Last data update: Jul 01, 2024. (Total: 47134 publications since 2009)
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Query Trace: Seema J [original query] |
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COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis - California and New York, May-November 2021.
León Tomás M, Dorabawila Vajeera, Nelson Lauren, Lutterloh Emily, Bauer Ursula E, Backenson Bryon, Bassett Mary T, Henry Hannah, Bregman Brooke, Midgley Claire M, Myers Jennifer F, Plumb Ian D, Reese Heather E, Zhao Rui, Briggs-Hagen Melissa, Hoefer Dina, Watt James P, Silk Benjamin J, Jain Seema, Rosenberg Eli S . MMWR. Morbidity and mortality weekly report 2022 1 (4) 125-131 By November 30, 2021, approximately 130,781 COVID-19-associated deaths, one in six of all U.S. deaths from COVID-19, had occurred in California and New York.* COVID-19 vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19), associated severe illness, and death (1,2); among those who survive, previous SARS-CoV-2 infection also confers protection against severe outcomes in the event of reinfection (3,4). The relative magnitude and duration of infection- and vaccine-derived protection, alone and together, can guide public health planning and epidemic forecasting. To examine the impact of primary COVID-19 vaccination and previous SARS-CoV-2 infection on COVID-19 incidence and hospitalization rates, statewide testing, surveillance, and COVID-19 immunization data from California and New York (which account for 18% of the U.S. population) were analyzed. Four cohorts of adults aged ≥18 years were considered: persons who were 1) unvaccinated with no previous laboratory-confirmed COVID-19 diagnosis, 2) vaccinated (14 days after completion of a primary COVID-19 vaccination series) with no previous COVID-19 diagnosis, 3) unvaccinated with a previous COVID-19 diagnosis, and 4) vaccinated with a previous COVID-19 diagnosis. Age-adjusted hazard rates of incident laboratory-confirmed COVID-19 cases in both states were compared among cohorts, and in California, hospitalizations during May 30-November 20, 2021, were also compared. During the study period, COVID-19 incidence in both states was highest among unvaccinated persons without a previous COVID-19 diagnosis compared with that among the other three groups. During the week beginning May 30, 2021, compared with COVID-19 case rates among unvaccinated persons without a previous COVID-19 diagnosis, COVID-19 case rates were 19.9-fold (California) and 18.4-fold (New York) lower among vaccinated persons without a previous diagnosis; 7.2-fold (California) and 9.9-fold lower (New York) among unvaccinated persons with a previous COVID-19 diagnosis; and 9.6-fold (California) and 8.5-fold lower (New York) among vaccinated persons with a previous COVID-19 diagnosis. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These relationships changed after the SARS-CoV-2 Delta variant became predominant (i.e., accounted for >50% of sequenced isolates) in late June and July. By the week beginning October 3, compared with COVID-19 cases rates among unvaccinated persons without a previous COVID-19 diagnosis, case rates among vaccinated persons without a previous COVID-19 diagnosis were 6.2-fold (California) and 4.5-fold (New York) lower; rates were substantially lower among both groups with previous COVID-19 diagnoses, including 29.0-fold (California) and 14.7-fold lower (New York) among unvaccinated persons with a previous diagnosis, and 32.5-fold (California) and 19.8-fold lower (New York) among vaccinated persons with a previous diagnosis of COVID-19. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These results demonstrate that vaccination protects against COVID-19 and related hospitalization, and that surviving a previous infection protects against a reinfection and related hospitalization. Importantly, infection-derived protection was higher after the Delta variant became predominant, a time when vaccine-induced immunity for many persons declined because of immune evasion and immunologic waning (2,5,6). Similar cohort data accounting for booster doses needs to be assessed, as new variants, including Omicron, circulate. Although the epidemiology of COVID-19 might change with the emergence of new variants, vaccination remains the safest strategy to prevent SARS-CoV-2 infections and associated complications; all eligible persons should be up to date with COVID-19 vaccination. Additional recommendations for vaccine doses might be warranted in the future as the virus and immunity levels change. |
Timely Intervention and Control of a Novel Coronavirus (COVID-19) Outbreak at a Large Skilled Nursing Facility - San Francisco, California, 2020.
