Last data update: Oct 28, 2024. (Total: 48004 publications since 2009)
Records 1-30 (of 58 Records) |
Query Trace: Erdman DD[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. |
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. |
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. |
Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation.
Payne DC , Biggs HM , Al-Abdallat MM , Alqasrawi S , Lu X , Abedi GR , Haddadin A , Iblan I , Alsanouri T , Al Nsour M , Sheikh Ali S , Rha B , Trivedi SU , Rasheed MAU , Tamin A , Lamers MM , Haagmans BL , Erdman DD , Thornburg NJ , Gerber SI . Open Forum Infect Dis 2018 5 (5) ofy095 Background: An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant's transmission patterns and epidemiology. Methods: We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization. Results: Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive. Conclusions: The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation. |
Reassessment of High Prevalence Human Adenovirus Detections Among Residents of Two Refugee Centers in Kenya Under Surveillance for Acute Respiratory Infections.
Wu X , Lu X , Schneider E , Ahmed JA , Njenga MK , Breiman RF , Eidex RB , Erdman DD . J Med Virol 2018 91 (3) 385-391 Human adenoviruses (HAdVs) were previously detected at high prevalence by real-time RT-PCR (rRT-PCR) in the upper respiratory tract of residents of two Kenyan refugee camps under surveillance for acute respiratory illness (ARI) between October 2006 and April 2008. We sought to confirm this finding and characterize the HAdVs detected. Of 2148 respiratory specimens originally tested, 511 (23.8%) screened positive for HAdV and 510 were available for retesting. Of these, 421 (82.4%) were confirmed positive by repeat rRT-PCR or PCR and sequencing. Other respiratory viruses were co-detected in 55.8% of confirmed HAdV-positive specimens. Species B and C viruses predominated at 82.8% and HAdV-C1, -C2, and -B3 were the most commonly identified types. Species A, D and F HAdVs, that are rarely associated with ARI, comprised the remainder. Viral loads were highest among species B HAdVs, particularly HAdV-B3. Species C showed the widest range of viral loads and species A, D and F were most often present at low loads and more often with co-detections. These findings suggest that many HAdV detections were incidental and not a primary cause of ARI among camp patients. Species/type, co-detections and viral load determinations may permit more accurate HAdV disease burden estimates in these populations. This article is protected by copyright. All rights reserved. |
Respiratory syncytial virus testing capabilities and practices among National Respiratory and Enteric Virus Surveillance System laboratories, United States, 2016
Allen KE , Chommanard C , Haynes AK , Erdman DD , Gerber SI , Kim L . J Clin Virol 2018 107 48-51 BACKGROUND: Laboratory tests to detect respiratory syncytial virus (RSV) vary in sensitivity and specificity. Diagnostic testing practices can impact RSV disease diagnosis and burden estimates. OBJECTIVES: We surveyed a sample of laboratories that participated in the National Respiratory and Enteric Virus Surveillance System (NREVSS) in 2015-2016 to understand RSV testing, diagnostic capabilities, and practices. STUDY DESIGN: We distributed surveys in fall 2016 to NREVSS laboratories using an internet survey platform. We conducted a descriptive analysis of survey responses and stratified results by self-identified children's hospital laboratories (CHL, i.e. laboratories affiliated with or in a children's hospital) or general hospital laboratories (GHL, i.e. laboratories that performed analysis on specimens from only adults or adults and children). RESULTS: We sampled 367 (82.5%) of 445 eligible NREVSS laboratories with a 35.7% response rate; 11.5% (n = 15) were CHLs. All CHLs had PCR-based assay capability to test for RSV compared to 48.7% of GHLs (p < 0.001), and it was the most frequent method used by CHLs (n = 9, 75.0%). GHLs used rapid antigen detection tests most frequently (n = 65, 60.2%) to detect RSV compared to CHLs (p = 0.02, n = 3, 25.0%). Almost half (n = 41, 48.2%) of GHLs reported specimen submission from adults >/=50 years for RADTs. CONCLUSIONS: Laboratory testing and diagnostic capabilities differed by whether laboratories self-identified as a CHL or GHL. Many GHLs reported use of RADTs in adults >/=50 years, a less sensitive diagnostic method for this population compared to PCR-based assays. RADT use in adults might miss RSV cases and affect diagnoses and disease burden estimates. |
Adenovirus type 4 respiratory infections among civilian adults, northeastern United States, 2011-2015(1)
