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Graham EE, Tetens MM, Bodilsen J, Andersen NS, Dessau R, Ellermann-Eriksen S, Franck K, Midgley S, Møller JK, Nielsen AC, Nielsen L, Søgaard KK, Østergaard C, Lebech AM, Nygaard U, Omland LH, Obel N. Neurological Disorders and Use of Healthcare Services After Enteroviral Meningitis in Childhood: A Nationwide, Population-Based Cohort Study. J Pediatric Infect Dis Soc 2025; 14:piae125. [PMID: 39931998 DOI: 10.1093/jpids/piae125] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 12/10/2024] [Indexed: 05/08/2025]
Abstract
BACKGROUND Nervous system infections are associated with long-term risks of neurological disorders and healthcare service utilization, but little data exist on the long-term risks of enteroviral meningitis in childhood. METHODS We performed a population-based, nationwide registry-based matched cohort study (1997-2021). We included 925 children with enteroviral meningitis aged <17 years, a comparison cohort, and a cohort of siblings of all individuals. To illustrate short- and long-term risks of neurological disorders, we calculated 1-year cumulative incidences and age- and sex-adjusted hazard ratios (aHRs) with 95% confidence intervals (95% CIs) during years 1-20 of follow-up. We further calculated the annual proportion of individuals using antiepileptic medication and healthcare services. RESULTS Young infants (0 to <90 days) and older children (≥90 days to <17 years) had slightly increased short- and long-term risks of neurological disorders after enteroviral meningitis compared to comparison cohort members (1-year cumulative incidence: 1.4% vs 0.6%, and 1.5% vs 0.4%, 1-20-year adjusted hazard ratio: 2.0 [95% CI: 1.2-3.2] and 1.7 [95% CI: 1.0-2.8]). Older children had increased use of antiepileptic medication, as well as the use of health care services both before and after enteroviral meningitis, with a similar trend among their siblings. CONCLUSIONS Enteroviral meningitis in childhood appears to be associated with increased risk of short- and long-term neurological morbidity, though our estimates in older children may be confounded by prior neurological morbidity or increased healthcare-seeking behavior. Our findings suggest a generally good prognosis after enteroviral meningitis, though clinicians should be aware of the risk of neurological disorders in selected patients.
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Affiliation(s)
- Emma E Graham
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Malte M Tetens
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Jacob Bodilsen
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Nanna S Andersen
- Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Microbiology, University of Southern Denmark, Odense, Denmark
| | - Ram Dessau
- Department of Clinical Microbiology, Zealand Hospital, Slagelse, Denmark
- Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | | | - Kristina Franck
- Department of Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark
| | - Sofie Midgley
- Department of Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark
| | - Jens Kjølseth Møller
- Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
- Department of Clinical Microbiology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | - Alex Christian Nielsen
- Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Lene Nielsen
- Department of Clinical Microbiology, Copenhagen University Hospital, Herlev Hospital, Herlev, Denmark
| | - Kirstine K Søgaard
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Christian Østergaard
- Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark
| | - Anne-Mette Lebech
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ulrikka Nygaard
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Pediatric and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Lars H Omland
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Niels Obel
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Graham EE, Tetens MM, Bodilsen J, Dessau R, Ellermann-Eriksen S, Andersen NS, Jørgensen CS, Pedersen M, Søgaard KK, Bangsborg J, Nielsen AC, Møller JK, Obel D, Lebech AM, Nygaard U, Omland LH, Obel N. Risk of psychiatric neurodevelopmental disorders after meningitis in childhood: a nationwide, population-based cohort study. Infect Dis (Lond) 2025; 57:89-99. [PMID: 39230517 DOI: 10.1080/23744235.2024.2399101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 08/01/2024] [Accepted: 08/27/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND Few studies have investigated the risk of psychiatric neurodevelopmental disorders (PNDD) after childhood meningitis. METHODS Nationwide population-based cohort study (Denmark, 1995-2021) of children with positive cerebrospinal fluid for bacteria or enterovirus, stratified on age as young infants (0 to <90 days, n = 637) or older children (≥90 days to <17 years, n = 1,218). We constructed a comparison cohort from the general population (n = 18,550), and cohorts of siblings of participants. As risk estimates of PNDD we calculated age- and sex-adjusted hazard ratios (aHRs) with 95% confidence intervals (95%CI). RESULTS Children with bacterial meningitis had increased risks of PNDD, especially learning and intellectual developmental disorders (young infants: aHR 4.2, 95%CI: 2.4-7.1; older children: aHR 1.5, 95%CI: 1.0-2.3), attention deficit disorder (ADHD) (young infants: aHR 2.8, 95%CI: 1.5-5.2; older children: 1.4, 95%CI: 0.9-2.2) and redemption of ADHD medication (young infants: aHR 2.2, 95%CI: 1.0-4.7; older children: 1.5, 95%CI: 1.0-2.3). Young infants with bacterial meningitis additionally had increased risks of autism spectrum disorders (aHR 1.9, 95%CI: 0.9-4.1) and behavioural and emotional disorders (aHR 2.0, 95%CI: 1.0-3.9). In young infants, the excess risk of PNDD was especially observed in premature children. Siblings of older children with bacterial meningitis also had increased risks of PNDD. Children with enteroviral meningitis at any age did not have increased risks of PNDD or redemption of ADHD medication. CONCLUSIONS Bacterial meningitis in childhood is associated with subsequent diagnosis of PNDD, while enteroviral meningitis is not. The association appears to be partly explained by prematurity and familial and socioeconomic factors.
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Affiliation(s)
- Emma E Graham
- Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Malte M Tetens
- Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Jacob Bodilsen
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Ram Dessau
- Department of Clinical Microbiology, Zealand Hospital, Slagelse, Denmark
- Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
| | | | - Nanna S Andersen
- Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Microbiology, University of Southern Denmark, Odense, Denmark
| | | | - Michael Pedersen
- Department of Clinical Microbiology, Copenhagen University Hospital - Hvidovre Hospital, Hvidovre, Denmark
| | - Kirstine K Søgaard
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Jette Bangsborg
- Department of Clinical Microbiology, Copenhagen University Hospital - Herlev Hospital, Herlev, Denmark
| | - Alex Christian Nielsen
- Department of Clinical Microbiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Jens Kjølseth Møller
- Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
- Department of Clinical Microbiology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | - Dorrit Obel
- Obel's Clinic for Children and Adolescents, Aarhus, Denmark
| | - Anne-Mette Lebech
- Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ulrikka Nygaard
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Pediatric and Adolescent Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Lars H Omland
- Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Niels Obel
- Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Draper CE, Yousafzai AK, McCoy DC, Cuartas J, Obradović J, Bhopal S, Fisher J, Jeong J, Klingberg S, Milner K, Pisani L, Roy A, Seiden J, Sudfeld CR, Wrottesley SV, Fink G, Nores M, Tremblay MS, Okely AD. The next 1000 days: building on early investments for the health and development of young children. Lancet 2024; 404:2094-2116. [PMID: 39571589 DOI: 10.1016/s0140-6736(24)01389-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 04/30/2024] [Accepted: 07/01/2024] [Indexed: 11/25/2024]
Abstract
Following the first 1000 days of life that span from conception to two years of age, the next 1000 days of a child's life from 2-5 years of age offer a window of opportunity to promote nurturing and caring environments, establish healthy behaviours, and build on early gains to sustain or improve trajectories of healthy development. This Series paper, the first of a two-paper Series on early childhood development and the next 1000 days, focuses on the transition to the next 1000 days of the life course, describes why this developmental period matters, identifies the environments of care, risks, and protective factors that shape children's development, estimates the number of children who receive adequate nurturing care, and examines whether current interventions are meeting children's needs. Paper 2 focuses on the cost of inaction and the implications of not investing in the next 1000 days. In low-income and middle-income countries (LMICs), only 62 million children aged 3 and 4 years (25·4%) currently receive adequate nurturing care during the next 1000 days, leaving 181·9 million children exposed to risks that jeopardise their healthy development. Inputs across nurturing care dimensions of health, nutrition, protection, responsive care, and learning vary substantially across countries. In LMICs, although 86·2% of children have a healthy weight in this period, less than one in three children have access to developmental stimulation or are protected from physical punishment, and only 38·8% have access to early childhood care and education services. Intervention research in LMICs in the next 1000 days is scarce. The continuity of developmentally appropriate nurturing care, coordination across health, education, and protection sectors, and the implementation of interventions to support caregivers and improve the quality of education and care remain top priorities in this period. These sectors play key roles in promoting quality early care and education for this age group, which will help maximise developmental potential and opportunities of children globally and help progress towards the achievement of the Sustainable Development Goals.
