Last data update: Mar 21, 2025. (Total: 48935 publications since 2009)
Records 1-30 (of 137 Records) |
Query Trace: Clarke K[original query] |
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Ratio of infections to COVID-19 cases and hospitalizations in the United States based on SARS-CoV-2 seroprevalence data, September 2021-February 2022
Deng Y , Kim Y , Bratcher A , Jones JM , Simuzingili M , Gundlapalli AV , Hagen MB , Iachan R , Clarke KEN . Open Forum Infect Dis 2025 12 (1) ofae719 ![]() BACKGROUND: Understanding the risk of hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can guide effective public health interventions and severity assessments. This study calculated infection-hospitalization ratios (IHRs) and infection-case ratios (ICRs) to understand the relationship between SARS-CoV-2 infections, cases, and hospitalizations among different age groups during periods of Delta and Omicron variant predominance. METHODS: After calculating antinucleocapsid SARS-CoV-2 antibody seroprevalence using residual commercial laboratory serum specimens, 2 ratios were computed: (1) IHRs using coronavirus disease 2019 hospitalization data and (2) ICRs using Centers for Disease Control and Prevention surveillance data. Ratios were calculated across age groups (0-17, 18-49, 50-69, and ≥70 years) for 2 time periods (September-December 2021 [Delta] and December 2021-February 2022 [Omicron]). RESULTS: Pediatric IHRs increased from 76.7 during Delta to 258.4 during Omicron. Adult IHRs ranged from 3.0 (≥70 years) to 21.6 (18-49 years) during Delta and from 10.0 (≥70 years) to 119.1 (18-49 years) during Omicron. The pediatric ICR was lower during the Delta period (2.7) compared with the Omicron period (3.7). Adult ICRs (Delta: 1.1 [18-49 years] to 2.1 [70+ years]; Omicron: 2.2 [>70+ years] to 2.9 [50-69 years]) were lower than pediatric ICRs during both time periods. CONCLUSIONS: All age groups exhibited a lower proportion of infections associated with hospitalization in the Omicron period than the Delta period; the proportion of infections associated with hospitalization increased with each older age group. A lower proportion of SARS-CoV-2 infections were associated with reported cases in the Omicron period than in the Delta period among all age groups. |
Anti-nucleocapsid SARS-CoV-2 antibody seroprevalence in previously infected persons with immunocompromising conditions-United States, 2020-2022
Bratcher A , Jones JM , Meyer WA 3rd , Waheed R , Yazgi H , Harris A , Gundlapalli AV , Clarke KEN . PLoS One 2025 20 (1) e0313620 People with immunocompromising conditions (IC) are at increased risk of severe COVID-19 and death. These individuals show weaker immunogenicity following vaccination than individuals without IC, yet immunogenicity after SARS-CoV-2 infection is poorly understood. To address this gap, the presence of infection-induced antibodies in sera following a positive COVID-19 test result was compared between patients with and without IC. A commercial laboratory provided patient data gathered during July 2020-February 2022 on COVID-19 viral test results and antibody assay results, which included infection-induced (anti-N) antibody presence. Participants were categorized into having or not having IC based on if there was an indicative diagnostic code on their health record for a five-year period prior to the study period. Anti-N presence in sera from people with a positive COVID-19 test result was compared by IC status for four post-infection periods: 14-90, 91-180, 181-365, and 365+ days. A longitudinal, logistic regression produced adjusted odds ratios comparing anti-N prevalence among specimens with and without associated IC, adjusted for age, sex, residence in a metro area, and social vulnerability index (SVI) tertile. Data included 17,025 anti-N test results from 14,690 patients, 1,424 (9.7%) of which had at least one IC on record. In an adjusted comparison to patients without IC, patients with any IC were 0.61 times as likely to have infection-induced antibodies (99% CI: 0.40-0.93), during the 14-90 days following infection. Similar patterns were found when comparing people with two specific types of IC to people without any IC: (1) solid malignancies and (2) other intrinsic immune conditions. These findings stress the importance of prevention measures for people with IC, such as additional vaccination doses and consistent mask use before and after a documented infection. |
Measles-rubella microarray patches phase III clinical trial framework: Proposal and considerations
Zehrung D , Innis BL , Suwantika AA , Ameri M , Biellik R , Birchall JC , Cravioto A , Jarrahian C , Fairlie L , Goodson JL , Kochhar S , Kretsinger K , Morgan C , Mvundura M , Rathi N , Clarke E , Mistilis JJ , Uwamwezi MC , Giersing B , Hasso-Agopsowicz M . Vaccines (Basel) 2024 12 (11) Background: The Measles-Rubella Microarray Patch (MR-MAP) is an important technology that is expected to reduce coverage and equity gaps for measles-containing vaccines (MCVs), reach zero-dose children, and contribute to elimination of measles and rubella. MR-MAPs are anticipated to be easier to deploy programmatically and could be delivered by lesser-trained health workers, thereby increasing immunization coverage. The most advanced MR-MAP has reached clinical proof-of-concept through a Phase I/II trial in the target population of infants and young children. The World Health Organization (WHO) and partners have developed the Phase III clinical trial framework for MR-MAPs presented in this article. Objectives and Methods: The purpose of such framework is to inform the considerations, design and approach for the pivotal clinical trial design, while considering the anticipated data requirements to inform regulatory approval, WHO prequalification, and policy decision. Results: The proposed Phase III trial would compare the immunogenicity and safety of an MR-MAP with MR vaccine delivered subcutaneously in 9- to 10-month-old infants. An analysis of non-inferiority (NI) of immunogenicity would occur six weeks after the first dose. Should regulatory agencies or policy makers require, a proportion of infants could receive a second dose of either the same or alternate MR vaccine presentation six months after the first dose, with those children returning six weeks after the second dose for a descriptive assessment of immunogenicity, and then followed up six months after the second dose for evaluation of safety and immunogenicity. It is anticipated that this proposed pivotal Phase III trial framework would generate the required clinical data for regulatory licensure and WHO prequalification (PQ) of MR-MAPs. However, the trial design would need to be reviewed and confirmed by a national regulatory authority (NRA) that will assess the product for regulatory licensure and the WHO PQ team. Additional research will likely be required to generate data on concomitant vaccine delivery, the safety and immunogenicity of MR-MAPs in other age groups such as children 1-5 years and infants younger than 9 months of age, and the impact of MR-MAPs on coverage and equity. Such studies could be conducted during or after clinical MR-MAP development. |
On alert for Ebola: public health risk assessment of travellers from Uganda to the U.S. during the 2022 outbreak
Fowler JJ , Preston LE , Gearhart SL , Figueroa A , LChristensen D , Mitchell C , Hernandez E , Grills AW , Morrison SM , Wilkinson M , Talib T , Marie Lavilla K , Watson T , Mitcham D , Nash R , Veguilla MAC , Hansen S , Cohen NJ , Nu Clarke SA , Smithson A , Shearer E , Pella DG , Morris JD , Meehan S , Aboukheir M , Adams K , Sunavala Z , Conley J , Abouattier M , Palo M , Pimentel LC , Berro A , Mainzer H , Byrkit R , Kim D , Katebi V , Alvarado-Ramy F , Roohi S , Wojno AE , Brown CM , Gertz AM . J Travel Med 2024 31 (5) BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers. |
Quantitative SARS-CoV-2 spike receptor-binding domain and neutralizing antibody titers in previously infected persons, United States, January 2021-February 2022
Bratcher A , Kao SY , Chun K , Petropoulos CJ , Gundlapalli AV , Jones J , Clarke KEN . Emerg Infect Dis 2024 30 (11) 2352-2361 ![]() We studied SARS-CoV-2 binding and neutralizing antibody titers among previously infected persons in the United States over time. We assayed SARS-CoV-2 spike protein receptor-binding domain and neutralizing antibody titers for a convenience sample of residual clinical serum specimens that had evidence of prior SARS-CoV-2 infection gathered during January 2021-February 2022. We correlated titers and examined them by age group (<18, 18-49, 50-64, and >65 years) across 4 different SARS-CoV-2 variant epochs. Among selected specimens, 30,967 had binding antibody titers and 744 had neutralizing titers available. Titers in specimens from children and adults correlated. In addition, mean binding antibody titers increased over time for all age groups, and mean neutralization titers increased over time for persons 16-49 and >65 years of age. Incorporating binding and neutralization antibody titers into infectious disease surveillance could provide a clearer picture of overall immunity and help target vaccination campaigns. |
CDC Program Evaluation Framework, 2024
Kidder DP , Fierro LA , Luna E , Salvaggio H , McWhorter A , Bowen SA , Murphy-Hoefer R , Thigpen S , Alexander D , Armstead TL , August E , Bruce D , Clarke SN , Davis C , Downes A , Gill S , House LD , Kerzner M , Kun K , Mumford K , Robin L , Schlueter D , Schooley M , Valverde E , Vo L , Williams D , Young K . MMWR Recomm Rep 2024 73 (6) 1-37 Program evaluation is a critical tool for understanding and improving organizational activities and systems. This report updates the 1999 CDC Framework for Program Evaluation in Public Health (CDC. Framework for program evaluation in public health. MMWR Recomm Rep 1999;48[No. RR-11];1-40) by integrating major advancements in the fields of evaluation and public health, lessons learned from practical applications of the original framework, and current Federal agency policies and practices. A practical, nonprescriptive tool, the updated 2024 framework is designed to summarize and organize essential elements of program evaluation, and can be applied at any level from individual programs to broader systems by novices and experts for planning and implementing an evaluation. Although many of the key aspects from the 1999 framework remain, certain key differences exist. For example, this updated framework also includes six steps that describe the general process of evaluation planning and implementation, but some content and step names have changed (e.g., the first step has been renamed Assess context). The standards for high-quality evaluation remain central to the framework, although they have been updated to the five Federal evaluation standards. The most substantial change from the 1999 framework is the addition of three cross-cutting actions that are core tenets to incorporate within each evaluation step: engage collaboratively, advance equity, and learn from and use insights. The 2024 framework provides a guide for designing and conducting evaluation across many topics within and outside of public health that anyone involved in program evaluation efforts can use alone or in conjunction with other evaluation approaches, tools, or methods to build evidence, understand programs, and refine evidence-based decision-making to improve all program outcomes. |
Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution
Pisanic N , Antar AAR , Hetrich MK , Demko ZO , Zhang X , Spicer K , Kruczynski KL , Detrick B , Clarke W , Knoll MD , Thomas DL , Dawood FS , Veguilla V , Karron RA , Manabe YC , Heaney CD . J Infect Dis 2024 BACKGROUND: High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government's Project NextGen and the Center for Epidemic Preparedness Innovations' goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration. METHODS: Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022. RESULTS: High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) post infection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to having COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 days (95% CI: 10-18) and recovered 9-10 days (95% CI: 6-14) earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms longer than four weeks was associated with lower anti-RBD SIgA 15-30 days after infection onset (p<0.001). CONCLUSION: Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines. |
School mask policies and SARS-CoV-2 seroprevalence among school-age children-United States, September to December 2021
Nycz E , Deng Y , Van Dyke ME , Bratcher A , Shi J , Iachan R , Berney K , Jones JM , Clarke KEN . Microbiol Spectr 2024 e0069124 During September to December 2021, school mask policies to mitigate SARS-CoV-2 transmission varied throughout the US. We compared infection-induced seroprevalence estimates and estimated seroconversion among children residing in areas with and without school mask requirements. We estimated infection-induced seroprevalence among children in three age groups (5-17, 5-11, and 12-17 years) in areas with and without school district mask requirements for two time points: September 1-30, 2021 and December 15, 2021 to January 14, 2022. Robust Poisson regression models estimated population seroconversion over the semester among initially seronegative children. Permutation tests assessed for significant differences in the estimated population seroconversion due to incident infections by school district mask policy. Residing in an area with no school mask requirement was associated with higher infection-induced seroprevalence among children aged 5-17 years (adjusted prevalence ratio [aPR] = 1.18, 95% confidence interval [CI]: 1.10, 1.26), and those aged 5-11 years (aPR) = 1.21, 95% CI: 1.10, 1.32) and those aged 12-17 years (aPR = 1.16, 95% CI: 1.07, 1.26), compared with areas requiring masks in school. Estimated population seroconversion during the semester was also significantly higher among children in districts without mask policies than those with school mask requirements among all age groups (5-17 years: 23.7% vs 18.1%, P < 0.001; 5-11 years: 6.4% vs 4.5%, P = 0.002;12-17 years: 27.2% vs 21.0%, P < 0.001). During the U.S. Fall 2021 