Centering Health Equity Within COVID-19 Contact Tracing: Connecticut's Community Outreach Specialist Program.

CONTEXT: The COVID-19 pandemic has disproportionately impacted vulnerable populations, including those who are non-English-speaking and those with lower socioeconomic status; yet, participation of these groups in contact tracing was initially low. Distrust of government agencies, anticipated COVID-19-related stigma, and language and cultural barriers between contact tracers and communities are common challenges. PROGRAM: The Community Outreach Specialist (COS) program was established within the Connecticut Department of Public Health (DPH) COVID-19 contact tracing program to encourage participation in contact tracing and address a need for culturally competent care and social and material support among socially vulnerable and non-English-speaking populations in 11 high-burden jurisdictions in Connecticut. IMPLEMENTATION: In partnership with state and local health departments, we recruited 25 COS workers with relevant language skills from target communities and trained them to deliver contact tracing services to vulnerable and non-English speaking populations. EVALUATION: We conducted a cross-sectional analysis using data from ContaCT, DPH's enterprise contact tracing system. Overall, the COS program enrolled 1938 cases and 492 contacts. The proportion of residents reached (ie, called and interviewed) in the COS program was higher than that in the regular contact tracing program for both cases (70% vs 57%, P < .001) and contacts (84% vs 64%, P < .001). After adjusting for client age, sex, race and ethnicity, language, and jurisdiction, we found that the COS program was associated with increased reach for contacts (odds ratio [OR] = 1.52; 95% confidence interval [95% CI], 1.17-1.99) but not for cases (OR = 0.78; 95% CI, 0.70-0.88). Rapid qualitative analysis of programmatic field notes and meeting reports provided evidence that the COS program was feasible and acceptable to clients and contributed to COVID-19 education and communication efforts. CONCLUSION: A COS program employing a client-centered, community-engaged strategy for reaching vulnerable and non-English-speaking populations was feasible and more effective at reaching contacts than standard COVID-19 contact tracing.

NLRP3 inflammasome signaling is activated by low-level lysosome disruption but inhibited by extensive lysosome disruption: roles for K+ efflux and Ca2+ influx.

Nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) is a cytosolic protein that nucleates assembly of inflammasome signaling platforms, which facilitate caspase-1-mediated IL-1ß release and other inflammatory responses in myeloid leukocytes. NLRP3 inflammasomes are assembled in response to multiple pathogen- or environmental stress-induced changes in basic cell physiology, including the destabilization of lysosome integrity and activation of K(+)-permeable channels/transporters in the plasma membrane (PM). However, the quantitative relationships between lysosome membrane permeabilization (LMP), induction of increased PM K(+) permeability, and activation of NLRP3 signaling are incompletely characterized. We used Leu-Leu-O-methyl ester (LLME), a soluble lysosomotropic agent, to quantitatively track the kinetics and extent of LMP in relation to NLRP3 inflammasome signaling responses (ASC oligomerization, caspase-1 activation, IL-1ß release) and PM cation fluxes in murine bone marrow-derived dendritic cells (BMDCs). Treatment of BMDCs with submillimolar (≤1 mM) LLME induced slower and partial increases in LMP that correlated with robust NLRP3 inflammasome activation and K(+) efflux. In contrast, supramillimolar (≥2 mM) LLME elicited extremely rapid and complete collapse of lysosome integrity that was correlated with suppression of inflammasome signaling. Supramillimolar LLME also induced dominant negative effects on inflammasome activation by the canonical NLRP3 agonist nigericin; this inhibition correlated with an increase in NLRP3 ubiquitination. LMP elicited rapid BMDC death by both inflammasome-dependent pyroptosis and inflammasome-independent necrosis. LMP also triggered Ca(2+) influx, which attenuated LLME-stimulated NLRP3 inflammasome signaling but potentiated LLME-induced necrosis. Taken together, these studies reveal a previously unappreciated signaling network that defines the coupling between LMP, changes in PM cation fluxes, cell death, and NLRP3 inflammasome activation.

Effect of vaccination coordinators on socioeconomic disparities in immunization among the 2006 Connecticut birth cohort.

OBJECTIVES: We examined socioeconomic status (SES) disparities and the influence of state Immunization Action Plan-funded vaccination coordinators located in low-SES areas of Connecticut on childhood vaccination up-to-date (UTD) status at age 24 months. METHODS: We examined predictors of underimmunization among the 2006 birth cohort (n = 34,568) in the state's Immunization Information System, including individual demographic and SES data, census tract SES data, and residence in an area with a vaccination coordinator. We conducted multilevel logistic regression analyses. RESULTS: Overall, 81% of children were UTD. Differences by race/ethnicity and census tract SES were typically under 5%. Not being UTD at age 7 months was the strongest predictor of underimmunization at age 24 months. Among children who were not UTD at age 7 months, only Medicaid enrollment (adjusted odds ratio [AOR] = 0.6; 95% confidence interval [CI] = 0.5, 0.7) and residence in an area with a vaccination coordinator (AOR = 0.7; 95% CI = 0.6, 0.9) significantly decreased the odds of subsequent underimmunization. CONCLUSIONS: SES disparities associated with underimmunization at age 24 months were limited. Efforts focused on vaccinating infants born in low SES circumstances can minimize disparities.

Claudin-23 reshapes epithelial tight junction architecture to regulate barrier function.

Claudin family tight junction proteins form charge- and size-selective paracellular channels that regulate epithelial barrier function. In the gastrointestinal tract, barrier heterogeneity is attributed to differential claudin expression. Here, we show that claudin-23 (CLDN23) is enriched in luminal intestinal epithelial cells where it strengthens the epithelial barrier. Complementary approaches reveal that CLDN23 regulates paracellular ion and macromolecule permeability by associating with CLDN3 and CLDN4 and regulating their distribution in tight junctions. Computational modeling suggests that CLDN23 forms heteromeric and heterotypic complexes with CLDN3 and CLDN4 that have unique pore architecture and overall net charge. These computational simulation analyses further suggest that pore properties are interaction-dependent, since differently organized complexes with the same claudin stoichiometry form pores with unique architecture. Our findings provide insight into tight junction organization and propose a model whereby different claudins combine to form multiple distinct complexes that modify epithelial barrier function by altering tight junction structure.

Changing disparities in invasive pneumococcal disease by socioeconomic status and race/ ethnicity in Connecticut, 1998-2008.

OBJECTIVES: We compared invasive pneumococcal disease (IPD) incidence by race/ethnicity and neighborhood poverty level and assessed their relative utility to describe disparities in IPD in 1998-1999 and again in 2007-2008, after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: We conducted laboratory surveillance for pneumococcal isolates from sterile body sites and serotyped the isolates. Home address was geocoded to the census-tract level. Census-tract data on the percentage of people below poverty were grouped into three categories. The difference in the magnitude of incidence by race/ethnicity and by census-tract socioeconomic status (SES) (high poverty minus low poverty) was compared for 1998-1999 and 2007-2008 for PCV7 and non-PCV7 serotypes. RESULTS: In 1998-1999, incidence difference (all per 100,000 population) for PCV7 serotypes for black people compared with white people was 14.3 and by poverty level was 13.9. The highest rate was among white people in high-poverty tracts (77.3). By 2007-2008, there were only slight differences between rates for black and white people (0.7) and SES (1.4). In 1998-1999, the incidence difference for non-PCV7 serotypes was 4.7 between black and white people and 6.0 by SES. By 2007-2008, the differences were 11.6 and 11.7, respectively. Among those living in the highest-poverty tracts, white people had the highest rate (42.9). CONCLUSIONS: In the absence of vaccine, IPD incidence is higher among people living in higher-poverty census tracts and among black people. Emerging serotypes also follow this trend. Differences in neighborhood poverty levels reveal disparities in rates of IPD as large as those seen by race/ethnicity and could be used to routinely describe disparities and target prevention.

Challenges and Effects of the COVID-19 Pandemic on Asylum Seeker Health at the U.S.-Mexico Border.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic presents health care challenges to asylum seekers living in congregate encampments, including those along the U.S.-Mexico border. It is necessary to understand the impact of the pandemic among this population to address health care needs, reduce transmission, and diminish COVID-19-related morbidity. Methods: Thirty interviews were conducted with asylum seekers and health care professionals in a temporary camp in Matamoros, Mexico to determine challenges, perceptions, and effects of the COVID-19 pandemic. Interviews were coded in NVivo12 by using a team-based approach. Results: The pandemic caused significant mental health burdens but no perceived adverse physical effects, with the U.S. border closure and health care access barriers as more pressing concerns. Participants reported access to information about COVID-19 but had varied levels of knowledge and adherence to disease reduction strategies due to camp conditions. Most participants believed that they had special protection from COVID-19, including strong immune systems or from God. The nongovernmental organizations providing health care and sanitation faced multiple challenges to implement new policies to manage COVID-19. The institution of required temperature checks and quarantine of COVID-19 positive patients led to distrust, decreased seeking of health care services among asylum seekers, and possible underreporting of COVID-19 cases. Conclusion: Our findings among asylum seekers in a Matamoros camp highlight the challenges to implementing disease reduction policies in low-resource congregate camps. Policies to address disease outbreaks focusing on the social determinants of health, health care access barriers, and community engagement may be more acceptable to asylum seekers, suggesting the need for effective strategies to provide prevention information that complements such measures.