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Affiliation(s)
- Catherine E Draper
- South African Medical Research Council, Developmental Pathways for Health Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
| | - Aisha K Yousafzai
- Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, MA, USA; Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Dana C McCoy
- Graduate School of Education, Harvard University, Cambridge, MA, USA
| | - Jorge Cuartas
- Graduate School of Education, Harvard University, Cambridge, MA, USA; Department of Applied Psychology, New York University, New York, NY, USA; Centro de Estudios Sobre Seguridad y Drogas, Universidad de los Andes, Bogota, Colombia
| | - Jelena Obradović
- Graduate School of Education, Stanford University, Stanford, CA, USA
| | - Sunil Bhopal
- Population Health Sciences Institute, Newcastle University, Newcastle, UK; Department of Population Health, London School of Hygiene & Tropical Medicine, London, UK; Born in Bradford, Bradford Institute for Health Research, Bradford, UK
| | - Jane Fisher
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Joshua Jeong
- Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, MA, USA
| | - Sonja Klingberg
- South African Medical Research Council, Developmental Pathways for Health Research Unit, University of the Witwatersrand, Johannesburg, South Africa
| | - Kate Milner
- Neurodisability and Rehabilitation Research Group, Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
| | | | - Aditi Roy
- Centre for Chronic Disease Control, Centre for Health Analytics Research and Trends, Ashoka University, Sonipat, India
| | - Jonathan Seiden
- Graduate School of Education, Harvard University, Cambridge, MA, USA
| | - Christopher R Sudfeld
- Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, MA, USA
| | - Stephanie V Wrottesley
- South African Medical Research Council, Developmental Pathways for Health Research Unit, University of the Witwatersrand, Johannesburg, South Africa
| | - Günther Fink
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Allschwil, Switzerland; University of Basel, Basel, Switzerland
| | - Milagros Nores
- National Institute for Early Education Research, Rutgers Graduate School of Education, New Brunswick, NJ, USA
| | - Mark S Tremblay
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada; Department of Pediatrics, University of Ottawa, ON, Canada
| | - Anthony D Okely
- School of Health and Society, University of Wollongong, Wollongong, NSW, Australia
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Davydenko MA, Churilova NS, Koroleva IS. Epidemiological Manifestations of Purulent Bacterial Meningitis in the Russian Federation. EPIDEMIOLOGY AND VACCINAL PREVENTION 2024; 23:33-41. [DOI: 10.31631/2073-3046-2024-23-5-33-41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Relevance. Although meningitis is largely preventable, it still causes hundreds of thousands of deaths worldwide each year. Significant progress has been made in reducing meningitis mortality over the past three decades. The incidence of meningococcal, pneumococcal, and Haemophilus influenzae type b meningitis has declined due to the introduction of vaccination into national immunization programs in countries around the world. Aim. To determine the epidemiological manifestations of purulent bacterial meningitis (GBM) in the Russian Federation (RF) in 2023. Materials and methods. An in-depth personalized system for recording purulent bacterial meningitis cases has been established at the Russian Reference Center for Bacterial Meningitis Monitoring. Since 2010, all territories of the Russian Federation have been included in the monitoring system. In 2023, the Reference Center received information on 1,837 cases of purulent bacterial meningitis. The paper uses a descriptive and evaluative epidemiological method: retrospective analysis. Results and discussion. The incidence of GBM in the Russian Federation over a fourteen-year observation period has a downward trend. Meningococcus, pneumococcus and Haemophilus influenzae are the causes of 85% of GBM cases in the Russian Federation, while the infections they cause are potentially vaccine-preventable. Meningococcus continues to occupy a leading position in the etiology of GBM in the Russian Federation, causing 50% of all laboratory-confirmed cases. Despite a slight decrease in the incidence of meningococcal infection in 2023, its increase in the age group at risk, children under 5 years of age, by 39% was noted. In the serogroup characteristics of meningococcus, for the first time in the studied period, the predominance of meningococcus serogroup W was revealed. In 2023, the highest mortality rate from meningococcal infection was noted – 21%. The incidence rate of pneumococcal meningitis in the age group at risk, children under 5 years old, increased to 28% in 2023, and categories of adults are defined as risk groups for mortality. The incidence of meningitis caused by Haemophilus influenzae among children under 5 years old decreased by 44%, and all cases of death, with the exception of one, were noted in this age group. Conclusion. The data obtained make it possible to track the etiology of GBM, age groups and risk areas, which can serve as a basis for developing tactics to combat the disease with priority use of vaccines.
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Affiliation(s)
- M. A. Davydenko
- Federal Budget Institute of Science «Central Research Institute of Epidemiology» of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
| | - N. S. Churilova
- Federal Budget Institute of Science «Central Research Institute of Epidemiology» of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
| | - I. S. Koroleva
- Federal Budget Institute of Science «Central Research Institute of Epidemiology» of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
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Martin NG, Williman J, Walls T, Sadarangani M, Grant CC. Neurodevelopmental Outcomes Following Childhood Viral Meningitis in Canterbury New Zealand. Pediatr Infect Dis J 2024; 43:924-930. [PMID: 38754002 DOI: 10.1097/inf.0000000000004398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/18/2024]
Abstract
BACKGROUND Most childhood meningitis is viral in countries with widespread conjugate vaccine use. This study assessed clinical features and neurodevelopmental outcomes in preschool children following enteroviral and parechoviral meningitis. METHODS Children 18-42 months of age in Canterbury, New Zealand were included, who had enterovirus (EV) or parechovirus (HPEV) meningitis from 2015 to 2021. Comprehensive neurodevelopmental assessments were completed by a psychologist using the Bayley Scale for Infant Development-3 (BSID-3). Mean composite and scaled scores and proportion below the cutoff were assessed in each domain. Clinical data was analyzed. RESULTS There were 79 children 18-42 months old with previous EV or HPEV meningitis. BSID assessments were completed for 33 children (55% male), median age 32 months, from 2019 to 2022 including 23 with EV and 10 HPEV meningitis. At diagnosis, 32 (97%) received intravenous/intramuscular antibiotics, and 6 received a fluid bolus. Parents reported developmental speech concerns in 6 children, and delayed motor milestones in 1 child. There was no reported sensorineural hearing loss. BSID mean composite scores were in the expected range for cognition 102 (confidence interval: 98-106), language 96 (93-100) and motor 102 (98-106) domains. Overall, 12/33 (36%) children had below expected scores in 1 developmental domain, including scores 1-2 SD below the normative mean for cognition (2/33; 6%), receptive language (6/33; 18%), expressive language (5/33; 15%) and gross motor (6/33; 18%). There were no differences between scores in EV and HPEV meningitis. CONCLUSION Following viral meningitis, more than a third of preschool children had a mild developmental delay with comprehensive neurodevelopmental assessment, suggesting targeted follow-up should be considered.
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Affiliation(s)
| | - Jonathan Williman
- Department of Population Health, University of Otago Christchurch, Christchurch, New Zealand
| | | | - Manish Sadarangani
- Vaccine Evaluation Center, BC Children's Hospital Research Institute
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Cameron C Grant
- Department of Paediatrics: Child and Youth Health, University of Auckland
- Department of Paediatrics, General Paediatrics, Starship Children's Hospital, Auckland, New Zealand
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Kadambari S, Harvala H, Nguyen D, Sadarangani M, Martin NG, Al-Rawahi GN, Sekirov I, Defres S, Solomon T, Golubchik T, Bowden R, Pollard AJ, Simmonds P. Characterising the molecular epidemiology of human parechovirus in young infants in the UK and Canada. J Clin Virol 2024; 174:105715. [PMID: 39074411 DOI: 10.1016/j.jcv.2024.105715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 07/12/2024] [Accepted: 07/22/2024] [Indexed: 07/31/2024]
Abstract
OBJECTIVES We evaluated the extent of virus heterogeneity in PeV infected infants in the UK, Canada and Australia. METHODS Samples were collected from PeV infected infants during 2013-16. Next generation sequencing was used to obtain sequencing data and construct phylogenetic trees based on analysis of the VP1 region. Comparison was made with sequencing data available from an outbreak in Australia. RESULTS We amplified and sequenced 58 samples. All obtained PeV sequences were genotype 3 apart from one UK sample which was PeV-A5. Phylogenetic analysis revealed that all strains clustered together on the same clade and showed no significant genetic variation. We saw no significant evidence of association between sequence and either clinical severity (defined by admission to paediatric intensive care), geographical origin (compared between Canada and U.K) or year of sample collection (samples sequenced during 2013 - 2018). CONCLUSIONS In this small cohort, sequencing data indicate that PeV circulating in the UK and Canada from 2013 to 18 are derived from a common ancestor. No association between disease severity and genetic sequence was seen in the UK or Canadian cohorts. Larger studies are required to support these findings.