Kajon AE , Lamson DM , Bair CR , Lu X , Landry ML , Menegus M , Erdman DD , St George K . Emerg Infect Dis 2018 24 (2) 201-209 Human adenovirus type 4 (HAdV-4) is most commonly isolated in military settings. We conducted detailed molecular characterization on 36 HAdV-4 isolates recovered from civilian adults with acute respiratory disease (ARD) in the northeastern United States during 2011-2015. Specimens came from college students, residents of long-term care facilities or nursing homes, a cancer patient, and young adults without co-morbidities. HAdV-4 genome types 4a1 and 4a2, the variants most frequently detected among US military recruits in basic training before the restoration of vaccination protocols, were isolated in most cases. Two novel a-like variants were recovered from students enrolled at a college in Tompkins County, New York, USA, and a prototype-like variant distinguishable from the vaccine strain was isolated from an 18-year-old woman visiting a physician's office in Ulster County, New York, USA, with symptoms of influenza-like illness. Our data suggest that HAdV-4 might be an underestimated causative agent of ARD among civilian adults. |
Human adenovirus surveillance - United States, 2003-2016
Binder AM , Biggs HM , Haynes AK , Chommanard C , Lu X , Erdman DD , Watson JT , Gerber SI . MMWR Morb Mortal Wkly Rep 2017 66 (39) 1039-1042 Human adenoviruses (HAdVs) are nonenveloped, double-stranded DNA viruses in the family Adenoviridae; seven species (A-G) and >60 genotypes are known to cause human infection. Clinical manifestations associated with HAdV infection include fever, acute respiratory illness, gastroenteritis, and conjunctivitis. HAdV infection can be severe, particularly among immunocompromised patients, and can cause respiratory failure, disseminated infection, hemorrhagic cystitis, neurologic disease, and death. Illness tends to occur sporadically and without demonstrated seasonality. Outbreaks of HAdV have been reported globally in communities, and in closed or crowded settings, including dormitories, health care settings, and among military recruits, for whom a vaccine against HAdV type 4 (HAdV-4) and HAdV type 7 (HAdV-7) has been developed. CDC summarized HAdV detections voluntarily reported through the National Adenovirus Type Reporting System (NATRS) after initiation of surveillance in 2014 to describe trends in reported HAdVs circulating in the United States. Reporting laboratories were also encouraged to report available results for specimens collected before surveillance began. Overall, the number of reporting laboratories and HAdV type identifications reported to NATRS has increased substantially from the start of official reporting in 2014 through 2016; this report describes specimens collected during 2003-2016. The most commonly reported HAdV types were HAdV type 3 (HAdV-3) and HAdV type 2 (HAdV-2), although HAdV types reported fluctuated considerably from year to year. In the United States, information on recently circulating HAdV types is needed to inform diagnostic and surveillance activities by clinicians and public health practitioners. Routine reporting to NATRS by all U.S. laboratories with the capacity to type HAdVs could help strengthen this surveillance system. |
Rhinovirus Viremia in Patients Hospitalized with Community Acquired Pneumonia.
Lu X , Schneider E , Jain S , Bramley AM , Hymas W , Stockmann C , Ampofo K , Arnold SR , Williams DJ , Self WH , Patel A , Chappell JD , Grijalva CG , Anderson EJ , Wunderink RG , McCullers JA , Edwards KM , Pavia AT , Erdman DD . J Infect Dis 2017 216 (9) 1104-1111 Background: Rhinoviruses (RVs) are ubiquitous respiratory pathogens that often cause mild or subclinical infections. Molecular detection of RV from the upper respiratory tract can be prolonged, complicating etiologic association in persons with severe lower respiratory tract infections. Little is known about RV viremia and its value as a diagnostic indicator in persons hospitalized with community-acquired pneumonia (CAP). Methods: Sera from RV-positive children and adults hospitalized with CAP were tested for RV by real-time RT-PCR. RV species and type were determined by partial genome sequencing. Results: Overall, 57/570 (10%) RV-positive patients were viremic and all were children <10 years old [57/375 (15.2%)]. Although RV-A was the most common RV species detected from respiratory specimens (48.8%), almost all viremias were RV-C (98.2%). Viremic patients had fewer co-detected pathogens and were more likely to have chest retractions, wheezing and a history of underlying asthma/reactive airway disease than patients without viremia. Conclusions: More than one out of seven RV-infected children <10 years old hospitalized with CAP were viremic. In contrast with other RV species, RV-C infections were highly associated with viremia and more often the only respiratory pathogen identified, suggesting that RV-C viremia may be an important diagnostic indicator in pediatric pneumonia. |
