Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
Records 1-30 (of 71 Records) |
Query Trace: Simmons S[original query] |
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Spike and nucleocapsid antibody dynamics following SARS-CoV-2 infection and vaccination: Implications for sourcing COVID-19 convalescent plasma from routinely collected blood donations
Di Germanio C , Deng X , Balasko BG , Simmons G , Martinelli R , Grebe E , Stone M , Spencer BR , Saa P , Yu EA , Lanteri MC , Green V , Wright D , Lartey I , Kleinman S , Jones J , Biggerstaff BJ , Contestable P , Busch MP . Transfusion 2024 BACKGROUND: COVID-19 convalescent plasma (CCP) remains a treatment option for immunocompromised patients; however, the current FDA qualification threshold of ≥200 BAU/mL of spike antibody appears to be relatively low. We evaluated the levels of binding (bAb) and neutralizing antibodies (nAb) on serial samples from repeat blood donors who were vaccinated and/or infected to inform criteria for qualifying CCP from routinely collected plasma components. METHODS: Donors were categorized into four groups: (1) infected, then vaccinated, (2) vaccinated then infected during the delta, or (3) omicron waves, (4) vaccinated without infection. IgG Spike and total Nuclecapsid bAb were measured, along with S variants and nAb titers using reporter viral particle neutralization. RESULTS: Mean S IgG bAb peaks after infection alone were lower than after primary and booster vaccinations, and higher after delta and omicron infection in previously vaccinated donors. Half-lives for S IgG ranged from 34 to 66 days after first infection/vaccination events and up to 108 days after second events. The levels of S IgG bAb and nAb were similar across different variants, except for omicron, which were lower. Better correlations of nAb with bAb were observed at higher levels (hybrid immunity) than at the current FDA CCP qualifying threshold. DISCUSSION: Routine plasma donations from donors with hybrid immunity had high S bAb and potent neutralizing activity for 3-6 months after infection. In donations with high (>4000 BAU/mL) S IgG, >95% had high nAb titers (>500) against ancestral and variant S, regardless of COVID-19 symptoms. These findings provide the basis for test-based criteria for qualifying CCP from routine blood donations. |
Tracking the burden, distribution, and impact of Post-COVID conditions in diverse populations for children, adolescents, and adults (Track PCC): passive and active surveillance protocols
Jones RM , Andrews JG , Dalton AF , Dixon BE , Dzomba BJ , Fernando SI , Pogreba-Brown KM , Ortiz MR , Sharma V , Simmons N , Saydah SH . BMC Public Health 2024 24 (1) 2345 BACKGROUND: Track PCC includes five geographic surveillance sites to conduct standardized population-based surveillance to estimate and track Post-COVID Conditions (PCC) by age, sex, race/ethnicity, geographic area, severity of initial infection, and risk factors among persons with evidence of SARS-CoV-2 infection (based on the Council of State and Territorial Epidemiologist [CSTE] case definitions for confirmed cases or laboratory-confirmed evidence of infection). METHODS: The study will estimate the incidence, prevalence, including temporal trends, and duration and severity of PCC symptoms, among children, adolescents, and adults. PCCs include a broad range of symptoms and conditions that continue or develop after acute SARS-CoV-2 infection or COVID-19 illness. Surveillance includes both passive and active components for diverse populations in Arizona, Indiana, and Utah as well as the Bronx Borough, NY, and part of Philadelphia County, PA. Passive surveillance will utilize electronic health records and health information exchanges within each site catchment area to longitudinally follow persons with COVID-19 to estimate PCC occurring at least 30 days after acute COVID-19 illness. Active surveillance will utilize self-report of PCCs from detailed surveys of persons ages 7 years and older with evidence of SARS-CoV-2 infection in the past 3 months. Respondents will complete follow-up surveys at 6-, 12- and 18-months post-infection. DISCUSSION: These data can help identify which groups are most affected by PCC, and what health differences among demographic groups exist, as well as indicate potential barriers to care. These additional levels of granularity can inform public health action and help direct needed clinical care for patients. |
Serological responses to trachoma antigens prior to the start of mass drug administration: Results from population-based baseline surveys, North Darfur, Sudan
Sanders AM , Elshafie BE , Abdalla Z , Simmons C , Goodhew EB , Gonzalez TA , Nute AW , Mohammed A , Callahan EK , Martin DL , Nash SD . Am J Trop Med Hyg 2024 After years of programmatic inaccessibility, in 2019-2020 the Sudan Federal Ministry of Health Trachoma Control Program conducted population-based trachoma surveys in three localities (districts) in North Darfur state, Sudan. These baseline surveys were to determine the prevalence of trachomatous inflammation-follicular (TF) among children aged 1-9 years and to further use serological markers to understand the historical trachoma burden within this mass drug administration (MDA)-naive area. Trained and certified graders collected trachoma clinical data, and trained nurses collected dried blood spot (DBS) samples. The DBSs were assayed on a multiplex bead array for antibody responses to the Chlamydia trachomatis antigens Pgp3 and CT694. Across the three localities, 3,613 individuals aged 1-9 years and 3,542 individuals aged ≥15 years were examined for clinical signs, and 8,322 DBSs were collected. The prevalence of TF among children aged 1-9 years was endemic (≥5%) in two localities (El Seraif, 15.6%, and Saraf Omrah, 11.0%) and below the TF elimination threshold (<5%) in the third (Kotom, 1.4%). The Pgp3 seroprevalence among children aged 1-9 years was 34.1% in El Seraif, 35.0% in Saraf Omrah, and 11.0% in Kotom. Locality prevalence results were similar for Pgp3 and CT694. Seroprevalence increased with age in all three localities. Serological data collected within these surveys demonstrate that all three localities have had a long history of exposure to Chlamydia trachomatis and that two of the three localities require MDA to reach elimination as a public health problem threshold. |
Use of U.S. Blood Donors for National Serosurveillance of SARS-CoV-2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program (preprint)
Stone M , Di Germanio C , Wright DJ , Sulaeman H , Dave H , Fink RV , Notari EP , Green V , Strauss D , Kessler D , Destree M , Saa P , Williamson PC , Simmons G , Stramer SL , Opsomer J , Jones JM , Kleinman S , Busch MP . medRxiv 2021 2021.05.01.21255576 Introduction The REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for SARS-CoV-2 antibodies on blood donors in six U.S. metropolitan regions to estimate the extent of SARS-COV-2 infections over time.Study Design/Methods During March-August 2020, approximately ≥1,000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences with the general population. Seroprevalence was compared with reported COVID-19 case rates over time.Results/Findings For all regions, seroprevalence was <1.0% in March 2020. New York experienced the biggest increase (peak seroprevalence, 15.8 % in May). All other regions experienced modest increases in seroprevalence(1-2% in May-June to 2-4% in July-August). Seroprevalence was higher in younger, non-Hispanic Black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case reported to CDC.Conclusion Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic Black and Hispanic blood donors than in non-Hispanic White blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.Summary SARS-CoV-2 serosurveillance data from blood donors in 6 US regions were used to estimate population weighted seroprevalence. Seroprevelance rates were higher in case rates. The study was expanded to a national donor serosurveillance program.Disclaimer The content is solely the responsibility of the authors and does not represent the policy of the National Institutes of Health or the Department of Health and Human Services. Any specific brandnames included in this manuscript are for identification purposes only and are not intended to represent an endorsement by CDC. The findings and conclusions in this report are those of the authorsand do not necessarily represent the official position of the Centers of Disease Control and Prevention.