Karmarkar E , Blanco I , Amornkul P , DuBois A , Deng X , Moonan PK , Rubenstein BL , Miller DA , Kennedy I , Yu J , Dauterman J , Ongpin M , Hathaway W , Hoo L , Trammell S , Ememu E , Yu G , Khwaja Z , Lu W , Talai N , Jain S , Louie J , Philip S , Federman S , Masinde G , Wadford DA , Bobba N , Stoltey J , Smith A , Epson E , Chiu C , Bennett A , Vasquez AM , Williams T . Infect Control Hosp Epidemiol 2020 42 (10) 1-20 ![]() ![]() OBJECTIVE: To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled nursing facility (SNF), and the strategies that controlled transmission. DESIGN, SETTING, AND PARTICIPANTS: Cohort study during March 22-May 4, 2020 of all staff and residents at a 780-bed SNF in San Francisco, California. METHODS: Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPS) in units with confirmed cases. Cases were confirmed by real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2; whole genome sequencing (WGS) characterized viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact to a confirmed case; restricting movements between units; implementing surgical face masking facility-wide; and recommended PPE (isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases. RESULTS: Of 725 staff and residents tested through targeted testing and serial PPS, twenty-one (3%) were SARS-CoV-2-positive; sixteen (76%) staff and 5 (24%) residents. Fifteen (71%) were linked to a single unit. Targeted testing identified 17 (81%) cases; PPS identified 4 (19%). Most (71%) cases were identified prior to IPC intervention. WGS was performed on SARS-CoV-2 isolates from four staff and four residents; five were of Santa Clara County lineage and the three others were distinct lineages. CONCLUSIONS: Early implementation of targeted testing, serial PPS, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF. |
Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020.
Havers FP , Reed C , Lim T , Montgomery JM , Klena JD , Hall AJ , Fry AM , Cannon DL , Chiang CF , Gibbons A , Krapiunaya I , Morales-Betoulle M , Roguski K , Rasheed MAU , Freeman B , Lester S , Mills L , Carroll DS , Owen SM , Johnson JA , Semenova V , Blackmore C , Blog D , Chai SJ , Dunn A , Hand J , Jain S , Lindquist S , Lynfield R , Pritchard S , Sokol T , Sosa L , Turabelidze G , Watkins SM , Wiesman J , Williams RW , Yendell S , Schiffer J , Thornburg NJ . JAMA Intern Med 2020 IMPORTANCE: Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. OBJECTIVE: To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the US. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study performed serologic testing on a convenience sample of residual sera obtained from persons of all ages. The serum was collected from March 23 through May 12, 2020, for routine clinical testing by 2 commercial laboratory companies. Sites of collection were San Francisco Bay area, California; Connecticut; south Florida; Louisiana; Minneapolis-St Paul-St Cloud metro area, Minnesota; Missouri; New York City metro area, New York; Philadelphia metro area, Pennsylvania; Utah; and western Washington State. EXPOSURES: Infection with SARS-CoV-2. MAIN OUTCOMES AND MEASURES: The presence of antibodies to SARS-CoV-2 spike protein was estimated using an enzyme-linked immunosorbent assay, and estimates were standardized to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). The number of infections in each site was estimated by extrapolating seroprevalence to site populations; estimated infections were compared with the number of reported coronavirus disease 2019 (COVID-19) cases as of last specimen collection date. RESULTS: Serum samples were tested from 16 025 persons, 8853 (55.2%) of whom were women; 1205 (7.5%) were 18 years or younger and 5845 (36.2%) were 65 years or older. Most specimens from each site had no evidence of antibodies to SARS-CoV-2. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). The estimated number of infections ranged from 6 to 24 times the number of reported cases; for 7 sites (Connecticut, Florida, Louisiana, Missouri, New York City metro area, Utah, and western Washington State), an estimated greater than 10 times more SARS-CoV-2 infections occurred than the number of reported cases. CONCLUSIONS AND RELEVANCE: During March to early May 2020, most persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2 virus. The estimated number of infections, however, was much greater than the number of reported cases in all sites. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population. |
Identification and Monitoring of International Travelers During the Initial Phase of an Outbreak of COVID-19 - California, February 3-March 17, 2020.
