Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
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Overview of U.S. COVID-19 vaccine safety surveillance systems
Gee J , Shimabukuro TT , Su JR , Shay D , Ryan M , Basavaraju SV , Broder KR , Clark M , Buddy Creech C , Cunningham F , Goddard K , Guy H , Edwards KM , Forshee R , Hamburger T , Hause AM , Klein NP , Kracalik I , Lamer C , Loran DA , McNeil MM , Montgomery J , Moro P , Myers TR , Olson C , Oster ME , Sharma AJ , Schupbach R , Weintraub E , Whitehead B , Anderson S . Vaccine 2024 The U.S. COVID-19 vaccination program, which commenced in December 2020, has been instrumental in preventing morbidity and mortality from COVID-19 disease. Safety monitoring has been an essential component of the program. The federal government undertook a comprehensive and coordinated approach to implement complementary safety monitoring systems and to communicate findings in a timely and transparent way to healthcare providers, policymakers, and the public. Monitoring involved both well-established and newly developed systems that relied on both spontaneous (passive) and active surveillance methods. Clinical consultation for individual cases of adverse events following vaccination was performed, and monitoring of special populations, such as pregnant persons, was conducted. This report describes the U.S. government's COVID-19 vaccine safety monitoring systems and programs used by the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the Department of Defense, the Department of Veterans Affairs, and the Indian Health Service. Using the adverse event of myocarditis following mRNA COVID-19 vaccination as a model, we demonstrate how the multiple, complementary monitoring systems worked to rapidly detect, assess, and verify a vaccine safety signal. In addition, longer-term follow-up was conducted to evaluate the recovery status of myocarditis cases following vaccination. Finally, the process for timely and transparent communication and dissemination of COVID-19 vaccine safety data is described, highlighting the responsiveness and robustness of the U.S. vaccine safety monitoring infrastructure during the national COVID-19 vaccination program. |
Estimating causes of death where there is no medical certification: evolution and state of the art of verbal autopsy
Chandramohan D , Fottrell E , Leitao J , Nichols E , Clark SJ , Alsokhn C , Cobos Munoz D , AbouZahr C , Di Pasquale A , Mswia R , Choi E , Baiden F , Thomas J , Lyatuu I , Li Z , Larbi-Debrah P , Chu Y , Cheburet S , Sankoh O , Mohamed Badr A , Fat DM , Setel P , Jakob R , de Savigny D . Glob Health Action 12/28/2021 14 1982486 Over the past 70 years, significant advances have been made in determining the causes of death in populations not served by official medical certification of cause at the time of death using a technique known as Verbal Autopsy (VA). VA involves an interview of the family or caregivers of the deceased after a suitable bereavement interval about the circumstances, signs and symptoms of the deceased in the period leading to death. The VA interview data are then interpreted by physicians or, more recently, computer algorithms, to assign a probable cause of death. VA was originally developed and applied in field research settings. This paper traces the evolution of VA methods with special emphasis on the World Health Organization's (WHO)'s efforts to standardize VA instruments and methods for expanded use in routine health information and vital statistics systems in low- and middle-income countries (LMICs). These advances in VA methods are culminating this year with the release of the 2022 WHO Standard Verbal Autopsy (VA) Toolkit. This paper highlights the many contributions the late Professor Peter Byass made to the current VA standards and methods, most notably, the development of InterVA, the most commonly used automated computer algorithm for interpreting data collected in the WHO standard instruments, and the capacity building in low- and middle-income countries (LMICs) that he promoted. This paper also provides an overview of the methods used to improve the current WHO VA standards, a catalogue of the changes and improvements in the instruments, and a mapping of current applications of the WHO VA standard approach in LMICs. It also provides access to tools and guidance needed for VA implementation in Civil Registration and Vital Statistics Systems at scale. |
Assessment of the standardized surveillance case definition for neonatal abstinence syndrome by the Council Of State and Territorial Epidemiologists, 4 jurisdictions, 2020-2021
Czarnik M , Oliver D , Goodson V , Nestoridi E , Michael Bryan J , Hinds D , Clark C , Green C , Small J , Pabst L . Public Health Rep 2024 Objectives: In 2019, the Council of State and Territorial Epidemiologists ratified a multitiered standardized surveillance case definition (SSCD) for neonatal abstinence syndrome (NAS) to minimize variability in definitions across states. This evaluation of the tier 1 NAS SSCD aimed to identify common challenges and opportunities for enhancement to support consistent implementation of the definition. Methods: This mixed-methods analysis consisted of 3 virtual focus groups in March 2021 with site principal investigators, medical record abstractors, and data analysts (1 focus group each) from 4 jurisdictions piloting the tier 1 NAS SSCD. We analyzed focus group transcripts to create a codebook. We collected written reports in February 2022 from the 4 jurisdictions, conducted thematic analysis of focus group transcripts and written reports to identify themes, and collected surveillance data on infants identified with NAS born from January 2020 through December 2021 from the pilot sites. We analyzed surveillance data to further inform identified themes. We examined agreement among tier 1 classifications assigned independently by each pilot site and the Centers for Disease Control and Prevention to cases of NAS. Results: Three major themes emerged in the data: challenges abstracting data on withdrawal signs from the medical record, difficulty determining the time frame of prenatal substance exposure, and challenges assigning case classifications. In a comparison of tier 1 classifications assigned by the Centers for Disease Control and Prevention and the sites, 82.1% of cases in the dataset were concordant. Conclusions: We identified several opportunities to modify the SSCD to promote consistency and ease implementation across jurisdictions. Promoting consistent implementation supports comparability of NAS incidence estimates across jurisdictions, evaluation of prevention efforts, and allocation of resources to support families. © 2024, Association of Schools and Programs of Public Health. |