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Affiliation(s)
- Seilesh Kadambari
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Paediatric Infectious Diseases and Immunology, Great Ormond Street Hospital, London, UK; University College London Great Ormond Street Institute of Child Health, London, UK.
| | - Heli Harvala
- Department of Infection and Immunity, University College of London, London, UK
| | - Dung Nguyen
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Manish Sadarangani
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Natalie G Martin
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Ghada N Al-Rawahi
- Department of Pathology and Laboratory Medicine, BC Children's Hospital and BC Women's Hospital & Health Centre, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC Canada
| | - Inna Sekirov
- Public Health Laboratory, BC Centre for Disease Control, Vancouver, British Columbia, Canada
| | | | - Tom Solomon
- The Pandemic Institute, Liverpool L7 3FA, UK; Department of Clinical Infection, Microbiology, and Immunology (CIMI), Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, L69 7BE UK; National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, L69 7BE, UK; Walton Centre NHS Foundation Trust, Liverpool, L9 7LJ, UK
| | - Tanya Golubchik
- Sydney Infectious Diseases Institute, Faculty of Medicine and Health, University of Sydney, Australia; Big data institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Rory Bowden
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, VIC, Australia
| | - Andrew J Pollard
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK
| | - Peter Simmonds
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Huff HV, Wilson-Murphy M. Neuroinfectious Diseases in Children: Pathophysiology, Outcomes, and Global Challenges. Pediatr Neurol 2024; 151:53-64. [PMID: 38103523 DOI: 10.1016/j.pediatrneurol.2023.09.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 08/22/2023] [Accepted: 09/24/2023] [Indexed: 12/19/2023]
Abstract
Pathogens with affinity for the central nervous system (CNS) in children are diverse in their mechanisms of infecting and attacking the brain. Infections can reach the CNS via hematogenous routes, transneurally thereby avoiding the blood-brain barrier, and across mucosal or skin surfaces. Once transmission occurs, pathogens can wreak havoc both by direct action on host cells and via an intricate interplay between the protective and pathologic actions of the host's immune system. Pathogen prevalence varies depending on region, and susceptibility differs based on epidemiologic factors such as age, immune status, and genetics. In addition, some infectious diseases are monophasic, whereas others may lie dormant for years, thereby causing a dynamic effect on outcomes. Outcomes in survivors are highly variable for each particular pathogen and depend on the vaccination and immune status of the patient as well as the speed by which the patient receives evidence-based treatments. Given pathogens cause communicable diseases that can cause morbidity and mortality on a population level when spread, the burden is often the greatest and the outcomes the worst in low-resource settings. Here we will focus on the most common infections with a propensity to affect a child's brain, the pathologic mechanisms by which they do so, and what is known about the developmental outcomes in children who are affected by these infections.
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Affiliation(s)
- Hanalise V Huff
- Department of Neurology, National Institutes of Health, Bethesda, Maryland
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8
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Katragkou A, Sheth A, Gagliardo C, Aquino J, Shah N, Nwaobasi-Iwuh E, Melchionne C, Black P, Chiu S, Di Pentima C. Human Parechovirus Central Nervous System Infection in a Young Infant Cohort. Pediatr Infect Dis J 2023; 42:e490-e492. [PMID: 37851979 PMCID: PMC10629600 DOI: 10.1097/inf.0000000000004122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/28/2023] [Indexed: 10/20/2023]
Abstract
In 2022, a surge in cases of pediatric human parechovirus (HPeV) central nervous system infections in young infants was seen at our institution. Despite the dramatic increase in the number of cases seen that year, the clinical features of the illness were similar to prior years. The recent pediatric HPeV surge highlights the need to evaluate treatment options and standardize follow-up to better understand the long-term prognosis of infants with HPeV infection.
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Affiliation(s)
- Aspasia Katragkou
- From the Infectious Diseases Division, Department of Pediatrics, Atlantic Health System, Goryeb Children's Hospital, Morristown, New Jersey
- Department of Pediatrics, Sidney Kimmel Medical College of Thomas Jefferson University[aff_start], [/aff_end]Philadelphia, Pennsylvania
| | | | - Christina Gagliardo
- From the Infectious Diseases Division, Department of Pediatrics, Atlantic Health System, Goryeb Children's Hospital, Morristown, New Jersey
- Department of Pediatrics, Sidney Kimmel Medical College of Thomas Jefferson University[aff_start], [/aff_end]Philadelphia, Pennsylvania
| | - Jessica Aquino
- Emergency Department, Atlantic Health System, Goryeb Children's Hospital, Morristown, New Jersey
| | | | | | - Christina Melchionne
- Emergency Department, Atlantic Health System, Goryeb Children's Hospital, Morristown, New Jersey
| | | | - Stephanie Chiu
- Atlantic Center for Research, Atlantic Health System[aff_start], [/aff_end]Morristown, New Jersey
| | - Cecilia Di Pentima
- From the Infectious Diseases Division, Department of Pediatrics, Atlantic Health System, Goryeb Children's Hospital, Morristown, New Jersey
- Department of Pediatrics, Sidney Kimmel Medical College of Thomas Jefferson University[aff_start], [/aff_end]Philadelphia, Pennsylvania
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Wunrow HY, Bender RG, Vongpradith A, Sirota SB, Swetschinski LR, Novotney A, Gray AP, Ikuta KS, Sharara F, Wool EE, Aali A, Abd-Elsalam S, Abdollahi A, Abdul Aziz JM, Abidi H, Aboagye RG, Abolhassani H, Abu-Gharbieh E, Adamu LH, Adane TD, Addo IY, Adegboye OA, Adekiya TA, Adnan M, Adnani QES, Afzal S, Aghamiri S, Aghdam ZB, Agodi A, Ahinkorah BO, Ahmad A, Ahmad S, Ahmadzade M, Ahmed A, Ahmed A, Ahmed JQ, Ahmed MS, Akinosoglou K, Aklilu A, Akonde M, Alahdab F, AL-Ahdal TMA, Alanezi FM, Albelbeisi AH, Alemayehu TBB, Alene KA, Al-Eyadhy A, Al-Gheethi AAS, Ali A, Ali BA, Ali L, Ali SS, Alimohamadi Y, Alipour V, Aljunid SM, Almustanyir S, Al-Raddadi RM, Alvis-Guzman N, Al-Worafi YM, Aly H, Ameyaw EK, Ancuceanu R, Ansar A, Ansari G, Anyasodor AE, Arabloo J, Aravkin AY, Areda D, Artamonov AA, Arulappan J, Aruleba RT, Asaduzzaman M, Atalell KA, Athari SS, Atlaw D, Atout MMW, Attia S, Awoke T, Ayalew MK, Ayana TM, Ayele AD, Azadnajafabad S, Azizian K, Badar M, Badiye AD, Baghcheghi N, Bagheri M, Bagherieh S, Bahadory S, Baig AA, Barac A, Barati S, Bardhan M, Basharat Z, Bashiri A, Basnyat B, Bassat Q, Basu S, Bayileyegn NS, Bedi N, et alWunrow HY, Bender RG, Vongpradith A, Sirota SB, Swetschinski LR, Novotney A, Gray AP, Ikuta KS, Sharara F, Wool EE, Aali A, Abd-Elsalam S, Abdollahi A, Abdul Aziz JM, Abidi H, Aboagye RG, Abolhassani H, Abu-Gharbieh E, Adamu LH, Adane TD, Addo IY, Adegboye OA, Adekiya TA, Adnan M, Adnani QES, Afzal S, Aghamiri S, Aghdam ZB, Agodi A, Ahinkorah BO, Ahmad A, Ahmad S, Ahmadzade M, Ahmed A, Ahmed A, Ahmed JQ, Ahmed MS, Akinosoglou K, Aklilu A, Akonde M, Alahdab F, AL-Ahdal TMA, Alanezi FM, Albelbeisi AH, Alemayehu TBB, Alene KA, Al-Eyadhy A, Al-Gheethi AAS, Ali A, Ali BA, Ali L, Ali SS, Alimohamadi Y, Alipour V, Aljunid SM, Almustanyir S, Al-Raddadi RM, Alvis-Guzman N, Al-Worafi YM, Aly H, Ameyaw EK, Ancuceanu R, Ansar A, Ansari G, Anyasodor AE, Arabloo J, Aravkin AY, Areda D, Artamonov AA, Arulappan J, Aruleba RT, Asaduzzaman M, Atalell KA, Athari SS, Atlaw D, Atout MMW, Attia S, Awoke T, Ayalew MK, Ayana TM, Ayele AD, Azadnajafabad S, Azizian K, Badar M, Badiye