Myers JF , Snyder RE , Porse CC , Tecle S , Lowenthal P , Danforth ME , Powers E , Kamali A , Jain S , Fritz CL , Chai SJ . MMWR Morb Mortal Wkly Rep 2020 69 (19) 599-602 The threat of introduction of coronavirus disease 2019 (COVID-19) into the United States with the potential for community transmission prompted U.S. federal officials in February 2020 to screen travelers from China, and later Iran, and collect and transmit their demographic and contact information to states for follow-up. During February 5-March 17, 2020, the California Department of Public Health (CDPH) received and transmitted contact information for 11,574 international travelers to 51 of 61 local health jurisdictions at a cost of 1,694 hours of CDPH personnel time. If resources permitted, local health jurisdictions contacted travelers, interviewed them, and oversaw 14 days of quarantine, self-monitoring, or both, based on CDC risk assessment criteria for COVID-19. Challenges encountered during follow-up included errors in the recording of contact information and variation in the availability of resources in local health jurisdictions to address the substantial workload. Among COVID-19 patients reported to CDPH, three matched persons previously reported as travelers to CDPH. Despite intensive effort, the traveler screening system did not effectively prevent introduction of COVID-19 into California. Effectiveness of COVID-19 screening and monitoring in travelers to California was limited by incomplete traveler information received by federal officials and transmitted to states, the number of travelers needing follow-up, and the potential for presymptomatic and asymptomatic transmission. More efficient methods of collecting and transmitting passenger data, including electronic provision of flight manifests by airlines to federal officials and flexible text-messaging tools, would help local health jurisdictions reach out to all at-risk travelers quickly, thereby facilitating timely testing, case identification, and contact investigations. State and local health departments should weigh the resources needed to implement incoming traveler monitoring against community mitigation activities, understanding that the priorities of each might shift during the COVID-19 pandemic. |
Transmission of COVID-19 to Health Care Personnel During Exposures to a Hospitalized Patient - Solano County, California, February 2020.
Heinzerling A , Stuckey MJ , Scheuer T , Xu K , Perkins KM , Resseger H , Magill S , Verani JR , Jain S , Acosta M , Epson E . MMWR Morb Mortal Wkly Rep 2020 69 (15) 472-476 On February 26, 2020, the first U.S. case of community-acquired coronavirus disease 2019 (COVID-19) was confirmed in a patient hospitalized in Solano County, California (1). The patient was initially evaluated at hospital A on February 15; at that time, COVID-19 was not suspected, as the patient denied travel or contact with symptomatic persons. During a 4-day hospitalization, the patient was managed with standard precautions and underwent multiple aerosol-generating procedures (AGPs), including nebulizer treatments, bilevel positive airway pressure (BiPAP) ventilation, endotracheal intubation, and bronchoscopy. Several days after the patient's transfer to hospital B, a real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) test for SARS-CoV-2 returned positive. Among 121 hospital A health care personnel (HCP) who were exposed to the patient, 43 (35.5%) developed symptoms during the 14 days after exposure and were tested for SARS-CoV-2; three had positive test results and were among the first known cases of probable occupational transmission of SARS-CoV-2 to HCP in the United States. Little is known about specific risk factors for SARS-CoV-2 transmission in health care settings. To better characterize and compare exposures among HCP who did and did not develop COVID-19, standardized interviews were conducted with 37 hospital A HCP who were tested for SARS-CoV-2, including the three who had positive test results. Performing physical examinations and exposure to the patient during nebulizer treatments were more common among HCP with laboratory-confirmed COVID-19 than among those without COVID-19; HCP with COVID-19 also had exposures of longer duration to the patient. Because transmission-based precautions were not in use, no HCP wore personal protective equipment (PPE) recommended for COVID-19 patient care during contact with the index patient. Health care facilities should emphasize early recognition and isolation of patients with possible COVID-19 and use of recommended PPE to minimize unprotected, high-risk HCP exposures and protect the health care workforce. |
Rapid Sentinel Surveillance for COVID-19 - Santa Clara County, California, March 2020.
