Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-25 (of 25 Records) |
Query Trace: Sakthivel SK[original query] |
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Outbreak of Acute Respiratory Illness Associated with Adenovirus Type 4 at the U.S. Naval Academy, 2016
Rogers AE , Lu X , Killerby M , Campbell E , Gallus L , Kamau E , Froh IB , Nowak G , Erdman DD , Sakthivel SK , Gerber SI , Schneider E , Watson JT , Johnson LA . MSMR 2019 26 (2) 21-27 Human adenoviruses (HAdVs) are known to cause respiratory illness outbreaks at basic military training (BMT) sites. HAdV type-4 and -7 vaccines are routinely administered at enlisted BMT sites, but not at military academies. During August-September 2016, U.S. Naval Academy clinical staff noted an increase in students presenting with acute respiratory illness (ARI). An investigation was conducted to determine the extent and cause of the outbreak. During 22 August-11 September 2016, 652 clinic visits for ARI were identified using electronic health records. HAdV-4 was confirmed by realtime polymerase chain reaction assay in 18 out of 33 patient specimens collected and 1 additional HAdV case was detected from hospital records. Two HAdV-4 positive patients were treated for pneumonia including 1 hospitalized patient. Molecular analysis of 4 HAdV-4 isolates identified genome type 4a1, which is considered vaccine-preventable. Understanding the impact of HAdV in congregate settings other than enlisted BMT sites is necessary to inform discussions regarding future HAdV vaccine strategy. |
Enhanced Throughput of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Real-Time RT-PCR Panel by Assay Multiplexing and Specimen Pooling.
Lu X , Sakthivel SK , Wang L , Lynch B , Dollard SM . J Virol Methods 2021 293 114149 ![]() ![]() A multiplex real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was developed based on the same primer and probe sequences of an existing U.S. CDC Emergency Use authorized test panel, targeting SARS-CoV-2 N1, N2 and human RNase P genes in singleplex. Both singleplex and multiplex assays demonstrated linear dynamic ranges of 8 orders of magnitude and analytical limits of detection of 5 RNA transcript copies/reaction. Both assays showed 100% agreement with 364 previously characterized clinical specimens (146 positive and 218 negative) for detection of SARS-CoV-2 RNA. To further increase testing throughput, 40 positive and 20 negative four-specimen pools were tested by the multiplex assay and showed 97.75% and 100% congruence with individual specimen tests, respectively. rRT-PCR assay multiplexing and sample pooling, individually or in combination, can substantially increase throughput of SARS-CoV-2 testing. |
Severe Acute Respiratory Syndrome Coronavirus 2 Prevalence, Seroprevalence, and Exposure among Evacuees from Wuhan, China, 2020.
Hallowell BD , Carlson CM , Jacobs JR , Pomeroy M , Steinberg J , Tenforde MW , McDonald E , Foster L , Feldstein LR , Rolfes MA , Haynes A , Abedi GR , Odongo GS , Saruwatari K , Rider EC , Douville G , Bhakta N , Maniatis P , Lindstrom S , Thornburg NJ , Lu X , Whitaker BL , Kamili S , Sakthivel SK , Wang L , Malapati L , Murray JR , Lynch B , Cetron M , Brown C , Roohi S , Rotz L , Borntrager D , Ishii K , Moser K , Rasheed M , Freeman B , Lester S , Corbett KS , Abiona OM , Hutchinson GB , Graham BS , Pesik N , Mahon B , Braden C , Behravesh CB , Stewart R , Knight N , Hall AJ , Killerby ME . Emerg Infect Dis 2020 26 (9) 1998-2004 To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States. |
US CDC Real-Time Reverse Transcription PCR Panel for Detection of Severe Acute Respiratory Syndrome Coronavirus 2.
Lu X , Wang L , Sakthivel SK , Whitaker B , Murray J , Kamili S , Lynch B , Malapati L , Burke SA , Harcourt J , Tamin A , Thornburg NJ , Villanueva JM , Lindstrom S . Emerg Infect Dis 2020 26 (8) 1654-65 ![]() ![]() Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent associated with coronavirus disease, which emerged in late 2019. In response, we developed a diagnostic panel consisting of 3 real-time reverse transcription PCR assays targeting the nucleocapsid gene and evaluated use of these assays for detecting SARS-CoV-2 infection. All assays demonstrated a linear dynamic range of 8 orders of magnitude and an analytical limit of detection of 5 copies/reaction of quantified RNA transcripts and 1 x 10(-1.5) 50% tissue culture infectious dose/mL of cell-cultured SARS-CoV-2. All assays performed comparably with nasopharyngeal and oropharyngeal secretions, serum, and fecal specimens spiked with cultured virus. We obtained no false-positive amplifications with other human coronaviruses or common respiratory pathogens. Results from all 3 assays were highly correlated during clinical specimen testing. On February 4, 2020, the Food and Drug Administration issued an Emergency Use Authorization to enable emergency use of this panel. |
Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient.
