Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-30 (of 202 Records) |
Query Trace: Steven Y [original query] |
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Genetics and genomics for the prevention and treatment of cardiovascular disease: update: a scientific statement from the American Heart Association.
Ganesh SK , Arnett DK , Assimes TL , Basson CT , Chakravarti A , Ellinor PT , Engler MB , Goldmuntz E , Herrington DM , Hershberger RE , Hong Y , Johnson JA , Kittner SJ , McDermott DA , Meschia JF , Mestroni L , O'Donnell CJ , Psaty BM , Vasan RS , Ruel M , Shen WK , Terzic A , Waldman SA . Circulation 2013 128 (25) 2813-51 Cardiovascular diseases (CVDs) are a major source of morbidity and mortality worldwide. Despite a decline of ≈30% over the past decade, heart disease remains the leading killer of Americans.1 For rare and familial forms of CVD, we are increasingly recognizing single-gene mutations that impart relatively large effects on individual phenotype. Examples include inherited forms of cardiomyopathy, arrhythmias, and aortic diseases. However, the prevalence of monogenic disorders typically accounts for a small proportion of the total CVD observed in the population. CVDs in the general population are complex diseases, with several contributing genetic and environmental factors. Although recent progress in monogenic disorders has occurred, we have seen a period of intense investigation to identify the genetic architecture of more common forms of CVD and related traits. | | Genomics serves several roles in cardiovascular health and disease, including disease prediction, discovery of genetic loci influencing CVD, functional evaluation of these genetic loci to understand mechanisms, and identification of therapeutic targets. For single-gene CVDs, progress has led to several clinically useful diagnostic tests, extending our ability to inform the management of afflicted patients and their family members. However, there has been little progress in developing genetic testing for complex CVD because individual common variants have only a modest impact on risk. The study of the genomics of complex CVDs is further challenged by the influence of environmental variables, phenotypic heterogeneity, and pathogenic complexity. Characterization of the clinical phenotype requires consideration of the clinical details of the diseases and traits under study. |
Phenylketonuria Scientific Review Conference: state of the science and future research needs.
Camp KM , Parisi MA , Acosta PB , Berry GT , Bilder DA , Blau N , Bodamer OA , Brosco JP , Brown CS , Burlina AB , Burton BK , Chang CS , Coates PM , Cunningham AC , Dobrowolski SF , Ferguson JH , Franklin TD , Frazier DM , Grange DK , Greene CL , Groft SC , Harding CO , Howell RR , Huntington KL , Hyatt-Knorr HD , Jevaji IP , Levy HL , Lichter-Konecki U , Lindegren ML , Lloyd-Puryear MA , Matalon K , MacDonald A , McPheeters ML , Mitchell JJ , Mofidi S , Moseley KD , Mueller CM , Mulberg AE , Nerurkar LS , Ogata BN , Pariser AR , Prasad S , Pridjian G , Rasmussen SA , Reddy UM , Rohr FJ , Singh RH , Sirrs SM , Stremer SE , Tagle DA , Thompson SM , Urv TK , Utz JR , van Spronsen F , Vockley J , Waisbren SE , Weglicki LS , White DA , Whitley CB , Wilfond BS , Yannicelli S , Young JM . Mol Genet Metab 2014 112 (2) 87-122 New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism. |
Poliovirus type 1 systemic humoral and intestinal mucosal immunity induced by monovalent oral poliovirus vaccine, fractional inactivated poliovirus vaccine, and bivalent oral poliovirus vaccine: A randomized controlled trial
Snider CJ , Zaman K , Wilkinson AL , Binte Aziz A , Yunus M , Haque W , Jones KAV , Wei L , Estivariz CF , Konopka-Anstadt JL , Mainou BA , Patel JC , Lickness JS , Pallansch MA , Wassilak SGF , Steven Oberste M , Anand A . Vaccine 2023 41 (41) 6083-6092 BACKGROUND: To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV). METHODS: We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004). FINDINGS: During 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines. INTERPRETATION: Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV. FUNDING: U.S. Centers for Disease Control and Prevention. |
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. |
Response to letters-to-the-editor for publication: "Defect-free care trends in the Paul Coverdell National Acute Stroke Program (PCNASP), 2008-2018. American Heart Journal. 2021;232:177-184. doi:10.1016/j.ahj.2020.11.010."
Overwyk K , Yin X , Tong X , Coleman King SM , Wiltz JL . Am Heart J 2021 236 112 Thank you for your letter. We recognize that stroke-related laws, policies, and funding vary by state, which impacts the provision of stroke care. Centers for disease control and prevention (CDC’s) Division for Heart Disease and Stroke Prevention has posted resources on stroke-related state policy and capacity at https://www.cdc.gov/dhdsp/pubs/stroke_resources.htm. We also recently published a report1 on evidence-supported state laws to advance stroke care. State-level data from nine funded states drive the Paul Coverdell National Acute Stroke Program’s (PCNASP’s) activities. For example, each PCNASP state receives quarterly reports on its quality improvement activities, and state summaries for each funding cycle and state success stories are shared publicly.2, 3 | | We appreciate Steven Thomas’s comment about evaluating stroke care during the current pandemic. PCNASP’s support for data collection to improve the quality of stroke care in its nine funded states is ongoing through the pandemic and into the future.4, 5 Additionally, national dissemination of the funded states’ successes helps extend these lessons beyond the Coverdell experience. |
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. |
Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis.
van Eijk AM , Larsen DA , Kayentao K , Koshy G , Slaughter DEC , Roper C , Okell LC , Desai M , Gutman J , Khairallah C , Rogerson SJ , Hopkins Sibley C , Meshnick SR , Taylor SM , Ter Kuile FO . Lancet Infect Dis 2019 19 (5) 546-556 BACKGROUND: Resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine threatens the antimalarial effectiveness of intermittent preventive treatment during pregnancy (IPTp) in sub-Saharan Africa. We aimed to assess the associations between markers of sulfadoxine-pyrimethamine resistance in P falciparum and the effectiveness of sulfadoxine-pyrimethamine IPTp for malaria-associated outcomes. METHODS: For this systematic review and meta-analysis, we searched databases (from Jan 1, 1990 to March 1, 2018) for clinical studies (aggregated data) or surveys (individual participant data) that reported data on low birthweight (primary outcome) and malaria by sulfadoxine-pyrimethamine IPTp dose, and for studies that reported on molecular markers of sulfadoxine-pyrimethamine resistance. Studies that involved only HIV-infected women or combined interventions were excluded. We did a random-effects meta-analysis (clinical studies) or multivariate log-binomial regression (surveys) to obtain summarised dose-response data (relative risk reduction [RRR]) and multivariate meta-regression to explore the modifying effects of sulfadoxine-pyrimethamine resistance (as indicated by Ala437Gly, Lys540Glu, and Ala581Gly substitutions in the dhps gene). This study is registered with PROSPERO, number 42016035540. FINDINGS: Of 1097 records screened, 57 studies were included in the aggregated-data meta-analysis (including 59 457 births). The RRR for low birthweight declined with increasing prevalence of dhps Lys540Glu (p(trend)=0·0060) but not Ala437Gly (p(trend)=0·35). The RRR was 7% (95% CI 0 to 13) in areas of high resistance to sulfadoxine-pyrimethamine (Lys540Glu ≥90% in east and southern Africa; n=11), 21% (14 to 29) in moderate-resistance areas (Ala437Gly ≥90% [central and west Africa], or Lys540Glu ≥30% to <90% [east and southern Africa]; n=16), and 27% (21 to 33) in low-resistance areas (Ala437Gly <90% [central and west Africa], or Lys540Glu <30% [east and southern Africa]; n=30; p(trend)=0·0054 [univariate], I(2)=69·5%). The overall RRR in all resistance strata was 21% (17 to 25). In the analysis of individual participant data from 13 surveys (42 394 births), sulfadoxine-pyrimethamine IPTp was associated with reduced prevalence of low birthweight in areas with a Lys540Glu prevalence of more than 90% and Ala581Gly prevalence of less than 10% (RRR 10% [7 to 12]), but not in those with an Ala581Gly prevalence of 10% or higher (pooled Ala581Gly prevalence 37% [range 29 to 46]; RRR 0·5% [-16 to 14]; 2326 births). INTERPRETATION: The effectiveness of sulfadoxine-pyrimethamine IPTp is reduced in areas with high resistance to sulfadoxine-pyrimethamine among P falciparum parasites, but remains associated with reductions in low birthweight even in areas where dhps Lys540Glu prevalence exceeds 90% but where the sextuple-mutant parasite (harbouring the additional dhps Ala581Gly mutation) is uncommon. Therapeutic alternatives to sulfadoxine-pyrimethamine IPTp are needed in areas where the prevalence of the sextuple-mutant parasite exceeds 37%. FUNDING: US Centers for Disease Control and Prevention, the Malaria in Pregnancy Consortium (funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine), Worldwide Antimalarial Resistance Network, European and Developing Countries Clinical Trials Partnership. |
Human plague: An old scourge that needs new answers.
Vallès X , Stenseth NC , Demeure C , Horby P , Mead PS , Cabanillas O , Ratsitorahina M , Rajerison M , Andrianaivoarimanana V , Ramasindrazana B , Pizarro-Cerda J , Scholz HC , Girod R , Hinnebusch BJ , Vigan-Womas I , Fontanet A , Wagner DM , Telfer S , Yazdanpanah Y , Tortosa P , Carrara G , Deuve J , Belmain SR , D'Ortenzio E , Baril L . PLoS Negl Trop Dis 2020 14 (8) e0008251 Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague's resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a "One Health" approach. |
An outbreak of malaria caused by increase in malaria breeding sites in swamps
Kabwama SN , Kwesiga B , Bulage L , Kadobera D , Ario AR , Harris JR . Pan Afr Med J 2022 41 5 On 10th June 2019, routine analysis of malaria surveillance data at the National Malaria Control Division, Ministry of Health in Uganda revealed that there was an unusual increase in the number of malaria cases reported in the Oyam District. On 11th June 2019, the District Health Officer in Oyam District convened a meeting with the District Health Team (DHT) in which the District Biostatistician confirmed that the number of malaria cases had indeed exceeded the upper limit, starting in epidemic week 24 (approximately the week of June 10). The District Health Officer issued a formal request to the Ministry of Health for assistance in dealing with the malaria outbreak in Oyam. Two field epidemiology residents were assigned to work with the District Health Team to investigate the outbreak. The residents followed the steps in conducting vector borne disease outbreak investigations including preparation for field work, establishment of the existence of an outbreak by analyzing surveillance data, descriptive data analysis, hypothesis generation, conducting environmental and entomological assessments, conducting analytic studies with a focus on the utility of retrospective cohort studies as well as reporting findings. This case study teaches trainees in Field Epidemiology and Laboratory Training Programs, public health students, public health workers who are interested or who may participate in vector borne disease outbreak investigation and response. © Steven Ndugwa et al. |
Identifying Cases of Shoulder Injury Related to Vaccine Administration (SIRVA) in the United States: Development and Validation of a Natural Language Processing Method.
Zheng C , Duffy J , Liu IA , Sy LS , Navarro RA , Kim SS , Ryan DS , Chen W , Qian L , Mercado C , Jacobsen SJ . JMIR Public Health Surveill 2022 8 (5) e30426 BACKGROUND: Shoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, due to the difficulty of finding SIRVA cases in large health care databases, population-based studies are scarce. OBJECTIVE: The goal of the research was to develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes. METHODS: We conducted the study among members of a large integrated health care organization who were vaccinated between April 1, 2016, and December 31, 2017, and had subsequent diagnosis codes indicative of shoulder injury. Based on a training data set with a chart review reference standard of 164 cases, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified 3 groups of positive SIRVA cases (definite, probable, and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated cases. We then applied the final automated NLP algorithm to a broader cohort of vaccinated persons with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases. RESULTS: In the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 cases without SIRVA. In the broader cohort of 53,585 vaccinations, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.5% (278/291), 67.7% (84/124), and 17.3% (9/52), respectively. CONCLUSIONS: The algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation. |
Evaluating stability of attenuated Sabin and two novel type 2 oral poliovirus vaccines in children.
Wahid R , Mercer L , Gast C , De Leon T , Sáez-Llorens X , Fix A , Macadam A , Stephens L , Chumakov K , Smits SL , Murreddu M , Konopka-Anstadt JL , Steven Oberste M , Burns CC , Andino R , Bachtiar NS , Tritama E , Bandyopadhyay AS , Aguirre G , Rüttimann R , Konz JO . NPJ Vaccines 2022 7 (1) 19 Novel oral poliovirus vaccine type 2 (nOPV2) is being developed to reduce the rare occurrence of disease and outbreaks associated with the genetic instability of the Sabin vaccine strains. Children aged 1 to 5 years were enrolled in two related clinical studies to assess safety, immunogenicity, shedding rates and properties of the shed virus following vaccination with nOPV2 (two candidates) versus traditional Sabin OPV type 2 (mOPV2). The anticipated pattern of reversion and increased virulence was observed for shed Sabin-2 virus, as assessed using a mouse model of poliovirus neurovirulence. In contrast, there were significantly reduced odds of mouse paralysis for shed virus for both nOPV2 candidates when compared to shed Sabin-2 virus. Next-generation sequencing of shed viral genomes was consistent with and further supportive of the observed neurovirulence associated with shed Sabin-2 virus, as well as the reduced reversion to virulence of shed candidate viruses. While shed Sabin-2 showed anticipated A481G reversion in the primary attenuation site in domain V in the 5' untranslated region to be associated with increased mouse paralysis, the stabilized domain V in the candidate viruses did not show polymorphisms consistent with reversion to neurovirulence. The available data from a key target age group for outbreak response confirm the superior genetic and phenotypic stability of shed nOPV2 strains compared to shed Sabin-2 and suggest that nOPV2 should be associated with less paralytic disease and potentially a lower risk of seeding new outbreaks. |
Characterizing and Identifying the Prevalence of Web-Based Misinformation Relating to Medication for Opioid Use Disorder: Machine Learning Approach.
ElSherief M , Sumner SA , Jones CM , Law RK , Kacha-Ochana A , Shieber L , Cordier L , Holton K , De Choudhury M . J Med Internet Res 2021 23 (12) e30753 BACKGROUND: Expanding access to and use of medication for opioid use disorder (MOUD) is a key component of overdose prevention. An important barrier to the uptake of MOUD is exposure to inaccurate and potentially harmful health misinformation on social media or web-based forums where individuals commonly seek information. There is a significant need to devise computational techniques to describe the prevalence of web-based health misinformation related to MOUD to facilitate mitigation efforts. OBJECTIVE: By adopting a multidisciplinary, mixed methods strategy, this paper aims to present machine learning and natural language analysis approaches to identify the characteristics and prevalence of web-based misinformation related to MOUD to inform future prevention, treatment, and response efforts. METHODS: The team harnessed public social media posts and comments in the English language from Twitter (6,365,245 posts), YouTube (99,386 posts), Reddit (13,483,419 posts), and Drugs-Forum (5549 posts). Leveraging public health expert annotations on a sample of 2400 of these social media posts that were found to be semantically most similar to a variety of prevailing opioid use disorder-related myths based on representational learning, the team developed a supervised machine learning classifier. This classifier identified whether a post's language promoted one of the leading myths challenging addiction treatment: that the use of agonist therapy for MOUD is simply replacing one drug with another. Platform-level prevalence was calculated thereafter by machine labeling all unannotated posts with the classifier and noting the proportion of myth-indicative posts over all posts. RESULTS: Our results demonstrate promise in identifying social media postings that center on treatment myths about opioid use disorder with an accuracy of 91% and an area under the curve of 0.9, including how these discussions vary across platforms in terms of prevalence and linguistic characteristics, with the lowest prevalence on web-based health communities such as Reddit and Drugs-Forum and the highest on Twitter. Specifically, the prevalence of the stated MOUD myth ranged from 0.4% on web-based health communities to 0.9% on Twitter. CONCLUSIONS: This work provides one of the first large-scale assessments of a key MOUD-related myth across multiple social media platforms and highlights the feasibility and importance of ongoing assessment of health misinformation related to addiction treatment. |
Suicide Risk and Protective Factors in Online Support Forum Posts: Annotation Scheme Development and Validation Study.
Chancellor S , Sumner SA , David-Ferdon C , Ahmad T , De Choudhury M . JMIR Ment Health 2021 8 (11) e24471 BACKGROUND: Online communities provide support for individuals looking for help with suicidal ideation and crisis. As community data are increasingly used to devise machine learning models to infer who might be at risk, there have been limited efforts to identify both risk and protective factors in web-based posts. These annotations can enrich and augment computational assessment approaches to identify appropriate intervention points, which are useful to public health professionals and suicide prevention researchers. OBJECTIVE: This qualitative study aims to develop a valid and reliable annotation scheme for evaluating risk and protective factors for suicidal ideation in posts in suicide crisis forums. METHODS: We designed a valid, reliable, and clinically grounded process for identifying risk and protective markers in social media data. This scheme draws on prior work on construct validity and the social sciences of measurement. We then applied the scheme to annotate 200 posts from r/SuicideWatch-a Reddit community focused on suicide crisis. RESULTS: We documented our results on producing an annotation scheme that is consistent with leading public health information coding schemes for suicide and advances attention to protective factors. Our study showed high internal validity, and we have presented results that indicate that our approach is consistent with findings from prior work. CONCLUSIONS: Our work formalizes a framework that incorporates construct validity into the development of annotation schemes for suicide risk on social media. This study furthers the understanding of risk and protective factors expressed in social media data. This may help public health programming to prevent suicide and computational social science research and investigations that rely on the quality of labels for downstream machine learning tasks. |
Characterizing the transport of aluminum-, silicon- and titanium-containing particles and nanoparticles in mainstream tobacco smoke
Fresquez MR , Watson CH , Valentin-Blasini L , Steven Pappas R . J Anal Toxicol 2021 45 (7) 722-729 The most commonly observed forms of aluminum, silicon and titanium in tobacco products are aluminum silicates (e.g., kaolin), silica and titanium(IV) oxide. These compounds are neither water soluble nor volatile at cigarette combustion temperatures. Rather, they are transported in mainstream tobacco smoke as particles after being freed by combustion from the tobacco filler and can induce pulmonary inflammation when inhaled. Aluminum silicate particles are the most frequently observed particles in the pulmonary macrophages of smokers and have become known as 'smokers' inclusions'. A relatively new technique, single particle triple quadrupole inductively coupled plasma-mass spectrometry was used to analyze aluminum-, silicon- and titanium-containing particle deliveries in cigarette and little cigar mainstream tobacco smoke, and to collect information on solid inorganic particles. The mass concentration of aluminum-containing particles transmitted in mainstream smoke was low (0.89-0.56 ng/cigarette), which was not surprising because aluminum silicates are not volatile. Although the collective masses (ng/cigarette) of aluminum-, silicon- and titanium-containing particles under 100 nm diameter transported in mainstream smoke were low, an abundance of 'ultrafine' particles (particles < 100 nm or nanoparticles) was observed. Limitations of the particle background equivalent diameter (the smallest detectable particle size (MassHunter 4.5 Software) due to the environmentally ubiquitous silicon background restricted the determination of silica nanoparticles, but silica particles slightly below 200 nm diameter were consistently detected. Aluminum- and titanium-containing nanoparticles were observed in all cigarette and little cigar samples, with titanium(IV) oxide particle deliveries consistently fewer in number and smaller in diameter than the other two types of particles. The highest concentrations of aluminum-containing particles (as kaolin) were in the nanoparticle range with much lower concentrations extending to the larger particle sizes (>100 nm). The number and range of particle sizes determined in mainstream smoke is consistent with pulmonary deposition of aluminum silicates described by other researchers as contributing to the 'smokers' inclusions' observed in pulmonary macrophages. |
Implementation of the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) study: Lessons learned for vision health systems strengthening in Sierra Leone.
Shantha JG , Crozier I , Kraft CS , Grant DG , Goba A , Hayek BR , Hartley C , Barnes KG , Uyeki TM , Schieffelin J , Garry RF , Bausch DG , Farmer PE , Mattia JG , Vandy MJ , Yeh S . PLoS One 2021 16 (7) e0252905 BACKGROUND: Following the West African Ebola virus disease (EVD) outbreak of 2013-2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting. METHODOLOGY/PRINCIPAL FINDINGS: Given the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo. CONCLUSIONS/SIGNIFICANCE: The EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings. |
Application of MALDI-TOF mass spectrometry, and DNA sequencing-based SLST and MLST analysis for the identification of Cronobacter spp. isolated from environmental surveillance samples.
Sulaiman IM , Tang K , Segars K , Miranda N , Sulaiman N , Simpson S . Arch Microbiol 2021 203 (8) 4813-4820 Cronobacter spp. are emerging infectious foodborne bacteria that can cause acute meningitis and necrotizing enterocolitis in neonates and immunocompromised individuals. Although, little is known about its reservoirs or transmission routes, it has been linked to powdered infant formula worldwide. Three Cronobacter spp. (C. sakazakii, C. malonaticus, and C. turicensis) have been described as more virulent, and isolated frequently from infant meningitis cases. The estimated mortality rates are as high as 80% in infants. Thus, surveillance and typing of Cronobacter spp. isolated from food and environmental samples is essential to prevent contamination and spread of this pathogen. In this study, we have characterized 83 Cronobacter isolates recovered from various environmental samples by conventional microbiologic protocols. Species identification was accomplished by VITEK 2 system and real-time PCR analysis. Subsequently, these isolates were analyzed using VITEK MS system. Single locus sequence typing (SLST) was achieved by characterizing the regions of 16S rRNA and rpoB genes. Multilocus sequence typing (MLST) was performed by sequence characterization of seven housekeeping genes (atpD, fusA, glnS, gltB, gyrB, infB, and pps) using ABI 3500XL Genetic Analyzer. VITEK MS system identified, the majority of isolates as Cronobacter sakazakii with a high confidence value (99.9%). MLST analysis ascertained 12 distinct clonal complexes (CC1, CC4, CC8, CC13, CC17, CC21, CC31, CC40, CC52, CC64, CC73, and CC83) for the recovered C. sakazakii isolates. The results suggest that the MALDI-TOF MS is a reliable diagnostic tool for rapid species identification whereas 7-loci MLST is a powerful technique to discriminate and differentiate Cronobacter spp. isolates. |
Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.
Son MBF , Murray N , Friedman K , Young CC , Newhams MM , Feldstein LR , Loftis LL , Tarquinio KM , Singh AR , Heidemann SM , Soma VL , Riggs BJ , Fitzgerald JC , Kong M , Doymaz S , Giuliano JS Jr , Keenaghan MA , Hume JR , Hobbs CV , Schuster JE , Clouser KN , Hall MW , Smith LS , Horwitz SM , Schwartz SP , Irby K , Bradford TT , Maddux AB , Babbitt CJ , Rowan CM , McLaughlin GE , Yager PH , Maamari M , Mack EH , Carroll CL , Montgomery VL , Halasa NB , Cvijanovich NZ , Coates BM , Rose CE , Newburger JW , Patel MM , Randolph AG . N Engl J Med 2021 385 (1) 23-34 BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.). |
U.S. Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines.
Gubernot D , Jazwa A , Niu M , Baumblatt J , Gee J , Moro P , Duffy J , Harrington T , McNeil MM , Broder K , Su J , Kamidani S , Olson CK , Panagiotakopoulos L , Shimabukuro T , Forshee R , Anderson S , Bennett S . Vaccine 2021 39 (28) 3666-3677 The Coronavirus Disease 2019 (COVID-19) pandemic has had a devastating impact on global health, and has resulted in an unprecedented, international collaborative effort to develop vaccines to control the outbreak, protect human lives, and avoid further social and economic disruption. Mass vaccination campaigns are underway in multiple countries and are expected worldwide once more vaccine becomes available. Some early candidate vaccines use novel platforms, such as mRNA encapsulated in lipid nanoparticles, and relatively new platforms, such as replication-deficient viral vectors. While these new vaccine platforms hold promise, limited safety data in humans are available. Serious health outcomes linked to vaccinations are rare, and some outcomes may occur incidentally in the vaccinated population. Knowledge of background incidence rates of these medical conditions is a critical component of vaccine safety monitoring to aid in the assessment of adverse events temporally associated with vaccination and to put these events into context with what would be expected due to chance alone. A list of 22 potential adverse events of special interest (AESI), including neurologic, autoimmune, and cardiovascular disorders, was compiled by subject matter experts at the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention. The most recently available U.S. background rates for these medical conditions, overall and by age, sex, and race/ethnicity (when available), were sourced from reported statistics (data published by medical panels/ associations or federal government reports), and literature reviews in PubMed. This review provides estimates of background incidence rates for medical conditions that may be monitored or studied as AESI during safety surveillance and research for COVID-19 vaccines and other new vaccines. |
Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2.
Payne AB , Gilani Z , Godfred-Cato S , Belay ED , Feldstein LR , Patel MM , Randolph AG , Newhams M , Thomas D , Magleby R , Hsu K , Burns M , Dufort E , Maxted A , Pietrowski M , Longenberger A , Bidol S , Henderson J , Sosa L , Edmundson A , Tobin-D'Angelo M , Edison L , Heidemann S , Singh AR , Giuliano JSJr , Kleinman LC , Tarquinio KM , Walsh RF , Fitzgerald JC , Clouser KN , Gertz SJ , Carroll RW , Carroll CL , Hoots BE , Reed C , Dahlgren FS , Oster ME , Pierce TJ , Curns AT , Langley GE , Campbell AP , Balachandran N , Murray TS , Burkholder C , Brancard T , Lifshitz J , Leach D , Charpie I , Tice C , Coffin SE , Perella D , Jones K , Marohn KL , Yager PH , Fernandes ND , Flori HR , Koncicki ML , Walker KS , Di Pentima MC , Li S , Horwitz SM , Gaur S , Coffey DC , Harwayne-Gidansky I , Hymes SR , Thomas NJ , Ackerman KG , Cholette JM . JAMA Netw Open 2021 4 (6) e2116420 IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. OBJECTIVE: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. EXPOSURES: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). MAIN OUTCOMES AND MEASURES: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. RESULTS: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). CONCLUSIONS AND RELEVANCE: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group. |
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. |
Genomic analysis of Clostridioides difficile in two regions of the United States reveals a diversity of strains and limited transmission.
Pecora N , Holzbauer S , Wang X , Gu Y , Taffner S , Hatwar T , Hardy D , Dziejman M , D'Heilly P , Pung K , Guh A , Qiu X , Gill S , Dumyati G . J Infect Dis 2021 225 (1) 121-129 BACKGROUND: The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole genome sequencing (WGS) across two CDC Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community and healthcare-associated disease and assess transmission. METHODS: C. difficile isolates from CDI cases over three months between 2016 and 2017 underwent WGS. Cases were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. Cases were epidemiologically classified as healthcare (HCA) or community (CA) associated. RESULTS: Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were ST42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%), and ST41 (77.8%). ST1 was more frequent in NY than MN (10.8% vs 3.1%). Thirty three pairs were closely related genomically, 14 of which had potential patient-patient transmission supported by chart review. DISCUSSION: The genomic epidemiology of C. difficile across two regions of the US indicates the presence of a diverse strain profile and limited direct transmission. |
Comparative neurotranscriptomics reveal widespread species differences associated with bonding.
Tripp JA , Berrio A , McGraw LA , Matz MV , Davis JK , Inoue K , Thomas JW , Young LJ , Phelps SM . BMC Genomics 2021 22 (1) 399 BACKGROUND: Pair bonding with a reproductive partner is rare among mammals but is an important feature of human social behavior. Decades of research on monogamous prairie voles (Microtus ochrogaster), along with comparative studies using the related non-bonding meadow vole (M. pennsylvanicus), have revealed many of the neural and molecular mechanisms necessary for pair-bond formation in that species. However, these studies have largely focused on just a few neuromodulatory systems. To test the hypothesis that neural gene expression differences underlie differential capacities to bond, we performed RNA-sequencing on tissue from three brain regions important for bonding and other social behaviors across bond-forming prairie voles and non-bonding meadow voles. We examined gene expression in the amygdala, hypothalamus, and combined ventral pallidum/nucleus accumbens in virgins and at three time points after mating to understand species differences in gene expression at baseline, in response to mating, and during bond formation. RESULTS: We first identified species and brain region as the factors most strongly associated with gene expression in our samples. Next, we found gene categories related to cell structure, translation, and metabolism that differed in expression across species in virgins, as well as categories associated with cell structure, synaptic and neuroendocrine signaling, and transcription and translation that varied among the focal regions in our study. Additionally, we identified genes that were differentially expressed across species after mating in each of our regions of interest. These include genes involved in regulating transcription, neuron structure, and synaptic plasticity. Finally, we identified modules of co-regulated genes that were strongly correlated with brain region in both species, and modules that were correlated with post-mating time points in prairie voles but not meadow voles. CONCLUSIONS: These results reinforce the importance of pre-mating differences that confer the ability to form pair bonds in prairie voles but not promiscuous species such as meadow voles. Gene ontology analysis supports the hypothesis that pair-bond formation involves transcriptional regulation, and changes in neuronal structure. Together, our results expand knowledge of the genes involved in the pair bonding process and open new avenues of research in the molecular mechanisms of bond formation. |
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. |
Serotype 2 oral poliovirus vaccine (OPV2) choices and the consequences of delaying outbreak response.
Kalkowska DA , Pallansch MA , Wassilak SGF , Cochi SL , Thompson KM . Vaccine 2021 41 Suppl 1 A136-A141 The Global Polio Eradication Initiative (GPEI) faces substantial challenges with managing outbreaks of serotype 2 circulating vaccine-derived polioviruses (cVDPV2s) in 2021. A full five years after the globally coordinated removal of serotype 2 oral poliovirus vaccine (OPV2) from trivalent oral poliovirus vaccine (tOPV) for use in national immunization programs, cVDPV2s did not die out. Since OPV2 cessation, responses to outbreaks caused by cVDPV2s mainly used serotype 2 monovalent OPV (mOPV2) from a stockpile. A novel vaccine developed from a genetically stabilized OPV2 strain (nOPV2) promises to potentially facilitate outbreak response with lower prospective risks, although its availability and properties in the field remain uncertain. Using an established global poliovirus transmission model and building on a related analysis that characterized the impacts of disruptions in GPEI activities caused by the COVID-19 pandemic, we explore the implications of trade-offs associated with delaying outbreak response to avoid using mOPV2 by waiting for nOPV2 availability (or equivalently, delayed responses waiting for national validation of meeting the criteria for nOPV2 initial use). Consistent with prior modeling, responding as quickly as possible with available mOPV2 promises to reduce the expected burden of disease in the outbreak population and to reduce the chances for the outbreak virus to spread to other areas. Delaying cVDPV2 outbreak response (e.g., modeled as no response January-June 2021) to wait for nOPV2 can considerably increase the total expected cases (e.g., by as many as 1,300 cVDPV2 cases in the African region during 2021-2023) and increases the likelihood of triggering the need to restart widescale preventive use of an OPV2-containing vaccine in national immunization programs that use OPV. Countries should respond to any cVDPV2 outbreaks quickly with rounds that achieve high coverage using any available OPV2, and plan to use nOPV2, if needed, once it becomes widely available based on evidence that it is as effective but safer in populations than mOPV2. |
Detection of Emerging Drugs Involved in Overdose via Diachronic Word Embeddings of Substances Discussed on Social Media.
Wright AP , Jones CM , Horng Chau D , Matthew Gladden R , Sumner SA . J Biomed Inform 2021 119 103824 Substances involved in overdose deaths have shifted over time and continue to undergo transition. Early detection of emerging drugs involved in overdose is a major challenge for traditional public health data systems. While novel social media data have shown promise, there is a continued need for robust natural language processing approaches that can identify emerging substances. Consequently, we developed a new metric, the relative similarity ratio, based on diachronic word embeddings to measure movement in the semantic proximity of individual substance words to 'overdose' over time. Our analysis of 64,420,376 drug-related posts made between January 2011 and December 2018 on Reddit, the largest online forum site, reveals that this approach successfully identified fentanyl, the most significant emerging substance in the overdose epidemic, >1 year earlier than traditional public health data systems. Use of diachronic word embeddings may enable improved identification of emerging substances involved in drug overdose, thereby improving the timeliness of prevention and treatment activities. |
The impact of disruptions caused by the COVID-19 pandemic on global polio eradication.
Kalkowska DA , Voorman A , Pallansch MA , Wassilak SGF , Cochi SL , Badizadegan K , Thompson KM . Vaccine 2021 41 Suppl 1 A12-A18 In early 2020, the COVID-19 pandemic led to substantial disruptions in global activities. The disruptions also included intentional and unintentional reductions in health services, including immunization campaigns against the transmission of wild poliovirus (WPV) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2). Building on a recently updated global poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model, we explored the implications of immunization disruption and restrictions of human interactions (i.e., population mixing) on the expected incidence of polio and on the resulting challenges faced by the Global Polio Eradication Initiative (GPEI). We demonstrate that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on January 1, 2021 of all polio immunization activities to pre-COVID-19 levels, the GPEI could largely mitigate the impact of COVID-19 to the delays incurred. The relative importance of reduced mixing (leading to potentially decreased incidence) and reduced immunization (leading to potentially increased expected incidence) depends on the timing of the effects. Following resumption of immunization activities, the GPEI will likely face similar barriers to eradication of WPV and elimination of cVDPV2 as before COVID-19. The disruptions from the COVID-19 pandemic may further delay polio eradication due to indirect effects on vaccine and financial resources. |
Adults Hospitalized with COVID-19 -United States, March-June and October-December 2020: Implications for the Potential Effects of COVID-19 Tier-1 Vaccination on Future Hospitalizations and Outcomes.
Sami S , Tenforde MW , Talbot HK , Lindsell CJ , Steingrub JS , Shapiro NI , Ginde AA , Douin DJ , Prekker ME , Erickson HL , Brown SM , Peltan ID , Gong MN , Khan A , Exline MC , Files DC , Gibbs KW , Rice TW , Casey JD , Grijalva CG , Stubblefield WB , Womack KN , Hager DN , Qadir N , Chang SY , Henning DJ , Wilson JG , Self WH , Patel MM . Clin Infect Dis 2021 73 S32-S37 BACKGROUND: Because of the increased risk for severe coronavirus disease 2019 (COVID-19), the Advisory Committee on Immunization Practices (ACIP) initially prioritized COVID-19 vaccination for persons in long-term care facilities (LTCF), persons aged ≥65 years, and persons aged 16-64 years with high-risk medical conditions when there is limited vaccine supply. We compared characteristics and severe outcomes of hospitalized patients with COVID-19 in the United States between early and later in the pandemic categorized by groups at higher risk of severe COVID-19. METHODS: Observational study of sampled patients aged ≥18 years who tested positive for SARS-CoV-2 and admitted to one of 14 academic hospitals in the United States during March-June and October-December 2020. Demographic and clinical information were gathered from electronic health record data. RESULTS: Among 647 patients, 91% met ≥1 of the following risk factors for severe COVID-19 [91% March-June (n=434); 90% October-December (n=213)]; 19% were LTCF residents, 45% were aged ≥65-years, and 84% had ≥1 high-risk condition. The proportion of patients who resided in a LTCF declined significantly (25% vs. 6%) from early to later pandemic periods. Compared with patients at lower risk for severe COVID-19, in-hospital mortality was higher among patients at high risk for severe COVID-19 (20% vs. 7%); these differences were consistently observed between March-June and October-December. CONCLUSIONS: Most adults hospitalized with COVID-19 were those recommended to be prioritized for vaccination based on risk for developing severe COVID-19. These findings highlight the urgency to vaccinate patients at high risk for severe COVID-19 and monitor vaccination impact on hospitalizations and outcomes. |
Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years - United States, January-March 2021.
Tenforde MW , Olson SM , Self WH , Talbot HK , Lindsell CJ , Steingrub JS , Shapiro NI , Ginde AA , Douin DJ , Prekker ME , Brown SM , Peltan ID , Gong MN , Mohamed A , Khan A , Exline MC , Files DC , Gibbs KW , Stubblefield WB , Casey JD , Rice TW , Grijalva CG , Hager DN , Shehu A , Qadir N , Chang SY , Wilson JG , Gaglani M , Murthy K , Calhoun N , Monto AS , Martin ET , Malani A , Zimmerman RK , Silveira FP , Middleton DB , Zhu Y , Wyatt D , Stephenson M , Baughman A , Womack KN , Hart KW , Kobayashi M , Verani JR , Patel MM . MMWR Morb Mortal Wkly Rep 2021 70 (18) 674-679 Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination(†) with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk. |
Early introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States.
Alpert T , Brito AF , Lasek-Nesselquist E , Rothman J , Valesano AL , MacKay MJ , Petrone ME , Breban MI , Watkins AE , Vogels CBF , Kalinich CC , Dellicour S , Russell A , Kelly JP , Shudt M , Plitnick J , Schneider E , Fitzsimmons WJ , Khullar G , Metti J , Dudley JT , Nash M , Beaubier N , Wang J , Liu C , Hui P , Muyombwe A , Downing R , Razeq J , Bart SM , Grills A , Morrison SM , Murphy S , Neal C , Laszlo E , Rennert H , Cushing M , Westblade L , Velu P , Craney A , Cong L , Peaper DR , Landry ML , Cook PW , Fauver JR , Mason CE , Lauring AS , St George K , MacCannell DR , Grubaugh ND . Cell 2021 184 (10) 2595-2604 e13 The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response. |
Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome.
LaRovere KL , Riggs BJ , Poussaint TY , Young CC , Newhams MM , Maamari M , Walker TC , Singh AR , Dapul H , Hobbs CV , McLaughlin GE , Son MBF , Maddux AB , Clouser KN , Rowan CM , McGuire JK , Fitzgerald JC , Gertz SJ , Shein SL , Munoz AC , Thomas NJ , Irby K , Levy ER , Staat MA , Tenforde MW , Feldstein LR , Halasa NB , Giuliano JS Jr , Hall MW , Kong M , Carroll CL , Schuster JE , Doymaz S , Loftis LL , Tarquinio KM , Babbitt CJ , Nofziger RA , Kleinman LC , Keenaghan MA , Cvijanovich NZ , Spinella PC , Hume JR , Wellnitz K , Mack EH , Michelson KN , Flori HR , Patel MM , Randolph AG . JAMA Neurol 2021 78 (5) 536-547 IMPORTANCE: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. OBJECTIVE: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. SETTING, DESIGN, AND PARTICIPANTS: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. EXPOSURES: Severe acute respiratory syndrome coronavirus 2. MAIN OUTCOMES AND MEASURES: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. RESULTS: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. CONCLUSIONS AND RELEVANCE: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown. |
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