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The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed three-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of 1.25-3.18). This study thus provides a detailed picture of viral evolution in the Delaware Valley and a geographically matched analysis of vaccine breakthroughs; it also introduces a rigorous statistical approach to interrogating enrichment of viral variants.ImportanceSARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in South Eastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a three-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.

Background Contact tracing is a critical component in controlling the spread of infectious diseases. During the COVID-19 pandemic, the demands for contract tracing far exceeded the resources available to infection prevention and control (IPC) programs. Leveraging our Poison Control Center, our organization established a Contact Tracing Center (CTC) with content expertise and oversight by IPC and Occupational Health. The CTC identifies exposed patients and employees, provides testing guidance and scheduling, and offers post-exposure recommendations for employees. We describe patient outcomes due to employee exposures in a pediatric healthcare system. Methods Exposure data about employee to patient exposures (EPE) were captured real-time by scripted telephone interviews by our CTC. Chart review was performed to determine outcomes of exposed patients. A concerning exposure from a direct patient care provider to a patient was defined as unprotected contact at less than 6 feet for greater than 5 minutes in the 24 hours prior to developing symptoms. Data were analyzed to determine COVID-19 conversion rates for children exposed to pre-symptomatic and symptomatic employees based upon exposure risk stratification, window of exposure, and employees who worked with symptoms. Results From March 2020 – present, we identified 38 EPE that involved 10 employees; 26 EPE were pre-symptomatic and 12 EPE symptomatic exposures. The average number of EPE per employee was 3.8 (SD 3.01). There were no secondary transmission events to patients from either pre-symptomatic or symptomatic employees. After instituting universal masking, the number of concerning exposures to patients were 3 compared to 35 prior to universal masking. Conclusion We describe the experience of a novel Contact Tracing Center, leveraging alternate staffing pools to track EPE resulting in no secondary transmission to patients either before or after universal masking. We credit sick policy adherence, high hand hygiene compliance, use of standard precautions, universal masking, robust contact tracing operations and a strong data collection system to identify process gaps. Disclosures All Authors: No reported disclosures

Immediately after the approval of direct-acting antiviral medications for the treatment of hepatitis C virus (HCV) in 2013, state Medicaid programs limited access to these expensive treatments based on liver disease stage, absence of active alcohol or substance use, and prescriber limitations. New York State fee-for-service (FFS) Medicaid eliminated these requirements in May 2016, but the effect on providers and patients obtaining prior authorization (PA) from Medicaid managed care organizations (MCOs) was unknown. We used a mixed methods approach to assess whether the removal of HCV treatment restrictions was associated with changes in Medicaid MCOs’ PA approval processes and length of time to treatment initiation at two large urban New York City provider organizations participating in Project INSPIRE, an HCV care coordination demonstration project. At baseline, the top criteria for clinic care coordinators ranking MCOs as being “most difficult” were liver staging criteria, delayed treatment, and requiring a urine toxicology test. At follow-up, liver staging criteria were replaced by medication formulary limitations. Univariate analysis of the Project INSPIRE participant data suggests a decrease in the percentage of participants with insurance/PA-related treatment delays pre- versus post-policy change (23% versus 15%, p value = 0.02). Interrupted time series analysis found a 2 percentage point decrease (p value = 0.02) in the proportion of PAs each month with insurance-related treatment delays that was attributable to policy change. These results from two urban clinics indicate New York State FFS Medicaid’s policy change for HCV treatment may have been associated with some changes in Medicaid MCO PA decisions, but MCO PA denials and treatment delays were still observed “on the ground” by clinic staff. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11524-020-00422-0) contains supplementary material, which is available to authorized users.