Harcourt J , Tamin A , Lu X , Kamili S , Sakthivel SK , Murray J , Queen K , Tao Y , Paden CR , Zhang J , Li Y , Uehara A , Wang H , Goldsmith C , Bullock HA , Wang L , Whitaker B , Lynch B , Gautam R , Schindewolf C , Lokugamage KG , Scharton D , Plante JA , Mirchandani D , Widen SG , Narayanan K , Makino S , Ksiazek TG , Plante KS , Weaver SC , Lindstrom S , Tong S , Menachery VD , Thornburg NJ . bioRxiv 2020 ![]() The etiologic agent of the outbreak of pneumonia in Wuhan China was identified as severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) in January, 2020. The first US patient was diagnosed by the State of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens, and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into two virus repositories, making it broadly available to the public health and research communities. We hope that open access to this important reagent will expedite development of medical countermeasures. |
Severe Acute Respiratory Syndrome Coronavirus 2 from Patient with Coronavirus Disease, United States.
Harcourt J , Tamin A , Lu X , Kamili S , Sakthivel SK , Murray J , Queen K , Tao Y , Paden CR , Zhang J , Li Y , Uehara A , Wang H , Goldsmith C , Bullock HA , Wang L , Whitaker B , Lynch B , Gautam R , Schindewolf C , Lokugamage KG , Scharton D , Plante JA , Mirchandani D , Widen SG , Narayanan K , Makino S , Ksiazek TG , Plante KS , Weaver SC , Lindstrom S , Tong S , Menachery VD , Thornburg NJ . Emerg Infect Dis 2020 26 (6) 1266-1273 The etiologic agent of an outbreak of pneumonia in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 in January 2020. A patient in the United States was given a diagnosis of infection with this virus by the state of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens from this patient and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into 2 virus repositories, making it broadly available to the public health and research communities. We hope that open access to this reagent will expedite development of medical countermeasures. |
Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States.
Kujawski SA , Wong KK , Collins JP , Epstein L , Killerby ME , Midgley CM , Abedi GR , Ahmed NS , Almendares O , Alvarez FN , Anderson KN , Balter S , Barry V , Bartlett K , Beer K , Ben-Aderet MA , Benowitz I , Biggs HM , Binder AM , Black SR , Bonin B , Bozio CH , Brown CM , Bruce H , Bryant-Genevier J , Budd A , Buell D , Bystritsky R , Cates J , Charles EM , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu V , Cody S , Cohen M , Conners EE , Curns AT , Dasari V , Dawson P , DeSalvo T , Diaz G , Donahue M , Donovan S , Duca LM , Erickson K , Esona MD , Evans S , Falk J , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Fricchione MJ , Friedman O , Fry A , Galang RR , Garcia MM , Gerber SI , Gerrard G , Ghinai I , Gounder P , Grein J , Grigg C , Gunzenhauser JD , Gutkin GI , Haddix M , Hall AJ , Han GS , Harcourt J , Harriman K , Haupt T , Haynes AK , Holshue M , Hoover C , Hunter JC , Jacobs MW , Jarashow C , Joshi K , Kamali T , Kamili S , Kim L , Kim M , King J , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Komatsu KK , Koppaka R , Layden JE , Li Y , Lindquist S , Lindstrom S , Link-Gelles R , Lively J , Livingston M , Lo K , Lo J , Lu X , Lynch B , Madoff L , Malapati L , Marks G , Marlow M , Mathisen GE , McClung N , McGovern O , McPherson TD , Mehta M , Meier A , Mello L , Moon SS , Morgan M , Moro RN , Murray J , Murthy R , Novosad S , Oliver SE , O’Shea J , Pacilli M , Paden CR , Pallansch MA , Patel M , Patel S , Pedraza I , Pillai SK , Pindyck T , Pray I , Queen K , Quick N , Reese H , Reporter R , Rha B , Rhodes H , Robinson S , Robinson P , Rolfes MA , Routh JA , Rubin R , Rudman SL , Sakthivel SK , Scott S , Shepherd C , Shetty V , Smith EA , Smith S , Stierman B , Stoecker W , Sunenshine R , Sy-Santos R , Tamin A , Tao Y , Terashita D , Thornburg NJ , Tong S , Traub E , Tural A , Uehara A , Uyeki TM , Vahey G , Verani JR , Villarino E , Wallace M , Wang L , Watson JT , Westercamp M , Whitaker B , Wilkerson S , Woodruff RC , Wortham JM , Wu T , Xie A , Yousaf A , Zahn M , Zhang J . Nat Med 2020 26 (6) 861-868 Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously(1-3). Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness. |
Outbreaks of adenovirus-associated respiratory illness on five college campuses in the United States.
