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Mallet MC, Trottier S, Baz M, Redah I, Duvvuri VR, Kozak R, Vachon ML, Daigneault P, Boissinot M, Bergeron MG, Tremblay C, Longtin Y, Huletsky A, Gilca R, Berthelot S, Isabel S. Clinical presentation of Enterovirus D68 in adults with acute respiratory infections consulting in emergency departments in Quebec, Canada. IJID REGIONS 2025; 15:100669. [PMID: 40575491 PMCID: PMC12197986 DOI: 10.1016/j.ijregi.2025.100669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 05/12/2025] [Accepted: 05/13/2025] [Indexed: 06/29/2025]
Abstract
Objectives Enterovirus D68 (EV-D68) is mainly studied in children, while data in adults are limited. We described the clinical presentation of EV-D68 in adults, compared with other enterovirus/rhinovirus (EV/RV) infections. Methods We used clinical and laboratory data from 1143 adults visiting four emergency departments in Quebec, Canada, for acute respiratory infections (February 2022 to March 2023). We analyzed nasopharyngeal swabs using a multiplex polymerase chain reaction; positive EV/RV samples were further tested with EV-D68-specific polymerase chain reaction assays. We calculated the Pandemic Medical Early Warning Score (PMEWS) to assess severity. Results Of 155 (14%) EV/RV samples, 19 (12%) were EV-D68 and occurred from July to October, 2022. Patients with EV-D68 more frequently lived with other people (100% vs 73%, P = 0.02) and tended to have more underlying chronic respiratory diseases (26% vs 20%) and respiratory symptoms (e.g., dyspnea: 84% vs 75%; wheezing: 63% vs 44%; and chest pain: 63% vs 49%), although these differences were not statistically significant. PMEWS, hospitalizations, and median time spent in the emergency department did not differ significantly between the EV-D68 and the other EV/RV group. Conclusions Respiratory symptoms tended to be more common among participants with EV-D68 than those with other EV/RV, although disease severity was similar. Larger studies are needed to better characterize EV-D68 infections in adults.
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Affiliation(s)
- Maria Christina Mallet
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
| | - Sylvie Trottier
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
- Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, Canada
| | - Mariana Baz
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
- Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, Canada
| | - Immanuel Redah
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
| | - Venkata R. Duvvuri
- Public Health Ontario, Toronto, Canada
- Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
- Laboratory for Industrial and Applied Mathematics, Department of Mathematics and Statistics, York University, Toronto, Canada
| | - Robert Kozak
- Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
- Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Marie-Louise Vachon
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
- Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, Canada
| | - Patrick Daigneault
- Division of Respiratory Medicine, Department of Pediatrics, CHU de Québec-Université Laval, Quebec, Canada
- Axe Reproduction, santé de la mère et de l’enfant, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
- Département de pédiatrie, Faculté de médecine, Université Laval, Québec, Canada
| | - Maurice Boissinot
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
| | - Michel G Bergeron
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
- Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, Canada
| | - Cécile Tremblay
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Canada
| | | | - Ann Huletsky
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
| | - Rodica Gilca
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
- Direction des risques biologiques, Institut national de santé publique du Québec, Québec, Canada
| | - Simon Berthelot
- Department of Family Medicine and Emergency Medicine, Faculté de médecine, Université Laval, Québec, Canada
- Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
| | - Sandra Isabel
- Axe Maladies infectieuses et immunitaires, Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
- Département de pédiatrie, Faculté de médecine, Université Laval, Québec, Canada
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Nguyen-Tran H, Butler M, Simmons D, Dominguez SR, Messacar K. Return of the Biennial Circulation of Enterovirus D68 in Colorado Children in 2024 Following the Large 2022 Outbreak. Viruses 2025; 17:673. [PMID: 40431685 PMCID: PMC12116100 DOI: 10.3390/v17050673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2025] [Revised: 05/01/2025] [Accepted: 05/03/2025] [Indexed: 05/29/2025] Open
Abstract
Enterovirus D68 (EV-D68) caused large biennial cyclical outbreaks of respiratory disease and cases of acute flaccid myelitis from 2014 to 2018 in the USA. An anticipated outbreak did not occur in 2020, likely due to non-pharmaceutical interventions targeting the COVID-19 pandemic. A large respiratory disease outbreak occurred again in 2022, but uncertainty remained regarding if circulation of EV-D68 would return to the pre-pandemic patterns. We conducted prospective active surveillance of clinical respiratory specimens from Colorado children for EV-D68 in 2023 and 2024. A subset of residual specimens positive for rhinovirus/enterovirus (RV/EV) were tested for EV-D68 via a validated in-house EV-D68 reverse transcription-PCR assay. During epi weeks 18-44 in 2023, 525 residual specimens positive for RV/EV all tested negative for EV-D68. In 2024, during epi weeks 18-44, 10 (1.8%) of the 546 RV/EV-positive specimens were EV-D68-positive. The EV-D68-positive cases were predominantly young children (median age 4.8 years) receiving treatment with asthma medications. Following the 2022 EV-D68 outbreak, an anticipated outbreak did not occur in 2023. While EV-D68 was detected in 2024, the number of cases was not as significant as in prior outbreak years. Continued surveillance for EV-D68 will be important to understand the future dynamics of EV-D68 circulation and prepare for future outbreaks.
