Last data update: Nov 11, 2024. (Total: 48109 publications since 2009)
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Severe monkeypox in hospitalized patients - United States, August 10-October 10, 2022
Miller MJ , Cash-Goldwasser S , Marx GE , Schrodt CA , Kimball A , Padgett K , Noe RS , McCormick DW , Wong JM , Labuda SM , Borah BF , Zulu I , Asif A , Kaur G , McNicholl JM , Kourtis A , Tadros A , Reagan-Steiner S , Ritter JM , Yu Y , Yu P , Clinton R , Parker C , Click ES , Salzer JS , McCollum AM , Petersen B , Minhaj FS , Brown E , Fischer MP , Atmar RL , DiNardo AR , Xu Y , Brown C , Goodman JC , Holloman A , Gallardo J , Siatecka H , Huffman G , Powell J , Alapat P , Sarkar P , Hanania NA , Bruck O , Brass SD , Mehta A , Dretler AW , Feldpausch A , Pavlick J , Spencer H , Ghinai I , Black SR , Hernandez-Guarin LN , Won SY , Shankaran S , Simms AT , Alarcón J , O'Shea JG , Brooks JT , McQuiston J , Honein MA , O'Connor SM , Chatham-Stephens K , O'Laughlin K , Rao AK , Raizes E , Gold JAW , Morris SB . MMWR Morb Mortal Wkly Rep 2022 71 (44) 1412-1417 As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.(§) Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox(¶) during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy(††) in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.(§§) Engaging all persons with HIV in sustained care remains a critical public health priority. |
Logically Inferred Tuberculosis Transmission (LITT): A Data Integration Algorithm to Rank Potential Source Cases.
Winglee K , McDaniel CJ , Linde L , Kammerer S , Cilnis M , Raz KM , Noboa W , Knorr J , Cowan L , Reynolds S , Posey J , Sullivan Meissner J , Poonja S , Shaw T , Talarico S , Silk BJ . Front Public Health 2021 9 667337 Understanding tuberculosis (TB) transmission chains can help public health staff target their resources to prevent further transmission, but currently there are few tools to automate this process. We have developed the Logically Inferred Tuberculosis Transmission (LITT) algorithm to systematize the integration and analysis of whole-genome sequencing, clinical, and epidemiological data. Based on the work typically performed by hand during a cluster investigation, LITT identifies and ranks potential source cases for each case in a TB cluster. We evaluated LITT using a diverse dataset of 534 cases in 56 clusters (size range: 2-69 cases), which were investigated locally in three different U.S. jurisdictions. Investigators and LITT agreed on the most likely source case for 145 (80%) of 181 cases. By reviewing discrepancies, we found that many of the remaining differences resulted from errors in the dataset used for the LITT algorithm. In addition, we developed a graphical user interface, user's manual, and training resources to improve LITT accessibility for frontline staff. While LITT cannot replace thorough field investigation, the algorithm can help investigators systematically analyze and interpret complex data over the course of a TB cluster investigation. Code available at: https://github.com/CDCgov/TB_molecular_epidemiology/tree/1.0; https://zenodo.org/badge/latestdoi/166261171. |
Isolation and characterization of novel reassortant mammalian orthoreovirus from pigs in the United States.
Wang L , Li Y , Walsh T , Shen Z , Li Y , Nath ND , Lee J , Zheng B , Tao Y , Paden CR , Queen K , Zhang S , Tong S , Ma W . Emerg Microbes Infect 2021 10 (1) 1-43 Mammalian orthoreovirus (MRV) infects multiple mammalian species including humans. A United States Midwest swine farm with approximately one thousand 3-month-old pigs experienced an event, in which more than 300 pigs showed neurological signs, like "down and peddling", with approximately 40% mortality. A novel MRV was isolated from the diseased pigs. Sequence and phylogenetic analysis revealed that the isolate was a reassortant virus containing viral gene segments from three MRV serotypes that infect human, bovine and swine. The M2 and S1 segment of the isolate showed 94% and 92% nucleotide similarity to the M2 of the MRV2 D5/Jones and the S1 of the MRV1 C/bovine/Indiana/MRV00304/2014, respectively; the remaining eight segments displayed 93%-94% nucleotide similarity to those of the MRV3 FS-03/Porcine/USA/2014. Pig studies showed that both MRV-infected and native contact pigs displayed fever, diarrhea and nasal discharge. MRV RNA was detected in different intestinal locations of both infected and contact pigs, indicating that the MRV isolate is pathogenic and transmissible in pigs. Seroconversion was also observed in experimentally infected pigs. A prevalence study on more than 180 swine serum samples collected from two states without disease revealed 40-52% positive to MRV. All results warrant the necessity to monitor MRV epidemiology and reassortment as the MRV could be an important pathogen for the swine industry and a novel MRV might emerge to threaten animal and public health. |
Introduction, Transmission Dynamics, and Fate of Early SARS-CoV-2 Lineages in Santa Clara County, California.