Kujawski SA , Lu X , Schneider E , Blythe D , Boktor S , Farrehi J , Haupt T , McBride D , Stephens E , Sakthivel SK , Bachaus B , Waller K , Bauman L , Marconi A , Lewis R , Dettinger L , Ernst R , Kinsey W , Lindstrom S , Gerber SI , Watson JT , Biggs HM . Clin Infect Dis 2020 72 (11) 1992-1999 ![]() ![]() BACKGROUND: Human adenoviruses (HAdVs) are commonly associated with acute respiratory illness. HAdV outbreaks are well documented in congregate military training settings, but less is known about outbreaks on college campuses. During fall 2018 and spring 2019, five U.S. colleges reported increases in HAdV-associated respiratory illness. Investigations were performed to better understand HAdV epidemiology in this setting. METHODS: A case was a student at one of the five colleges with acute respiratory illness and laboratory-confirmed HAdV infection during October 2018-December 2018 or March-May 2019. Available respiratory specimens were typed by HAdV type-specific real-time PCR assays, and for a subset, whole genome sequencing was performed. We reviewed available medical records and cases were invited to complete a questionnaire, which included questions on symptom presentation, social history, and absenteeism. RESULTS: We identified 168 HAdV cases. Median age was 19 (range: 17-22) years and 102 cases (61%) were male. Eleven cases were hospitalized, 10 with pneumonia; two cases died. Among questionnaire respondents, 80% (75/94) missed >/=1 day of class because of their illness. Among those with a type identified (79%), HAdV types 4 and 7 were equally detected, with frequency of each varying by site. Genome types 4a1 and 7d were identified, respectively, by whole genome sequence analysis. CONCLUSIONS: HAdV respiratory illness was associated with substantial morbidity and missed class time among young, generally healthy adults on five U.S. college campuses. HAdVs should be considered a cause of respiratory illness outbreaks in congregate settings such as college campuses. |
Isolation and growth characterization of novel full length and deletion mutant human MERS-CoV strains from clinical specimens collected during 2015.
Tamin A , Queen K , Paden CR , Lu X , Andres E , Sakthivel SK , Li Y , Tao Y , Zhang J , Kamili S , Assiri AM , Alshareef A , Alaifan TA , Altamimi AM , Jokhdar H , Watson JT , Gerber SI , Tong S , Thornburg NJ . J Gen Virol 2019 100 (11) 1523-1529 ![]() ![]() Middle East respiratory syndrome (MERS) is a viral respiratory illness first reported in Saudi Arabia in September 2012 caused by the human coronavirus (CoV), MERS-CoV. Using full-genome sequencing and phylogenetic analysis, scientists have identified three clades and multiple lineages of MERS-CoV in humans and the zoonotic host, dromedary camels. In this study, we have characterized eight MERS-CoV isolates collected from patients in Saudi Arabia in 2015. We have performed full-genome sequencing on the viral isolates, and compared them to the corresponding clinical specimens. All isolates were clade B, lineages 4 and 5. Three of the isolates carry deletions located on three independent regions of the genome in the 5'UTR, ORF1a and ORF3. All novel MERS-CoV strains replicated efficiently in Vero and Huh7 cells. Viruses with deletions in the 5'UTR and ORF1a exhibited impaired viral release in Vero cells. These data emphasize the plasticity of the MERS-CoV genome during human infection. |
Respiratory viral surveillance of healthcare personnel and patients at an adult long-term care facility
O'Neil CA , Kim L , Prill MM , Talbot HK , Whitaker B , Sakthivel SK , Zhang Y , Zhang J , Tong S , Stone N , Garg S , Gerber SI , Babcock HM . Infect Control Hosp Epidemiol 2019 40 (11) 1-4 We conducted active surveillance of acute respiratory viral infections (ARIs) among residents and healthcare personnel (HCP) at a long-term care facility during the 2015-2016 respiratory illness season. ARIs were observed among both HCP and patients, highlighting the importance of including HCP in surveillance programs. |
Middle East respiratory syndrome coronavirus infection dynamics and antibody responses among clinically diverse patients, Saudi Arabia
Al-Abdely HM , Midgley CM , Alkhamis AM , Abedi GR , Lu X , Binder AM , Alanazi KH , Tamin A , Banjar WM , Lester S , Abdalla O , Dahl RM , Mohammed M , Trivedi S , Algarni HS , Sakthivel SK , Algwizani A , Bafaqeeh F , Alzahrani A , Alsharef AA , Alhakeem RF , Jokhdar HAA , Ghazal SS , Thornburg NJ , Erdman DD , Assiri AM , Watson JT , Gerber SI . Emerg Infect Dis 2019 25 (4) 753-766 Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV-positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics. |
Respiratory Illness Associated With Emergent Human Adenovirus Genome Type 7d, New Jersey, 2016-2017.