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Affiliation(s)
- Hai Nguyen-Tran
- Department of Pediatrics, University of Colorado School of Medicine, 13001 E 17th Place, Aurora, CO 80045, USA; (S.R.D.); (K.M.)
- Children’s Hospital Colorado, 13123 E 16th Ave, Aurora, CO 80045, USA; (M.B.); (D.S.)
| | - Molly Butler
- Children’s Hospital Colorado, 13123 E 16th Ave, Aurora, CO 80045, USA; (M.B.); (D.S.)
| | - Dennis Simmons
- Children’s Hospital Colorado, 13123 E 16th Ave, Aurora, CO 80045, USA; (M.B.); (D.S.)
| | - Samuel R. Dominguez
- Department of Pediatrics, University of Colorado School of Medicine, 13001 E 17th Place, Aurora, CO 80045, USA; (S.R.D.); (K.M.)
- Children’s Hospital Colorado, 13123 E 16th Ave, Aurora, CO 80045, USA; (M.B.); (D.S.)
| | - Kevin Messacar
- Department of Pediatrics, University of Colorado School of Medicine, 13001 E 17th Place, Aurora, CO 80045, USA; (S.R.D.); (K.M.)
- Children’s Hospital Colorado, 13123 E 16th Ave, Aurora, CO 80045, USA; (M.B.); (D.S.)
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Murayama Y, Aizawa Y, Ikuse T, Izumita R, Nukaga S, Kaneko M, Yamada T, Ono T, Matsui K, Suda M, Saitoh A. Acute Flaccid Myelitis With Human Rhinovirus A19 Detection: Case Report and Literature Review. Pediatr Infect Dis J 2024; 43:708-710. [PMID: 38451987 DOI: 10.1097/inf.0000000000004317] [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: 03/09/2024]
Abstract
Human rhinovirus (HRV) has been sporadically detected in patients with acute flaccid myelitis (AFM). We report a case of AFM in a 2-year-old boy with severe neurologic sequelae, whose nasopharyngeal and stool samples tested positive for HRV-A19. Clinical information related to AFM with HRV is limited. Further study of the association of AFM with HRV is warranted.
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Affiliation(s)
- Yurie Murayama
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences
| | - Yuta Aizawa
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences
| | - Tatsuki Ikuse
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences
| | - Ryohei Izumita
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences
| | - Shunsuke Nukaga
- Department of Pediatrics, Niigata Prefectural Central Hospital, Niigata, Japan
| | - Masahiro Kaneko
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences
| | - Takeshi Yamada
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences
| | - Takeshi Ono
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences
| | - Ko Matsui
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences
| | - Masashi Suda
- Department of Pediatrics, Niigata Prefectural Central Hospital, Niigata, Japan
| | - Akihiko Saitoh
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences
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4
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Ikuse T, Aizawa Y, Kachikawa R, Kamata K, Osada H, Win SMK, Di Ja L, Win NC, Thein KN, Thida A, Tun A, Ito A, Kyaw Y, Tin HH, Shobugawa Y, Watanabe H, Saito R, Saitoh A. Detection of enterovirus D68 among children with severe acute respiratory infection in Myanmar. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2024; 57:238-245. [PMID: 38233293 DOI: 10.1016/j.jmii.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 12/05/2023] [Accepted: 01/02/2024] [Indexed: 01/19/2024]
Abstract
BACKGROUND Enterovirus D68 (EV-D68) is an important reemerging pathogen that causes severe acute respiratory infection and acute flaccid paralysis, mainly in children. Since 2014, EV-D68 outbreaks have been reported in the United States, Europe, and east Asia; however, no outbreaks have been reported in southeast Asian countries, including Myanmar, during the previous 10 years. METHODS EV-D68 was detected in nasopharyngeal swabs from children with acute lower respiratory infections in Myanmar. The samples were previously collected from children aged 1 month to 12 years who had been admitted to the Yankin Children Hospital in Yangon, Myanmar, between May 2017 and January 2019. EV-D68 was detected with a newly developed EV-D68-specific real-time PCR assay. The clade was identified by using a phylogenetic tree created with the Bayesian Markov chain Monte Carlo method. RESULTS During the study period, nasopharyngeal samples were collected from 570 patients. EV-D68 was detected in 42 samples (7.4 %)-11 samples from 2017 to 31 samples from 2018. The phylogenetic tree revealed that all strains belonged to clade B3, which has been the dominant clade worldwide since 2014. We estimate that ancestors of currently circulating genotypes emerged during the period 1980-2004. CONCLUSIONS To our knowledge, this is the first report of EV-D68 detection in children with acute lower respiratory infections in Yangon, Myanmar, in 2017-2018. Detection and detailed virologic analyses of EV-D68 in southeast Asia is an important aspect of worldwide surveillance and will likely be useful in better understanding the worldwide epidemiologic profile of EV-D68 infection.
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Affiliation(s)
- Tatsuki Ikuse
- Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, 1-754, Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Yuta Aizawa
- Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, 1-754, Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Ryotaro Kachikawa
- Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, 1-754, Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Kazuhiro Kamata
- Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, 1-754, Asahimachi-dori, Chuo-ku, Niigata, Japan; Infectious Diseases Research Center of Niigata University in Myanmar, 35, Maw Koon Tike St., Pyay (East) Ward, Dagon, Yangon, Myanmar
| | - Hidekazu Osada
- Infectious Diseases Research Center of Niigata University in Myanmar, 35, Maw Koon Tike St., Pyay (East) Ward, Dagon, Yangon, Myanmar
| | - Su Mon Kyaw Win
- Infectious Diseases Research Center of Niigata University in Myanmar, 35, Maw Koon Tike St., Pyay (East) Ward, Dagon, Yangon, Myanmar
| | - Lasham Di Ja
- Infectious Diseases Research Center of Niigata University in Myanmar, 35, Maw Koon Tike St., Pyay (East) Ward, Dagon, Yangon, Myanmar
| | - Nay Chi Win
- Infectious Diseases Research Center of Niigata University in Myanmar, 35, Maw Koon Tike St., Pyay (East) Ward, Dagon, Yangon, Myanmar
| | - Khin Nyo Thein
- Yankin Children Hospital, 90, Thitsar Rd., Kanbe, Yankin Township, Yangon, Myanmar
| | - Aye Thida
- University of Medicine 2, Khaymar Thi Rd, Yangon, Myanmar
| | - Aye Tun
- Ministry of Health, Office No.4, Nay Pyi Taw, Myanmar
| | - Ai Ito
- Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, 1-754, Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Yadanar Kyaw
- University of Medicine 2, Khaymar Thi Rd, Yangon, Myanmar
| | - Htay Htay Tin
- University of Medical Technology, Insein Township, Yangon Yangon Division, Myanmar
| | - Yugo Shobugawa
- Division of International Health, Graduate School of Medical and Dental Science, Niigata University, 1-754, Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Hisami Watanabe
- Division of International Health, Graduate School of Medical and Dental Science, Niigata University, 1-754, Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Reiko Saito
- Division of International Health, Graduate School of Medical and Dental Science, Niigata University, 1-754, Asahimachi-dori, Chuo-ku, Niigata, Japan
| | - Akihiko Saitoh
- Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, 1-754, Asahimachi-dori, Chuo-ku, Niigata, Japan.
