Postnatal Zika and Dengue Infection and their Effects on Neurodevelopment Among Children Living in Rural Guatemala.
| Title: | Postnatal Zika and Dengue Infection and their Effects on Neurodevelopment Among Children Living in Rural Guatemala. |
|---|---|
| Authors: | Asturias EJ; From the Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.; Center for Global Health or Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado.; Connery AK; Center for Global Health or Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado.; Department of Rehabilitation Medicine, University of Colorado School of Medicine, Aurora, Colorado.; Olson D; From the Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.; Center for Global Health or Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado.; Lamb MM; Center for Global Health or Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado.; Paniagua-Avila A; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, New York.; Anderson EJ; Emory University, Atlanta, Georgia.; Focht C; Emmes Company, LLC, Rockville, Maryland.; Colbert AM; Department of Rehabilitation Medicine, University of Colorado School of Medicine, Aurora, Colorado.; Natrajan M; Emory University, Atlanta, Georgia.; Waggoner JJ; Emory University, Atlanta, Georgia.; Scherer E; Emory University, Atlanta, Georgia.; Calvimontes DM; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Bolaños GA; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Bauer D; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Arroyave P; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Hernández S; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Martinez MA; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Ralda AV; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Rojop N; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Barrios EE; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Chacon A; Fundacion para la Salud Integral de los Guatemaltecos, Retalhuleu, Guatemala.; Dempsey W; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.; Tomashek KM; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.; Keitel WA; Department of Medicine, Baylor College of Medicine, Houston, Texas.; Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas.; El Sahly HM; Department of Medicine, Baylor College of Medicine, Houston, Texas.; Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas.; Muñoz FM; Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas.; Department of Pediatrics, Baylor College of Medicine, Texas. |
| Source: | The Pediatric infectious disease journal [Pediatr Infect Dis J] 2025 Apr 01; Vol. 44 (4), pp. 290-298. Date of Electronic Publication: 2024 Dec 06. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Williams & Wilkins Country of Publication: United States NLM ID: 8701858 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-0987 (Electronic) Linking ISSN: 08913668 NLM ISO Abbreviation: Pediatr Infect Dis J Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Baltimore, Md. : Williams & Wilkins, c1987- |
| MeSH Terms: | Zika Virus Infection*/epidemiology ; Zika Virus Infection*/complications ; Dengue*/epidemiology ; Dengue*/complications ; Neurodevelopmental Disorders*/epidemiology ; Neurodevelopmental Disorders*/virology ; Neurodevelopmental Disorders*/etiology; Guatemala/epidemiology ; Microcephaly/epidemiology ; Microcephaly/virology ; Humans ; Female ; Infant ; Child, Preschool ; Male ; Rural Population ; Prospective Studies ; Infant, Newborn ; Pregnancy ; Zika Virus ; Dengue Virus |
| Abstract: | Background: Prenatal Zika virus (ZIKV) infection leads to microcephaly and adverse neurodevelopment. The effects of postnatal ZIKV infection on the developing brain are unknown. We assessed the neurodevelopmental outcomes of children exposed postnatally during the ZIKV epidemic.; Methods: A prospective study enrolled infants 0-3 months of age and their mothers, and children 1.5-3.5 years of age in rural Guatemala from 2017 and were followed for 12 months until 2019. Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL). ZIKV and dengue virus (DENV) infections were identified by polymerase chain reaction (PCR) using active surveillance. Serological analyses, stratified by age group flavivirus serostatus at enrollment, were conducted using a focus reduction neutralization test.; Results: Of 1371 enrolled participants, 1187 (86.6%) completed the study. No PCR-confirmed ZIKV infections were identified during the study period. One-third of 1.5-3.5-year-old children were ZIKV-seropositive at enrollment (likely postnatal infection). Twenty participants (5.8%) tested positive for DENV by PCR (11 infants, 5 children and 4 mothers); 15 (75%) were DENV-3 infections and 5 were DENV-2. The incidence of DENV infection in infants was 2.6%. No significant differences in MSEL scores were found between infants born seropositive versus seronegative for ZIKV or DENV. DENV seropositivity at enrollment in 1.5-5-year-old children was associated with lower MSEL scores for fine motor, visual reception and language, and microcephaly at 12 months versus seronegative children (all P < 0.05).; Conclusions: Postnatal ZIKV infection in children from rural Guatemala was not associated with worse neurodevelopmental outcomes. DENV seropositivity was associated with a higher risk of microcephaly in infants and worse neurodevelopmental outcomes in children.; (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) |
| Competing Interests: | E.J.A. has served on safety monitoring and advisory boards for Moderna, Hillevax, Inovio, Sanofi and Merck, and his institution receives funds to conduct clinical research unrelated to this manuscript from Pfizer, Biofire, and Roche. F.M.M. has served on safety monitoring and advisory boards for Moderna, Pfizer, Sanofi, Aztra Zeneca and Merck and has conducted research funded by the US Centers for Disease Control and Prevention, Pfizer, Gilead. D.O. has received research support from Roche. Other authors have no conflicts of interest to disclose. |
| References: | Pan American Health Organization. Neurological syndrome, congenital malformations, and Zika virus infection. Implications for public health in the Americas—epidemiological alert. 1 Dec 2015. 2015.; Lopes Moreira ME, Nielsen-Saines K, Brasil P, et al. Neurodevelopment in infants exposed to Zika Virus In Utero. N Engl J Med. 2018;379:2377–2379.; Nielsen-Saines K, Brasil P, Kerin T, et al. Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children. Nat Med. 2019;25:1213–1217.; Faiçal AV, de Oliveira JC, Oliveira JVV, et al. Neurodevelopmental delay in normocephalic children with in utero exposure to Zika virus. BMJ Paediatr open. 2019;3:e000486.; Tiene SF, Cranston JS, Nielsen-Saines K, et al. Early predictors of poor neurologic outcomes in a prospective cohort of infants with antenatal exposure to Zika virus. Pediatr Infect Dis J. 2022;41:255–262.; Rasmussen SA, Jamieson DJ, Honein MA, et al. Zika virus and birth defects--reviewing the evidence for causality. N Engl J Med. 2016;374:1981–1987.; Mavigner M, Raper J, Kovacs-Balint Z, et al. Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques. Sci Transl Med. 2018;10:eaao6975.; Paniagua-Avila A, Olson D, Connery A, et al. Challenges and lessons learned from the rapid operationalization of a prospective cohort to study the natural history and neurodevelopmental outcomes of postnatal Zika virus infection among infants and children in rural Guatemala. PLoS NeglTrop Dis. 2022;16:e0010480.; Colbert AM, Lamb MM, Asturias EJ, et al. Reliability and validity of an adapted and translated version of the mullen scales of early learning (AT-MSEL) in rural Guatemala. Child Care Health Dev. 2020;46:327–335.; Connery AK, Berrios-Siervo G, Arroyave P, et al. Responding to the Zika epidemic: preparation of a neurodevelopmental testing protocol to evaluate young children in rural Guatemala. Am J Trop Med Hyg. 2019;100:438–444.; Colbert AM, Connery AK, Lamb MM, et al. Caregiver rating of early childhood development: reliability and validity of the ASQ-3 in rural Guatemala. Early Hum Dev. 2021;161:105453.; Balmaseda A, Zambrana JV, Collado D, et al. Comparison of four serological methods and two reverse transcription-PCR assays for diagnosis and surveillance of Zika virus infection. J Clin Microbiol. 2018;56:e01785–e01717.; Balmaseda A, Stettler K, Medialdea-Carrera R, et al. Antibody-based assay discriminates Zika virus infection from other flaviviruses. Proc Natl Acad Sci USA. 2017;114:8384–8389.; Waggoner JJ, Stittleburg V, Natrajan MS, et al. Sensitive and prolonged detection of dengue virus RNA in whole blood. Am J Trop Med Hyg. 2021;104:1734–1736.; Waggoner JJ, Gresh L, Mohamed-Hadley A, et al. Single-reaction multiplex reverse transcription PCR for detection of Zika, chikungunya, and dengue viruses. Emerg Infect Dis. 2016;22:1295–1297.; Rosado LEP, Martelli CMT, Brickley EB, et al. Risk of adverse pregnancy and infant outcomes associated with prenatal Zika virus infection: a post-epidemic cohort in Central-West Brazil. Sci Rep. 2023;13:7335.; Pérez-Vera LA, Herrera-García V, Pérez-Matos MC, et al. Clinical features and neurodevelopmental outcomes for infants with perinatal vertical transmission of Zika virus, Colombia. Emerg Infect Dis. 2022;28:453–456.; Sobral da Silva PF, Eickmann SH, Ximenes RAA, et al. On Behalf Of The Microcephaly Epidemic Research Group Merg. Neurodevelopment in children exposed to Zika virus: What are the consequences for children who do not present with microcephaly at birth? Viruses. 2021;13:1427.; Andrade LM, Baker Meio MD, Gomes SC Jr., et al. Language delay was associated with a smaller head circumference at birth in asymptomatic infants prenatally exposed to the Zika virus. Acta Paediatr (Oslo, Norway: 1992). 2021;110:2375–2381.; Cavalcante TB, Ribeiro MRC, Sousa PDS, et al. Congenital Zika syndrome: growth, clinical, and motor development outcomes up to 36 months of age and differences according to microcephaly at birth. Int J Infect Dis. 2021;105:399–408.; Marbán-Castro E, Vazquez Guillamet LJ, Pantoja PE, et al. Neurodevelopment in normocephalic children exposed to Zika virus in utero with no observable defects at birth: a systematic review with meta-analysis. Int J Environ Res Public Health. 2022;19:7319.; Zare Mehrjardi M, Carteaux G, Poretti A, et al. Neuroimaging findings of postnatally acquired Zika virus infection: a pictorial essay. JPN J Radiol. 2017;35:341–349.; Valdes V, Zorrilla CD, Gabard-Durnam L, et al. Cognitive development of infants exposed to the Zika virus in Puerto Rico. JAMA Netw Open. 2019;2:e1914061.; Ramond A, Lobkowicz L, Clemente NS, et al. Postnatal symptomatic Zika virus infections in children and adolescents: a systematic review. PLoS NeglTrop Dis. 2020;14:e0008612.; Domingues RB, Kuster GW, Onuki-Castro FL, et al. Involvement of the central nervous system in patients with dengue virus infection. J Neurol Sci. 2008;267:36–40.; Laureti M, Narayanan D, Rodriguez-Andres J, et al. Flavivirus receptors: diversity, identity, and cell entry. Front Immunol. 2018;9:2180.; Donowitz JR, Cook H, Alam M, et al. Role of maternal health and infant inflammation in nutritional and neurodevelopmental outcomes of two-year-old Bangladeshi children. PLoS NeglTrop Dis. 2018;12:e0006363.; Bach AM, Xie W, Piazzoli L, et al. Systemic inflammation during the first year of life is associated with brain functional connectivity and future cognitive outcomes. Dev Cogn Neurosci. 2022;53:101041.; Azziz-Baumgartner E, Gonzalez R, Davis W, et al. Lower cognitive scores among toddlers in birth cohorts with acute respiratory illnesses, fevers, and laboratory-confirmed influenza. Influenza Other Respir Viruses. 2022;16:101–112.; Katzelnick LC, Zambrana JV, Elizondo D, et al. Dengue and Zika virus infections in children elicit cross-reactive protective and enhancing antibodies that persist long term. Sci Transl Med. 2021;13:eabg9478.; Rick AM, Domek G, Cunningham M, et al. High background congenital microcephaly in rural Guatemala: implications for neonatal congenital Zika virus infection screening. Glob Health Sci Pract. 2017;5:686–696.; Connery AK, Lamb MM, Colbert AM, et al. A prospective cohort study of head circumference and its association with neurodevelopmental outcomes in infants and young children in rural Guatemala. J Dev Orig Health Dis. 2022;13:779–786. |
| Grant Information: | HHSN272201300015C United States AI NIAID NIH HHS; HHSN272201300015I United States AI NIAID NIH HHS; T32 MH013043 United States MH NIMH NIH HHS; UM1 AI148575 United States AI NIAID NIH HHS |
| Entry Date(s): | Date Created: 20241205 Date Completed: 20250427 Latest Revision: 20260510 |
| Update Code: | 20260510 |
| PubMed Central ID: | PMC11893259 |
| DOI: | 10.1097/INF.0000000000004646 |
| PMID: | 39637296 |
| Database: | MEDLINE |
Journal Article