JAMA Netw Open. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr El Arifeen reported receiving grants from Emory University and the Bill and Melinda Gates Foundation (BMGF) during the conduct of the study. Dr Gurley reported receiving grants from Emory University and the BMGF during the conduct of the study. Dr Kotloff reported receiving grants from Emory University during the conduct of the study. Dr Tapia reported receiving grants from Emory University during the conduct of the study. Dr Madhi reported receiving grants (paid to the University of the Witwatersrand) from the BMGF during the conduct of the study and from Pfizer, MinervaX, Merck & Co., and the European and Developing Countries Clinical Trials Partnership outside the submitted work. Dr Dangor reported receiving grants from the BMGF during the conduct of the study. Dr Whitney reported receiving grants from the BMGF during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Patients With Neurological Signs and Fever and Their Overlap
Euler diagrams are presented for neonates (A), infants (B), and children (C). Patients who went under lumbar puncture (LP) are pinpointed (each point represents 1 LP) according to their clinical presentation. Point colors represent the ultimate neurological diagnosis after evaluation by the DeCoDe panel. The bar beneath each age group represents the proportion of final diagnoses among children who underwent an LP (46 neonates, 31 infants, and 18 children). Dots outside of the bars represent children without any neurological symptoms who underwent an LP. Euler diagram errors: 0.001 in all age groups; stress: less than 0.01 in all age groups. AM indicates altered mental status; DeCoDe, Determination of Cause of Death; F, fever; MS, meningeal sign; and S, seizure.
Figure 2.
Figure 2.. Cause of Death Involving the Central Nervous System, Stratified by Age Group
Cause of death is presented for neonates (A), infants (B), and children (C). Data are presented for 520 of 1330 patients (representing 39.1% of the cohort).
Figure 3.
Figure 3.. Premortem Management of the 3 Most Common Neurological Diagnoses Present in the Chain of Events Leading to Death and the Proportion of Deaths Considered Preventable
Management (left) and preventive measures (right) are presented for patients with hypoxic events (A), meningoencephalitis (B), and cerebral malaria (C). The median number of preventive measures to be implemented in each case of death was 2 (IQR, 1-3) in all 3 groups. ANC indicates antenatal care; LP, lumbar puncture.
See this image and copyright information in PMC

References

    1. Orman G, Rossi A, Meoded A, Huisman T. Children with acute neurological emergency. In: Hodler J, Kubik-Huch RA, von Schulthess GK, eds. Diseases of the Brain, Head and Neck, Spine 2020-2023: Diagnostic Imaging. IDKD Springer Series; 2020:179-190. doi:10.1007/978-3-030-38490-6_14 - DOI
    1. Saigal G, Ezuddin NS, Vega G. Neurologic emergencies in pediatric patients including accidental and nonaccidental trauma. Neuroimaging Clin N Am. 2018;28(3):453-470. doi:10.1016/j.nic.2018.03.007 - DOI - PubMed
    1. Mousa A, Al-Taiar A, Anstey NM, et al. . The impact of delayed treatment of uncomplicated P. falciparum malaria on progression to severe malaria: a systematic review and a pooled multicentre individual-patient meta-analysis. PLoS Med. 2020;17(10):e1003359. doi:10.1371/journal.pmed.1003359 - DOI - PMC - PubMed
    1. Tebeila ND, Dangor Z, Madhi SA, Cutland C, Groome MJ. Incidence of febrile seizures and associated factors in children in Soweto, South Africa. S Afr Med J. 2021;111(8):796-802. doi:10.7196/SAMJ.2021.v111i8.15431 - DOI - PubMed
    1. Owusu-Ofori A, Agbenyega T, Ansong D, Scheld WM. Routine lumbar puncture in children with febrile seizures in Ghana: should it continue? Int J Infect Dis. 2004;8(6):353-361. doi:10.1016/j.ijid.2003.12.008 - DOI - PubMed

Publication types