Villarino E , Deng X , Kemper CA , Jorden MA , Bonin B , Rudman SL , Han GS , Yu G , Wang C , Federman S , Bushnell B , Wadford DA , Lin W , Tao Y , Paden CR , Bhatnagar J , MacCannell T , Tong S , Batson J , Chiu CY . J Infect Dis 2021 224 (2) 207-217 We combined viral genome sequencing with contact tracing to investigate introduction and evolution of SARS-CoV-2 lineages in Santa Clara County, California from January 27 to March 21, 2020. Of 558 persons with COVID-19, 101 genomes from 143 available clinical samples comprised 17 different lineages including SCC1 (n=41), WA1 (n=9, including the first 2 reported deaths in the United States, diagnosed post-mortem), D614G (n=4), ancestral Wuhan Hu-1 (n=21), and 13 others (n=26). Public health intervention may have curtailed the persistence of lineages that appeared transiently during February-March. By August, only D614G lineages introduced after March 21 were circulating in SCC. |
Tuberculosis Outbreak Associated With Delayed Diagnosis and Long Infectious Periods in Rural Arkansas, 2010-2018.
Labuda SM , McDaniel C , Talwar A , Braumuller A , Parker S , McGaha S , Blissett C , Wortham J , Mukasa L , Stewart RJ . Public Health Rep 2021 137 (1) 33354921999167 OBJECTIVES: During 2010-2018, the Arkansas Department of Health reported 21 genotype-matched cases of tuberculosis (TB) among residents of a rural county in Arkansas with a low incidence of TB and in nearby counties. The Arkansas Department of Health and the Centers for Disease Control and Prevention investigated to determine the extent of TB transmission and provide recommendations for TB control. METHODS: We reviewed medical and public health records, interviewed patients, and reviewed patients' social media posts to describe patient characteristics, identify epidemiologic links, and establish likely chains of transmission. RESULTS: We identified 21 cases; 11 reported during 2010-2013 and 10 during 2016-2018. All case patients were US-born non-Hispanic Black people. Eighteen case patients had the outbreak genotype, and 3 clinically diagnosed (non-culture-confirmed) case patients had epidemiologic links to patients with the outbreak genotype. Social media reviews revealed epidemiologic links among 10 case patients not previously disclosed during interviews. Eight case patients (38%) had ≥1 health care visit during their infectious period, and 7 patients had estimated infectious periods of >12 months. CONCLUSIONS: Delayed diagnoses and prolonged infectiousness led to TB transmission in this rural community. TB education and awareness is critical to reducing transmission, morbidity, and mortality, especially in areas where health care providers have limited TB experience. Use of social media can help elucidate people at risk, especially when traditional TB investigation techniques are insufficient. |
Developing National Genotype-Independent Indicators for Recent Mycobacterium Tuberculosis Transmission Using Pediatric Cases-United States, 2011-2017
Harrist AV , McDaniel CJ , Wortham JM , Althomsons SP . Public Health Rep 2021 137 (1) 81-86 INTRODUCTION: Pediatric tuberculosis (TB) cases are sentinel events for Mycobacterium tuberculosis transmission in communities because children, by definition, must have been infected relatively recently. However, these events are not consistently identified by genotype-dependent surveillance alerting methods because many pediatric TB cases are not culture-positive, a prerequisite for genotyping. METHODS: We developed 3 potential indicators of ongoing TB transmission based on identifying counties in the United States with relatively high pediatric (aged <15 years) TB incidence: (1) a case proportion indicator: an above-average proportion of pediatric TB cases among all TB cases; (2) a case rate indicator: an above-average pediatric TB case rate; and (3) a statistical model indicator: a statistical model based on a significant increase in pediatric TB cases from the previous 8-quarter moving average. RESULTS: Of the 249 US counties reporting ≥2 pediatric TB cases during 2009-2017, 240 and 249 counties were identified by the case proportion and case rate indicators, respectively. The statistical model indicator identified 40 counties with a significant increase in the number of pediatric TB cases. We compared results from the 3 indicators with an independently generated list of 91 likely transmission events involving ≥2 pediatric cases (ie, known TB outbreaks or case clusters with reported epidemiologic links). All counties with likely transmission events involving multiple pediatric cases were identified by ≥1 indicator; 23 were identified by all 3 indicators. PRACTICE IMPLICATIONS: This retrospective analysis demonstrates the feasibility of using routine TB surveillance data to identify counties where ongoing TB transmission might be occurring, even in the absence of available genotyping data. |
Rapid Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in Detention Facility, Louisiana, USA, May-June, 2020.
