Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
Records 1-22 (of 22 Records) |
Query Trace: Dominguez SR [original query] |
---|
Duration of enterovirus d68 RNA shedding in the upper respiratory tract and transmission among household contacts, Colorado, USA
Nguyen-Tran H , Thompson C , Butler M , Miller KR , Pyle L , Jung S , Rogers S , Ng TFF , Routh J , Dominguez SR , Messacar K . Emerg Infect Dis 2023 29 (11) 2315-2324 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. |
Serological and metagenomic interrogation of cerebrospinal fluid implicates enteroviruses in pediatric acute flaccid myelitis (preprint)
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . bioRxiv 2019 666230 Background Since 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.Methods We interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.Results The most significantly enriched viral family by VirScan of CSF in AFM versus OND controls was Picornaviridae (mean rpK 11,266 versus mean rpK 950, p-adjusted < 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). Enriched Picornaviridae peptides belonged almost entirely to the genus Enterovirus. The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value < 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.Conclusion Despite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM. |
Kathryn V. Holmes: A Career of Contributions to the Coronavirus Field.
Bonavia A , Dominguez SR , Dveksler G , Gagneten S , Howard M , Jeffers S , Qian Z , Smith MK , Thackray LB , Tresnan DB , Wentworth DE , Wessner DR , Williams RK , Miura TA . Viruses 2022 14 (7) Over the past two years, scientific research has moved at an unprecedented rate in response to the COVID-19 pandemic. The rapid development of effective vaccines and therapeutics would not have been possible without extensive background knowledge on coronaviruses developed over decades by researchers, including Kathryn (Kay) Holmes. Kay's research team discovered the first coronavirus receptors for mouse hepatitis virus and human coronavirus 229E and contributed a wealth of information on coronaviral spike glycoproteins and receptor interactions that are critical determinants of host and tissue specificity. She collaborated with several research laboratories to contribute knowledge in additional areas, including coronaviral pathogenesis, epidemiology, and evolution. Throughout her career, Kay was an extremely dedicated and thoughtful mentor to numerous graduate students and post-doctoral fellows. This article provides a review of her contributions to the coronavirus field and her exemplary mentoring. |
Evaluation for arboviral infection among children hospitalized in Colorado with aseptic meningitis and encephalitis
Gould CV , Messacar K , Dominguez SR , Panella A , Tobolowsky F , Fischer M . Pediatr Infect Dis J 2020 39 (11) e382-e384 Among 39 children hospitalized in Colorado with aseptic meningitis or encephalitis, 16 (41%) had an etiology identified, including 2 (5%) with West Nile virus infection. Despite extensive testing, no other arboviral infections were identified. Arboviral infection should be considered in children with neuroinvasive disease during arboviral season with testing directed toward viruses endemic to the region and type of exposure. |
Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort study
Messacar K , Spence-Davizon E , Osborne C , Press C , Schreiner TL , Martin J , Messer R , Maloney J , Burakoff A , Barnes M , Rogers S , Lopez AS , Routh J , Gerber SI , Oberste MS , Nix WA , Abzug MJ , Tyler KL , Herlihy R , Dominguez SR . Lancet Infect Dis 2019 20 (2) 230-239 BACKGROUND: In May, 2018, Children's Hospital Colorado noted an outbreak of enterovirus A71 (EV-A71) neurological disease. We aimed to characterise the clinical features of EV-A71 neurological disease during this outbreak. METHODS: In this retrospective observational cohort study, children (younger than 18 years) who presented to Children's Hospital Colorado (Aurora, CO, USA) between March 1 and November 30, 2018, with neurological disease (defined by non-mutually exclusive criteria, including