Zwald ML , Lin W , Sondermeyer Cooksey GL , Weiss C , Suarez A , Fischer M , Bonin BJ , Jain S , Langley GE , Park BJ , Moulia D , Benedict R , Nguyen N , Han GS . MMWR Morb Mortal Wkly Rep 2020 69 (14) 419-421 On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19. |
First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA.
Ghinai I , McPherson TD , Hunter JC , Kirking HL , Christiansen D , Joshi K , Rubin R , Morales-Estrada S , Black SR , Pacilli M , Fricchione MJ , Chugh RK , Walblay KA , Ahmed NS , Stoecker WC , Hasan NF , Burdsall DP , Reese HE , Wallace M , Wang C , Moeller D , Korpics J , Novosad SA , Benowitz I , Jacobs MW , Dasari VS , Patel MT , Kauerauf J , Charles EM , Ezike NO , Chu V , Midgley CM , Rolfes MA , Gerber SI , Lu X , Lindstrom S , Verani JR , Layden JE . Lancet 2020 395 (10230) 1137-1144 BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. METHODS: Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. FINDINGS: Patient 1-a woman in her 60s-returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. INTERPRETATION: Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected. FUNDING: None. |
Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study.
Onwuamah CK , Okpokwu J , Audu R , Imade G , Meloni ST , Okwuraiwe A , Chebu P , Musa AZ , Chaplin B , Dalhatu I , Agbaji O , Samuels J , Ezechi O , Ahmed M , Odaibo G , Olaleye DO , Okonkwo P , Salako BL , Raizes E , Yang C , Kanki PJ , Idigbe EO . BMC Microbiol 2020 20 (1) 17 ![]() ![]() BACKGROUND: We identified a HIV-positive cohort in virologic failure (VF) who re-suppressed without drug switch. We characterized their drug resistance mutations (DRM) and adherence profiles to learn how to better manage HIV drug resistance. A retrospective cohort study utilizing clinical data and stored samples. Patients received ART at three Nigerian treatment centres. Plasma samples stored when they were in VF were genotyped. RESULT: Of 126 patients with samples available, 57 were successfully genotyped. From ART initiation, the proportion of patients with adherence >/=90% increased steadily from 54% at first high viral load (VL) to 67% at confirmed VF, and 81% at time of re-suppressed VL. Sixteen (28%) patients had at least one DRM. Forty-six (81%) patients had full susceptibility to the three drugs in their first-line (1 L) regimen. Thirteen (23%) were resistant to at least one antiretroviral drug but three were resistant to drugs not used in Nigeria. Ten patients had resistance to their 1 L drug(s) and six were fully susceptible to the three drugs in the recommended second-line regimen. CONCLUSION: This cohort had little drug resistance mutations. We conclude that if adherence is not assured, patients could exhibit virologic failure without having developed mutations associated with drug resistance. |
Use of TaqMan Array card for the detection of respiratory viral pathogens in children under 5 years old hospitalised with acute medical illness in Ballabgarh, Haryana, India.
