Last data update: Nov 11, 2024. (Total: 48109 publications since 2009)
Records 1-30 (of 90 Records) |
Query Trace: Pillai S[original query] |
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Breast and cervical cancer screenings: A systematic economic review of patient navigation services
Chattopadhyay SK , Pillai A , Reynolds J , Jacob V , Ekwueme D , Peng Y , Cuellar AE . Am J Prev Med 2024 INTRODUCTION: This paper examined the economic evidence of patient navigation services to increase breast and cervical cancer screenings among historically disadvantaged racial and ethnic populations and people with lower incomes. METHODS: The literature search strategy for this systematic review included English-language studies conducted in high-income countries that were published from database inception to December 2022. Studies on patients with existing cancer or without healthcare system involvement were excluded. Analysis was completed in January 2023. All monetary values reported are in 2022 U.S. dollars. RESULTS: The search yielded 3 breast cancer, 2 cervical cancer, and 2 multiple cancer studies that combined breast and cervical cancer with other cancer screenings. For breast cancer screening, the intervention cost per patient ranged from $109 to $10,245. Two studies reported $154 and $740 as intervention cost per additional person screened. Changes in healthcare cost per person from 2 studies were $202 and $2,437. Two studies reported cost per quality-adjusted life year (QALY) gained of $3,852 and $39,159 while one study reported cost per life year (LY) gained of $22,889. For cervical cancer, two studies reported intervention cost per person ($103 and $794) and per additional person screened ($56 and $533) with one study reporting a cost per QALY gained ($924). DISCUSSION: All estimates of cost per QALY/LY saved for breast cancer screening were below a conservative threshold of $50,000 indicating that patient navigation services for breast cancer screening were cost-effective. There is limited evidence to determine cost-effectiveness of patient navigation services for cervical cancer screening. |
A pan-respiratory antiviral chemotype targeting a transient host multi-protein complex
Michon M , Müller-Schiffmann A , Lingappa AF , Yu SF , Du L , Deiter F , Broce S , Mallesh S , Crabtree J , Lingappa UF , Macieik A , Müller L , Ostermann PN , Andrée M , Adams O , Schaal H , Hogan RJ , Tripp RA , Appaiah U , Anand SK , Campi TW , Ford MJ , Reed JC , Lin J , Akintunde O , Copeland K , Nichols C , Petrouski E , Moreira AR , Jiang IT , DeYarman N , Brown I , Lau S , Segal I , Goldsmith D , Hong S , Asundi V , Briggs EM , Phyo NS , Froehlich M , Onisko B , Matlack K , Dey D , Lingappa JR , Prasad DM , Kitaygorodskyy A , Solas D , Boushey H , Greenland J , Pillai S , Lo MK , Montgomery JM , Spiropoulou CF , Korth C , Selvarajah S , Paulvannan K , Lingappa VR . Open Biol 2024 14 (6) 230363 We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease. |
Understanding psychosocial determinants of malaria behaviours in low-transmission settings: a scoping review
Casella A , Monroe A , Toso M , Hunter G , Underwood C , Pillai R , Hughes J , Van Lith LM , Cash S , Hwang J , Babalola S . Malar J 2024 23 (1) 15 BACKGROUND: Recent estimates show progress toward malaria elimination is slowing in many settings, underscoring the need for tailored approaches to fight the disease. In addition to essential structural changes, human behaviour plays an important role in elimination. Engagement in malaria behaviours depends in part on psychosocial determinants such as knowledge, perceived risk, and community norms. Understanding the state of research on psychosocial determinants in low malaria transmission settings is important to augment social and behaviour change practice. This review synthesizes research on psychosocial factors and malaria behaviours in low-transmission settings. METHODS: A systematic search of peer-reviewed literature and supplemental manual search of grey literature was conducted using key terms and eligibility criteria defined a priori. Publications from 2000-2020 in the English language were identified, screened, and analysed using inductive methods to determine the relationship between the measured psychosocial factors and malaria behaviours. RESULTS: Screening of 961 publications yielded 96 for inclusion. Nineteen articles collected data among subpopulations that are at increased risk of malaria exposure in low-transmission settings. Purposive and cluster randomized sampling were common sampling approaches. Quantitative, qualitative, and mixed-methods study designs were used. Knowledge, attitudes, and perceived risk were commonly measured psychosocial factors. Perceived response-efficacy, perceived self-efficacy, and community norms were rarely measured. Results indicate positive associations between malaria knowledge and attitudes, and preventive and care-seeking behaviour. Studies generally report high rates of correct knowledge, although it is comparatively lower among studies of high-risk groups. There does not appear to be sufficient extant evidence to determine the relationship between other psychosocial variables and behaviour. CONCLUSIONS: The review highlights the need to deploy more consistent, comprehensive measures of psychosocial factors and the importance of reaching subpopulations at higher risk of transmission in low transmission contexts. Malaria-related knowledge is generally high, even in settings of low transmission. Programmes and research should work to better understand the psychosocial factors that have been positively associated with prevention and care-seeking behaviours, such as norms, perceived response efficacy, perceived self-efficacy, and interpersonal communication. These factors are not necessarily distinct from that which research has shown are important in settings of high malaria transmission. However, the importance of each factor and application to malaria behaviour change programming in low-transmission settings is an area in need of further research. Existing instruments and approaches are available to support more systematic collection of psychosocial determinants and improved sampling approaches and should be applied more widely. Finally, while human behaviour is critical, health systems strengthening, and structural interventions are essential to achieve malaria elimination goals. |
Impact of age at vaccination and cervical HPV infection status on binding and neutralizing antibody titers at 10 years after receiving single or higher doses of quadrivalent HPV vaccine