Wallace M , James AE , Silver R , Koh M , Tobolowsky FA , Simonson S , Gold JAW , Fukunaga R , Njuguna H , Bordelon K , Wortham J , Coughlin M , Harcourt JL , Tamin A , Whitaker B , Thornburg NJ , Tao Y , Queen K , Uehara A , Paden CR , Zhang J , Tong S , Haydel D , Tran H , Kim K , Fisher KA , Marlow M , Tate JE , Doshi RH , Sokol T , Curran KG . Emerg Infect Dis 2021 27 (2) 421-429 To assess transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a detention facility experiencing a coronavirus disease outbreak and evaluate testing strategies, we conducted a prospective cohort investigation in a facility in Louisiana, USA. We conducted SARS-CoV-2 testing for detained persons in 6 quarantined dormitories at various time points. Of 143 persons, 53 were positive at the initial test, and an additional 58 persons were positive at later time points (cumulative incidence 78%). In 1 dormitory, all 45 detained persons initially were negative; 18 days later, 40 (89%) were positive. Among persons who were SARS-CoV-2 positive, 47% (52/111) were asymptomatic at the time of specimen collection; 14 had replication-competent virus isolated. Serial SARS-CoV-2 testing might help interrupt transmission through medical isolation and quarantine. Testing in correctional and detention facilities will be most effective when initiated early in an outbreak, inclusive of all exposed persons, and paired with infection prevention and control. |
SARS-CoV-2 Transmission Dynamics in a Sleep-Away Camp.
Szablewski CM , Chang KT , McDaniel CJ , Chu VT , Yousaf AR , Schwartz NG , Brown M , Winglee K , Paul P , Cui Z , Slayton RB , Tong S , Li Y , Uehara A , Zhang J , Sharkey SM , Kirking HL , Tate JE , Dirlikov E , Fry AM , Hall AJ , Rose DA , Villanueva J , Drenzek C , Stewart RJ , Lanzieri TM . Pediatrics 2021 147 (4) OBJECTIVES: In late June 2020, a large outbreak of coronavirus disease 2019 (COVID-19) occurred at a sleep-away youth camp in Georgia, affecting primarily persons </=21 years. We conducted a retrospective cohort study among campers and staff (attendees) to determine the extent of the outbreak and assess factors contributing to transmission. METHODS: Attendees were interviewed to ascertain demographic characteristics, known exposures to COVID-19 and community exposures, and mitigation measures before, during, and after attending camp. COVID-19 case status was determined for all camp attendees on the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results and reported symptoms. We calculated attack rates and instantaneous reproduction numbers and sequenced SARS-CoV-2 viral genomes from the outbreak. RESULTS: Among 627 attendees, the median age was 15 years (interquartile range: 12-16 years); 56% (351 of 627) of attendees were female. The attack rate was 56% (351 of 627) among all attendees. On the basis of date of illness onset or first positive test result on a specimen collected, 12 case patients were infected before arriving at camp and 339 case patients were camp associated. Among 288 case patients with available symptom information, 45 (16%) were asymptomatic. Despite cohorting, 50% of attendees reported direct contact with people outside their cabin cohort. On the first day of camp session, the instantaneous reproduction number was 10. Viral genomic diversity was low. CONCLUSIONS: Few introductions of SARS-CoV-2 into a youth congregate setting resulted in a large outbreak. Testing strategies should be combined with prearrival quarantine, routine symptom monitoring with appropriate isolation and quarantine, cohorting, social distancing, mask wearing, and enhanced disinfection and hand hygiene. Promotion of mitigation measures among younger populations is needed. |
Evidence of SARS-CoV-2 Replication and Tropism in the Lungs, Airways and Vascular Endothelium of Patients with Fatal COVID-19: An Autopsy Case-Series.
Bhatnagar J , Gary J , Reagan-Steiner S , Estetter LB , Tong S , Tao Y , Denison AM , Lee E , DeLeon-Carnes M , Li Y , Uehara A , Paden CR , Leitgeb B , Uyeki TM , Martines RB , Ritter JM , Paddock CD , Shieh WJ , Zaki SR . J Infect Dis 2021 223 (5) 752-764 BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of SARS-CoV-2 tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case-patients (age range: 1 month to 84 years; COVID-19 confirmed n=21, suspected n=43) by SARS-CoV-2 RT-PCR. For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in-situ hybridization (ISH), subgenomic RNA RT-PCR, and whole genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case-patients (confirmed n=21 and suspected n=11). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case-patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes and macrophages of lungs, epithelial cells of airways, and in endothelial cells and vessels wall of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. D614G variant was detected in 9 RT-PCR-positive case-patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes. |
COVID-19 in Americans aboard the Diamond Princess cruise ship.