COVID-19 Vaccine Safety Technical (VaST) work group: Enhancing vaccine safety monitoring during the pandemic
Markowitz LE , Hopkins RH Jr , Broder KR , Lee GM , Edwards KM , Daley MF , Jackson LA , Nelson JC , Riley LE , McNally VV , Schechter R , Whitley-Williams PN , Cunningham F , Clark M , Ryan M , Farizo KM , Wong HL , Kelman J , Beresnev T , Marshall V , Shay DK , Gee J , Woo J , McNeil MM , Su JR , Shimabukuro TT , Wharton M , Keipp Talbot H . Vaccine 2024 During the COVID-19 pandemic, candidate COVID-19 vaccines were being developed for potential use in the United States on an unprecedented, accelerated schedule. It was anticipated that once available, under U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) or FDA approval, COVID-19 vaccines would be broadly used and potentially administered to millions of individuals in a short period of time. Intensive monitoring in the post-EUA/licensure period would be necessary for timely detection and assessment of potential safety concerns. To address this, the Centers for Disease Control and Prevention (CDC) convened an Advisory Committee on Immunization Practices (ACIP) work group focused solely on COVID-19 vaccine safety, consisting of independent vaccine safety experts and representatives from federal agencies - the ACIP COVID-19 Vaccine Safety Technical Work Group (VaST). This report provides an overview of the organization and activities of VaST, summarizes data reviewed as part of the comprehensive effort to monitor vaccine safety during the COVID-19 pandemic, and highlights selected actions taken by CDC, ACIP, and FDA in response to accumulating post-authorization safety data. VaST convened regular meetings over the course of 29 months, from November 2020 through April 2023; through March 2023 FDA issued EUAs for six COVID-19 vaccines from four different manufacturers and subsequently licensed two of these COVID-19 vaccines. The independent vaccine safety experts collaborated with federal agencies to ensure timely assessment of vaccine safety data during this time. VaST worked closely with the ACIP COVID-19 Vaccines Work Group; that work group used safety data and VaST's assessments for benefit-risk assessments and guidance for COVID-19 vaccination policy. Safety topics reviewed by VaST included those identified in safety monitoring systems and other topics of scientific or public interest. VaST provided guidance to CDC's COVID-19 vaccine safety monitoring efforts, provided a forum for review of data from several U.S. government vaccine safety systems, and assured that a diverse group of scientists and clinicians, external to the federal government, promptly reviewed vaccine safety data. In the event of a future pandemic or other biological public health emergency, the VaST model could be used to strengthen vaccine safety monitoring, enhance public confidence, and increase transparency through incorporation of independent, non-government safety experts into the monitoring process, and through strong collaboration among federal and other partners. |
Extended post-exposure protection against vaginal SHIV infection with tenofovir alafenamide fumarate/elvitegravir inserts in macaques
Makarova N , Singletary T , Peet MM , Mitchell J , Bachman S , Holder A , Dinh C , Lipscomb J , Agrahari V , Mendoza M , Pan Y , Heneine W , Clark MR , García-Lerma JG , Doncel GF , Smith JM . J Infect Dis 2023 Vaginal inserts that can be used on demand before or after sex may be a desirable HIV prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF/20mg) and elvitegravir (EVG/16mg) were highly protective against repeated SHIV vaginal exposures when administered to macaques 4h before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8h or 24h after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women. |
Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance
Ko ER , Reller ME , Tillekeratne LG , Bodinayake CK , Miller C , Burke TW , Henao R , McClain MT , Suchindran S , Nicholson B , Blatt A , Petzold E , Tsalik EL , Nagahawatte A , Devasiri V , Rubach MP , Maro VP , Lwezaula BF , Kodikara-Arachichi W , Kurukulasooriya R , De Silva AD , Clark DV , Schully KL , Madut D , Dumler JS , Kato C , Galloway R , Crump JA , Ginsburg GS , Minogue TD , Woods CW . Sci Rep 2023 13 (1) 22554 Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant (USA, Sri Lanka) discovery cohort with adjudicated viral or bacterial infections of diverse etiology or non-infectious disease mimics. We then derived and cross-validated gene expression classifiers including: 1) a single model to distinguish bacterial vs. viral (Global Fever-Bacterial/Viral [GF-B/V]) and 2) a two-model system to discriminate bacterial and viral in the context of noninfection (Global Fever-Bacterial/Viral/Non-infectious [GF-B/V/N]). We then translated to a multiplex RT-PCR assay and independent validation involved 101 participants (USA, Sri Lanka, Australia, Cambodia, Tanzania). The GF-B/V model discriminated bacterial from viral infection in the discovery cohort an area under the receiver operator curve (AUROC) of 0.93. Validation in an independent cohort demonstrated the GF-B/V model had an AUROC of 0.84 (95% CI 0.76-0.90) with overall accuracy of 81.6% (95% CI 72.7-88.5). Performance did not vary with age, demographics, or site. Host transcriptional response diagnostics distinguish bacterial and viral illness across global sites with diverse endemic pathogens. |
Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women--Advisory Committee on Immunization Practices (ACIP), 2012
Centers for Disease Control and Prevention , Sawyer M , Liang JL , Messonnier N , Clark TA . MMWR Morb Mortal Wkly Rep 2013 62 (7) 131-5 In October 2011, in an effort to reduce the burden of pertussis in infants, the Advisory Committee on Immunization Practices (ACIP) recommended that unvaccinated pregnant women receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap). Vaccination of women with Tdap during pregnancy is expected to provide some protection to infants from pertussis until they are old enough to be vaccinated themselves. Tdap given to pregnant women will stimulate the development of maternal antipertussis antibodies, which will pass through the placenta, likely providing the newborn with protection against pertussis in early life, and will protect the mother from pertussis around the time of delivery, making her less likely to become infected and transmit pertussis to her infant. The 2011 Tdap recommendation did not call for vaccinating pregnant women previously vaccinated with Tdap. On October 24, 2012, ACIP voted to recommend use of Tdap during every pregnancy. This report summarizes data considered and conclusions made by ACIP and provides guidance for implementing its recommendations. These updated recommendations on use of Tdap in pregnant women aim to optimize strategies for preventing pertussis morbidity and mortality in infants. |
Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP)
Cohn AC , MacNeil JR , Clark TA , Ortega-Sanchez IR , Briere EZ , Meissner HC , Baker CJ , Messonnier NE . MMWR Recomm Rep 2013 62 1-28 Meningococcal disease describes the spectrum of infections caused by Neisseria meningiditis, including meningitdis, bacteremia, and bacteremic pneumonia. Two quadrivalent meningococcal polysaccharide-protein conjugate vaccines that provide protection against meningococcal serogroups A, C, W, and Y (MenACWY-D [Menactra, manufactured by Sanofi Pasteur, Inc., Swiftwater, Pennsylvania] and MenACWY-CRM [Menveo, manufactured by Novartis Vaccines, Cambridge, Massachusetts]) are licensed in the United States for use among persons aged 2 through 55 years. MenACWY-D also is licensed for use among infants and toddlers aged 9 through 23 months. Quadrivalent meningococcal polysaccharide vaccine (MPSV4 [Menommune, manufactured by sanofi pasteur, Inc., Swiftwater, Pennsylvania]) is the only vaccine licensed for use among persons aged ≥56 years. A bivalent meningococcal polysaccharide protein conjugate vaccine that provides protection against meningococcal serogroups C and Y along with Haemophilus influenzae type b (Hib) (Hib-MenCY-TT [MenHibrix, manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium]) is licensed for use in children aged 6 weeks through 18 months. This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of meningococcal disease in the United States, specifically the changes in the recommendations published since 2005 (CDC. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2005;54 [No. RR-7]). As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians as a resource. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination for persons at increased risk for meningococcal disease (i.e., persons who have persistent complement component deficiencies, persons who have anatomic or functional asplenia, microbiologists who routinely are exposed to isolates of N. meningitidis, military recruits, and persons who travel to or reside in areas in which meningococcal disease is hyperendemic or epidemic). Guidelines for antimicrobial chemoprophylaxis and for evaluation and management of suspected outbreaks of meningococcal disease also are provided. |
Use of inactivated polio vaccine among U.S. adults: Updated recommendations of the Advisory Committee on Immunization Practices - United States, 2023
Kidd S , Clark T , Routh J , Cineas S , Bahta L , Brooks O . MMWR Morb Mortal Wkly Rep 2023 72 (49) 1327-1330 Poliovirus can cause poliomyelitis and lifelong paralysis. Although wild poliovirus types 2 and 3 have been eradicated, wild poliovirus type 1 and vaccine-derived polioviruses are still circulating in multiple countries worldwide. In 2022, a case of paralytic polio caused by vaccine-derived poliovirus type 2 was identified in an unvaccinated young adult in New York. This case and subsequent detection of community transmission underscored the ongoing risk for importation of poliovirus into the United States and risk for poliomyelitis among unvaccinated persons. However, previous Advisory Committee on Immunization Practices (ACIP) recommendations for adult polio vaccination were limited to adults known to be at increased risk for exposure. During October 2022-June 2023, the ACIP Polio Vaccine Work Group reviewed data on poliovirus surveillance and epidemiology, safety and effectiveness of inactivated poliovirus vaccine (IPV), and other considerations outlined in the ACIP Evidence to Recommendations Framework. On June 21, 2023, ACIP voted to recommend that all U.S. adults aged ≥18 years who are known or suspected to be unvaccinated or incompletely vaccinated against polio complete a primary polio vaccination series with IPV. This report summarizes evidence considered for this recommendation and provides clinical guidance for the use of IPV in adults. |
Agreement between cause of death assignment by computer-coded verbal autopsy methods and physician coding of verbal autopsy interviews in South Africa
Groenewald P , Thomas J , Clark SJ , Morof D , Joubert JD , Kabudula C , Li Z , Bradshaw D . Glob Health Action 2023 16 (1) 2285105 BACKGROUND: The South African national cause of death validation (NCODV 2017/18) project collected a national sample of verbal autopsies (VA) with cause of death (COD) assignment by physician-coded VA (PCVA) and computer-coded VA (CCVA). OBJECTIVE: The performance of three CCVA algorithms (InterVA-5, InSilicoVA and Tariff 2.0) in assigning a COD was compared with PCVA (reference standard). METHODS: Seven performance metrics assessed individual and population level agreement of COD assignment by age, sex and place of death subgroups. Positive predictive value (PPV), sensitivity, overall agreement, kappa, and chance corrected concordance (CCC) assessed individual level agreement. Cause-specific mortality fraction (CSMF) accuracy and Spearman's rank correlation assessed population level agreement. RESULTS: A total of 5386 VA records were analysed. PCVA and CCVAs all identified HIV/AIDS as the leading COD. CCVA PPV and sensitivity, based on confidence intervals, were comparable except for HIV/AIDS, TB, maternal, diabetes mellitus, other cancers, and some injuries. CCVAs performed well for identifying perinatal deaths, road traffic accidents, suicide and homicide but poorly for pneumonia, other infectious diseases and renal failure. Overall agreement between CCVAs and PCVA for the top single cause (48.2-51.6) indicated comparable weak agreement between methods. Overall agreement, for the top three causes showed moderate agreement for InterVA (70.9) and InSilicoVA (73.8). Agreement based on kappa (-0.05-0.49)and CCC (0.06-0.43) was weak to none for all algorithms and groups. CCVAs had moderate to strong agreement for CSMF accuracy, with InterVA-5 highest for neonates (0.90), Tariff 2.0 highest for adults (0.89) and males (0.84), and InSilicoVA highest for females (0.88), elders (0.83) and out-of-facility deaths (0.85). Rank correlation indicated moderate agreement for adults (0.75-0.79). CONCLUSIONS: Whilst CCVAs identified HIV/AIDS as the leading COD, consistent with PCVA, there is scope for improving the algorithms for use in South Africa. |
A conceptual framework for nomenclatural stability and validity of medically important fungi: a proposed global consensus guideline for fungal name changes supported by ABP, ASM, CLSI, ECMM, ESCMID-EFISG, EUCAST-AFST, FDLC, IDSA, ISHAM, MMSA, and MSGERC
de Hoog S , Walsh TJ , Ahmed SA , Alastruey-Izquierdo A , Alexander BD , Arendrup MC , Babady E , Bai FY , Balada-Llasat JM , Borman A , Chowdhary A , Clark A , Colgrove RC , Cornely OA , Dingle TC , Dufresne PJ , Fuller J , Gangneux JP , Gibas C , Glasgow H , Gräser Y , Guillot J , Groll AH , Haase G , Hanson K , Harrington A , Hawksworth DL , Hayden RT , Hoenigl M , Hubka V , Johnson K , Kus JV , Li R , Meis JF , Lackner M , Lanternier F , Leal SM Jr , Lee F , Lockhart SR , Luethy P , Martin I , Kwon-Chung KJ , Meyer W , Nguyen MH , Ostrosky-Zeichner L , Palavecino E , Pancholi P , Pappas PG , Procop GW , Redhead SA , Rhoads DD , Riedel S , Stevens B , Sullivan KO , Vergidis P , Roilides E , Seyedmousavi A , Tao L , Vicente VA , Vitale RG , Wang QM , Wengenack NL , Westblade L , Wiederhold N , White L , Wojewoda CM , Zhang SX . J Clin Microbiol 2023 61 (11) e0087323 The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way. |
Estimating the global impact of rotavirus vaccines on child mortality
Clark A , Mahmud S , Debellut F , Pecenka C , Jit M , Perin J , Tate J , Soeters HM , Black RE , Santosham M , Sanderson C . Int J Infect Dis 2023 137 90-97 OBJECTIVES: To estimate the global impact of rotavirus vaccines on under-five deaths by year. METHODS: We used a proportionate outcomes model with a finely disaggregated age structure to estimate rotavirus deaths prevented by vaccination over the period 2006-2019 in 186 countries. We ran deterministic and probabilistic uncertainty analyses and compared our estimates to surveillance-based estimates in 20 countries. RESULTS: We estimate that rotavirus vaccines prevented 139,000 under-five rotavirus deaths (95% uncertainty interval 98,000 - 201,000) in the period 2006-2019. In 2019 alone, rotavirus vaccines prevented 15% (95% UI 11-21%) of under-five rotavirus deaths (0.5% of child mortality). Assuming global use of rotavirus vaccines and coverage equivalent to other co-administered vaccines could prevent 37% of under-five rotavirus deaths (1.2% of child mortality). Our estimates were sensitive to the choice of rotavirus mortality burden data and several vaccine impact modelling assumptions. WHO's recommendation to remove age restrictions in 2012 could have prevented up to 17,000 rotavirus deaths in the period 2013-2019. Our modelled estimates of rotavirus vaccine impact were broadly consistent with estimates from post-vaccination surveillance sites. CONCLUSIONS: Rotavirus vaccines have made a valuable contribution to global public health. Enhanced rotavirus mortality prevention strategies are needed in countries with high mortality in under-5-year-old children. |
Elucidating regulatory processes of intense physical activity by multi-omics analysis
Nakayasu ES , Gritsenko MA , Kim YM , Kyle JE , Stratton KG , Nicora CD , Munoz N , Navarro KM , Claborne D , Gao Y , Weitz KK , Paurus VL , Bloodsworth KJ , Allen KA , Bramer LM , Montes F , Clark KA , Tietje G , Teeguarden J , Burnum-Johnson KE . Mil Med Res 2023 10 (1) 48 BACKGROUND: Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment. METHODS: To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student's t-test followed by pathway analysis and comparison between the different omics modalities. RESULTS: Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection. CONCLUSION: This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs. |
Enhanced broad spectrum in vitro antiviral efficacy of 3-F-4-MeO-Bn, 3-CN, and 4-CN derivatives of lipid remdesivir nucleoside monophosphate prodrugs
McMillan RE , Lo MK , Zhang XQ , Beadle JR , Valiaeva N , Garretson AF , Clark AE , Freshman J , Murphy J , Montgomery JM , Spiropoulou CF , Schooley RT , Hostetler KY , Carlin AF . Antiviral Res 2023 219 105718 Broad spectrum oral antivirals are urgently needed for the early treatment of many RNA viruses of clinical concern. We previously described the synthesis of 1-O-octadecyl-2-O-benzyl-glycero-3-phospho-RVn (V2043), an orally bioavailable lipid prodrug of remdesivir nucleoside (RVn, GS-441524) with broad spectrum antiviral activity against viruses with pandemic potential. Here we compared the relative activity of V2043 with new RVn lipid prodrugs containing sn-1 alkyl ether or sn-2 glycerol modifications. We found that 3-F-4-MeO-Bn, 3-CN-Bn, and 4-CN-Bn sn-2 glycerol modifications improved antiviral activity compared to V2043 when tested in vitro against clinically important RNA viruses from 5 virus families. These results support the continued development of V2043 and sn-2 glycerol modified RVn lipid prodrugs for the treatment of a broad range of RNA viruses for which there are limited therapies. |
Seasonal trends in emergency department visits for mental and behavioral health conditions among children and adolescents aged 5-17 years - United States, January 2018-June 2023
Radhakrishnan L , Carey K , Pell D , Ising A , Brathwaite D , Waller A , Gay J , Watson-Smith H , Person M , Zamore K , Brumsted T , Price C , Clark PM , Haas GA , Gracy L , Johnston S , Chen Y , Muñoz K , Henry M , Willis B , Nevels D , Asaolu I , Lee S , Wilkins NJ , Bacon S , Sheppard M , Kite-Powell A , Blau G , King M , Whittaker M , Leeb RT . MMWR Morb Mortal Wkly Rep 2023 72 (38) 1032-1040 Mental and behavioral health conditions among school-aged children, including substance use disorders and overall emotional well-being, are a public health concern in the United States. Timely data on seasonal patterns in child and adolescent conditions can guide optimal timing of prevention and intervention strategies. CDC examined emergency department (ED) visit data from the National Syndromic Surveillance Program for 25 distinct conditions during January 2018-June 2023 among U.S. children and adolescents aged 5-17 years, stratified by age group. Each year, during 2018-2023, among persons aged 10-14 and 15-17 years, the number and proportion of weekly ED visits for eight conditions increased in the fall school semester and remained elevated throughout the spring semester; ED visits were up to twice as high during school semesters compared with the summer period. Among children aged 5-9 years, the number and proportion of visits increased for five mental and behavioral health conditions. Seasonal increases in ED visits for some conditions among school-aged children warrant enhanced awareness about mental distress symptoms and the challenges and stressors in the school environment. Systemic changes that prioritize protective factors (e.g., physical activity; nutrition; sleep; social, community, or faith-based support; and inclusive school and community environments) and incorporate preparedness for increases in conditions during back-to-school planning might improve child and adolescent mental health. |
Urban malaria vector bionomics and human sleeping behavior in three cities in Senegal
Diop A , Ndiaye F , Sturm-Ramirez K , Konate L , Senghor M , Diouf EH , Dia AK , Diedhiou S , Samb B , Sene D , Zohdy S , Dotson E , Diouf MB , Koscelnik V , Gerberg L , Bangoura A , Faye O , Clark T , Niang EHA , Chabi J . Parasit Vectors 2023 16 (1) 331 BACKGROUND: Malaria is endemic in Senegal, with seasonal transmission, and the entire population is at risk. In recent years, high malaria incidence has been reported in urban and peri-urban areas of Senegal. An urban landscape analysis was conducted in three cities to identify the malaria transmission indicators and human behavior that may be driving the increasing malaria incidence occurring in urban environments. Specifically, mosquito vector bionomics and human sleeping behaviors including outdoor sleeping habits were assessed to guide the optimal deployment of targeted vector control interventions. METHODS: Longitudinal entomological monitoring using human landing catches and pyrethrum spray catches was conducted from May to December 2019 in Diourbel, Kaolack, and Touba, the most populous cities in Senegal after the capital Dakar. Additionally, a household survey was conducted in randomly selected houses and residential Koranic schools in the same cities to assess house structures, sleeping spaces, sleeping behavior, and population knowledge about malaria and vector control measures. RESULTS: Of the 8240 Anopheles mosquitoes collected from all the surveyed sites, 99.4% (8,191) were An. gambiae s.l., and predominantly An. arabiensis (99%). A higher number of An. gambiae s.l. were collected in Kaolack (77.7%, n = 6496) than in Diourbel and Touba. The overall mean human biting rate was 14.2 bites per person per night (b/p/n) and was higher outdoors (15.9 b/p/n) than indoors (12.5 b/p/n). The overall mean entomological inoculation rates ranged from 3.7 infectious bites per person per year (ib/p/y) in Diourbel to 40.2 ib/p/y in Kaolack. Low anthropophilic rates were recorded at all sites (average 35.7%). Of the 1202 households surveyed, about 24.3% of household members slept outdoors, except during the short rainy season between July and October, despite understanding how malaria is transmitted and the vector control measures used to prevent it. CONCLUSION: Anopheles arabiensis was the primary malaria vector in the three surveyed cities. The species showed an outdoor biting tendency, which represents a risk for the large proportion of the population sleeping outdoors. As all current vector control measures implemented in the country target endophilic vectors, these data highlight potential gaps in population protection and call for complementary tools and approaches targeting outdoor biting malaria vectors. |
Outbreak of locally acquired mosquito-transmitted (autochthonous) malaria - Florida and Texas, May-July 2023
Blackburn D , Drennon M , Broussard K , Morrison AM , Stanek D , Sarney E , Ferracci C , Huard S , Brennan W , Eaton J , Nealeigh S , Barber N , Zimler RA , Adams JN , Blackmore C , Gordillo M , Mercado R , Vore H , Scanlan K , Motie I , Stanfield L , Farooq A , Widel K , Tomson K , Kerr N , Nasir J , Cone M , Rice C , Larkin T , Hernandez E , Bencie J , Lesser CR , Dersch M , Ramirez-Lachmann S , Clark M , Rollo S , Bashadi A , Tyler R , Bolling B , Moore B , Sullivan B , Fonken E , Castillo R , Gonzalez Y , Olivares G , Mace KE , Sayre D , Lenhart A , Sutcliffe A , Dotson E , Corredor C , Rogers E , Raphael BH , Sapp SGH , Qvarnstrom Y , Ridpath AD , McElroy PD . MMWR Morb Mortal Wkly Rep 2023 72 (36) 973-978 Eight cases of locally acquired, mosquito-transmitted (i.e., autochthonous) Plasmodium vivax malaria, which has not been reported in the United States since 2003, were reported to CDC from state health departments in Florida and Texas during May 18-July 17, 2023. As of August 4, 2023, case surveillance, mosquito surveillance and control activities, and public outreach and education activities continue in both states. U.S. clinicians need to consider a malaria diagnosis in patients with unexplained fever, especially in areas where autochthonous malaria has been recently reported, although the risk for autochthonous malaria in the United States remains very low. Prompt diagnosis and treatment of malaria can prevent severe disease or death and limit ongoing transmission to local Anopheles mosquitoes and other persons. Preventing mosquito bites and controlling mosquitoes at home can prevent mosquitoborne diseases, including malaria. Before traveling internationally to areas with endemic malaria, travelers should consult with a health care provider regarding recommended malaria prevention measures, including potentially taking malaria prophylaxis. Malaria is a nationally notifiable disease; continued reporting of malaria cases to jurisdictional health departments and CDC will also help ensure robust surveillance to detect and prevent autochthonous malaria in the United States. |
A model for accelerating access to care and treatment for children and adolescents living with HIV in Nigeria, Tanzania, Uganda, and Zambia: The Faith-Based Action for Scaling-Up Testing and Treatment for the Epidemic Response (FASTER) Initiative