Killerby ME , Rozwadowski F , Lu X , Caulcrick-Grimes M , McHugh L , Haldeman AM , Fulton T , Schneider E , Sakthivel SK , Bhatnagar J , Rabeneck DB , Zaki S , Gerber SI , Watson JT . Open Forum Infect Dis 2019 6 (2) ofz017 ![]() ![]() Background: Human adenoviruses (HAdVs) are known causes of respiratory illness outbreaks in congregate settings, but cases and clusters are less well described from community settings in the United States. During December 2016-February 2017, the New Jersey Department of Health received reports of HAdV infections from 3 sources in 3 adjacent counties. We investigated to characterize the epidemiologic, laboratory, and clinical features of this HAdV outbreak. Methods: A case was defined as a New Jersey resident with acute respiratory illness during December 1, 2016-March 31, 2017 with laboratory identification of HAdV genome type 7d (HAdV-7d). Human adenovirus was detected by real-time and conventional polymerase chain reaction and molecular typed by partial hexon capsid protein gene sequencing. The HAdV genome type was identified by whole genome sequencing analysis. Available medical, public health, and surveillance records were reviewed. Results: We identified 12 cases, including 3 treatment facility patients, 7 college students, and 2 cases at a tertiary-care hospital. Four cases died; all had underlying comorbidities. Nine HAdV-7d whole genome sequences obtained from all 3 sites were nearly identical. Conclusions: Transmission of HAdV-7d occurred in community and congregate settings across 3 counties and resulted in severe morbidity and mortality in some cases with underlying comorbidities. Clinicians and local and state health departments should consider HAdV in patients with severe respiratory infection. |
Outbreak of respiratory illness associated with human adenovirus type 7 among persons attending Officer Candidates School, Quantico, Virginia, 2017.
Bautista-Gogel J , Madsen CM , Lu X , Sakthivel SK , Froh I , Kamau E , Gerber SI , Watson JT , Cooper SS , Schneider E . J Infect Dis 2019 221 (5) 697-700 ![]() ![]() A respiratory outbreak associated with adenovirus-7 (HAdV-7) occurred among unvaccinated officer candidates attending initial military training. Respiratory infections associated with HAdV-7 can be severe resulting in significant morbidity. Genomic sequencing revealed HAdV-7d, a genome type recently remerging in the US as a significant respiratory pathogen, following reports from Southeast Asia. Twenty-nine outbreak cases were identified; this likely represents an underestimate. Although the HAdV-4 and -7 vaccine is currently given to US military enlisted recruit trainees, it is not routinely given to officer candidates. Administration of the HAdV-4 and -7 vaccine may benefit this cohort. |
Scope and extent of healthcare-associated Middle East respiratory syndrome coronavirus transmission during two contemporaneous outbreaks in Riyadh, Saudi Arabia, 2017.
