Consideration for alpha-gal syndrome in two critically ill persons with group O blood who received group B plasma.

BACKGROUND: The U.S. Centers for Disease Control and Prevention (CDC) has reported increasing rates of alpha-gal syndrome, an allergic response after meat ingestion (AGS). AGS has been associated with prior exposure to tick bites or other biologics characterized by a life-threatening immunoglobulin E (IgE)-mediated hypersensitivity to galactose-alpha-1,3-galactose (alpha-gal) an oligosaccharide structurally similar to the group B antigen on red blood cells (RBC) found in most non-primate mammalian meat and products derived from these mammals. In 2023, Transfusion reported 3 group O recipients of group B plasma in the Washington, D.C. metropolitan area with no history of meat allergy who had anaphylactic transfusion reactions compatible with AGS. AIMS: We investigated allergic reactions in 2 additional patients who received ABO minor-incompatible blood products at 2 hospitals in the D.C. area during fall 2023. METHODS: For both patients, a medical chart review was performed and IgE levels to alpha-gal were measured. RESULTS: The first patient, a 64-year-old, O-positive patient status post heart transplant with no known allergies, was admitted with acute COVID-19 induced antibody-mediated transplant rejection and placed on extracorporeal membrane oxygenation (ECMO). While undergoing plasma exchange (PLEX) (50% albumin/50% fresh frozen plasma (FFP)), the patient tolerated 2 units of group O FFP and 1 unit of group A FFP before becoming hemodynamically unstable during transfusion of 1 unit of B-positive FFP. PLEX was stopped. The patient later died of sepsis from underlying causes. The second patient, a 57-year-old O-positive man with a history of melanoma and neuro fibromatosis type 1, was undergoing an abdominal resection including transfusion of 3 units of O-positive RBC when he suffered hypotension and ventricular tachycardia requiring intraoperative code after receiving 2 units of group B FFP. Hiveswere noted after resuscitation. The patient had a history of tick bites but no known allergies. He is alive 5 months after the possible allergic event. Both patients had full transfusion reaction evaluations and immunology testing results above the positive cutoff for anti-alpha-gal IgE. DISCUSSION AND CONCLUSION: Two patients with O-positive blood and no known allergies experience danaphyl axis after transfusion with group B FFP. The symptoms cannot definitively be imputed to an allergic transfusion reaction, but the presence of IgE against alpha-gal supports an association. Medicating patients with antihistamines and IV steroids pre-transfusion may prevent allergic reactions. Restricting group B plasma-containing products (plasma, platelets, cryoprecipitate) for patients who experience AGS-like symptoms may be considered.

A technology-enabled multi-disciplinary team-based care model for the management of Long COVID and other fatiguing illnesses within a federally qualified health center: protocol for a two-arm, single-blind, pragmatic, quality improvement professional cluster randomized controlled trial.

BACKGROUND: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. METHODS: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. DISCUSSION: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.

Case Report: Kinetics and durability of humoral and cellular response of SARS-CoV-2 messenger RNA vaccine in a lung and kidney transplant recipient.

We present a case report of a 63-year-old female health care worker who is 15 years status post double lung transplant and six years status post living related donor kidney transplant who is healthy on a chronic immunosuppression regimen including prednisone, mycophenolate, and tacrolimus who received the SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech BNT162b2) primary series and had poor initial humoral response to the COVID-19 mRNA vaccine, then demonstrated a robust, sustained immune response against S1 and S2 antigens for over seven months after receiving the recommended vaccine doses, including booster dose, without developing COVID-19 or other serious adverse events. Her immune response to vaccination indicates effective formation of anti-spike T cell memory despite chronic immunosuppression. This case report provides a comprehensive characterization of her immune response to this SARS-CoV-2 vaccination series. As vaccine effectiveness data is updated, and as better understanding of immune response including hybrid immunity emerges, these findings may reassure that recipients of SOTs may be capable of durable immune responses to emerging variants of SARS-CoV-2.

The Mould That Changed the World-A Musical Paean to Penicillin.

This Arts and Medicine feature reviews The Mould That Changed the World, a musical about the history of penicillin that uses fringe set design, eccentric staging, and quirky lyrics to teach audiences the importance of antimicrobial stewardship.

Post-COVID conditions and healthcare utilization among adults with and without disabilities-2021 Porter Novelli FallStyles survey.