meningitis, encephalitis, acute flaccid myelitis, and seizures) and enterovirus detected from any biological specimen were eligible for study inclusion. The clinical characteristics of children with neurological disease associated with EV-A71 were compared with those of children with neurological disease associated with other enteroviruses during the same period. To explore the differences in clinical presentation of acute flaccid myelitis, we also used a subgroup analysis to compare clinical findings in children with EV-A71-associated acute flaccid myelitis during the study period with these findings in those with enterovirus D68 (EV-D68)-associated acute flaccid myelitis at the same hospital between 2013 and 2018. FINDINGS: Between March 10 and Nov 10, 2018, 74 children presenting to Children's Hospital Colorado were found to have enterovirus neurological disease; EV-A71 was identified in 43 (58%) of these children. The median age of the children with EV-A71 neurological disease was 22.7 months (IQR 4.0-31.9), and most of these children were male (34 [79%] children). 40 (93%) children with EV-A71 neurological disease had findings suggestive of meningitis, 31 (72%) children showed evidence of encephalitis, and ten (23%) children met our case definition of acute flaccid myelitis. All children with EV-A71 disease had fever and 18 (42%) children had hand, foot, or mouth lesions at or before neurological onset. Children with EV-A71 disease were best differentiated from those with other enteroviruses (n=31) by the neurological findings of myoclonus, ataxia, weakness, and autonomic instability. Of the specimens collected from children with EV-A71, this enterovirus was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. 39 (93%) of 42 children with EV-A71 neurological disease who could be followed up showed complete recovery by 1-2 months. Compared with children with EV-D68-associated acute flaccid myelitis, children with EV-A71-associated acute flaccid myelitis were younger, showed neurological onset earlier after prodromal symptom onset, had milder weakness, showed more rapid improvement, and were more likely to completely recover. INTERPRETATION: This outbreak of EV-A71 neurological disease, the largest reported in the Americas, was characterised by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in most patients. Because EV-A71 epidemiology outside of Asia remains difficult to predict, identification of future outbreaks will be aided by prompt recognition of these distinct clinical findings, testing of non-sterile and sterile site specimens, and enhanced enterovirus surveillance. FUNDING: None. |
Pan-viral serology implicates enteroviruses in acute flaccid myelitis.
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . Nat Med 2019 25 (11) 1748-1752 Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)(1-6). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)(2). CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM. |
Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection
Venkatesan S , Myles PR , Bolton KJ , Muthuri SG , Al Khuwaitir T , Anovadiya AP , Azziz-Baumgartner E , Bajjou T , Bassetti M , Beovic B , Bertisch B , Bonmarin I , Booy R , Borja-Aburto VH , Burgmann H , Cao B , Carratala J , Chinbayar T , Cilloniz C , Denholm JT , Dominguez SR , Duarte PAD , Dubnov-Raz G , Fanella S , Gao Z , Gerardin P , Giannella M , Gubbels S , Herberg J , Higuera Iglesias AL , Hoeger PH , Hu XY , Islam QT , Jimenez MF , Keijzers G , Khalili H , Kusznierz G , Kuzman I , Langenegger E , Lankarani KB , Leo YS , Libster RP , Linko R , Madanat F , Maltezos E , Mamun A , Manabe T , Metan G , Mickiene A , Mikic D , Mohn KGI , Oliva ME , Ozkan M , Parekh D , Paul M , Rath BA , Refaey S , Rodriguez AH , Sertogullarindan B , Skret-Magierlo J , Somer A , Talarek E , Tang JW , To K , Tran D , Uyeki TM , Vaudry W , Vidmar T , Zarogoulidis P , Nguyen-Van-Tam JS . J Infect Dis 2019 221 (3) 356-366 BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment. |
Notes from the Field: Enterovirus A71 neurologic disease in children - Colorado, 2018