semester, areas with school mask requirements had lower infection-induced seroprevalence and an estimated lower proportion of seroconversion due to incident infection among school-aged children compared with areas without school mask requirements; causality cannot necessarily be inferred from these associations. IMPORTANCE: During the U.S. Fall 2021 school semester, the estimated proportion of previously uninfected school-aged children who experienced a first infection with SARS-CoV-2 was lower in areas where public school district policies required masks for all staff and students compared with areas where the school districts had no mask requirements. Because children are more likely than adults to experience asymptomatic or mild SARS-CoV-2 infections, the presence of infection-induced antibodies is a more accurate measure of infection history than clinical testing. The proportion of children with these antibodies (i.e., seroprevalence) can improve our understanding of SARS-CoV-2 by detecting more infections and eliminating potential bias due to local testing and reporting practices. Enhanced robustness of surveillance for respiratory infections in children, including records of mitigation policies in communities and schools, as well as seroprevalence data, would establish a better evidence base for policy decisions and response measures during future respiratory outbreaks. |
Best practices and lessons learned from the public health disability specialists program: Addressing the needs of people with disabilities during COVID-19
Cree RA , Wray A , Evans A , Lyons S , Burrous H , Nilz M , Clarke C , Li J , Baio J . J Public Health Manag Pract 2024 CONTEXT: The Association of State and Territorial Health Officials (ASTHO) and the National Association of County and City Health Officials (NACCHO) applied funding issued by the US Centers for Disease Control and Prevention (CDC) to implement the Public Health Disability Specialists Program, part of a project to address the needs of people with disabilities during the COVID-19 pandemic. Disability specialists (subject matter experts) were embedded within state, territorial, and city/county health departments to help ensure disability inclusion in emergency planning, mitigation, and recovery efforts. OBJECTIVE: To evaluate the success of the Disability Specialists Program in improving emergency response planning, mitigation, and recovery efforts for people with disabilities within participating jurisdictions. DESIGN: Disability specialists worked with their assigned jurisdictions to conduct standardized baseline health department needs assessments to identify existing gaps and inform development and implementation of improvement plans. CDC, ASTHO, and NACCHO implemented a mixed methods framework to evaluate specialists' success. SETTING: State, territorial, and local health departments across 28 jurisdictions between January 2021 and July 2022. MAIN OUTCOME MEASURES: Average number of categories of gaps addressed and qualitative documentation of strategies, barriers, and promising practices. RESULTS: Specialists identified 1010 gaps (approximately 36 per jurisdiction) across eight needs assessment categories, most related to mitigation, recovery, resilience, and sustainability efforts (n = 213) and communication (n = 193). Specialists addressed an average of three categories of gaps identified; common focus areas included equitable COVID-19 vaccine distribution and accessible communications. Specialists commonly mentioned barriers related to limited health agency capacity (eg, resources) and community mistrust. Promising practices to address barriers included sharing best practices through peer-to-peer networks and building and strengthening partnerships between health departments and the disability community. CONCLUSIONS: Embedding disability specialists within state, territorial, and local health departments improved jurisdictional ability to meet evolving public health needs for the entire community, including people with disabilities. |
Comparison of SARS-CoV-2 seroprevalence estimates between commercial lab serum specimens and blood donor specimens, United States, September-December 2021
Kao SZ , Nycz E , Benoit TJ , Clarke KEN , Jones JM . Microbiol Spectr 2024 e0012324 We estimated monthly cross-sectional seroprevalence rates of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies to severe acute respiratory syndrome coronavirus 2 in two U.S. nationwide studies. The nationwide blood donor seroprevalence (NBDS) study included specimens from blood donors, while the nationwide commercial laboratory seroprevalence (NCLS) study included residual serum specimens tested in commercial laboratories for reasons unrelated to the assessment of coronavirus disease 2019 infection. In September-December 2021, specimens collected from both nationwide studies were tested for anti-N antibodies. In September-October 2021, specimens from both studies within a five-state area were tested for anti-S antibodies. We used raking methods to adjust all seroprevalence estimates by the population distribution of key demographics in included states. Seroprevalence estimates of each antibody type were compared across the two studies for specimens drawn in the same U.S. states during the same time period. Our analysis revealed that over a 4-month period, national NCLS monthly anti-N estimates were 0.5-1.9 percentage points higher than NBDS estimates. In contrast, across five states during a 2-month period, NBDS anti-S estimates were 7.6 and 8.2 percentage points higher than NCLS estimates. The observed differences in seroprevalence estimates between the NBDS and NCLS studies may be attributed to variations in the characteristics of the study sample populations, particularly with respect to health status, health behaviors, and vaccination status. These differences should be considered in the interpretation of seroprevalence study results based on blood donors or commercial lab residual specimens. IMPORTANCE: This study was the first systematic comparison between two nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) studies which estimated seroprevalence, or the proportion of the population with antibodies to the virus, using differing convenience sample populations. One study tested blood donor specimens; the other study tested specimens left over from clinical blood tests. The seroprevalence of anti-nucleocapsid and anti-spike antibodies was compared in the same states during the same months with statistical adjustments based on state demographics. Similar anti-nucleocapsid antibody seroprevalence estimates produced by two independent studies using differing convenience samples build confidence in the generalizability of their anti-nucleocapsid findings. Due to high blood donor vaccine rates, blood donor SARS-CoV-2 anti-spike antibody estimates might overestimate general population seroprevalence, an important consideration for interpreting national seroprevalence study results. Furthermore, because laboratory residuals and blood donations are two common sources of specimens for seroprevalence studies, study findings may be informative for other respiratory virus seroepidemiology studies. |