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe authors were supported by research contracts from the National Heart, Lung, and Blood Institute (NHLBI Contracts HHSN 75N92019D00032 and HHSN 75N92019D00033) as well as with funding support from the National Institute of Allergies and Infectious Diseases (NIAID), NIH.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study was reviewed by the UCSF Committee for Human Research and determined to meet the definition of research as defined in 46.102(l) but did not involve human subjects based on anonymization of data and routine consent for blood donation testing that includes use of residual samples for research purposes (as defined in 46.103(e)(1) consistent with applicable federal law and CDC policy (45 C.F.R. part 46; 21 C.F.R. part 56; 42 U.S.C. p241(d), 5 U.S.C. p552a, 44 U.S.C. p3501)).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a pros ective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe data is not being made publicly available for privacy reasons related to federal regulations but a limited dataset may be made available upon request after formal review by NHLBI and CDC's privacy office before release. |
Evaluation of commercially available high-throughput SARS-CoV-2 serological assays for serosurveillance and related applications (preprint)
Stone M , Grebe E , Sulaeman H , Di Germanio C , Dave H , Kelly K , Biggerstaff BJ , Crews BO , Tran N , Jerome KR , Denny TN , Hogema B , Destree M , Jones JM , Thornburg N , Simmons G , Krajden M , Kleinman S , Dumont LJ , Busch MP . medRxiv 2021 2021.09.04.21262414 SARS-CoV-2 serosurveys can estimate cumulative incidence for monitoring epidemics but require characterization of employed serological assays performance to inform testing algorithm development and interpretation of results. We conducted a multi-laboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serological assays using blinded panels of 1,000 highly-characterized blood-donor specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%) and precision (IIC 0.55-0.99). Durability of antibody detection in longitudinal samples was dependent on assay format and immunoglobulin target, with anti-spike, direct, or total Ig assays demonstrating more stable, or increasing reactivity over time than anti-nucleocapsid, indirect, or IgG assays. Assays with high sensitivity, specificity and durable antibody detection are ideal for serosurveillance. Less sensitive assays demonstrating waning reactivity are appropriate for other applications, including characterizing antibody responses after infection and vaccination, and detection of anamnestic boosting by reinfections and vaccine breakthrough infections. Assay performance must be evaluated in the context of the intended use.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by research contracts from the Centers for Disease Control and Prevention (CDC Contract 75D30120C08170).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All blood donors consented to use of de-identified, residual specimens for further research purposes. UCSF IRB provided explicit approval for VRI self-certification that use of the de-identified CCP donations in this study does not meet the criteria for human subjects research. CDC investigators reviewed and relied on this determination as consistent with applicable federal law and CDC policy (45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe analytic data set is available upon request. |
Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Masks with Maintenance of Integrity and Fit (preprint)
Lendvay TS , Chen J , Harcourt BH , Scholte FE , Lin YL , Kilinc-Balci FS , Lamb MM , Homdayjanakul K , Cui Y , Price A , Heyne B , Sahni J , Kabra KB , Lin YC , Evans D , Mores CN , Page K , Chu LF , Haubruge E , Thiry E , Ludwig-Begall LF , Wielick C , Clark T , Wagner T , Timm E , Gallagher T , Faris P , Macia N , Mackie CJ , Simmons SM , Reader S , Malott R , Hope K , Davies JM , Tritsch SR , Dams L , Nauwynck H , Willaert JF , De Jaeger S , Liao L , Zhao M , Laperre J , Jolois O , Smit SJ , Patel AN , Mayo M , Parker R , Molloy-Simard V , Lemyre JL , Chu S , Conly JM , Chu MC . medRxiv 2020 2020.12.11.20236919 Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in severe shortages of personal protective equipment (PPE) necessary to protect front-line healthcare personnel. These shortages underscore the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed PPE enabling safe reuse of masks and respirators. Efficient decontamination must be available not only in low-resourced settings, but also in well-resourced settings affected by PPE shortages. Methylene blue (MB) photochemical treatment, hitherto with many clinical applications including those used to inactivate virus in plasma, presents a novel approach for widely applicable PPE decontamination. Dry heat (DH) treatment is another potential low-cost decontamination method.Methods MB and light (MBL) and DH treatments were used to inactivate coronavirus on respirator and mask material. We tested three N95 filtering facepiece respirators (FFRs), two medical masks (MMs), and one cloth community mask (CM). FFR/MM/CM materials were inoculated with SARS-CoV-2 (a Betacoronavirus), murine hepatitis virus (MHV) (a Betacoronavirus), or porcine respiratory coronavirus (PRCV) (an Alphacoronavirus), and treated with 10 µM MB followed by 50,000 lux of broad-spectrum light or 12,500 lux of red light for 30 minutes, or with 75°C DH for 60 minutes. In parallel, we tested respirator and mask integrity using several standard methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. Intact FFRs/MMs/CM were subjected to five cycles of decontamination (5CD) to assess integrity using International Standardization Organization (ISO), American Society for Testing and Materials (ASTM) International, National Institute for Occupational Safety and Health (NIOSH), and Occupational Safety and Health Administration (OSHA) test methods.Findings Overall, MBL robustly and consistently inactivated all three coronaviruses with at least a 4-log reduction. DH yielded similar results, with the exception of MHV, which was only reduced by 2-log after treatment. FFR/MM integrity was maintained for 5 cycles of MBL or DH treatment, whereas one FFR failed after 5 cycles of VHP+O3. Baseline performance for the CM was variable, but reduction of integrity was minimal.Interpretation Methylene blue with light and DH treatment decontaminated masks and respirators by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination of masks is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings. These attractive features support the utilization and continued development of this novel PPE decontamination method.Competing Interest StatementAuthors Thomas S. Lendvay, James Chen are Co-Founders and equity owners of Singletto, Inc. (Seattle, WA, USA) Authors Yi Cui and Steven Chu are Co-Founders and equity owners of 4C Air, Inc. (Sunnyvale, CA)Funding StatementThis study was funded by Open Philanthropy; Amazon Inc./University of Washington Catalyst Award; University of Liege (Belgium) and the Walloon Region, Belgium; Li Ka Shing Institute; Alberta Health Services; and an Anonymous donor to the University of Washington, Department of Urology.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Stanford University and Alberta Health Services/University of Calgary were exempt from IRB as the human fit testing was considered Quality Improvement. ERB for clinical specimen use: A clinical saliva specimen with a SARS-CoV-2 was provided by Dr. John Conly from Calgary, Alberta with Calgary ERB approval (ID# Pro00099761).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective inte ventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData will be freely shared post publication on reasonable request by contacting the corresponding author of the study. |