Notes from the field: Epidemic keratoconjunctivitis outbreak associated with human adenovirus type 8 - U.S. Virgin Islands, June-November 2016
Killerby ME , Stuckey MJ , Guendel I , Sakthivel S , Lu X , Erdman DD , Schneider E , Fagan R , Davis MS , Watson JT , Gerber SI , Biggs HM , Ellis EM . MMWR Morb Mortal Wkly Rep 2017 66 (30) 811-812 On October 11, 2016, the U.S. Virgin Islands Department of Health (USVI DOH) was notified by a local ophthalmologist of an unexpected increase in the number of patients with suspected epidemic keratoconjunctivitis (EKC) during the preceding month. EKC is a severe form of acute conjunctivitis caused by human adenoviruses (HAdVs). Clinical illness typically lasts 1 to 3 weeks and is usually self-limited; treatment is supportive. HAdVs can survive for weeks in the environment and are resistant to common disinfectants. USVI DOH and CDC investigated during October 11-November 29, 2016 to determine the scope of the outbreak, and provide infection control recommendations. |
Acute respiratory infections among returning Hajj pilgrims-Jordan, 2014
Al-Abdallat MM , Rha B , Alqasrawi S , Payne DC , Iblan I , Binder AM , Haddadin A , Nsour MA , Alsanouri T , Mofleh J , Whitaker B , Lindstrom SL , Tong S , Ali SS , Dahl RM , Berman L , Zhang J , Erdman DD , Gerber SI . J Clin Virol 2017 89 34-37 BACKGROUND: The emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) has prompted enhanced surveillance for respiratory infections among pilgrims returning from the Hajj, one of the largest annual mass gatherings in the world. OBJECTIVES: To describe the epidemiology and etiologies of respiratory illnesses among pilgrims returning to Jordan after the 2014 Hajj. STUDY DESIGN: Surveillance for respiratory illness among pilgrims returning to Jordan after the 2014 Hajj was conducted at sentinel health care facilities using epidemiologic surveys and molecular diagnostic testing of upper respiratory specimens for multiple respiratory pathogens, including MERS-CoV. RESULTS: Among the 125 subjects, 58% tested positive for at least one virus; 47% tested positive for rhino/enterovirus. No cases of MERS-CoV were detected. CONCLUSIONS: The majority of pilgrims returning to Jordan from the 2014 Hajj with respiratory illness were determined to have a viral etiology, but none were due to MERS-CoV. A greater understanding of the epidemiology of acute respiratory infections among returning travelers to other countries after Hajj should help optimize surveillance systems and inform public health response practices. |
Exposures among MERS case-patients, Saudi Arabia, January-February 2016
Alhakeem RF , Midgley CM , Assiri AM , Alessa M , Al Hawaj H , Saeed AB , Almasri MM , Lu X , Abedi GR , Abdalla O , Mohammed M , Algarni HS , Al-Abdely HM , Alsharef AA , Nooh R , Erdman DD , Gerber SI , Watson JT . Emerg Infect Dis 2016 22 (11) 2020-2022 Risk factors for primary acquisition of Middle East respiratory syndrome (MERS) coronavirus (CoV) include recent direct contact with dromedary camels (1), but secondary transmission, associated with healthcare settings (2–4) or household contact (5), accounts for most reported cases. Because persons with MERS often do not report any of these risk factors, we investigated MERS cases in Saudi Arabia during an apparent period of limited hospital transmission. Through telephone interviews of case-patients and information from routine investigations, we aimed to characterize exposures and to explore additional factors potentially important in disease transmission. We also genetically sequenced MERS-CoV from respiratory specimens to identify circulating strains. | For confirmed MERS cases (6) reported in Saudi Arabia during January–February 2016, we assessed exposures during the 2 weeks before illness onset (exposure period), including direct (1) and indirect camel contact; indirect contact was defined as 1) having visited settings where camels were kept but without having direct contact or 2) exposure to friends or household members who themselves had direct camel exposure (1). We assessed whether case-patients had worked at, visited, or been admitted to a healthcare setting or had contact with a person known to have MERS during the case-patient’s exposure period. We also asked about recent travel and if any household members were healthcare personnel. For persons too ill to participate or deceased, we interviewed relatives or close friends. |
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. |
Increase in Middle East Respiratory Syndrome-Coronavirus Cases in Saudi Arabia Linked to Hospital Outbreak With Continued Circulation of Recombinant Virus, July 1-August 31, 2015.