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5
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Messacar K, Matzinger S, Berg K, Weisbeck K, Butler M, Pysnack N, Nguyen-Tran H, Davizon ES, Bankers L, Jung SA, Birkholz M, Wheeler A, Dominguez SR. Multimodal Surveillance Model for Enterovirus D68 Respiratory Disease and Acute Flaccid Myelitis among Children in Colorado, USA, 2022. Emerg Infect Dis 2024; 30:423-431. [PMID: 38407198 PMCID: PMC10902548 DOI: 10.3201/eid3003.231223] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2024] Open
Abstract
Surveillance for emerging pathogens is critical for developing early warning systems to guide preparedness efforts for future outbreaks of associated disease. To better define the epidemiology and burden of associated respiratory disease and acute flaccid myelitis (AFM), as well as to provide actionable data for public health interventions, we developed a multimodal surveillance program in Colorado, USA, for enterovirus D68 (EV-D68). Timely local, state, and national public health outreach was possible because prospective syndromic surveillance for AFM and asthma-like respiratory illness, prospective clinical laboratory surveillance for EV-D68 among children hospitalized with respiratory illness, and retrospective wastewater surveillance led to early detection of the 2022 outbreak of EV-D68 among Colorado children. The lessons learned from developing the individual layers of this multimodal surveillance program and how they complemented and informed the other layers of surveillance for EV-D68 and AFM could be applied to other emerging pathogens and their associated diseases.
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Aizawa Y, Ikuse T, Izumita R, Habuka R, Yamanaka T, Saitoh A. Human Rhinovirus as a Cause of Fever in Neonates and Young Infants During the COVID-19 Pandemic, 2020-2022. Pediatr Infect Dis J 2024; 43:130-135. [PMID: 37851974 DOI: 10.1097/inf.0000000000004139] [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: 10/20/2023]
Abstract
BACKGROUND Human rhinovirus (HRV) was predominant and persistent during the coronavirus disease 2019 (COVID-19) pandemic despite nonpharmaceutical interventions. The data whether HRV persistence also occurred in neonates and young infants were very limited. METHODS This prospective observational study was conducted in Niigata, Japan, between January 2020 and September 2022. The participants were hospitalized neonates and infants less than 4 months of age with fever. We excluded patients with evidence of bacterial infection or obvious sick contact with influenza or respiratory syncytial virus infection, as confirmed by rapid antigen detection tests. COVID-19 diagnosed by polymerase chain reaction (PCR) or rapid antigen detection tests were also excluded. Parechovirus and enterovirus were examined by PCR using serum and/or cerebrospinal fluid. FilmArray Respiratory Panel v1.7 was conducted on nasopharyngeal swabs. If HRV was positive, the genotype was identified. RESULTS We included 72 patients (median age, 54 days; interquartile range, 28.5-79 days), and sepsis was diagnosed in 31 (43.1%) patients. In total, 27 (37.5%) patients had had positive multiplex PCR tests. These patients were more likely to have rhinorrhea ( P = 0.004), cough ( P = 0.01), and sick contact ( P < 0.001) than those who with negative multiplex PCR. HRV was the most frequently detected virus (n = 23, 85.2%), and species A (n = 15, 71.4%) and C (n = 6, 28.6%) were genotyped. No seasonality or monthly predominance of the specific HRV types was observed. CONCLUSIONS HRV was an important cause of fever in neonates and young infants during the COVID-19 pandemic, 2020 to 2022.
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Affiliation(s)
- Yuta Aizawa
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Tatsuki Ikuse
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Ryohei Izumita
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Department of Pediatrics, Niigata City General Hospital, Niigata, Japan
| | - Rie Habuka
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Department of Pediatrics, Niigata City General Hospital, Niigata, Japan
| | - Takayuki Yamanaka
- Department of Pediatrics, Niigata City General Hospital, Niigata, Japan
| | - Akihiko Saitoh
- From the Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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7
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Nguyen-Tran H, Thompson C, Butler M, Miller KR, Pyle L, Jung S, Rogers S, Ng TFF, Routh J, Dominguez SR, Messacar K. Duration of Enterovirus D68 RNA Shedding in the Upper Respiratory Tract and Transmission among Household Contacts, Colorado, USA. Emerg Infect Dis 2023; 29:2315-2324. [PMID: 37877582 PMCID: PMC10617331 DOI: 10.3201/eid2911.230947] [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] [Indexed: 10/26/2023] Open
Abstract
Enterovirus D68 (EV-D68) causes cyclical outbreaks of respiratory disease and acute flaccid myelitis. EV-D68 is primarily transmitted through the respiratory route, but the duration of shedding in the respiratory tract is unknown. We prospectively enrolled 9 hospitalized children with EV-D68 respiratory infection and 16 household contacts to determine EV-D68 RNA shedding dynamics in the upper respiratory tract through serial midturbinate specimen collections and daily symptom diaries. Five (31.3%) household contacts, including 3 adults, were EV-D68-positive. The median duration of EV-D68 RNA shedding in the upper respiratory tract was 12 (range 7-15) days from symptom onset. The most common symptoms were nasal congestion (100%), cough (92.9%), difficulty breathing (78.6%), and wheezing (57.1%). The median illness duration was 20 (range 11-24) days. Understanding the duration of RNA shedding can inform the expected rate and timing of EV-D68 detection in associated acute flaccid myelitis cases and help guide public health measures.