Using the NCBI AMRFinder Tool to Determine Antimicrobial Resistance Genotype-Phenotype Correlations Within a Collection of NARMS Isolates (preprint)
Feldgarden M , Brover V , Haft DH , Prasad AB , Slotta DJ , Tolstoy I , Tyson GH , Zhao S , Hsu CH , McDermott PF , Tadesse DA , Morales C , Simmons M , Tillman G , Wasilenko J , Folster JP , Klimke W . bioRxiv 2019 550707 Antimicrobial resistance (AMR) is a major public health problem that requires publicly available tools for rapid analysis. To identify acquired AMR genes in whole genome sequences, the National Center for Biotechnology Information (NCBI) has produced a high-quality, curated, AMR gene reference database consisting of up-to-date protein and gene nomenclature, a set of hidden Markov models (HMMs), and a curated protein family hierarchy. Currently, the Bacterial Antimicrobial Resistance Reference Gene Database contains 4,579 antimicrobial resistance gene proteins and more than 560 HMMs.Here, we describe AMRFinder, a tool that uses this reference dataset to identify AMR genes. To assess the predictive ability of AMRFinder, we measured the consistency between predicted AMR genotypes from AMRFinder against resistance phenotypes of 6,242 isolates from the National Antimicrobial Resistance Monitoring System (NARMS). This included 5,425 Salmonella enterica, 770 Campylobacter spp., and 47 Escherichia coli phenotypically tested against various antimicrobial agents. Of 87,679 susceptibility tests performed, 98.4% were consistent with predictions.To assess the accuracy of AMRFinder, we compared its gene symbol output with that of a 2017 version of ResFinder, another publicly available resistance gene database. Most gene calls were identical, but there were 1,229 gene symbol differences between them, with differences due to both algorithmic differences and database composition. AMRFinder missed 16 loci that Resfinder found, while Resfinder missed 1,147 loci AMRFinder identified. Two missing drug classes from the 2017 version of ResFinder contributed 81% of missed loci. Based on these results, AMRFinder appears to be a highly accurate AMR gene detection system.Importance Antimicrobial resistance is a major public health problem. Traditionally, antimicrobial resistance has been identified using phenotypic assays. With the advent of genome sequencing, we now can identify resistance genes and deduce if an isolate could be resistant to antibiotics. We describe a database of 4,579 acquired antimicrobial resistance genes, the largest publicly available, and a software tool to identify genes in bacterial genomes, AMRFinder. Unlike other tools, AMRFinder uses a gene hierarchy to prevent overpredicting what the correct gene call should be, enabling more accurate assessment. To assess these resources, we determined the resistance gene content of over 6,200 bacterial isolates from the National Antimicrobial Resistance Monitoring System that have been assayed using traditional methods and that also have had their genomes sequenced. We also compared our gene assessments to those of a popularly used tool. We found that AMRFinder has a high overall consistency between genotypes and phenotypes. |
Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission (preprint)
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Barrett KMS , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . medRxiv 2022 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Evaluation of three automated nontreponemal rapid plasma reagin (RPR) tests for the laboratory diagnosis of syphilis
Shukla MR , Pereira L , Gaynor AM , Sun Y , Edwards D , Simmons T , Andrews CW , Park IU , Hong J , Cao W , Kersh EN , Fakile Y . J Clin Microbiol 2023 61 (6) e0016823 Automated nontreponemal rapid plasma reagin (RPR) tests were recently introduced in the United States for syphilis testing and limited performance data are available. In collaboration with the Association of Public Health Laboratories, three public health laboratories (PHL) were chosen through a competitive selection process to evaluate the performance of three FDA-cleared automated RPR test systems: BioPlex 2200 Syphilis Total & RPR assay (Bio-Rad Laboratories), AIX 1000 (Gold Standard Diagnostics), and ASI Evolution (Arlington Scientific). Panels prepared at the CDC included: a qualitative panel comprised of 734 syphilis reactive/nonreactive sera; a quantitative panel of 50 syphilis reactive sera (RPR titer 1:64 to 1:1,024); and a reproducibility panel of 15 nonreactive and reactive sera (RPR titer 1:1 to 1:64). Panels were shipped frozen to the PHL and tested on the automated RPR systems following manufacturers' instructions. Prior test results were blinded to all laboratories. When compared to manual RPR (Arlington Scientific) performed at the CDC as a reference test, the qualitative panel results demonstrated an overall concordance of 95.9% for AIX 1000, 94.6% for ASI Evolution, and 92.6% for Bioplex RPR; quantitative panel showed within range titer of 2-fold for 94% of specimens for AIX 1000, 68% for ASI Evolution, and 64% for BioPlex RPR, and the reproducibility testing panel demonstrated point estimates ranging from 69 to 95%. Automated RPR instruments could reduce turnaround time and minimize interpretation errors. However, additional evaluations with more specimens could assist laboratories with implementing automated RPR tests and understanding their limitations. |
Considerations to improve pediatric HIV testing and close the treatment gap in 16 African countries
Gross J , Medley A , Rivadeneira E , Battey K , Srivastava M , Grillo M , Wolf H , Simmons P , Hast M , Patel M . Pediatr Infect Dis J 2023 42 (2) 110-118 BACKGROUND: In 2019, South Africa, Nigeria, Tanzania, Democratic Republic of Congo, Uganda, Mozambique, Zambia, Angola, Cameroon, Zimbabwe, Ghana, Ethiopia, Malawi, Kenya, South Sudan and Côte d'Ivoire accounted for 80% of children living with HIV (CLHIV) not receiving HIV treatment. This manuscript describes pediatric HIV testing to inform case-finding strategies. METHODS: We analyzed US President's Emergency Plan for AIDS Relief monitoring, evaluation, and reporting data (October 1, 2018 to September 30, 2019) for these 16 countries. Number of HIV tests and positive results were reported by age band, country, treatment coverage and testing modality. The number needed to test (NNT) to identify 1 new CLHIV 1-14 years was measured by testing modality and country. The pediatric testing gap was estimated by multiplying the estimated number of CLHIV unaware of their status by NNT per country. RESULTS: Among children, 6,961,225 HIV tests were conducted, and 101,762 CLHIV were identified (NNT 68), meeting 17.6% of the pediatric testing need. Index testing accounted for 13.0% of HIV tests (29.7% of positive results, NNT 30), provider-initiated testing and counseling 65.9% of tests (43.6% of positives, NNT 103), and universal testing at sick entry points 5.3% of tests (6.5% of positives, NNT 58). CONCLUSIONS: As countries near HIV epidemic control for adults, the need to increase pediatric testing continues. Each testing modality - PITC, universal testing at sick entry points, and index testing - offers unique benefits. These results illustrate the comparative advantages of including a strategic mix of testing modalities in national programs to increase pediatric HIV case finding. |
