Healthcare personnel with laboratory-confirmed mpox in California during the 2022 outbreak.

The California Department of Public Health (CDPH) reviewed 109 cases of healthcare personnel (HCP) with laboratory-confirmed mpox to understand transmission risk in healthcare settings. Overall, 90% of HCP with mpox had nonoccupational exposure risk factors. One occupationally acquired case was associated with sharps injury while unroofing a patient's lesion for diagnostic testing.

Possible Exposures Among Mpox Patients Without Reported Male-to-Male Sexual Contact - Six U.S. Jurisdictions, November 1-December 14, 2022.

The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC.

Epidemiologic and Clinical Features of Mpox-Associated Deaths - United States, May 10, 2022-March 7, 2023.

As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States,† predominantly among cisgender men§ who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox¶ (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5).

Knockout of the neonatal Fc receptor alters immune complex trafficking and lysosomal function in cultured podocytes.

Podocytes are key to preventing the filtration of serum proteins into the urine. Recent evidence also suggests that in immune mediated kidney diseases, podocytes are the targets of immune complexes (ICs). The mechanisms whereby podocytes handle and respond to ICs remain unknown. The neonatal Fc receptor (FcRn) is involved in IgG handling in podocytes and is also required in dendritic cells to traffic ICs to the lysosome for proteolytic degradation of antigen and presentation on MHC II. Here we examine the role of FcRn in handling ICs in podocytes. We show that knockout of FcRn in podocytes results in decreased trafficking of ICs to the lysosome and increases IC trafficking to recycling endosomes. FcRn KO also alters lysosomal distribution, decreases lysosomal surface area and decreases cathepsin B expression and activity. We demonstrate that signaling pathways in cultured podocytes differ after treatment with IgG alone versus ICs and that podocyte proliferation in both WT and KO podocytes is suppressed by IC treatment. Our findings suggest that podocytes respond differentially to IgG versus ICs and that FcRn modifies the lysosomal response to ICs. Elucidating the mechanisms underlying podocyte handling of ICs may provide novel pathways to modulate immune mediated kidney disease progression.

Transitioning Long-Acting Products to a Generic Marketplace: What's Missing?

Development of and increased access to generic oral medications to treat high-burden diseases including human immunodeficiency virus (HIV), tuberculosis, viral hepatitis, and malaria have had a major impact on reducing global morbidity and mortality. However, access and adherence to these life-saving treatments remains limited for some of the most vulnerable and underserved populations, for whom stigma, control, and discretion are critical to decisions around care. Current efforts to develop long-acting formulations to treat and prevent these conditions could overcome many of these barriers. However, generic manufacturing of these innovative products will be required to ensure affordable access to the communities and patients in greatest need. Strategic investments in new infrastructure will be required even before markets and manufacturing costs are clear, to ensure that access to these new products is not delayed, particularly for patients in low- and middle-income countries. Unlike conventional oral medications, long-acting products require greater investment for formulation, packaging, and delivery. The requirement for long-term bioequivalence studies will introduce additional delays in regulatory approval of generic long-acting products, and expedited approval pathways must be developed. Lessons learned from the development of long-acting hormonal contraceptives and long-acting antiretroviral products may provide a way forward.

Enhancing Hospital-Wide Patient Flow to Reduce Emergency Department Crowding and Boarding.

INTRODUCTION: ED overcrowding and boarding is a global phenomenon that negatively affects patients, hospital staff, and hospital-wide operations. Poor patient flow has been identified as a major contributing factor to ED overcrowding and boarding, which is directly linked to negative patient outcomes. This project implemented a multidisciplinary rounding team that addressed barriers to patient flow in real time. By reducing the inpatient length of stay bed capacity will improve, which in turn will help alleviate ED boarding and overcrowding. METHODS: This before-and-after process improvement project took place on a 30-bed, inpatient medicine floor of a level-I trauma, tertiary, regional transfer center. Multidisciplinary rounding was used to improve care team communication and collaboration. Concepts from a Real-Time Demand Capacity model were used in this project to help develop a plan for capacity issues regarding bed supply and demand. Outcome variables included inpatient length of stay and ED boarding hours. RESULTS: Implementation of multidisciplinary rounding resulted in a statistically significant reduction of 0.83 days in the length of stay for patients on this floor. By increasing inpatient bed capacity, ED boarding hours for patients targeted to the 3000-medicine floor was reduced by an average of 8.83 hours per month, a reduction > 50% from baseline. DISCUSSION: Increasing inpatient bed capacity helps decrease ED access block, and contributes to reducing ED overcrowding. Implementing a daily multidisciplinary rounding structure on the inpatient floor helped hospital throughput by expediting discharges, which in turn created inpatient bed capacity.