Messacar K , Burakoff A , Nix WA , Rogers S , Oberste MS , Gerber SI , Spence-Davizon E , Herlihy R , Dominguez SR . MMWR Morb Mortal Wkly Rep 2018 67 (36) 1017-1018 On May 10, 2018, the Colorado Department of Public Health and Environment (CDPHE) was notified by Children’s Hospital Colorado (CHCO) of an increase in pediatric cases of meningitis and encephalitis in which patients tested positive for enterovirus (EV). CDPHE surveillance data for May 2018 showed a 2.75-fold increase in encephalitis of unknown etiology compared with the 5-year (May 2013–2017) average; this coincided with a threefold rise in enterovirus/rhinovirus (EV/RV) detections from clinical testing at CHCO during the same period. Specimens from children with neurologic disease were tested by EV reverse transcription–polymerase chain reaction (RT-PCR) at CHCO and VP1 sequencing at CDC (1). As of August 26, 2018, EV-A71 was identified in 34 children with neurologic disease. This report describes the clinical, laboratory, and radiologic findings for the first 13 children identified with EV-A71 neurologic disease for whom complete information is available. |
Encephalitis in US children
Messacar K , Fischer M , Dominguez SR , Tyler KL , Abzug MJ . Infect Dis Clin North Am 2017 32 (1) 145-162 Encephalitis is an uncommon but severe disease characterized by neurologic dysfunction with central nervous system inflammation. Children with encephalitis should receive supportive care and empiric therapies for common and treatable causes while prioritizing diagnostic evaluation for common, treatable, and high-risk conditions. Even with an extensive diagnostic workup, an infectious cause is identified in less than half of cases, suggesting a role for postinfectious or noninfectious processes. |
Epidemiology and Molecular Characteristics of Mycoplasma pneumoniae During an Outbreak of M. pneumoniae-Associated Stevens-Johnson Syndrome.
Watkins LK , Olson D , Diaz MH , Lin X , Demirjian A , Benitez AJ , Winchell JM , Robinson CC , Bol KA , Glode MP , Dominguez SR , Miller LA , Kutty PK . Pediatr Infect Dis J 2017 36 (6) 564-571 BACKGROUND: An increase in Mycoplasma pneumoniae-associated Stevens-Johnson syndrome (SJS) cases at a Colorado pediatric hospital led to an outbreak investigation. We describe the epidemiologic and molecular characteristics of M. pneumoniae among SJS case-patients and surrounding community members during the outbreak. METHODS: M. pneumoniae PCR-positive respiratory specimens from 5 Colorado hospitals and 4 referral laboratories underwent confirmatory PCR testing; positive specimens then underwent multilocus variable-number tandem-repeat analysis (MLVA) and macrolide resistance testing. Three SJS-M. pneumoniae case-patient households were surveyed using a standardized questionnaire, and nasopharyngeal/oropharyngeal swabs were obtained from all consenting/assenting household contacts. ICD-9 codes were used to identify pneumonia cases among Colorado patients aged 5-21 years from January 2009- March 2014. RESULTS: Three different M. pneumoniae MLVA types were identified among the 5 SJS case-patients with confirmed infection; MLVA type 3-X-6-2 was seen more commonly in SJS case-patients (60%) than in 69 non-SJS community specimens (29%). Macrolide resistance was identified in 7% of community specimens but not among SJS case-patients. Of 15 household contacts, 5 (33%) were M. pneumoniae-positive; all MLVA types were identical to those of the corresponding SJS case-patient, although the specimen from one contact was macrolide-resistant. Overall pneumonia cases as well as those caused by M. pneumoniae specifically peaked in October, 2013, coinciding with the SJS outbreak. CONCLUSIONS: The outbreak of M. pneumoniae-associated SJS may have been associated with a community outbreak of M. pneumoniae; clinicians should be aware of the M. pneumoniae-SJS relationship. Household transmission of M. pneumoniae was common within the households investigated. |
Enterovirus D68 in critically ill children: A comparison with pandemic H1N1 influenza