Alanazi KH , Killerby ME , Biggs HM , Abedi GR , Jokhdar H , Alsharef AA , Mohammed M , Abdalla O , Almari A , Bereagesh S , Tawfik S , Alresheedi H , Alhakeem RF , Hakawi A , Alfalah H , Amer H , Thornburg NJ , Tamin A , Trivedi S , Tong S , Lu X , Queen K , Li Y , Sakthivel SK , Tao Y , Zhang J , Paden CR , Al-Abdely HM , Assiri AM , Gerber SI , Watson JT . Infect Control Hosp Epidemiol 2019 40 (1) 79-88 ![]() ![]() OBJECTIVE: To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications. DESIGN: Outbreak investigation. SETTING: Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit. METHODS: Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases. RESULTS: In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to >/=5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive. CONCLUSIONS: We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission. |
Infectious MERS-CoV isolated from a mildly ill patient, Saudi Arabia
Al-Abdely HM , Midgley CM , Alkhamis AM , Abedi GR , Tamin A , Binder AM , Alanazi K , Lu X , Abdalla O , Sakthivel SK , Mohammed M , Queen K , Algarni HS , Li Y , Trivedi S , Algwizani A , Alhakeem RF , Thornburg NJ , Tong S , Ghazal SS , Erdman DD , Assiri AM , Gerber SI , Watson JT . Open Forum Infect Dis 2018 5 (6) ofy111 Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with a wide range of clinical presentations, from asymptomatic or mildly ill to severe respiratory illness including death. We describe isolation of infectious MERS-CoV from the upper respiratory tract of a mildly ill 27-year-old female in Saudi Arabia 15 days after illness onset. |
Severe respiratory illness outbreak associated with human coronavirus NL63 in a long-term care facility
Hand J , Rose EB , Salinas A , Lu X , Sakthivel SK , Schneider E , Watson JT . Emerg Infect Dis 2018 24 (10) 1964-1966 We describe an outbreak of severe respiratory illness associated with human coronavirus NL63 in a long-term care facility in Louisiana in November 2017. Six of 20 case-patients were hospitalized with pneumonia, and 3 of 20 died. Clinicians should consider human coronavirus NL63 for patients in similar settings with respiratory disease. |
Non-mumps viral parotitis during the 2014-2015 influenza season in the United States
Elbadawi LI , Talley P , Rolfes MA , Millman AJ , Reisdorf E , Kramer NA , Barnes JR , Blanton L , Christensen J , Cole S , Danz T , Dreisig JJ , Garten R , Haupt T , Isaac BM , Jackson MA , Kocharian A , Leifer D , Martin K , McHugh L , McNall RJ , Palm J , Radford KW , Robinson S , Rosen JB , Sakthivel SK , Shult P , Strain AK , Turabelidze G , Webber LA , Weinberg MP , Wentworth DE , Whitaker BL , Finelli L , Jhung MA , Lynfield R , Davis JP . Clin Infect Dis 2018 67 (4) 493-501 Background: During the 2014-2015 US influenza season, 320 cases of non-mumps parotitis (NMP) among residents of 21 states were reported to the Centers for Disease Control and Prevention (CDC). We conducted an epidemiologic and laboratory investigation to determine viral etiologies and clinical features of NMP during this unusually large occurrence. Methods: NMP was defined as acute parotitis or other salivary gland swelling of >2 days duration in a person with a mumps- negative laboratory result. Using a standardized questionnaire, we collected demographic and clinical information. Buccal samples were tested at the CDC for selected viruses, including mumps, influenza, human parainfluenza viruses (HPIVs) 1-4, adenoviruses, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses (HSVs) 1 and 2, and human herpes viruses (HHVs) 6A and 6B. Results: Among the 320 patients, 65% were male, median age was 14.5 years (range, 0-90), and 67% reported unilateral parotitis. Commonly reported symptoms included sore throat (55%) and fever (48%). Viruses were detected in 210 (71%) of 294 NMP patients with adequate samples for testing, >/=2 viruses were detected in 37 samples, and 248 total virus detections were made among all samples. These included 156 influenza A(H3N2), 42 HHV6B, 32 EBV, 8 HPIV2, 2 HPIV3, 3 adenovirus, 4 HSV-1, and 1 HSV-2. Influenza A(H3N2), HHV6B, and EBV were the most frequently codetected viruses. Conclusions: Our findings suggest that, in addition to mumps, clinicians should consider respiratory viral (influenza) and herpes viral etiologies for parotitis, particularly among patients without epidemiologic links to mumps cases or outbreaks. |