Gaur B , Saha S , Iuliano AD , Rai SK , Krishnan A , Jain S , Whitaker B , Winchell J , Lal RB , Broor S . Indian J Med Microbiol 2019 37 (1) 105-108 ![]() Historical specimens collected from hospitalized children were tested for the following 13 viruses: influenza A and B; respiratory syncytial virus (RSV); parainfluenza viruses 1-3; human metapneumovirus; rhinovirus; coronaviruses 229E, OC43, NL63 and HKU1 and Adenovirus using monoplex real-time reverse transcriptase polymerase chain reaction (rRT-PCR). They were retested using TaqMan Array Card (TAC), a micro-fluidic system, capable of simultaneous multi-pathogen testing, to evaluate its sensitivity and specificity against monoplex rRT-PCR. TAC showed high sensitivity (71%-100%) and specificity (98%-100%) for these viruses in comparison to monoplex rRT-PCR. Multi-specimen detection with high sensitivity and specificity makes TAC a potentially useful tool for both surveillance and outbreak investigations. |
Multidrug-Resistant Aspergillus fumigatus Carrying Mutations Linked to Environmental Fungicide Exposure - Three States, 2010-2017.
Beer KD , Farnon EC , Jain S , Jamerson C , Lineberger S , Miller J , Berkow EL , Lockhart SR , Chiller T , Jackson BR . MMWR Morb Mortal Wkly Rep 2018 67 (38) 1064-1067 ![]() ![]() The environmental mold Aspergillus fumigatus is the primary cause of invasive aspergillosis. In patients with high-risk conditions, including stem cell and organ transplant recipients, mortality exceeds 50%. Triazole antifungals have greatly improved survival (1); however, triazole-resistant A. fumigatus infections are increasingly reported worldwide and are associated with increased treatment failure and mortality (2). Of particular concern are resistant A. fumigatus isolates carrying either TR34/L98H or TR46/Y121F/T289A genetic resistance markers, which have been associated with environmental triazole fungicide use rather than previous patient exposure to antifungals (3,4). Reports of these triazole-resistant A. fumigatus strains have become common in Europe (2,3), but U.S. reports are limited (5). Because of the risk posed to immunocompromised patients, understanding the prevalence of such isolates in patients is important to guide clinical and public health decision-making. In 2011, CDC initiated passive laboratory monitoring for U.S. triazole-resistant A. fumigatus isolates through outreach to clinical laboratories. This system identified five TR34/L98H isolates collected from 2016 to 2017 (6), in addition to two other U.S. isolates collected in 2010 and 2014 and reported in 2015 (5). Four of these seven isolates were reported from Pennsylvania, two from Virginia, and one from California. Three isolates were collected from patients with invasive pulmonary aspergillosis, and four patients had no known previous triazole exposure. A. fumigatus resistant to all triazole medications is emerging in the United States, and clinicians and public health personnel need to be aware that resistant infections are possible even in patients not previously exposed to these medications. |
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. |
Human Bocavirus Capsid Messenger RNA Detection in Children With Pneumonia.
Schlaberg R , Ampofo K , Tardif KD , Stockmann C , Simmon KE , Hymas W , Flygare S , Kennedy B , Blaschke A , Eilbeck K , Yandell M , McCullers JA , Williams DJ , Edwards K , Arnold SR , Bramley A , Jain S , Pavia AT . J Infect Dis 2017 216 (6) 688-696 ![]() Background: The role of human bocavirus (HBoV) in respiratory illness is uncertain. HBoV genomic DNA is frequently detected in both ill and healthy children. We hypothesized that spliced viral capsid messenger RNA (mRNA) produced during active replication might be a better marker for acute infection. Methods: As part of the Etiology of Pneumonia in the Community (EPIC) study, children aged <18 years who were hospitalized with community-acquired pneumonia (CAP) and children asymptomatic at the time of elective outpatient surgery (controls) were enrolled. Nasopharyngeal/oropharyngeal specimens were tested for HBoV mRNA and genomic DNA by quantitative polymerase chain reaction. Results: HBoV DNA was detected in 10.4% of 1295 patients with CAP and 7.5% of 721 controls (odds ratio [OR], 1.4 [95% confidence interval {CI}, 1.0-2.0]); HBoV mRNA was detected in 2.1% and 0.4%, respectively (OR, 5.1 [95% CI, 1.6-26]). When adjusted for age, enrollment month, and detection of other respiratory viruses, HBoV mRNA detection (adjusted OR, 7.6 [95% CI, 1.5-38.4]) but not DNA (adjusted OR, 1.2 [95% CI, .6-2.4]) was associated with CAP. Among children with no other pathogens detected, HBoV mRNA (OR, 9.6 [95% CI, 1.9-82]) was strongly associated with CAP. Conclusions: Detection of HBoV mRNA but not DNA was associated with CAP, supporting a pathogenic role for HBoV in CAP. HBoV mRNA could be a useful target for diagnostic testing. |
Viral Pathogen Detection by Metagenomics and Pan Viral Group PCR in Children with Pneumonia Lacking Identifiable Etiology.