Data equity as a building block for health equity: Improving surveillance data for people with disabilities, with substance use disorder, or experiencing homelessness, United States
Meehan AA , Flemming SS , Lucas S , Schoonveld M , Matjasko JL , Ward ME , Clarke KEN . Public Health Rep 2024 333549241245624 OBJECTIVES: People with disabilities, people experiencing homelessness, and people who have substance use disorders face unique health challenges. Gaps in public health surveillance data limit the identification of public health needs of these groups and data-driven action. This study aimed to identify current practices, challenges, and opportunities for collecting and reporting COVID-19 surveillance data for these populations. METHODS: We used a rapid qualitative assessment to explore COVID-19 surveillance capacities. From July through October 2021, we virtually interviewed key informants from the Centers for Disease Control and Prevention, state and local health departments, and health care providers across the United States. We thematically analyzed and contextualized interview notes, peer-reviewed articles, and participant documents using a literature review. RESULTS: We identified themes centered on foundational structural and systems issues that hinder actionable surveillance data for these and other populations that are disproportionately affected by multiple health conditions. Qualitative data analysis of 61 interviews elucidated 4 primary challenges: definitions and policies, resources, data systems, and articulation of the purpose of data collection to these groups. Participants noted the use of multisector partnerships, automated data collection and integration, and data scorecards to circumvent challenges. CONCLUSIONS: This study highlights the need for multisector, systematic improvements in surveillance data collection and reporting to advance health equity. Improvements must be buttressed with adequate investment in data infrastructure and promoted through clear communication of how data are used to protect health. |
Who gets sick from COVID-19? Sociodemographic correlates of severe adult health outcomes during Alpha- and Delta-variant predominant periods, 9/2020-11/2021
Wei SC , Freeman D , Himschoot A , Clarke KEN , Van Dyke ME , Adjemian J , Ahmad FB , Benoit TJ , Berney K , Gundlapalli AV , Hall AJ , Havers F , Henley SJ , Hilton C , Johns D , Opsomer JD , Pham HT , Stuckey MJ , Taylor CA , Jones JM . J Infect Dis 2024 229 (1) 122-132 ![]() BACKGROUND: Because COVID-19 case data do not capture most SARS-CoV-2 infections, the actual risk of severe disease and death per infection is unknown. Integrating sociodemographic data into analysis can show consequential health disparities. METHODS: Data were merged from September 2020 to November 2021 from 6 national surveillance systems in matched geographic areas and analyzed to estimate numbers of COVID-19-associated cases, emergency department visits, and deaths per 100 000 infections. Relative risks of outcomes per infection were compared by sociodemographic factors in a data set including 1490 counties from 50 states and the District of Columbia, covering 71% of the US population. RESULTS: Per infection with SARS-CoV-2, COVID-19-related morbidity and mortality were higher among non-Hispanic American Indian and Alaska Native persons, non-Hispanic Black persons, and Hispanic or Latino persons vs non-Hispanic White persons; males vs females; older people vs younger; residents in more socially vulnerable counties vs less; those in large central metro areas vs rural; and people in the South vs the Northeast. DISCUSSION: Meaningful disparities in COVID-19 morbidity and mortality per infection were associated with sociodemography and geography. Addressing these disparities could have helped prevent the loss of tens of thousands of lives. |
A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial
Adigweme I , Yisa M , Ooko M , Akpalu E , Bruce A , Donkor S , Jarju LB , Danso B , Mendy A , Jeffries D , Segonds-Pichon A , Njie A , Crooke S , El-Badry E , Johnstone H , Royals M , Goodson JL , Prausnitz MR , McAllister DV , Rota PA , Henry S , Clarke E . Lancet 2024 BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation. |
Investigation of presumptive HIV transmission associated with receipt of platelet-rich plasma microneedling facials at a spa among former spa clients - New Mexico, 2018-2023
Stadelman-Behar AM , Gehre MN , Atallah L , Clarke T , Leonso AA , Jojola F , Zheng H , Jia H , Lyss SB , Switzer WM , Grytdal SP , Durham M , Salas NM , Sievers M , Smelser C . MMWR Morb Mortal Wkly Rep 2024 73 (16) 372-376 ![]() ![]() HIV transmitted through cosmetic injection services via contaminated blood has not been previously documented. During summer 2018, the New Mexico Department of Health (NMDOH) was notified of a diagnosis of HIV infection in a woman with no known HIV risk factors who reported exposure to needles from cosmetic platelet-rich plasma microneedling facials (vampire facials) received at a spa in spring 2018. An investigation of the spa's services began in summer 2018, and NMDOH and CDC identified four former spa clients, and one sexual partner of a spa client, all of whom received HIV infection diagnoses during 2018-2023, despite low reported behavioral risks associated with HIV acquisition. Nucleotide sequence analysis revealed highly similar HIV strains among all cases. Although transmission of HIV via unsterile injection practices is a known risk, determining novel routes of HIV transmission among persons with no known HIV risk factors is important. This investigation identified an HIV cluster associated with receipt of cosmetic injection services at an unlicensed facility that did not follow recommended infection control procedures or maintain client records. Requiring adequate infection control practices and maintenance of client records at spa facilities offering cosmetic injection services can help prevent the transmission of HIV and other bloodborne pathogens and ensure adequate traceback and notification in the event of adverse clinical outcomes, respectively. |
Recommendations for use of p16/Ki67 dual stain for management of individuals testing positive for human papillomavirus
Clarke MA , Wentzensen N , Perkins RB , Garcia F , Arrindell D , Chelmow D , Cheung LC , Darragh TM , Egemen D , Guido R , Huh W , Locke A , Lorey TS , Nayar R , Risley C , Saslow D , Smith RA , Unger ER , Massad LS . J Low Genit Tract Dis 2024 ![]() OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations. |
Enduring consensus guidelines for cervical cancer screening and management: Introduction to the scope and process
Wentzensen N , Garcia F , Clarke MA , Massad LS , Cheung LC , Egemen D , Guido R , Huh W , Saslow D , Smith RA , Unger ER , Perkins RB . J Low Genit Tract Dis 2024 OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. METHODS AND RESULTS: The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. CONCLUSIONS: The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available. |