Notes from the field: Fatalities associated with human adenovirus type 7 at a substance abuse rehabilitation facility - New Jersey, 2017
Rozwadowski F , Caulcrick-Grimes M , McHugh L , Haldeman A , Fulton T , Killerby M , Schneider E , Lu X , Sakthivel SK , Bhatnagar J , Rabeneck DB , Zaki S , Watson J . MMWR Morb Mortal Wkly Rep 2018 67 (12) 371-372 On February 3, 2017, a local health department notified the New Jersey Department of Health (NJDOH) of a severe respiratory illness outbreak, including two hospitalizations and one death, at a substance abuse treatment facility. During December 2016–January 2017, NJDOH surveillance for noninfluenza respiratory viruses identified multiple human adenovirus (HAdV) cases in the surrounding community. HAdVs can cause severe respiratory illness, and outbreaks of HAdV type 4 (HAdV-4) and HAdV type 7 (HAdV-7) have been associated with communal living facilities, including military barracks (1). A combined HAdV-4 and HadV-7 live oral vaccine is available but is currently limited to military use (2). NJDOH and the local health department investigated the outbreak in consultation with CDC to describe outbreak scope and provide infection control recommendations in this communal facility. |
Severe respiratory illness associated with rhinovirus during the EV-D68 outbreak in the United States, August - November, 2014
Prill MM , Dahl R , Midgley CM , Chern SW , Lu X , Feikin D , Sakthivel SK , Nix WA , Watson J , Gerber SI , Oberste MS . Clin Infect Dis 2017 66 (10) 1528-1534 BACKGROUND: In 2014, a nationwide outbreak of severe respiratory illness occurred in the United States, primarily associated with enterovirus D-68 (EV-D68). A proportion of illness was associated with rhinoviruses and other enteroviruses, which we aimed to characterize further. METHODS: Respiratory specimens from pediatric and adult patients with respiratory illness were submitted to CDC during August - November 2014. While initial laboratory testing focused on identification of EV-D68, the negative specimens were typed by molecular sequencing to identify additional enterovirus (EV) and rhinovirus (RV) types. Testing for other pathogens was not conducted. We compared available clinical and epidemiologic characteristics among patients with EV-D68 and RV species A-C identified. RESULTS: Among 2629 typed specimens, 1012 were EV-D68 (39%) and 81 (3.1%) represented 24 other EV types; 968 were RVs (37%) covering 114 types and grouped into three human RV species (RV-A=446, RV-B=133, RV-C=389); and 568 (22%) had no RV or EV detected. EV-D68 was more frequently identified in patients presenting earlier in the investigation period. Among patients with EV-D68, RV-A, RV-B, or RV-C identified, the age distributions markedly differed. Clinical syndromes and ICU admissions by age were largely similar among those with EV-D68 and RV species. CONCLUSIONS: RVs were commonly associated with severe respiratory illness, alongside EV-D68, during the nationwide outbreak. Clinical characteristics were largely similar among those with EV-D68, RV-A, RV-B, or RV-C. A better understanding of the epidemiology of RVs and EVs is needed to help inform development and use of diagnostic tests, therapeutics, and preventive measures. |
Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia.
Zhang Y , Sakthivel SK , Bramley A , Jain S , Haynes A , Chappell JD , Hymas W , Lenny N , Patel A , Qi C , Ampofo K , Arnold SR , Self WH , Williams DJ , Hillyard D , Anderson EJ , Grijalva CG , Zhu Y , Wunderink RG , Edwards KM , Pavia AT , McCullers JA , Erdman DD . J Clin Microbiol 2016 55 (1) 79-89 ![]() Both molecular and serological assays have been used previously to determine the etiology of community-acquired pneumonia (CAP). However, the correlation of these methods and added diagnostic value of serology has not been fully evaluated. Using data from patients enrolled in the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, we compared real-time RT-PCR and serology for diagnosis of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza viruses 1-3 (PIV) and adenovirus (AdV) infections. Of 5126 patients enrolled, RT-PCR and serology test results were available for 2023, including 1087 children <18 years of age and 936 adults. For RSV, 287 (14.2%) patients were positive by RT-PCR and 234 (11.6%) were positive by serology; HMPV, 172 (8.5%) tested positive by RT-PCR and 147 (7.3%) by serology; PIVs, 94 (4.6%) tested positive by RT-PCR and 92 (4.6%) by serology; and AdV, 111 (5.5%) positive by RT-PCR and 62 (3.1%) by serology. RT-PCR provided the most positive detections overall, but serology increased diagnostic yield for RSV (by 11.8%), HMPV (by 25.0%), AdV (by 32.4%), and PIV (by 48.9%). Method concordance estimated by Cohen's kappa (kappa) coefficient ranged from good (RSV, 0.73 kappa) to fair (AdV, 0.27 kappa). Heterotypic seroresponses observed between PIV and persistent low-level AdV shedding may account for higher method discordance observed with each of these viruses. Serology can be a helpful adjunct to RT-PCR for research-based assessment of the etiologic contribution of non-influenza respiratory viruses to CAP. |
Elevation of alanine aminotransferase activity occurs after activation of the cell-death signaling initiated by pattern-recognition receptors but before activation of cytolytic effectors in NK or CD8+ T cells in the liver during acute HCV infection
Choi YH , Jin N , Kelly F , Sakthivel SK , Yu T . PLoS One 2016 11 (10) e0165533 Pattern-recognition receptors (PRRs) promote host defenses against HCV infection by binding to their corresponding adapter molecules leading to the initiation of innate immune responses including cell death. We investigated the expression of PRR genes, biomarkers of liver cell-death, and T cell and NK cell activation/inhibition-related genes in liver and serum obtained from three experimentally infected chimpanzees with acute HCV infection, and analyzed the correlation between gene expression levels and clinical profiles. Our results showed that expression of hepatic RIG-I, TLR3, TLR7, 2OAS1, and CXCL10 mRNAs was upregulated as early as 7 days post-inoculation and peaked 12 to 83 days post-inoculation. All of the three HCV infected chimpanzees exhibited significant elevations of serum alanine aminotransferase (ALT) activity between 70 and 95 days after inoculation. Elevated levels of serum cytokeratin 18 (CK-18) and caspases 3 and 7 activity coincided closely with the rise of ALT activity, and were preceded by significant increases in levels of caspase 3 and caspase 7 mRNAs in the liver. Particularly we found that significant positive auto-correlations were observed between RIG-I, TLR3, CXCL10, 2OAS1, and PD-L1 mRNA and ALT activity at 3 to 12 days before the peak of ALT activity. However, we observed substantial negative auto-correlations between T cell and NK cell activation/inhibition-related genes and ALT activity at 5 to 32 days after the peak of ALT activity. Our results indicated cell death signaling is preceded by early induction of RIG-I, TLR3, 2OAS1, and CXCL10 mRNAs which leads to elevation of ALT activity and this signaling pathway occurs before the activation of NK and T cells during acute HCV infection. Our study suggests that PRRs and type I IFN response may play a critical role in development of liver cell injury related to viral clearance during acute HCV infection. |
Acute flaccid myelitis in the United States-August - December 2014: Results of nation-wide surveillance
Sejvar JJ , Lopez AS , Cortese MM , Leshem E , Pastula DM , Miller L , Glaser C , Kambhampati A , Shioda K , Aliabadi N , Fischer M , Gregoricus N , Lanciotti R , Nix WA , Sakthivel SK , Schmid DS , Seward JF , Tong S , Oberste MS , Pallansch M , Feikin D . Clin Infect Dis 2016 63 (6) 737-745 BACKGROUND: During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the U.S., coincident with a national outbreak of enterovirus-D68 (EV-D68)-associated severe respiratory illness. METHODS: Clinicians and health departments reported to Centers for Disease Control and Prevention (CDC) standardized clinical, epidemiologic, and radiologic information on AFM cases, and submitted biological samples for testing. Cases were≤21 years old, with acute onset of limb weakness 01 August-31 December 2014 and spinal MRI showing lesions predominantly restricted to gray matter. RESULTS: From August-December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8-12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but one case was hospitalized; none died. CSF pleocytosis (>5 white blood cells/mm3) was common (81%). At CDC, one CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time PCR, although the specimen had >3,000 red blood cells/mm3 The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 14 AFM cases reported from 11 states. CONCLUSIONS: Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology and etiology of AFM. |
Epidemiology of a Novel Recombinant MERS-CoV in Humans in Saudi Arabia.
Assiri AM , Midgley CM , Abedi GR , Bin Saeed A , Almasri MM , Lu X , Al-Abdely HM , Abdalla O , Mohammed M , Algarni HS , Alhakeem RF , Sakthivel SK , Nooh R , Alshayab Z , Alessa M , Srinivasamoorthy G , AlQahtani SY , Kheyami A , HajOmar WH , Banaser TM , Esmaeel A , Hall AJ , Curns AT , Tamin A , Alsharef AA , Erdman D , Watson JT , Gerber SI . J Infect Dis 2016 214 (5) 712-21 ![]() BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans. Fundamental questions about circulating viruses and transmission routes remain. METHODS: We assessed routinely collected epidemiologic data for MERS-CoV cases reported in Saudi Arabia during January 01 - June 30, 2015, and conducted a more detailed investigation of cases reported during February 2015. Available respiratory specimens were obtained for sequencing. RESULTS: During the study period, 216 MERS-CoV cases were reported. Spike gene or full genome sequences (n=17) were obtained from 99 individuals. Most (72 of 99, 73%) sequences formed a discrete, novel recombinant clade (NRC-2015), which was detected in 6 regions and became predominant by June, 2015. No clinical differences were noted between clades. Among 87 cases reported during February 2015, 13 had no recognized risks for secondary acquisition; 12 of these 13 also denied camel contact. Most viruses (8 of 9) from these 13 individuals belonged to NRC-2015. DISCUSSION: Our findings document the spread and eventual predominance of NRC-2015 in humans in Saudi Arabia during the first half of 2015. Our identification of cases without recognized risk factors but with similar virus sequences suggests that additional study is needed to better understand risk factors for MERS-CoV infection. |
Real-time reverse transcription-PCR assay panel for Middle East respiratory syndrome coronavirus.
Lu X , Whitaker B , Sakthivel SK , Kamili S , Rose LE , Lowe L , Mohareb E , Elassal EM , Al-Sanouri T , Haddadin A , Erdman DD . J Clin Microbiol 2014 52 (1) 67-75 ![]() A new human coronavirus (CoV), subsequently named Middle East respiratory syndrome (MERS)-CoV, was first reported in Saudi Arabia in September 2012. In response, we developed two real-time reverse transcription-PCR (rRT-PCR) assays targeting the MERS-CoV nucleocapsid (N) gene and evaluated these assays as a panel with a previously published assay targeting the region upstream of the MERS-CoV envelope gene (upE) for the detection and confirmation of MERS-CoV infection. All assays detected ≤10 copies/reaction of quantified RNA transcripts, with a linear dynamic range of 8 log units and 1.3 x 10(-3) 50% tissue culture infective doses (TCID50)/ml of cultured MERS-CoV per reaction. All assays performed comparably with respiratory, serum, and stool specimens spiked with cultured virus. No false-positive amplifications were obtained with other human coronaviruses or common respiratory viral pathogens or with 336 diverse clinical specimens from non-MERS-CoV cases; specimens from two confirmed MERS-CoV cases were positive with all assay signatures. In June 2012, the U.S. Food and Drug Administration authorized emergency use of the rRT-PCR assay panel as an in vitro diagnostic test for MERS-CoV. A kit consisting of the three assay signatures and a positive control was assembled and distributed to public health laboratories in the United States and internationally to support MERS-CoV surveillance and public health responses. |
Comparison of fast-track diagnostics respiratory pathogens multiplex real-time RT-PCR assay with in-house singleplex assays for comprehensive detection of human respiratory viruses.
Sakthivel SK , Whitaker B , Lu X , Oliveira DB , Stockman LJ , Kamili S , Oberste MS , Erdman DD . J Virol Methods 2012 185 (2) 259-66 ![]() Fast-track Diagnostics Respiratory Pathogens (FTDRP) multiplex real-time RT-PCR assay was compared with in-house singleplex real-time RT-PCR assays for detection of 16 common respiratory viruses. The FTDRP assay correctly identified 26 diverse respiratory virus strains, 35 of 41 (85%) external quality assessment samples spiked with cultured virus and 232 of 263 (88%) archived respiratory specimens that tested positive for respiratory viruses by in-house assays. Of 308 prospectively tested respiratory specimens selected from children hospitalized with acute respiratory illness, 270 (87.7%) and 265 (86%) were positive by FTDRP and in-house assays for one or more viruses, respectively, with combined test results showing good concordance (K=0.812, 95% CI=0.786 - 0.838). Individual FTDRP assays for adenovirus, respiratory syncytial virus and rhinovirus showed the lowest comparative sensitivities with in-house assays, with most discrepancies occurring with specimens containing low virus loads and failed to detect some rhinovirus strains, even when abundant. The FTDRP enterovirus and human bocavirus assays appeared to be more sensitive than the in-house assays with some specimens. With the exceptions noted above, most FTDRP assays performed comparably with in-house assays for most viruses while offering enhanced throughput and easy integration by laboratories using conventional real-time PCR instrumentation. |
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