AD, Baghcheghi N, Bagheri M, Bagherieh S, Bahadory S, Baig AA, Barac A, Barati S, Bardhan M, Basharat Z, Bashiri A, Basnyat B, Bassat Q, Basu S, Bayileyegn NS, Bedi N, Behnoush AH, Bekel AA, Belete MA, Bello OO, Bhagavathula AS, Bhandari D, Bhardwaj P, Bhaskar S, Bhat AN, Bijani A, Bineshfar N, Boloor A, Bouaoud S, Buonsenso D, Burkart K, Cámera LA, Castañeda-Orjuela CA, Cernigliaro A, Charan J, Chattu VK, Ching PR, Chopra H, Choudhari SG, Christopher DJ, Chu DT, Couto RAS, Cruz-Martins N, Dadras O, Dai X, Dandona L, Dandona R, Das S, Dash NR, Dashti M, De la Hoz FP, Debela SA, Dejen D, Dejene H, Demeke D, Demeke FM, Demessa BH, Demetriades AK, Demissie S, Dereje D, Dervišević E, Desai HD, Dessie AM, Desta F, Dhama K, Djalalinia S, Do TC, Dodangeh M, Dodangeh M, Dominguez RMV, Dongarwar D, Dsouza HL, Durojaiye OC, Dziedzic AM, Ekat MH, Ekholuenetale M, Ekundayo TC, El Sayed Zaki M, El-Abid H, Elhadi M, El-Hajj VG, El-Huneidi W, El-Sakka AA, Esayas HL, Fagbamigbe AF, Falahi S, Fares J, Fatehizadeh A, Fatima SAF, Feasey NA, Fekadu G, Fetensa G, Feyissa D, Fischer F, Foroutan B, Gaal PA, Gadanya MA, Gaipov A, Ganesan B, Gebrehiwot M, Gebrekidan KG, Gebremeskel TG, Gedef GM, Gela YY, Gerema U, Gessner BD, Getachew ME, Ghadiri K, Ghaffari K, Ghamari SH, Ghanbari R, Ghazy RMM, Ghozali G, Gizaw ABAB, Glushkova EV, Goldust M, Golechha M, Guadie HA, Guled RA, Gupta M, Gupta S, Gupta VB, Gupta VK, Gupta VK, Hadi NR, Haj-Mirzaian A, Haller S, Hamidi S, Haque S, Harapan H, Hasaballah AI, Hasan I, Hasani H, Hasanian M, Hassankhani H, Hassen MB, Hayat K, Heidari M, Heidari-Foroozan M, Heidari-Soureshjani R, Hezam K, Holla R, Horita N, Hossain MM, Hosseini MS, Hosseinzadeh M, Hostiuc S, Hussain S, Hussein NR, Ibitoye SE, Ilesanmi OS, Ilic IM, Ilic MD, Imam MT, Iregbu KC, Ismail NE, Iwu CCD, Jaja C, Jakovljevic M, Jamshidi E, Javadi Mamaghani A, Javidnia J, Jokar M, Jomehzadeh N, Joseph N, Joshua CE, Jozwiak JJ, Kabir Z, Kalankesh LR, Kalhor R, Kamal VK, Kandel H, Karaye IM, Karch A, Karimi H, Kaur H, Kaur N, Keykhaei M, Khajuria H, Khalaji A, Khan A, Khan IA, Khan M, Khan T, Khatab K, Khatatbeh MM, Khayat Kashani HR, Khubchandani J, Kim MS, Kisa A, Kisa S, Kompani F, Koohestani HR, Kothari N, Krishan K, Krishnamoorthy Y, Kulimbet M, Kumar M, Kumaran SD, Kuttikkattu A, Kwarteng A, Laksono T, Landires I, Laryea DO, Lawal BK, Le TTT, Ledda C, Lee SW, Lee S, Lema GK, Levi M, Lim SS, Liu X, Lopes G, Lutzky Saute R, Machado Teixeira PH, Mahmoodpoor A, Mahmoud MA, Malakan Rad E, Malhotra K, Malik AA, Martinez-Guerra BA, Martorell M, Mathur V, Mayeli M, Medina JRC, Melese A, Memish ZA, Mentis AFA, Merza MA, Mestrovic T, Michalek IM, Minh LHN, Mirahmadi A, Mirmosayyeb O, Misganaw A, Misra AK, Moghadasi J, Mohamed NS, Mohammad Y, Mohammadi E, Mohammed S, Mojarrad Sani M, Mojiri-forushani H, Mokdad AH, Momtazmanesh S, Monasta L, Moni MA, Mossialos E, Mostafavi E, Motaghinejad M, Mousavi Khaneghah A, Mubarik S, Muccioli L, Muhammad JS, Mulita F, Mulugeta T, Murillo-Zamora E, Mustafa G, Muthupandian S, Nagarajan AJ, Nainu F, Nair TS, Nargus S, Nassereldine H, Natto ZS, Nayak BP, Negoi I, Negoi RI, Nejadghaderi SA, Nguyen HQ, Nguyen PT, Nguyen VT, Niazi RK, Noroozi N, Nouraei H, Nuñez-Samudio V, Nuruzzaman KM, Nwatah VE, Nzoputam CI, Nzoputam OJ, Oancea B, Obaidur RM, Odetokun IA, Ogunsakin RE, Okonji OC, Olagunju AT, Olana LT, Olufadewa II, Oluwafemi YD, Oumer KS, Ouyahia A, P A M, Pakshir K, Palange PN, Pardhan S, Parikh RR, Patel J, Patel UK, Patil S, Paudel U, Pawar S, Pensato U, Perdigão J, Pereira M, Peres MFP, Petcu IR, Pinheiro M, Piracha ZZ, Pokhrel N, Postma MJ, Prates EJS, Qattea I, Raghav PR, Rahbarnia L, Rahimi-Movaghar V, Rahman M, Rahman MA, Rahmanian V, Rahnavard N, Ramadan H, Ramasubramani P, Rani U, Rao IR, Rapaka D, Ratan ZA, Rawaf S, Redwan EMM, Reiner Jr RC, Rezaei N, Riad A, Ribeiro da Silva TM, Roberts T, Robles Aguilar G, Rodriguez JAB, Rosenthal VD, Saddik B, Sadeghian S, Saeed U, Safary A, Saheb Sharif-Askari F, Saheb Sharif-Askari N, Sahebkar A, Sahu M, Sajedi SA, Saki M, Salahi S, Salahi S, Saleh MA, Sallam M, Samadzadeh S, Samy AM, Sanjeev RK, Satpathy M, Seylani A, Sha'aban A, Shafie M, Shah PA, Shahrokhi S, Shahzamani K, Shaikh MA, Sham S, Shannawaz M, Sheikh A, Shenoy SM, Shetty PH, Shin JI, Shokri F, Shorofi SA, Shrestha S, Sibhat MM, Siddig EE, Silva LMLR, Singh H, Singh JA, Singh P, Singh S, Sinto R, Skryabina AA, Socea B, Sokhan A, Solanki R, Solomon Y, Sood P, Soshnikov S, Stergachis A, Sufiyan MB, Suliankatchi Abdulkader R, Sultana A, T Y SS, Taheri E, Taki E, Tamuzi JJLL, Tan KK, Tat NY, Temsah MH, Terefa DR, Thangaraju P, Tibebu NS, Ticoalu JHV, Tillawi T, Tincho MB, Tleyjeh II, Toghroli R, Tovani-Palone MR, Tufa DG, Turner P, Ullah I, Umeokonkwo CD, Unnikrishnan B, Vahabi SM, Vaithinathan AG, Valizadeh R, Varthya SB, Vos T, Waheed Y, Walde MT, Wang C, Weerakoon KG, Wickramasinghe ND, Winkler AS, Woldemariam M, Worku NA, Wright C, Yada DY, Yaghoubi S, Yahya GATY, Yenew CYY, Yesiltepe M, Yi S, Yiğit V, You Y, Yusuf H, Zakham F, Zaman M, Zaman SB, Zare I, Zareshahrabadi Z, Zarrintan A, Zastrozhin MS, Zhang H, Zhang J, Zhang ZJ, Zheng P, Zoladl M, Zumla A, Hay SI, Murray CJL, Naghavi M, Kyu HH. Global, regional, and national burden of meningitis and its aetiologies, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2023; 22:685-711. [PMID: 37479374 PMCID: PMC10356620 DOI: 10.1016/s1474-4422(23)00195-3] [Show More Authors] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/28/2023] [Accepted: 05/05/2023] [Indexed: 07/23/2023]
Abstract
BACKGROUND Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by 2030, and assessing trends in the global meningitis burden can help track progress and identify gaps in achieving these goals. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we aimed to assess incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990 to 2019, for 204 countries and territories. METHODS We modelled meningitis mortality using vital registration, verbal autopsy, sample-based vital registration, and mortality surveillance data. Meningitis morbidity was modelled with a Bayesian compartmental model, using data from the published literature identified by a systematic review, as well as surveillance data, inpatient hospital admissions, health insurance claims, and cause-specific meningitis mortality estimates. For aetiology estimation, data from multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature studies were analysed by use of a network analysis model to estimate the proportion of meningitis deaths and cases attributable to the following aetiologies: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Staphylococcus aureus, viruses, and a residual other pathogen category. FINDINGS In 2019, there were an estimated 236 000 deaths (95% uncertainty interval [UI] 204 000-277 000) and 2·51 million (2·11-2·99) incident cases due to meningitis globally. The burden was greatest in children younger than 5 years, with 112 000 deaths (87 400-145 000) and 1·28 million incident cases (0·947-1·71) in 2019. Age-standardised mortality rates decreased from 7·5 (6·6-8·4) per 100 000 population in 1990 to 3·3 (2·8-3·9) per 100 000 population in 2019. The highest proportion of total all-age meningitis deaths in 2019 was attributable to S pneumoniae (18·1% [17·1-19·2]), followed by N meningitidis (13·6% [12·7-14·4]) and K pneumoniae (12·2% [10·2-14·3]). Between 1990 and 2019, H influenzae showed the largest reduction in the number of deaths among children younger than 5 years (76·5% [69·5-81·8]), followed by N meningitidis (72·3% [64·4-78·5]) and viruses (58·2% [47·1-67·3]). INTERPRETATION Substantial progress has been made in reducing meningitis mortality over the past three decades. However, more meningitis-related deaths might be prevented by quickly scaling up immunisation and expanding access to health services. Further reduction in the global meningitis burden should be possible through low-cost multivalent vaccines, increased access to accurate and rapid diagnostic assays, enhanced surveillance, and early treatment. FUNDING Bill & Melinda Gates Foundation.