Oliver D , Mabirizi D , Hast M , Alwano MG , Chungu C , Kelemani A , Mbanefo C , Gross J , Parris K , Dowling S , Clark A , Williams A , Simao L , Amole C , Suggu K , Kama J , Mpasela F , Mtui L , Nabitaka V , Saunders R , Williamson D , Rivadeneira ED , Hrapcak S , Nantume S , Nazziwa E , Itoh M , Machage E , Onyenuobi C , Munthali G , Rwebembera A , Mwiya M , Katureebe C , Ikpeazu A , Fenn T . J Int Assoc Provid AIDS Care 2023 22 23259582231186701 The number of children newly infected with HIV dropped by 50%, from 320 000 in 2010 to 160 000 in 2021. Despite progress, ongoing gaps persist in diagnosis, continuity of care, and treatment optimization. In response, the United States President's Emergency Plan for AIDS Relief created the Faith-based Action for Scaling-Up Testing and Treatment for Epidemic Response (FASTER). Faith-based Action for Scaling-Up Testing and Treatment for Epidemic Response addressed gaps in countries with the highest unmet need by working with government to operationalize innovative interventions and ensure alignment with national priorities and with communities living with HIV to ensure the change was community-led. Between 2019 and 2021, FASTER's interventions were incorporated into national policies, absorbed by Ministries of Health, and taken up in subsequent awards and country operating plans. Continued effort is needed to sustain gains made during the FASTER initiative and to continue scaling evidence-based interventions to ensure that children and adolescents are not left behind in the global HIV response. |
Survey of invasive mosquito surveillance and control capacity in Southeastern USA reveals training and resource needs
Nguyen V , Weaver-Romero AL , Wang X , Tavares Y , Bauer A , McDowell RC , Dorsainvil C , Eason MD , Malcolm AN , Raz CD , Byrd BD , Riegel C , Clark M , Ber J , Harrison RL , Evans CL , Zohdy S , Allen B , Campbell LP , Killingsworth D , Grey EW , Riles MT , Lee Y , Giordano BV . J Am Mosq Control Assoc 2023 39 (2) 108-121 Several invasive mosquito species that are nuisances or of medical and veterinary importance have been introduced into the Southeastern region of the USA, posing a threat to other species and the local ecosystems and/or increasing the risk of pathogen transmission to people, livestock, and domestic pets. Prompt and effective monitoring and control of invasive species is essential to prevent them from spreading and causing harmful effects. However, the capacity for invasive mosquito species surveillance is highly variable among mosquito control programs in the Southeast, depending on a combination of factors such as regional geography and climate, access to resources, and the ability to interact with other programs. To facilitate the development of invasive mosquito surveillance in the region, we, the Mosquito BEACONS (Biodiversity Enhancement and Control of Non-native Species) working group, conducted a survey on the capacities of various public health agencies and pest control agencies engaged in mosquito surveillance and control in seven Southeastern states (Alabama, Florida, Georgia, Louisiana, Mississippi, North Carolina, and South Carolina). Ninety control programs completed the survey, representing an overall response rate of 25.8%. We report key findings from our survey, emphasizing the training and resource needs, and discuss their implications for future invasive mosquito surveillance and control capacity building. By increasing communication and collaboration opportunities (e.g., real-time sharing of collection records, coordinated multistate programs), the establishment of Mosquito BEACONS and the implementation of this survey can accelerate knowledge transfer and improve decision support capacity in response to or in preparation for invasive mosquito surveillance and can establish infrastructure that can be used to inform programs around the world. |
Estimating the number of symptomatic SARS-CoV-2 infections among vaccinated individuals in the United States—January–April, 2021 (preprint)
Kugeler KJ , Williamson J , Curns AT , Healy JM , Nolen LD , Clark TA , Martin SW , Fischer M . medRxiv 2021 2021.08.03.21261442 As of March 2021, three COVID-19 vaccines have been authorized by the U.S. Food and Drug Administration (FDA) for use in the United States. Each has substantial efficacy in preventing COVID-19. However, as efficacy from trials was <100% for all three vaccines, disease in vaccinated people is expected to occur. We created a spreadsheet-based tool to estimate the number of symptomatic vaccine breakthrough infections based on published vaccine efficacy (VE) data, percent of the population that has been fully vaccinated, and average number of COVID-19 cases reported per day. We estimate that approximately 51,000 symptomatic vaccine breakthrough infections (95% CI: ∼48,000–55,000 cases) occurred in the United States during January–April 2021 among >77 million fully vaccinated people, reflecting <0.5% of COVID-19 cases that occurred during that time. With ongoing SARS-CoV-2 transmission and increasing numbers of people vaccinated in the United States, vaccine breakthrough infections will continue to accumulate before population immunity is sufficient to interrupt transmission. Understanding expectations regarding number of vaccine breakthrough infections enables accurate public health messaging to help ensure that the occurrence of such cases does not negatively affect vaccine perceptions, confidence, and uptake.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was received.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:This activity was conducted consistent with applicable federal policy.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll input data are publicly available |
Enhanced Contact Investigations for Nine Early Travel-Related Cases of SARS-CoV-2 in the United States (preprint)
Burke RM , Balter S , Barnes E , Barry V , Bartlett K , Beer KD , Benowitz I , Biggs HM , Bruce H , Bryant-Genevier J , Cates J , Chatham-Stephens K , Chea N , Chiou H , Christiansen D , Chu VT , Clark S , Cody SH , Cohen M , Conners EE , Dasari V , Dawson P , DeSalvo T , Donahue M , Dratch A , Duca L , Duchin J , Dyal JW , Feldstein LR , Fenstersheib M , Fischer M , Fisher R , Foo C , Freeman-Ponder B , Fry AM , Gant J , Gautom R , Ghinai I , Gounder P , Grigg CT , Gunzenhauser J , Hall AJ , Han GS , Haupt T , Holshue M , Hunter J , Ibrahim MB , Jacobs MW , Jarashow MC , Joshi K , Kamali T , Kawakami V , Kim M , Kirking HL , Kita-Yarbro A , Klos R , Kobayashi M , Kocharian A , Lang M , Layden J , Leidman E , Lindquist S , Lindstrom S , Link-Gelles R , Marlow M , Mattison CP , McClung N , McPherson TD , Mello L , Midgley CM , Novosad S , Patel MT , Pettrone K , Pillai SK , Pray IW , Reese HE , Rhodes H , Robinson S , Rolfes M , Routh J , Rubin R , Rudman SL , Russell D , Scott S , Shetty V , Smith-Jeffcoat SE , Soda EA , Spitters C , Stierman B , Sunenshine R , Terashita D , Traub E , Vahey GM , Verani JR , Wallace M , Westercamp M , Wortham J , Xie A , Yousaf A , Zahn M . medRxiv 2020 2020.04.27.20081901 Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be available upon reasonable request. |