Association between social vulnerability and SARS-CoV-2 seroprevalence in specimens collected from commercial laboratories, United States, September 2021-February 2022
Benoit TJ , Kim Y , Deng Y , Li Z , Harding L , Wiegand R , Deng X , Jones JM , Ronaldo I , Clarke KEN . Public Health Rep 2024 333549231223140 OBJECTIVE: We conducted a national US study of SARS-CoV-2 seroprevalence by Social Vulnerability Index (SVI) that included pediatric data and compared the Delta and Omicron periods during the COVID-19 pandemic. The objective of the current study was to assess the association between SVI and seroprevalence of infection-induced SARS-CoV-2 antibodies by period (Delta vs Omicron) and age group. METHODS: We used results of infection-induced SARS-CoV-2 antibody assays of clinical sera specimens (N = 406 469) from 50 US states from September 2021 through February 2022 to estimate seroprevalence overall and by county SVI tercile. Bivariate analyses and multilevel logistic regression models assessed the association of seropositivity with SVI and its themes by age group (0-17, ≥18 y) and period (Delta: September-November 2021; Omicron: December 2021-February 2022). RESULTS: Aggregate infection-induced SARS-CoV-2 antibody seroprevalence increased at all 3 SVI levels; it ranged from 25.8% to 33.5% in September 2021 and from 53.1% to 63.5% in February 2022. Of the 4 SVI themes, socioeconomic status had the strongest association with seroprevalence. During the Delta period, we found significantly more infections per reported case among people living in a county with high SVI (odds ratio [OR] = 2.76; 95% CI, 2.31-3.21) than in a county with low SVI (OR = 1.65; 95% CI, 1.33-1.97); we found no significant difference during the Omicron period. Otherwise, findings were consistent across subanalyses by age group and period. CONCLUSIONS: Among both children and adults, and during both the Delta and Omicron periods, counties with high SVI had significantly higher SARS-CoV-2 antibody seroprevalence than counties with low SVI did. These disparities reinforce SVI's value in identifying communities that need tailored prevention efforts during public health emergencies and resources to recover from their effects. |
A qualitative assessment of cleaning and hand hygiene practices at shelters serving people experiencing homelessness during the COVID-19 pandemic, Atlanta, GA - May-June, 2020
Besrat BN , Mosites E , Montgomery MP , Garcia-Williams AG , Trautner E , Clarke KEN , Marshall B , Vassell C , Rutt C , Jones SL . BMC Public Health 2024 24 (1) 247 BACKGROUND: Cleaning practices and hand hygiene are important behaviors to prevent and control the spread of infectious disease, especially in congregate settings. This project explored hygiene- and cleaning-related experiences in shelters serving people experiencing homelessness (PEH) during May-June 2020 of the COVID-19 pandemic. METHODS: We conducted qualitative, in-depth interviews by phone with 22 staff from six shelters in Atlanta, Georgia. The interview guide included questions about cleaning routines, cleaning barriers and facilitators, cleaning promotion, hand hygiene promotion, and hand hygiene barriers and facilitators. We analyzed interview transcripts using thematic analysis. RESULTS: Multiple individuals, such as shelter individuals (clients), volunteers, and staff, played a role in shelter cleaning. Staff reported engaging in frequent hand hygiene and cleaning practices. Barriers to cleaning included staffing shortages and access to cleaning supplies. Staff reported barriers (e.g., differing perceptions of cleanliness) for clients who were often involved in cleaning activities. Barriers to hand hygiene included limited time to wash hands, forgetting, and inconvenient handwashing facilities. Specific guidance about when and how to clean, and what supplies to use, were requested. CONCLUSION: During the early months of the COVID-19 pandemic, shelters serving PEH in the Atlanta-metro area needed resources and support to ensure sufficient staffing and supplies for cleaning activities. As part of future pandemic planning and outbreak prevention efforts, shelters serving PEH could benefit from specific guidance and training materials on cleaning and hand hygiene practices. |
Tolerability, safety, and immunogenicity of the novel oral polio vaccine type 2 in children aged 6 weeks to 59 months in an outbreak response campaign in The Gambia: an observational cohort study
Bashorun AO , Kotei L , Jawla O , Jallow AF , Saidy AJ , Kinteh MA , Kujabi A , Jobarteh T , Kanu FJ , Donkor SA , Ezeani E , Fofana S , Njie M , Ceesay L , Jafri B , Williams A , Jeffries D , Kotanmi B , Mainou BA , Ooko M , Clarke E . Lancet Infect Dis 2024 BACKGROUND: Novel oral polio vaccine type 2 (nOPV2) has been used to interrupt circulating vaccine-derived poliovirus type 2 outbreaks following its WHO emergency use listing. This study reports data on the safety and immunogenicity of nOPV2 over two rounds of a campaign in The Gambia. METHODS: This observational cohort study collected baseline symptoms (vomiting, diarrhoea, irritability, reduced feeding, and reduced activity) and axillary temperature from children aged 6 weeks to 59 months in The Gambia before a series of two rounds of a nOPV2 campaign that took place on Nov 20-26, 2021, and March 19-22, 2022. Serum and stool samples were collected from a subset of the participants. The same symptoms were re-assessed during the week following each dose of nOPV2. Stool samples were collected on days 7 and 28, and serum was collected on day 28 following each dose. Adverse events, including adverse events of special interest, were documented for 28 days after each campaign round. Serum neutralising antibodies were measured by microneutralisation assay, and stool poliovirus excretion was measured by real-time RT-PCR. FINDINGS: Of the 5635 children eligible for the study, 5504 (97·7%) received at least one dose of nOPV2. There was no increase in axillary temperature or in any of the baseline symptoms following either rounds of the campaigns. There were no adverse events of special interest and no other safety signals of concern. Poliovirus type 2 seroconversion rates were 70% (95% CI 62 to 78; 87 of 124 children) following one dose of nOPV2 and 91% (85 to 95; 113 of 124 children) following two doses. Poliovirus excretion on day 7 was lower after the second round (162 of 459 samples; 35·3%, 95% CI 31·1 to 39·8) than after the first round (292 of 658 samples; 44·4%, 40·6 to 48·2) of the campaign (difference -9·1%; 95% CI -14·8 to -3·3), showing the induction of mucosal immunity. INTERPRETATION: In a campaign in west Africa, nOPV2 was well tolerated and safe. High rates of seroconversion and evidence of mucosal immunity support the licensure and WHO prequalification of this vaccine. FUNDING: Bill & Melinda Gates Foundation. |
Considerations for defining homelessness in public health data collection