Schlaberg R , Queen K , Simmon K , Tardif K , Stockmann C , Flygare S , Kennedy B , Voelkerding K , Bramley A , Zhang J , Eilbeck K , Yandell M , Jain S , Pavia AT , Tong S , Ampofo K . J Infect Dis 2017 215 (9) 1407-1415 ![]() Background: Community-acquired pneumonia (CAP) is a leading cause of pediatric hospitalization. Pathogen identification fails in ~20% of children but is critical for optimal treatment and prevention of hospital-acquired infections. We used two broad-spectrum detection strategies to identify pathogens in test-negative children with CAP and asymptomatic controls. Methods: Nasopharyngeal/oropharyngeal (NP/OP) swabs from 70 children <5 years with CAP of unknown etiology and 90 asymptomatic controls were tested by next-generation sequencing (RNA-seq) and pan viral group (PVG) PCR for 19 viral families. Association of viruses with CAP was assessed by adjusted odds ratios (aOR) and 95% confidence intervals controlling for season and age group. Results: RNA-seq/PVG PCR detected previously missed, putative pathogens in 34% of patients. Putative viral pathogens included human parainfluenza virus 4 (aOR 9.3, p=0.12), human bocavirus (aOR 9.1, p<0.01), Coxsackieviruses (aOR 5.1, p=0.09), rhinovirus A (aOR 3.5, p=0.34), and rhinovirus C (aOR 2.9, p=0.57). RNA-seq was more sensitive for RNA viruses whereas PVG PCR detected more DNA viruses. Conclusion: RNA-seq and PVG PCR identified additional viruses, some known to be pathogenic, in NP/OP specimens from one-third of children hospitalized with CAP without a previously identified etiology. Both broad-range methods could be useful tools in future epidemiologic and diagnostic studies. |
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. |
Association of sputum microbiota profiles with severity of community-acquired pneumonia in children.
Pettigrew MM , Gent JF , Kong Y , Wade M , Gansebom S , Bramley AM , Jain S , Arnold SL , McCullers JA . BMC Infect Dis 2016 16 317 ![]() BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48-0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02-2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02-2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP. |
Taxonomer: an interactive metagenomics analysis portal for universal pathogen detection and host mRNA expression profiling.
Flygare S , Simmon K , Miller C , Qiao Y , Kennedy B , Di Sera T , Graf EH , Tardif KD , Kapusta A , Rynearson S , Stockmann C , Queen K , Tong S , Voelkerding KV , Blaschke A , Byington CL , Jain S , Pavia A , Ampofo K , Eilbeck K , Marth G , Yandell M , Schlaberg R . Genome Biol 2016 17 (1) 111 ![]() BACKGROUND: High-throughput sequencing enables unbiased profiling of microbial communities, universal pathogen detection, and host response to infectious diseases. However, computation times and algorithmic inaccuracies have hindered adoption. RESULTS: We present Taxonomer, an ultrafast, web-tool for comprehensive metagenomics data analysis and interactive results visualization. Taxonomer is unique in providing integrated nucleotide and protein-based classification and simultaneous host messenger RNA (mRNA) transcript profiling. Using real-world case-studies, we show that Taxonomer detects previously unrecognized infections and reveals antiviral host mRNA expression profiles. To facilitate data-sharing across geographic distances in outbreak settings, Taxonomer is publicly available through a web-based user interface. CONCLUSIONS: Taxonomer enables rapid, accurate, and interactive analyses of metagenomics data on personal computers and mobile devices. |
Identification of Bacterial and Viral Codetections With Mycoplasma pneumoniae Using the TaqMan Array Card in Patients Hospitalized With Community-Acquired Pneumonia.