Vital Signs: Use of recommended health care measures to prevent selected complications of sickle cell anemia in children and adolescents - Selected U.S. States, 2019
Schieve LA , Simmons GM , Payne AB , Abe K , Hsu LL , Hulihan M , Pope S , Rhie S , Dupervil B , Hooper WC . MMWR Morb Mortal Wkly Rep 2022 71 (39) 1241-1246 INTRODUCTION: Sickle cell disease (SCD), a group of inherited blood cell disorders that primarily affects Black or African American persons, is associated with severe complications and a >20-year reduction in life expectancy. In 2014, an expert panel convened by the National Heart, Lung, and Blood Institute issued recommendations to prevent or reduce complications in children and adolescents with the most severe SCD subtypes, known as sickle cell anemia (SCA); recommendations included 1) annual screening of children and adolescents aged 2-16 years with transcranial Doppler (TCD) ultrasound to identify those at risk for stroke and 2) offering hydroxyurea therapy to children and adolescents aged ≥9 months to reduce the risk for several life-threatening complications. METHODS: Data from the IBM MarketScan Multi-State Medicaid Database were analyzed. TCD screening and hydroxyurea use were examined for 3,352 children and adolescents with SCA aged 2-16 years and continuously enrolled in Medicaid during 2019. Percentage change during 2014-2019 and variation by health subgroups were assessed. Analyses were stratified by age. RESULTS: During 2014-2019, TCD screening increased 27% among children and adolescents aged 10-16 years; hydroxyurea use increased 27% among children aged 2-9 years and 23% among children and adolescents aged 10-16 years. However, in 2019, only 47% and 38% of children and adolescents aged 2-9 and 10-16 years, respectively, had received TCD screening and 38% and 53% of children and adolescents aged 2-9 years and 10-16 years, respectively, used hydroxyurea. For both prevention strategies, usage was highest among children and adolescents with high levels of health care utilization and evidence of previous complications indicative of severe disease. CONCLUSION AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Despite increases since 2014, TCD screening and hydroxyurea use remain low among children and adolescents with SCA. Health care providers should implement quality care strategies within their clinics and partner with patients, families, and community-based organizations to address barriers to delivering and receiving recommended care. |
Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Schiabor Barrett KM , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . Nature 2022 609 (7925) 101-108 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases(1-3). SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing(4,5). Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
The Use of Whole-Genome Sequencing by the Federal Interagency Collaboration for Genomics for Food and Feed Safety in the United States.
Stevens EL , Carleton HA , Beal J , Tillman GE , Lindsey RL , Lauer AC , Pightling A , Jarvis KG , Ottesen A , Ramachandran P , Hintz L , Katz LS , Folster JP , Whichard JM , Trees E , Timme RE , McDermott P , Wolpert B , Bazaco M , Zhao S , Lindley S , Bruce BB , Griffin PM , Brown E , Allard M , Tallent S , Irvin K , Hoffmann M , Wise M , Tauxe R , Gerner-Smidt P , Simmons M , Kissler B , Defibaugh-Chavez S , Klimke W , Agarwala R , Lindsay J , Cook K , Austerman SR , Goldman D , McGarry S , Hale KR , Dessai U , Musser SM , Braden C . J Food Prot 2022 85 (5) 755-772 This multi-agency report developed under the Interagency Collaboration for Genomics for Food and Feed Safety (Gen-FS) provides an overview of the use of and transition to Whole-Genome Sequencing (WGS) technology to detect and characterize pathogens transmitted commonly by food and identify their sources. We describe foodborne pathogen analysis, investigation, and harmonization efforts among federal agencies, including the National Institutes of Health (NIH); the Department of Health and Human Services' Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA); and the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS), Agricultural Research Service (ARS), and Animal and Plant Health Inspection Service (APHIS). We describe single nucleotide polymorphism (SNP), core-genome (cg) and whole-genome multi-locus sequence typing (wgMLST) data analysis methods as used in CDC's PulseNet and FDA's GenomeTrakr networks, underscoring the complementary nature of the results for linking genetically related foodborne pathogens during outbreak investigations while allowing flexibility to meet the specific needs of Gen-FS agency partners. We highlight how we apply WGS to pathogen characterization (virulence and antimicrobial resistance profiles), source attribution efforts, and increasing transparency by making the sequences and other data publicly available through the National Center for Biotechnology Information (NCBI). Finally, we highlight the impact of current trends in the use of culture-independent diagnostics tests (CIDT) for human diagnostic testing on analytical approaches related to food safety. Lastly, we highlight what is next for WGS in food safety. |
Evaluation of Commercially Available High-Throughput SARS-CoV-2 Serologic Assays for Serosurveillance and Related Applications.
Stone M , Grebe E , Sulaeman H , Di Germanio C , Dave H , Kelly K , Biggerstaff BJ , Crews BO , Tran N , Jerome KR , Denny TN , Hogema B , Destree M , Jones JM , Thornburg N , Simmons G , Krajden M , Kleinman S , Dumont LJ , Busch MP . Emerg Infect Dis 2022 28 (3) 672-683 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys can estimate cumulative incidence for monitoring epidemics, requiring assessment of serologic assays to inform testing algorithm development and interpretation of results. We conducted a multilaboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serologic assays using blinded panels of 1,000 highly characterized specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%), and precision (intraclass correlation coefficient 0.55-0.99). Durability of antibody detection was dependent on antigen and immunoglobulin targets; antispike and total Ig assays demonstrated more stable longitudinal reactivity than antinucleocapsid and IgG assays. Assays with high sensitivity, specificity, and durable antibody detection are ideal for serosurveillance, but assays demonstrating waning reactivity are appropriate for other applications, including correlation with neutralizing activity and detection of anamnestic boosting by reinfections. Assay performance must be evaluated in context of intended use, particularly in the context of widespread vaccination and circulation of SARS-CoV-2 variants. |
Modeling complex effects of exposure to particulate matter and extreme heat during pregnancy on congenital heart defects: A U.S. population-based case-control study in the National Birth Defects Prevention Study.
Simmons W , Lin S , Luben TJ , Sheridan SC , Langlois PH , Shaw GM , Reefhuis J , Romitti PA , Feldkamp ML , Nembhard WN , Desrosiers TA , Browne ML , Stingone JA . Sci Total Environ 2021 808 152150 BACKGROUND/OBJECTIVE: Research suggests gestational exposure to particulate matter ≤2.5 μm (PM(2.5)) and extreme heat may independently increase risk of birth defects. We investigated whether duration of gestational extreme heat exposure modifies associations between PM(2.5) exposure and specific congenital heart defects (CHDs). We also explored nonlinear exposure-outcome relationships. METHODS: We identified CHD case children (n = 2824) and non-malformed live-birth control children (n = 4033) from pregnancies ending between 1999 and 2007 in the National Birth Defects Prevention Study, a U.S. population-based multicenter case-control study. We assigned mothers 6-week averages of PM(2.5) exposure during the cardiac critical period (postconceptional weeks 3-8) using the closest monitor within 50 km of maternal residence. We assigned a count of extreme heat days (EHDs, days above the 90th percentile of daily maximum temperature for year, season, and weather station) during this period using the closest weather station. Using generalized additive models, we explored logit-nonlinear exposure-outcome relationships, concluding logistic models were reasonable. We estimated joint effects of PM(2.5) and EHDs on six CHDs using logistic regression models adjusted for mean dewpoint and maternal age, education, and race/ethnicity. We assessed multiplicative and additive effect modification. RESULTS: Conditional on the highest observed EHD count (15) and at least one critical period day during spring/summer, each 5 μg/m(3) increase in average PM(2.5) exposure was significantly associated with perimembranous ventricular septal defects (VSDpm; OR: 1.54 [95% CI: 1.01, 2.41]). High EHD counts (8+) in the same population were positively, but non-significantly, associated with both overall septal defects and VSDpm. Null or inverse associations were observed for lower EHD counts. Multiplicative and additive effect modification estimates were consistently positive in all septal models. CONCLUSIONS: Results provide limited evidence that duration of extreme heat exposure modifies the PM(2.5)-septal defects relationship. Future research with enhanced exposure assessment and modeling techniques could clarify these relationships. |
Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021.
Jones JM , Stone M , Sulaeman H , Fink RV , Dave H , Levy ME , Di Germanio C , Green V , Notari E , Saa P , Biggerstaff BJ , Strauss D , Kessler D , Vassallo R , Reik R , Rossmann S , Destree M , Nguyen KA , Sayers M , Lough C , Bougie DW , Ritter M , Latoni G , Weales B , Sime S , Gorlin J , Brown NE , Gould CV , Berney K , Benoit TJ , Miller MJ , Freeman D , Kartik D , Fry AM , Azziz-Baumgartner E , Hall AJ , MacNeil A , Gundlapalli AV , Basavaraju SV , Gerber SI , Patton ME , Custer B , Williamson P , Simmons G , Thornburg NJ , Kleinman S , Stramer SL , Opsomer J , Busch MP . JAMA 2021 326 (14) 1400-1409 IMPORTANCE: People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. OBJECTIVE: To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. DESIGN, SETTING, AND PARTICIPANTS: In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. EXPOSURE: Calendar time. MAIN OUTCOMES AND MEASURES: Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. RESULTS: Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. CONCLUSIONS AND RELEVANCE: Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population. |
Use of U.S. Blood Donors for National Serosurveillance of SARS-CoV-2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program.
Stone M , Di Germanio C , Wright DJ , Sulaeman H , Dave H , Fink RV , Notari EP , Green V , Strauss D , Kessler D , Destree M , Saa P , Williamson PC , Simmons G , Stramer SL , Opsomer J , Jones JM , Kleinman S , Busch MP . Clin Infect Dis 2021 74 (5) 871-881 INTRODUCTION: The REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for SARS-CoV-2 antibodies on blood donors in six U.S. metropolitan regions to estimate the extent of SARS-COV-2 infections over time. STUDY DESIGN/METHODS: During March-August 2020, approximately ≥1,000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences with the general population. Seroprevalence was compared with reported COVID-19 case rates over time. RESULTS/FINDINGS: For all regions, seroprevalence was <1.0% in March 2020. New York experienced the biggest increase (peak seroprevalence, 15.8 % in May). All other regions experienced modest increases in seroprevalence(1-2% in May-June to 2-4% in July-August). Seroprevalence was higher in younger, non-Hispanic Black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case reported to CDC. CONCLUSION: Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic Black and Hispanic blood donors than in non-Hispanic White blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico. |
Addressing personal protective equipment (PPE) decontamination: Methylene blue and light inactivates severe acute respiratory coronavirus virus 2 (SARS-CoV-2) on N95 respirators and medical masks with maintenance of integrity and fit.