Rao S , Messacar K , Torok MR , Rick AM , Holzberg J , Montano A , Bagdure D , Curtis DJ , Oberste MS , Nix WA , de Masellis G , Robinson CC , Dominguez SR . Pediatr Crit Care Med 2016 17 (11) 1023-1031 OBJECTIVE: In 2014, the Unites States experienced an outbreak of enterovirus D68 associated with severe respiratory illness. The clinical characteristics associated with severe illness from enterovirus D68 during this outbreak compared with those associated with the 2009 H1N1 influenza virus outbreak are unknown. DESIGN AND SETTING: In this retrospective cohort study, we characterized the clinical features of children with enterovirus D68 admitted to the PICU between August 1, 2014, and November 1, 2014, and compared them with critically ill children infected with H1N1 influenza during the pandemic admitted between May 1, 2009, and January 31, 2010. PATIENTS: PICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-seven severely ill children with enterovirus D68 infections were compared with 68 children infected with H1N1 influenza during the 2009 pandemic. Children with enterovirus D68 were more likely to have asthma (62% vs 23%; p < 0.001) and present with reactive airway disease exacerbations, with greater receipt of albuterol (94% vs 49%) and steroids (89% vs 40%; p < 0.0001 for both). Although more children with enterovirus D68 were admitted to the ICU compared with those with H1N1 influenza, they had a shorter hospital length of stay (4 vs 7 d; p < 0.0001), with lower intubation rates (7% vs 44%), vasopressor use (3% vs 32%), acute respiratory distress syndrome (3% vs 24%), shock (0% vs 16%), and death (0% vs 12%; p < 0.05 for all). Compared with children with other enteroviruses and rhinoviruses, children with enterovirus D68 were more likely to have a history of asthma (64% vs 45%) or multiple prior wheezing episodes (54% vs 34%; p < 0.01 for both). CONCLUSIONS: Critically ill children with enterovirus D68 were more likely to present with reactive airway disease exacerbations, whereas children with H1N1 influenza were more likely to present with pneumonia. Compared with the pandemic H1N1 influenza outbreak, the enterovirus D68 outbreak resulted in more children requiring admission to the ICU, but was associated with less severe outcomes. |
Enterovirus D68 infection in children with acute flaccid myelitis, Colorado, USA, 2014
Aliabadi N , Messacar K , Pastula DM , Robinson CC , Leshem E , Sejvar JJ , Nix WA , Oberste MS , Feikin DR , Dominguez SR . Emerg Infect Dis 2016 22 (8) 1387-94 During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. |
Visual diagnosis: 19-year-old boy with syncope and bradycardia
Nelson CA , Farina MA , Olson D , Dominguez SR , McFarland EJ . Pediatr Rev 2016 37 (7) e25-8 A 19-year-old adolescent with Asperger syndrome experiences a syncopal episode during which he falls and strikes his head while standing outdoors with friends. The episode occurs in June in Colorado, where the patient and his family live. Emergency medical personnel find the patient conscious but experiencing bradycardia upon their arrival. The patient does not remember the episode, does not report any presyncopal symptoms, and states that he had been feeling well earlier that day. He has no prior history of syncopal episodes or cardiac conditions. | Two weeks earlier the patient was seen by his primary care physician for an annual physical examination and noted to have bradycardia, with a heart rate of approximately 40 beats per minute. He was otherwise well and reported no recent constitutional symptoms, respiratory illness, rash, or cardiac-related symptoms such as palpitations. Sinus bradycardia was confirmed by electrocardiography (ECG) with no other abnormalities, and the patient was referred for outpatient cardiology evaluation. A pre-visit 24-hour ambulatory ECG demonstrated predominantly sinus rhythm with second-degree (Wenckebach also known as Mobitz type 1 block.) atrioventricular (AV) block (Fig 1A) and periods of complete AV block (Fig 1B). However, this result and findings from the cardiology evaluation were pending at the time of the syncopal episode. |
Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an IPD meta-analysis