Diaz MH , Cross KE , Benitez AJ , Hicks LA , Kutty P , Bramley AM , Chappell JD , Hymas W , Patel A , Qi C , Williams DJ , Arnold SR , Ampofo K , Self WH , Grijalva CG , Anderson EJ , McCullers JA , Pavia AT , Wunderink RG , Edwards KM , Jain S , Winchell JM . Open Forum Infect Dis 2016 3 (2) ofw071 ![]() Mycoplasma pneumoniae was detected in a number of patients with community-acquired pneumonia in a recent prospective study. To assess whether other pathogens were also detected in these patients, TaqMan Array Cards were used to test 216 M pneumoniae-positive respiratory specimens for 25 additional viral and bacterial respiratory pathogens. It is interesting to note that 1 or more codetections, predominantly bacterial, were identified in approximately 60% of specimens, with codetections being more common in children. |
Multistate Outbreak of Respiratory Infections among Unaccompanied Children, June-July 2014.
Tomczyk S , Arriola CS , Beall B , Benitez A , Benoit SR , Berman L , Bresee J , da Gloria Carvalho M , Cohn A , Cross K , Diaz MH , Francois Watkins LK , Gierke R , Hagan JE , Harris A , Jain S , Kim L , Kobayashi M , Lindstrom S , McGee L , McMorrow M , Metcalf BL , Moore MR , Moura I , Nix WA , Nyangoma E , Oberste MS , Olsen SJ , Pimenta F , Socias C , Thurman K , Waller J , Waterman SH , Westercamp M , Wharton M , Whitney CG , Winchell JM , Wolff B , Kim C . Clin Infect Dis 2016 63 (1) 48-56 ![]() BACKGROUND: From January-July 2014, >46,000 unaccompanied children (UC) from Central America crossed the U.S.-Mexico border. In June-July, UC aged 9-17 years in four shelters and a processing center in four U.S. states were hospitalized with acute respiratory illness. We conducted a multistate investigation to interrupt disease transmission. METHODS: Medical charts were abstracted for hospitalized UC. Non-hospitalized UC with influenza-like illness were interviewed, and nasopharyngeal and oropharyngeal swabs for PCR-based detection of respiratory pathogens were collected. Nasopharyngeal swabs were used to assess pneumococcal colonization in symptomatic and asymptomatic UC. Pneumococcal blood isolates from hospitalized UC and nasopharyngeal isolates were characterized by serotyping (Quellung) and whole-genome sequencing. RESULTS: Among the 15 hospitalized UC, 4 (44%) of 9 tested positive for influenza viruses, and 6 (43%) of 14 with blood cultures grew pneumococcus, all serotype 5. Among 48 non-hospitalized children with influenza-like illness, >1 respiratory pathogen was identified in 46 (96%). Among 774 non-hospitalized UC, 185 (24%) yielded pneumococcus, and 70 (38%) were serotype 5. UC who transferred through the processing center were more likely than others to be colonized with serotype 5 (OR 3.8; 95% CI, 2.1-6.9). Analysis of the core pneumococcal genomes detected two related, yet independent, clusters. No pneumococcus cases were reported after pneumococcal and influenza immunization campaigns were implemented. CONCLUSIONS: This outbreak of respiratory disease was due to multiple pathogens, including Streptococcus pneumoniae serotype 5 and influenza viruses. Pneumococcal and influenza vaccinations prevented further transmission. Future efforts to prevent similar outbreaks will benefit from use of both vaccines. |
Molecular Detection and Characterization of Mycoplasma pneumoniae Among Patients Hospitalized With Community-Acquired Pneumonia in the United States.
