A safe insect-based Chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques.

Chikungunya virus (CHIKV), which induces chikungunya fever and chronic arthralgia, is an emerging public health concern. Safe and efficient vaccination strategies are needed to prevent or mitigate virus-associated acute and chronic morbidities for preparation of future outbreaks. Eilat (EILV)/CHIKV, a chimeric alphavirus which contains the structural proteins of CHIKV and the non-structural proteins of EILV, does not replicate in vertebrate cells. The chimeric virus was previously reported to induce protective adaptive immunity in mice. Here, we assessed the capacity of the virus to induce quick and durable protection in cynomolgus macaques. EILV/CHIKV protected macaques from wild-type (WT) CHIKV infection one year after a single dose vaccination. Transcriptome and in vitro functional analyses reveal that the chimeric virus triggered toll-like receptor signaling and T cell, memory B cell and antibody responses in a dose-dependent manner. Notably, EILV/CHIKV preferentially induced more durable, robust, and broader repertoire of CHIKV-specific T cell responses, compared to a live attenuated CHIKV 181/25 vaccine strain. The insect-based chimeric virus did not cause skin hypersensitivity reactions in guinea pigs sensitized to mosquito bites. Furthermore, EILV/CHIKV induced strong neutralization antibodies and protected cynomolgus macaques from WT CHIKV infection within six days post vaccination. Transcriptome analysis also suggest that the chimeric virus induction of multiple innate immune pathways, including Toll-like receptor signaling, type I IFN and IL-12 signaling, antigen presenting cell activation, and NK receptor signaling. Our findings suggest that EILV/CHIKV is a safe, highly efficacious vaccine, and provides both rapid and long-lasting protection in cynomolgus macaques.

Epidemiological assessment of Anaplasma marginale, Babesia bigemina, and Babesia bovis infections in Colombian creole cattle breeds: A molecular survey in northeastern Colombia.

Anaplasmosis and babesiosis are globally distributed arthropod-borne diseases known for causing substantial economic losses due to their high morbidity and mortality rates. This study aims to assess the frequency and epidemiological features associated with the infection of Anaplasma marginale, Babesia bigemina, and Babesia bovis in three Creole cattle breeds (Chino Santandereano (Chino), Casanareño (CAS), and Sanmartinero (SM)) in northeastern Colombia. Between June 2019 and March 2020, a total of 252 Creole cattle were sampled, with Chino, CAS, and SM accounting for 42.8%, 29.5%, and 29.5% of the samples, respectively. Blood samples were subjected to molecular analysis to detect the DNA of A. marginale, B. bigemina, and B. bovis, using species-specific primers. Additionally, Packed Cell Volume (PCV), total serum proteins, and body condition were evaluated. Molecular analyses revealed the presence of B. bigemina, A. marginale, and B. bovis in 83.7% (211/252; 95% CI = 79.1%-88.3%), 59.9% (151/252; 95% CI = 53.8%-66.1%), and 40.9% (103/252; 95% CI = 34.7%-46.9%) of the samples, respectively, with 69% (174/252; 95% CI = 57.8%-80.3%) exhibiting coinfections. Notably, in infected animals, no significant alterations in PCV, total serum proteins, or body condition were observed. Multivariate analyses indicated a statistically significant association between the frequency of A. marginale infection and the breed and season, with a higher frequency in SM during the rainy season (P < 0.05). To our knowledge, this is the first molecular survey that evaluates multiple arthropod-borne pathogens in Colombian Creole breeds. The results revel a high frequency of B. bigemina and A. marginale infections, coupled with a notable frequency of coinfections, all without significant alteration in the PCV, total serum proteins and body conditions. Our findings enhance the understanding of the epidemiological aspects of arthropod-borne pathogens in Colombian Creole breed and contribute to the improvement of sanitary programs for these animals.

An Evaluation of Messages to Promote Parental Intent to Vaccinate Children Aged <12 Years Against COVID-19.