Assiri AM , Biggs HM , Abedi GR , Lu X , Bin Saeed A , Abdalla O , Mohammed M , Al-Abdely HM , Algarni HS , Alhakeem RF , Almasri MM , Alsharef AA , Nooh R , Erdman DD , Gerber SI , Watson JT . Open Forum Infect Dis 2016 3 (3) ofw165 During July-August 2015, the number of cases of Middle East respiratory syndrome (MERS) reported from Saudi Arabia increased dramatically. We reviewed the 143 confirmed cases from this period and classified each based upon likely transmission source. We found that the surge in cases resulted predominantly (90%) from secondary transmission largely attributable to an outbreak at a single healthcare facility in Riyadh. Genome sequencing of MERS coronavirus from 6 cases demonstrated continued circulation of the recently described recombinant virus. A single unique frameshift deletion in open reading frame 5 was detected in the viral sequence from 1 case. |
A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques
Lee S , Nguyen MT , Currier MG , Jenkins JB , Strobert EA , Kajon AE , Madan-Lala R , Bochkov YA , Gern JE , Roy K , Lu X , Erdman DD , Spearman P , Moore ML . Nat Commun 2016 7 12838 As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types. |
Spike gene deletion quasispecies in serum of patient with acute MERS-CoV infection.
Lu X , Rowe LA , Frace M , Stevens J , Abedi GR , El Nile O , Banassir T , Al-Masri M , Watson JT , Assiri A , Erdman DD . J Med Virol 2016 89 (3) 542-545 The spike glycoprotein of the Middle East respiratory coronavirus (MERS-CoV) facilitates receptor binding and cell entry. During investigation of a multi-facility outbreak of MERS-CoV in Taif, Saudi Arabia, we identified a mixed population of wild-type and variant sequences with a large 530 nucleotide deletion in the spike gene from the serum of one patient. The out of frame deletion predicted loss of most of the S2 subunit of the spike protein leaving the S1 subunit with an intact receptor binding domain. This finding documents human infection with a novel genetic variant of MERS-CoV present as a quasispecies. |
Quantitative Real-time PCR Assays for Detection and Type-Specific Identification of the Endemic Species C Human Adenoviruses.
Lu X , Erdman DD . J Virol Methods 2016 237 174-178 Human adenoviruses (HAdVs) are medically important respiratory pathogens. Among the 7 recognized species (A-G), species C HAdVs (serotypes 1, 2, 5 and 6) are globally endemic and infect most people early in life. Species C HAdV infections are most often subclinical or mild and can lead to persistent shedding from the gastrointestinal and upper respiratory tracts. They can also cause severe disseminated disease in newborn and immunocompromised persons, where rapid and quantitative detection and identification of the virus would help guide therapeutic intervention. To this end, we developed quantitative type-specific real-time PCR (qPCR) assays for HAdV-1, -2, -5 and -6 targeting the HAdV hexon gene. All type-specific qPCR assays reproducibly detected as few as 5 copies/reaction of quantified hexon recombinant plasmids with a linear dynamic range of 8 log units (5 to 5x107 copies). No non-specific amplifications were observed with concentrated nucleic acid from other HAdV types or other common respiratory pathogens. Of 199 previously typed HAdV field isolates and positive clinical specimens, all were detected and correctly identified to type by the qPCR assays; 10 samples had 2 HAdV types and 1 sample had 3 types identified which were confirmed by amplicon sequencing. The species C HAdV qPCR assays permit rapid, sensitive, specific and quantitative detection and identification of four recognized endemic HAdVs. Together with our previously developed qPCR assays for the epidemic respiratory HAdVs, these assays provide a convenient alternative to classical typing methods. |
Human adenovirus associated with severe respiratory infection, Oregon, USA, 2013-2014
Scott MK , Chommanard C , Lu X , Appelgate D , Grenz L , Schneider E , Gerber SI , Erdman DD , Thomas A . Emerg Infect Dis 2016 22 (6) 1044-51 Several human adenoviruses (HAdVs) can cause respiratory infections, some severe. HAdV-B7, which can cause severe respiratory disease, has not been recently reported in the United States but is reemerging in Asia. During October 2013-July 2014, Oregon health authorities identified 198 persons with respiratory symptoms and an HAdV-positive respiratory tract specimen. Among 136 (69%) hospitalized persons, 31% were admitted to the intensive care unit and 18% required mechanical ventilation; 5 patients died. Molecular typing of 109 specimens showed that most (59%) were HAdV-B7, followed by HAdVs-C1, -C2, -C5 (26%); HAdVs-B3, -B21 (15%); and HAdV-E4 (1%). Molecular analysis of 7 HAdV-B7 isolates identified the virus as genome type d, a strain previously identified only among strains circulating in Asia. Patients with HAdV-B7 were significantly more likely than those without HAdV-B7 to be adults and to have longer hospital stays. HAdV-B7 might be reemerging in the United States, and clinicians should consider HAdV in persons with severe respiratory infection. |
Deletion variants of Middle East respiratory syndrome coronavirus from humans, Jordan, 2015
Lamers MM , Raj VS , Shafei M , Ali SS , Abdallh SM , Gazo M , Nofal S , Lu X , Erdman DD , Koopmans MP , Abdallat M , Haddadin A , Haagmans BL . Emerg Infect Dis 2016 22 (4) 716-9 We characterized Middle East respiratory syndrome coronaviruses from a hospital outbreak in Jordan in 2015. The viruses from Jordan were highly similar to isolates from Riyadh, Saudi Arabia, except for deletions in open reading frames 4a and 3. Transmissibility and pathogenicity of this strain remains to be determined. |
Multiorgan WU polyomavirus infection in bone marrow transplant recipient
Siebrasse EA , Nguyen NL , Willby MJ , Erdman DD , Menegus MA , Wang D . Emerg Infect Dis 2016 22 (1) 24-31 WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient's lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient. |
Multifacility Outbreak of Middle East Respiratory Syndrome in Taif, Saudi Arabia.