Lendvay TS , Chen J , Harcourt BH , Scholte FE , Lin YL , Kilinc-Balci FS , Lamb MM , Homdayjanakul K , Cui Y , Price A , Heyne B , Sahni J , Kabra KB , Lin YC , Evans D , Mores CN , Page K , Chu LF , Haubruge E , Thiry E , Ludwig-Begall LF , Wielick C , Clark T , Wagner T , Timm E , Gallagher T , Faris P , Macia N , Mackie CJ , Simmons SM , Reader S , Malott R , Hope K , Davies JM , Tritsch SR , Dams L , Nauwynck H , Willaert JF , De Jaeger S , Liao L , Zhao M , Laperre J , Jolois O , Smit SJ , Patel AN , Mayo M , Parker R , Molloy-Simard V , Lemyre JL , Chu S , Conly JM , Chu MC . Infect Control Hosp Epidemiol 2021 43 (7) 1-83 OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE) underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed masks and respirators. We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus. DESIGN: The two arms of the study included: 1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment, and 2) PPE treatment with MBL for 5 cycles of decontamination (5CD) to determine maintenance of PPE performance. METHODS: MBL treatment was used to inactivate coronaviruses on three N95 filtering facepiece respirator (FFR) and two medical mask (MM) models. We inoculated FFR and MM materials with three coronaviruses, including SARS-CoV-2, and treated with 10 µM MB and exposed to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5CD using multiple US and international test methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. RESULTS: Overall, MBL robustly and consistently inactivated all three coronaviruses with 99.8 - to >99.9% virus inactivation across all FFRs and MMs tested. FFR and MM integrity was maintained after 5 cycles of MBL treatment, whereas one FFR model failed after 5 cycles of VHP+O3. CONCLUSIONS: MBL treatment decontaminated respirators and masks by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings. |
The Specificity of the Persistent IgM Neutralizing Antibody Response in Zika Viral Infections Among Individuals with Prior Dengue Virus Exposure
Calvert AE , Horiuchi K , Boroughs KL , Ong YT , Anderson KM , Biggerstaff BJ , Stone M , Simmons G , Busch MP , Huang CY . J Clin Microbiol 2021 59 (8) e0040021 Dengue viruses (DENV) and Zika virus (ZIKV) are related mosquito-borne flaviviruses with similar disease manifestations, vector ecology and geographic range. The ability to differentiate these viruses serologically is vital due to the teratogenic nature of ZIKV and the potential confounding of pre-existing cross-reactive anti-DENV antibodies. Here we illustrate the kinetics of the IgM neutralizing antibody (NAb) response using longitudinal samples ranging from acute ZIKV infection to late convalescence from individuals with evidence of prior DENV infection. By serially depleting antibody isotypes prior to neutralization assay, we determined that IgM contributes predominantly to ZIKV neutralization, and it is less cross-reactive than the IgG NAb. The IgM NAb peaked around 14 days (95% CI: 13-15) with a median duration of 257 days (95% CI: 133-427). These results demonstrate the persistence of IgM NAb after ZIKV infections and imply its potential role in diagnosis, vaccine evaluation, serosurveillance, and research of flaviviral-host interactions. |
Outbreak of hepatitis B and hepatitis C virus infections associated with a cardiology clinic, West Virginia, 2012-2014.
Tressler SR , Del Rosario MC , Kirby MD , Simmons AN , Scott MA , Ibrahim S , Forbi JC , Thai H , Xia GL , Lyman M , Collier MG , Patel PR , Bixler D . Infect Control Hosp Epidemiol 2021 42 (12) 1-6 OBJECTIVE: To stop transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in association with myocardial perfusion imaging (MPI) at a cardiology clinic. DESIGN: Outbreak investigation and quasispecies analysis of HCV hypervariable region 1 genome. SETTING: Outpatient cardiology clinic. PATIENTS: Patients undergoing MPI. METHODS: Case patients met definitions for HBV or HCV infection. Cases were identified through surveillance registry cross-matching against clinic records and serological screening. Observations of clinic practices were performed. RESULTS: During 2012-2014, 7 cases of HCV and 4 cases of HBV occurred in 4 distinct clusters among patients at a cardiology clinic. Among 3 case patients with HCV infection who had MPI on June 25, 2014, 2 had 98.48% genetic identity of HCV RNA. Among 4 case patients with HCV infection who had MPI on March 13, 2014, 3 had 96.96%-99.24% molecular identity of HCV RNA. Also, 2 clusters of 2 patients each with HBV infection had MPI on March 7, 2012, and December 4, 2014. Clinic staff reused saline vials for >1 patient. No infection control breaches were identified at the compounding pharmacy that supplied the clinic. Patients seen in clinic through March 27, 2015, were encouraged to seek testing for HBV, HCV, and human immunodeficiency virus. The clinic switched to all single-dose medications and single-use intravenous flushes on March 27, 2015, and no further cases were identified. CONCLUSIONS: This prolonged healthcare-associated outbreak of HBV and HCV was most likely related to breaches in injection safety. Providers should follow injection safety guidelines in all practice settings. |
Carriage and Gene Content Variability of the pESI-Like Plasmid Associated with Salmonella Infantis Recently Established in United States Poultry Production.
McMillan EA , Wasilenko JL , Tagg KA , Chen JC , Simmons M , Gupta SK , Tillman GE , Folster J , Jackson CR , Frye JG . Genes (Basel) 2020 11 (12) Salmonella Infantis carrying extended spectrum β-lactamase bla(CTX-M-65) on a pESI-like megaplasmid has recently emerged in United States poultry. In order to determine the carriage rate and gene content variability of this plasmid in U.S. Salmonella Infantis, whole genome sequences of Salmonella isolates from humans and animals in the U.S. and internationally containing the pESI-like plasmid were analyzed. The U.S. Department of Agriculture Food Safety and Inspection Service (FSIS) identified 654 product sampling isolates containing pESI-like plasmids through hazard analysis and critical control point (HACCP) verification testing in 2017 and 2018. The Centers for Disease Control and Prevention identified 55 isolates with pESI-like plasmids in 2016-2018 through the National Antimicrobial Resistance Monitoring System. Approximately 49% of pESI-like plasmids from FSIS verification isolates and 71% from CDC NARMS contained bla(CTX-M-65). Pan-plasmid genome analysis was also performed. All plasmids contained traN and more than 95% contained 172 other conserved genes; 61% contained bla(CTX-M-65). In a hierarchical clustering analysis, some plasmids from U.S. animal sources clustered together and some plasmids from South America clustered together, possibly indicating multiple plasmid lineages. However, most plasmids contained similar genes regardless of origin. Carriage of the pESI-like plasmid in U.S. appears to be limited to Salmonella Infantis and carriage rates increased from 2017 to 2018. |
Evolving viral and serological stages of Zika virus RNA-positive blood donors and estimation of incidence of infection during the 2016 Puerto Rican Zika epidemic: an observational cohort study.