Plucinski MM , Wallace M , Uehara A , Kurbatova EV , Tobolowsky FA , Schneider ZD , Ishizumi A , Bozio CH , Kobayashi M , Toda M , Stewart A , Wagner RL , Moriarty LF , Murray R , Queen K , Tao Y , Paden C , Mauldin MR , Zhang J , Li Y , Elkins CA , Lu X , Herzig CTA , Novak R , Bower W , Medley AM , Acosta AM , Knust B , Cantey PT , Pesik NT , Halsey ES , Cetron MS , Tong S , Marston BJ , Friedman CR . Clin Infect Dis 2020 72 (10) e448-e457 BACKGROUND: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSION: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in U.S. waters in March 2020. |
SARS-CoV-2 Transmission and Infection Among Attendees of an Overnight Camp - Georgia, June 2020.
Szablewski CM , Chang KT , Brown MM , Chu VT , Yousaf AR , Anyalechi N , Aryee PA , Kirking HL , Lumsden M , Mayweather E , McDaniel CJ , Montierth R , Mohammed A , Schwartz NG , Shah JA , Tate JE , Dirlikov E , Drenzek C , Lanzieri TM , Stewart RJ . MMWR Morb Mortal Wkly Rep 2020 69 (31) 1023-1025 Limited data are available about transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), among youths. During June 17-20, an overnight camp in Georgia (camp A) held orientation for 138 trainees and 120 staff members; staff members remained for the first camp session, scheduled during June 21-27, and were joined by 363 campers and three senior staff members on June 21. Camp A adhered to the measures in Georgia's Executive Order* that allowed overnight camps to operate beginning on May 31, including requiring all trainees, staff members, and campers to provide documentation of a negative viral SARS-CoV-2 test ≤12 days before arriving. Camp A adopted most(†) components of CDC's Suggestions for Youth and Summer Camps(§) to minimize the risk for SARS-CoV-2 introduction and transmission. Measures not implemented were cloth masks for campers and opening windows and doors for increased ventilation in buildings. Cloth masks were required for staff members. Camp attendees were cohorted by cabin and engaged in a variety of indoor and outdoor activities, including daily vigorous singing and cheering. On June 23, a teenage staff member left camp A after developing chills the previous evening. The staff member was tested and reported a positive test result for SARS-CoV-2 the following day (June 24). Camp A officials began sending campers home on June 24 and closed the camp on June 27. On June 25, the Georgia Department of Public Health (DPH) was notified and initiated an investigation. DPH recommended that all attendees be tested and self-quarantine, and isolate if they had a positive test result. |
Severe Acute Respiratory Syndrome Coronavirus 2 from Patient with Coronavirus Disease, United States.
Harcourt J , Tamin A , Lu X , Kamili S , Sakthivel SK , Murray J , Queen K , Tao Y , Paden CR , Zhang J , Li Y , Uehara A , Wang H , Goldsmith C , Bullock HA , Wang L , Whitaker B , Lynch B , Gautam R , Schindewolf C , Lokugamage KG , Scharton D , Plante JA , Mirchandani D , Widen SG , Narayanan K , Makino S , Ksiazek TG , Plante KS , Weaver SC , Lindstrom S , Tong S , Menachery VD , Thornburg NJ . Emerg Infect Dis 2020 26 (6) 1266-1273 The etiologic agent of an outbreak of pneumonia in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 in January 2020. A patient in the United States was given a diagnosis of infection with this virus by the state of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens from this patient and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into 2 virus repositories, making it broadly available to the public health and research communities. We hope that open access to this reagent will expedite development of medical countermeasures. |
Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient.
Harcourt J , Tamin A , Lu X , Kamili S , Sakthivel SK , Murray J , Queen K , Tao Y , Paden CR , Zhang J , Li Y , Uehara A , Wang H , Goldsmith C , Bullock HA , Wang L , Whitaker B , Lynch B , Gautam R , Schindewolf C , Lokugamage KG , Scharton D , Plante JA , Mirchandani D , Widen SG , Narayanan K , Makino S , Ksiazek TG , Plante KS , Weaver SC , Lindstrom S , Tong S , Menachery VD , Thornburg NJ . bioRxiv 2020 The etiologic agent of the outbreak of pneumonia in Wuhan China was identified as severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) in January, 2020. The first US patient was diagnosed by the State of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens, and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into two virus repositories, making it broadly available to the public health and research communities. We hope that open access to this important reagent will expedite development of medical countermeasures. |
Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California.
Deng X , Gu W , Federman S , du Plessis L , Pybus OG , Faria N , Wang C , Yu G , Bushnell B , Pan CY , Guevara H , Sotomayor-Gonzalez A , Zorn K , Gopez A , Servellita V , Hsu E , Miller S , Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Chu HY , Shendure J , Jerome KR , Anderson C , Gangavarapu K , Zeller M , Spencer E , Andersen KG , MacCannell D , Paden CR , Li Y , Zhang J , Tong S , Armstrong G , Morrow S , Willis M , Matyas BT , Mase S , Kasirye O , Park M , Masinde G , Chan C , Yu AT , Chai SJ , Villarino E , Bonin B , Wadford DA , Chiu CY . Science 2020 369 (6503) 582-587 The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, with >52,000 cases in California as of May 4, 2020. Here we investigate the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning 9 counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least 7 different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington State, with lack of a predominant lineage and limited transmission between communities. Lineages associated with outbreak clusters in 2 counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain SARS-CoV-2 spread in California and other states. |
Tuberculosis transmission across three states: the story of a solid organ donor born in an endemic country, 2018.
Jones JM , Vikram HR , Lauzardo M , Hill A , Jones J , Haley C , Seaworth B , Oldham S , Brown M , Gutierrez F , Basavaraju SV . Transpl Infect Dis 2020 22 (6) e13357 Transmission of tuberculosis (TB) from a deceased solid organ donor to recipients can result in severe morbidity and mortality. In 2018, four solid organ transplant recipients residing in three states but sharing a common organ donor were diagnosed with TB disease. Two recipients were hospitalized and none died. The organ donor was born in a country with a high incidence of TB and experienced 8 weeks of headache and fever prior to death, but was not tested for TB during multiple hospitalizations or prior to organ procurement. TB isolates of two organ recipients and a close contact of the donor had identical TB genotypes and closely related whole-genome sequencing results. Donors with risk factors for TB, in particular birth or residence in countries with a higher TB incidence, should be carefully evaluated for TB. |
Characteristics of Health Care Personnel with COVID-19 - United States, February 12-April 9, 2020.
CDC COVID-19 Response Team , Burrer Sherry L , de Perio Marie A , Hughes Michelle M , Kuhar David T , Luckhaupt Sara E , McDaniel Clinton J , Porter Rachael M , Silk Benjamin , Stuckey Matthew J , Walters Maroya . MMWR Morb Mortal Wkly Rep 2020 69 (15) 477-481 As of April 9, 2020, the coronavirus disease 2019 (COVID-19) pandemic had resulted in 1,521,252 cases and 92,798 deaths worldwide, including 459,165 cases and 16,570 deaths in the United States (1,2). Health care personnel (HCP) are essential workers defined as paid and unpaid persons serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials (3). During February 12-April 9, among 315,531 COVID-19 cases reported to CDC using a standardized form, 49,370 (16%) included data on whether the patient was a health care worker in the United States; including 9,282 (19%) who were identified as HCP. Among HCP patients with data available, the median age was 42 years (interquartile range [IQR] = 32-54 years), 6,603 (73%) were female, and 1,779 (38%) reported at least one underlying health condition. Among HCP patients with data on health care, household, and community exposures, 780 (55%) reported contact with a COVID-19 patient only in health care settings. Although 4,336 (92%) HCP patients reported having at least one symptom among fever, cough, or shortness of breath, the remaining 8% did not report any of these symptoms. Most HCP with COVID-19 (6,760, 90%) were not hospitalized; however, severe outcomes, including 27 deaths, occurred across all age groups; deaths most frequently occurred in HCP aged ≥65 years. These preliminary findings highlight that whether HCP acquire infection at work or in the community, it is necessary to protect the health and safety of this essential national workforce. |
Isolation and growth characterization of novel full length and deletion mutant human MERS-CoV strains from clinical specimens collected during 2015.
Tamin A , Queen K , Paden CR , Lu X , Andres E , Sakthivel SK , Li Y , Tao Y , Zhang J , Kamili S , Assiri AM , Alshareef A , Alaifan TA , Altamimi AM , Jokhdar H , Watson JT , Gerber SI , Tong S , Thornburg NJ . J Gen Virol 2019 100 (11) 1523-1529 Middle East respiratory syndrome (MERS) is a viral respiratory illness first reported in Saudi Arabia in September 2012 caused by the human coronavirus (CoV), MERS-CoV. Using full-genome sequencing and phylogenetic analysis, scientists have identified three clades and multiple lineages of MERS-CoV in humans and the zoonotic host, dromedary camels. In this study, we have characterized eight MERS-CoV isolates collected from patients in Saudi Arabia in 2015. We have performed full-genome sequencing on the viral isolates, and compared them to the corresponding clinical specimens. All isolates were clade B, lineages 4 and 5. Three of the isolates carry deletions located on three independent regions of the genome in the 5'UTR, ORF1a and ORF3. All novel MERS-CoV strains replicated efficiently in Vero and Huh7 cells. Viruses with deletions in the 5'UTR and ORF1a exhibited impaired viral release in Vero cells. These data emphasize the plasticity of the MERS-CoV genome during human infection. |
Scope and extent of healthcare-associated Middle East respiratory syndrome coronavirus transmission during two contemporaneous outbreaks in Riyadh, Saudi Arabia, 2017.