Background Individuals infected with hepatitis C (HCV) often present with co-morbidities and complex socio-behavioral risk factors. Project INSPIRE was a care coordination and telementoring demonstration project which aimed to treat and cure HCV-infected patients while providing them with services and education to improve overall health outcomes and self-sufficiency. We examined changes in HCV-related health and behavior associated with completion of Project INSPIRE (the “intervention”). Methods Patients were enrolled into Project INSPIRE at clinical sites where they received HCV clinical care paired with care coordination services. Baseline and post-intervention surveys were distributed to participants in-person at a clinical site and/or via mail at two time-points, one before and one after the intervention. Surveys were mailed back to the researchers by participants, and participant-identifying information was used to link survey responses to clinical data for each respondent. Logistic models using generalized estimating equations to account for partially overlapping observations examined the association between intervention participation and changes in self-reported overall health, emergency department (ED) visits and hospitalizations in the past 6 months, drug and alcohol use in the past 6 months, HCV knowledge, and general self-efficacy, adjusting for potential demographic and sociobehavioral confounding variables. Results The response rates for complete and partial surveys were 14.0% of 883 for baseline and 9.9% of 1,552 for post-intervention. In multivariable analyses (N=269, of which 50 were paired and 219 were unpaired), INSPIRE intervention participation was associated with a decreased odds of self-reported ED visits (OR: 0.34, 95% CI: 0.20–0.57), hospitalizations (OR: 0.30, 95% CI: 0.16–0.57), alcohol use (OR: 0.35, 95% CI: 0.18–0.69), and injection drug use (OR: 0.09, 95% CI: 0.02–0.34), and a 6.8% (CI: 1.6-12.2%) increase in reported self-efficacy (p=0.01). Conclusions Survey results suggest that INSPIRE successfully improved participant health behavior and self-efficacy, indicating the intervention’s value to patients, providers, and insurance companies beyond the immediate benefits of HCV treatment and cure. Participants also had a generally positive experience working with their care teams, indicating that further research should explore how an individualized care team can improve retention and patient referral rates compared with the HCV standard of care.

Objective To assess the accuracy of a surveillance-based definition for hepatitis B treatment eligibility among New York City residents with chronic hepatitis B infection. Introduction Approximately 100,000 New York City (NYC) residents are currently diagnosed with chronic hepatitis B virus (HBV) infection. 1 Routine monitoring and treatment, where indicated, are necessary to reduce HBV disease progression. Using the 2017 European Association for the Study of the Liver (EASL) 2 guidelines on HBV infection management, we developed a surveillance-based definition for treatment eligibility. Validation of this definition will support the creation of a population-level HBV care continuum, which will allow us to monitor gaps from HBV diagnosis to viral suppression and to develop public health interventions to address these gaps. Methods Laboratories everywhere are required to electronically report the following HBV tests to the NYC Department of Health and Mental Hygiene (DOHMH) for all NYC residents: positive and negative (as of April 2018) DNA, positive surface antigen, positive e antigen, positive core IgM, and Alanine aminotransferase (ALT) (when ordered at the same time as another reportable HBV test). Using reportable HBV tests, treatment eligibility was defined as ever having an HBV DNA result >2000 IU/mL and ALT>40 U/L. We assessed the accuracy of the surveillance-based definition by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) by applying the definition to the test data of people participating in two DOHMH programs that included clinical information on treatment eligibility: the Enhanced Surveillance Project (provider interviews conducted for 300 randomly selected patients with chronic HBV) and the Check Hep B Patient Navigation Program (program providing HBV-related patient navigation at community organizations, health centers, and hospitals). Everyone meeting inclusion criteria in the Enhanced Surveillance Project who were also identified as being in care and being monitored (two or more HBV DNA results reported at any time) were included in our analysis. For Check Hep B, we included everyone enrolled prior December 31, 2017 who also met our criteria of being in care and being monitored. To determine treatment eligibility using surveillance data, we used all HBV DNA and ALT results reported prior to January 31 st , 2016 for the Enhanced Surveillance project and prior to December 31 st , 2017 for Check Hep B. Results Treatment eligibility was 62.0% (145/234) among people from the Enhanced Surveillance Project (Table 1A) and 40.0% (161/402) among people enrolled in Check Hep B (Table 1B). Sensitivity of the surveillance-based definition was low using both data sources (Enhanced Surveillance Project: 26.2%; Check Hep B: 24.2%) and specificity high (Enhanced Surveillance Project: 92.1%; Check Hep B: 94.2%). PPV was 84.4% and 73.6% for the Enhanced Surveillance project and Check Hep B, respectively, while NPV was 43.4% and 65.0% for the Enhanced Surveillance project and Check Hep B respectively. Conclusions Our surveillance-based definition had high specificity, indicating that the great majority of patients who were truly not treatment-eligible were correctly classified. However, sensitivity was low, indicating that the surveillance-based definition was unable to accurately identify those considered treatment-eligible from either data source. Low sensitivity suggests that clinicians are likely using other clinical factors not included in laboratory-based reporting to assess a patient’s eligibility for treatment, such as fibrosis and cirrhosis, and that clinicians might be using guidelines other than EASL (e.g., American Association for the Study of Liver Diseases (AASLD) 3 ) to determine treatment eligibility. We will conduct chart reviews to better understand the variability in criteria being used. These chart reviews will allow us to further refine our surveillance-based definition (e.g., by incorporating different HBV tests or for clinical criteria that are not laboratory-based, including information from external sources such as Regional Health Information Organizations (RHIOs)), eventually supporting the creation of an HBV care continuum for NYC. References 1. France AM, Bornschlegel K, Lazaroff J, Kennedy J, Balter S. Estimating the prevalence of chronic hepatitis B virus infection--New York City, 2008. Journal of urban health: bulletin of the New York Academy of Medicine 2012 ; 89(2): 373-83. 2. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017 ; 67(2): 370-98. 3. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–83. https://doi.org/10.1002/hep.28156.