Williamson PC , Biggerstaff BJ , Simmons G , Stone M , Winkelman V , Latoni G , Alsina J , Bakkour S , Newman C , Pate LL , Galel SA , Kleinman S , Busch MP . Lancet Infect Dis 2020 20 (12) 1437-1445 BACKGROUND: Puerto Rico began screening blood donations for Zika virus RNA with nucleic acid amplification tests (NAATs) on April 3, 2016, because of an emerging Zika virus outbreak. We followed up positive donors to assess the dynamics of viral and serological markers during the early stages of Zika virus infection and update the estimate of infection incidence in the Puerto Rican population during the outbreak. METHODS: Blood donations from volunteer donors in Puerto Rico were screened for the presence of Zika virus RNA using the cobas Zika NAAT. Positive donations were further tested to confirm infection, estimate viral load, and identify Zika virus-specific IgM antibodies. Individuals with positive blood donations were invited to attend follow-up visits. Donations with confirmed infection (defined as detection of Zika virus RNA or IgM on additional testing of index or follow-up samples) were assessed for stage of infection according to Zika virus RNA detectability in simulated minipools, viral load, and Zika virus IgM status. A three-step process was used to estimate the mean duration of NAAT reactivity of Zika virus in human plasma from individuals identified pre-seroconversion with at least one follow up visit and to update the 2016 incidence estimate of Zika virus infection. FINDINGS: Between April 3 and Dec 31, 2016, 53 112 blood donations were screened for Zika virus, of which 351 tested positive, 339 had confirmed infections, and 319 could be staged. Compared with IgM-positive index donations (n=110), IgM-negative index donations (n=209) had higher mean viral loads (1.1 x 10(6)vs 8.3 x 10(4) international units per mL) and were more likely to be detected in simulated minipools (93% [n=194] vs 26% [n=29]). The proportions of donations with confirmed infections that had viral RNA detected only in individual-donation NAATs (ie, not in simulated minipools) and were IgM positive increased as the epidemic evolved. The estimated mean duration of NAAT detectability in the 140 donors included in the follow-up study was 11.70 days (95% CI 10.06-14.36). Applying this detection period to the observed proportion of donations that were confirmed NAAT positive yielded a Zika virus seasonal incidence estimate of 21.1% (95% CI 18.1-24.1); 768 101 infections in a population of 3 638 773 in 2016. INTERPRETATION: Characterisation of early Zika virus infection has implications for blood safety because infectivity of blood donations and utility of screening methods likely correlate with viral load and serological stage of infection. Our findings also have implications for diagnostic testing, public health surveillance, and epidemiology, and we estimate that around 21% of the Puerto Rican population was infected during the 2016 outbreak. FUNDING: Biomedical Advanced Research and Development Authority, National Heart, Lung, and Blood Institute. |
Evidence for Limited Early Spread of COVID-19 Within the United States, January-February 2020.
CDC COVID-19 Response Team , Jorden MA , Rudman SL , Villarino E , Hoferka S , Patel MT , Bemis K , Simmons CR , Jespersen M , Iberg Johnson J , Mytty E , Arends KD , Henderson JJ , Mathes RW , Weng CX , Duchin J , Lenahan J , Close N , Bedford T , Boeckh M , Chu HY , Englund JA , Famulare M , Nickerson DA , Rieder MJ , Shendure J , Starita LM , Armstrong Gregory L , Butler Jay C , Coletta Michael A , Kite-Powell Aaron , Bhatnagar Julu , Reagan-Steiner Sarah , Tong Suxiang , Flannery Brendan , Ferdinands Jill M , Chung Jessie R . MMWR Morb Mortal Wkly Rep 2020 69 (22) 680-684 From January 21 through February 23, 2020, public health agencies detected 14 U.S. cases of coronavirus disease 2019 (COVID-19), all related to travel from China (1,2). The first nontravel-related U.S. case was confirmed on February 26 in a California resident who had become ill on February 13 (3). Two days later, on February 28, a second nontravel-related case was confirmed in the state of Washington (4,5). Examination of four lines of evidence provides insight into the timing of introduction and early transmission of SARS-CoV-2, the virus that causes COVID-19, into the United States before the detection of these two cases. First, syndromic surveillance based on emergency department records from counties affected early by the pandemic did not show an increase in visits for COVID-19-like illness before February 28. Second, retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20. Third, analysis of viral RNA sequences from early cases suggested that a single lineage of virus imported directly or indirectly from China began circulating in the United States between January 18 and February 9, followed by several SARS-CoV-2 importations from Europe. Finally, the occurrence of three cases, one in a California resident who died on February 6, a second in another resident of the same county who died February 17, and a third in an unidentified passenger or crew member aboard a Pacific cruise ship that left San Francisco on February 11, confirms cryptic circulation of the virus by early February. These data indicate that sustained, community transmission had begun before detection of the first two nontravel-related U.S. cases, likely resulting from the importation of a single lineage of virus from China in late January or early February, followed by several importations from Europe. The widespread emergence of COVID-19 throughout the United States after February highlights the importance of robust public health systems to respond rapidly to emerging infectious threats. |
Outbreak of human infections with uncommon Salmonella serotypes linked to pet bearded dragons, 2012-2014
Kiebler CA , Bottichio L , Simmons L , Basler C , Klos R , Gurfield N , Roberts E , Kimura A , Lewis LS , Bird K , Stiles F , Schlater LK , Lantz K , Edling T , Barton Behravesh C . Zoonoses Public Health 2020 67 (4) 425-434 Reptiles are one of the fastest growing sectors in the United States pet industry. Reptile-associated salmonellosis (RAS) continues to be an important public health problem, especially among children. We investigated an outbreak of human Salmonella infections resulting from serotypes Cotham and Kisarawe, predominately occurring among children. An outbreak of illnesses was identified in persons with exposure to pet bearded dragon lizards. Human and animal health officials, in cooperation with the pet industry, conducted epidemiologic, traceback and laboratory investigations. Onsite sampling was conducted at two US breeding facilities, one foreign breeding facility, and a large pet retail chain. A total of 166 patients in 36 states were identified with illness onset dates from 02/2012-06/2014. The median patient age was 3 years (range, <1-79 years), 57% were aged </=5 years, and 37% were aged </=1 year. Forty-four patients (37%) were hospitalized, predominantly children. Sampling at breeding facilities and a national pet store chain resulted in isolation of outbreak serotypes at each facility; isolation proportions ranged from 2%-24% of samples collected at each facility.Epidemiologic, microbiologic and traceback evidence linked an outbreak of uncommon Salmonella serotypes to contact with pet bearded dragons. The high proportion of infants involved in this outbreak highlights the need to educate owners about the risk of RAS in children and the potential for household contamination by pet reptiles or their habitats. Strategies should be developed to improve breeding practices, biosecurity and monitoring protocols to reduce Salmonella in the pet reptile trade. |
Seroreactivity against Marburg or related filoviruses in West and Central Africa
Steffen I , Lu K , Hoff NA , Mulembakani P , Okitolonda Wemakoy E , Muyembe-Tamfum JJ , Ndembi N , Brennan CA , Hackett J Jr , Switzer WM , Saragosti S , Mbensa GO , Laperche S , Rimoin AW , Simmons G . Emerg Microbes Infect 2020 9 (1) 124-128 A serological survey of 2,430 archived serum samples collected between 1997 and 2012 was conducted to retrospectively determine the prevalence of Marburg virus in five African countries. Serum samples were screened for neutralizing antibodies in a pseudotype micro-neutralization assay and confirmed by enzyme-linked immunosorbent assay (ELISA). Surprisingly, a seroprevalence for Marburg virus of 7.5 and 6.3% was found in Cameroon and Ghana, respectively, suggesting the circulation of filoviruses or related viruses outside of known endemic areas that remain undetected by current surveillance efforts. However, due to the lack of validated assays and appropriate positive controls, these results must be considered preliminary. |
Multistate outbreak of Salmonella infections linked to raw turkey products - United States, 2017-2019
Hassan R , Buuck S , Noveroske D , Medus C , Sorenson A , Laurent J , Rotstein D , Schlater L , Freiman J , Douris A , Simmons M , Donovan D , Henderson J , Tewell M , Snyder K , Oni O , Von Stein D , Dassie K , Leeper M , Adediran A , Dowell N , Gieraltowski L , Basler C . MMWR Morb Mortal Wkly Rep 2019 68 (46) 1045-1049 During 2018–2019, CDC, local and state public health partners, the U.S. Department of Agriculture (USDA), and the Food and Drug Administration (FDA) investigated a multistate outbreak of 356 Salmonella Reading infections from 42 states and the District of Columbia (DC) linked to turkey. The outbreak strain was isolated from raw turkey products, raw turkey pet food, and live turkeys. In July 2018, CDC and USDA’s Food Safety and Inspection Service (FSIS) shared outbreak investigation results with representatives from the U.S. turkey industry, engaging with an industry group rather than a specific company for the first time during an outbreak, and CDC issued a public investigation notice. During the investigation, four recalls of turkey products were issued. Evidence suggested that the outbreak strain of Salmonella was widespread in the turkey industry, and therefore, interventions should target all parts of the supply chain, including slaughter and processing facilities and upstream farm sources. |
Validating the NCBI AMRFinder Tool and Resistance Gene Database Using Antimicrobial Resistance Genotype-Phenotype Correlations in a Collection of NARMS Isolates.