Diaz MH , Benitez AJ , Cross KE , Hicks LA , Kutty P , Bramley AM , Chappell JD , Hymas W , Patel A , Qi C , Williams DJ , Arnold SR , Ampofo K , Self WH , Grijalva CG , Anderson EJ , McCullers JA , Pavia AT , Wunderink RG , Edwards KM , Jain S , Winchell JM . Open Forum Infect Dis 2015 2 (3) ofv106 ![]() BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP). The molecular characteristics of M pneumoniae detected in patients hospitalized with CAP in the United States are poorly described. METHODS: We performed molecular characterization of M pneumoniae in nasopharyngeal/oropharyngeal swabs from children and adults hospitalized with CAP in the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, including P1 typing, multilocus variable-number tandem-repeat analysis (MLVA), and macrolide susceptibility genotyping. RESULTS: Of 216 M pneumoniae polymerase chain reaction-positive specimens, 40 (18.5%) were obtained from adults and 176 (81.5%) from children. P1 type distribution differed between adults (64% type 1 and 36% type 2) and children (84% type 1, 13% type 2, and 3% variant) (P < .05) and among sites (P < .01). Significant differences in the proportions of MLVA types 4/5/7/2 and 3/5/6/2 were also observed by age group (P < .01) and site (P < .01). A macrolide-resistant genotype was identified in 7 (3.5%) specimens, 5 of which were from patients who had recently received macrolide therapy. No significant differences in clinical characteristics were identified among patients with various strain types or between macrolide-resistant and -sensitive M pneumoniae infections. CONCLUSIONS: The P1 type 1 genotype and MLVA type 4/5/7/2 predominated, but there were differences between children and adults and among sites. Macrolide resistance was rare. Differences in strain types did not appear to be associated with differences in clinical outcomes. Whole genome sequencing of M pneumoniae may help identify better ways to characterize strains. |
Characterization of hospitalized community-onset staphylococcus aureus lower respiratory tract infections among generally healthy persons 50 years of age or younger
Tosh PK , Bulens SN , Nadle J , Dumyati G , Lynfield R , Schaffner W , Ray SM , Seema J , Scott F , Sievert D . Infect Dis Clin Pract (Baltim Md) 2013 21 (6) 359-365 BACKGROUND: Case series have described severe lower respiratory tract infection (LRI) in healthy, community-dwelling persons caused by methicillin-resistant Staphylococcus aureus (MRSA). Evaluating populations at risk is needed. METHODS: Surveillance for patients aged 50 years or younger hospitalized with LRI who had S aureus isolated from blood or respiratory specimen during September 2008 to August 2010 was performed at 25 hospitals in 5 US metropolitan areas. Persons with recent health care exposure were excluded. Lower respiratory tract infection diagnosis required supporting radiographic or clinical evidence. Clinical characteristics of LRI were compared by methicillin resistance phenotype. RESULTS: In total, 94 hospitalized community-onset S aureus LRI cases were identified. Lower respiratory tract infection cases were identified in both young adults and children (60%, 35-50 years; and 19%, younger than 17 years), without any seasonality or association with influenza circulation. Among the 94 case patients with LRI, 34 patients (36%) had bacteremia, 36 patients (40%) required ICU admission, and 6 patients (6%) died; proportions were similar between cases with methicillin-susceptible S aureus and MRSA. Lower respiratory tract infection cases with MRSA had longer median length of stay compared with those with methicillin-susceptible S aureus (9 vs. 6 days; P = 0.04). Lower respiratory tract infection cases with evidence of influenza infection had higher mortality compared with LRI cases without influenza infection (31% vs. 2%; P = 0.003). During influenza circulation, 35 (55%) of 64 case patients with LRI were tested for influenza, and 9 (26%) of the 35 case patients tested positive. CONCLUSIONS: S aureus LRI occurred in both adults and children, without any seasonality or association with MRSA and with and without evidence of influenza infection, although case fatality was higher among those with evidence of influenza infection. 2013 by Lippincott Williams & Wilkins. |
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