Bhatla N , Muwonge R , Malvi SG , Joshi S , Poli URR , Lucas E , Esmy PO , Verma Y , Shah A , Zomawia E , Pimple S , Jayant K , Hingmire S , Chiwate A , Vashist S , Mishra G , Jadhav R , Siddiqi M , Anantharaman D , Panicker G , Butt J , Sankaran S , Kannan Tpra , Varghese R , Kartha P , Pillai MR , Waterboer T , Müller M , Sehr P , Unger ER , Sankaranarayanan R , Basu P . Hum Vaccin Immunother 2023 19 (3) 2289242 Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier. |
From cultivation to cancer: formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications
Stanfill SB , Hecht SS , Joerger AC , González PJ , Maia LB , Rivas MG , Moura JJG , Gupta AK , Le Brun NE , Crack JC , Hainaut P , Sparacino-Watkins C , Tyx RE , Pillai SD , Zaatari GS , Henley SJ , Blount BC , Watson CH , Kaina B , Mehrotra R . Crit Rev Toxicol 2023 53 (10) 1-44 Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N′-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients. ©, This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law. |
Evaluation of the US COVID-19 Scenario Modeling Hub for informing pandemic response under uncertainty
Howerton E , Contamin L , Mullany LC , Qin M , Reich NG , Bents S , Borchering RK , Jung SM , Loo SL , Smith CP , Levander J , Kerr J , Espino J , van Panhuis WG , Hochheiser H , Galanti M , Yamana T , Pei S , Shaman J , Rainwater-Lovett K , Kinsey M , Tallaksen K , Wilson S , Shin L , Lemaitre JC , Kaminsky J , Hulse JD , Lee EC , McKee CD , Hill A , Karlen D , Chinazzi M , Davis JT , Mu K , Xiong X , Pastore YPiontti A , Vespignani A , Rosenstrom ET , Ivy JS , Mayorga ME , Swann JL , España G , Cavany S , Moore S , Perkins A , Hladish T , Pillai A , Ben Toh K , Longini I Jr , Chen S , Paul R , Janies D , Thill JC , Bouchnita A , Bi K , Lachmann M , Fox SJ , Meyers LA , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Hurt B , Chen J , Mortveit H , Wilson A , Marathe M , Hoops S , Bhattacharya P , Machi D , Cadwell BL , Healy JM , Slayton RB , Johansson MA , Biggerstaff M , Truelove S , Runge MC , Shea K , Viboud C , Lessler J . Nat Commun 2023 14 (1) 7260 Our ability to forecast epidemics far into the future is constrained by the many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify the future state of critical epidemic drivers. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make months ahead projections of SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a function of both scenario validity and model calibration. We show scenarios remained close to reality for 22 weeks on average before the arrival of unanticipated SARS-CoV-2 variants invalidated key assumptions. An ensemble of participating models that preserved variation between models (using the linear opinion pool method) was consistently more reliable than any single model in periods of valid scenario assumptions, while projection interval coverage was near target levels. SMH projections were used to guide pandemic response, illustrating the value of collaborative hubs for longer-term scenario projections. |
Enterobacterales draft genome sequences: 15 historical (1998-2004) and 30 contemporary (2015-2016) clinical isolates from Pakistan
Crawford MA , Lascols C , Lomonaco S , Timme RE , Fisher DJ , Anderson K , Hodge DR , Morse SA , Pillai SP , Sharma SK , Khan E , Allard MW , Hughes MA . Microbiol Resour Announc 2023 12 (9) e0016323 The continued emergence and spread of antimicrobial resistance among pathogenic bacteria are ever-growing threats to health and economy. Here, we report the draft genomes for 45 Enterobacterales clinical isolates, including historical and contemporary drug-resistant organisms, obtained in Pakistan between 1998 and 2016: 5 Serratia, 3 Salmonella, 3 Enterobacter, and 34 Klebsiella. |
The US Federal Retail Pharmacy Program: Optimizing COVID-19 vaccine delivery through a strategic public-private partnership
Kim C , Guo A , Yassanye D , Link-Gelles R , Yates K , Duggar C , Moore L , El Kalach R , Jones-Jack N , Walker C , Gibbs Scharf L , Pillai SK , Patel A . Public Health Rep 2023 138 (6) 333549231186606 To help achieve the initial goal of providing universal COVID-19 vaccine access to approximately 258 million adults in 62 US jurisdictions, the federal government launched the Federal Retail Pharmacy Program (FRPP) on February 11, 2021. We describe FRPP's collaboration among the federal government, US jurisdictions, federal entity partners, and 21 national chain and independent pharmacy networks to provide large-scale access to COVID-19 vaccines, particularly in communities disproportionately affected by COVID-19 (eg, people aged ≥65 years, people from racial and ethnic minority groups). FRPP initially provided 10 000 vaccination sites for people to access COVID-19 vaccines, which was increased to >35 000 vaccination sites by May 2021 and sustained through January 31, 2022. From February 11, 2021, through January 31, 2022, FRPP vaccination sites received 293 million doses and administered 219 million doses, representing 45% of all COVID-19 immunizations provided nationwide (38% of all first doses, 72% of all booster doses). This unprecedented public-private partnership allowed the federal government to rapidly adapt and scale up an equitable vaccination program to reach adults, later expanding access to vaccine-eligible children, during the COVID-19 pandemic. As the largest federal COVID-19 vaccination program, FRPP exemplifies how public-private partnerships can expand access to immunizations during a public health emergency. Pharmacies can help meet critical national public health goals by serving as convenient access points for sustained health services. Lessons learned from this effort-including the importance of strong coordination and communication, efficient reporting systems and data quality, and increasing access to and demand for vaccine, among others-may help improve future immunization programs and support health system resiliency, emphasizing community-level access and health equity during public health emergencies. |
Enhanced Contact Investigations for Nine Early Travel-Related Cases of SARS-CoV-2 in the United States (preprint)
Burke RM , Balter S , Barnes E , Barry V , Bartlett K , Beer KD , Benowitz I , Biggs HM , Bruce H , Bryant-Genevier J , Cates J , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu VT , Clark S , Cody SH , Cohen M , Conners EE , Dasari V , Dawson P , DeSalvo T , Donahue M , Dratch A , Duca L , Duchin J , Dyal JW , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Freeman-Ponder B , Fry AM , Gant J , Gautom R , Ghinai I , Gounder P , Grigg CT , Gunzenhauser J , Hall AJ , Han GS , Haupt T , Holshue M , Hunter J , Ibrahim MB , Jacobs MW , Jarashow MC , Joshi K , Kamali T , Kawakami V , Kim M , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Lang M , Layden J , Leidman E , Lindquist S , Lindstrom S , Link-Gelles R , Marlow M , Mattison CP , McClung N , McPherson TD , Mello L , Midgley CM , Novosad S , Patel MT , Pettrone K , Pillai SK , Pray IW , Reese HE , Rhodes H , Robinson S , Rolfes M , Routh J , Rubin R , Rudman SL , Russell D , Scott S , Shetty V , Smith-Jeffcoat SE , Soda EA , Spitters C , Stierman B , Sunenshine R , Terashita D , Traub E , Vahey GM , Verani JR , Wallace M , Westercamp M , Wortham J , Xie A , Yousaf A , Zahn M . medRxiv 2020 2020.04.27.20081901 Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll 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.YesData may be available upon reasonable request. |
COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support (preprint)
Shea K , Borchering RK , Probert WJM , Howerton E , Bogich TL , Li S , van Panhuis WG , Viboud C , Aguás R , Belov A , Bhargava SH , Cavany S , Chang JC , Chen C , Chen J , Chen S , Chen Y , Childs LM , Chow CC , Crooker I , Valle SYD , España G , Fairchild G , Gerkin RC , Germann TC , Gu Q , Guan X , Guo L , Hart GR , Hladish TJ , Hupert N , Janies D , Kerr CC , Klein DJ , Klein E , Lin G , Manore C , Meyers LA , Mittler J , Mu K , Núñez RC , Oidtman R , Pasco R , Piontti APY , Paul R , Pearson CAB , Perdomo DR , Perkins TA , Pierce K , Pillai AN , Rael RC , Rosenfeld K , Ross CW , Spencer JA , Stoltzfus AB , Toh KB , Vattikuti S , Vespignani A , Wang L , White L , Xu P , Yang Y , Yogurtcu ON , Zhang W , Zhao Y , Zou D , Ferrari M , Pannell D , Tildesley M , Seifarth J , Johnson E , Biggerstaff M , Johansson M , Slayton RB , Levander J , Stazer J , Salerno J , Runge MC . medRxiv 2020 Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes. |
A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex (preprint)
Muller-Schiffmann A , Michon M , Lingappa AF , Yu SF , Du L , Deiter F , Broce S , Mallesh S , Crabtree J , Lingappa UF , Macieik A , Muller L , Ostermann PN , Andree M , Adams O , Schaal H , Hogan RJ , Tripp RA , Appaiah U , Anand SK , Campi TW , Ford MJ , Reed JC , Lin J , Akintunde O , Copeland K , Nichols C , Petrouski E , Moreira AR , Jiang IT , DeYarman N , Brown I , Lau S , Segal I , Goldsmith D , Hong S , Asundi V , Briggs EM , Phyo NS , Froehlich M , Onisko B , Matlack K , Dey D , Lingappa JR , Prasad MD , Kitaygorodskyy A , Solas D , Boushey H , Greenland J , Pillai S , Lo MK , Montgomery JM , Spiropoulou CF , Korth C , Selvarajah S , Paulvannan K , Lingappa VR . bioRxiv 2021 18 We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Equipment-free detection of SARS-CoV-2 and Variants of Concern using Cas13 (preprint)
Arizti-Sanz J , Bradley AD , Zhang YB , Boehm CK , Freije CA , Grunberg ME , Kosoko-Thoroddsen TSF , Welch NL , Pillai PP , Mantena S , Kim G , Uwanibe JN , John OG , Eromon PE , Kocher G , Gross R , Lee JS , Hensley LE , Happi CT , Johnson J , Sabeti PC , Myhrvold C . medRxiv 2021 02 The COVID-19 pandemic, and the recent rise and widespread transmission of SARS-CoV-2 Variants of Concern (VOCs), have demonstrated the need for ubiquitous nucleic acid testing outside of centralized clinical laboratories. Here, we develop SHINEv2, a Cas13-based nucleic acid diagnostic that combines quick and ambient temperature sample processing and lyophilized reagents to greatly simplify the test procedure and assay distribution. We benchmarked a SHINEv2 assay for SARS-CoV-2 detection against state-of-the-art antigen-capture tests using 96 patient samples, demonstrating 50-fold greater sensitivity and 100% specificity. We designed SHINEv2 assays for discriminating the Alpha, Beta, Gamma and Delta VOCs, which can be read out visually using lateral flow technology. We further demonstrate that our assays can be performed without any equipment in less than 90 minutes. SHINEv2 represents an important advance towards rapid nucleic acid tests that can be performed in any location. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Investigation of multidrug-resistant plasmids from carbapenemase-producing Klebsiella pneumoniae clinical isolates from Pakistan
Lascols C , Cherney B , Conley AB , Rishishwar L , Crawford MA , Morse SA , Fisher DJ , Anderson K , Hodge DR , Pillai SP , Hughes MA , Khan E , Sue D . Front Microbiol 2023 14 1192097 OBJECTIVES: The study aim was to investigate multidrug-resistant (MDR) plasmids from a collection of 10 carbapenemase-producing Klebsiella pneumoniae clinical isolates identified within the same healthcare institution in Pakistan. Full characterization of the MDR plasmids including structure, typing characteristics, and AMR content as well as determination of their plasmid-based antimicrobial susceptibility profiles were carried out. METHODS: Plasmids were isolated from 10 clinical isolates of Klebsiella pneumoniae, and from a corresponding set of Escherichia coli transconjugants, then sequenced using Nanopore/Illumina technology to generate plasmid hybrid assemblies. Full characterization of MDR plasmids, including determination of next generation sequencing (NGS)-based AMR profiles, plasmid incompatibility groups, and types, was carried out. The structure of MDR plasmids was analyzed using the Galileo AMR platform. For E. coli transconjugants, the NGS-based AMR profiles were compared to NGS-predicted AMR phenotypes and conventional broth microdilution (BMD) antimicrobial susceptibility testing (AST) results. RESULTS: All carbapenemase-producing K. pneumoniae isolates (carrying either bla(NDM-1), or/and bla(OXA-48)) carried multiple AMR plasmids encoding 34 antimicrobial resistance genes (ARGs) conferring resistance to antimicrobials from 6 different classes. The plasmid incompatibility groups and types identified were: IncC (types 1 and 3), IncFIA (type 26) IncFIB, IncFII (types K1, K2, K7, and K9), IncHI1B, and IncL. None of the bla(NDM-1) and bla(ESBL)-plasmids identified in this study were previously described. Most bla(NDM-1-)plasmids shared identical AMR regions suggesting potential genetic material/plasmid exchange between K. pneumoniae isolates of this collection. The majority of NGS-based AMR profiles from the E. coli transconjugants correlated well with both NGS-based predicted and conventional AST results. CONCLUSION: This study highlights the complexity and diversity of the plasmid-based genetic background of carbapenemase-producing clinical isolates from Pakistan. This study emphasizes the need for characterization of MDR plasmids to determine their complete molecular background and monitor AMR through plasmid transmission between multi-resistant bacterial pathogens. |
Application of multi-criteria decision analysis techniques and decision support framework for informing select agent designation for agricultural animal pathogens
Pillai SP , West T , Anderson K , Fruetel JA , McNeil C , Hernandez P , Ball C , Beck N , Morse SA . Front Bioeng Biotechnol 2023 11 1185743 The United States Department of Agriculture (USDA), Division of Agricultural Select Agents and Toxins (DASAT) established a list of biological agents and toxins (Select Agent List) that potentially threaten agricultural health and safety, the procedures governing the transfer of those agents, and training requirements for entities working with them. Every 2 years the USDA DASAT reviews the Select Agent List, using subject matter experts (SMEs) to perform an assessment and rank the agents. To assist the USDA DASAT biennial review process, we explored the applicability of multi-criteria decision analysis (MCDA) techniques and a Decision Support Framework (DSF) in a logic tree format to identify pathogens for consideration as select agents, applying the approach broadly to include non-select agents to evaluate its robustness and generality. We conducted a literature review of 41 pathogens against 21 criteria for assessing agricultural threat, economic impact, and bioterrorism risk and documented the findings to support this assessment. The most prominent data gaps were those for aerosol stability and animal infectious dose by inhalation and ingestion routes. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for accuracy, particularly for pathogens with very few known cases, or where proxy data (e.g., from animal models or similar organisms) were used to address data gaps. The MCDA analysis supported the intuitive sense that select agents should rank high on the relative risk scale when considering agricultural health consequences of a bioterrorism attack. However, comparing select agents with non-select agents indicated that there was not a clean break in scores to suggest thresholds for designating select agents, requiring subject matter expertise collectively to establish which analytical results were in good agreement to support the intended purpose in designating select agents. The DSF utilized a logic tree approach to identify pathogens that are of sufficiently low concern that they can be ruled out from consideration as a select agent. In contrast to the MCDA approach, the DSF rules out a pathogen if it fails to meet even one criteria threshold. Both the MCDA and DSF approaches arrived at similar conclusions, suggesting the value of employing the two analytical approaches to add robustness for decision making. |
Multiple models for outbreak decision support in the face of uncertainty
Shea K , Borchering RK , Probert WJM , Howerton E , Bogich TL , Li SL , van Panhuis WG , Viboud C , Aguás R , Belov AA , Bhargava SH , Cavany SM , Chang JC , Chen C , Chen J , Chen S , Chen Y , Childs LM , Chow CC , Crooker I , Del Valle SY , España G , Fairchild G , Gerkin RC , Germann TC , Gu Q , Guan X , Guo L , Hart GR , Hladish TJ , Hupert N , Janies D , Kerr CC , Klein DJ , Klein EY , Lin G , Manore C , Meyers LA , Mittler JE , Mu K , Núñez RC , Oidtman RJ , Pasco R , Pastore YPiontti A , Paul R , Pearson CAB , Perdomo DR , Perkins TA , Pierce K , Pillai AN , Rael RC , Rosenfeld K , Ross CW , Spencer JA , Stoltzfus AB , Toh KB , Vattikuti S , Vespignani A , Wang L , White LJ , Xu P , Yang Y , Yogurtcu ON , Zhang W , Zhao Y , Zou D , Ferrari MJ , Pannell D , Tildesley MJ , Seifarth J , Johnson E , Biggerstaff M , Johansson MA , Slayton RB , Levander JD , Stazer J , Kerr J , Runge MC . Proc Natl Acad Sci U S A 2023 120 (18) e2207537120 Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020. |
Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak - United States, December 31, 2019-February 4, 2020.
Patel A , Jernigan DB , 2019-nCOV CDC Response Team , Abdirizak Fatuma , Abedi Glen , Aggarwal Sharad , Albina Denise , Allen Elizabeth , Andersen Lauren , Anderson Jade , Anderson Megan , Anderson Tara , Anderson Kayla , Bardossy Ana Cecilia , Barry Vaughn , Beer Karlyn , Bell Michael , Berger Sherri , Bertulfo Joseph , Biggs Holly , Bornemann Jennifer , Bornstein Josh , Bower Willie , Bresee Joseph , Brown Clive , Budd Alicia , Buigut Jennifer , Burke Stephen , Burke Rachel , Burns Erin , Butler Jay , Cantrell Russell , Cardemil Cristina , Cates Jordan , Cetron Marty , Chatham-Stephens Kevin , Chatham-Stevens Kevin , Chea Nora , Christensen Bryan , Chu Victoria , Clarke Kevin , Cleveland Angela , Cohen Nicole , Cohen Max , Cohn Amanda , Collins Jennifer , Conners Erin , Curns Aaron , Dahl Rebecca , Daley Walter , Dasari Vishal , Davlantes Elizabeth , Dawson Patrick , Delaney Lisa , Donahue Matthew , Dowell Chad , Dyal Jonathan , Edens William , Eidex Rachel , Epstein Lauren , Evans Mary , Fagan Ryan , Farris Kevin , Feldstein Leora , Fox LeAnne , Frank Mark , Freeman Brandi , Fry Alicia , Fuller James , Galang Romeo , Gerber Sue , Gokhale Runa , Goldstein Sue , Gorman Sue , Gregg William , Greim William , Grube Steven , Hall Aron , Haynes Amber , Hill Sherrasa , Hornsby-Myers Jennifer , Hunter Jennifer , Ionta Christopher , Isenhour Cheryl , Jacobs Max , Jacobs Slifka Kara , Jernigan Daniel , Jhung Michael , Jones-Wormley Jamie , Kambhampati Anita , Kamili Shifaq , Kennedy Pamela , Kent Charlotte , Killerby Marie , Kim Lindsay , Kirking Hannah , Koonin Lisa , Koppaka Ram , Kosmos Christine , Kuhar David , Kuhnert-Tallman Wendi , Kujawski Stephanie , Kumar Archana , Landon Alexander , Lee Leslie , Leung Jessica , Lindstrom Stephen , Link-Gelles Ruth , Lively Joana , Lu Xiaoyan , Lynch Brian , Malapati Lakshmi , Mandel Samantha , Manns Brian , Marano Nina , Marlow Mariel , Marston Barbara , McClung Nancy , McClure Liz , McDonald Emily , McGovern Oliva , Messonnier Nancy , Midgley Claire , Moulia Danielle , Murray Janna , Noelte Kate , Noonan-Smith Michelle , Nordlund Kristen , Norton Emily , Oliver Sara , Pallansch Mark , Parashar Umesh , Patel Anita , Patel Manisha , Pettrone Kristen , Pierce Taran , Pietz Harald , Pillai Satish , Radonovich Lewis , Reagan-Steiner Sarah , Reel Amy , Reese Heather , Rha Brian , Ricks Philip , Rolfes Melissa , Roohi Shahrokh , Roper Lauren , Rotz Lisa , Routh Janell , Sakthivel Senthil Kumar Sarmiento Luisa , Schindelar Jessica , Schneider Eileen , Schuchat Anne , Scott Sarah , Shetty Varun , Shockey Caitlin , Shugart Jill , Stenger Mark , Stuckey Matthew , Sunshine Brittany , Sykes Tamara , Trapp Jonathan , Uyeki Timothy , Vahey Grace , Valderrama Amy , Villanueva Julie , Walker Tunicia , Wallace Megan , Wang Lijuan , Watson John , Weber Angie , Weinbaum Cindy , Weldon William , Westnedge Caroline , Whitaker Brett , Whitaker Michael , Williams Alcia , Williams Holly , Willams Ian , Wong Karen , Xie Amy , Yousef Anna . Am J Transplant 2020 20 (3) 889-895 This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance. |
Editorial: Biosafety and biosecurity approaches to counter SARS-CoV-2: From detection to best practices and risk assessment Volume 2
Pillai SP , Morse SA . Front Bioeng Biotechnol 2022 10 1118544 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the causative agent of Coronavirus Disease-19, commonly referred to as COVID-19. SARS-CoV- 2 was discovered in 2019 and is currently responsible for a global pandemic that has resulted in more than 642.7 million cases and 6.625 million deaths worldwide as of 19 November 2022. However, there have been a large number of asymptomatic cases that have gone unreported, which likely results in an overestimation of the case fatality rate of 1.03%. It is also important to note that many deaths due to SARS-CoV-2 have gone unreported. |
Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination
Joshi S , Anantharaman D , Muwonge R , Bhatla N , Panicker G , Butt J , Rani Reddy Poli U , Malvi SG , Esmy PO , Lucas E , Verma Y , Shah A , Zomawia E , Pimple S , Jayant K , Hingmire S , Chiwate A , Divate U , Vashist S , Mishra G , Jadhav R , Siddiqi M , Sankaran S , Pillai Rameshwari Ammal Kannan T , Kartha P , Shastri SS , Sauvaget C , Radhakrishna Pillai M , Waterboer T , Müller M , Sehr P , Unger ER , Sankaranarayanan R , Basu P . Vaccine 2022 41 (1) 236-245 BACKGROUND: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women. METHODS: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women. RESULTS: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination. CONCLUSION: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination. |
The development and use of decision support framework for informing selection of select agent toxins with modelling studies to inform permissible toxin amounts
Pillai SP , West T , Levinson R , Fruetel JA , Anderson K , Edwards D , Morse SA . Front Bioeng Biotechnol 2022 10 1003127 Many countries have worked diligently to establish and implement policies and processes to regulate high consequence pathogens and toxins that could have a significant public health impact if misused. In the United States, the Antiterrorism and Effective Death Penalty Act of 1996 (Public Law 104-132, 1996), as amended by the Bioterrorism Preparedness and Response Act of 2002 (Public Law 107-188, 2002) requires that the Department of Health and Human Services (HHS) [through the Centers for Disease Control and Prevention (CDC)] establish a list of bacteria, viruses, and toxins that have the potential to pose a severe threat to public health and safety. Currently, this list is reviewed and updated on a biennial basis using input from subject matter experts (SMEs). We have developed decision support framework (DSF) approaches to facilitate selection of select toxins and, where toxicity data are known, conducted modelling studies to inform selection of toxin amounts that should be excluded from select agent regulations. Exclusion limits allow laboratories to possess toxins under an established limit to support their research or teaching activities without the requirement to register with the Federal Select Agent Program. Fact sheets capturing data from a previously vetted SME workshop convened by CDC, literature review and SME input were developed to assist in evaluating toxins using the DSF approach. The output of the DSF analysis agrees with the current select toxin designations, and no other toxins evaluated in this study were recommended for inclusion on the select agent and toxin list. To inform the selection of exclusion limits, attack scenarios were developed to estimate the amount of toxin needed to impact public health. Scenarios consisted of simulated aerosol releases of a toxin in high-population-density public facilities and the introduction of a toxin into a daily consumable product supply chain. Using published inhalation and ingestion median toxic dose (TD(50)) and median lethal dose (LD(50)) values, where available, a range of toxin amounts was examined to estimate the number of people exposed to these amounts in these scenarios. Based on data generated by these models, we proposed toxin exclusion values corresponding to levels below those that would trigger a significant public health response (i.e., amounts estimated to expose up to ten people by inhalation or one hundred people by ingestion to LD(50) or TD(50) levels of toxin in the modeled scenarios). |
Investigation of a Cluster of Rapidly Growing Mycobacteria Infections Associated with Joint Replacement Surgery in a Kentucky Hospital, 2013-2014 with 8-year Follow-up.
Groenewold MR , Flinchum A , Pillai A , Konkle S , Meissner HM , Tosh PK , Thoroughman DA . Am J Infect Control 2022 51 (4) 454-460 BACKGROUND: We describe the investigation of a nosocomial outbreak of rapidly growing mycobacteria (RGM) infections and the results of mitigation efforts after 8 years. METHODS: A cluster of RGM cases in a Kentucky hospital in 2013 prompted an investigation into RGM surgical site infections following joint replacement surgery. A case-control study was conducted to identify risk factors. RESULTS: Eight cases were identified, five caused by M. wolinskyi and three by M. goodii. The case-control study showed the presence of a particular nurse in the operating room was significantly associated with infection. Environmental sampling at the nurse's home identified an outdoor hot tub as the likely source of M. wolinskyi, confirmed by pulsed-field gel electrophoresis and whole genome sequencing. The hot tub reservoir was eliminated, and hospital policies were revised to correct infection control lapses. No new cases of RGM infections have been identified as of 2021. DISCUSSION: Breaches in infection control practices at multiple levels may have led to a chain of infection from a nurse's hot tub to surgical sites via indirect person-to-person transmission from a colonized health care worker (HCW). CONCLUSION: The multifactorial nature of the outbreak's cause highlights the importance of overlapping or redundant layers of protection preventing patient harm. Future investigations of RGM outbreaks should consider the potential role of colonized HCWs as a transmission vector. |
Simplified Cas13-based assays for the fast identification of SARS-CoV-2 and its variants.
Arizti-Sanz J , Bradley A , Zhang YB , Boehm CK , Freije CA , Grunberg ME , Kosoko-Thoroddsen TF , Welch NL , Pillai PP , Mantena S , Kim G , Uwanibe JN , John OG , Eromon PE , Kocher G , Gross R , Lee JS , Hensley LE , MacInnis BL , Johnson J , Springer M , Happi CT , Sabeti PC , Myhrvold C . Nat Biomed Eng 2022 6 (8) 932-943 The widespread transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for rapid nucleic acid diagnostics that are easy to use outside of centralized clinical laboratories. Here we report the development and performance benchmarking of Cas13-based nucleic acid assays leveraging lyophilised reagents and fast sample inactivation at ambient temperature. The assays, which we named SHINEv.2 (for 'streamlined highlighting of infections to navigate epidemics, version 2'), simplify the previously reported RNA-extraction-free SHINEv.1 technology by eliminating heating steps and the need for cold storage of the reagents. SHINEv.2 detected SARS-CoV-2 in nasopharyngeal samples with 90.5% sensitivity and 100% specificity (benchmarked against the reverse transcription quantitative polymerase chain reaction) in less than 90 min, using lateral-flow technology and incubation in a heat block at 37 °C. SHINEv.2 also allows for the visual discrimination of the Alpha, Beta, Gamma, Delta and Omicron SARS-CoV-2 variants, and can be run without performance losses by using body heat. Accurate, easy-to-use and equipment-free nucleic acid assays could facilitate wider testing for SARS-CoV-2 and other pathogens in point-of-care and at-home settings. |
Rapid capsular antigen immunoassay for diagnosis of inhalational anthrax: Preclinical studies and evaluation in a nonhuman primate model
Gates-Hollingsworth MA , Kolton CB , Hoffmaster AR , Meister GT , Moore AE , Green HR , Pogoda JM , Pillai SP , Kozel TR . mBio 2022 13 (3) e0093122 Inhalational anthrax is a fatal infectious disease. Rapid and effective treatment is critically dependent on early and accurate diagnosis. Blood culture followed by identification and confirmation may take days to provide clinically relevant information. In contrast, immunoassay for a shed antigen, the capsular polypeptide gamma-d-polyglutamate (γDPGA), can provide rapid results at the point of care. In this study, a lateral flow immunoassay for γDPGA was evaluated in a robust nonhuman primate model of inhalational anthrax. The results showed that the time to a positive result with the rapid test using either serum or blood as a clinical specimen was similar to the time after infection when a blood culture became positive. In vitro testing showed that the test was equally sensitive with cultures of the three major clades of Bacillus anthracis. Cultures from other Bacillus spp. that are known to produce γDPGA also produced positive results. The test was negative with human sera from 200 normal subjects and 45 subjects with culture-confirmed nonanthrax bacterial or fungal sepsis. Taken together, the results showed that immunoassay for γDPGA is an effective surrogate for blood culture in a relevant cynomolgus monkey model of inhalational anthrax. The test would be a valuable aid in early diagnosis of anthrax, which is critical for rapid intervention and a positive outcome. Use of the test could facilitate triage of patients with signs and symptoms of anthrax in a mass-exposure incident and in low-resource settings where laboratory resources are not readily available. IMPORTANCE Patient outcome in anthrax is critically dependent on early diagnosis followed by effective treatment. We describe a rapid lateral flow immunoassay that detects capsular antigen of Bacillus anthracis that is shed into blood during infection. The test was evaluated in a robust cynomolgus monkey model of inhalational anthrax. Rapid detection of capsular antigen is an effective surrogate for the time-consuming and laboratory-intensive diagnosis by blood culture, direct fluorescent antibody staining, or other molecular testing. The test can be performed at the point of patient contact, is rapid and inexpensive, and can be used by individuals with minimal training. |
COVID-19 Vaccine Provider Access and Vaccination Coverage Among Children Aged 5-11 Years - United States, November 2021-January 2022.
Kim C , Yee R , Bhatkoti R , Carranza D , Henderson D , Kuwabara SA , Trinidad JP , Radesky S , Cohen A , Vogt TM , Smith Z , Duggar C , Chatham-Stephens K , Ottis C , Rand K , Lim T , Jackson AF , Richardson D , Jaffe A , Lubitz R , Hayes R , Zouela A , Kotulich DL , Kelleher PN , Guo A , Pillai SK , Patel A . MMWR Morb Mortal Wkly Rep 2022 71 (10) 378-383 On October 29, 2021, the Pfizer-BioNTech pediatric COVID-19 vaccine received Emergency Use Authorization for children aged 5-11 years in the United States.() For a successful immunization program, both access to and uptake of the vaccine are needed. Fifteen million doses were initially made available to pediatric providers to ensure the broadest possible access for the estimated 28 million eligible children aged 5-11 years, especially those in high social vulnerability index (SVI)() communities. Initial supply was strategically distributed to maximize vaccination opportunities for U.S. children aged 5-11 years. COVID-19 vaccination coverage among persons aged 12-17 years has lagged (1), and vaccine confidence has been identified as a concern among parents and caregivers (2). Therefore, COVID-19 provider access and early vaccination coverage among children aged 5-11 years in high and low SVI communities were examined during November 1, 2021-January 18, 2022. As of November 29, 2021 (4 weeks after program launch), 38,732 providers were enrolled, and 92% of U.S. children aged 5-11 years lived within 5 miles of an active provider. As of January 18, 2022 (11 weeks after program launch), 39,786 providers had administered 13.3 million doses. First dose coverage at 4 weeks after launch was 15.0% (10.5% and 17.5% in high and low SVI areas, respectively; rate ratio [RR]=0.68; 95% CI=0.60-0.78), and at 11 weeks was 27.7% (21.2% and 29.0% in high and low SVI areas, respectively; RR=0.76; 95% CI=0.68-0.84). Overall series completion at 11 weeks after launch was 19.1% (13.7% and 21.7% in high and low SVI areas, respectively; RR=0.67; 95% CI=0.58-0.77). Pharmacies administered 46.4% of doses to this age group, including 48.7% of doses in high SVI areas and 44.4% in low SVI areas. Although COVID-19 vaccination coverage rates were low, particularly in high SVI areas, first dose coverage improved over time. Additional outreach is critical, especially in high SVI areas, to improve vaccine confidence and increase coverage rates among children aged 5-11 years. |
Alternative Methods for Grouping Race and Ethnicity to Monitor COVID-19 Outcomes and Vaccination Coverage.
Yoon P , Hall J , Fuld J , Mattocks SL , Lyons BC , Bhatkoti R , Henley J , McNaghten AD , Daskalakis D , Pillai SK . MMWR Morb Mortal Wkly Rep 2021 70 (32) 1075-1080 Population-based analyses of COVID-19 data, by race and ethnicity can identify and monitor disparities in COVID-19 outcomes and vaccination coverage. CDC recommends that information about race and ethnicity be collected to identify disparities and ensure equitable access to protective measures such as vaccines; however, this information is often missing in COVID-19 data reported to CDC. Baseline data collection requirements of the Office of Management and Budget's Standards for the Classification of Federal Data on Race and Ethnicity (Statistical Policy Directive No. 15) include two ethnicity categories and a minimum of five race categories (1). Using available COVID-19 case and vaccination data, CDC compared the current method for grouping persons by race and ethnicity, which prioritizes ethnicity (in alignment with the policy directive), with two alternative methods (methods A and B) that used race information when ethnicity information was missing. Method A assumed non-Hispanic ethnicity when ethnicity data were unknown or missing and used the same population groupings (denominators) for rate calculations as the current method (Hispanic persons for the Hispanic group and race category and non-Hispanic persons for the different racial groups). Method B grouped persons into ethnicity and race categories that are not mutually exclusive, unlike the current method and method A. Denominators for rate calculations using method B were Hispanic persons for the Hispanic group and persons of Hispanic or non-Hispanic ethnicity for the different racial groups. Compared with the current method, the alternative methods resulted in higher counts of COVID-19 cases and fully vaccinated persons across race categories (American Indian or Alaska Native [AI/AN], Asian, Black or African American [Black], Native Hawaiian or Other Pacific Islander [NH/PI], and White persons). When method B was used, the largest relative increase in cases (58.5%) was among AI/AN persons and the largest relative increase in the number of those fully vaccinated persons was among NH/PI persons (51.6%). Compared with the current method, method A resulted in higher cumulative incidence and vaccination coverage rates for the five racial groups. Method B resulted in decreasing cumulative incidence rates for two groups (AI/AN and NH/PI persons) and decreasing cumulative vaccination coverage rates for AI/AN persons. The rate ratio for having a case of COVID-19 by racial and ethnic group compared with that for White persons varied by method but was <1 for Asian persons and >1 for other groups across all three methods. The likelihood of being fully vaccinated was highest among NH/PI persons across all three methods. This analysis demonstrates that alternative methods for analyzing race and ethnicity data when data are incomplete can lead to different conclusions about disparities. These methods have limitations, however, and warrant further examination of potential bias and consultation with experts to identify additional methods for analyzing and tracking disparities when race and ethnicity data are incomplete. |
Comprehensive laboratory evaluation of a specific lateral flow assay for the presumptive identification of Francisella tularensis in suspicious white powders and aerosol samples
Pillai SP , DePalma L , Prentice KW , Ramage JG , Chapman C , Sarwar J , Parameswaran N , Petersen J , Yockey B , Young J , Singh A , Pillai CA , Manickam G , Thirunavkkarasu N , Avila JR , Sharma S , Morse SA , Venkateswaran K , Anderson K , Hodge DR . Health Secur 2020 18 (2) 83-95 We conducted a comprehensive, multi-phase laboratory evaluation of the Tularemia BioThreat Alert(®) (BTA) test, a lateral flow assay (LFA) for the rapid detection of Francisella tularensis. The study, conducted at 2 sites, evaluated the limit of detection (LOD) of this assay using the virulent SchuS4 strain and the avirulent LVS strain of F. tularensis. In 6-phase evaluation (linear dynamic range and reproducibility, inclusivity, near-neighbor, environmental background, white powder, and environmental filter extract), 13 diverse strains of F. tularensis, 8 Francisella near neighbors, 61 environmental background organisms, 26 white powders, and a pooled aerosol extract were tested. In the 937 tests performed, the Tularemia BTA demonstrated an LOD of 10(7) to 10(8) cfu/mL, with a sensitivity of 100.00%, specificity of 98.08%, and accuracy of 98.84%. These performance data are important for accurate interpretation of qualitative results arising from screening suspicious white powders in the field. |
Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States.
Burke RM , Balter S , Barnes E , Barry V , Bartlett K , Beer KD , Benowitz I , Biggs HM , Bruce H , Bryant-Genevier J , Cates J , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu VT , Clark S , Cody SH , Cohen M , Conners EE , Dasari V , Dawson P , DeSalvo T , Donahue M , Dratch A , Duca L , Duchin J , Dyal JW , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Freeman-Ponder B , Fry AM , Gant J , Gautom R , Ghinai I , Gounder P , Grigg CT , Gunzenhauser J , Hall AJ , Han GS , Haupt T , Holshue M , Hunter J , Ibrahim MB , Jacobs MW , Jarashow MC , Joshi K , Kamali T , Kawakami V , Kim M , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Lang M , Layden J , Leidman E , Lindquist S , Lindstrom S , Link-Gelles R , Marlow M , Mattison CP , McClung N , McPherson TD , Mello L , Midgley CM , Novosad S , Patel MT , Pettrone K , Pillai SK , Pray IW , Reese HE , Rhodes H , Robinson S , Rolfes M , Routh J , Rubin R , Rudman SL , Russell D , Scott S , Shetty V , Smith-Jeffcoat SE , Soda EA , Spitters C , Stierman B , Sunenshine R , Terashita D , Traub E , Vahey GM , Verani JR , Wallace M , Westercamp M , Wortham J , Xie A , Yousaf A , Zahn M . PLoS One 2020 15 (9) e0238342 Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19. |
Investigation and Serologic Follow-Up of Contacts of an Early Confirmed Case-Patient with COVID-19, Washington, USA.