BACKGROUND: Adults with disabilities are at increased risk for SARS-CoV-2 infection and severe disease; whether adults with disabilities are at an increased risk for ongoing symptoms after acute SARS-CoV-2 infection is unknown. OBJECTIVES: To estimate the frequency and duration of long-term symptoms (>4 weeks) and health care utilization among adults with and without disabilities who self-report positive or negative SARS-CoV-2 test results. METHODS: Data from a nationwide survey of 4510 U.S. adults administered from September 24, 2021-October 7, 2021, were analyzed for 3251 (79%) participants who self-reported disability status, symptom(s), and SARS-CoV-2 test results (a positive test or only negative tests). Multivariable models were used to estimate the odds of having ≥1 COVID-19-like symptom(s) lasting >4 weeks by test result and disability status, weighted and adjusted for socio-demographics. RESULTS: Respondents who tested positive for SARS-CoV-2 had higher odds of reporting ≥1 long-term symptom (with disability: aOR = 4.50 [95% CI: 2.37, 8.54] and without disability: aOR = 9.88 [95% CI: 7.13, 13.71]) compared to respondents testing negative. Among respondents who tested positive, those with disabilities were not significantly more likely to experience long-term symptoms compared to respondents without disabilities (aOR = 1.65 [95% CI: 0.78, 3.50]). Health care utilization for reported symptoms was higher among respondents with disabilities who tested positive (40%) than among respondents without disabilities who tested positive (18%). CONCLUSIONS: Ongoing symptoms among adults with and without disabilities who also test positive for SARS-CoV-2 are common; however, the frequency of health care utilization for ongoing symptoms is two-fold among adults with disabilities.

Human Papillomavirus Detection in Scrotal Squamous Cell Carcinoma: Case Series from a Population-Based Cancer Registry.

Introduction: Scrotal squamous cell carcinomas (SCCs) are rare malignancies that are not considered to be associated with the human papillomavirus (HPV) by the International Agency for Research on Cancer. However, recent studies have detected HPV in these cancers. We sought to determine the presence of HPV types among scrotal cancer cases identified through population-based cancer registries. Methods: Primary scrotal SCCs diagnosed from 2014 to 2015 were identified, and tissue sections from formalin-fixed, paraffin-embedded tissue blocks were obtained for laboratory testing. A pathology review was performed to confirm morphology. HPV testing was performed using L1 consensus polymerase chain reaction analysis. Immunohistochemistry was used to evaluate p16INK4a (p16) expression. Results: Five cases of scrotal SCC were identified from 1 cancer registry. Age at diagnosis ranged from 34 to 75 years (median, 56 years). Four cases were non-Hispanic White, and 1 was non-Hispanic Black. The morphologic subtype of 4 cases was keratinizing (usual), and 1 case was verrucous (warty) histologic subtype. Two of the usual cases of SCC were HPV-negative and p16-negative, and 2 were positive for HPV16 and p16. The verrucous (warty) SCC subtype case was HPV6-positive and p16-negative. Conclusions: The presence of HPV16 and p16 overexpression in the examined tissue specimens lends additional support for the role of HPV in the etiology of scrotal SCC.

Severe Monkeypox in Hospitalized Patients - United States, August 10-October 10, 2022.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.§ Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox¶ during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy†† in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.§§ Engaging all persons with HIV in sustained care remains a critical public health priority.

Association of Trends in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Seroprevalence and State-Issued Nonpharmaceutical Interventions: United States, 1 August 2020 to 30 March 2021.

BACKGROUND: We assess if state-issued nonpharmaceutical interventions (NPIs) are associated with reduced rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as measured through anti-nucleocapsid (anti-N) seroprevalence, a proxy for cumulative prior infection that distinguishes seropositivity from vaccination. METHODS: Monthly anti-N seroprevalence during 1 August 2020 to 30 March 2021 was estimated using a nationwide blood donor serosurvey. Using multivariable logistic regression models, we measured the association of seropositivity and state-issued, county-specific NPIs for mask mandates, gathering bans, and bar closures. RESULTS: Compared with individuals living in a county with all three NPIs in place, the odds of having anti-N antibodies were 2.2 (95% confidence interval [CI]: 2.0-2.3) times higher for people living in a county that did not have any of the 3 NPIs, 1.6 (95% CI: 1.5-1.7) times higher for people living in a county that only had a mask mandate and gathering ban policy, and 1.4 (95% CI: 1.3-1.5) times higher for people living in a county that had only a mask mandate. CONCLUSIONS: Consistent with studies assessing NPIs relative to COVID-19 incidence and mortality, the presence of NPIs were associated with lower SARS-CoV-2 seroprevalence indicating lower rates of cumulative infections. Multiple NPIs are likely more effective than single NPIs.