Pediatric COVID-19 Therapeutics: Seizing the Right Research and Development Opportunities to Accelerate Access for Children.

Children, although at lower risk of poor outcomes from COVID-19 relative to adults, still stand to benefit from therapeutic interventions. Understanding of COVID-19 clinical presentation and prognosis in children is essential to optimize therapeutic trials design. This perspective illustrates how to collectively accelerate pediatric COVID-19 therapeutic research and development, based on the experience of the Global Accelerator for Paediatric Formulations.

Severe Acute Respiratory Syndrome Coronavirus 2 and Respiratory Virus Sentinel Surveillance, California, USA, May 10, 2020-June 12, 2021.

State and local health departments established the California Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Respiratory Virus Sentinel Surveillance System to conduct enhanced surveillance for SARS-CoV-2 and other respiratory pathogens at sentinel outpatient testing sites in 10 counties throughout California, USA. We describe results obtained during May 10, 2020‒June 12, 2021, and compare persons with positive and negative SARS-CoV-2 PCR results by using Poisson regression. We detected SARS-CoV-2 in 1,696 (19.6%) of 8,662 specimens. Among 7,851 specimens tested by respiratory panel, rhinovirus/enterovirus was detected in 906 (11.5%) specimens and other respiratory pathogens in 136 (1.7%) specimens. We also detected 23 co-infections with SARS-CoV-2 and another pathogen. SARS-CoV-2 positivity was associated with male participants, an age of 35-49 years, Latino race/ethnicity, obesity, and work in transportation occupations. Sentinel surveillance can provide useful virologic and epidemiologic data to supplement other disease monitoring activities and might become increasingly useful as routine testing decreases.

Podocyte-specific knockout of the neonatal Fc receptor (FcRn) results in differential protection depending on the model of glomerulonephritis.

Podocytes have been proposed to be antigen presenting cells (APCs). In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against glomerulonephritis. Since podocytes express FcRn, we sought to determine whether the absence of podocyte FcRn ameliorates immune-mediated disease. We examined MHCII and costimulatory markers expression in cultured wild type (WT) and FcRn knockout (KO) podocytes. Interferon gamma (IFNγ) induced MHCII expression in both WT and KO podocytes but did not change CD80 expression. Neither WT nor KO expressed CD86 or inducible costimulatory ligand (ICOSL) at baseline or with IFNγ. Using an antigen presentation assay, WT podocytes but not KO treated with immune complexes induced a modest increase in IL-2. Induction of the anti-glomerular basement membrane (anti-GBM) model resulted in a significant decrease in glomerular crescents in podocyte-specific FcRn knockout mouse (podFcRn KO) versus controls but the overall percentage of crescents was low. To examine the effects of the podocyte-specific FcRn knockout in a model with a longer autologous phase, we used the nephrotoxic serum nephritis (NTS) model. We found that the podFcRn KO mice had significantly reduced crescent formation and glomerulosclerosis compared to control mice. This study demonstrates that lack of podocyte FcRn is protective in immune mediated kidney disease that is dependent on an autologous phase. This study also highlights the difference between the anti-GBM model and NTS model of disease.

The Effects of Age at Weaning and Length of Lipid Supplementation on Growth, Metabolites, and Marbling of Young Steers.

The objective of this study was to determine how weaning age, days on supplements, and lipid supplementation affected the growth and marbling deposition of steers. Steers from a single sire were early weaned (n = 24) at 150 ± 11 days of age or traditionally weaned (n = 24) at 210 ± 11 days of age. Steers were assigned to control (n = 12/weaning group) or an isocaloric, isonitrogenous rumen by-pass lipid (RBL, n = 12/weaning group) for either 45 (n = 6/treatment) or 90 (n=6/treatment) days then harvested. Steer body weight (BW) was recorded on days -14 and -7, then BW and blood samples were collected on days 0, 22, 45, 66, and 90. The right rib section of each animal was collected for proximate analysis. Longissimus dorsi from RBL steers had increased lipids compared with control steers (3.6 ± 0.2 vs. 2.4 ± 0.2% on a wet basis; p < 0.0001). Steers fed for 90 days had greater (p = 0.02) concentrations of Longissimus dorsi lipid (3.3 ± 0.2%) than those fed for 45 days (2.7 ± 0.2%). There was a weaning age by treatment by days on feed interaction for intramuscular adipocyte diameter (p = 0.02) in which early weaned RBL fed for 90 days steers had an increased adipocyte diameter compared to the early weaned control fed for 90 and early weaned fed for 45 days steers with all other treatment groups as intermediates. Supplementation of RBL increased concentrations of C18:2, C20:4, and total fatty acids on days 45 and 90 (p ≤ 0.05). Data show that RBL supplementation increased the marbling content of the Longissimus dorsi. Furthermore, a longer period of supplementation resulted in increased adipose diameter.

Outbreak of Norovirus Illness Among Wildfire Evacuation Shelter Populations - Butte and Glenn Counties, California, November 2018.

The Camp Fire, California's deadliest wildfire, began November 8, 2018, and was extinguished November 25 (1). Approximately 1,100 evacuees from the fire sought emergency shelter. On November 10, acute gastroenteritis (AGE) was reported in two evacuation shelters; norovirus illness was suspected, because it is commonly detected in shelter-associated AGE outbreaks. Norovirus is highly contagious and resistant to several disinfectants. Butte County Public Health Department (BCPHD), assisted by the California Department of Public Health (CDPH), initiated active surveillance to identify cases, confirm the etiology, and assess shelter infection prevention and control (IPC) practices to guide recommendations. During November 8-30, a total of 292 patients with AGE were identified among nine evacuation shelters; norovirus was detected in 16 of 17 unique patient stool specimens. Shelter IPC assessments revealed gaps in illness surveillance, isolation practices, cleaning, disinfection, and handwashing. CDPH and BCPHD collaborated with partner agencies to implement AGE screening, institute isolation protocols and 24-hour cleaning services, and promote proper hand hygiene. During disasters with limited resources, damaged infrastructure, and involvement of multiple organizations, establishing shelter disease surveillance and IPC is difficult. However, prioritizing effective surveillance and IPC at shelter activation is necessary to prevent, identify, and contain outbreaks.

Outbreak of human infections with uncommon Salmonella serotypes linked to pet bearded dragons, 2012-2014.

Reptiles are one of the fastest growing sectors in the United States pet industry. Reptile-associated salmonellosis (RAS) continues to be an important public health problem, especially among children. We investigated an outbreak of human Salmonella infections resulting from serotypes Cotham and Kisarawe, predominately occurring among children. An outbreak of illnesses was identified in persons with exposure to pet bearded dragon lizards. Human and animal health officials, in cooperation with the pet industry, conducted epidemiologic, traceback and laboratory investigations. Onsite sampling was conducted at two US breeding facilities, one foreign breeding facility, and a large pet retail chain. A total of 166 patients in 36 states were identified with illness onset dates from 02/2012-06/2014. The median patient age was 3 years (range, <1-79 years), 57% were aged ≤5 years, and 37% were aged ≤1 year. Forty-four patients (37%) were hospitalized, predominantly children. Sampling at breeding facilities and a national pet store chain resulted in isolation of outbreak serotypes at each facility; isolation proportions ranged from 2%-24% of samples collected at each facility.Epidemiologic, microbiologic and traceback evidence linked an outbreak of uncommon Salmonella serotypes to contact with pet bearded dragons. The high proportion of infants involved in this outbreak highlights the need to educate owners about the risk of RAS in children and the potential for household contamination by pet reptiles or their habitats. Strategies should be developed to improve breeding practices, biosecurity and monitoring protocols to reduce Salmonella in the pet reptile trade.

Knockout of the neonatal Fc receptor in cultured podocytes alters IL-6 signaling and the actin cytoskeleton.

The neonatal Fc receptor (FcRn) has been shown to be required for antigen presentation in dendritic cells, and global knockout of FcRn attenuates immune-mediated kidney disease. Podocytes express interleukin-6 (IL-6) receptor and produce IL-6 under proinflammatory conditions. Here we examined the role of FcRn in the IL-6-mediated inflammatory response in podocytes. We examined IL-6 production by ELISA and expression by qPCR in wild type (WT) and FcRn knockout (KO) podocytes after treatment with proinflammatory stimuli as well as IL-6-mediated signaling via the JAK/STAT pathway. We also examined podocyte motility in cultured WT and KO podocytes after a proinflammatory challenge. We found that FcRn KO podocytes produced minimal amount of IL-6 after treatment with albumin, IgG, or immune complexes whereas WT podocytes had a robust response. FcRn KO podocytes also had minimal expression of IL-6 compared with WT. By Western blotting, there was significantly less phosphorylated STAT3 in KO podocytes after treatment with IFNγ or immune complexes. In a scratch assay, FcRn KO podocytes showed increased motility comparted KO, suggesting a defect in actin dynamics. Cultured FcRn KO podocytes also demonstrated abnormal stress fibers compared with WT and the defect could be rescued by IL-6 treatment. This study shows that in podocytes, FcRn modulates the IL-6 mediated response to proinflammatory stimuli and regulates podocytes actin structure, motility and synaptopodin expression.

Differential trafficking of albumin and IgG facilitated by the neonatal Fc receptor in podocytes in vitro and in vivo.

Proteinuria is strongly associated with kidney disease progression but the mechanisms underlying podocyte handling of serum proteins such as albumin and IgG remain to be elucidated. We have previously shown that albumin and IgG are transcytosed by podocytes in vitro. In other epithelial cells, the neonatal Fc receptor (FcRn) is required to salvage albumin and IgG from the degradative pathway thereby allowing these proteins to be transcytosed or recycled. Here we directly examine the role of FcRn in albumin and IgG trafficking in podocytes by studying handling of these proteins in FcRn knockout (KO) podocytes in vitro and in a podocyte-specific FcRn knockout mice in vivo. In vitro, we find that knockout of FcRn leads to IgG accumulation in podocytes but does not alter albumin trafficking. Similarly, in vivo, podocyte-specific knockout of FcRn does not result in albumin accumulation in podocytes in vivo as measured by mean albumin fluorescence intensity whereas these mice demonstrate significant intraglomerular accumulation of IgG over time. In addition we find that podocyte-specific FcRn KO mice demonstrate mesangial expansion as they age and activation of mesangial cells as demonstrated by increased expression of α-smooth muscle actin. Taken together, these results suggest that trafficking pathways for albumin and IgG differ in podocytes and that sustained disruption of trafficking of plasma proteins alters glomerular structure.

Catalysing the development and introduction of paediatric drug formulations for children living with HIV: a new global collaborative framework for action.

Progress in the development and introduction of paediatric formulations for key infectious diseases is poor in low-income and middle-income countries (LMICs). Although major steps have been made in the scale-up of antiretroviral medicines in LMICs, the development and deployment of formulations for infants and children is suboptimal. Of the children living with HIV globally (most in Africa), only 43% are receiving antiretroviral therapy (ART), many with suboptimal formulations. These shortfalls pose a series of challenges to meeting global treatment targets of 1·6 million children (aged 0-14 years) on ART by the end of 2018 (95% coverage) and to ensuring that 95% of those on ART are virologically suppressed. The Global Accelerator for Paediatric Formulations (GAP-f) has been developed to accelerate research, development, regulatory filing, introduction, and uptake of prioritised paediatric antiretrovirals in age-appropriate formulations by 2020, with innovative, strategic, and sustainable financing. The GAP-f will build on existing efforts to maximise coordination and alignment of policy makers, research networks, regulatory agencies, funding organisations, and manufacturers in paediatric HIV and other paediatric diseases, including tuberculosis, viral hepatitis, and other infectious diseases. Paediatric drug development and scale-up will require special efforts to bring greater visibility and new solutions to ensure that children in LMICs have access to effective and appropriate treatment options.

Shortening the decade-long gap between adult and paediatric drug formulations: a new framework based on the HIV experience in low- and middle-income countries.

INTRODUCTION: Despite the coordinated efforts by several stakeholders to speed up access to HIV treatment for children, development of optimal paediatric formulations still lags 8 to 10 years behind that of adults, due mainly to lack of market incentives and technical complexities in manufacturing. The small and fragmented paediatric market also hinders launch and uptake of new formulations. Moreover, the problems affecting HIV similarly affect other disease areas where development and introduction of optimal paediatric formulations is even slower. Therefore, accelerating processes for developing and commercializing optimal paediatric drug formulations for HIV and other disease areas is urgently needed. DISCUSSION: The Global Accelerator for Paediatric Formulations (GAP-f) is an innovative collaborative model that will accelerate availability of optimized treatment options for infectious diseases, such as HIV, tuberculosis and viral hepatitis, affecting children in low- and middle-income countries (LMICs). It builds on the HIV experience and existing efforts in paediatric drug development, formalizing collaboration between normative bodies, research networks, regulatory agencies, industry, supply and procurement organizations and funding bodies. Upstream, the GAP-f will coordinate technical support to companies to design and study optimal paediatric formulations, harmonize efforts with regulators and incentivize manufacturers to conduct formulation development. Downstream, the GAP-f will reinforce coordinated procurement and communication with suppliers. The GAP-f will be implemented in a three-stage process: (1) development of a strategic framework and promotion of key regulatory efficiencies; (2) testing of feasibility and results, building on the work of existing platforms such as the Paediatric HIV Treatment Initiative (PHTI) including innovative approaches to incentivize generic development and (3) launch as a fully functioning structure. CONCLUSIONS: GAP-f is a key partnership example enhancing North-South and international cooperation on and access to science and technology and capacity building, responding to Sustainable Development Goal (SDG) 17.6 (technology) and 17.9. (capacity-building). By promoting access to the most needed paediatric formulations for HIV and high-burden infectious diseases in low-and middle-income countries, GAP-f will support achievement of SDG 3.2 (infant mortality), 3.3 (end of AIDS and combat other communicable diseases) and 3.8 (access to essential medicines), and be an essential component of meeting the global Start Free, Stay Free, AIDS Free super-fast-track targets.

Whole-Genome Sequence of Human Rhinovirus C47, Isolated from an Adult Respiratory Illness Outbreak in Butte County, California, 2017.

Here, we report the full coding sequence of rhinovirus C47 (RV-C47), obtained from a patient respiratory sample collected during an acute respiratory illness investigation in Butte County, California, in January 2017. This is the first whole-genome sequence of RV-C47 to be reported.

Optimizing Research to Speed Up Availability of Pediatric Antiretroviral Drugs and Formulations.

Globally 1.8 million children are living with human immunodeficiency virus (HIV), yet only 51% of those eligible actually start treatment. Research and development (R&D) for pediatric antiretrovirals (ARVs) is a lengthy process and lags considerably behind drug development in adults. Providing safe, effective, and well-tolerated drugs for children remains critical to ensuring scale-up globally. We review current approaches to R&D for pediatric ARVs and suggest innovations to enable simplified, faster, and more comprehensive strategies to develop optimal formulations. Several approaches could be adopted, including focusing on a limited number of prioritized formulations and strengthening existing partnerships to ensure that pediatric investigation plans are developed early in the drug development process. Simplified and more efficient mechanisms to undertake R&D need to be put in place, and financing mechanisms must be made more sustainable. Lessons learned from HIV should be shared to support progress in developing pediatric formulations for other diseases, including tuberculosis and viral hepatitis.

Admissions Criteria that Influence Dental Hygiene Students' Performance on Board Examinations.

Purpose: The purpose of the study is to assess which dental hygiene program admission variables contribute to the selection of students who are successful in passing the National Board Dental Hygiene Examination (NBDHE) and a clinical dental hygiene board examination.Methods: A retrospective study was conducted by investigating 121 educational records and application forms from graduates through the years 2008 to 2011 from one educational institution. Predictor variables included re-application status, student GPA, age, race/ethnicity, type of school attended for pre-requisite coursework, number of times the pre-requisite courses needed to be retaken, course load while taking the pre-requisites, previous degrees obtained, American College Test (ACT) scores and student participation in the university's lower division (LD) or upper pre-placement (UPP) program. Graduate success is defined by NBDHE scores and clinical board scores.Results: The data was analyzed using univariate analyses and multivariate regression statistical techniques. Univariate analyses did not identify any predictor variables to be significantly associated with the dental hygiene student's clinical board score. However, the variables of ACT scores and type of student, specifically the UPP students, demonstrated a significant relationship with NBDHE scores.Conclusion: ACT scores are a variable that is positively associated with higher NBDHE results. Results indicate that UPP students benefit from participating in supportive educational services while fulfilling requirements for admissions in the dental hygiene program. Results also indicate that there were no significant variables identified to predict clinical board scores.

Meeting the goal of concurrent adolescent and adult licensure of HIV prevention and treatment strategies.

The ability of adolescents to access safe and effective new products for HIV prevention and treatment is optimised by adolescent licensure at the same time these products are approved and marketed for adults. Many adolescent product development programmes for HIV prevention or treatment products may proceed simultaneously with adult phase III development programmes. Appropriately implemented, this strategy is not expected to delay licensure as information regarding product efficacy can often be extrapolated from adults to adolescents, and pharmacokinetic properties of drugs in adolescents are expected to be similar to those in adults. Finally, adolescents enrolled in therapeutic HIV prevention and treatment research can be considered adults, based on US Food and Drug Administration (FDA) regulations and the appropriate application of state law. The FDA permits local jurisdictions to apply state and local HIV/sexually transmitted infection minor treatment laws so that adolescents who are HIV-positive or at risk of contracting HIV may be enrolled in therapeutic or prevention trials without obtaining parental permission.