Assiri A , Abedi GR , Saeed AA , Abdalla MA , Al-Masry M , Choudhry AJ , Lu X , Erdman DD , Tatti K , Binder AM , Rudd J , Tokars J , Miao C , Alarbash H , Nooh R , Pallansch M , Gerber SI , Watson JT . Emerg Infect Dis 2016 22 (1) 32-40 Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is a novel respiratory pathogen first reported in 2012. During September 2014-January 2015, an outbreak of 38 cases of MERS was reported from 4 healthcare facilities in Taif, Saudi Arabia; 21 of the 38 case-patients died. Clinical and public health records showed that 13 patients were healthcare personnel (HCP). Fifteen patients, including 4 HCP, were associated with 1 dialysis unit. Three additional HCP in this dialysis unit had serologic evidence of MERS-CoV infection. Viral RNA was amplified from acute-phase serum specimens of 15 patients, and full spike gene-coding sequencing was obtained from 10 patients who formed a discrete cluster; sequences from specimens of 9 patients were closely related. Similar gene sequences among patients unlinked by time or location suggest unrecognized viral transmission. Circulation persisted in multiple healthcare settings over an extended period, underscoring the importance of strengthening MERS-CoV surveillance and infection-control practices. |
CDC’s early response to a novel viral disease, Middle East respiratory syndrome coronavirus (MERS-CoV), September 2012-May 2014
Williams HA , Dunville RL , Gerber SI , Erdman DD , Pesik N , Kuhar D , Mason KA , Haynes L , Rotz L , Pierre JS , Poser S , Bunga S , Pallansch MA , Swerdlow DL . Public Health Rep 2015 130 (4) 307-317 The first ever case of Middle East Respiratory Syndrome Coronavirus (MERSCoV) was reported in September 2012. This report describes the approaches taken by CDC, in collaboration with the World Health Organization (WHO) and other partners, to respond to this novel virus, and outlines the agency responses prior to the first case appearing in the United States in May 2014. During this time, CDC’s response integrated multiple disciplines and was divided into three distinct phases: before, during, and after the initial activation of its Emergency Operations Center. CDC’s response to MERS-CoV required a large effort, deploying at least 353 staff members who worked in the areas of surveillance, laboratory capacity, infection control guidance, and travelers’ health. This response built on CDC’s experience with previous outbreaks of other pathogens and provided useful lessons for future emerging threats. |
MERS-CoV in upper respiratory tract and lungs of dromedary camels, Saudi Arabia, 2013-2014
Khalafalla AI , Lu X , Al-Mubarak AI , Dalab AH , Al-Busadah KA , Erdman DD . Emerg Infect Dis 2015 21 (7) 1153-8 To assess the temporal dynamics of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels, specimens were collected at 1-2 month intervals from 2 independent groups of animals during April 2013-May 2014 in Al-Ahsa Province, Saudi Arabia, and tested for MERS-CoV RNA by reverse transcription PCR. Of 96 live camels, 28 (29.2%) nasal swab samples were positive; of 91 camel carcasses, 56 (61.5%) lung tissue samples were positive. Positive samples were more commonly found among young animals (<4 years of age) than adults (>4 years of age). The proportions of positive samples varied by month for both groups; detection peaked during November 2013 and January 2014 and declined in March and May 2014. These findings further our understanding of MERS-CoV infection in dromedary camels and may help inform intervention strategies to reduce zoonotic infections. |
Laboratory investigation and phylogenetic analysis of an imported Middle East respiratory syndrome coronavirus case in Greece.