Knowledge, attitudes, and practices associated with zoonotic disease transmission risk in North Sulawesi, Indonesia.

BACKGROUND: Hunters, vendors, and consumers are key actors in the wildlife trade value chain in North Sulawesi, Indonesia, and potentially face an elevated risk of exposure to zoonotic diseases. Understanding the knowledge, attitudes, and practices (KAP) associated with the risk of zoonotic disease transmission in these communities is therefore critical for developing recommendations to prevent or mitigate zoonotic outbreaks in the future. METHODS: Qualitative and quantitative methods were combined to understand KAP associated zoonotic diseases transmission risk in communities involved in the wildlife trade in North Sulawesi. Qualitative data were collected through semi-structured ethnographic interviews and focus group discussions (FGDs) while quantitative data were collected using questionnaires. We conducted 46 ethnographic interviews and 2 FGDs in 2016, and 477 questionnaire administrations in 2017-2018 in communities from five districts in North Sulawesi. We also collected biological specimens, including nasal swab, oropharyngeal swab, and blood, from 254 participants. The study sites were targeted based on known wildlife consumption and trade activities. The participants for qualitative data collection were purposively selected while participants for quantitative data collection were randomly selected. Biological samples were tested for five viral families including Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. RESULTS: Knowledge regarding disease transmission from animals to humans was similar across the participants in qualitative focus groups, including knowledge of rabies and bird flu as zoonotic diseases. However, only a small fraction of the participants from the quantitative group (1%) considered that contact with wild animals could cause sickness. Our biological specimen testing identified a single individual (1/254, 0.004%) who was sampled in 2018 with serological evidence of sarbecovirus exposure. Overall, participants were aware of some level of risk in working with open wounds while slaughtering or butchering an animal (71%) but most did not know what the specific risks were. However, significant differences in the attitudes or beliefs around zoonotic disease risk and health seeking behaviors were observed across our study sites in North Sulawesi. CONCLUSIONS: Our study showed variable levels of knowledge, attitudes, and practices associated with the risk of zoonotic disease transmission among study participants. These findings can be used to develop locally responsive recommendations to mitigate zoonotic disease transmission.

How do we form and coordinate a national serosurvey of SARS-CoV-2 within the blood collection industry?

BACKGROUND: A national serosurvey of U.S. blood donors conducted in partnership with the Centers for Disease Control and Prevention (CDC) was initiated to estimate the prevalence of SARS-CoV-2 infections and vaccinations. METHODS: Beginning in July 2020, the Nationwide Blood Donor Seroprevalence Study collaborated with multiple blood collection organizations, testing labs, and leadership from government partners to capture, test, and analyze approximately 150,000 blood donation specimens per month in a repeated, cross-sectional seroprevalence survey. RESULTS: A CDC website (https://covid.cdc.gov/covid-data-tracker/#nationwide-blood-donor-seroprevalence) provided stratified, population-level results to public health professionals and the general public. DISCUSSION: The study adapted operations as the pandemic evolved, changing specimen flow and testing algorithms, and collecting additional data elements in response to changing policies on universal blood donation screening and administration of SARS-CoV-2 spike-based vaccines. The national serosurvey demonstrated the utility of serosurveillance testing of residual blood donations and highlighted the role of the blood collection industry in public-private partnerships during a public health emergency.

Environmental Change and Zoonotic Disease Risk at Human-Macaque Interfaces in Bangladesh.

Anthropogenic land-use changes increase the frequency of interactions and habitat overlap between humans and macaques which play an important role in zoonotic disease transmission. This exploratory qualitative study aimed to examine connections between land-use change and macaque-human interactions and assess the chance of zoonotic disease transmission. We conducted ethnographic interviews and focus group discussions in Old Dhaka, Madaripur, and Chandpur, Bangladesh. Participants reported significant anthropogenic landscape transformations leading to increased human-macaque contact in the study areas. Participants also reported that all three sites underwent substantial landscape alteration from natural or agricultural land to a human-altered environment with roads, commercial, and residential buildings. Participants noted that the disappearance of forestland appeared to increase the macaque dependence on backyard fruit trees. Where rivers and ponds were filled to support local construction, macaques were also observed as becoming more dependent upon human water sources. These changed may help expanding the macaques' foraging areas, and they appear to be invading new areas where people are not culturally habituated to living with them. In response, many residents reported reacting aggressively toward the macaques, which they believed led to more bites and scratches. However, other respondents accepted the presence of macaques around their homes. Few participants considered macaques to be a source of disease transmission. This study revealed that local environmental changes, deforestation, urban expansion, construction, and water bodies' disappearance are linked to increasing human-macaque interactions. Understanding these interactions is critical to develop successful mitigation interventions at interfaces with a high risk for viral disease spillover.

Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021.

Importance: People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. Objective: To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. Design, Setting, and Participants: In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. Exposure: Calendar time. Main Outcomes and Measures: Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. Results: Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. Conclusions and Relevance: Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population.

How do I facilitate a rapid response to a public health emergency requiring plasma collection with a public-private partnership?

In March 2020, there were no treatment options for COVID-19. Passive immune therapy including anti-SARS-CoV-2 hyperimmune globulin (hIVIG) was a logical candidate for COVID-19 therapeutic trials, given past success treating emerging pathogens with endogenous neutralizing antibodies. We established a plasma collection protocol for persons recovered from COVID-19. To speed recruitment in the first U.S. hotspot, Seattle, Washington, federal and state public health agencies collaborated with Bloodworks Northwest to collect convalescent plasma (CP) for manufacturing hIVIG. During March-December 2020, we identified and recruited prospective CP donors via letters to persons recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection. Prospective donors were pre-screened and administered a medical history survey. Anti-SARS-CoV-2 neutralizing antibody (NAb) titers were classified as qualifying (≥1:80) or non-qualifying (<1:80) for enrollment based on a live virus neutralization assay. Generalized estimating equations were used to identify characteristics of donors associated with qualifying versus nonqualifying NAb titers. Overall, 21,359 letters resulted in 3207 inquiries, 2159 prescreenings with laboratory-confirmed SARS-CoV-2 infection, and 573 donors (27% of all pre-screenings with confirmed infection) who provided a screening plasma donation. Of 573 donors screened, 254 (44%) provided plasma with qualifying NAb titers, resulting in 1284 units for hIVIG manufacture. In a multivariable model, after adjusting for other factors, time (60 days) from COVID-19 symptom onset to screening was associated with lower odds of qualifying NAb (adjusted odds ratio = 0.67, 95% CI: 0.48-0.94). The collaboration facilitated a rapid response to develop and provide hIVIG for clinical trials and CP for transfusion. Only 1 in 12 donor inquiries resulted in a qualifying plasma donation. Challenges included recruitment and the relatively low percentage of persons with high NAb titers and limited screening capacity. This resource-intensive collaboration may not be scalable but informs preparedness and response strategies for plasma collection in future epidemics. Operational readiness plans with templates for screening, consent, and data collection forms are recommended.

Assessment of Coagulation and Hemostasis Biomarkers in a Subset of Patients With Chronic Cardiovascular Disease.

Measurement of a single marker of coagulation may not provide a complete picture of hemostasis activation and fibrinolysis in patients with chronic cardiovascular diseases. We assessed retrospective orders of a panel which included prothrombin fragment 1.2 (PF1.2), thrombin: antithrombin complexes, fibrin monomers, and D-dimers in patients with heart assist devices, cardiomyopathies, atrial fibrillation and intracardiac thrombosis (based on ordering ICD-10 codes). During 1 year there were 117 panels from 81 patients. Fifty-six (69%) patients had heart assist devices, cardiomyopathy was present in 17 patients (21%) and 29 patients (36%) had more than 1 condition. PF1.2 was most frequently elevated in patients with cardiomyopathy (61.1%) compared to those with cardiac assist devices (15.7%; P = 0.0002). D-dimer elevation was more frequent in patients with cardiac assist devices (98.8%) compared to those patients with cardiomyopathy (83.3%; P = 0.014). Patients with cardiomyopathy show increases of PF1.2 suggesting thrombin generation. In contrast, elevations of D-dimers without increase in other coagulation markers in patients with cardiac assist devices likely reflect the presence of the intravascular device and not necessarily evidence of hemostatic activation.

Severe Acute Respiratory Syndrome Coronavirus 2 Testing Trends Among Persons Aged <18 Years in an Outpatient Pediatric Practice - Metropolitan Atlanta, Georgia, May-December 2020.

PURPOSE: The purpose of this study was to analyze trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and test positivity among persons aged <18 years in a three-site outpatient pediatric practice in Atlanta, Georgia, serving approximately 35,000 pediatric patients. METHODS: Using electronic medical records, weekly trends in SARS-CoV-2 tests performed and the 14-day moving average of test positivity were examined, overall and by age group, during May 24-December 5, 2020. RESULTS: Among 4,995 patients who received at least 1 SARS-CoV-2 test, 6,813 total tests were completed. Overall test positivity was 5.4% and was higher among older pediatric patients (<5 years: 3.3%; 5-11 years: 4.1%; 12-17 years: 8.6%). The number of tests and test positivity increased after holidays and school breaks. CONCLUSIONS: Families might benefit from communication focused on reducing SARS-CoV-2 transmission during holidays. In addition, given higher test positivity in children aged 12-17 years, tailoring public health messaging to older adolescents could help limit SARS-CoV-2 transmission risk in this population.

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats.

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development's (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security.

Impact of COVID-19 on Cervical Cancer Screening Rates Among Women Aged 21-65 Years in a Large Integrated Health Care System - Southern California, January 1-September 30, 2019, and January 1-September 30, 2020.

On March 19, 2020, the governor of California issued a statewide stay-at-home order to contain the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).* The order reduced accessibility to and patient attendance at outpatient medical visits,† including preventive services such as cervical cancer screening. In-person clinic visits increased when California reopened essential businesses on June 12, 2020.§ Electronic medical records of approximately 1.5 million women served by Kaiser Permanente Southern California (KPSC), a large integrated health care system, were examined to assess cervical cancer screening rates before, during, and after the stay-at-home order. KPSC policy is to screen women aged 21-29 years every 3 years with cervical cytology alone (Papanicolaou [Pap] test); those aged 30-65 years were screened every 5 years with human papillomavirus (HPV) testing and cytology (cotesting) through July 15, 2020, and after July 15, 2020, with HPV testing alone, consistent with the latest recommendations from U.S. Preventive Services Task Force.¶ Compared with the 2019 baseline, cervical cancer screening rates decreased substantially during the stay-at-home order. Among women aged 21-29 years, cervical cytology screening rates per 100 person-months declined 78%. Among women aged 30-65 years, HPV test screening rates per 100 person-months decreased 82%. After the stay-at-home order was lifted, screening rates returned to near baseline, which might have been aided by aspects of KPSC's integrated, organized screening program (e.g., reminder systems and tracking persons lost to follow-up). As the pandemic continues, groups at higher risk for developing cervical cancers and precancers should be evaluated first. Ensuring that women receive preventive services, including cancer screening and appropriate follow-up in a safe and timely manner, remains important.

Refractory thrombotic thrombocytopenic purpura related to checkpoint inhibitor immunotherapy.

BACKGROUND: Checkpoint inhibitors enhance T-lymphocyte-mediated antitumor responses, resulting in increased survival for patients with neoplastic disease. However, a subset of patients receiving checkpoint inhibitor therapy may experience adverse complications that include the development of autoimmune conditions, such as thrombotic thrombocytopenic purpura (TTP). Given the potential etiologic differences of checkpoint inhibitor-related autoimmunity, TTP that develops in the presence of checkpoint inhibitors may be refractory to current treatment methods and therefore may require additional treatment and prognostic consideration. CASE REPORT: Herein, we describe the unique clinical course of a patient who was treated with the combined checkpoint inhibitors nivolumab and ipilimumab for Stage IV malignant melanoma, who subsequently developed TTP. Unlike many patients with TTP, this patient failed to develop a sustained response to therapeutic plasma exchange. Additional use of steroids, anti-CD20, and plasma cell-targeting therapy (bortezomib) also failed to substantially reverse thrombocytopenia in a sustainable fashion. During this time, her melanoma progressed, and she ultimately succumbed. CONCLUSION: This case illustrates not only that TTP may be a potential complication of checkpoint inhibitor therapy, but also that TTP developing in this setting may result in an unpredictable response to commonly employed TTP treatment modalities. Ultimately, checkpoint inhibitor-related TTP may require distinct management approaches and prognostic considerations.