Meehan AA , Waddell CJ , Marx GE , Clarke KEN , Bratcher A , Montgomery MP , Marcus R , Ramirez V , Mosites E . Public Health Rep 2023 333549231215850 Public health problems cannot be addressed without timely and accurate data. However, data that provide insight into populations that may be at disproportionate risk for disease, including people experiencing homelessness, are insufficiently captured. Although the associations between homelessness and disease have been well documented,1-6 data on housing status are not universally or consistently collected in routine public health data.7 Improving collection of data on housing status in public health data collection efforts is necessary to address health disparities among people experiencing homelessness and advance health equity research and practice. | Collecting data related to homelessness and disease is complicated for several reasons, but one of the most salient reasons is that defining homelessness is challenging. Several federal agencies use their own definitions to identify people who might be eligible for assistance programs, creating confusion about which definition should be used for public health purposes. In addition, definitions of homelessness at federal agencies have changed over time, further complicating the collection of homelessness data. The US Department of Housing and Urban Development (HUD) defines homelessness as lacking a fixed, regular, and adequate nighttime residence8; this definition includes both people with a primary nighttime residence of a public or private place not meant for human habitation (eg, cars, parks, public spaces, abandoned buildings) and people residing in temporary shelters (eg, emergency homeless shelter, transitional housing). The US Department of Education (DOE) uses a broader lens, defining homelessness to include school-aged children whose housing situation meets the HUD criteria for homelessness while also including those who share housing with other people by doubling up or couch surfing; those who live in motels, hotels, or trailer parks; and those who are abandoned at hospitals.9 |
Racial, ethnic, sex, and age differences in COVID-19 cases, hospitalizations, and deaths among incarcerated people and staff in correctional facilities in six jurisdictions, United States, March-July 2020
D'Inverno AS , Myles RL , Jamison CR , Williams SP , Hagan LM , Handanagic S , Lambert LA , Clarke KEN , Allen J , Beard O , Dusseau C , Feldman R , Huebsch R , Hutchinson J , Kall D , King-Mohr J , Long M , McClure ES , Meddaugh P , Pontones P , Rose J , Sredl M , VonBank B , Zipprich J . J Racial Ethn Health Disparities 2023 OBJECTIVES: To examine disparities by sex, age group, and race and ethnicity in COVID-19 confirmed cases, hospitalizations, and deaths among incarcerated people and staff in correctional facilities. METHODS: Six U.S. jurisdictions reported data on COVID-19 confirmed cases, hospitalizations, and deaths stratified by sex, age group, and race and ethnicity for incarcerated people and staff in correctional facilities during March 1- July 31, 2020. We calculated incidence rates and rate ratios (RR) and absolute rate differences (RD) by sex, age group, and race and ethnicity, and made comparisons to the U.S. general population. RESULTS: Compared with the U.S. general population, incarcerated people and staff had higher COVID-19 case incidence (RR = 14.1, 95% CI = 13.9-14.3; RD = 6,692.2, CI = 6,598.8-6,785.5; RR = 6.0, CI = 5.7-6.3; RD = 2523.0, CI = 2368.1-2677.9, respectively); incarcerated people also had higher rates of COVID-19-related deaths (RR = 1.6, CI = 1.4-1.9; RD = 23.6, CI = 14.9-32.2). Rates of COVID-19 cases, hospitalizations, and deaths among incarcerated people and corrections staff differed by sex, age group, and race and ethnicity. The COVID-19 hospitalization (RR = 0.9, CI = 0.8-1.0; RD = -48.0, CI = -79.1- -16.8) and death rates (RR = 0.8, CI = 0.6-1.0; RD = -11.8, CI = -23.5- -0.1) for Black incarcerated people were lower than those for Black people in the general population. COVID-19 case incidence, hospitalizations, and deaths were higher among older incarcerated people, but not among staff. CONCLUSIONS: With a few exceptions, living or working in a correctional setting was associated with higher risk of COVID-19 infection and resulted in worse health outcomes compared with the general population; however, Black incarcerated people fared better than their U.S. general population counterparts. |
A randomized controlled trial of antibody response to 2019-20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults (preprint)
Williams KV , Zhai B , Alcorn JF , Patricia Nowalk M , Levine MZ , Kim SS , Flannery B , Moehling Geffel K , Jaber Merranko A , Nagg JP , Collins M , Susick M , Clarke KS , Zimmerman RK , Martin JM . medRxiv 2021 2021.09.02.21263043 Background Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children and young adult HAI titers against the 2019-2020 LAIV4 and ccIIV4.Methods Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n =100) or LAIV4 (n=98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers.Results GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p<0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p<0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p<0.05) than cell-grown GMTs [ccIIV4 day 28: egg=205 (95% CI: 178-237); cell=136 (95% CI:113-165); LAIV4 day 28: egg=96 (95% CI: 83-112); cell=63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR.Conclusion The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. For both vaccines, the A/H3N2 cell-grown antigen levels were lower than egg-grown, but the GMFR for cell-grown and egg-grown did not differ significantly within vaccine type.Clinical Trials No NCT03982069Competing Interest StatementConflict of Interest: RKZ has received funding by Sanofi for an unrelated study. MPN has research funding from Merck & Co., Inc. for an unrelated study. JMM has received funding from Merck, Sharp and Dohme for an unrelated study.Clinical TrialClinical Trials No.: NCT03982069Funding StatementThis work was supported by the Centers for Disease Control and Prevention (CDC) [5U01IP001035] and by National Institutes of Health (NIH) [UL1TR001857], [KL2 TR001856], and/or [TL1 TR001858]. This work represents the views of the authors and not the CDC or NIH. Pennsylvania Statewide Immunization Information System (PA-SIIS) vaccine registry was used to verify vaccination status. These data were supplied in part by the Bureau of Health Statistics & Registries, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. REDCap and the Department of Biomedical Informatics grant support (Clinical and Translational Sciences Institute at the University of Pittsburgh Grant Number UL1-TR-001857). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Pittsburgh. Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Institutional Review Boards at the University of Pittsburgh and the Centers for Disease Control and Prevention (CDC) approved this study. Written informed consent and assent, where appropriate, were obtained from all participants and/or their parents/legal guardians prior to beginning study procedures.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 expla ning 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 can be made available upon request.HAIhemagglutination inhibition assayIIVinactivated influenza vaccineccIIV4cell-culture-based inactivated influenza vaccine quadrivalentLAIV4Egg-based live attenuated influenza vaccine quadrivalentEMRElectronic medical recordRDEReceptor-destroying enzymePBSPhosphate-buffered salineCDCCenters for Disease Control and PreventionFDAFood and Drug AdministrationGMTGeometric mean titersGMFRGeometric mean fold riseACIPAdvisory Committee on Immunization PracticePA-SIISPennsylvania Statewide Immunization Information System |