Alanazi KH , Killerby ME , Biggs HM , Abedi GR , Jokhdar H , Alsharef AA , Mohammed M , Abdalla O , Almari A , Bereagesh S , Tawfik S , Alresheedi H , Alhakeem RF , Hakawi A , Alfalah H , Amer H , Thornburg NJ , Tamin A , Trivedi S , Tong S , Lu X , Queen K , Li Y , Sakthivel SK , Tao Y , Zhang J , Paden CR , Al-Abdely HM , Assiri AM , Gerber SI , Watson JT . Infect Control Hosp Epidemiol 2019 40 (1) 79-88 OBJECTIVE: To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications. DESIGN: Outbreak investigation. SETTING: Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit. METHODS: Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases. RESULTS: In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to >/=5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive. CONCLUSIONS: We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission. |
Medical countermeasure actions - a historical perspective
LeBlanc TT , Ekperi L , Avchen RN , Kosmos C . Am J Public Health 2018 108 S175-s176 On March 20, 1995, Sarin gas was released during morning rush hour in the Tokyo, Japan, subway system, killing 13 individuals and causing illness among thousands.1 The event received significant media coverage and signaled a call for action among officials in charge of national security. As a component of preparedness efforts against acts of bioterrorism, then President Clinton launched the first national biological weapons defense initiative, and in 1999, Congress appropriated $50 million dollars for the Department of Health and Humans Services, Centers for Disease Control and Prevention (CDC) to mobilize the public health system for protection against harmful biological agents.2 Ensuring safety of the public’s health led to the development of the National Pharmaceutical Stockpile, a repository of pharmaceuticals and medical supplies available for rapid deployment, and provision of direct support to local, state, and territorial health departments in the event of a large-scale public health emergency.3 |
Comprehensive viral enrichment enables sensitive respiratory virus genomic identification and analysis by next generation sequencing.
O'Flaherty BM , Li Y , Tao Y , Paden CR , Queen K , Zhang J , Dinwiddie DL , Gross SM , Schroth GP , Tong S . Genome Res 2018 28 (6) 869-877 Next generation sequencing (NGS) technologies have revolutionized the genomics field and are becoming more commonplace for identification of human infectious diseases. However, due to the low abundance of viral nucleic acids (NAs) in relation to host, viral identification using direct NGS technologies often lacks sufficient sensitivity. Here, we describe an approach based on two complementary enrichment strategies that significantly improves the sensitivity of NGS-based virus identification. To start, we developed two sets of DNA probes to enrich virus NAs associated with respiratory diseases. The first set of probes spans the genomes, allowing for identification of known viruses and full genome sequencing, while the second set targets regions conserved among viral families or genera, providing the ability to detect both known and potentially novel members of those virus groups. Efficiency of enrichment was assessed by NGS testing reference virus and clinical samples with known infection. We show significant improvement in viral identification using enriched NGS compared to unenriched NGS. Without enrichment, we observed an average of 0.3% targeted viral reads per sample. However, after enrichment, 50%-99% of the reads per sample were the targeted viral reads for both the reference isolates and clinical specimens using both probe sets. Importantly, dramatic improvements on genome coverage were also observed following virus-specific probe enrichment. The methods described here provide improved sensitivity for virus identification by NGS, allowing for a more comprehensive analysis of disease etiology. |
Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews
Nurse-Findlay S , Taylor MM , Savage M , Mello MB , Saliyou S , Lavayen M , Seghers F , Campbell ML , Birgirimana F , Ouedraogo L , Newman Owiredu M , Kidula N , Pyne-Mercier L . PLoS Med 2017 14 (12) e1002473 BACKGROUND: Benzathine penicillin G (BPG) is the only recommended treatment to prevent mother-to-child transmission of syphilis. Due to recent reports of country-level shortages of BPG, an evaluation was undertaken to quantify countries that have experienced shortages in the past 2 years and to describe factors contributing to these shortages. METHODS AND FINDINGS: Country-level data about BPG shortages were collected using 3 survey approaches. First, a survey designed by the WHO Department of Reproductive Health and Research was distributed to 41 countries and territories in the Americas and 41 more in Africa. Second, WHO conducted an email survey of 28 US Centers for Disease Control and Prevention country directors. An additional 13 countries were in contact with WHO for related congenital syphilis prevention activities and also reported on BPG shortages. Third, the Clinton Health Access Initiative (CHAI) collected data from 14 countries (where it has active operations) to understand the extent of stock-outs, in-country purchasing, usage behavior, and breadth of available purchasing options to identify stock-outs worldwide. CHAI also conducted in-person interviews in the same 14 countries to understand the extent of stock-outs, in-country purchasing and usage behavior, and available purchasing options. CHAI also completed a desk review of 10 additional high-income countries, which were also included. BPG shortages were attributable to shortfalls in supply, demand, and procurement in the countries assessed. This assessment should not be considered globally representative as countries not surveyed may also have experienced BPG shortages. Country contacts may not have been aware of BPG shortages when surveyed or may have underreported medication substitutions due to desirability bias. Funding for the purchase of BPG by countries was not evaluated. In all, 114 countries and territories were approached to provide information on BPG shortages occurring during 2014-2016. Of unique countries and territories, 95 (83%) responded or had information evaluable from public records. Of these 95 countries and territories, 39 (41%) reported a BPG shortage, and 56 (59%) reported no BPG shortage; 10 (12%) countries with and without BPG shortages reported use of antibiotic alternatives to BPG for treatment of maternal syphilis. Market exits, inflexible production cycles, and minimum order quantities affect BPG supply. On the demand side, inaccurate forecasts and sole sourcing lead to under-procurement. Clinicians may also incorrectly prescribe BPG substitutes due to misperceptions of quality or of the likelihood of adverse outcomes. CONCLUSIONS: Targets for improvement include drug forecasting and procurement, and addressing provider reluctance to use BPG. Opportunities to improve global supply, demand, and use of BPG should be prioritized alongside congenital syphilis elimination efforts. |
Diversity of Middle East respiratory syndrome coronaviruses in 109 dromedary camels based on full-genome sequencing, Abu Dhabi, United Arab Emirates.