Hepatitis C (HCV) is a viral infection that if left untreated can severely damage the liver. Project INSPIRE was a 3 year HCV care coordination programme in New York City (NYC) that aimed to address barriers to treatment initiation and cure by providing patients with supportive services and health promotion. We examined whether enrolment in Project INSPIRE was associated with differences in HCV treatment and cure compared with a demographically similar group not enrolled in the programme. INSPIRE participants in 2015 were matched with a cohort of HCV-infected persons identified in the NYC surveillance registry, using full optimal matching on propensity scores and stratified by INSPIRE enrolment status. Conditional logistic regression was used to assess group differences in the two treatment outcomes. Two follow-up sensitivity analyses using individual pair-matched sets and the full unadjusted cohort were also conducted. Treatment was initiated by 72% (790/1130) of INSPIRE participants and 36% (11 960/32 819) of study-eligible controls. Among initiators, 65% (514/790) of INSPIRE participants compared with 47% (5641/11 960) of controls achieved cure. In the matched analysis, enrolment in INSPIRE increased the odds of treatment initiation (OR: 5.25, 95% CI: 4.47-6.17) and cure (OR: 2.52, 95% CI: 2.00-3.16). Results from the sensitivity analyses showed agreement with the results from the full optimal match. Participation in the HCV care coordination programme significantly increased the probability of treatment initiation and cure, demonstrating that care coordination for HCV-infected individuals improves treatment outcomes.

Background Dengue is a major public health problem in Mexico, where the use of chemical insecticides to control the principal dengue vector, Aedes aegypti, is widespread. Resistance to insecticides has been reported in multiple sites, and the frequency of kdr mutations associated with pyrethroid resistance has increased rapidly in recent years. In the present study, we characterized patterns of insecticide resistance in Ae. aegypti populations in five small towns surrounding the city of Merida, Mexico. Methods A cross-sectional, entomological survey was performed between June and August 2013 in 250 houses in each of the five towns. Indoor resting adult mosquitoes were collected in all houses and four ovitraps were placed in each study block. CDC bottle bioassays were conducted using F0-F2 individuals reared from the ovitraps and kdr allele (Ile1016 and Cys1534) frequencies were determined. Results High, but varying, levels of resistance to chorpyrifos-ethyl was detected in all study towns, complete susceptibility to bendiocarb in all except one town, and variations in resistance to deltamethrin between towns, ranging from 63–88 % mortality. Significant associations were detected between deltamethrin resistance and the presence of both kdr alleles. Phenotypic resistance was highly predictive of the presence of both alleles, however, not all mosquitoes containing a mutant allele were phenotypically resistant. An analysis of genotypic differentiation (exact G test) between the five towns based on the adult female Ae. aegypti collected from inside houses showed highly significant differences (p