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Item 5 ways that colleges and universities are pitching in to deal with the coronavirus pandemic(The Conversation US, Inc., 2020-04-21) Shaker, Genevieve; Plater, William; Lilly Family School of PhilanthropyItem Acceptability of multipurpose human papillomavirus vaccines among providers and mothers of adolescent girls: A mixed-methods study in five countries(Elsevier, 2017-06) Vielot, Nadja A.; Goldberg, Shoshana K.; Zimet, Gregory; Smith, Sara B.; McDonald, Mary Anne; Ramos, Silvina; Morgan, Karen; Kim, Chan Joo; Richter, Karin L.; Peris, Merce; Whaley, Kevin J.; Smith, Jennifer S.; Medicine, School of MedicineINTRODUCTION: Multipurpose vaccines (MPVs) could be formulated to prevent multiple sexually transmitted infections simultaneously. Little is known about acceptability of MPVs among vaccine health care providers (HCPs) or mothers of adolescent girls. METHODS: 151 adolescent vaccine providers and 118 mothers of adolescent girls aged 9-14 were recruited from five geographically-diverse countries: Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providers' preferences for single-purpose human papillomavirus (HPV) vaccine versus MPVs (including HPV+herpes simplex virus (HSV)-2, HPV+HIV, or HPV+HSV-2+HIV) via quantitative surveys. Maternal MPV attitudes were assessed in four focus group discussions (FGDs) in each country. RESULTS: Most providers preferred MPVs over single-purpose HPV vaccination, with preference ranging from 61% in Malaysia to 96% in South Africa. HPV+HSV-2+HIV was the most preferred MPV formulation (56-82%). Overall, 53% of the mothers preferred MPVs over single-purpose HPV vaccines, with strongest support in South Africa (90%) and lowest support in South Korea (29%). Convenience and trust in the health care system were commonly-cited reasons for MPV acceptability. Safety and efficacy concerns were common barriers to accepting MPVs, though specific concerns differed by country. Across FGDs, additional safety and efficacy information on MPVs were requested, particularly from trusted sources like HCPs. CONCLUSIONS: Though maternal acceptability of MPVs varied by country, MPV acceptability would be enhanced by having HCPs provide parents with additional MPV vaccine safety and efficacy information. While most providers preferred MPVs, future health behavior research should identify acceptability barriers, and targeted provider interventions should equip providers to improve vaccination discussions with parents.Item Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: a systematic review and meta-analysis(BMC, 2021-10) Alhumaid, Saad; Al Mutair, Abbas; Al Alawi, Zainab; Rabaan, Ali A.; Tirupathi, Raghavendra; Alomari, Mohammed A.; Alshakhes, Aqeel S.; Alshawi, Abeer M.; Ahmed, Gasmelseed Y.; Almusabeh, Hassan M.; Alghareeb, Tariq T.; Alghuwainem, Abdulaziz A.; Alsulaiman, Zainab A.; Alabdulmuhsin, Mohammed A.; AlBuwaidi, Emad A.; Dukhi, Amjad K. Bu; Mufti, Hani N.; Al-Qahtani, Manaf; Dhama, Kuldeep; Al-Tawfiq, Jaffar A.; Al-Omari, Awad; Medicine, School of MedicineBackground Currently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population. Objectives To estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases. Design A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed. Methods Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis, non-anaphylaxis, anaphylactic reaction, nonanaphylactic reaction, anaphylactic/anaphylactoid shock, hypersensitivity, allergy reaction, allergic reaction, immunology reaction, immunologic reaction, angioedema, loss of consciousness, generalized erythema, urticaria, urticarial rash, cyanosis, grunting, stridor, tachypnoea, wheezing, tachycardia, abdominal pain, diarrhea, nausea, vomiting and tryptase. We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses. Results Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9 to 7.2, I2 = 81%, p = < 0.0001), while the overall pooled prevalence estimate of nonanaphylactic reactions to both vaccines was 53.9 (95% CI 0.0 to 116.1, I2 = 99%, p = < 0.0001). Vaccination with Pfizer-BioNTech resulted in higher anaphylactic reactions compared to Moderna (8.0, 95% CI 0.0 to 11.3, I2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I2 = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I2 = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of anaphylaxis and nonanaphylactic reactions associated with mRNA COVID-19 immunization based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger’s tests confirmed asymmetry by producing p values < 0.05. Across the included studies, the most commonly identified risk factors for anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines were female sex and personal history of atopy. The key triggers to anaphylactic and nonanaphylactic reactions identified in these studies included foods, medications, stinging insects or jellyfish, contrast media, cosmetics and detergents, household products, and latex. Previous history of anaphylaxis; and comorbidities such as asthma, allergic rhinitis, atopic and contact eczema/dermatitis and psoriasis and cholinergic urticaria were also found to be important. Conclusion The prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low; and nonanaphylactic reactions occur at higher rate, however, cutaneous reactions are largely self-limited. Both anaphylactic and nonanaphylactic reactions should not discourage vaccination.Item Author Correction: Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C(Springer Nature, 2022-08-12) Tang, Juanjie; Novak, Tanya; Hecker, Julian; Grubbs, Gabrielle; Zahra, Fatema Tuz; Bellusci, Lorenza; Pourhashemi, Sara; Chou, Janet; Moffitt, Kristin; Halasa, Natasha B.; Schwartz, Stephanie P.; Walker, Tracie C.; Tarquinio, Keiko M.; Zinter, Matt S.; Staat, Mary A.; Gertz, Shira J.; Cvijanovich, Natalie Z.; Schuster, Jennifer E.; Loftis, Laura L.; Coates, Bria M.; Mack, Elizabeth H.; Irby, Katherine; Fitzgerald, Julie C.; Rowan, Courtney M.; Kong, Michele; Flori, Heidi R.; Maddux, Aline B.; Shein, Steven L.; Crandall, Hillary; Hume, Janet R.; Hobbs, Charlotte V.; Tremoulet, Adriana H.; Shimizu, Chisato; Burns, Jane C.; Chen, Sabrina R.; Moon, Hye Kyung; Lange, Christoph; Randolph, Adrienne G.; Khurana, Surender; Pediatrics, School of MedicineCorrection to: Nature Communications 10.1038/s41467-022-30649-1, published online 27 May 2022Item A Case of Autoimmune Hemolytic Anemia after the First Dose of COVID-19 mRNA-1273 Vaccine with Undetected Pernicious Anemia(Hindawi, 2022-01-29) Jaydev, Fnu; Kumar, Vinod; Khatri, Jaikumar; Shahani, Shobha; Beganovic, Sead; Medicine, School of MedicineBy this time, multiple vaccines have been approved to limit the spread of SARS-CoV-2 worldwide. These include new-generation vaccines that contain mRNA of the target organism. Some common side effects were identified and reported during phase 3 clinical trials of vaccination, but more rare adverse events were reported in the literature. One such concern is autoimmune conditions that SARS-CoV-2 viral antigens could have possibly incited. We are presenting here a case of a young female with no known autoimmune diseases, diagnosed with autoimmune hemolytic anemia about a week after receiving her first dose of the COVID-19 mRNA vaccine. We discuss the possible culprit for precipitation of autoimmune hemolytic anemia after the SARS-CoV-2 mRNA vaccine, which encodes virus spike protein. This case highlights the importance of being vigilant for identifying rare adverse events that could appear during mass vaccination.Item A Class I Haemophilus ducreyi Strain Containing a Class II hgbA Allele Is Partially Attenuated in Humans: Implications for HgbA Vaccine Efficacy Trials(American Society for Microbiology, 2019-07) Leduc, Isabelle; Fortney, Kate R.; Janowicz, Diane M.; Zwickl, Beth; Ellinger, Sheila; Katz, Barry P.; Lin, Huaiying; Dong, Qunfeng; Spinola, Stanley M.; Microbiology and Immunology, School of MedicineHaemophilus ducreyi causes chancroid and is a major cause of cutaneous ulcers in children. Due to environmental reservoirs, both class I and class II H. ducreyi strains persist in cutaneous ulcer regions of endemicity following mass drug administration of azithromycin, suggesting the need for a vaccine. The hemoglobin receptor (HgbA) is a leading vaccine candidate, but its efficacy in animal models is class specific. Controlled human infection models can be used to evaluate vaccines, but only a class I strain (35000HP) has been characterized in this model. As a prelude to evaluating HgbA vaccines in the human model, we tested here whether a derivative of 35000HP containing a class II hgbA allele (FX548) is as virulent as 35000HP in humans. In eight volunteers infected at three sites with each strain, the papule formation rate was 95.8% for 35000HP versus 62.5% for FX548 (P = 0.021). Excluding doses of FX548 that were ≥2-fold higher than those of 35000HP, the pustule formation rate was 25% for 35000HP versus 11.7% for FX548 (P = 0.0053). By Western blot analysis, FX548 and 35000HP expressed equivalent amounts of HgbA in whole-cell lysates and outer membranes. The growth of FX548 and 35000HP was similar in media containing hemoglobin or hemin. By whole-genome sequencing and single-nucleotide polymorphism analysis, FX548 contained no mutations in open reading frames other than hgbA. We conclude that by an unknown mechanism, FX548 is partially attenuated in humans and is not a suitable strain for HgbA vaccine efficacy trials in the model.Item Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C(Springer Nature, 2022-05-27) Tang, Juanjie; Novak, Tanya; Hecker, Julian; Grubbs, Gabrielle; Tuz Zahra, Fatema; Bellusci, Lorenza; Pourhashemi, Sara; Chou, Janet; Moffitt, Kristin; Halasa, Natasha B.; Schwartz, Stephanie P.; Walker, Tracie C.; Tarquinio, Keiko M.; Zinter, Matt S.; Staat, Mary A.; Gertz, Shira J.; Cvijanovich, Natalie Z.; Schuster, Jennifer E.; Loftis, Laura L.; Coates, Bria M.; Mack, Elizabeth H.; Irby, Katherine; Fitzgerald, Julie C.; Rowan, Courtney M.; Kong, Michele; Flori, Heidi R.; Maddux, Aline B.; Shein, Steven L.; Crandall, Hillary; Hume, Janet R.; Hobbs, Charlotte V.; Tremoulet, Adriana H.; Shimizu, Chisato; Burns, Jane C.; Chen, Sabrina R.; Moon, Hye Kyung; Lange, Christoph; Randolph, Adrienne G.; Khurana, Surender; Pediatrics, School of MedicineNeutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5-11, 12-21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron. Children <5 years of age hospitalized with severe acute COVID-19 have lower neutralizing antibodies to SARS-CoV-2 variants compared with patients >5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children.Item Development of Combination Vaccine Conferring Optimal Protection against Six Pore-Forming Toxins of Staphylococcus aureus(American Society for Microbiology, 2021) Zhang, QingFeng; Jiang, TingTing; Mao, Xinrui; Kim, Jae Deog; Ahn, Dong Ho; Jung, Yunjin; Bae, Taeok; Lee, Bok Luel; Microbiology and Immunology, School of MedicineIn the Gram-positive pathogen Staphylococcus aureus, pore-forming toxins (PFTs), such as leukocidins and hemolysins, play prominent roles in staphylococcal pathogenesis by killing host immune cells and red blood cells (RBCs). However, it remains unknown which combination of toxin antigens would induce the broadest protective immune response against those toxins. In this study, by targeting six major staphylococcal PFTs (i.e., gamma-hemolysin AB [HlgAB], gamma-hemolysin CB [HlgCB], leukocidin AB [LukAB], leukocidin ED [LukED], Panton-Valentine leukocidin [LukSF-PV], and alpha-hemolysin [Hla]), we generated 10 recombinant toxins or toxin subunits, 3 toxoids, and their rabbit antibodies. Using the cytolytic assay for RBCs and polymorphonuclear cells (PMNs), we determined the best combination of toxin antibodies conferring the broadest protection against those staphylococcal PFTs. Although anti-HlgA IgG (HlgA-IgG) showed low cross-reactivity to other toxin components, it was essential to protect rabbit and human RBCs and human PMNs. For the protection of rabbit RBCs, HlaH35L toxoid-IgG was also required, whereas for human PMNs, LukS-IgG and LukAE323AB-IgG were essential too. When the toxin/toxoid antigens HlgA, LukS-PV, HlaH35L, and LukAE323AB were used to immunize rabbits, they increased rabbit survival; however, they did not block staphylococcal abscess formation in kidneys. Based on these results, we proposed that the combination of HlgA, LukS, HlaH35L, and LukAE323AB is the optimal vaccine component to protect human RBCs and PMNs from staphylococcal PFTs. We also concluded that a successful S. aureus vaccine requires not only those toxin antigens but also other antigens that can induce immune responses blocking staphylococcal colonization.Item Efficacy of tailored messages to improve behavioral intent to accept HPV vaccination among mothers may be moderated by sociodemographics(Elsevier, 2021-05-29) Feemster, Kristen A.; Head, Katharine J.; Panozzo, Catherine A.; O'Dell, Sean M.; Zimet, Gregory D.; Kornides, Melanie L.; Pediatrics, School of MedicineWe assessed differences in response to a tailored recommendation intervention for HPV vaccine by participants’ sociodemographic characteristics in this exploratory sub-analysis of a larger web-based, randomized-controlled trial on tailored messaging among mothers with low intent to vaccinate their 11–14-year-old child against HPV. The intervention consisted of pre-recorded video messages tailored to 1–5 common concerns about HPV vaccine. In these exploratory analyses, we used generalized linear models to assess differences in post-intervention intent across intervention arms, stratified by sociodemographic characteristics among 496 trial participants. We found significantly higher post-intervention intent in the intervention participants versus the control group among mothers: 1) with younger children; 2) with white vs. black children; 3) with Non-Hispanic children; 4) who were younger; 5) with some college or vocational training; with household incomes of ≥$100,000; and 7) with 1–2 children. Our findings of effect modification by certain sociodemographic factors such as age, race/ethnicity, and household income should be considered when designing similar tailored messaging interventions.Item Emergency preparedness is a healthcare issue: COVID-19 pandemic's influence on attitudes and behaviors among a national sample of parents(Elsevier, 2023) Glauberman, Gary; Zimet, Gregory; Michel, Alexandra; Fontenot, Holly B.; Pediatrics, School of MedicineBackground: Improving household emergency preparedness (EP) is a public health priority, yet little is known about what influence the COVID-19 pandemic had on families' EP. This study aimed to explore current EP attitudes and behaviors. Methods: We conducted online focus groups in Winter 2022 with a nationwide sample of parents of adolescents. We held six 90-min focus groups of 9-15 participants using a semi-structured interview script that elicited parental knowledge and attitudes related to household EP. Two researchers conducted qualitative content analysis on focus group transcripts. First-level coding within and across scripts was used to identify broad categories or themes regarding EP. The process was reviewed continuously to verify data and coding procedures. Three investigators independently verified the final themes that emerged. Results: Participants (N = 64) were mostly female (n = 54, 84.3%), white (n = 46, 71.9%), and college-educated (n = 49, 76.6%). Major themes included: 1) Expanded awareness and behavioral change related to EP due to the COVID-19 pandemic, 2) Reconceptualization of planning for family health as part of EP, 3) Changing perspectives related to vaccination as a component of EP, and 4) Perspectives related to discussing EP with their health care provider. Conclusions: EP was described as a healthcare issue and healthcare providers were identified as trusted sources of EP information. Interventions to support providers' ability to assist with individual EP health action plans, including discussing vaccination as part of preparedness are needed.