Kossyvakis A , Tao Y , Lu X , Pogka V , Tsiodras S , Emmanouil M , Mentis AF , Tong S , Erdman DD , Antoniadis A . PLoS One 2015 10 (4) e0125809 Rapid and reliable laboratory diagnosis of persons suspected of Middle East respiratory syndrome coronavirus (MERS-CoV) infection is important for timely implementation of infection control practices and disease management. In addition, monitoring molecular changes in the virus can help elucidate chains of transmission and identify mutations that might influence virus transmission efficiency. This was illustrated by a recent laboratory investigation we conducted on an imported MERS-CoV case in Greece. Two oropharyngeal swab specimens were collected on the 1st and 2nd day of patient hospitalization and tested using two real-time RT-PCR (rRT-PCR) assays targeting the UpE and Orf-1a regions of the MERS-CoV genome and RT-PCR and partial sequencing of RNA-dependent RNA polymerase and nucleocapsid genes. Serum specimens were also collected and serological test were performed. Results from the first swab sample were inconclusive while the second swab was strongly positive for MERS-CoV RNA by rRT-PCR and confirmed positive by RT-PCR and partial gene sequencing. Positive serologic test results further confirmed MERS-CoV infection. Full-length nucleocapsid and spike gene coding sequences were later obtained from the positive swab sample. Phylogenetic analysis revealed that the virus was closely related to recent human-derived MERS-CoV strains obtained in Jeddah and Makkah, Saudi Arabia, in April 2014 and dromedary camels in Saudi Arabia and Qatar. These findings were consistent with the patient's history. We also identified a unique amino acid substitution in the spike receptor binding domain that may have implications for receptor binding efficiency. Our initial inconclusive rRT-PCR results highlight the importance of collecting multiple specimens from suspect MERS-CoV cases and particularly specimens from the lower respiratory tract. |
Severe acute respiratory infection in children in a densely populated urban slum in Kenya, 2007-2011
Breiman RF , Cosmas L , Njenga MK , Williamson J , Mott JA , Katz MA , Erdman DD , Schneider E , Oberste MS , Neatherlin JC , Njuguna H , Ondari DM , Odero K , Okoth GO , Olack B , Wamola N , Montgomery JM , Fields BS , Feikin DR . BMC Infect Dis 2015 15 (95) 95 BACKGROUND: Reducing acute respiratory infection burden in children in Africa remains a major priority and challenge. We analyzed data from population-based infectious disease surveillance for severe acute respiratory illness (SARI) among children <5 years of age in Kibera, a densely populated urban slum in Nairobi, Kenya. METHODS: Surveillance was conducted among a monthly mean of 5,874 (range=5,778-6,411) children <5 years old in two contiguous villages in Kibera. Participants had free access to the study clinic and their health events and utilization were noted during biweekly home visits. Patients meeting criteria for SARI (WHO-defined severe or very severe pneumonia, or oxygen saturation <90%) from March 1, 2007-February 28, 2011 had blood cultures processed for bacteria, and naso- and oro-pharyngeal swabs collected for quantitative real-time reverse transcription polymerase chain reaction testing for influenza viruses, parainfluenza viruses (PIV), respiratory syncytial virus (RSV), adenovirus, and human metapneumovirus (hMPV). Swabs collected during January 1, 2009-February 28, 2010 were also tested for rhinoviruses, enterovirus, parechovirus, Mycoplasma pneumoniae, and Legionella species. Swabs were collected for simultaneous testing from a selected group of control-children visiting the clinic without recent respiratory or diarrheal illnesses. RESULTS: SARI overall incidence was 12.4 cases/100 person-years of observation (PYO) and 30.4 cases/100 PYO in infants. When comparing detection frequency in swabs from 815 SARI cases and 115 healthy controls, only RSV and influenza A virus were significantly more frequently detected in cases, although similar trends neared statistical significance for PIV, adenovirus and hMPV. The incidence for RSV was 2.8 cases/100 PYO and for influenza A was 1.0 cases/100 PYO. When considering all PIV, the rate was 1.1 case/100 PYO and the rate per 100 PYO for SARI-associated disease was 1.5 for adenovirus and 0.9 for hMPV. RSV and influenza A and B viruses were estimated to account for 16.2% and 6.7% of SARI cases, respectively; when taken together, PIV, adenovirus, and hMPV may account for >20% additional cases. CONCLUSIONS: Influenza viruses and RSV (and possibly PIV, hMPV and adenoviruses) are important pathogens to consider when developing technologies and formulating strategies to treat and prevent SARI in children. |
Molecular characterization of respiratory syncytial viruses infecting children reported to have received palivizumab immunoprophylaxis.
Oliveira DB , Iwane MK , Prill MM , Weinberg GA , Williams JV , Griffin MR , Szilagyi PG , Edwards KM , Staat MA , Hall CB , Durigon EL , Erdman DD . J Clin Virol 2015 65 26-31 BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory infections in children. Palivizumab (PZ) is the only RSV-specific immunoprophylaxis approved by the U.S. Food and Drug Administration. Mutations leading to amino acid substitutions in the PZ binding site of the RSV F protein have been associated with breakthrough RSV infections in patients receiving PZ. OBJECTIVE: To detect PZ resistance conferring mutations in RSV strains from children who received PZ. STUDY DESIGN: Children aged ≤24 months on October 31 who were hospitalized or had outpatient visits for respiratory illness and/or fever during October-May 2001-2008 in 3 US counties were included. PZ receipt was obtained from parent interviews and medical records among children subsequently infected with RSV. Archived nasal/throat swab specimens were tested for RSV by real-time RT-PCR. The coding region of the PZ binding site of the RSV F protein was sequenced using both Sanger and pyrosequencing methods. RESULTS: Of 8762 enrolled children, 375 (4.3%) were tested for RSV and had a history of PZ receipt, of which 56 (14.9%) were RSV-positive and 45 of these had available archived specimens. Molecular typing identified 42 partial F gene sequences in specimens from 39 children: 19 single RSV subgroup A, 17 subgroup B and 3 mixed infections. Nucleotide substitutions were identified in 12/42 (28.6%) RSV strains. PZ resistance mutations were identified in 4 (10.2%) of the 39 children, of which one had documented PZ receipt. CONCLUSIONS: Although RSV PZ resistance mutations were infrequent, most RSV-associated illnesses in children with a history of PZ receipt were not due to strain resistance. |
Serologic cross-reactions between nucleocapsid proteins of human respiratory syncytial virus and human metapneumovirus
Zhang Y , Pohl J , Brooks WA , Erdman DD . J Clin Microbiol 2015 53 (5) 1609-15 Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) share virologic and epidemiologic features and cause clinically similar respiratory illness in predominantly young children. In a previous study of acute febrile respiratory illness in Bangladesh, we tested paired serum specimens from of 852 children presenting fever and cough for diagnostic antibody rises to hRSV and hMPV by enzyme immunoassay (EIA). Unexpectedly, of 93 serum pairs that showed a ≥4-fold antibody rise to hRSV, 24 (25.8%) showed a concurrent rise to hMPV; of 91 pairs showing a rise to hMPV, 13 (14.3%) showed a concurrent rise to hRSV. We speculated that common antigens shared by these viruses could explain this finding. Since the nucleocapsid (N) proteins of these viruses show the greatest sequence homology, we tested hyperimmune antisera prepared to each virus against baculovirus expressed recombinant N (recN) proteins for potential cross-reactivity. The antisera were reciprocally reactive with both proteins. To localize common antigenic regions, we first expressed the carboxy domain of the hMPV N protein that was the most highly conserved region within the hRSV N protein. Although reciprocally reactive with antisera by Western blot, this truncated protein did not react with hMPV IgG positive human sera by EIA. Using 5 synthetic peptides that spanned the amino-terminal portion of the hMPV N protein, we identified a single peptide that was cross-reactive with human sera positive for either virus. Antiserum prepared to this peptide was reactive with recN proteins of both viruses, indicating that a common immunoreactive site exists in this region. |
Unraveling the mysteries of Middle East respiratory syndrome coronavirus
Watson JT , Hall AJ , Erdman DD , Swerdlow DL , Gerber SI . Emerg Infect Dis 2014 20 (6) 1054-6 Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel CoV known to cause severe acute respiratory illness in humans; ≈40% of confirmed cases have been fatal. Human-to-human transmission and multiple outbreaks of respiratory illness have been attributed to MERS-CoV, and severe respiratory illness caused by this virus continues to be identified. MERS-CoV was first reported in September 2012, and subsequent investigations documented illness onsets as early as April 2012 (1). As of February 23, 2014, the World Health Organization has reported 182 laboratory-confirmed cases of MERS-CoV infection, including 79 deaths, indicating an ongoing risk for transmission to humans in the Arabian Peninsula (2). The median age of reported case-patients is 52 years (range 2–94 years); most case-patients are male (3). Most index case-patients have at least 1 reported chronic comorbid condition (4) and have resided in, or recently traveled to, Jordan, Qatar, United Arab Emirates, Oman, Kuwait, or Saudi Arabia (3). Confirmed cases of MERS-CoV have been identified in travelers returning from