Yusof MF , Queen K , Eltahir YM , Paden CR , Al Hammadi Zmah , Tao Y , Li Y , Khalafalla AI , Shi M , Zhang J , Mohamed Msae , Abd Elaal Ahmed MH , Azeez IA , Bensalah OK , Eldahab ZS , Al Hosani FI , Gerber SI , Hall AJ , Tong S , Al Muhairi SS . Emerg Microbes Infect 2017 6 (11) e101 Middle East respiratory syndrome coronavirus (MERS-CoV) was identified on the Arabian Peninsula in 2012 and is still causing cases and outbreaks in the Middle East. When MERS-CoV was first identified, the closest related virus was in bats; however, it has since been recognized that dromedary camels serve as a virus reservoir and potential source for human infections. A total of 376 camels were screened for MERS-Cov at a live animal market in the Eastern Region of the Emirate of Abu Dhabi, UAE. In all, 109 MERS-CoV-positive camels were detected in week 1, and a subset of positive camels were sampled again weeks 3 through 6. A total of 126 full and 3 nearly full genomes were obtained from 139 samples. Spike gene sequences were obtained from 5 of the 10 remaining samples. The camel MERS-CoV genomes from this study represent 3 known and 2 potentially new lineages within clade B. Within lineages, diversity of camel and human MERS-CoV sequences are intermixed. We identified sequences from market camels nearly identical to the previously reported 2015 German case who visited the market during his incubation period. We described 10 recombination events in the camel samples. The most frequent recombination breakpoint was the junctions between ORF1b and S. Evidence suggests MERS-CoV infection in humans results from continued introductions of distinct MERS-CoV lineages from camels. This hypothesis is supported by the camel MERS-CoV genomes sequenced in this study. Our study expands the known repertoire of camel MERS-CoVs circulating on the Arabian Peninsula. |
Identification of diverse viruses in upper respiratory samples in dromedary camels from United Arab Emirates.
Li Y , Khalafalla AI , Paden CR , Yusof MF , Eltahir YM , Al Hammadi ZM , Tao Y , Queen K , Hosani FA , Gerber SI , Hall AJ , Al Muhairi S , Tong S . PLoS One 2017 12 (9) e0184718 Camels are known carriers for many viral pathogens, including Middle East respiratory syndrome coronavirus (MERS-CoV). It is likely that there are additional, as yet unidentified viruses in camels with the potential to cause disease in humans. In this study, we performed metagenomic sequencing analysis on nasopharyngeal swab samples from 108 MERS-CoV-positive dromedary camels from a live animal market in Abu Dhabi, United Arab Emirates. We obtained a total of 846.72 million high-quality reads from these nasopharyngeal swab samples, of which 2.88 million (0.34%) were related to viral sequences while 512.63 million (60.5%) and 50.87 million (6%) matched bacterial and eukaryotic sequences, respectively. Among the viral reads, sequences related to mammalian viruses from 13 genera in 10 viral families were identified, including Coronaviridae, Nairoviridae, Paramyxoviridae, Parvoviridae, Polyomaviridae, Papillomaviridae, Astroviridae, Picornaviridae, Poxviridae, and Genomoviridae. Some viral sequences belong to known camel or human viruses and others are from potentially novel camel viruses with only limited sequence similarity to virus sequences in GenBank. A total of five potentially novel virus species or strains were identified. Co-infection of at least two recently identified camel coronaviruses was detected in 92.6% of the camels in the study. This study provides a comprehensive survey of viruses in the virome of upper respiratory samples in camels that have extensive contact with the human population. |
Ensuring quality: a key consideration in scaling-up HIV-related point-of-care testing programs
Fonjungo PN , Osmanov S , Kuritsky J , Ndihokubwayo JB , Bachanas P , Peeling RW , Timperi R , Fine G , Stevens W , Habiyambere V , Nkengasong JN . AIDS 2016 30 (8) 1317-23 OBJECTIVE: The objective of the World Health Organization (WHO)/U.S. President's Emergency Plan for AIDS Relief (PEPFAR) consultation was to discuss innovative strategies, offer guidance and develop a comprehensive policy framework for implementing quality-assured HIV-related point-of-care testing (POCT). METHODS: The consultation was attended by representatives from international agencies (WHO, UNICEF, UNITAID, Clinton Health Access Initiative [CHAI]), USAID, Centers for Disease Control and Prevention [CDC]/PEPFAR Cooperative Agreement Partners, and experts from more than 25 countries including policy makers, clinicians, laboratory experts and program implementers. MAIN OUTCOMES: There was strong consensus among all participants that ensuring access to quality of POCT represents one of the key challenges for the success of HIV prevention, treatment and care programs. The following four strategies were recommended: 1) implement a newly proposed concept of a sustainable quality assurance cycle that includes (a) careful planning; (b) definition of goals and targets; (c) timely implementation; (d) continuous monitoring; (e) improvements and adjustments, where necessary; and (f) a detailed evaluation; 2) the importance of supporting a cadre of workers (e.g. volunteer quality corps [Q-Corps]) with the role to ensure that the quality assurance cycle is followed and sustained; 3) implementation of the new strategy should be seen as a step-wise process, supported by development of appropriate policies and tools; and 4) joint partnership under the leadership of the Ministries of Health to ensure sustainability of implementing novel approaches. CONCLUSIONS: The outcomes of this consultation have been well received by program implementers in the field. The recommendations also laid the groundwork for developing key policy and quality documents for the implementation of HIV-related POCT. |
Stringent HIV viral load threshold for virological failure using dried blood spots: is the perfect the enemy of the good?
Inzaule SC , Hamers RL , Zeh CE , Rinke de Wit TF . J Acquir Immune Defic Syndr 2015 71 (1) e30-3 Since 2013, World Health Organization (WHO) recommends plasma HIV viral load (VL) as the preferred monitoring strategy of antiretroviral therapy (ART), complementing clinical and immunological criteria.1 VL monitoring enables accurate detection of virological failure prompting timely adherence counseling and regimen switches before drug resistance accumulates,2 and also prevention of inappropriate switching to more costly second-line regimens.2 | Despite significant progress,3 there are major obstacles to scaling up VL testing in low-income and middle-income countries (LMICs), including high costs, complex sample logistics, limited laboratory infrastructure, and shortage of skilled staff. With point-of-care applications still largely unavailable,4 dried blood spots (DBS), rather than plasma, are propagated,5,6 because of the advantages of easy sample collection through finger prick (eliminating phlebotomy and centrifugation) and easy shipment to a reference laboratory at ambient temperature (eliminating cold-chain transportation).7–9 However, potential limitations of DBS include lower amplification sensitivity (due to small sample volumes) and lower specificity (contribution by cell-associated viruses may overestimate VL).7–10 | To account for these limitations, WHO previously recommended a VL threshold for virological failure of 3000–5000 copies per milliliter with DBS, compared to 1000 copies per milliliter with plasma.1 However, a 2014 WHO technical update revised the threshold with DBS to 1000 copies per milliliter, citing provisional data from a review by Clinton Health Access Initiative on 5 commercial VL assays, which suggested sufficient sensitivities for this threshold.6 |
Vaccine-preventable disease among homeschooled children: two cases of tetanus in Oklahoma
Johnson MG , Bradley KK , Mendus S , Burnsed L , Clinton R , Tiwari T . Pediatrics 2013 132 (6) e1686-9 Homeschooled children represent an increasing proportion of school-aged children in the United States. Immunization rates among homeschooled children are largely unknown because they are usually not subject to state-based school-entry vaccination requirements. Geographic foci of underimmunized children can increase the risk for outbreaks of vaccine-preventable diseases. In 2012, 2 cases of tetanus were reported in Oklahoma; both cases involved homeschooled children without documentation of diphtheria-tetanus-acellular pertussis vaccination. We describe the characteristics of both patients and outline innovative outreach measures with the potential to increase vaccination access and coverage among homeschooled children. |
A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.
Milton JN , Sebastiani P , Solovieff N , Hartley SW , Bhatnagar P , Arking DE , Dworkis DA , Casella JF , Barron-Casella E , Bean CJ , Hooper WC , Debaun MR , Garrett ME , Soldano K , Telen MJ , Ashley-Koch A , Gladwin MT , Baldwin CT , Steinberg MH , Klings ES . PLoS One 2012 7 (4) e34741 Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5x10(-8)). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08x10(-25)). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15x10(-4)). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities. |
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