Feldgarden M , Brover V , Haft DH , Prasad AB , Slotta DJ , Tolstoy I , Tyson GH , Zhao S , Hsu CH , McDermott PF , Tadesse DA , Morales C , Simmons M , Tillman G , Wasilenko J , Folster JP , Klimke W . Antimicrob Agents Chemother 2019 63 (11) Antimicrobial resistance (AMR) is a major public health problem that requires publicly available tools for rapid analysis. To identify AMR genes in whole genome sequences, the National Center for Biotechnology Information (NCBI) has produced AMRFinder, a tool that identifies AMR genes using a high-quality curated AMR gene reference database. The Bacterial Antimicrobial Resistance Reference Gene Database consists of up-to-date gene nomenclature, a set of hidden Markov models (HMMs), and a curated protein family hierarchy. Currently, it contains 4,579 antimicrobial resistance proteins and more than 560 HMMs.Here, we describe AMRFinder and its associated database. To assess the predictive ability of AMRFinder, we measured the consistency between predicted AMR genotypes from AMRFinder and resistance phenotypes of 6,242 isolates from the National Antimicrobial Resistance Monitoring System (NARMS). This included 5,425 Salmonella enterica, 770 Campylobacter spp., and 47 Escherichia coli phenotypically tested against various antimicrobial agents. Of 87,679 susceptibility tests performed, 98.4% were consistent with predictions.To assess the accuracy of AMRFinder, we compared its gene symbol output with that of a 2017 version of ResFinder, another publicly available resistance gene detection system. Most gene calls were identical, but there were 1,229 gene symbol differences (8.8%) between them, with differences due to both algorithmic differences and database composition. AMRFinder missed 16 loci that Resfinder found, while Resfinder missed 216 loci AMRFinder identified. Based on these results, AMRFinder appears to be a highly accurate AMR gene detection system. |
Serologic Prevalence of Ebola Virus in Equatorial Africa
Steffen I , Lu K , Yamamoto LK , Hoff NA , Mulembakani P , Wemakoy EO , Muyembe-Tamfum JJ , Ndembi N , Brennan CA , Hackett J Jr , Stramer SL , Switzer WM , Saragosti S , Mbensa GO , Laperche S , Rimoin AW , Simmons G . Emerg Infect Dis 2019 25 (5) 911-918 We conducted a serologic survey of 2,430 serum samples collected during 1997-2012 for various studies to determine the prevalence of the hemorrhagic fever virus Ebola virus (EBOV) in equatorial Africa. We screened serum samples for neutralizing antibodies by using a pseudotype microneutralization assay and a newly developed luciferase immunoprecipitation system assay. Specimens seroreactive for EBOV were confirmed by using an ELISA. Our results suggest a serologic prevalence of 2%-3.5% in the Republic of the Congo and the Democratic Republic of the Congo, which have reported outbreaks of infection with EBOV. In addition we detected a seroprevalence of 1.3% in southern Cameroon, which indicated a low risk for exposure in this region. |
Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission
Cooke GS , Andrieux-Meyer I , Applegate TL , Atun R , Burry JR , Cheinquer H , Dusheiko G , Feld JJ , Gore C , Griswold MG , Hamid S , Hellard ME , Hou J , Howell J , Jia J , Kravchenko N , Lazarus JV , Lemoine M , Lesi OA , Maistat L , McMahon BJ , Razavi H , Roberts TR , Simmons B , Sonderup MW , Spearman CW , Taylor BE , Thomas DL , Waked I , Ward JW , Wiktor SZ . Lancet Gastroenterol Hepatol 2019 4 (2) 135-184 Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals. |
Neutralizing antibodies inhibit chikungunya virus budding at the plasma membrane
Jin J , Galaz-Montoya JG , Sherman MB , Sun SY , Goldsmith CS , O'Toole ET , Ackerman L , Carlson LA , Weaver SC , Chiu W , Simmons G . Cell Host Microbe 2018 24 (3) 417-428 e5 Neutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. In addition, antibodies can engage Fc receptors (FcRs) on immune cells to activate antiviral responses. We describe a mechanism by which NAbs inhibit chikungunya virus (CHIKV), the most common alphavirus infecting humans, by preventing virus budding from infected human cells and activating IgG-specific Fcgamma receptors. NAbs bind to CHIKV glycoproteins on the infected cell surface and induce glycoprotein coalescence, preventing budding of nascent virions and leaving structurally heterogeneous nucleocapsids arrested in the cytosol. Furthermore, NAbs induce clustering of CHIKV replication spherules at sites of budding blockage. Functionally, these densely packed glycoprotein-NAb complexes on infected cells activate Fcgamma receptors, inducing a strong, antibody-dependent, cell-mediated cytotoxicity response from immune effector cells. Our findings describe a triply functional antiviral pathway for NAbs that might be broadly applicable across virus-host systems, suggesting avenues for therapeutic innovation through antibody design. |
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