OBJECTIVES: Effective health communication can increase intent to vaccinate. We compared 8 messages that may influence parents' intent to vaccinate their children against COVID-19. METHODS: In a cross-sectional survey of adults in the United States administered online in August 2021, 1837 parents and legal guardians were exposed to 8 messages (individual choice, gain/practical benefits, nonexpert, health care provider recommendation, altruism/community good, safety/effectiveness, safety, and effectiveness) to determine message reception and influence on intent to vaccinate their children. Parents responded to 10 questions using a Likert scale. We computed odds ratios (ORs) for each message, with an OR >1.0 indicating greater observed odds of participant agreement with the follow-up statement as compared with a reference message. We compared outcomes individually across messages with ordinal logistic regression fit using generalized estimating equations. RESULTS: The individual choice message had the highest odds of agreement for understanding intent (OR = 2.10; 95% CI, 1.94-2.27), followed by the health care provider recommendation message (OR = 1.58; 95% CI, 1.46-1.71). The individual choice message had the highest odds of memorability, relatability, and trustworthiness. The altruism/community good message was at or near second best. The altruism/community good message had the highest or near-highest odds of increasing parents' intent to vaccinate their children, asking friends and family for their thoughts, and searching for additional information. The message that most motivated parents to vaccinate their children depended on parental intent to vaccinate prior to being exposed to the tested messages. CONCLUSIONS: Messages with themes of individual choice, health care provider recommendation, and altruism/community good may be used in future message campaigns. Further research is needed to refine message concepts related to altruism/community good.

Strengthening COVID-19 vaccine confidence & demand during the US COVID-19 emergency response.

In October 2020, the CDC's Vaccinate with Confidence strategy specific to COVID-19 vaccines rollout was published. Adapted from an existing vaccine confidence framework for childhood immunization, the Vaccinate with Confidence strategy for COVID-19 aimed to improve vaccine confidence, demand, and uptake of COVID-19 vaccines in the US. The objectives for COVID-19 were to 1. build trust, 2. empower healthcare personnel, and 3. engage communities and individuals. This strategy was implemented through a dedicated unit, the Vaccine Confidence and Demand (VCD) team, which collected behavioral insights; developed and disseminated toolkits and best practices in collaboration with partners; and collaborated with health departments and community-based organizations to engage communities and individuals in behavioral interventions to strengthen vaccine demand and increase COVID-19 vaccine uptake. The VCD team collected and used social and behavioral data through establishing the Insights Unit, implementing rapid community assessments, and conducting national surveys. To strengthen capacity at state and local levels, the VCD utilized "Bootcamps," a rapid training of trainers on vaccine confidence and demand, "Confidence Consults", where local leaders could request tailored advice to address local vaccine confidence challenges from subject matter experts, and utilized surge staffing to embed "Vaccine Demand Strategists" in state and local public health agencies. In addition, collaborations with Prevention Research Centers, the Institute of Museum and Library Services, and the American Psychological Association furthered work in behavioral science, community engagement, and health equity. The VCD team operationalized CDC's COVID-19 Vaccine with Confidence strategy through behavioral insights, capacity building opportunities, and collaborations to improve COVID-19 vaccine confidence, demand, and uptake in the US. The inclusion of applied behavioral science approaches were a critical component of the COVID-19 vaccination program and provides lessons learned for how behavioral science can be integrated in future emergency responses.

COVID-19 Vaccine Hesitancy Among US Adults: Safety and Effectiveness Perceptions and Messaging to Increase Vaccine Confidence and Intent to Vaccinate.