Methods for Estimation of SARS-CoV-2 Seroprevalence and Reported COVID-19 Cases in U.S. Children, August 2020—May 2021 (preprint)
Couture A , Lyons BC , Mehrotra ML , Sosa L , Ezike N , Ahmed FS , Brown CM , Yendell S , Azzam IA , Katić BJ , Cope A , Dickerson K , Stone J , Traxler LB , Dunn JR , Davis LB , Reed C , Clarke KEN , Flannery B , Charles MD . medRxiv 2021 2021.09.26.21263756 Background and Objectives Case-based surveillance of pediatric COVID-19 cases underestimates the prevalence of SARS-CoV-2 infections among children and adolescents. Our objectives were to: 1) estimate monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years and 2) calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 14 U.S. states.Methods Using data from commercial laboratory seroprevalence surveys, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years from August 2020 through May 2021. Seroprevalence estimates were based on SARS-CoV-2 anti-nucleocapsid immunoassays from February to May 2021. We compared estimated numbers of children infected with SARS-CoV-2 by May 2021 to cumulative incidence of confirmed and probable COVID-19 cases from case-based surveillance, and calculated infection: case ratios by state and type of anti-SARS-CoV-2 nucleocapsid immunoassay used for seroprevalence testing.Results Analyses included 67,321 serum specimens tested for SARS-CoV-2 antibodies among children in 14 U.S. states. Estimated ratios of SARS-CoV-2 infections to reported confirmed and probable COVID-19 cases among children and adolescents varied by state and type of immunoassay, ranging from 0.8-13.3 in May 2021.Conclusions Through May 2021, the majority of children in selected states did not have detectable SARS-CoV-2 nucleocapsid antibodies. Case-based surveillance underestimated the number of children infected with SARS-CoV-2, however the predicted extent of the underestimate varied by state, immunoassay, and over time. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFunding for this work was supported by CDC (Atlanta, Georgia).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 reviewed by Centers for Disease Control and Prevention and determined to be consistent with non human participant research activity. Informed consent was waived, as data were deidentified. 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.YesDeidentified individual participant data will not be made available.CDCCenters of Disease Control and PreventionMIS-CMultisystem inflammatory syndrome in childrenEUAEmergency Use AuthorizationFDAU.S. Food and Drug AdministrationACIPAdvisory Committee on Immunizations PracticesNNucleocapsidSSpikeIgImmunoglobulinCIConfidence intervals |
Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci (preprint)
Azarian T , Mitchell PK , Georgieva M , Thompson CM , Ghouila A , Pollard AJ , von Gottberg A , du Plessis M , Antonio M , Kwambana-Adams BA , Clarke SC , Everett D , Cornick J , Sadowy E , Hryniewicz W , Skoczynska A , Moisi JC , McGee L , Beall B , Metcalf BJ , Breiman RF , Ho PL , Reid R , O'Brien KL , Gladstone RA , Bentley SD , Hanage WP . bioRxiv 2018 314880 ![]() Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the United States, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3–31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identify a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939–1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.Author Summary Streptococcus pneumoniae is a leading cause of bacterial pneumoniae, meningitis, and otitis media. Despite inclusion in the most recent pneumococcal conjugate vaccine, PCV13, serotype 3 remains epidemiologically important globally. We investigated the persistence of serotype 3 using whole-genome sequencing data form 301 isolates collected among 24 countries from 1993–2014. Through phylogenetic analysis, we identified three distinct lineages within a single clonal complex, CC180, and found one has recently emerged and grown in prevalence. We then compared genomic difference among lineages as well as variations in pneumococcal vaccine use among sampled countries. We found that the recently emerged lineage, termed Clade II, has a higher prevalence of antibiotic resistance compared to other lineages, diverse surface protein antigens, and a higher rate of recombination, a process by which bacteria can uptake and incorporate genetic material from its surroundings. Differences in vaccine use among sampled countries did not appear to be associated with the emergence of Clade II. We highlight the need to routine, representative sampling of bacterial isolates from diverse geographic areas and show the utility of genomic data in resolving epidemiological differences within a pathogen population. |
SARS-CoV-2 convalescent sera binding and neutralizing antibody concentrations compared with COVID-19 vaccine efficacy estimates against symptomatic infection (preprint)
Schuh AJ , Satheshkumar PS , Dietz S , Bull-Otterson L , Charles M , Edens C , Jones JM , Bajema KL , Clarke KEN , McDonald LC , Patel S , Cuffe K , Thornburg NJ , Schiffer J , Chun K , Bastidas M , Fernando M , Petropoulos CJ , Wrin T , Cai S , Adcock D , Sesok-Pizzini D , Letovsky S , Fry AM , Hall AJ , Gundlapalli AV . medRxiv 2021 26 Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, ~88% of neutralizing and ~63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; ~30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 - February 2022 (preprint)
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Geffel KM , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M , Arroliga A , Beeram M , Dunnigan K , Ettlinger J , Graves A , Hoffman E , Jatla M , McKillop A , Murthy K , Mutnal M , Priest E , Raiyani C , Rao A , Requenez L , Settele N , Smith M , Stone K , Thomas J , Volz M , Walker K , Zayed M , Annan E , Daley P , Kniss K , Merced-Morales A , Ayala E , Amundsen B , Aragones M , Calderon R , Hong V , Jimenez G , Kim J , Ku J , Lewin B , McDaniel A , Reyes A , Shaw S , Takhar H , Torres A , Burganowski R , Kiniry E , Moser KA , Nguyen M , Park S , Wellwood S , Wickersham B , Alvarado-Batres J , Benz S , Berger H , Bissonnette A , Blake J , Boese K , Botten E , Boyer J , Braun M , Breu B , Burbey G , Cravillion C , Delgadillo C , Donnerbauer A , Dziedzic T , Eddy J , Edgren H , Ermeling A , Ewert K , Fehrenbach C , Fernandez R , Frome W , Guzinski S , Heeren L , Herda D , Hertel M , Heuer G , Higdon E , Ivacic L , Jepsen L , Kaiser S , Karl J , Keffer B , King J , Koepel TK , Kohl S , Kohn S , Kohnhorst D , Kronholm E , Le T , Lemieux A , Marcis C , Maronde M , McCready I , McGreevey K , Meece J , Mehta N , Miesbauer D , Moon V , Moran J , Nikolai C , Olson B , Olstadt J , Ott L , Pan N , Pike C , Polacek D , Presson M , Price N , Rayburn C , Reardon C , Rotar M , Rottscheit C , Salzwedel J , Saucedo J , Scheffen K , Schug C , Seyfert K , Shrestha R , Slenczka A , Stefanski E , Strupp M , Tichenor M , Watkins L , Zachow A , Zimmerman B , Bauer S , Beney K , Cheng CK , Faraj N , Getz A , Grissom M , Groesbeck M , Harrison S , Henson K , Jermanus K , Johnson E , Kaniclides A , Kimberly A , Lamerato LE , Lauring A , Lehmann-Wandell R , McSpadden EJ , Nabors L , Truscon R , Balasubramani GK , Bear T , Bobeck J , Bowser E , Clarke K , Clarke LG , Dauer K , Deluca C , Dierks B , Haynes L , Hickey R , Johnson M , Jonsson A , Luosang N , McKown L , Peterson A , Phaturos D , Rectenwald A , Sax TM , Stiegler M , Susick M , Suyama J , Taylor L , Walters S , Weissman A , Williams JV , Blair M , Carter J , Chappell J , Copen E , Denney M , Graes K , Halasa N , Lindsell C , Liu Z , Longmire S , McHenry R , Short L , Tan HN , Vargas D , Wrenn J , Wyatt D , Zhu Y . medRxiv 2022 10 Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
A randomized controlled trial to compare immunogenicity to cell-based versus live-attenuated influenza vaccines in children
Williams KV , Li ZN , Zhai B , Alcorn JF , Nowalk MP , Levine MZ , Kim SS , Flannery B , Moehling Geffel K , Merranko AJ , Collins M , Susick M , Clarke KS , Zimmerman RK , Martin JM . J Pediatric Infect Dis Soc 2023 12 (6) 342-352 BACKGROUND: Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. METHODS: Participants ages 4-21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. RESULTS: The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. CONCLUSIONS: Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. CLINICAL TRIALS NO: NCT03982069. |
Analysis of metapopulation models of the transmission of SARS-CoV-2 in the United States
Vo M , Feng Z , Glasser JW , Clarke KEN , Jones JN . J Math Biol 2023 87 (2) 24 During the COVID-19 pandemic, renewal equation estimates of time-varying effective reproduction numbers were useful to policymakers in evaluating the need for and impact of mitigation measures. Our objective here is to illustrate the utility of mechanistic expressions for the basic and effective (or intrinsic and realized) reproduction numbers, [Formula: see text] and related quantities derived from a Susceptible-Exposed-Infectious-Removed (SEIR) model including features of COVID-19 that might affect transmission of SARS-CoV-2, including asymptomatic, pre-symptomatic, and symptomatic infections, with which people may be hospitalized. Expressions from homogeneous host population models can be analyzed to determine the effort needed to reduce [Formula: see text] from [Formula: see text] to 1 and contributions of modeled mitigation measures. Our model is stratified by age, 0-4, 5-9, …, 75+ years, and location, the 50 states plus District of Columbia. Expressions from such heterogeneous host population models include subpopulation reproduction numbers, contributions from the above-mentioned infectious states, metapopulation numbers, subpopulation contributions, and equilibrium prevalence. While the population-immunity at which [Formula: see text] has captured the popular imagination, the metapopulation [Formula: see text] could be attained in an infinite number of ways even if only one intervention (e.g., vaccination) were capable of reducing [Formula: see text] However, gradients of expressions derived from heterogeneous host population models,[Formula: see text] can be evaluated to identify optimal allocations of limited resources among subpopulations. We illustrate the utility of such analytical results by simulating two hypothetical vaccination strategies, one uniform and other indicated by [Formula: see text] as well as the actual program estimated from one of the CDC's nationwide seroprevalence surveys conducted from mid-summer 2020 through the end of 2021. |
Innovative approaches to improve COVID-19 case investigation and contact tracing among refugees, immigrants, and migrants: Lessons learned from a newly established National Resource Center
Mann EM , Weinberg M , Dawson-Hahn E , Clarke SK , Olmsted M , Bertelsen N , Arun R , Keaveney M , Miko S , Kircher A , Pendleton AE , Hendel-Paterson B , Prasad S , Stauffer WM . J Immigr Minor Health 2023 1-9 Effective COVID-19 case investigation and contact tracing (CICT) among refugee, immigrant, and migrant (RIM) communities requires innovative approaches to address linguistic, cultural and community specific preferences. The National Resource Center for Refugees, Immigrants, and Migrants (NRC-RIM) is a CDC-funded initiative to support state and local health departments with COVID-19 response among RIM communities, including CICT. This note from the field will describe NRC-RIM and initial outcomes and lessons learned, including the use of human-centered design to develop health messaging around COVID-19 CICT; training developed for case investigators, contact tracers, and other public health professionals working with RIM community members; and promising practices and other resources related to COVID-19 CICT among RIM communities that have been implemented by health departments, health systems, or community-based organizations. |
Reaching the First 90: Improving Inpatient Pediatric Provider-Initiated HIV Testing and Counseling Using a Quality Improvement Collaborative Strategy in Tanzania
Dougherty G , Panya M , Madevu-Matson C , Anyalechi GE , Clarke K , Fayorsey R , Kamonga M , Kimambo S , Lutkam D , Mugisha V , Mtiro H , Msuke S , Ramadhani A , Sipemba J , Urasa P , Rabkin M . J Assoc Nurses AIDS Care 2019 30 (6) 682-690 Although the United Republic of Tanzania has made remarkable progress in scaling up HIV services, substantial gaps in pediatric coverage remain (Joint United Nations Programme on HIV/AIDS, 2013). Tanzania is among the countries with the world's lowest pediatric antiretroviral therapy coverage (Joint United Nations Programme on HIV/AIDS, 2013), and the Ministry of Health (MOH), Community, Development, Gender, Elderly and Children has prioritized expanding access to HIV testing, care, and treatment for children (United Republic of Tanzania Ministry of Health and Social Welfare, 2012). | | Improving the identification of children living with HIV is a critical first step to expanding treatment coverage. In countries with generalized HIV epidemics, ill children presenting to health facilities have a higher HIV prevalence than the general pediatric population (Cohn, Whitehouse, Tuttle, Lueck, & Tran, 2016; Kankasa et al., 2009; Preidis, 2013; Wagner et al., 2015). Offering routine opt-out HIV testing to at-risk pediatric subpopulations (those presenting to health care with signs of illness or for admission, malnutrition, or tuberculosis treatment) is a high-yield identification strategy (Mutanga et al., 2012). Because these children and their caregivers are actively seeking health services and are easy to reach, they present a unique opportunity to identify those most in need of HIV care and to initiate treatment rapidly. |
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