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8
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Nguyen-Tran H, Reno S, Mwangi E, Mentel M, Hengartner R, Dominguez SR, Messacar K, Jung SA. Qualitative detection of enterovirus D68 from PrimeStore® molecular transport medium: implications for home- and self-collection. Diagn Microbiol Infect Dis 2023; 106:115976. [PMID: 37267740 PMCID: PMC10330550 DOI: 10.1016/j.diagmicrobio.2023.115976] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 04/18/2023] [Accepted: 04/29/2023] [Indexed: 06/04/2023]
Abstract
To ensure proper specimen handling for detecting pathogens, like Enterovirus D68 (EV-D68), from home- and self-collection, alternative techniques are needed to ensure safe transport and reliable testing. PrimeStore® Molecular Transport Medium (MTM) may be an option since it does not require cold storage and inactivates virus while preserving RNA for detection. The purpose of this validation study was to demonstrate the ability to detect EV-D68 via rRT-PCR in MTM. Using a quantified EV-D68 positive control standard, MTM limit of detection for EV-D68 RNA is 104 cp/mL and RNA remains stable up to 30 days unfrozen. Positive and negative residual respiratory specimens from the 2018 EV-D68 outbreak were used for clinical testing. There was an 80% positive and 100% negative agreement with samples in MTM compared to reference. This study demonstrates the feasibility of EV-D68 detection from respiratory specimens collected and stored in PrimeStore® MTM, with implications for home- and self-collection.
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Affiliation(s)
- Hai Nguyen-Tran
- Department of Pediatrics, Section of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO, USA
| | - Samantha Reno
- Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO, USA
| | - Eric Mwangi
- Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO, USA
| | - Marta Mentel
- Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO, USA
| | - Randy Hengartner
- Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO, USA
| | - Samuel R Dominguez
- Department of Pediatrics, Section of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO, USA; Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO, USA
| | - Kevin Messacar
- Department of Pediatrics, Section of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO, USA
| | - Sarah A Jung
- Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO, USA.
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9
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Su W, Zeng Q, Geng J, Liu J, Xie H, Li K, Qin P, Xie C, Di B. Simultaneous detection of enterovirus-D68 and vaccine-related poliovirus 3 in the stool samples of a 5-month hospitalized child with acute respiratory disease: A case report. BIOSAFETY AND HEALTH 2023; 5:250-253. [PMID: 40078228 PMCID: PMC11895007 DOI: 10.1016/j.bsheal.2023.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 06/28/2023] [Accepted: 07/03/2023] [Indexed: 03/14/2025] Open
Abstract
Human enterovirus (EV) infections can lead to various manifestations, with variable correlations between genotypes and symptoms. Human enterovirus D68 (EV-D68) was considered to be associated with acute respiratory disease and acute flaccid myelitis. In this short report, both EV-D68 and poliovirus 3 were detected in the stool of a hospitalized 5-month child who presented with acute respiratory symptoms and who was recently vaccinated with oral polio vaccine (OPV), using a metatranscriptomic high-throughput sequencing method. The nearly full-length genome sequences with complete open reading frames of EV-D68 and poliovirus 3 were assembled. One previously-reported neurovirulence-related amino acid substitution (T860N) in the EV-D68 VP1 region was observed, but the patient showed no neurological symptoms. More attention should be paid to EV-D68, and continuous multiple syndrome-based surveillance on non-polio enterovirus is called for.
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Affiliation(s)
- Wenzhe Su
- Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
- Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
| | - Qing Zeng
- Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
- Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
| | - Jinmei Geng
- Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
- Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
| | - Jingwen Liu
- Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
- Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
| | - Huaping Xie
- Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
- Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
| | - Kuibiao Li
- Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
- Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
| | - Pengzhe Qin
- Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
- Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
| | - Chaojun Xie
- Huadu Center for Disease Control and Prevention, Guangzhou 510803, China
| | - Biao Di
- Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
- Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention, Guangzhou 510000, China
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Hayes LH, Hopkins SE, Liu S, Pardo CA, Garcia-Dominguez MA, Oleszek J, Yea C, Ciftci-Kavaklioglu B, Yeh EA, Dean J, Sadowsky CL, Desai J, Wiegand S, Farias-Moeller R, Nash K, Thakur KT, Vargas WS, Hong-Routson SJ, Yeshokumar A, Zhou MS, Makhani N, Wilson-Murphy M, Bove R, Zhang B, Benson LA. Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications. J Pediatr 2023; 253:55-62.e4. [PMID: 36115622 DOI: 10.1016/j.jpeds.2022.09.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 09/07/2022] [Accepted: 09/09/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.
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Affiliation(s)
- Leslie H Hayes
- Department of Neurology, Boston Children's Hospital, Boston, MA
| | - Sarah E Hopkins
- Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, MA
| | - Shanshan Liu
- Department of Neurology and Institutional Centers for Clinical and Translational Research Biostatistics and Research Design Center, Boston Children's Hospital, Harvard Medical School, Boston, MA
| | - Carlos A Pardo
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MA
| | | | - Joyce Oleszek
- Department of Physical Medicine & Rehabilitation, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO
| | - Carmen Yea
- Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada
| | | | - E Ann Yeh
- Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Janet Dean
- Department of Physical Medicine and Rehabilitation, International Center for Spinal Cord Injury, Johns Hopkins School of Medicine, Kennedy Krieger Institute, Baltimore, MD
| | - Cristina L Sadowsky
- Department of Physical Medicine and Rehabilitation, International Center for Spinal Cord Injury, Johns Hopkins School of Medicine, Kennedy Krieger Institute, Baltimore, MD
| | - Jay Desai
- Department of Neurology, Children's Hospital Los Angeles, Los Angeles, CA
| | - Sarah Wiegand
- Department of Neurology, Children's Hospital Los Angeles, Los Angeles, CA
| | - Raquel Farias-Moeller
- Division of Child Neurology, Department of Neurology, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI
| | - Kendall Nash
- Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA
| | - Kiran T Thakur
- Division of Critical Care and Hospitalist Neurology, Department of Neurology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY
| | - Wendy S Vargas
- Division of Critical Care and Hospitalist Neurology, Department of Neurology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY
| | - Sue J Hong-Routson
- Division of Critical Care, Departments of Pediatrics & Neurology, Lurie Children's Hospital of Chicago, Chicago, IL
| | - Anusha Yeshokumar
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Melissa S Zhou
- Department of Pediatrics, Yale School of Medicine, New Haven, CT; Department of Neurology, Yale School of Medicine, New Haven, CT
| | - Naila Makhani
- Department of Pediatrics, Yale School of Medicine, New Haven, CT; Department of Neurology, Yale School of Medicine, New Haven, CT
| | | | - Riley Bove
- Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA
| | - Bo Zhang
- Department of Neurology and Institutional Centers for Clinical and Translational Research Biostatistics and Research Design Center, Boston Children's Hospital, Harvard Medical School, Boston, MA
| | - Leslie A Benson
- Department of Neurology, Boston Children's Hospital, Boston, MA.
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Monitoring of Enterovirus D68 Outbreak in Israel by a Parallel Clinical and Wastewater Based Surveillance. Viruses 2022; 14:v14051010. [PMID: 35632752 PMCID: PMC9144596 DOI: 10.3390/v14051010] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 04/30/2022] [Accepted: 05/03/2022] [Indexed: 11/16/2022] Open
Abstract
Enterovirus D68 (EVD68) was recently identified as an important cause of respiratory illness and acute flaccid myelitis (AFM), mostly in children. Here, we examined 472 pediatric patients diagnosed with severe respiratory illness and screened for EVD68 between April and October 2021. In parallel, samples collected from a wastewater treatment plant (WWTP) covering the residential area of the hospitalized patients were also tested for EVD68. Of the 472 clinical samples evaluated, 33 (7%) patients were positive for EVD68 RNA. All wastewater samples were positive for EVD68, with varying viral genome copy loads. Calculated EVD68 genome copies increased from the end of May until July 2021 and dramatically decreased at the beginning of August. A similar trend was observed in both clinical and wastewater samples during the period tested. Sequence analysis of EVD68-positive samples indicated that all samples originated from the same branch of subclade B3. This study is the first to use wastewater-based epidemiology (WBE) to monitor EVD68 dynamics by quantitative detection and shows a clear correlation with clinically diagnosed cases. These findings highlight the potential of WBE as an important tool for continuous surveillance of EVD68 and other enteroviruses.
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