France, Germany, Italy, United Kingdom, and Tunisia (3). Although some have speculated that a zoonotic reservoir of MERS-CoV exists, very little is known about the specific exposures that result in primary human cases. | MERS-CoV infection causes severe acute hypoxemic respiratory failure, extrapulmonary organ dysfunction, and high rates of death; however, the spectrum of illness and clinical course are not fully defined (5). Evidence suggests that MERS-CoV is capable of limited human-to-human transmission, which results in outbreaks in family and health care settings (5,6). The 182 reported cases include multiple distinct spatiotemporal clusters and 32 identified infections in health care workers (3). Modeling performed to assess the extent of human infection and the transmission potential of MERS-CoV (as of August 2013) estimated that most symptomatic case-patients had not been detected but that chains of transmission were not self-sustaining when infection control was implemented (7). Despite evidence of human-to-human transmission, the number of contacts infected by persons with confirmed infections appears to be limited; sustained transmission in the community has not been documented (3). The Hajj, the annual religious pilgrimage to Saudi Arabia, involved 1.37 million pilgrims from 188 countries in 2013 but resulted in no reports of confirmed cases in the weeks after the pilgrimage (3). |
Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description
Al-Abdallat MM , Payne DC , Alqasrawi S , Rha B , Tohme RA , Abedi GR , Al Nsour M , Iblan I , Jarour N , Farag NH , Haddadin A , Al-Sanouri T , Tamin A , Harcourt JL , Kuhar DT , Swerdlow DL , Erdman DD , Pallansch MA , Haynes LM , Gerber SI . Clin Infect Dis 2014 59 (9) 1225-33 BACKGROUND: In April 2012, the Jordan Ministry of Health (JMoH) investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; two fatal cases were retrospectively confirmed by rRT-PCR to be the first detected cases of Middle East Respiratory Syndrome (MERS-CoV). METHODS: Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical chart reviews and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using three U.S. Centers for Disease Control and Prevention (CDC) serologic tests for detection of anti-MERS-CoV antibodies. RESULTS: Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti-MERS-CoV antibodies by at least two of three serologic tests, in addition to two fatal cases identified by rRT-PCR. The case fatality rate among the nine total cases was 22%. Six cases were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at two transfer hospitals having acceptable infection control practices. CONCLUSION: Novel serological tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts of a Jordan hospital-associated respiratory illness outbreak in April 2012, resulting in a total of nine test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most cases had no major, underlying medical conditions; none were on hemodialysis. Our observed case fatality was lower than has been reported from outbreaks elsewhere. |
A duplex recombinant viral nucleoprotein microbead immunoassay for simultaneous detection of seroresponses to human respiratory syncytial virus and metapneumovirus infections
Zhang Y , Brooks WA , Goswami D , Rahman M , Luby SP , Erdman DD . J Virol Methods 2014 206 55-62 Serologic diagnosis of human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) infections has been shown to complement virus detection methods in epidemiologic studies. Enzyme immunoassays (EIAs) using cultured virus lysate antigens are often used to diagnose infection by demonstration of a ≥4-fold rises in antibody titer between acute and convalescent serum pairs. In this study, hRSV and hMPV nucleocapsid (recN) proteins were expressed in a baculovirus system and their performance compared with virus culture lysate antigen in EIAs using paired serum specimens collected from symptomatic children. The recN proteins were also used to develop a duplex assay based on the Luminex microbead-based suspension array technology, where diagnostic rises in antibody levels could be determined simultaneously at a single serum dilution. Antibody levels measured by the recN and viral lysate EIAs correlated moderately (hRSV, r2=0.72; hMPV, r2=0.76); the recN EIAs identified correctly 35 of 37 (94.6%) and 48 of 50 (96%) serum pairs showing diagnostic antibody rises by viral lysate EIAs. Purified recN proteins were then coupled to microbeads and serum pairs were tested at a single dilution on a Luminex MAGPIX(R) analyzer. The duplex recN assay identified correctly 33 of 39 (85%) and 41 of 47 (86.7%) serum pairs showing diagnostic rises to hRSV and hMPV, respectively. The recN assay permitted simultaneous testing for acute hRSV and hMPV infections and offers a platform for expanded multiplexing of other respiratory virus assays. |
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