Muthuri SG , Venkatesan S , Myles PR , Leonardi-Bee J , Lim WS , Mamun AA , Anovadiya AP , Araujo WN , Azziz-Baumgartner E , Baez C , Bantar C , Barhoush MM , Bassetti M , Beovic B , Bingisser R , Bonmarin I , Borja-Aburto VH , Cao B , Carratala J , Cuezzo MR , Denholm JT , Dominguez SR , Duarte PA , Dubnov-Raz G , Echavarria M , Fanella S , Fraser J , Gao Z , Gerardin P , Giannella M , Gubbels S , Herberg J , Iglesias AL , Hoeger PH , Hoffmann M , Hu X , Islam QT , Jimenez MF , Kandeel A , Keijzers G , Khalili H , Khandaker G , Knight M , Kusznierz G , Kuzman I , Kwan AM , Amine IL , Langenegger E , Lankarani KB , Leo YS , Linko R , Liu P , Madanat F , Manabe T , Mayo-Montero E , McGeer A , Memish ZA , Metan G , Mikic D , Mohn KG , Moradi A , Nymadawa P , Ozbay B , Ozkan M , Parekh D , Paul M , Poeppl W , Polack FP , Rath BA , Rodriguez AH , Siqueira MM , Skret-Magierlo J , Talarek E , Tang JW , Torres A , Torun SH , Tran D , Uyeki TM , van Zwol A , Vaudry W , Velyvyte D , Vidmar T , Zarogoulidis P , Nguyen-Van-Tam JS . Influenza Other Respir Viruses 2015 10 (3) 192-204 BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on Influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data (IPD) from 20,634 hospitalised patients with laboratory confirmed A(H1N1)pdm09 (n=20,021) or clinically diagnosed (n=613) 'pandemic influenza'. The primary outcome was radiologically confirmed influenza-related pneumonia (IRP). Odds ratios (OR) were estimated using generalized linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Among 20,634 included participants, 5,978 (29.0%) had IRP; conversely, 3,349 (16.2%) had confirmed absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0.83 (95%CI 0.64 - 1.06; p=0.136)]. Among the 5,978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR=0.72 (0.44-1.17; p=0.180)] or likelihood of requiring ventilatory support [adj. OR=1.17 (0.71-1.92; p=0.537)]; but early treatment versus later significantly reduced mortality [adj. OR=0.70 (0.55-0.88; p=0.003)] and likelihood of requiring ventilatory support [adj. OR=0.68 (0.54-0.85; p=0.001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support. |
Investigation of a cluster of Clostridium difficile infections in a pediatric oncology setting
Dantes R , Epson EE , Dominguez SR , Dolan S , Wang F , Hurst A , Parker SK , Johnston H , West K , Anderson L , Rasheed JK , Moulton-Meissner H , Noble-Wang J , Limbago B , Dowell E , Hilden JM , Guh A , Pollack LA , Gould CV . Am J Infect Control 2015 44 (2) 138-45 BACKGROUND: We investigated an increase in Clostridium difficile infection (CDI) among pediatric oncology patients. METHODS: CDI cases were defined as first C difficile positive stool tests between December 1, 2010, and September 6, 2012, in pediatric oncology patients receiving inpatient or outpatient care at a single hospital. A case-control study was performed to identify CDI risk factors, infection prevention and antimicrobial prescribing practices were assessed, and environmental sampling was conducted. Available isolates were strain-typed by pulsed-field gel electrophoresis. RESULTS: An increase in hospital-onset CDI cases was observed from June-August 2012. Independent risk factors for CDI included hospitalization in the bone marrow transplant ward and exposure to computerized tomography scanning or cefepime in the prior 12 weeks. Cefepime use increased beginning in late 2011, reflecting a practice change for patients with neutropenic fever. There were 13 distinct strain types among 22 available isolates. Hospital-onset CDI rates decreased to near-baseline levels with enhanced infection prevention measures, including environmental cleaning and prolonged contact isolation. CONCLUSION: C difficile strain diversity associated with a cluster of CDI among pediatric oncology patients suggests a need for greater understanding of modes and sources of transmission and strategies to reduce patient susceptibility to CDI. Further research is needed on the risk of CDI with cefepime and its use as primary empirical treatment for neutropenic fever. |
Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation
Midgley CM , Watson JT , Nix WA , Curns AT , Rogers SL , Brown BA , Conover C , Dominguez SR , Feikin DR , Gray S , Hassan F , Hoferka S , Jackson MA , Johnson D , Leshem E , Miller L , Nichols JB , Nyquist AC , Obringer E , Patel A , Patel M , Rha B , Schneider E , Schuster JE , Selvarangan R , Seward JF , Turabelidze G , Oberste MS , Pallansch MA , Gerber SI . Lancet Respir Med 2015 3 (11) 879-87 BACKGROUND: Enterovirus D68 (EV-D68) has been infrequently reported historically, and is typically associated with isolated cases or small clusters of respiratory illness. Beginning in August, 2014, increases in severe respiratory illness associated with EV-D68 were reported across the USA. We aimed to describe the clinical, epidemiological, and laboratory features of this outbreak, and to better understand the role of EV-D68 in severe respiratory illness. METHODS: We collected regional syndromic surveillance data for epidemiological weeks 23 to 44, 2014, (June 1 to Nov 1, 2014) and hospital admissions data for epidemiological weeks 27 to 44, 2014, (June 29 to Nov 1, 2014) from three states: Missouri, Illinois and Colorado. Data were also collected for the same time period of 2013 and 2012. Respiratory specimens from severely ill patients nationwide, who were rhinovirus-positive or enterovirus-positive in hospital testing, were submitted between Aug 1, and Oct 31, 2014, and typed by molecular sequencing. We collected basic clinical and epidemiological characteristics of EV-D68 cases with a standard data collection form submitted with each specimen. We compared patients requiring intensive care with those who did not, and patients requiring ventilator support with those who did not. Mantel-Haenszel chi2 tests were used to test for statistical significance. FINDINGS: Regional and hospital-level data from Missouri, Illinois, and Colorado showed increases in respiratory illness between August and September, 2014, compared with in 2013 and 2012. Nationwide, 699 (46%) of 1529 patients tested were confirmed as EV-D68. Among the 614 EV-D68-positive patients admitted to hospital, age ranged from 3 days to 92 years (median 5 years). Common symptoms included dyspnoea (n=513 [84%]), cough (n=500 [81%]), and wheezing (n=427 [70%]); 294 (48%) patients had fever. 338 [59%] of 574 were admitted to intensive care units, and 145 (28%) of 511 received ventilator support; 322 (52%) of 614 had a history of asthma or reactive airway disease; 200 (66%) of 304 patients with a history of asthma or reactive airway disease required intensive care compared with 138 (51%) of 270 with no history of asthma or reactive airway disease (p=0.0004). Similarly, 89 (32%) of 276 patients with a history of asthma or reactive airway disease required ventilator support compared with 56 (24%) of 235 patients with no history of asthma or reactive airway disease (p=0.039). INTERPRETATION: In 2014, EV-D68 caused widespread severe respiratory illness across the USA, disproportionately affecting those with asthma. This unexpected event underscores the need for robust surveillance of enterovirus types, enabling improved understanding of virus circulation and disease burden. FUNDING: None. |
Comparison of Whole-Genome Sequencing and Molecular-Epidemiological Techniques for Clostridium difficile Strain Typing.
Dominguez SR , Anderson LJ , Kotter CV , Littlehorn CA , Arms LE , Dowell E , Todd JK , Frank DN . J Pediatric Infect Dis Soc 2015 5 (3) 329-32 We analyzed in parallel 27 pediatric Clostridium difficile isolates by repetitive sequence-based polymerase chain reaction (RepPCR), pulsed-field gel electrophoresis (PFGE), and whole-genome next-generation sequencing. Next-generation sequencing distinguished 3 groups of isolates that were indistinguishable by RepPCR and 1 isolate that clustered in the same PFGE group as other isolates. |
Outbreak of Mycoplasma pneumoniae-associated Stevens-Johnson Syndrome