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. |
Laboratory Analysis of an Outbreak of Candida auris in New York from 2016 to 2018-Impact and Lessons Learned (preprint)
Zhu Y , O'Brien B , Leach L , Clark A , Bates M , Adams E , Ostrowsky B , Quinn M , Dufort E , Southwick K , Erazo R , Haley VB , Bucher C , Chaturvedi V , Limberger RJ , Blog D , Lutterloh E , Chaturvedi S . bioRxiv 2019 760090 Candida auris is a multidrug-resistant yeast which has emerged in healthcare facilities worldwide, however little is known about identification methods, patient colonization, spread, environmental survival, and drug resistance. Colonization on both biotic and abiotic surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in NY from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/non-selective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of ribosomal genes for C. auris genotyping. Results included: a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates, as well as identification of 277 clinical cases and 350 colonized cases from 151 healthcare facilities including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, c) demonstration of relatively heavier colonization of C. auris in nares compared to the axilla/groin, and d) predominance of the South Asia Clade I with intrinsic resistance to fluconazole and elevated minimum inhibitory concentration (MIC) to voriconazole (81%), amphotericin B (61%), 5-FC (3%) and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak. |
Reduced long-lasting insecticidal net efficacy and pyrethroid insecticide resistance are associated with over-expression of CYP6P4, CYP6P3 and CYP6Z1 in populations of Anopheles coluzzii from South-East Côte d’Ivoire (preprint)
Meiwald A , Clark E , Kristan M , Edi C , Jeffries CL , Pelloquin B , Irish SR , Walker T , Messenger LA . bioRxiv 2020 2020.09.24.311639 Background Resistance to major public health insecticides in Côte d’Ivoire has intensified and now threatens the long-term effectiveness of malaria vector control interventions.Methods This study evaluated the bioefficacy of conventional and next-generation long-lasting insecticidal nets (LLINs), determined resistance profiles, and characterized molecular and metabolic mechanisms in wild Anopheles coluzzii from South-East Côte d’Ivoire in 2019.Results Phenotypic resistance was intense: more than 25% of mosquitoes survived exposure to ten times the doses of pyrethroids required to kill susceptible populations. Similarly, 24-hour mortality to deltamethrin-only LLINs was very low and not significantly different to an untreated net. Sub-lethal pyrethroid exposure did not induce significant delayed vector mortality 72 hours later. In contrast, LLINs containing the synergist piperonyl butoxide (PBO), or new insecticides, clothianidin and chlorfenapyr, were highly toxic to An. coluzzii. Pyrethroid-susceptible An. coluzzii were significantly more likely to be infected with malaria, compared to those that survived insecticidal exposure. Pyrethroid resistance was associated with significant over-expression of CYP6P4, CPY6Z1 and CYP6P3.Conclusions Study findings raise concerns regarding the operational failure of standard LLINs and support the urgent deployment of vector control interventions incorporating PBO, chlorfenapyr or clothianidin in areas of high resistance intensity in Côte d’Ivoire.Competing Interest StatementThe authors have declared no competing interest. |
CDC-funded HIV testing services outcomes and social determinants of health in Ending the HIV Epidemic in the U.S. Jurisdictions
Patel D , Clark HA , Williams WO , Taylor-Aidoo N , Wright C . AIDS Behav 2023 We performed an ecological analysis to examine associations between CDC-funded HIV testing services outcomes and social determinants of health (SDOH) among Ending the HIV Epidemic in the U.S. jurisdictions. Using National HIV Prevention Program Monitoring & Evaluation (2020) and American Community Survey (2016-2020) data, we ran robust Poisson models (adjusted for race/ethnicity). In healthcare settings, a 10% absolute increase in percentage without health insurance was associated with a 40% lower prevalence of newly diagnosed positivity (aPR = 0.60, 95% CI: 0.43-0.83); a $5,000 increase in median household income (aPR = 1.04, 95% CI: 1.03-1.06) and a 10% absolute increase in percentage unemployed (aPR = 1.80, 95% CI: 1.31-2.46) were associated with 4% and 80%, respectively, higher prevalence of percentage linked to HIV medical care within 30 days of diagnosis (i.e., linkage). In non-healthcare settings, a 10% absolute increase in percentage with less than high school diploma (aPR = 0.53, 95% CI: 0.29-0.96) was associated with a 47% lower prevalence of newly diagnosed positivity, whereas a 10% absolute increase in percentage without health insurance (aPR = 1.92, 95% CI: 1.29-2.88) was associated with a 92% higher prevalence of newly diagnosed positivity; a 10% absolute increase in percentage with less than high school diploma was associated with a 35% lower prevalence of linkage (aPR = 0.65, 95% CI: 0.43-0.97). Addressing SDOH in HIV prevention programs will play an important role in ending the HIV epidemic. |
Notes from the field: Pediatric intracranial infections - Clark County, Nevada, January-December 2022
Penney JA , Zhang Y , Bragg T , Bryant R , Lockett C . MMWR Morb Mortal Wkly Rep 2023 72 (22) 606-607 In October 2022, the Southern Nevada Health District (SNHD) was notified of a higher-than-expected number of pediatric patients hospitalized with intracranial abscesses; similar concerns were previously reported nationally (1,2). This rare infection is associated with significant morbidity (3,4). When SNHD received the report in October 2022, 14 cases had been diagnosed in the largest pediatric hospital in southern Nevada. SNHD investigated the reported increase to confirm that a cluster had been detected, identify common risk factors for infection, report findings to the community, and recommend measures to prevent future cases. |
Rapid Increase in Suspected SARS-CoV-2 Reinfections, Clark County, Nevada, USA, December 2021.
Ruff J , Zhang Y , Kappel M , Rathi S , Watkins K , Zhang L , Lockett C . Emerg Infect Dis 2022 28 (10) 1977-1981 Genetic differences between SARS-CoV-2 variants raise concerns about reinfection. Public health authorities monitored the incidence of suspected reinfection in Clark County, Nevada, USA, during March 2020-March 2022. Suspected reinfections, defined as a second positive PCR test collected >90 days after an initial positive test, were monitored through an electronic disease surveillance system. We calculated the proportion of all new cases per week that were suspected reinfections and rates per 1,000 previously infected persons by demographic groups. The rate of suspected reinfection remained <2.7% until December 2021, then increased to ≈11%, corresponding with local Omicron variant detection. Reinfection rates were higher among adults 18-50 years of age, women, and minority groups, especially persons identifying as American Indian/Alaska Native. Suspected reinfection became more common in Clark County after introduction of the Omicron variant, and some demographic groups are disproportionately affected. Public health surveillance could clarify the SARS-CoV-2 reinfection burden in communities. |
Identification of pregnancies and their outcomes in healthcare claims data, 2008-2019: An algorithm
Ailes EC , Zhu W , Clark EA , Huang YA , Lampe MA , Kourtis AP , Reefhuis J , Hoover KW . PLoS One 2023 18 (4) e0284893 Pregnancy is a condition of broad interest across many medical and health services research domains, but one not easily identified in healthcare claims data. Our objective was to establish an algorithm to identify pregnant women and their pregnancies in claims data. We identified pregnancy-related diagnosis, procedure, and diagnosis-related group codes, accounting for the transition to International Statistical Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis and procedure codes, in health encounter reporting on 10/1/2015. We selected women in Merative MarketScan commercial databases aged 15-49 years with pregnancy-related claims, and their infants, during 2008-2019. Pregnancies, pregnancy outcomes, and gestational ages were assigned using the constellation of service dates, code types, pregnancy outcomes, and linkage to infant records. We describe pregnancy outcomes and gestational ages, as well as maternal age, census region, and health plan type. In a sensitivity analysis, we compared our algorithm-assigned date of last menstrual period (LMP) to fertility procedure-based LMP (date of procedure + 14 days) among women with embryo transfer or insemination procedures. Among 5,812,699 identified pregnancies, most (77.9%) were livebirths, followed by spontaneous abortions (16.2%); 3,274,353 (72.2%) livebirths could be linked to infants. Most pregnancies were among women 25-34 years (59.1%), living in the South (39.1%) and Midwest (22.4%), with large employer-sponsored insurance (52.0%). Outcome distributions were similar across ICD-9 and ICD-10 eras, with some variation in gestational age distribution observed. Sensitivity analyses supported our algorithm's framework; algorithm- and fertility procedure-derived LMP estimates were within a week of each other (mean difference: -4 days [IQR: -13 to 6 days]; n = 107,870). We have developed an algorithm to identify pregnancies, their gestational age, and outcomes, across ICD-9 and ICD-10 eras using administrative data. This algorithm may be useful to reproductive health researchers investigating a broad range of pregnancy and infant outcomes. |
Perceived benefits and barriers of a COVID-19 test to stay program in a school district serving Black or African American people with low income, December 2021
Kamitani E , Holman EJ , Philpott D , Parasram VD , Ruth LJ , Onyeuku C , Carter B , Gwynn E , Beck TW , Regan K , Hagler LR , Clark A , Shelley G , Thomas ES . Public Health Rep 2023 333549231155472 OBJECTIVES: Quarantine after exposure to COVID-19 has resulted in substantial loss of in-person learning in schools from prekindergarten through grade 12. Test to Stay (TTS), a strategy that limits the spread of SARS-CoV-2 while prioritizing in-person learning, requires substantial investment in resources. The objective of this study was to assess the perceived benefits, barriers, and facilitators of implementing TTS in an urban school district in the Midwest serving primarily Black or African American people with low income. METHODS: In December 2021, we used a concurrent mixed-methods approach to understand perceived benefits, barriers, and facilitators of implementing TTS by combining quantitative analysis of telephone surveys conducted with parents (n = 124) and a qualitative inquiry involving key informants from the school district and local health department (n = 22). We analyzed quantitative data using descriptive statistics. We used thematic analysis to analyze qualitative data. RESULTS: Quantitative findings showed that parents supported TTS because it was convenient (n = 83, 97%) and effective (n = 82, 95%) in keeping students learning in person (n = 82, 95%) and preventing the spread of COVID-19 (n = 80, 93%). Qualitative interviews with informants found that having a clear protocol and assigning staff to specified tasks allowed for successful TTS implementation. However, insufficient staffing and testing resources, parent mistrust of testing, and lack of communication from schools were perceived barriers. CONCLUSION: The school community strongly supported TTS despite the many implementation challenges faced. This study emphasized the importance of ensuring resources for equitable implementation of COVID-19 prevention strategies and the critical role of communication. |
High rates of observed face mask use at Colorado universities align with students' opinions about masking and support the safety and viability of in-person higher education during the COVID-19 pandemic
Clark KC , Bailey MJ , Wasshuber S , Huntley R , Bjorkman KK , Bauer LC , Paige CL , Sawyer SL , Czarnik M , Riggs MA , Gutilla MJ , Alderete TL . BMC Public Health 2023 23 (1) 299 BACKGROUND: Over the course of the COVID-19 pandemic, colleges and universities have focused on creating policies, such as mask mandates, to minimize COVID-19 transmission both on their campuses and in the surrounding community. Adherence to and opinions about these policies remain largely unknown. METHODS: The Centers for Disease Control and Prevention (CDC) developed a cross-sectional study, the Mask Adherence and Surveillance at Colleges and Universities Project (MASCUP!), to objectively and inconspicuously measure rates of mask use at institutes of higher education via direct observation. From February 15 through April 11, 2021 the University of Colorado Boulder (CU, n = 2,808 observations) and Colorado State University Fort Collins (CSU, n = 3,225 observations) participated in MASCUP! along with 52 other institutes of higher education (n = 100,353 observations) spanning 21 states and the District of Columbia. Mask use was mandatory at both Colorado universities and student surveys were administered to assess student beliefs and attitudes. RESULTS: We found that 91.7%, 93.4%, and 90.8% of persons observed at indoor locations on campus wore a mask correctly at University of Colorado, Colorado State University, and across the 52 other schools, respectively. Student responses to questions about masking were in line with these observed rates of mask use where 92.9% of respondents at CU and 89.8% at CSU believe that wearing masks can protect the health of others. Both Colorado universities saw their largest surges in COVID-19 cases in the fall of 2020, with markedly lower case counts during the mask observation window in the spring of 2021. CONCLUSION: High levels of mask use at Colorado's two largest campuses aligned with rates observed at other institutes across the country. These high rates of use, coupled with positive student attitudes about mask use, demonstrate that masks were widely accepted and may have contributed to reduced COVID-19 case counts. This study supports an emerging body of literature substantiating masks as an effective, low-cost measure to reduce disease transmission and establishes masking (with proper education and promotion) as a viable tactic to reduce respiratory disease transmission on college campuses. |
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