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Abeywickrema M, Kelly D, Kadambari S. Management of neonatal central nervous system viral infections: Knowledge gaps and research priorities. Rev Med Virol 2023; 33:e2421. [PMID: 36639694 DOI: 10.1002/rmv.2421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 12/22/2022] [Accepted: 12/27/2022] [Indexed: 01/15/2023]
Abstract
Congenital CMV, enteroviruses, human parechovirus and herpes simplex virus are all common causes of severe central nervous system (CNS) infection in neonates. The introduction of screening (i.e. newborn hearing screening programme), integration of molecular syndromic testing (i.e. multiplex polymerase chain reaction assays) and increase in sexually transmitted infections (i.e. anogenital herpes) have contributed to increases in each of these infections over the last decade. However, therapeutic options are highly limited in part due to the lack of epidemiological data informing trials. This review will describe our current understanding of the clinical burden and epidemiology of these severe neonatal CNS infections, outline the novel antiviral and vaccines in the pipeline and suggest future research studies which could help develop new therapeutics.
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Affiliation(s)
- Movin Abeywickrema
- Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Dominic Kelly
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK
| | - Seilesh Kadambari
- Department of Paediatric Infectious Diseases, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.,University College London, Great Ormond Street Institute of Child Health, London, UK
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McBride M, Williman J, Best E, Walls T, Sadarangani M, Grant CC, Martin NG. The epidemiology of aseptic meningitis in New Zealand children from 1991 to 2020. J Paediatr Child Health 2022; 58:1980-1989. [PMID: 35861029 PMCID: PMC9796418 DOI: 10.1111/jpc.16131] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 06/19/2022] [Accepted: 07/06/2022] [Indexed: 01/01/2023]
Abstract
AIM Aseptic meningitis, including culture negative and viral meningitis, contributes a significant health-care burden, including unnecessary antibiotic use and hospitalisation to treat possible bacterial meningitis. This study analysed aseptic meningitis hospitalisations in New Zealand (NZ) children over 29 years. METHODS In this population-based study, aseptic meningitis hospitalisations in NZ children <15 years old were analysed from 1991 to 2020. Incident rate ratios were calculated using Poisson regression models. Variations in hospitalisations by age, year, sex, ethnicity, geographical region and socio-economic deprivation were analysed. RESULTS There were 5142 paediatric aseptic meningitis hospitalisations from 1991 to 2020. Most were unspecified viral meningitis (64%), followed by enterovirus (29%). Hospitalisation rates varied annually with a median of 18.4/100 000 children including a peak in 2001 of 56.4/100 000 (51.7-61.6). From 2002 to 2019, rates increased by 8.4%/year (7.2-9.5%) in infants <90 days old but decreased in all other age groups. In 2020, a reduction in hospitalisations to 9.6/100 000 (7.9-11.8) occurred, and in infants <90 days old were 0.37 times expected. Hospitalisations were 1.50 times (1.49-1.68) higher in males than females; higher in children of Māori (P < 0.001) and Pacific (P < 0.001) versus European ethnicity; and higher for children living in the most (2.44 times, (2.16-2.75)) versus least deprived households; and in northern versus southern NZ. CONCLUSIONS Aseptic meningitis hospitalisations increased in young infants during 29 years of surveillance, apart from 2020 when admissions reduced during the COVID-19 pandemic. In contrast, hospitalisations decreased in children aged >1 year. Further investigation into reasons for higher admissions by ethnic group, geographical location and increased deprivation are required.
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Affiliation(s)
- Michelia McBride
- Department of PaediatricsUniversity of Otago ChristchurchChristchurchNew Zealand
| | - Jonathan Williman
- Department of Population HealthUniversity of Otago ChristchurchChristchurchNew Zealand
| | - Emma Best
- Department of Paediatrics: Child and Youth HealthUniversity of AucklandAucklandNew Zealand,Department of Paediatric Infectious DiseasesStarship Children's HospitalAucklandNew Zealand
| | - Tony Walls
- Department of PaediatricsUniversity of Otago ChristchurchChristchurchNew Zealand
| | - Manish Sadarangani
- Vaccine Evaluation CenterBC Children's Hospital Research InstituteVancouverBritish ColumbiaCanada,Department of PediatricsUniversity of British ColumbiaVancouverBritish ColumbiaCanada
| | - Cameron C Grant
- Department of Paediatrics: Child and Youth HealthUniversity of AucklandAucklandNew Zealand
| | - Natalie G Martin
- Department of PaediatricsUniversity of Otago ChristchurchChristchurchNew Zealand
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Al-Qahtani SM, Shati AA, Alqahtani YA, Ali AS. Etiology, Clinical Phenotypes, Epidemiological Correlates, Laboratory Biomarkers and Diagnostic Challenges of Pediatric Viral Meningitis: Descriptive Review. Front Pediatr 2022; 10:923125. [PMID: 35783317 PMCID: PMC9249085 DOI: 10.3389/fped.2022.923125] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 05/25/2022] [Indexed: 12/04/2022] Open
Abstract
Meningitis is an inflammation of the brain and spinal cord meninges caused by infectious and non-infectious agents. Infectious agents causing meningitis include viruses, bacteria, and fungi. Viral meningitis (VM), also termed aseptic meningitis, is caused by some viruses, such as enteroviruses (EVs), herpesviruses, influenza viruses, and arboviruses. However, EVs represent the primary cause of VM. The clinical symptoms of this neurological disorder may rapidly be observed after the onset of the disease, or take prolonged time to develop. The primary clinical manifestations of VM include common flu-like symptoms of headache, photophobia, fever, nuchal rigidity, myalgia, and fatigue. The severity of these symptoms depends on the patient's age; they are more severe among infants and children. The course of infection of VM varies between asymptomatic, mild, critically ill, and fatal disease. Morbidities and mortalities of VM are dependent on the early recognition and treatment of the disease. There were no significant distinctions in the clinical phenotypes and symptoms between VM and meningitis due to other causative agents. To date, the pathophysiological mechanisms of VM are unclear. In this scientific communication, a descriptive review was performed to give an overview of pediatric viral meningitis (PVM). PVM may occasionally result in severe neurological consequences such as mental retardation and death. Clinical examinations, including Kernig's, Brudzinski's, and nuchal rigidity signs, were attempted to determine the clinical course of PVM with various success rates revealed. Some epidemiological correlates of PVM were adequately reviewed and presented in this report. They were seen depending mainly on the causative virus. The abnormal cytological and biochemical features of PVM were also discussed and showed potentials to distinguish PVM from pediatric bacterial meningitis (PBM). The pathological, developmental, behavioral, and neuropsychological complications of PVM were also presented. All the previously utilized techniques for the etiological diagnosis of PVM which include virology, serology, biochemistry, and radiology, were presented and discussed to determine their efficiencies and limitations. Finally, molecular testing, mainly PCR, was introduced and showed 100% sensitivity rates.