Chu VT , Freeman-Ponder B , Lindquist S , Spitters C , Kawakami V , Dyal JW , Clark S , Bruce H , Duchin JS , DeBolt C , Podczervinski S , D'Angeli M , Pettrone K , Zacks R , Vahey G , Holshue ML , Lang M , Burke RM , Rolfes MA , Marlow M , Midgley CM , Lu X , Lindstrom S , Hall AJ , Fry AM , Thornburg NJ , Gerber SI , Pillai SK , Biggs HM . Emerg Infect Dis 2020 26 (8) 1671-1678 We describe the contact investigation for an early confirmed case of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the United States. Contacts of the case-patient were identified, actively monitored for symptoms, interviewed for a detailed exposure history, and tested for SARS-CoV-2 infection by real-time reverse transcription PCR (rRT-PCR) and ELISA. Fifty contacts were identified and 38 (76%) were interviewed, of whom 11 (29%) reported unprotected face-to-face interaction with the case-patient. Thirty-seven (74%) had respiratory specimens tested by rRT-PCR, and all tested negative. Twenty-three (46%) had ELISA performed on serum samples collected approximately 6 weeks after exposure, and none had detectable antibodies to SARS-CoV-2. Among contacts who were tested, no secondary transmission was identified in this investigation, despite unprotected close interactions with the infectious case-patient. |
Draft Genome Sequences of Two Extensively Drug-Resistant Strains of Acinetobacter baumannii Isolated from Clinical Samples in Pakistan.
Lomonaco S , Crawford MA , Lascols C , Fisher DJ , Anderson K , Hodge DR , Pillai SP , Morse SA , Khan E , Hughes MA , Allard MW , Sharma SK . Microbiol Resour Announc 2020 9 (20) Infections in immunocompromised patients that are caused by extensively drug-resistant (XDR) Acinetobacter baumannii strains have been increasingly reported worldwide. In particular, carbapenem-resistant A. baumannii strains are a prominent cause of health care-associated infections. Here, we report draft genome assemblies for two clinical XDR A. baumannii isolates obtained from hospitalized patients in Pakistan. |
Strategies for Optimizing the Supply of N95 Filtering Facepiece Respirators During the Coronavirus Disease 2019 (COVID-19) Pandemic.
de Perio MA , Dowell CH , Delaney LJ , Radonovich LJ , Kuhar D , Gupta N , Patel A , Pillai SK , D'Alessandro M . Disaster Med Public Health Prep 2020 14 (5) 1-23 N95 respirators are the personal protective equipment most often used to control exposures to infections transmitted via the airborne route. Supplies of N95 respirators can become depleted during pandemics or when otherwise in high demand. In this paper, we offer strategies for optimizing supplies of N95 respirators in healthcare settings while maximizing the level of protection offered to healthcare personnel when there is limited supply in the United States during the Coronavirus Disease 2019 (COVID-19) pandemic. The strategies are intended for use by professionals who manage respiratory protection programs, occupational health services, and infection prevention programs in healthcare facilities to protect healthcare personnel from job-related risks of exposure to infectious respiratory illnesses. Consultation with federal, state, and local public health officials is also important. We use the framework of surge capacity and the occupational health and safety hierarchy of controls approach to discuss specific engineering control, administrative control, and personal protective equipment measures that may help in optimizing N95 respirator supplies. |
Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States.
Kujawski SA , Wong KK , Collins JP , Epstein L , Killerby ME , Midgley CM , Abedi GR , Ahmed NS , Almendares O , Alvarez FN , Anderson KN , Balter S , Barry V , Bartlett K , Beer K , Ben-Aderet MA , Benowitz I , Biggs HM , Binder AM , Black SR , Bonin B , Bozio CH , Brown CM , Bruce H , Bryant-Genevier J , Budd A , Buell D , Bystritsky R , Cates J , Charles EM , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu V , Cody S , Cohen M , Conners EE , Curns AT , Dasari V , Dawson P , DeSalvo T , Diaz G , Donahue M , Donovan S , Duca LM , Erickson K , Esona MD , Evans S , Falk J , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Fricchione MJ , Friedman O , Fry A , Galang RR , Garcia MM , Gerber SI , Gerrard G , Ghinai I , Gounder P , Grein J , Grigg C , Gunzenhauser JD , Gutkin GI , Haddix M , Hall AJ , Han GS , Harcourt J , Harriman K , Haupt T , Haynes AK , Holshue M , Hoover C , Hunter JC , Jacobs MW , Jarashow C , Joshi K , Kamali T , Kamili S , Kim L , Kim M , King J , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Komatsu KK , Koppaka R , Layden JE , Li Y , Lindquist S , Lindstrom S , Link-Gelles R , Lively J , Livingston M , Lo K , Lo J , Lu X , Lynch B , Madoff L , Malapati L , Marks G , Marlow M , Mathisen GE , McClung N , McGovern O , McPherson TD , Mehta M , Meier A , Mello L , Moon SS , Morgan M , Moro RN , Murray J , Murthy R , Novosad S , Oliver SE , O’Shea J , Pacilli M , Paden CR , Pallansch MA , Patel M , Patel S , Pedraza I , Pillai SK , Pindyck T , Pray I , Queen K , Quick N , Reese H , Reporter R , Rha B , Rhodes H , Robinson S , Robinson P , Rolfes MA , Routh JA , Rubin R , Rudman SL , Sakthivel SK , Scott S , Shepherd C , Shetty V , Smith EA , Smith S , Stierman B , Stoecker W , Sunenshine R , Sy-Santos R , Tamin A , Tao Y , Terashita D , Thornburg NJ , Tong S , Traub E , Tural A , Uehara A , Uyeki TM , Vahey G , Verani JR , Villarino E , Wallace M , Wang L , Watson JT , Westercamp M , Whitaker B , Wilkerson S , Woodruff RC , Wortham JM , Wu T , Xie A , Yousaf A , Zahn M , Zhang J . Nat Med 2020 26 (6) 861-868 Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously(1-3). Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness. |
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