OBJECTIVE: Public health agencies have a critical role in providing effective messaging about mitigation strategies during a public health emergency. The objectives of this study were (1) to understand perceptions of COVID-19 vaccines, including concerns about side effects, safety, and effectiveness and how these perceptions influence vaccine decision-making among US adults and (2) to learn what messages might motivate vaccine uptake. METHODS: In April and May 2021, we conducted 14 online focus groups with non-Hispanic English-speaking and English- and Spanish-speaking Hispanic adults (N = 99) not vaccinated against COVID-19. We oversampled adults aged 18-39 years and rural residents and systematically assessed 10 test messages. Researchers used a standardized guide and an a priori codebook for focus group discussions, coding transcripts, and thematic analysis. RESULTS: Vaccine hesitancy factors included fear of the unknown; long-term side effects, including infertility; and beliefs that the vaccines were developed too quickly and were not sufficiently effective. Motivating factors for receiving vaccination included the ability to safely socialize and travel. Health care providers were considered important trusted messengers. Participants were critical of most messages tested. Messages that came across as "honest" about what is not yet known about COVID-19 vaccines were perceived more positively than other messages tested. Messages were seen as ineffective if perceived as vague or lacking in data and specificity. CONCLUSIONS: Messages that were simple and transparent about what is unknown about vaccines relative to emerging science were viewed most favorably. Health care providers, friends, and family were considered influential in vaccination decision-making. Findings underscore the benefits of research-informed strategies for developing and disseminating effective messages addressing critical issues in a public health emergency.

A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity.

An attenuated SARS-CoV-2 virus with modified viral transcriptional regulatory sequences and deletion of open-reading frames 3, 6, 7 and 8 (∆3678) was previously reported to protect hamsters from SARS-CoV-2 infection and transmission. Here we report that a single-dose intranasal vaccination of ∆3678 protects K18-hACE2 mice from wild-type or variant SARS-CoV-2 challenge. Compared with wild-type virus infection, the ∆3678 vaccination induces equivalent or higher levels of lung and systemic T cell, B cell, IgA, and IgG responses. The results suggest ∆3678 as an attractive mucosal vaccine candidate to boost pulmonary immunity against SARS-CoV-2.

A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity.

An attenuated SARS-CoV-2 virus with modified viral transcriptional regulatory sequences and deletion of open-reading frames 3, 6, 7 and 8 (∆3678) was previously reported to protect hamsters from SARS-CoV-2 infection and transmission. Here we report that a single-dose intranasal vaccination of ∆3678 protects K18-hACE2 mice from wild-type or variant SARS-CoV-2 challenge. Compared with wild-type virus infection, the ∆3678 vaccination induces equivalent or higher levels of lung and systemic T cell, B cell, IgA, and IgG responses. The results suggest ∆3678 as an attractive mucosal vaccine candidate to boost pulmonary immunity against SARS-CoV-2.

Oral Supplementation with AHCC®, a Standardized Extract of Cultured Lentinula edodes Mycelia, Enhances Host Resistance against SARS-CoV-2 Infection.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global public health safety and the economy. Multiple antiviral drugs have been developed, and some have received regulatory approval and/or authorization. The use of nutraceuticals can be beneficial for preventing and treating COVID-19 complications. AHCC is a standardized, cultured extract of an edible mushroom Lentinula edodes of the Basidiomycete family of fungi that is enriched in acylated α-1,4-glucans. Here, we evaluated the effects of the oral administration of AHCC on the host response to SARS-CoV-2 infection in two murine models, K18-hACE2 transgenic mice and immunocompetent BALB/c mice. Oral administration of AHCC every other day for one week before and one day post SARS-CoV-2 infection in both strains of mice decreased the viral load and attenuated inflammation in the lungs. AHCC treatment also significantly reduced SARS-CoV-2-induced lethality in the K18-hACE2 mice. AHCC administration enhanced the expansion of γδ T cells in the spleen and lungs before and after viral infection and promoted T helper 1-prone mucosal and systemic T cell responses in both models. In AHCC-fed BALB/c mice, SARS-CoV-2 specific IgG responses were also enhanced. In summary, AHCC supplementation enhances host resistance against mild and severe COVID-19 infection primarily via the promotion of innate and adaptive T cell immune responses in mice.

Racotumomab in Non-Small Cell Lung Cancer as Maintenance and Second-Line Treatment.

INTRODUCTION: Racotumomab is a therapeutic vaccine based on a monoclonal anti-idiotypic antibody developed by the Molecular Immunology Center in Havana, Cuba, that is registered in Cuba and Argentina for treatment of non-small cell lung cancer. It induces a specific humoral and cellular immune response against the N-glycolyl GM3 (NeuGcGM3) ganglioside present in tumor cells, thereby provoking the death of these cells. OBJECTIVE: Evaluate racotumomab vaccine use as switch maintenance and second-line therapy for patients with inoperable non-small cell lung cancer in routine clinical practice, outside the framework of clinical studies, and assess the overall survival, stage-specific survival and safety in these patients. METHODS: A descriptive, retrospective study was carried out in patients diagnosed with non-small cell lung cancer not suitable for surgical treatment, who received racotumomab as a part of switch maintenance or second-line treatments. Overall survival was defined from diagnosis and from the first immunization, until death. RESULTS: We included 71 patients treated with racotumomab, 57.7% (41/71) of whom were in stages IIIB and IV of non-small cell lung cancer. Of the patients, 84.5% (60/71) had no adverse events, and 15.5% (11/71) had mild adverse reactions. The median overall survival was 24.5 months, calculated from the first immunization, 17.2 months for those who received racotumomab as switch maintenance and 6.8 months for patients who had progressed after the first line of treatment. CONCLUSIONS: Racotumomab in routine clinical practice prolonged overall survival in patients with non-small cell lung cancer treated in switch maintenance, and in stage IV patients who received the treatment as second-line therapy. The vaccine was well tolerated.

Disparities in Tdap Vaccination and Vaccine Information Needs Among Pregnant Women in the United States.

Objectives The Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) recommend that pregnant women receive the Tdap vaccine during every pregnancy. The objectives of this paper are to evaluate disparities in Tdap vaccination among pregnant women in the U.S., and to assess whether race/ethnicity and other characteristics are associated with factors that inform pregnant women's decisions about Tdap vaccination. Methods We conducted a nationwide cross-sectional web-based survey of pregnant women in the U.S. during June-July 2014. The primary outcome was self-reported vaccination status with Tdap during pregnancy, categorized as vaccinated, unvaccinated with intent to be vaccinated during the current pregnancy, and unvaccinated with no intent to be vaccinated during the current pregnancy. Secondary outcomes included factors that influenced women's decisions about vaccination and information needs. We used multivariable logistic regression models to estimate odds ratios for associations between race/ethnicity and the outcomes. Results Among pregnant women who completed the survey, 41% (95% CI 36-45%) reported that they had received Tdap during the current pregnancy. Among those women in the third trimester at the time of survey, 52% (95% CI 43-60%) had received Tdap during the current pregnancy. Hispanic women had higher Tdap vaccination than white women and black women (53%, p < 0.05, compared with 38 and 36%, respectively). In logistic regression models adjusting for maternal age, geographic region, education, and income, Hispanic women were more likely to have been vaccinated with Tdap compared with white women (aOR 2.29, 95% CI 1.20-4.37). Higher income and residing in the western U.S. were also independently associated with Tdap vaccination during pregnancy. Twenty-six percent of surveyed women had not been vaccinated with Tdap yet but intended to receive the vaccine during the current pregnancy; this proportion did not differ significantly by race/ethnicity. The most common factor that influenced women to get vaccinated was a health care provider (HCP) recommendation. The most common reason for not getting vaccinated was a concern about safety of the vaccine. Conclusions This study found that some disparities exist in Tdap vaccination among pregnant women in the U.S., and HCPs have an important role in providing information and recommendations about the maternal Tdap recommendation to pregnant women so they can make informed vaccination decisions.

Understanding barriers and predictors of maternal immunization: Identifying gaps through an exploratory literature review.

BACKGROUND: The Advisory Committee for Immunization Practices recommends that all pregnant women receive the seasonal influenza vaccine and the tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine during every pregnancy. However, vaccination coverage rates are suboptimal among pregnant women in the United States, leaving these women and their unborn children at risk of vaccine-preventable diseases and their complications. OBJECTIVES: We sought to understand the current landscape of published literature regarding maternal immunization, including barriers to and predictors of vaccine acceptance, and identify gaps in the research in order to inform strategies for future programmatic improvement. METHODS: We conducted a literature search using MEDLINE (OVID), PsychINFO, and CINAHL (Ebsco) databases. The search included published, English-language manuscripts that identified patient, provider, or system-level barriers to, predictors of, or interventions that improved uptake of maternal vaccines among pregnant women in the US. Studies were reviewed using an inductive thematic analysis approach. RESULTS: We included 75 studies in our review. Pregnant women identified 25 different barriers to accepting recommended maternal immunizations; barriers related to vaccine safety perceptions were the most common. Healthcare providers identified 24 different barriers to vaccinating their pregnant patients. The most commonly cited barriers among healthcare providers were financial concerns. Eighteen different predictors of vaccine acceptance were identified. Receipt of a healthcare provider's recommendation was the factor most frequently reported as a reason for vaccination among pregnant women. CONCLUSIONS: We were able to identify gaps in the literature regarding maternal immunization and make recommendations for future research. Efforts to address the challenges of maternal immunization in the United States should include increasing the focus on Tdap, implementing more high-level assessments of safety perceptions and associated concerns, and determining most effective interventions.

Provider insight on surmounting specialty practice challenges to improve Tdap immunization rates among pregnant women.

BACKGROUND: Pertussis, or "whooping cough," is an acute, contagious pulmonary disease that, despite being vaccine-preventable, has become an increasingly widespread problem in the United States. As a result, the Advisory Committee on Immunization Practices and American College of Obstetricians and Gynecologists updated recommendations stating clinicians should give a Tdap dose during every pregnancy, preferably at 27-36 weeks. Despite this recommendation, reported Tdap vaccine receipt rates during pregnancy vary from 16-61%, and previous studies have shown that clinician recommendation and vaccine administration are strongly associated with vaccine uptake among pregnant women. METHODS: Our aim was to inform new strategies to increase uptake of the Tdap vaccine among pregnant women and, ultimately, reduce pertussis-related morbidity and mortality in infants. We conducted interviews with a sample of 24 ob-gyns. We subsequently performed grounded theory analyses of transcripts using deductive and inductive coding strategies followed by intercoder reliability assessment. RESULTS: All physicians interviewed were familiar with the most recent recommendation of giving the Tdap vaccine during the third trimester of every pregnancy, and the majority of physicians stated that they felt that the vaccine was important and effective due to the transfer of pertussis antibodies from the mother to the fetus. Most physicians indicated that they recommended the vaccine to patients during pregnancy, but not all reported administering it on site because it was not stocked at their practice. Implementation challenges for physicians included insurance reimbursement and other challenges (i.e., patient refusal). Tdap vaccination during pregnancy was a lower clinical priority for some physicians. Physicians recognized the benefits associated with Tdap vaccination during pregnancy. CONCLUSIONS: Findings indicate while most ob-gyns recognize the benefits of Tdap and recommend vaccination during pregnancy, barriers such as insurance reimbursement and financial concerns for the practice can outweigh the perceived benefits. This resulted in some ob-gyns reporting choosing not to stock and administer the vaccine in their practice. Recommendations to address these concerns include 1) structural support for Tdap vaccine administration in ob-gyns practices; 2) Continuing medical education-equivalent educational interventions that address management techniques, vaccine coding, and other relevant information; and 3) interventions to assist physicians in communicating the importance of Tdap vaccination during pregnancy.

Using a board game to reinforce learning.

Experiential gaming strategies offer a variation on traditional learning. A board game was used to present synthesized content of fundamental catheter care concepts and reinforce evidence-based practices relevant to nursing. Board games are innovative educational tools that can enhance active learning.

Changing Behavior among Nurses to Track Indwelling Urinary Catheters in Hospitalized Patients.

Catheter-associated urinary tract infections (CAUTIs) are preventable complications of hospitalization. An interdisciplinary team developed a curriculum to increase awareness of the presence of indwelling urinary catheters (IUCs) in hospitalized patients, addressed practical, primarily nurse-controlled inpatient risk-reduction interventions, and promoted the use of the IUC labels ("tags"). Five thirty-minute educational sessions were cycled over three daily nursing shifts on two inpatient medical floors over a 1-year period; participants were surveyed (n = 152) to elicit feedback and provide real-time insight on the learning objectives. Nurse self-reported IUC tagging was early and sustained; after the IUC tag was introduced, there was a significant increase in tagging reported by the end of the block of educational sessions (from 46.2% to 84.6%, P = 0.001). Early engagement combined with a targeted educational initiative led to increased knowledge, changes in behavior, and renewed CAUTI awareness in hospitalized patients with IUCs. The processes employed in this small-scale project can be applied to broader, hospitalwide initiatives and to large-scale initiatives for healthcare interventions. As first-line providers with responsibility for the placement and daily maintenance of IUCs, nurses are ideally positioned to implement efforts addressing CAUTIs in the hospital setting.

A better fit: industry collaboration with nurse-clinicians in the development and redesign of a pneumatic compression device.

BACKGROUND: Intermittent pneumatic compression (IPC) devices offer a safe and effective means of thromboprophylaxis but are often uncomfortable, leading to poor compliance. METHODS: Two multicenter, prospective trials compared traditional IPC sleeves with newly designed IPC sleeves. The primary outcome measure was overall patient acceptance. Secondary measures involved nurses' impressions, patients' experiences, and device safety. RESULTS: In Trial 1 (n = 110), 87% of patients preferred the new knee-length sleeve compared with the traditional knee-length sleeve. Thigh-length sleeve enrollment was discontinued early (n = 38), because nurses reported that the new sleeve did not remain in place. Following redesign of the thigh-length sleeve, Trial 2 (n = 110) was executed and 82% of patients preferred this sleeve compared with the traditional thigh-length sleeve. Patients' experiences and clinicians' impressions were better with the new sleeves. No device-related adverse events were reported. CONCLUSIONS: Collaboration with nurses yielded a more comfortable IPC sleeve with properties that should improve compliance and optimize patient outcomes.

Establishing tolerance levels for customer complaints.

Customer complaints data are usually expressed as counts for a period of time and are governed by a Poisson process. This process is stationary when the number of complaints is constant, while a change in these numbers would indicate a potential change in the product performance. In this paper we describe an approach for establishing the maximum tolerance level for the number of complaints received within a month. Tolerance level is based on a relatively stable period of time when the Poisson process is stationary. A change-point analysis is performed to the complaints data that exhibit large changes to partition the relatively stable period from the problematic period. Examples that illustrate this approach are provided.

Linearity evaluation of analytical methods that count particles.

Linearity evaluation of an analytical method is important for both manufacturers of diagnostic devices and laboratory users. Some of the statistical assumptions for estimation and testing in linear regression are violated in analytical methods that count particles per unit of volume or/and time, leading to potential erroneous evaluation of linearity. The objective of this paper is to provide an approach for evaluating linearity in these cases. The number of counts for each concentration level has a Poisson probability distribution that is linear, second-, or higher-order polynomial function of the concentration. Maximum likelihood approach is used to estimate the parameters of the models. Deviance of a particular model and the likelihood ratio test are used to test for linearity. An evaluation of linearity of an analytical method in multiple experiments is also described. No particular changes to the standard testing protocols and data collections are necessary. There are several statistical software packages that can perform the calculations. Formulas and SAS codes presented in this article can also assist in estimation and statistical testing.