Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-30 (of 354 Records) |
Query Trace: Mark J [original query] |
---|
Telemedicine-based risk program to prevent falls among older adults: Study protocol for a randomized quality improvement trial
Rein DB , Hackney ME , Haddad YK , Sublett FA , Moreland B , Imhof L , Peterson C , Legha JK , Mark J , Vaughan CP , Johnson Ii TM , Bergen G . JMIR Res Protoc 2024 13 e54395 BACKGROUND: The Center for Disease Control and Prevention's Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative offers health care providers tools and resources to assist with fall risk screening and multifactorial fall risk assessment and interventions. Its effectiveness has never been evaluated in a randomized trial. OBJECTIVE: This study aims to describe the protocol for the STEADI Options Randomized Quality Improvement Trial (RQIT), which was designed to evaluate the impact on falls and all-cause health expenditures of a telemedicine-based form of STEADI implemented among older adults aged 65 years and older, within a primary care setting. METHODS: STEADI Options was a pragmatic RQIT implemented within a health system comparing a telemedicine version of the STEADI fall risk assessment to the standard of care (SOC). Before screening, we randomized all eligible patients in participating clinics into the STEADI arm or SOC arm based on their scheduled provider. All received the Stay Independent screener (SIS) to determine fall risk. Patients were considered at risk for falls if they scored 4 or more on the SIS or answered affirmatively to any 1 of the 3 key questions within the SIS. Patients screened at risk for falls and randomized to the STEADI arm were offered a registered nurse (RN)-led STEADI assessment through telemedicine; the RN provided assessment results and recommendations to the providers, who were advised to discuss fall-prevention strategies with their patients. Patients screened at risk for falls and randomized to the SOC arm were asked to participate in study data collection only. Data on recruitment, STEADI assessments, use of recommended prevention services, medications, and fall occurrences were collected using electronic health records and patient surveys. Using staff time diaries and administrative records, the study prospectively collected data on STEADI implementation costs and all-cause outpatient and inpatient charges incurred over the year following enrollment. RESULTS: The study enrolled 720 patients (n=307, 42.6% STEADI arm; n=353, 49% SOC arm; and n=60, 8.3% discontinued arm) from September 2020 to December 2021. Follow-up data collection was completed in January 2023. As of February 2024, data analysis is complete, and results are expected to be published by the end of 2025. CONCLUSIONS: The STEADI RQIT evaluates the impact of a telemedicine-based, STEADI-based fall risk assessment on falls and all-cause health expenditures and can provide information on the intervention's effectiveness and cost-effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT05390736, http://clinicaltrials.gov/ct2/show/NCT05390736. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/54395. |
Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2)
Navas-Acien A , Santella RM , Joubert BR , Huang Z , Lokhnygina Y , Ujueta F , Gurvich I , LoIacono NJ , Ravalli F , Ward CD , Jarrett JM , Salazar AL , Boineau R , Jones TLZ , Mark DB , Newman JD , Nathan DM , Anstrom KJ , Lamas GA . Am Heart J 2024 BACKGROUND: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes. METHODS: TACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2's participants. RESULTS: At baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m(2), 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) μg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) μg/L and 0.30 (0.18, 0.51) μg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset. CONCLUSIONS: TACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185. |
Efficacy of unregulated minimum risk tick repellent products evaluated with Ixodes scapularis nymphs in a human skin bioassay
Burtis JC , Ford SL , Parise CM , Eisen RJ , Eisen L . Parasit Vectors 2024 17 (1) 50 BACKGROUND: The majority of vector-borne disease cases in the USA are caused by pathogens spread by ticks, most commonly the blacklegged tick, Ixodes scapularis. Personal protection against tick bites, including use of repellents, is the primary defense against tick-borne diseases. Tick repellents registered by the Environmental Protection Agency (EPA) are well documented to be safe as well as effective against ticks. Another group of tick repellent products, 25(b) exempt or minimum risk products, use alternative, mostly botanically derived, active ingredients. These are considered to pose minimal risk to human health and therefore are exempt from EPA registration; efficacy testing is not mandated for these products. METHODS: We used a finger bioassay to evaluate the repellency against I. scapularis nymphs for 11 formulated 25(b) exempt products together with two positive control DEET-based EPA registered products. Repellency was assessed hourly from 0.5 to 6.5 h after product application. RESULTS: The DEET-based products showed ≥ 97% repellency for all examined timepoints. By contrast, an average of 63% of ticks were repelled in the first 1.5 h after application across the 11 25(b) exempt products, and the average fell to 3% repelled between 2.5 and 6.5 h. Ten of the 11 25(b) exempt products showed statistically similar efficacy to DEET-based products at 30 min after application (repellency of 79-97%). However, only four 25(b) exempt products maintained a level of repellency similar to DEET-based products (> 72%) at the 1.5-h mark, and none of these products were effective in repelling ticks at the timepoints from 2.5 to 6.5 h after application. CONCLUSIONS: Neither the claims on the labels nor specific active ingredients and their concentrations appeared to predict the duration of efficacy we observed for the 25(b) exempt products. These products are not registered with the EPA, so the methods used to determine the application guidelines on their labels are unclear. Consumers should be aware that both the level of efficacy and the duration of repellency may differ among unregulated 25(b) exempt repellent products labeled for use against ticks. We encourage more research on these products and the 25(b) exempt active ingredients they contain to help determine and improve their efficacy as repellents under different conditions. |
Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus to the United States.
Kapoor M , Pringle K , Kumar A , Dearth S , Liu L , Lovchik J , Perez O , Pontones P , Richards S , Yeadon-Fagbohun J , Breakwell L , Chea N , Cohen NJ , Schneider E , Erdman D , Haynes L , Pallansch M , Tao Y , Tong S , Gerber S , Swerdlow D , Feikin DR . Clin Infect Dis 2014 59 (11) 1511-8 BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered September 2012 in the Kingdom of Saudi Arabia (KSA). The first US case of MERS-CoV was confirmed on 2 May 2014. METHODS: We summarize the clinical symptoms and signs, laboratory and radiologic findings, and MERS-CoV-specific tests. RESULTS: The patient is a 65-year-old physician who worked in a hospital in KSA where MERS-CoV patients were treated. His illness onset included malaise, myalgias, and low-grade fever. He flew to the United States on day of illness (DOI) 7. His first respiratory symptom, a dry cough, developed on DOI 10. On DOI 11, he presented to an Indiana hospital as dyspneic, hypoxic, and with a right lower lobe infiltrate on chest radiography. On DOI 12, his serum tested positive by real-time reverse transcription polymerase chain reaction (rRT-PCR) for MERS-CoV and showed high MERS-CoV antibody titers, whereas his nasopharyngeal swab was rRT-PCR negative. Expectorated sputum was rRT-PCR positive the following day, with a high viral load (5.31 × 10(6) copies/mL). He was treated with antibiotics, intravenous immunoglobulin, and oxygen by nasal cannula. He was discharged on DOI 22. The genome sequence was similar (>99%) to other known MERS-CoV sequences, clustering with those from KSA from June to July 2013. CONCLUSIONS: This patient had a prolonged nonspecific prodromal illness before developing respiratory symptoms. Both sera and sputum were rRT-PCR positive when nasopharyngeal specimens were negative. US clinicians must be vigilant for MERS-CoV in patients with febrile and/or respiratory illness with recent travel to the Arabian Peninsula, especially among healthcare workers. |
Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.
Pop M , Walker AW , Paulson J , Lindsay B , Antonio M , Hossain MA , Oundo J , Tamboura B , Mai V , Astrovskaya I , Corrada Bravo H , Rance R , Stares M , Levine MM , Panchalingam S , Kotloff K , Ikumapayi UN , Ebruke C , Adeyemi M , Ahmed D , Ahmed F , Alam MT , Amin R , Siddiqui S , Ochieng JB , Ouma E , Juma J , Mailu E , Omore R , Morris JG , Breiman RF , Saha D , Parkhill J , Nataro JP , Stine OC . Genome Biol 2014 15 (6) R76 BACKGROUND: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. RESULTS: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. CONCLUSIONS: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques. |
Phylogeny of Zika Virus in Western Hemisphere, 2015.
Lanciotti RS , Lambert AJ , Holodniy M , Saavedra S , Signor Ldel C . Emerg Infect Dis 2016 22 (5) 933-5 Zika virus belongs to the genus Flavivirus, family Flaviviridae, and is transmitted by Aedes spp. mosquitoes. Clinical signs and symptoms of human infection include fever, headache, malaise, maculopapular rash, and conjunctivitis. | | Zika virus was first isolated in 1947 from the blood of a febrile sentinel rhesus monkey during a study of yellow fever in the Zika Forest of Uganda (1). During the next 20 years, Zika virus isolates were obtained primarily from East and West Africa during arbovirus surveillance studies in the absence of epidemics. During those 20 years, cases of Zika virus infection were detected sporadically; however, given the clinical similarity of Zika virus and dengue virus infections and the extensive cross-reactivity of Zika virus antibodies with dengue viruses, it is possible that Zika virus was associated with epidemics that were incorrectly attributed to dengue viruses. Beginning in 2007, substantial Zika virus outbreaks were reported first in Yap Island (Federated States of Micronesia), then in French Polynesia, and then in other Pacific Islands (2–4). |
Detection of fungal DNA in human body fluids and tissues during a multistate outbreak of fungal meningitis and other infections.
Gade L , Scheel CM , Pham CD , Lindsley MD , Iqbal N , Cleveland AA , Whitney AM , Lockhart SR , Brandt ME , Litvintseva AP . Eukaryot Cell 2013 12 (5) 677-83 Exserohilum rostratum was the major cause of an outbreak of fungal infections linked to injections of contaminated methylprednisolone acetate. Because almost 14,000 persons were exposed to product that was possibly contaminated with multiple fungal pathogens, there was unprecedented need for a rapid throughput diagnostic test that could detect both E. rostratum and other unusual agents of fungal infection. Here we report development of a novel PCR test that allowed for rapid and specific detection of fungal DNA in cerebrospinal fluid (CSF), other body fluids and tissues of infected individuals. The test relied on direct purification of free-circulating fungal DNA from fluids and subsequent PCR amplification and sequencing. Using this method, we detected Exserohilum rostratum DNA in 123 samples from 114 case-patients (28% of 413 case-patients for whom 627 samples were available), and Cladosporium DNA in one sample from one case-patient. PCR with novel Exserohilum-specific ITS-2 region primers detected 25 case-patients with samples that were negative using broad-range ITS primers. Compared to fungal culture, this molecular test was more sensitive: of 139 case-patients with an identical specimen tested by culture and PCR, E. rostratum was recovered in culture from 19 (14%), but detected by PCR in 41 (29%), showing a diagnostic sensitivity of 29% for PCR compared to 14% for culture in this patient group. The ability to rapidly confirm the etiologic role of E. rostratum in these infections provided an important contribution in the public health response to this outbreak. |
Sterile Insect Technique: Lessons From the Past.
Benedict MQ . J Med Entomol 2021 58 (5) 1974-1979 When E.F. Knipling conceived of the release of sexually sterile insects to suppress wild populations, he laid down several fundamental qualities that characterized suitable target species-some of which mosquitoes generally violate-including high reproductive rates and large population numbers. Regardless of this, their global importance in public health has led numerous research teams to attempt to use the mosquito sterile insect technique against several species. Because of the degree of financial commitment required for suppression programs, most releases have consisted of preliminary investigations of male performance, population characteristics, and production methods. Those that have accomplished suppression provide important insights regarding the challenges of production, dispersal, and immigration. Insights gained from these studies remain relevant today, regardless of the genetic control technology being applied. In this article, I highlight studies that were notable for the insights that were gained, the intrinsic difficulties that mosquitoes present, and synthesize these into recommendations for successful applications of the sterile insect technique and newer technologies to mosquitoes. |
SARS-CoV-2, Mannerism, Marten, Mink, and Man
Swancutt M , Chorba T . Emerg Infect Dis 2021 27 (7) 2003-2005 Girolamo Francesco Maria Mazzola (1503–1540), known as Parmigianino (the little one from Parma), was a painter and printmaker. He was born into a family of painters in Parma, in what was then the Duchy of Milan, and died in Cremona, in northern Italy. He was among the first and most prominent artists of the Mannerist school of art of the Late Renaissance that came after the High Renaissance. The High Renaissance is known for the works of Raphael and the early works of Michelangelo, and its art is treasured for perfection of elegance and qualities of balance, proportion, and absoluast, in Mannerism, compositions are said to be exaggerated, almost to a fault, as a reaction to the art of the High Renaissance or perhaps as an attempt to improve on it. In general, it is characterized by realist but decorous art in which there is subtle, unsettling elongation of figures with stylized features and poses. | | Among Parmigianino’s more renowned works is a portrait painting from 1531‒1534 of a young woman, Antea, which appears on the cover of this month’s journal. It is unknown if the painting is an image of a specific person or a stylized composition. We behold a beautiful young woman facing forward, with elongated bodily proportions, as is characteristic of Mannerist works. With a small oval head set upon a large torso and with wide shoulders, her arms and hands appear exaggerated in size, as if the parts of her body were proportioned for different paintings. Yet despite these physical disproportions, the viewer has an impression of great beauty, a testimony to the subtlety and success of this Mannerist portrait. Contributing to the incongruousness of the image of this young lady, we also note that she is clad in the garments of an older woman, or a woman of an age with which we more commonly associate wealth; Antea is bejeweled, fingering a gold chain with her left hand, and dressed luxuriously. Among her layers of garments are a gold blouse with a fine white apron, a detailed gold satin dress, leather gloves, and a marten fur stole complete with the animal’s head, on which the nose is pierced with a ring still attached to a chain. |
Dengue
Paz-Bailey G , Adams LE , Deen J , Anderson KB , Katzelnick LC . Lancet 2024 Dengue, caused by four closely related viruses, is a growing global public health concern, with outbreaks capable of overwhelming health-care systems and disrupting economies. Dengue is endemic in more than 100 countries across tropical and subtropical regions worldwide, and the expanding range of the mosquito vector, affected in part by climate change, increases risk in new areas such as Spain, Portugal, and the southern USA, while emerging evidence points to silent epidemics in Africa. Substantial advances in our understanding of the virus, immune responses, and disease progression have been made within the past decade. Novel interventions have emerged, including partially effective vaccines and innovative mosquito control strategies, although a reliable immune correlate of protection remains a challenge for the assessment of vaccines. These developments mark the beginning of a new era in dengue prevention and control, offering promise in addressing this pressing global health issue. |
Predictors of willingness to participate in COVID-19 screening testing from a pilot school survey in the United States
Mark-Carew M , Swanson M , Eller B , Cullen T , Valenzuela MO , LaBelle M , Persad N , Barrios LC , Szucs LE . J Sch Health 2023 93 (12) 1061-1069 BACKGROUND: COVID-19 screening testing (ST) can detect asymptomatic or pre-symptomatic cases, allowing for prompt identification of cases and close contacts. This study examined parents' and school staffs' knowledge and attitudes toward to a pilot school-based ST program in a school district in southern Arizona. METHODS: In May 2021, online surveys to parents and school staff were administered to examine attitudes toward ST and impacts of the COVID-19 pandemic. Unweighted percent estimates were calculated, and bivariate differences were examined by demographics. Associations were assessed using chi-square tests and logistic regression. RESULTS: The survey had response rates of 10% (606/6085) and 22% (187/849) among parents and staff, respectively. Approximately one-third of responding parents (35%) would or already allow their child to participate in school-based ST, 37% would not participate; 28% were unsure. Among responding staff, 46% would or already participate in ST, 33% would not; 21% were unsure. The top concern (38%) among responding staff was taking job-related leave if testing positive. CONCLUSION: Schools work to balance the needs of students, families, and staff by implementing supportive and flexible policies and practices founded on buy-in and acceptance from their communities. |
Understanding COVID-19 vaccine hesitancy among K-12 staff, parents, and students: District of Columbia, February to April, 2022
Mark-Carew M , van Zyl A , Tatti KM , Chong M , Rose C , Sifre K , Jarris D , Still W , Aynalem G , Welton M , Thomas ES , Hall L , Samson ME . J Sch Health 2023 93 (12) 1079-1090 OBJECTIVE: Despite widespread availability of COVID-19 vaccines, millions of Americans have not received the recommended vaccine doses. In the District of Columbia (DC), COVID-19 vaccination rates are lowest among residents who are Non-Hispanic (NH) Black and among school-aged children. We assessed COVID-19 vaccine hesitancy among staff and parents of students in DC K-12 public and public charter schools. METHODS: We conducted a telephone-based survey from February 6 to April 16, 2022 to staff, students, and parents of students who participated in school-based COVID-19 screening testing. COVID-19-related survey items included: vaccination status, reasons for not getting vaccinated, perceived vaccine access, and trusted COVID-19 information sources. Utilizing time-to-event analyses, we evaluated differences across demographic groups. RESULTS: The interview response rate was 25.8% (308/1193). Most unvaccinated participants were NH Black and ages 5 to 11 years. Median time from vaccine eligibility to uptake was 236 days for NH Black participants vs. 10 days for NH White participants. Vaccine safety was the top concern among unvaccinated participants. Government and healthcare providers were the most trusted COVID-19 information sources. CONCLUSIONS: Differences in timing of vaccine uptake among respondents and greater vaccine hesitancy among NH Black participants compared to other racial/ethnic groups highlight a need for continued tailored outreach and communication using trusted sources to convey the importance, benefits, and safety of COVID-19 vaccination. |
Pragmatic selection of larval mosquito diets for insectary rearing of Anopheles gambiae and Aedes aegypti (preprint)
Benedict MQ , Hunt CM , Vella MG , Gonzalez KM , Dotson EM , Collins CM . bioRxiv 2019 740142 Larval mosquitoes are aquatic omnivorous scavengers which scrape food from submerged surfaces and collect suspended food particles with their mouth brushes. The composition of diets that have been used in insectaries varies widely though necessarily provides sufficient nutrition to allow colonies to be maintained. Issues such as cost, availability and experience influence which diet is selected. One component of larval diets, essential fatty acids, appears to be necessary for normal flight though deficiencies may not be evident in laboratory cages and are likely more important when mosquitoes are reared for release into the field in e.g. mark-release-recapture and genetic control activities.In this study, four diets were compared for rearing Anopheles gambiae and Aedes aegypti, all of which provide these essential fatty acids. Two diets were custom formulations specifically designed for mosquitoes (Damiens) and two were commercially available fish foods: Doctors Foster and Smith Koi Staple Diet and TetraMin Plus Flakes. Development rate, survival, dry weight and adult longevity of mosquitoes reared with these four diets were measured. The method of presentation of one diet, Koi pellets, was additionally fed in two forms, pellets or a slurry, to determine any effect of food presentation on survival and development rate.While various criteria might be selected to choose ‘the best’ food, the readily-available Koi pellets resulted in development rates and adult longevity equal to the other diets, high survival to the adult stage and, additionally, this is available at low cost. |
Comparative genomics of the major parasitic worms (preprint)
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . bioRxiv 2017 236539 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause. |
Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission (preprint)
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Barrett KMS , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . medRxiv 2022 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Certifying the interruption of wild poliovirus transmission in the WHO African region on the turbulent journey to a polio-free world
Africa Regional Commission for the Certification of Poliomyelitis Eradication , Leke Rose Gana Fomban , Kaboré B Jean , King Arlene , Pallansch Mark A , Tomori Oyewale , Jack Abdoulie D , Sadrizadeh Bijan , Kane Ibrahima , Kironde Naddumba Edward , Lopes-Feio Raul Jorge , Chunsuttiwat Supamit , Maiga Zakaria , Kouassi Beugré , Khomo Ngokoana Esther , Tangermann Rudolf H , Matuja William Bahati Pungu , Mkanda Pascal . Lancet Glob Health 2020 8 (10) e1345-e1351 On Aug 25 2020, the Africa Regional Commission for the Certification of Poliomyelitis Eradication declared that the WHO African region had interrupted transmission of all indigenous wild polioviruses. This declaration marks the African region as the fifth of the six WHO regions to celebrate this extraordinary achievement. Following the Yaoundé Declaration on Polio Eradication in Africa by heads of state and governments in 1996, Nelson Mandela launched the Kick Polio out of Africa campaign. In this Health Policy paper, we describe the long and turbulent journey to the certification of the interruption of wild poliovirus transmission, focusing on 2016-20, lessons learned, and the strategies and analyses that convinced the Regional Commission that the African region is free of wild polioviruses. This certification of the WHO African region shows the feasibility of polio eradication in countries with chronic insecurity, inaccessible and hard-to-reach populations, and weak health systems. Challenges have been daunting and the sacrifices enormous-dozens of health workers and volunteers have lost their lives in the pursuit of a polio-free Africa. |
Comparative genomics of the major parasitic worms
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . Nat Genet 2019 51 (1) 163-174 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms. |
Differences in Evaluating Fall Risk by Primary Care Provider Type
Mark JA , Haddad YK , Burns ER . J Nurse Pract 2020 16 (7) 528-532 This study assessed differences in clinical fall risk assessment of older adults (65+) and clinical resources used by primary care providers (PCP). We used Porter Novelli's 2016 DocStyles survey to examine clinical behavior data from PCPs (n=1128). Compared to other practitioners, nurse practitioners (NP) reported a higher percentage of their patients were older adults. The majority of NPs reported screening for falls risk routinely, but most did not use standardized fall-risk assessments to assess risk factors. There were also differences in the types of clinical resources used by NPs and other PCPs to evaluate the safety profile of medications. |
A Public Health Research Agenda for Managing Infodemics: Methods and Results of the First WHO Infodemiology Conference.
Calleja N , AbdAllah A , Abad N , Ahmed N , Albarracin D , Altieri E , Anoko JN , Arcos R , Azlan AA , Bayer J , Bechmann A , Bezbaruah S , Briand SC , Brooks I , Bucci LM , Burzo S , Czerniak C , De Domenico M , Dunn AG , Ecker UKH , Espinosa L , Francois C , Gradon K , Gruzd A , Gülgün BS , Haydarov R , Hurley C , Astuti SI , Ishizumi A , Johnson N , Johnson Restrepo D , Kajimoto M , Koyuncu A , Kulkarni S , Lamichhane J , Lewis R , Mahajan A , Mandil A , McAweeney E , Messer M , Moy W , Ndumbi Ngamala P , Nguyen T , Nunn M , Omer SB , Pagliari C , Patel P , Phuong L , Prybylski D , Rashidian A , Rempel E , Rubinelli S , Sacco P , Schneider A , Shu K , Smith M , Sufehmi H , Tangcharoensathien V , Terry R , Thacker N , Trewinnard T , Turner S , Tworek H , Uakkas S , Vraga E , Wardle C , Wasserman H , Wilhelm E , Würz A , Yau B , Zhou L , Purnat TD . JMIR Infodemiology 2021 1 (1) e30979 BACKGROUND: An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. OBJECTIVE: The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. METHODS: As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. RESULTS: The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. CONCLUSIONS: Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider. |
Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers - Eight U.S. Locations, December 2020-March 2021.
Thompson MG , Burgess JL , Naleway AL , Tyner HL , Yoon SK , Meece J , Olsho LEW , Caban-Martinez AJ , Fowlkes A , Lutrick K , Kuntz JL , Dunnigan K , Odean MJ , Hegmann KT , Stefanski E , Edwards LJ , Schaefer-Solle N , Grant L , Ellingson K , Groom HC , Zunie T , Thiese MS , Ivacic L , Wesley MG , Lamberte JM , Sun X , Smith ME , Phillips AL , Groover KD , Yoo YM , Gerald J , Brown RT , Herring MK , Joseph G , Beitel S , Morrill TC , Mak J , Rivers P , Harris KM , Hunt DR , Arvay ML , Kutty P , Fry AM , Gaglani M . MMWR Morb Mortal Wkly Rep 2021 70 (13) 495-500 Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine.(†) Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days.(§) In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons. |
Recommended Adult Immunization Schedule, United States, 2021.
Freedman MS , Bernstein H , Ault KA , Advisory Committee on Immunization Practices , Cohn Amanda . Ann Intern Med 2021 174 (3) 374-384 In October 2020, the Advisory Committee on Immunization Practices (ACIP) voted to approve the Recommended Adult Immunization Schedule for Ages 19 Years or Older, United States, 2021. Following Emergency Use Authorization of Pfizer-BioNTech COVID-19 vaccine by the U.S. Food and Drug Administration, ACIP issued an interim recommendation at its 12 December 2020 emergency meeting for use of Pfizer-BioNTech COVID-19 vaccine in persons aged 16 years or older (1). In addition, ACIP approved an amendment to include COVID-19 vaccine recommendations in the child and adolescent and adult immunization schedules. Following Emergency Use Authorization of Moderna COVID-19 vaccine by the U.S. Food and Drug Administration, ACIP issued an interim recommendation at its 19 December 2020 emergency meeting for use of Moderna COVID-19 vaccine in persons aged 18 years or older (2). The 2021 adult immunization schedule, available at www.cdc.gov/vaccines/schedules/hcp/imz/adult.html, summarizes ACIP recommendations in 2 tables and accompanying notes (Figure). The full ACIP recommendations for each vaccine are available at www.cdc.gov/vaccines/hcp/acip-recs/index.html. The 2021 schedule has also been approved by the director of the Centers for Disease Control and Prevention (CDC) and by the American College of Physicians (www.acponline.org), the American Academy of Family Physicians (www.aafp.org), the American College of Obstetricians and Gynecologists (www.acog.org), the American College of Nurse-Midwives (www.midwife.org), and the American Academy of Physician Assistants |
Cryptic transmission of SARS-CoV-2 in Washington State.
Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Huang ML , Nalla A , Pepper G , Reinhardt A , Xie H , Shrestha L , Nguyen TN , Adler A , Brandstetter E , Cho S , Giroux D , Han PD , Fay K , Frazar CD , Ilcisin M , Lacombe K , Lee J , Kiavand A , Richardson M , Sibley TR , Truong M , Wolf CR , Nickerson DA , Rieder MJ , Englund JA , Hadfield J , Hodcroft EB , Huddleston J , Moncla LH , Müller NF , Neher RA , Deng X , Gu W , Federman S , Chiu C , Duchin J , Gautom R , Melly G , Hiatt B , Dykema P , Lindquist S , Queen K , Tao Y , Uehara A , Tong S , MacCannell D , Armstrong GL , Baird GS , Chu HY , Shendure J , Jerome KR . medRxiv 2020 Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding. |
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. |
Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing.
Allix-Béguec C , Arandjelovic I , Bi L , Beckert P , Bonnet M , Bradley P , Cabibbe AM , Cancino-Muñoz I , Caulfield MJ , Chaiprasert A , Cirillo DM , Clifton DA , Comas I , Crook DW , De Filippo MR , de Neeling H , Diel R , Drobniewski FA , Faksri K , Farhat MR , Fleming J , Fowler P , Fowler TA , Gao Q , Gardy J , Gascoyne-Binzi D , Gibertoni-Cruz AL , Gil-Brusola A , Golubchik T , Gonzalo X , Grandjean L , He G , Guthrie JL , Hoosdally S , Hunt M , Iqbal Z , Ismail N , Johnston J , Khanzada FM , Khor CC , Kohl TA , Kong C , Lipworth S , Liu Q , Maphalala G , Martinez E , Mathys V , Merker M , Miotto P , Mistry N , Moore DAJ , Murray M , Niemann S , Omar SV , Ong RT , Peto TEA , Posey JE , Prammananan T , Pym A , Rodrigues C , Rodrigues M , Rodwell T , Rossolini GM , Sánchez Padilla E , Schito M , Shen X , Shendure J , Sintchenko V , Sloutsky A , Smith EG , Snyder M , Soetaert K , Starks AM , Supply P , Suriyapol P , Tahseen S , Tang P , Teo YY , Thuong TNT , Thwaites G , Tortoli E , van Soolingen D , Walker AS , Walker TM , Wilcox M , Wilson DJ , Wyllie D , Yang Y , Zhang H , Zhao Y , Zhu B . N Engl J Med 2018 379 (15) 1403-1415 BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.). |
Ventilation improvements among K-12 public school districts - United States, August-December 2022
Mark-Carew M , Kang G , Pampati S , Mead KR , Martin SB Jr , Barrios LC . MMWR Morb Mortal Wkly Rep 2023 72 (14) 372-376 Improving ventilation has been one of several COVID-19 prevention strategies implemented by kindergarten through grade 12 (K-12) schools to stay open for safe in-person learning. Because transmission of SARS-CoV-2 occurs through inhalation of infectious viral particles, it is important to reduce the concentration of and exposure time to infectious aerosols (1-3). CDC examined reported ventilation improvement strategies among U.S. K-12 public school districts using telephone survey data collected during August-December 2022. Maintaining continuous airflow through school buildings during active hours was the most frequently reported strategy by school districts (50.7%); 33.9% of school districts reported replacement or upgrade of heating, ventilation, and air conditioning (HVAC) systems; 28.0% reported installation or use of in-room air cleaners with high-efficiency particulate air (HEPA) filters; and 8.2% reported installation of ultraviolet (UV) germicidal irradiation (UVGI) devices, which use UV light to kill airborne pathogens, including bacteria and viruses. School districts in National Center for Education Statistics (NCES) city locales, the West U.S. Census Bureau region, and those designated by U.S. Census Bureau Small Area Income Poverty Estimates (SAIPE) as high-poverty districts reported the highest percentages of HVAC system upgrades and HEPA-filtered in-room air cleaner use, although 28%-60% of all responses were unknown or missing. Federal funding remains available to school districts to support ventilation improvements. Public health departments can encourage K-12 school officials to use available funding to improve ventilation and help reduce transmission of respiratory diseases in K-12 settings. |
A pilot reverse virtual screening study suggests toxic exposures caused long-term epigenetic changes in Gulf War Illness.
Jean-Pierre M , Michalovicz LT , Kelly KA , O'Callaghan JP , Nathanson L , Klimas N , JACraddock T . Comput Struct Biotechnol J 2022 20 6206-6213 Gulf War Illness (GWI) is a chronic illness that affects upward of 32% of deployed Veterans to the 1991 Gulf War (GW). The symptoms are medically unexplained, ranging across cognitive deficits, fatigue, gastrointestinal problems, and musculoskeletal pain. Research indicates that chemical warfare agents play a key role in the onset and progression of GWI. The Khamisiyah ammunition storage that housed chemical warfare agents such as sarin, an acetylcholinesterase (AChE) inhibitor, was demolished during the GW, releasing toxicants into the atmosphere affecting deployed troops. Exposure to other chemical agents such as pyridostigmine bromide, N,N-diethyl-m-toluamide, permethrin and chlorpyrifos, were also prevalent during the war. These additional chemical agents have also been shown to inhibit AChE. AChE inhibition induces an acetylcholine build-up, disrupting signals between nerves and muscles, which in high doses leads to asphyxiation. Little is known about low dose exposure. As bioactive compounds tend to interact with multiple proteins with various physiological effect, we aimed to identify other potential shared targets to understand the extent in which these chemicals could lead to GWI. We followed a reverse screening approach where each chemical is computationally docked to a library of protein targets. The programs PharmMapper and TargetNet were used for this purpose, and further analyses were conducted to mark significant changes in participants with GWI. Previously published work on DNA methylation status in GWI was reanalyzed focusing specifically on the predicted shared targets indicating significant changes in DNA methylation of the associated genes. Our findings thus suggest that exposure to GWI-related agents may converge on similar targets with roles in inflammation, neurotransmitter and lipid metabolism, and detoxification which may have impacts on neurodegenerative-like disease and oxidative stress in Veterans with GWI. |
Serological responses to the MVA-based JYNNEOS monkeypox vaccine in a cohort of participants from the Democratic Republic of Congo
Priyamvada L , Carson WC , Ortega E , Navarra T , Tran S , Smith TG , Pukuta E , Muyamuna E , Kabamba J , Nguete BU , Likafi T , Kokola G , Lushima RS , Tamfum JM , Okitolonda EW , Kaba DK , Monroe BP , McCollum AM , Petersen BW , Satheshkumar PS , Townsend MB . Vaccine 2022 40 (50) 7321-7327 The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation. |
Circulating Poliovirus in New York - New Instance of an Old Problem.
Pallansch Mark A. The New England journal of medicine 2022 387(19) 1725-1728 . The New England journal of medicine 2022 387(19) 1725-1728 Pallansch Mark A. The New England journal of medicine 2022 387(19) 1725-1728 |
Test-to-Stay Implementation in Four Pre-K-12 School Districts.
Lammie SL , Ford L , Swanson M , Guinn AS , Kamitani E , van Zyl A , Rose CE , Marynak K , Shields J , Donovan CV , Holman EJ , Mark-Carew M , Welton M , Thomas ES , Neatherlin J . Pediatrics 2022 150 (4) OBJECTIVE: Globally, COVID-19 has affected how children learn. We evaluated the impact of Test to Stay (TTS) on secondary and tertiary transmission of SARS-CoV-2 and potential impact on in-person learning in four school districts in the United States from September 13-November 19, 2021. METHODS: Implementation of TTS varied across school districts. Data on index cases, school-based close contacts, TTS participation, and testing results were obtained from four school districts in diverse geographic regions. Descriptive statistics, secondary and tertiary attack risk, and a theoretical estimate of impact on in-person learning were calculated. RESULTS: Fifty-one schools in four school districts reported 374 COVID-19 index cases and 2,520 school-based close contacts eligible for TTS. The proportion participating in TTS ranged from 22%-79%. By district, the secondary attack risk (SAR) and tertiary attack risk (TAR) among TTS participants ranged between 2.2%-11.1% and 0%-17.6%, respectively. Nine clusters were identified among secondary cases and two among tertiary cases. The theoretical maximum number of days of in-person learning saved by using TTS was 976-4,650 days across jurisdictions. CONCLUSIONS: TTS preserves in-person learning days. Decisions to participate in TTS may have been influenced by ease of access to testing, communication between schools and families, testing logistics, and school resources. TAR determination became more complicated when numbers of close contacts increased. Minimizing exposure through continued implementation of layered prevention strategies is imperative. To ensure adequate resources for implementation of TTS, community transmission levels should be considered. |
Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Schiabor Barrett KM , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . Nature 2022 609 (7925) 101-108 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases(1-3). SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing(4,5). Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Sep 16, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure