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With the declaration of the COVID-19 pandemic by the World Health Organization in March 2020, many elements of society were faced with attempting to assimilate public health recommendations for infectious control. Vital social organizations had to balance delivering their social services while attempting to stay up to date with COVID-19 information and comply with evolving regulations. In the realm of schools and school systems, guidance on how to best adapt to COVID-19 was often limited. School officials and staff had to assist with multiple public health crises as a consequence of the pandemic, from the pandemic’s transmission prevention strategies (e.g., face masks and physical distancing) to the recognition that students would have personal tragedies related to COVID-19. In this review, we highlight the process and feasibility of implementing an international COVID-19 school-based initiative over two years of the pandemic, the Health Education and Training (HEAT) Corps program.

Background Interventions to reduce community-onset (CO) Clostridioides difficile Infection (CDI) are not usually hospital-based due to the perception that they are often acquired outside the hospital. We determined the proportion of admitted CO CDI that might be associated with previous hospitalization. Methods The CDC’s Emerging Infections Program conducts population-based CDI surveillance in 10 US sites. We defined an incident case as a C. difficile-positive stool collected in 2017 from a person aged ≥ 1 year admitted to a hospital with no positive tests in the prior 8 weeks. Cases were defined as CO if stool was collected within 3 days of hospitalization. CO cases were classified into four categories: long-term care facility (LTCF)-onset if patient was admitted from an LTCF; long-term acute care hospital (LTACH)-onset if patient was admitted from an LTACH; CO-healthcare-facility associated (CO-HCFA) if patient was admitted from a private residence but had a prior healthcare-facility admission in the past 12 weeks; or community-associated (CA) if there was no admission to a healthcare facility in the prior 12 weeks. We excluded hospitals with < 10 cases among admitted catchment-area residents. Results Of 4724 cases in 86 hospitals, 2984 (63.2%) were CO (median per hospital: 65.8%; interquartile range [IQR]: 58.3%-70.7%). Among the CO cases, 1424 (47.7%) were CA (median per hospital: 48.1%; IQR: 40.3%-57.7%), 1201 (40.3%) were CO-HCFA (median per hospital: 41.0%; IQR: 32.9%-47.8%), 350 (11.7%) were LTCF-onset (median per hospital: 10.0%; IQR: 0.6%-14.4%), and 9 (0.3%) were LTACH-onset. Of 1201 CO-HCFA cases, 1174 (97.8%) had a prior hospitalization; among these, 978 (83.3%) (median per hospital: 83.3%; IQR: 69.2%-90.6%), which consists of 32.8% of all hospitalized CO cases, had been discharged from the same hospital (Figure), and 84.4% of the 978 cases (median per hospital: 88.2%: IQR: 76.5%-100.0%) had received antibiotics sometime in the prior 12 weeks. Figure. Frequency of Cases Discharged in the 12 Weeks Prior to Readmission with Clostridioides difficile Infection (N=1138*) Conclusion A third of hospitalized CO CDI had been recently discharged from the same hospital, and most had received antibiotics during or soon after the last admission. Hospital-based and post-discharge antibiotic stewardship interventions could help reduce subsequent CDI hospitalizations. Disclosures Ghinwa Dumyati, MD, Roche Diagnostics (Consultant)

SUMMARY Along with Parkin, PINK1 plays a critical role in maintaining mitochondrial quality control. Although PINK1 is expressed constitutively, its level is kept low in healthy mitochondria by polyubiquitination and ensuing proteasomal degradation of its mature, 52 kDa, form. We show here that the target of PINK1 polyubiquitination is the mature form and is mediated by ubiquitination of a conserved lysine at position 137. Notably, the full-length protein also contains Lys-137 but is not ubiquitinated. On the basis of our data, we propose that cleavage of full-length PINK1 at Phe-104 disrupts the major hydrophobic membrane-spanning domain in the protein, inducing a conformation change in the resultant mature form that exposes Lys-137 to the cytosol for subsequent modification by the ubiquitination machinery. Thus, the balance between the full-length and mature PINK1 allows its levels to be regulated via ubiquitination of the mature form and ensures that PINK1 functions as a mitochondrial quality control factor., In Brief PINK1 mutations cause Parkinson’s disease. PINK1 is cleaved into a shorter 52-kDa form at the mitochondrial membrane, but regulation of the turnover of cleaved PINK1 is unknown. Liu et al. show that polyubiquitination of cleaved PINK1 regulates its degradation via the proteasome.

Background Few data suggest that Clostridioides difficile infections (CDIs) detected by toxin enzyme immunoassay (EIA) are more severe and have worse outcomes than those detected by nucleic acid amplification tests (NAATs) only. We compared toxin- positive and NAAT-positive-only CDI across geographically diverse sites. Methods A case was defined as a positive C. difficile test in a person ≥1 year old with no positive tests in the prior 8 weeks. Cases were detected during 2014–2015 by a testing algorithm (specimens initially tested by glutamate dehydrogenase and toxin EIA; if discordant results, specimens were reflexed to NAAT) and classified as toxin positive or NAAT positive only. Medical charts were reviewed. Multivariable logistic regression models were used to compare CDI-related complications, recurrence, and 30-day mortality between the 2 groups. Results Of 4878 cases, 2160 (44.3%) were toxin positive and 2718 (55.7%) were NAAT positive only. More toxin-positive than NAAT-positive-only cases were aged ≥65 years (48.2% vs 38.0%; P < .0001), had ≥3 unformed stools for ≥1 day (43.9% vs 36.6%; P < .0001), and had white blood cell counts ≥15 000 cells/µL (31.4% vs 21.4%; P < .0001). In multivariable analysis, toxin positivity was associated with recurrence (adjusted odds ratio [aOR], 1.89; 95% confidence interval [CI], 1.61–2.23), but not with CDI-related complications (aOR, 0.91; 95% CI, .67–1.23) or 30-day mortality (aOR, 0.95; 95% CI, .73–1.24). Conclusions Toxin-positive CDI is more severe, but there were no differences in adjusted CDI-related complication and mortality rates between toxin-positive and NAAT-positive-only CDI that were detected by an algorithm that utilized an initial glutamate dehydrogenase screening test.

Maintaining a pool of functional mitochondria requires degradation of damaged ones within the cell. PINK1 is critical in this quality-control process: loss of mitochondrial membrane potential causes PINK1 to accumulate on the mitochondrial surface, triggering mitophagy. However, little is known about how PINK1 is regulated. Recently, we showed that PINK1 content is kept low in healthy mitochondria by continuous ubiquitination and proteasomal degradation of its mature form via a mechanism inconsistent with the proposed N-end rule process. Using both human female and monkey cell lines, we now demonstrate that once generated within the mitochondria, 52 kDa PINK1 adopts a mitochondrial topology most consistent with it being at the mitochondrial–endoplasmic reticulum (ER) interface. From this particular submitochondrial location, PINK1 interacts with components of the ER-associated degradation pathway, such as the E3 ligases gp78 and HRD1, which cooperate to catalyze PINK1 ubiquitination. The valosin-containing protein and its cofactor, UFD1, then target ubiquitinated PINK1 for proteasomal degradation. Our data show that PINK1 in healthy mitochondria is negatively regulated via an interplay between mitochondria and ER, and shed light on how this mitochondrial protein gains access to the proteasome. SIGNIFICANCE STATEMENT Regulation of mitochondrial content of PINK1, a contributor to mitophagy, is an important area of research. Recently, we found that PINK1 content is kept low in healthy mitochondria by continuous ubiquitination and proteasomal degradation. We now extend and refine this novel finding by showing that PINK1 localizes at the mitochondrial–endoplasmic reticulum (ER) interface, from where it interacts with the ER-associated degradation machinery, which catalyzes its ubiquitination and transfer to the proteasome. Thus, these data show that PINK1 in healthy mitochondria is negatively regulated via a mitochondria and ER interplay, and how this mitochondrial protein gains access to the proteasome.

We have developed a simple, reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of bisphenol A (BPA) in thermal paper cash register receipts (CRs). The method is suitable for analysis of other types of bisphenols and it involves an overnight extraction of CRs with acetonitrile (AN) at 50 °C followed by the HPLC analysis on a Supelcosil LC18 column (150 × 4.6 mm, particle size: 5 μ) using 50% AN in water as the mobile phase (5 min, isocratic). The composition of AN in the mobile phase changed to 100% over a 10 min period (linear gradient) and then held at 100% AN for 10 min (isocratic). The flow rate was set at 1 mL/min (injection volume: 20 μL) and the eluent was monitored at 234 nm. The authentic BPA eluted with a retention time of 5.9 min and gave a linear detector response in the concentration range of 0.23-50 mg/L. BPA in the CR extracts also eluted with the same retention and had identical absorbance properties as the standard. When CR extracts were co-injected with authentic BPA, they were resolved as a single peak. Further, GC/MS/EI analysis of authentic BPA and the HPLC-purified CR extracts have identical ion chromatograms and fragmentation of the molecular ion (m/z = 228). We have analyzed 170 CRs collected from 62 different vendors including supermarkets, fast food restaurants, gas stations and banking outlets. Almost all cash receipts (n = 168) showed the presence of BPA in the concentration range of 0.45-4.26% (M ± SD, 1.54 ± 0.73%).

Background US laboratories are increasingly using nucleic acid amplification tests (NAAT) to diagnose Clostridium difficile infection (CDI) due to their increased sensitivity over toxin enzyme immunoassays (EIA), but NAATs may be more likely than toxin EIAs to detect colonization rather than true disease. Limited data indicate patients positive by toxin EIA (toxin+) have worse outcomes than those positive by NAAT (NAAT+) only, suggesting toxin EIA detects true infection more often than NAAT. We used multisite CDI surveillance data from the Centers for Disease Control and Prevention’s Emerging Infections Program to compare clinical course and outcomes between toxin+ and NAAT+ only patients. Methods A case was defined as a positive C. difficile test in a person ≥1 year old with no positive tests in the prior 8 weeks. Cases detected during 2014–2015 by a testing algorithm using toxin EIA and NAAT were classified as toxin+ or NAAT+ only. Medical charts were reviewed. Death data were obtained from state death registries. Multivariable logistic regression models were used to compare CDI recurrence and 90-day mortality between the two groups, adjusting for age, sex, race, Charlson comorbidity index, and receipt of oral vancomycin. For the outcome of recurrence, we also adjusted for history of CDI in the prior 6 months. Results Of 4,878 cases, 2160 (44%) were toxin+ and 2,718 (56%) were NAAT+ only. Toxin+ cases were more likely than NAAT+ only cases to be ≥65 years old (48% vs. 38%; P < 0.0001), have white blood cells ≥15,000/µL (483/1,539 [31%] vs. 423/1,978 [21%]; P < 0.0001), and have received oral vancomycin ≤3 days of diagnosis (32% vs. 29%; P = 0.03). Comparing toxin+ to NAAT+ only cases, 21% vs. 11% had a recurrence (P < 0.0001), of which 71% vs. 33% had a toxin+ recurrence (P < 0.0001), and 10% vs. 9% died ≤90 days of diagnosis (P = 0.12). In multivariable analysis, a toxin+ result was associated with recurrence (adjusted odds ratio [aOR]: 1.89, 95% CI: 1.61–2.22) but not with 90-day mortality (aOR: 0.99; 95% CI: 0.81–1.22). Conclusion Toxin+ CDI is more severe by some markers and more likely to recur as toxin+. However, there was no difference in adjusted mortality, which may reflect an effect on mortality in NAAT+ only cases from mild CDI, receipt of unnecessary CDI treatment, or other factors. Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.

Background Clostridium difficile infection (CDI) is a common healthcare-associated infection, particularly among older adults. We used laboratory-confirmed CDI surveillance data from 8 states participating in the Centers for Disease Control and Prevention’s Emerging Infections Program linked to claims data for Centers for Medicare and Medicaid Services (CMS) beneficiaries to measure variation in 1-year outcomes associated with CDI. Methods A CDI case was defined as a positive C. difficile stool test in 2014 in a person without a positive test in the prior 8 weeks. Cases aged ≥65 years were linked to their CMS beneficiary ID using unique combinations of date of birth, sex, and zip code. Each case was matched to five control beneficiaries who did not link to any case and were residents of the same catchment area. Inclusion criteria were continuous fee-for-service Medicare for the entire study period (1 year before and after event date), and no hospitalization or skilled nursing facility stay with an ICD-9-CM code for CDI in the year prior to their match date. Multivariable logistic regression models were used to compare mortality and hospitalization for 1 year following the event date between beneficiaries with and without CDI, adjusting for age, sex, race, catchment area, chronic conditions, number of hospitalizations in the prior year, and hospitalization status at the time of and 7 days preceding the event date. Results Of 5,097 cases aged ≥65, 3,082 (60%) were linked to a CMS ID, and 1,832 (59%) met inclusion criteria. In crude analysis, 34% of beneficiaries with CDI died within 1 year, compared with 5% of beneficiaries without CDI. Beneficiaries with CDI were also more likely to be hospitalized in the subsequent year (54% vs. 17%). Beneficiaries with CDI had a higher adjusted odds of death (adjusted OR 3.01, 95% CI: 2.46, 3.69) and hospitalization within 1 year (adjusted OR 1.93, 95% CI: 1.65, 2.25) than those without CDI. Conclusion Older adults with CDI were three times more likely to die in the year following infection and nearly two times more likely to be hospitalized compared with those without CDI, revealing independent long-term risk of poor outcomes. This excess morbidity and mortality supports the need to develop novel CDI prevention strategies for this population. Disclosures All authors: No reported disclosures.

Background School-located influenza vaccination (SLIV) programs are a promising strategy for increasing vaccination coverage among schoolchildren. However, questions of economic sustainability have dampened enthusiasm for this approach in the United States. We evaluated SLIV sustainability of a health department led, county-wide SLIV program in Alachua County, Florida. Based on Alachua's outcome data, we modeled the sustainability of SLIV programs statewide using two different implementation costs and at different vaccination rates, reimbursement amount, and Vaccines for Children (VFC) coverage. Methods Mass vaccination clinics were conducted at 69 Alachua County schools in 2013 using VFC (for Medicaid and uninsured children) and non-VFC vaccines. Claims were processed after each clinic and submitted to insurance providers for reimbursement ($5 Medicaid and $47.04 from private insurers). We collected programmatic expenditures and volunteer hours to calculate fixed and variable costs for two different implementation costs (with or without in-kind costs included). We project program sustainability for Florida using publicly available county-specific student populations and health insurance enrollment data. Results Approximately 42% (n = 12,853) of pre-kindergarten – 12th grade students participated in the SLIV program in Alachua. Of the 13,815 doses provided, 58% (8042) were non-VFC vaccine. Total implementation cost was $14.95/dose or $7.93/dose if “in-kind” costs were not included. The program generated a net surplus of $24,221, despite losing $4.68 on every VFC dose provided to Medicaid and uninsured children. With volunteers, 99% of Florida counties would be sustainable at a 50% vaccination rate and average reimbursement amount of $3.25 VFC and $37 non-VFC. Without volunteers, 69% of counties would be sustainable at 50% vaccination rate if all VFC recipients were on Medicaid and its reimbursement increased from $5 to $10 (amount private practices receive). Conclusions and relevance Key factors that contributed to the sustainability and success of an SLIV program are: targeting privately insured children and reducing administration cost through volunteers. Counties with a high proportion of VFC eligible children may not be sustainable without subsidies at $5 Medicaid reimbursement.