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Affiliation(s)
- Saleh M. Al-Qahtani
- Department of Child Health, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Ayed A. Shati
- Department of Child Health, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Youssef A. Alqahtani
- Department of Child Health, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Abdelwahid Saeed Ali
- Department of Microbiology and Clinical Parasitology, College of Medicine, King Khalid University, Abha, Saudi Arabia
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Bucci S, Coltella L, Martini L, Santisi A, De Rose DU, Piccioni L, Campi F, Ronchetti MP, Longo D, Lucignani G, Dotta A, Auriti C. Clinical and Neurodevelopmental Characteristics of Enterovirus and Parechovirus Meningitis in Neonates. Front Pediatr 2022; 10:881516. [PMID: 35669403 PMCID: PMC9165715 DOI: 10.3389/fped.2022.881516] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 05/02/2022] [Indexed: 11/25/2022] Open
Abstract
Background Non-polio-enteroviruses (EV) and human parechoviruses (HPeV) are small RNA viruses, which in newborns cause infections with a wide range of severity. Today molecular biology tools allow us to diagnose viral meningitis in neonates, sparing patients from useless antibiotics. Data on neurodevelopmental outcome of children who contract enterovirus meningitis in early childhood are still limited in the literature. Aims To evaluate the neurodevelopmental outcome of newborns with documented enterovirus and parechovirus meningitis contracted within the first months of life. Methods Enterovirus and parechovirus were detected on cerebrospinal fluid (CSF) and plasma by RT-PCR. The virological typing was done according to WHO recommendations. During the hospitalization each neonate underwent many diagnostic and instrumental examinations, to evaluate any neurological lesions attributable to the infection. After the discharge children entered in an outpatient interdisciplinary assessment process, comprehensive of the administration of Bayley III scales up to 12 months old. Results We observed longitudinally 30 children, born at term (mean GA 39.7 ± 0.8 weeks, mean birthweight was 3,457 ± 405 grams), who contracted enterovirus and parechovirus meningitis within the first month of life (mean age at diagnosis was 15.8 ± 7.33 days). We were able to perform the genetic typing only on 15/30 (50.0%) cerebrospinal fluid (CSF) samples from 15 neonates. We found MRI anomalies in 9/26 observed neonates (34.6%): one of them presented brainstem abnormality that are specific of enteroviral central nervous system (CNS) involvement. During the follow up children displayed an overall normal neurodevelopment and no deficit in visual and hearing areas. The mean cognitive (105.19 ± 8.71), speech (100.23 ± 8.22) and motor (97.00 ± 8.98) composite scores, assessed by Bayley III, were normal in 29/30 (96.7%). Despite this, children with pathological brain magnetic resonance imaging (MRI) scored significantly lower (p = 0.01) than children with normal brain MRI on cognitive subscale at 12 months of life. Conclusions Early enterovirus infections can be associated to brain MRI abnormalities, more frequently the earlier the infection. Although within a normal range, our children with pathological brain MRI scored significantly lower than those with normal brain MRI on cognitive subscale at 12 months of life.
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Affiliation(s)
- Silvia Bucci
- Department of Neurosciences, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Luana Coltella
- Department of Microbiology and Virology, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Ludovica Martini
- Medical and Surgical Department of Fetus-Newborn-Infant, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Alessandra Santisi
- Medical and Surgical Department of Fetus-Newborn-Infant, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Domenico Umberto De Rose
- Medical and Surgical Department of Fetus-Newborn-Infant, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Livia Piccioni
- Department of Microbiology and Virology, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Francesca Campi
- Medical and Surgical Department of Fetus-Newborn-Infant, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Maria Paola Ronchetti
- Medical and Surgical Department of Fetus-Newborn-Infant, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Daniela Longo
- Department of Imaging, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Giulia Lucignani
- Department of Imaging, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Andrea Dotta
- Medical and Surgical Department of Fetus-Newborn-Infant, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
| | - Cinzia Auriti
- Medical and Surgical Department of Fetus-Newborn-Infant, “Bambino Gesù” Children's Hospital Scientific Hospitalization and Treatment Institute (IRCCS), Rome, Italy
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Paul SP, Balakumar V, Kirubakaran A, Niharika J, Heaton PA, Turner PC. Turnaround times for molecular testing of pediatric viral cerebrospinal fluid samples in United Kingdom laboratories. World J Clin Pediatr 2022; 11:289-294. [PMID: 35663004 PMCID: PMC9134154 DOI: 10.5409/wjcp.v11.i3.289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/01/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Rapid molecular testing has revolutionized the management of suspected viral meningitis and encephalitis by providing an etiological diagnosis in < 90 min with potential to improve outcomes and shorten inpatient stays. However, use of molecular assays can vary widely.
AIM To evaluate current practice for molecular testing of pediatric cerebrospinal fluid (CSF) samples across the United Kingdom using a structured questionnaire.
METHODS A structured telephone questionnaire survey was conducted between July and August 2020. Data was collected on the availability of viral CSF nucleic acid amplification testing (NAAT), criteria used for testing and turnaround times including the impact of the coronavirus disease 2019 pandemic.
RESULTS Of 196/212 (92%) microbiology laboratories responded; 63/196 (32%) were excluded from final analysis as they had no on-site microbiology laboratory and outsourced their samples. Of 133 Laboratories included in the study, 47/133 (35%) had onsite facilities for viral CSF NAAT. Hospitals currently undertaking onsite NAAT (n = 47) had much faster turnaround times with 39 centers (83%) providing results in ≤ 24 h as compared to those referring samples to neighboring laboratories (5/86; 6%).
CONCLUSION Onsite/near-patient rapid NAAT (including polymerase chain reaction) is recommended wherever possible to optimize patient management in the acute setting.
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Affiliation(s)
- Siba Prosad Paul
- Department of Paediatrics, Yeovil District Hospital, Yeovil BA21 4AT, Somerset, United Kingdom
| | | | - Arangan Kirubakaran
- Department of Paediatrics, Hillingdon Hospital, Uxbridge UB8 3NN, United Kingdom
| | | | - Paul Anthony Heaton
- Department of Paediatrics, Yeovil District Hospital, Yeovil BA21 4AT, Somerset, United Kingdom
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15
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Paul SP, Balakumar V, Kirubakaran A, Niharika J, Heaton PA, Turner PC. Turnaround times for molecular testing of pediatric viral cerebrospinal fluid samples in United Kingdom laboratories. World J Clin Pediatr 2022. [DOI: 10.5409/wjcp.v11.i3.290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Rapid molecular testing has revolutionized the management of suspected viral meningitis and encephalitis by providing an etiological diagnosis in < 90 min with potential to improve outcomes and shorten inpatient stays. However, use of molecular assays can vary widely.
AIM To evaluate current practice for molecular testing of pediatric cerebrospinal fluid (CSF) samples across the United Kingdom using a structured questionnaire.
METHODS A structured telephone questionnaire survey was conducted between July and August 2020. Data was collected on the availability of viral CSF nucleic acid amplification testing (NAAT), criteria used for testing and turnaround times including the impact of the coronavirus disease 2019 pandemic.
RESULTS Of 196/212 (92%) microbiology laboratories responded; 63/196 (32%) were excluded from final analysis as they had no on-site microbiology laboratory and outsourced their samples. Of 133 Laboratories included in the study, 47/133 (35%) had onsite facilities for viral CSF NAAT. Hospitals currently undertaking onsite NAAT (n = 47) had much faster turnaround times with 39 centers (83%) providing results in ≤ 24 h as compared to those referring samples to neighboring laboratories (5/86; 6%).
CONCLUSION Onsite/near-patient rapid NAAT (including polymerase chain reaction) is recommended wherever possible to optimize patient management in the acute setting.
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Affiliation(s)
- Siba Prosad Paul
- Department of Paediatrics, Yeovil District Hospital, Yeovil BA21 4AT, Somerset, United Kingdom
| | | | - Arangan Kirubakaran
- Department of Paediatrics, Hillingdon Hospital, Uxbridge UB8 3NN, United Kingdom
| | | | - Paul Anthony Heaton
- Department of Paediatrics, Yeovil District Hospital, Yeovil BA21 4AT, Somerset, United Kingdom
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16
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Lee EY, Tan JHY, Choong CT, Tee NWS, Chong CY, Thoon KC, Maiwald M, Tan MSS, Tan NWH. Hearing and Neurodevelopmental Outcomes of Young Infants with Parechovirus-A and Enterovirus Meningitis: Cohort Study in Singapore Children and Literature Review. JOURNAL OF PEDIATRIC NEUROLOGY 2021. [DOI: 10.1055/s-0040-1716366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Abstract
Parechovirus-A (PeV-A) and Enterovirus (EV) commonly cause childhood aseptic meningitis. Bacterial meningitis in children has been associated with devastating long-term sequelae. However, developmental outcomes are unclear in Parechovirus meningitis. This study aims to review the clinical findings and developmental outcomes of infants with PeV-A and EV meningitis. We performed a retrospective study of infants aged 90 days or younger being admitted to our hospital with PeV-A meningitis between November 2015 and July 2017, with positive cerebrospinal fluid (CSF) PeV-A PCR and negative blood and CSF bacterial cultures. Hearing and neurodevelopmental outcomes were compared with a previous cohort of infants aged 90 days or younger with EV meningitis admitted from January 2015 to December 2015. A total of 161 infants were included in our study, of which 68 infants (42.2%) had PeV-A meningitis and 93 infants (57.8%) had EV meningitis. We assessed their developmental outcome at 6 months, 1 year, and 2 years post-meningitis. At 2 years post-meningitis, three infants with PeV-A meningitis had developmental delay (5.5%), whereas none with EV meningitis had developmental delay. One patient had speech delay and autism spectrum disorder, while two had mild speech delay. When compared with our cohort of EV meningitis ≤90 days old, children with PeV-A meningitis ≤90 days old were more likely to have developmental delay 2 years post-meningitis (odds ratio 2.4, 95% confidence interval 2.0–3.0, p = 0.043). None of the patients with PeV-A or EV meningitis had sensorineural hearing loss or neurological sequelae, such as cortical blindness, oropharyngeal dysphagia, hydrocephalus, epilepsy, or cerebral palsy. Infants with PeV-A meningitis had a significant risk of developmental delay 2 years post-meningitis compared with those with EV meningitis. It is important to follow-up the developmental milestones of infants diagnosed with PeV-A meningitis for at least 2 years; and when they develop developmental delay, to ensure that they receive appropriate intervention.
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Affiliation(s)
- Elis Yuexian Lee
- Department of Pediatrics, KK Women's and Children's Hospital, Singapore, Singapore
| | - Jessica Hui Yin Tan
- Department of Pediatrics, KK Women's and Children's Hospital, Singapore, Singapore
| | - Chew Thye Choong
- Department of Pediatrics, Neurology Service, KK Women's and Children's Hospital, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Nancy Wen Sim Tee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Laboratory Medicine, National University Hospital, Singapore, Singapore
| | - Chia Yin Chong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Pediatrics, Infectious Disease Service, KK Women's and Children's Hospital, Singapore, Singapore
| | - Koh Cheng Thoon
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Pediatrics, Infectious Disease Service, KK Women's and Children's Hospital, Singapore, Singapore
| | - Matthias Maiwald
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Singapore
| | - Melody Si Shan Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Natalie Woon Hui Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Pediatrics, Infectious Disease Service, KK Women's and Children's Hospital, Singapore, Singapore
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17
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Stephens C, Reynolds C, Cremin M, Barry R, Morley U, Gibson L, De Gascun CF, Felsenstein S. Parent-administered Neurodevelopmental Follow up in Children After Picornavirus CNS Infections. Pediatr Infect Dis J 2021; 40:867-872. [PMID: 34260497 DOI: 10.1097/inf.0000000000003192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Data on the neurodevelopment of children who experienced central nervous system (CNS) infections with enteroviruses (EV) or parechoviruses (hPeV) is scarce and mostly limited to follow up of short-term outcomes. METHODS Parents of children who presented between 2014 and 2019, underwent a lumbar puncture and whose cerebrospinal fluid was polymerase chain reaction positive for EV or hPeV, were asked to complete a care-giver-administered neurodevelopmental assessment tool (The Ages and Stages Instrument [ASQ3]). Clinical data of the infective episode were collected from patient notes. RESULTS Of 101 children, 43 (10 hPeV+, 33 EV+) submitted ASQ3 results. Median age at assessment was 38.9 months (interquartile range, 15.4-54.8), the follow-up interval 3 years (median 37 months; interquartile range, 13.9-53.1). Age, inflammatory markers, and cerebrospinal fluid pleocytosis during the infective event were not associated with ASQ3 scores. In 23 children (17 EV+, 6 hPeV+), no neurodevelopmental concerns were reported. Two more had preexisting developmental delay and were excluded. Of the remaining, 18/41 (43.9%) reported ASQ3 scores indicating need for monitoring or professional review in at least 1 category, not differing by pathogen (EV 14/31, 45.2%; hPeV 4/10, 40%; P = 0.71). Seven children will require formal review, scoring ≥2 SD below the mean in at least 1 category (6/31 EV+, 1/10 hPeV+, P = 0.7), 3 scored ≥2 SD below the mean in more than 1 area. CONCLUSIONS Parent-administered developmental assessment of children with a history of early picornavirus infection of the CNS identified a subgroup that requires formal neurodevelopmental review. Wider application of community-based developmental screening will complement our understanding of the impact of CNS infections in early childhood.
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Affiliation(s)
- Carol Stephens
- From the Department of Pediatrics, Cork University Hospital, Wilton, Cork, Republic of Ireland
| | - Clare Reynolds
- From the Department of Pediatrics, Cork University Hospital, Wilton, Cork, Republic of Ireland
| | - Molly Cremin
- From the Department of Pediatrics, Cork University Hospital, Wilton, Cork, Republic of Ireland
| | - Rachel Barry
- Department of Microbiology, Cork University Hospital, Wilton, Cork, Republic of Ireland
| | - Ursula Morley
- National Virus Reference Laboratory, University College Dublin, Dublin, Republic of Ireland
| | - Louise Gibson
- From the Department of Pediatrics, Cork University Hospital, Wilton, Cork, Republic of Ireland
| | - Cillian F De Gascun
- National Virus Reference Laboratory, University College Dublin, Dublin, Republic of Ireland
| | - Susana Felsenstein
- Department of Infectious Diseases, Alder Hey Children's Hospital NHS Trust, East Prescot Road, Liverpool, Great Britain
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18
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de Ceano-Vivas M, García ML, Velázquez A, Martín del Valle F, Menasalvas A, Cilla A, Epalza C, Romero MP, Cabrerizo M, Calvo C. Neurodevelopmental Outcomes of Infants Younger Than 90 Days Old Following Enterovirus and Parechovirus Infections of the Central Nervous System. Front Pediatr 2021; 9:719119. [PMID: 34650940 PMCID: PMC8505960 DOI: 10.3389/fped.2021.719119] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/30/2021] [Indexed: 11/24/2022] Open
Abstract
Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of central nervous system (CNS) infection in young infants. They have been implicated in neurodevelopmental delay, however limited data are available. The aim of this study is to describe the clinical outcome of young infants and to assess and compare the medium-term neurodevelopment following CNS infections caused by EV and HPeV. A multicentre observational ambispective study was conducted between May 2013 and March 2018. Children under 3 months of age with EV or HPeV CNS infection excluding encephalitis were included. Infants were contacted 1 year after the acute infection and their neurological development was evaluated using the Ages and Stages Questionnaire-3 (ASQ-3). If any area assessed was abnormal during the first round of tests, a second round was completed 6 to 12 months later. Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) were positive for EV and 15 (31.3%) for HPeV. At first assessment 14 out of 29 EV (48.3%) and 3 out of 15 HPeV (20%) positive cases presented some developmental concern in the ASQ-3 test. EV-positive infants showed mild and moderate alteration in all domains analyzed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (31 vs. 0%, p = 0.016). At second assessment 4 out of 13 EV-positive patients (30.8%) showed mild to moderate concerns in communication and gross motor function domains and 3 out of 13 (23.1%) showed significant concern in fine motor function. Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months almost half of the EV-infected infants (48.3%) and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3 test. We recommend monitor the neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation of psychomotor development if necessary.
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Affiliation(s)
| | - M. Luz García
- Department of Pediatrics, Severo Ochoa University Hospital, Madrid, Spain
| | - Ana Velázquez
- Department of Pediatrics, La Paz University Hospital, Madrid, Spain
| | | | - Ana Menasalvas
- Department of Pediatrics, Virgen de la Arixaca University Hospital, Murcia, Spain
| | - Amaia Cilla
- Department of Pediatrics, Burgos University Hospital, Burgos, Spain
| | - Cristina Epalza
- Department of Pediatrics, 12 de Octubre University Hospital, Madrid, Spain
| | - M. Pilar Romero
- Department of Microbiology, La Paz University Hospital, Madrid, Spain
| | - María Cabrerizo
- National Centre for Microbiology, Instituto de Salud Carlos III, CIBER de Epidemiología y Salud Pública, Madrid, Spain
| | - Cristina Calvo
- Department of Pediatric Infectious Diseases, La Paz University Hospital and La Paz Research Institute (IdiPaz), Madrid, Spain
- Translational Research Network in Pediatric Infectious Diseases (Red de Investigación Traslacional en Infectología Pediátrica), Madrid, Spain
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19
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Raouf M, El-Din OS, Khadr NA, Mokhless N. Clinical and laboratory detection of nonpolio enteroviruses among different age groups of aseptic meningitis patients in Alexandria, Egypt. J Med Virol 2021; 93:3389-3396. [PMID: 32880992 DOI: 10.1002/jmv.26480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 07/05/2020] [Accepted: 08/25/2020] [Indexed: 11/11/2022]
Abstract
BACKGROUND Viral meningitis is the most common type of meningitis. Worldwide, nonpolio enteroviruses (NPEVs) account for 23%-60% of all cases of viral meningitis. We aimed to detect NPEV among aseptic meningitis cases using reverse transcription-polymerase chain reaction (RT-PCR) and evaluate molecular testing versus clinical and laboratory parameters. PATIENTS AND METHODS A 2-year prospective study was conducted for all clinically suspected meningitis patients, who underwent lumbar puncture in Alshatby University and Alexandria Fever Hospitals. Clinical manifestations were reviewed; cytological, microbiological, and biochemical examinations were done. One-step RT-PCR for NPEV was introduced to a routine workflow using Pan-Enterovirus primers. RESULTS Out of 2519 patients, 994 (40%) patients were found to have positive cerebrospinal fluid findings, out of which 716 (72%) patients had positive findings of aseptic meningitis. Ninety-four samples were randomly selected and divided across four age groups: neonates, infants, children, and adults. The significant difference was found among adult patients regarding fever, vomiting, headache, signs of meningeal irritation, cranial nerve affection, and focal neurological deficits (p ≤ .05). Seven cases (7.4%) were found to be NPEV positive by RT-PCR. Positive NPEV PCR samples were shown to be statistically significant among neonates (p ≤ .05). The statistical significance was found among the NPEV group regarding the length of hospital stay and duration of IV antibiotic intake while no statistical significance was found with any clinical or laboratory findings. CONCLUSION RT-PCR was reliable to identify NPEV while clinical and laboratory findings were inconclusive. NPEV showed low incidence and slight seasonal variation which rings the bell to investigate other causes of viral meningitis throughout the year.