Olson D , Watkins LK , Demirjian A , Lin X , Robinson CC , Pretty K , Benitez AJ , Winchell JM , Diaz MH , Miller LA , Foo TA , Mason MD , Lauper UL , Kupfer O , Kennedy J , Glode MP , Kutty PK , Dominguez SR . Pediatrics 2015 136 (2) e386-94 BACKGROUND: Stevens-Johnson syndrome (SJS) is an uncommon, sporadic disease and outbreaks are rare. In November 2013, an outbreak of SJS was identified at Children's Hospital Colorado. METHODS: Outbreak cases were children aged 5-21 with a discharge diagnosis of SJS admitted from September 1 to November 30, 2013. Medical charts were reviewed using standardized data collection forms. Respiratory specimens were tested for viruses and Mycoplasma pneumoniae (Mp) by polymerase chain reaction (PCR). We conducted a separate 4-year retrospective case-control study comparing hospitalized SJS cases with and without evidence of Mp infection. RESULTS: During the outbreak, 8 children met SJS criteria. Median age was 11.5 years (range 8-16 years); 5 (63%) were boys and 5 (63%) were Mp-PCR-positive. Of the 5 PCR-positive children, none had preceding medication exposure, and all had radiographic pneumonia. All outbreak Mp isolates were macrolide susceptible. The retrospective case-control analysis showed that Mp-associated SJS episodes (n = 17) were more likely to have pneumonia (odds ratio [OR] 10.0, confidence interval [CI] 1.3-5.1), preceding respiratory symptoms (OR 30.0, CI 1.6-72.6), an erythrocyte sedimentation rate ≥35 mg/dL (OR 22.8, CI 2.1-244.9), and ≤3 affected skin sites (OR 4.5, CI 1.2-17.4) than non-Mp-associated SJS episodes (n = 23). CONCLUSIONS: We report the largest outbreak of SJS in children, which was also predominately associated with Mp infection. Mp-associated SJS was associated with a distinct clinical presentation that included less extensive skin disease, an elevated erythrocyte sedimentation rate, and evidence of a preceding respiratory infection. |
A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA
Messacar K , Schreiner TL , Maloney JA , Wallace A , Ludke J , Oberste MS , Nix WA , Robinson CC , Glode MP , Abzug MJ , Dominguez SR . Lancet 2015 385 (9978) 1662-71 BACKGROUND: Clusters of acute flaccid paralysis or cranial nerve dysfunction in children are uncommon. We aimed to assess a cluster of children with acute flaccid paralysis and cranial nerve dysfunction geographically and temporally associated with an outbreak of enterovirus-D68 respiratory disease. METHODS: We defined a case of neurological disease as any child admitted to Children's Hospital Colorado (Aurora, CO, USA) with acute flaccid paralysis with spinal-cord lesions involving mainly grey matter on imaging, or acute cranial nerve dysfunction with brainstem lesions on imaging, who had onset of neurological symptoms between Aug 1, 2014, and Oct 31, 2014. We used Poisson regression to assess whether the numbers of cases during the outbreak period were significantly greater than baseline case numbers from a historical control period (July 31, 2010, to July 31, 2014). FINDINGS: 12 children met the case definition (median age 11.5 years [IQR 6.75-15]). All had a prodromal febrile illness preceding neurological symptoms by a median of 7 days (IQR 5.75-8). Neurological deficits included flaccid limb weakness (n=10; asymmetric n=7), bulbar weakness (n=6), and cranial nerve VI (n=3) and VII (n=2) dysfunction. Ten (83%) children had confluent, longitudinally extensive spinal-cord lesions of the central grey matter, with predominant anterior horn-cell involvement, and nine (75%) children had brainstem lesions. Ten (91%) of 11 children had cerebrospinal fluid pleocytosis. Nasopharyngeal specimens from eight (73%) of 11 children were positive for rhinovirus or enterovirus. Viruses from five (45%) of 11 children were typed as enterovirus D68. Enterovirus PCR of cerebrospinal fluid, blood, and rectal swabs, and tests for other causes, were negative. Improvement of cranial nerve dysfunction has been noted in three (30%) of ten children. All ten children with limb weakness have residual deficits. INTERPRETATION: We report the first geographically and temporally defined cluster of acute flaccid paralysis and cranial nerve dysfunction in children associated with an outbreak of enterovirus-D68 respiratory illness. Our findings suggest the possibility of an association between enterovirus D68 and neurological disease in children. If enterovirus-D68 infections continue to happen in an endemic or epidemic pattern, development of effective antiviral or immunomodulatory therapies and vaccines should become scientific priorities. FUNDING: National Center for Advancing Translational Sciences, National Institutes of Health. |
Acute neurologic illness of unknown etiology in children - Colorado, August-September 2014
Pastula DM , Aliabadi N , Haynes AK , Messacar K , Schreiner T , Maloney J , Dominguez SR , Davizon ES , Leshem E , Fischer M , Nix WA , Oberste MS , Seward J , Feikin D , Miller L . MMWR Morb Mortal Wkly Rep 2014 63 (40) 901-2 On September 12, 2014, CDC was notified by the Colorado Department of Public Health and Environment of a cluster of nine children evaluated at Children's Hospital Colorado with acute neurologic illness characterized by extremity weakness, cranial nerve dysfunction (e.g., diplopia, facial droop, dysphagia, or dysarthria), or both. Neurologic illness onsets occurred during August 8-September 15, 2014. The median age of the children was 8 years (range = 1-18 years). Other than neck, back, or extremity pain in some patients, all had normal sensation. All had a preceding febrile illness, most with upper respiratory symptoms, occurring 3-16 days (median = 7 days) before onset of neurologic illness. Seven of eight patients with magnetic resonance imaging of the spinal cord had nonenhancing lesions of the gray matter of the spinal cord spanning multiple levels, and seven of nine with magnetic resonance imaging of the brain had nonenhancing brainstem lesions (most commonly the dorsal pons). Two of five with magnetic resonance imaging of the lumbosacral region had gadolinium enhancement of the ventral nerve roots of the cauda equina. Eight children were up to date on polio vaccination. Eight have not yet fully recovered neurologically. |
High colonization rate and prolonged shedding of Clostridium difficile in pediatric oncology patients
Dominguez SR , Dolan SA , West K , Dantes RB , Epson E , Friedman D , Littlehorn CA , Arms LE , Walton K , Servetar E , Frank DN , Kotter CV , Dowell E , Gould CV , Hilden JM , Todd JK . Clin Infect Dis 2014 59 (3) 401-3 Surveillance testing for Clostridium difficile among pediatric oncology patients identified stool colonization in 29% of patients without gastrointestinal symptoms and in 55% of patients with prior C. difficile infection (CDI). A high prevalence of C. difficile colonization and diarrhea complicates the diagnosis of CDI in this population. |
Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data
Muthuri SG , Venkatesan S , Myles PR , Leonardi-Bee J , Al Khuwaitir TS , Al Mamun A , Anovadiya AP , Azziz-Baumgartner E , Baez C , Bassetti M , Beovic B , Bertisch B , Bonmarin I , Booy R , Borja-Aburto VH , Burgmann H , Cao B , Carratala J , Denholm JT , Dominguez SR , Duarte PA , Dubnov-Raz G , Echavarria M , Fanella S , Gao Z , Gerardin P , Giannella M , Gubbels S , Herberg J , Iglesias AL , Hoger PH , Hu X , Islam QT , Jimenez MF , Kandeel A , Keijzers G , Khalili H , Knight M , Kudo K , Kusznierz G , Kuzman I , Kwan AM , Amine IL , Langenegger E , Lankarani KB , Leo YS , Linko R , Liu P , Madanat F , Mayo-Montero E , McGeer A , Memish Z , Metan G , Mickiene A , Mikic D , Mohn KG , Moradi A , Nymadawa P , Oliva ME , Ozkan M , Parekh D , Paul M , Polack FP , Rath BA , Rodriguez AH , Sarrouf EB , Seale AC , Sertogullarindan B , Siqueira MM , Skret-Magierlo J , Stephan F , Talarek E , Tang JW , To KK , Torres A , Torun SH , Tran D , Uyeki TM , Van Zwol A , Vaudry W , Vidmar T , Yokota RT , Zarogoulidis P , Nguyen-Van-Tam JS . Lancet Respir Med 2014 2 (5) 395-404 BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29 234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0.81; 95% CI 0.70-0.93; p=0.0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0.48; 95% CI 0.41-0.56; p<0.0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0.50; 95% CI 0.37-0.67; p<0.0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1.23] [95% CI 1.18-1.28]; p<0.0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Jun 03, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure