Previously established World Health Organization (WHO) International Standards (IS) for anti-HPV16 and HPV18 antibodies are used to harmonize results across human papillomavirus (HPV) serology assays. Here, we present an international collaborative study to establish ISs for antibodies against HPV6 (NIBSC code 19/298), HPV11 (20/174), HPV31 (20/176), HPV33 (19/290), HPV45 (20/178), HPV52 (19/296) and HPV58 (19/300). The candidate standards were prepared using sera from naturally infected individuals. Each candidate was shown to be monospecific for reactivity against its indicated HPV type except for the HPV11 candidate, which was also reactive against other types. Expression of antibody levels relative to the relevant candidate IS reduced inter-laboratory variation allowing greater comparability between laboratories. Based on these results, the WHO Expert Committee on Biological Standardization established each of the 7 candidates as the 1st IS for antiserum to its indicated HPV type for use in the standardization of HPV pseudovirion-based neutralization and antibody-binding assays.

Given the need to provide clear communication to diverse audiences in the United States during public health emergencies, this assessment of images in COVID-19 communication materials identified ways to improve visual communication design. Qualitative interviews were conducted with 74 participants from various racial and ethnic backgrounds to gauge the clarity of images without associated text used in two infographics. Most images were understood by participants, but for each image at least some participants had an interpretation different from intended or only captured a portion of the message. Some images were interpreted by most or all participants as representing something other than intended. Participant recommendations were used to develop seven practical ways to improve image clarity: realistic graphics, exaggerated body position and actions, details to show image context and background, icons to encourage or discourage actions, symbols to show movement, consistency in recommended behavior in each image, and closely matching image to associated text. These elements can be applied in combination with existing health equity guiding principles for creating visual communication products before testing and validating products with intended audiences of different sociodemographic and cultural background to ensure appropriateness and clarity of images.

BACKGROUND: There is limited evidence on COVID-19 vaccination uptake among people living with HIV (PLHIV) and health care workers (HCWs), with the current evidence concentrated in high-income countries. There is also limited documentation in the published literature regarding the feasibility and lessons from implementing targeted vaccination strategies to reach PLHIV and HCWs in low- and middle-income countries. PROGRAM DEVELOPMENT, PILOTING, AND IMPLEMENTATION: We designed and implemented multifaceted strategies to scale up targeted COVID-19 vaccination among PLHIV and HCWs in 11 administrative regions on the mainland of Tanzania plus Zanzibar. An initial 6-week intensification strategy was implemented using a diverse partnership model comprising key stakeholders at the national- and subnational levels. A layered package of strategies included expanding the number of certified vaccinators, creating vaccination points within HIV clinics, engaging HCWs to address their concerns, and building the capacity of HCWs as "champions" to promote and facilitate vaccination. We then closely monitored COVID-19 vaccination uptake in 562 high-volume HIV clinics. Between September 2021 and September 2022, the proportion of fully vaccinated adult PLHIV increased from <1% to 97% and fully vaccinated HCWs increased from 23% to 80%. LESSONS AND IMPLICATIONS: Our intra-action review highlighted the importance of leveraging a strong foundation of existing partnerships and platforms, integrating COVID-19 vaccination points within HIV clinics, and refining strategies to increase vaccination demand while ensuring continuity of vaccine supply to meet the increased demand. Lessons from Tanzania can inform targeted vaccination of vulnerable groups in future health emergencies.

INTRODUCTION: Countries use the WHO Joint External Evaluation (JEE) tool-part of the WHO International Health Regulations (2005) Monitoring and Evaluation Framework-for voluntary evaluation of global health security (GHS) capacities. After releasing the JEE first edition (E1) in 2016, WHO released the JEE second edition (E2) in 2018 with language changes to multiple indicators and associated capacity levels. To understand the effect of language changes on countries' ability to meet requirements in each edition, we conducted a Delphi study-a method where a panel of experts reach consensus on a topic through iterative, anonymous surveys-to solicit feedback from 40+ GHS experts with expertise in one or more of the 19 JEE technical areas. METHODS: We asked experts first to compare the language changes for each capacity level within each indicator and identify how these changes affected the indicator overall; then to assess the ability of a country to achieve the same capacity level using E2 as compared with E1 using a Likert-style score (1-5), where '1' was 'significantly easier' and '5' was 'significantly harder'; and last to provide a qualitative justification for score selections. We analysed the medians and IQR of responses to determine where experts reached consensus. RESULTS: Results demonstrate that 14 indicators and 49 capacity levels would be harder to achieve in E2. CONCLUSION: Findings underscore the importance of considering how language alterations impact how the JEE measures GHS capacity and the feasibility of using the JEE to monitor changes in capacity over time.

This paper describes the factors that support recovery of public health infrastructure (PHI), including conditions that facilitated or hindered recovery in United States (US) territories impacted by hurricanes Irma and Maria. A deductive approach was used to categorize data from five organizations that received crisis hurricane recovery (CHR) funds from the Centers for Disease Control and Prevention.* Spending was grouped into five infrastructure gaps: (1) human resources, (2) informatic upgrades, (3) equipment, (4) minor repairs, and (5) preventive maintenance. Unanticipated PHI costs, facilitators, and hinderances to PHI recovery were identified. Most (72 percent) of the $53,529,823 CHR funding was used to address infrastructure gaps in (1) human resources (56 percent), (2) informatics (16 percent), (3) equipment (13 percent), (4) minor repairs (10 percent), and (5) preventive maintenance (5 percent). Most of the requests (56 percent) to redirect funds were associated with unanticipated costs in initial work plans and budgets. The use of administrative partners, planning tools, dedicated staff, streamlined procedures, eg, contracts, and cost sharing facilitated PHI recovery. The most common hindrance to PHI recovery were delays in procurement and shipping. In summary, investments in dedicated funding to upgrade, repair, or replace critical structures and systems for infectious disease surveillance, laboratory capacity, vector control, environmental health inspections, and vaccine storage and administration in Puerto Rico and the US Virgin Islands after Hurricanes Irma and Maria contributed to their recovery capacity. These findings may inform funding and resource allocation considerations for PHI recovery in the US territories.

Farmworkers, a group of essential workers, experience a disproportionately high burden of COVID-19 due to their living and working conditions. This project characterized farmworker mobility in and around Yuma County, Arizona, to identify opportunities to improve farmworker access to COVID-19 vaccination. We collected qualitative and geospatial data through a series of in-person and virtual focus group discussions, key informant interviews, and intercept interviews with participatory mapping. Participants included farmworkers, employers, and representatives of local institutions who serve or interact with farmworkers. We identified participants through purposive and referential sampling and grouped people by sociodemographic characteristics for interviews. We used qualitative and geospatial analyses to identify common themes and mobility patterns. The team interviewed 136 people from February 26 to April 2, 2021. Common themes emerged about how farmworkers have little or no access to COVID-19 vaccination unless offered at their workplaces or at locations where they congregate at convenient times. Further, farmworkers described how their demanding work schedules, long commute times, and caretaker commitments make it challenging to access vaccination services. Geospatial analyses identified three geographic areas in Yuma County where farmworkers reported living and working that did not have a COVID-19 vaccine clinic within walking distance. Coordination between local public health authorities and key partners, including employers and trusted representatives from local community-based organizations or the Mexican consulate, to offer vaccination at worksites or other locations where farmworkers congregate can help improve access to COVID-19 vaccines and booster doses for this population.

Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted by hematophagous reduviid bugs within the subfamily Triatominae. These vectors take blood meals from a wide range of hosts, and their feeding behaviors have been used to investigate the ecology and epidemiology of T. cruzi. In this study we describe two PCR-based methodologies that amplify a fragment of the 16S mitochondrial rDNA, aimed to improve the identification of blood meal sources for Triatoma infestans: a.--Sequence analyses of two heminested PCRs that allow the identification of mammalian and avian species, and b.--restriction fragment length polymorphism (RFLP) analysis from the mammalian PCR to identify and differentiate multi-host blood meals. Findings from both methodologies indicate that host DNA could be detected and the host species identified in samples from laboratory reared and field collected triatomines. The implications of this study are two-fold. First, these methods can be used in areas where the fauna diversity and feeding behavior of the triatomines are unknown. Secondly, the RFLP method led to the identification of multi-host DNA from T. infestans gut contents, enhancing the information provided by this assay. These tools are important contributions for ecological and epidemiological studies of vector-borne diseases.

BACKGROUND: The impact of work-related asthma (WRA) on quality of life (QoL) and work productivity remains largely neglected/uncertain despite its high prevalence. OBJECTIVE: To investigate the association of WRA with QoL and work productivity as compared with subjects with non-WRA and those without asthma and rhinitis. METHODS: A cross-sectional survey was carried out among workers during their periodic occupational health visit in Belgium. The Mini Asthma Quality of Life Questionnaire, the 8-item Medical Outcome Study Short Form instrument, and the Work Productivity and Activity Impairment-General Health questionnaire were administered. Survey participants were divided into 3 groups: (1) WRA (current asthma with ≥2 respiratory symptoms at work; n = 89); (2) non-WRA (current asthma without work-related respiratory symptoms; n = 119); and (3) the reference group (no asthma and no lower respiratory, nasal, or eye symptoms; n = 815). Associations of QoL and work productivity with WRA were evaluated by multivariable regression analyses. RESULTS: WRA and having poor asthma control were significantly associated with lower global Mini Asthma Quality of Life Questionnaire scores compared with non-WRA. Asthmatic subjects had significantly lower physical and mental health component scores of the 8-item Medical Outcome Study Short Form instrument and overall work productivity compared with the reference group, with greater impairment in workers with WRA than in those without WRA. Moreover, workers with WRA had higher percentages of doctor visits and income reduction because of respiratory symptoms than those with non-WRA. Work-related rhinitis and depression were associated with reduced QoL, independent of the effect of WRA. CONCLUSIONS: WRA should be managed comprehensively to reduce the worsening of QoL and work productivity of those affected.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

Background: Vaccine access, coupled with the belief that vaccines are important, beneficial, and safe, plays a pivotal role in achieving high levels of vaccination to reduce the spread and severity of COVID-19 in the United States (U.S.) and globally. Many factors can influence vaccine intentions and uptake. Method(s): We conducted a scoping review of factors (e.g., access-related factors, racism) known to influence vaccine intentions and uptake, using publications from various databases and websites published December 1, 2020-April 30, 2021. Descriptive statistics were used to present results. Result(s): Overall, 1094 publications were identified through the database search, of which 133 were included in this review. Among the publications included, over 60% included mistrust in vaccines and vaccine-safety concerns, 43% included racism/discrimination, 35% included lack of vaccine access (35%), and 8% had no contextual factors when reporting on vaccine intentions and disparities in vaccine uptake. Conclusion(s): Findings revealed during a critical period when there was a well-defined goal for adult COVID-19 vaccination in the U.S., some publications included several contextual factors while others provided limited or no contextual factors when reporting on disparities in vaccine intentions and uptake. Failing to contextualize inequities and other factors that influence vaccine intentions and uptake might be perceived as placing responsibility for vaccination status on the individual, consequently, leaving social and structural inequities that impact vaccination rates and vaccine confidence, among people of color, intact. 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.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

A workforce with the adequate field epidemiology knowledge, skills and abilities is the foundation of a strong and effective animal health system. Field epidemiology training is conducted in several countries to meet the increased global demand for such a workforce. However, core competencies for field veterinary epidemiology have not been identified and agreed upon globally, leading to the development of different training curricula. Having a set of agreed core competencies can harmonize field veterinary epidemiology training. The Food and Agriculture Organization of the United Nations (FAO) initiated a collective, iterative, and participative process to achieve this and organized two expert consultative workshops in 2018 to develop core competencies for field veterinary epidemiology at the frontline and intermediate levels. Based on these expert discussions, 13 competencies were identified for the frontline and intermediate levels. These competencies were organized into three domains: epidemiological surveillance and studies; field investigation, preparedness and response; and One Health, communication, ethics and professionalism. These competencies can be used to facilitate the development of field epidemiology training curricula for veterinarians, adapted to country training needs, or customized for training other close disciplines. The competencies can also be useful for mentors and employers to monitor and evaluate the progress of their mentees, or to guide the selection process during the recruitment of new staff.

The language used when reporting racial and ethnic disparities in vaccine intentions and uptake must evolve to reflect social and structural inequities. To achieve health equity, we must acknowledge the extent to which racism and health inequities serve as barriers to vaccine-seeking behaviours among people of colour. | | During the early stages of the rollout of COVID-19 vaccines in the USA, uptake of COVID-19 vaccines was higher among White, non-Hispanic persons as compared with people of colour (that is, American Indian or Alaska Native, non-Hispanic; Black, non-Hispanic; Hispanic; and Native Hawaiian or Pacific Islander, non-Hispanic persons). These early racial and ethnic disparities in vaccination rates led many news stories, journal articles and other reports to perpetuate a narrative that disparities in the uptake of COVID-19 vaccines among people of colour were largely driven by vaccine hesitancy, while neglecting to focus on health inequities and other factors as drivers of disparities in vaccine intentions and uptake.

BACKGROUND: The continued spread of insecticide resistance in mosquito vectors of malaria and arboviral diseases may lead to operational failure of insecticide-based interventions if resistance is not monitored and managed efficiently. This study aimed to develop and validate a new WHO glass bottle bioassay method as an alternative to the WHO standard insecticide tube test to monitor mosquito susceptibility to new public health insecticides with particular modes of action, physical properties or both. METHODS: A multi-centre study involving 21 laboratories worldwide generated data on the susceptibility of seven mosquito species (Aedes aegypti, Aedes albopictus, Anopheles gambiae sensu stricto [An. gambiae s.s.], Anopheles funestus, Anopheles stephensi, Anopheles minimus and Anopheles albimanus) to seven public health insecticides in five classes, including pyrethroids (metofluthrin, prallethrin and transfluthrin), neonicotinoids (clothianidin), pyrroles (chlorfenapyr), juvenile hormone mimics (pyriproxyfen) and butenolides (flupyradifurone), in glass bottle assays. The data were analysed using a Bayesian binomial model to determine the concentration-response curves for each insecticide-species combination and to assess the within-bioassay variability in the susceptibility endpoints, namely the concentration that kills 50% and 99% of the test population (LC(50) and LC(99), respectively) and the concentration that inhibits oviposition of the test population by 50% and 99% (OI(50) and OI(99)), to measure mortality and the sterilizing effect, respectively. RESULTS: Overall, about 200,000 mosquitoes were tested with the new bottle bioassay, and LC(50)/LC(99) or OI(50)/OI(99) values were determined for all insecticides. Variation was seen between laboratories in estimates for some mosquito species-insecticide combinations, while other test results were consistent. The variation was generally greater with transfluthrin and flupyradifurone than with the other compounds tested, especially against Anopheles species. Overall, the mean within-bioassay variability in mortality and oviposition inhibition were < 10% for most mosquito species-insecticide combinations. CONCLUSION: Our findings, based on the largest susceptibility dataset ever produced on mosquitoes, showed that the new WHO bottle bioassay is adequate for evaluating mosquito susceptibility to new and promising public health insecticides currently deployed for vector control. The datasets presented in this study have been used recently by the WHO to establish 17 new insecticide discriminating concentrations (DCs) for either Aedes spp. or Anopheles spp. The bottle bioassay and DCs can now be widely used to monitor baseline insecticide susceptibility of wild populations of vectors of malaria and Aedes-borne diseases worldwide.

The HPV Serology Laboratory in the Frederick National Laboratory for Cancer Research is working in partnership with the scientific community with the goal of standardizing and harmonizing current HPV serology assay platforms in response to the increasing number of immunobridging trials relying on serology data for approval of new vaccine dosing schedules and new formulations. A virtual meeting was held on June 29-30, 2021, to review the progress of the standardization initiative thus far and to bridge scientific gaps and outstanding questions. The main aims and outcomes of the meeting were to discuss: 1) standardization of assays and reagents; 2) International Standard calibration procedures; 3) assay cut-off values; 4) current immunobridging clinical trials; and 5) gaps and challenges in standardization of HPV serology.

BACKGROUND: The development of resistance against insecticides in Aedes aegypti can lead to operational failures in control programs. Knowledge of the spatial and temporal trends of this resistance is needed to drive effective monitoring campaigns, which in turn provide data on which vector control decision-making should be based. METHODS: Third-stage larvae (L3) from the F1 and F2 generations of 39 Peruvian field populations of Ae. aegypti mosquitoes from established laboratory colonies were evaluated for resistance against the organophosphate insecticide temephos. The 39 populations were originally established from eggs collected in the field with ovitraps in eight departments of Peru during 2018 and 2019. Dose-response bioassays, at 11 concentrations of the insecticide, were performed following WHO recommendations. RESULTS: Of the 39 field populations of Ae. aegypti tested for resistance to temephos , 11 showed high levels of resistance (resistance ratio [RR] > 10), 16 showed moderate levels of resistance (defined as RR values between 5 and 10) and only 12 were susceptible (RR < 5). The results segregated the study populations into two geographic groups. Most of the populations in the first geographic group, the coastal region, were resistant to temephos, with three populations (AG, CR and LO) showing RR values > 20 (AG 21.5, CR 23.1, LO 39.4). The populations in the second geographic group, the Amazon jungle and the high jungle, showed moderate levels of resistance, with values ranging between 5.1 (JN) and 7.1 (PU). The exception in this geographic group was the population from PM, which showed a RR value of 28.8 to this insecticide. CONCLUSIONS: The results of this study demonstrate that Ae. aegypti populations in Peru present different resistance intensities to temephos, 3 years after temephos use was discontinued. Resistance to this larvicide should continue to be monitored because it is possible that resistance to temephos could decrease in the absence of routine selection pressures.

BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.

The United States of America has a diverse population of over 331 million people.1 Groups historically identified as racial and ethnic minorities (which make up more than one third of the US population)1 have been economically and socially marginalized, leading to lower access to education, health care and financial capital, therefore putting some of these groups at increased risk for poor health outcomes.2 The coronavirus disease 2019 (COVID-19) pandemic has amplified existing health inequities; disparities in COVID-19 cases, hospitalizations and deaths, and now vaccination rates, have been identified.3,4 Here, we provide a high-level summary of strategies implemented by the United States Centers for Disease Control and Prevention (CDC) to address COVID-19 inequities impacting racial and ethnic minority groups.

The emergence of SARS-CoV-2 created a crucial need for serology assays to detect anti-SARS-CoV-2 antibodies, which led to many serology assays entering the market. A trans-government collaboration was created in April 2020 to independently evaluate the performance of commercial SARS-CoV-2 serology assays and help inform U.S. Food and Drug Administration (FDA) regulatory decisions. To assess assay performance, three evaluation panels with similar antibody titer distributions were assembled. Each panel consisted of 110 samples with positive (n = 30) serum samples with a wide range of anti-SARS-CoV-2 antibody titers and negative (n = 80) plasma and/or serum samples that were collected before the start of the COVID-19 pandemic. Each sample was characterized for anti-SARS-CoV-2 antibodies against the spike protein using enzyme-linked immunosorbent assays (ELISA). Samples were selected for the panel when there was agreement on seropositivity by laboratories at National Cancer Institute's Frederick National Laboratory for Cancer Research (NCI-FNLCR) and Centers for Disease Control and Prevention (CDC). The sensitivity and specificity of each assay were assessed to determine Emergency Use Authorization (EUA) suitability. As of January 8, 2021, results from 91 evaluations were made publicly available (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html). Sensitivity ranged from 27% to 100% for IgG (n = 81), from 10% to 100% for IgM (n = 74), and from 73% to 100% for total or pan-immunoglobulins (n = 5). The combined specificity ranged from 58% to 100% (n = 91). Approximately one-third (n = 27) of the assays evaluated are now authorized by FDA for emergency use. This collaboration established a framework for assay performance evaluation that could be used for future outbreaks and could serve as a model for other technologies. IMPORTANCE The SARS-CoV-2 pandemic created a crucial need for accurate serology assays to evaluate seroprevalence and antiviral immune responses. The initial flood of serology assays entering the market with inadequate performance emphasized the need for independent evaluation of commercial SARS-CoV-2 antibody assays using performance evaluation panels to determine suitability for use under EUA. Through a government-wide collaborative network, 91 commercial SARS-CoV-2 serology assay evaluations were performed. Three evaluation panels with similar overall antibody titer distributions were assembled to evaluate performance. Nearly one-third of the assays evaluated met acceptable performance recommendations, and two assays had EUAs revoked and were removed from the U.S. market based on inadequate performance. Data for all serology assays evaluated are available at the FDA and CDC websites (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html).

The codon usage and dinucleotide frequencies of an organism depend mostly on its nucleotide composition, but also on the evolutionary forces that have acted on its genome including mutation, genetic drift, and selection. Different selection pressures may contribute to shape the genome composition and codon usage of viruses: | | - Codon usage and dinucleotide biases may result from the need to maintain RNA secondary structures involved in splicing and gene expression (Takata et al., 2018). | - Dinucleotide bias may result from the need to evade cell defense mechanisms. UpA, and particularly CpG, dinucleotides may be perceived as pathogen-associated molecular patterns by host cells and consequently their frequencies in viral genomes tend to decrease (Atkinson et al., 2014). | - Codon usage may also result from translation selection. Abundant codons, pairing with abundant tRNAs, would be selected over rare codons, pairing with non-abundant tRNAs, to improve the efficiency and accuracy of translation. On the contrary, rare codons would persist through mutational pressure and genetic drift (Duret, 2002; Hershberg and Petrov, 2008). Viruses do not code for tRNAs, and instead they use the host tRNA pool for their own translation, making even harder to discern the role of selection on shaping their codon usage. Although a similar codon usage between viruses and their hosts may be anticipated, excessive similarity may impede host translation, with the associated deleterious effects; consequently, viruses have evolved to an optimal range of codon usage bias (Moratorio et al., 2013; Chen et al., 2020). | - Codon usage may also be shaped by selection for the control of the translation rate. The scarcity of rare codon pairing tRNAs may result in ribosome stalling, slowing down the mRNA translation speed. In doing so, rare codons may play a role in controlling the co-translational folding (Chaney and Clark, 2015; Yu et al., 2015; Zhao et al., 2017; D'Andrea et al., 2019; Pintó and Bosch, 2021). | - Additionally, codon usage may be selected to maintain mutational robustness. Codons one mutation apart from a stop codon may tend to be avoided in genomes (Moratorio et al., 2017; Carrau et al., 2019).

On September 6 and 20, 2017, Hurricanes Irma and Maria made landfall as major hurricanes in the US Caribbean Territories of the Virgin Islands and Puerto Rico with devastating effects. As part of the initial response, a public health team (PHT) was initially deployed as part of the US Department of Health and Human Services Incident Response Coordination Team. As a result of increased demands for additional expertise and resources, a public health branch (PHB) was established for coordinating a broad spectrum of public health response activities in support of the affected territories. This paper describes the conceptual framework for organizing these activities; summarizes some key public health activities and roles; outlines partner support and coordination with key agencies; and defines best practices and areas for improvement in disaster future operations. © 2021 Weston Medical Publishing. All rights reserved.

BACKGROUND: This study aims to clarify relationships of maternal psychiatric conditions and selective serotonin reuptake inhibitor (SSRI) use during preconception and pregnancy with risk of neurodevelopmental disorders in offspring. METHODS: We used data from the Study to Explore Early Development, a multisite case-control study conducted in the United States among children born between 2003 and 2011. Final study group classifications of autism spectrum disorder (ASD) (n = 1367), developmental delays or disorders (DDs) (n = 1750), and general population controls (n = 1671) were determined by an in-person standardized developmental assessment. Maternal psychiatric conditions and SSRI use during pregnancy were ascertained from both self-report and medical records. We used logistic regression to evaluate associations of ASD and DDs (vs. population controls) with maternal psychiatric conditions and SSRI treatment in pregnancy. To reduce confounding by indication, we also examined SSRI associations in analyses restricted to mothers with psychiatric conditions during pregnancy. RESULTS: Psychiatric conditions and SSRI use during pregnancy were significantly more common among mothers of children with either ASD or DDs than among population controls. Odds of ASD were similarly elevated among mothers with psychiatric conditions who did not use SSRIs during pregnancy (adjusted odds ratio 1.81, 95% confidence interval 1.44-2.27) as in mothers who did use SSRIs (adjusted odds ratio 2.05, 95% confidence interval 1.50-2.80). Among mothers with psychiatric conditions, SSRI use was not significantly associated with ASD in offspring (adjusted odds ratio 1.14, 95% confidence interval 0.80-1.62). Primary findings for DDs exhibited similar relationships to those observed with ASD. CONCLUSIONS: Maternal psychiatric conditions but not use of SSRIs during pregnancy were associated with increased risk of neurodevelopmental disorders in offspring.

BACKGROUND: With limited SARS-CoV-2 testing capacity in the US at the start of the epidemic (January - March), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic. METHODS: All of Us study participants in all 50 US states provided blood specimens during study visits from January 2 to March 18, 2020. A participant was considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. Sensitivity and specificity of the Abbott and EUROIMMUNE ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated with 95% confidence intervals. RESULTS: The estimated sensitivity of Abbott and EUROIMMUN was 100% (107/107 [96.6%, 100%]) and 90.7% (97/107 [83.5%, 95.4%]), respectively. The estimated specificity of Abbott and EUROIMMUN was 99.5% (995/1,000 [98.8%, 99.8%]) and 99.7% (997/1,000 [99.1%, 99.9%), respectively. The net sensitivity and specificity of our sequential testing algorithm was 90.7% (97/107 [83.5%, 95.4%]) and 100.0% (1,000/1,000 [99.6%, 100%]), respectively. Of the 24,079 study participants with blood specimens from January 2 to March 18, 2020, 9 were seropositive, 7 of whom were seropositive prior to the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi. CONCLUSIONS: Our findings indicate SARS-CoV-2 infections weeks prior to the first recognized cases in 5 US states.

Clostridioides difficile is an important organism causing healthcare-associated infections. It has been documented that specific strains caused multiple outbreaks globally, and patients infected with those strains are more likely to develop severe C. difficile infection (CDI). With the appearance of a variant strain, BI/NAP1 ribotype 027, responsible for several outbreaks and high mortality rates worldwide, the epidemiology of the CDI changed drastically in the United States, Europe, and some Latin American countries. Although the epidemic strain 027 was not yet detected in Brazil, there are ribotypes exclusively found in the country, such as, 131, 132, 133, 135, 142 and 143, which are responsible for outbreaks in Brazilian hospitals and nursing homes. Although PCR-ribotyping is the most used method in epidemiology studies of C. difficile, it is not available in Brazil. This study aimed to develop and validate an in-house database for detecting C. difficile ribotypes, usually involved in CDI in Brazilian hospitals, by using MALDI-TOF MS. A database with 19 different ribotypes, 13 with worldwide circulation and 6 Brazilian-restricted, was created based on 27 spectra readings of each ribotype. After BioNumerics analysis, neighbor-joining trees revealed that spectra were distributed in clusters according to ribotypes, showing that MALDI-TOF MS could discriminate all 19 ribotypes. Moreover, each ribotype showed a different profile with 42 biomarkers detected in total. Based on their intensity and occurrence, 13 biomarkers were chosen to compose ribotype-specific profiles, and in silico analysis showed that most of these biomarkers were uncharacterized proteins or well-conserved peptides, such as ribosomal proteins. A double-blind assessment using the 13 biomarkers correctly assigned the ribotype in 73% of the spectra analyzed, with 94% to 100% of correct hits for 027 and for Brazilian ribotypes. Although further analyses are required, our results show that MALDI-TOF MS might be a reliable, fast and feasible alternative for epidemiological surveillance of C. difficile in Brazil.

Gastrointestinal symptoms (GIS) are commonly reported in children with autism spectrum disorder (ASD). This multi-site study evaluated the prevalence of GIS in preschool-aged children with ASD/(n = 672), with other developmental delays (DD)/(n = 938), and children in the general population (POP)/(n = 851). After adjusting for covariates, children in the ASD group were over 3 times more likely to have parent-reported GIS than the POP group, and almost 2 times more likely than the DD group. Children with GIS from all groups had more behavioral and sleep problems. Within the ASD group, children with developmental regression had more GIS than those without; however, there were no differences in autism severity scores between children with and without GIS. These findings have implications for clinical management.

Coronavirus disease 2019 (COVID-19) is a viral respiratory illness caused by SARS-CoV-2. During January 21-July 25, 2020, in response to official requests for assistance with COVID-19 emergency public health response activities, CDC deployed 208 teams to assist 55 state, tribal, local, and territorial health departments. CDC deployment data were analyzed to summarize activities by deployed CDC teams in assisting state, tribal, local, and territorial health departments to identify and implement measures to contain SARS-CoV-2 transmission (1). Deployed teams assisted with the investigation of transmission in high-risk congregate settings, such as long-term care facilities (53 deployments; 26% of total), food processing facilities (24; 12%), correctional facilities (12; 6%), and settings that provide services to persons experiencing homelessness (10; 5%). Among the 208 deployed teams, 178 (85%) provided assistance to state health departments, 12 (6%) to tribal health departments, 10 (5%) to local health departments, and eight (4%) to territorial health departments. CDC collaborations with health departments have strengthened local capacity and provided outbreak response support. Collaborations focused attention on health equity issues among disproportionately affected populations (e.g., racial and ethnic minority populations, essential frontline workers, and persons experiencing homelessness) and through a place-based focus (e.g., persons living in rural or frontier areas). These collaborations also facilitated enhanced characterization of COVID-19 epidemiology, directly contributing to CDC data-informed guidance, including guidance for serial testing as a containment strategy in high-risk congregate settings, targeted interventions and prevention efforts among workers at food processing facilities, and social distancing.

CONTEXT: In September 2017, Hurricanes Irma and Maria impacted Puerto Rico, causing significant disruption of immunization services and vaccine losses due to widespread infrastructure and electrical grid damage and resulting cold chain failures. OBJECTIVE: To describe posthurricane efforts undertaken to restore and strengthen immunization services provided by Puerto Rico's federally funded Vaccines for Children (VFC) Program, a network of clinics that provide vaccines to eligible children. DESIGN: Historical records were reviewed to characterize Puerto Rico's prehurricane immunization system. Site visits to assess VFC clinic posthurricane operational status were conducted by the Puerto Rico Department of Health, working with the Centers for Disease Control and Prevention and other partners. Infrastructure repair and acquisition of backup generators, temperature data loggers, and replacement vaccines were carried out to restore operations. RESULTS: Prior to the hurricanes, 224 VFC clinics throughout the island provided immunizations. An initial assessment 10 days after Hurricane Maria showed that only 11 (5%) of the clinics were operational. Reasons included ongoing power outages; difficulties in obtaining generator fuel; equipment or facility damage; and damaged vaccines. The VFC clinics were restored incrementally; 123 (55%) were operational by December 2017, 193 (86%) by May 2018, and 204 (91%) by May 2019. Long-term recovery activities are underway and focus on strengthening Puerto Rico's immunization system to withstand future disasters, including improving backup power systems. CONCLUSION: Through coordinated efforts of the Puerto Rico Department of Health, the Centers for Disease Control and Prevention, and other partners, the operational status of VFC clinics posthurricanes was assessed and operations restored. Emergency plans for vaccine storage and handling, which called for alternative vaccine storage locations and backup generators, were inadequate to address disasters of the magnitude of Hurricanes Irma and Maria; such plans need to consider the possibility of large-scale disasters that result in long-term power outages.

INTRODUCTION: Whether existing serological assays are sufficiently robust to measure the lower antibody levels expected following single-dose HPV vaccination is unknown. METHODS: We evaluated seven assays measuring HPV-16/18 immunological responses overall and by number of doses in 530 serum samples from participants receiving varying doses of Cervarix or Gardasil up to 36-months post-vaccination. Serum was evaluated by simplex (HPV-16 ELISA, HPV-18 ELISA), multiplex (LIA-4, VLP-MIA, M9ELISA, GST-L1), and high-throughput pseudovirion-based neutralization assays (HT-PBNA), and results were compared to the gold standard HPV-16/18 secreted alkaline phosphatase neutralization assay (SEAP-NA). Reproducibility was assessed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Percent agreement, Pearson correlation, and weighted-kappa were used to assess validity. Determinants of seronegativity were evaluated by chi-squared test. RESULTS: HPV-16: Seropositivity range was 97.1-99.5% for single dose and 98.8-99.8% overall. CV range was 4.0-18.0% for single dose and 2.9-19.5% overall. ICC range was 0.77-0.99 for single dose and 0.74-0.99 overall. Correlation with SEAP-NA range was 0.43-0.85 for single dose and 0.51-0.90 overall. Weighted-kappa range was 0.34-0.82 for single dose and 0.45-0.84 overall. HPV-18: Seropositivity range was 63.9-94.7% for single dose and 86.2-97.9% overall. CV range was 8.1-18.2% for single dose and 4.6-18.6% overall. ICC range was 0.75-0.99 for single dose and 0.83-0.99 overall. Correlation with SEAP-NA range was 0.31-0.99 for single dose and 0.27-0.96 overall. Weighted-kappa range was 0.35-0.83 for single dose and 0.45-0.84 overall. HPV-16 seronegativity was <5% for all assays. HPV-18 seronegativity range was 5.5-17.3%. For LIA-4 and GST-L1 where the proportion of seronegativity was >10%, the strongest correlates of seronegativity were receiving a single vaccine dose and receiving Gardasil. CONCLUSIONS: These results support the utility of existing serological assays to monitor antibody responses following single-dose HPV vaccination.

A variety of imaging and analytical methods have been developed to study nanoparticles in cells. Each has its benefits, limitations, and varying degrees of expense and difficulties in implementation. High-resolution analytical scanning transmission electron microscopy (HRSTEM) has the unique ability to image local cellular environments adjacent to a nanoparticle at near atomic resolution and apply analytical tools to these environments such as energy dispersive spectroscopy and electron energy loss spectroscopy. These tools can be used to analyze particle location, translocation and potential reformation, ion dispersion, and in vivo synthesis of second-generation nanoparticles. Such analyses can provide in depth understanding of tissue-particle interactions and effects that are caused by the environmental "invader" nanoparticles. Analytical imaging can also distinguish phases that form due to the transformation of "invader" nanoparticles in contrast to those that are triggered by a response mechanism, including the commonly observed iron biomineralization in the form of ferritin nanoparticles. The analyses can distinguish ion species, crystal phases, and valence of parent nanoparticles and reformed or in vivo synthesized phases throughout the tissue. This article will briefly review the plethora of methods that have been developed over the last 20 years with an emphasis on the state-of-the-art techniques used to image and analyze nanoparticles in cells and highlight the sample preparation necessary for biological thin section observation in a HRSTEM. Specific applications that provide visual and chemical mapping of the local cellular environments surrounding parent nanoparticles and second-generation phases are demonstrated, which will help to identify novel nanoparticle-produced adverse effects and their associated mechanisms.

Congregate work and residential locations are at increased risk for infectious disease transmission including respiratory illness outbreaks. SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is primarily spread person to person through respiratory droplets. Nationwide, the meat and poultry processing industry, an essential component of the U.S. food infrastructure, employs approximately 500,000 persons, many of whom work in proximity to other workers (1). Because of reports of initial cases of COVID-19, in some meat processing facilities, states were asked to provide aggregated data concerning the number of meat and poultry processing facilities affected by COVID-19 and the number of workers with COVID-19 in these facilities, including COVID-19-related deaths. Qualitative data gathered by CDC during on-site and remote assessments were analyzed and summarized. During April 9-27, aggregate data on COVID-19 cases among 115 meat or poultry processing facilities in 19 states were reported to CDC. Among these facilities, COVID-19 was diagnosed in 4,913 (approximately 3%) workers, and 20 COVID-19-related deaths were reported. Facility barriers to effective prevention and control of COVID-19 included difficulty distancing workers at least 6 feet (2 meters) from one another (2) and in implementing COVID-19-specific disinfection guidelines.* Among workers, socioeconomic challenges might contribute to working while feeling ill, particularly if there are management practices such as bonuses that incentivize attendance. Methods to decrease transmission within the facility include worker symptom screening programs, policies to discourage working while experiencing symptoms compatible with COVID-19, and social distancing by workers. Source control measures (e.g., the use of cloth face covers) as well as increased disinfection of high-touch surfaces are also important means of preventing SARS-CoV-2 exposure. Mitigation efforts to reduce transmission in the community should also be considered. Many of these measures might also reduce asymptomatic and presymptomatic transmission (3). Implementation of these public health strategies will help protect workers from COVID-19 in this industry and assist in preserving the critical meat and poultry production infrastructure (4).