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MESH Headings
- Adolescent
- Adult
- Child
- Child, Preschool
- Clinical Laboratory Techniques/statistics & numerical data
- Egypt/epidemiology
- Enterovirus/classification
- Enterovirus/genetics
- Enterovirus/isolation & purification
- Enterovirus/pathogenicity
- Enterovirus Infections/diagnosis
- Enterovirus Infections/epidemiology
- Female
- Humans
- Infant
- Infant, Newborn
- Male
- Meningitis, Aseptic/cerebrospinal fluid
- Meningitis, Aseptic/epidemiology
- Meningitis, Aseptic/virology
- Meningitis, Viral/cerebrospinal fluid
- Meningitis, Viral/diagnosis
- Meningitis, Viral/epidemiology
- Meningitis, Viral/virology
- Prospective Studies
- RNA, Viral/genetics
- Young Adult
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Affiliation(s)
- May Raouf
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ola Salah El-Din
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Nashwa Abo Khadr
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Nadia Mokhless
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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20
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Kohil A, Jemmieh S, Smatti MK, Yassine HM. Viral meningitis: an overview. Arch Virol 2021; 166:335-345. [PMID: 33392820 PMCID: PMC7779091 DOI: 10.1007/s00705-020-04891-1] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 10/04/2020] [Indexed: 12/14/2022]
Abstract
Meningitis is a serious condition that affects the central nervous system. It is an inflammation of the meninges, which is the membrane that surrounds both the brain and the spinal cord. Meningitis can be caused by bacterial, viral, or fungal infections. Many viruses, such as enteroviruses, herpesviruses, and influenza viruses, can cause this neurological disorder. However, enteroviruses have been found to be the underlying cause of most viral meningitis cases worldwide. With few exceptions, the clinical manifestations and symptoms associated with viral meningitis are similar for the different causative agents, which makes it difficult to diagnose the disease at early stages. The pathogenesis of viral meningitis is not clearly defined, and more studies are needed to improve the health care of patients in terms of early diagnosis and management. This review article discusses the most common causative agents, epidemiology, clinical features, diagnosis, and pathogenesis of viral meningitis.
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Affiliation(s)
- Amira Kohil
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - Sara Jemmieh
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - Maria K Smatti
- Biomedical Research Center, Qatar University, Doha, Qatar
| | - Hadi M Yassine
- Biomedical Research Center, Qatar University, Doha, Qatar.
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21
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Aldriweesh MA, Shafaay EA, Alwatban SM, Alkethami OM, Aljuraisi FN, Bosaeed M, Alharbi NK. Viruses Causing Aseptic Meningitis: A Tertiary Medical Center Experience With a Multiplex PCR Assay. Front Neurol 2020; 11:602267. [PMID: 33424752 PMCID: PMC7793969 DOI: 10.3389/fneur.2020.602267] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 11/10/2020] [Indexed: 12/11/2022] Open
Abstract
Background: Central nervous system (CNS) infection is associated with high rates of morbidity and mortality, and despite advancements in molecular testing, aseptic meningitis remains challenging to diagnose. Aseptic meningitis cases are often underreported worldwide, which impacts the quality of patient care. Therefore, we aimed to assess the results of BioFire® FilmArray® meningitis/encephalitis (ME) PCR panel, clinical characteristics, and etiologies of aseptic meningitis patients. Methods: From January 2018 to January 2020, all pediatric and adult patients in a large tertiary medical center who underwent lumbar puncture and cerebrospinal fluid (CSF) testing by a ME multiplex PCR panel and who fit the aseptic meningitis definition were retrospectively reviewed. Results: Data were reviewed from 1,607 patients; 240 met the inclusion criteria (54.6% males; 68.8% <4 years of age). The rate of detected viral causes of aseptic meningitis was 40.4%; therefore, 59.6% of the patients remained with unidentified etiology. Among the identified viral meningitis, enterovirus and human herpesvirus 6 (HHV-6) were the most common (25 and 7.9%, respectively). The median length of hospital stay was 6 days, and it was longer in patients with unidentifiable aseptic meningitis (p < 0.0001). Conclusion: Aseptic meningitis is common among suspected meningitis patients, but most cases remained of unknown etiology. The most common identified viruses were enterovirus followed by HHV-6, and there is predominance in males and the pediatric age group. These results highlight that further research is needed to identify other etiologies and possible additional viral pathogens for aseptic meningitis in the current diagnostic methods.
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Affiliation(s)
- Mohammed A Aldriweesh
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Edi A Shafaay
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Saud M Alwatban
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Obeid M Alkethami
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Faisal N Aljuraisi
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mohammad Bosaeed
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.,Division of Infectious Diseases, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Naif Khalaf Alharbi
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.,Department of Infectious Disease Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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22
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van Hinsbergh TMT, Elbers RG, Hans Ket JCF, van Furth AM, Obihara CC. Neurological and neurodevelopmental outcomes after human parechovirus CNS infection in neonates and young children: a systematic review and meta-analysis. THE LANCET CHILD & ADOLESCENT HEALTH 2020; 4:592-605. [PMID: 32710840 DOI: 10.1016/s2352-4642(20)30181-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 05/04/2020] [Accepted: 05/11/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND Human parechoviruses are a major cause of CNS infection in neonates and young children. They have been implicated in neurological sequelae and neurodevelopmental delay. However, the magnitude of this effect has not been systematically reviewed or assessed with meta-analyses. We investigated short-term, medium-term, and long-term neurological sequelae and neurodevelopmental delay in neonates and young children after parechovirus-CNS-infection. METHODS In this systematic review and meta-analyses of studies, we searched PubMed, Embase, and PsycInfo, from the inception of the database until March 18, 2019, for reviews, systematic reviews, cohort studies, case series, and case control studies reporting on neurological or neurodevelopmental outcomes of children 3 months or younger with parechovirus infection of the CNS. Studies that were published after Dec 31, 2007, assessed children younger than 16 years, detailed parechoviruses infection of the CNS (confirmed by PCR), and followed up on neurological and neurodevelopmental outcomes were included. Studies published before Dec 31, 2007, were excluded. The predefined primary outcomes were the proportions of children with neurological sequelae, impairment in auditory or visual functions, or gross motor function delay. The proportion of children in whom neurological or neurodevelopmental outcomes were reported was pooled in meta-analyses. For each outcome variable we calculated the pooled proportion with 95% CI. The proportion of children in whom neurological or neurodevelopmental outcomes were reported was extracted by one author and checked by another. Two authors independently assessed the methodological quality of the studies. FINDINGS 20 studies were eligible for quantitative synthesis. The meta-analyses showed an increasing proportion of children with neurological sequelae over time: 5% during short-term follow-up (pooled proportion 0·05 [95% CI 0·03-0·08], I2=0·00%; p=0·83) increasing to 27% during long-term follow-up (0·27 [0·17-0·40], I2=52·74%; p=0·026). The proportion of children with suspected neurodevelopmental delay was 9% or more during long-term follow-up. High heterogeneity and methodological issues in the included studies mean that the results should be interpreted with caution. INTERPRETATION This systematic review suggests the importance of long follow-up, preferably up to preschool or school age (5-6 years), of children with parechovirus infection of the CNS. Although not clinically severe, we found an increasing proportion of neonates and young children with CNS infection had associated neurological sequelae and neurodevelopmental delay over time. We recommend the use of standardised methods to assess neurological and neurodevelopmental functions of these children and to compare results with age-matched reference groups. FUNDING No funding was received for this study.
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Affiliation(s)
| | - Roy G Elbers
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Medical Faculty, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - J C F Hans Ket
- Medical Library, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - A Marceline van Furth
- Department of Paediatric Infectious Diseases and Immunology, Amsterdam University Medical Center, Amsterdam, Netherlands
| | - Charlie C Obihara
- Department of Paediatrics, Elisabeth-Tweesteden Hospital, Tilburg, Netherlands
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