A Multifaceted Evaluation of a COVID-19 Contact Tracing Program in King County, Washington.

CONTEXT: Despite the massive scale of COVID-19 case investigation and contact tracing (CI/CT) programs operating worldwide, the evidence supporting the intervention's public health impact is limited. OBJECTIVE: To evaluate the Public Health-Seattle & King County (PHSKC) CI/CT program, including its reach, timeliness, effect on isolation and quarantine (I&Q) adherence, and potential to mitigate pandemic-related hardships. DESIGN: This program evaluation used descriptive statistics to analyze surveillance records, case and contact interviews, referral records, and survey data provided by a sample of cases who had recently ended isolation. SETTING: The PHSKC is one of the largest governmental local health departments in the United States. It serves more than 2.2 million people who reside in Seattle and 38 other municipalities. PARTICIPANTS: King County residents who were diagnosed with COVID-19 between July 2020 and June 2021. INTERVENTION: The PHSKC integrated COVID-19 CI/CT with prevention education and service provision. RESULTS: The PHSKC CI/CT team interviewed 42 900 cases (82% of cases eligible for CI/CT), a mean of 6.1 days after symptom onset and 3.4 days after SARS-CoV-2 testing. Cases disclosed the names and addresses of 10 817 unique worksites (mean = 0.8/interview) and 11 432 other recently visited locations (mean = 0.5/interview) and provided contact information for 62 987 household members (mean = 2.7/interview) and 14 398 nonhousehold contacts (mean = 0.3/interview). The CI/CT team helped arrange COVID-19 testing for 5650 contacts, facilitated grocery delivery for 7253 households, and referred 9127 households for financial assistance. End of I&Q Survey participants (n = 304, 54% of sampled) reported self-notifying an average of 4 nonhousehold contacts and 69% agreed that the information and referrals provided by the CI/CT team helped them stay in isolation. CONCLUSIONS: In the 12-month evaluation period, CI/CT reached 42 611 households and identified thousands of exposure venues. The timing of CI/CT relative to infectiousness and difficulty eliciting nonhousehold contacts may have attenuated the intervention's effect. Through promotion of I&Q guidance and services, CI/CT can help mitigate pandemic-related hardships.

Ganglioside GM1-mediated transcytosis of cholera toxin bypasses the retrograde pathway and depends on the structure of the ceramide domain.

Cholera toxin causes diarrheal disease by binding ganglioside GM1 on the apical membrane of polarized intestinal epithelial cells and trafficking retrograde through sorting endosomes, the trans-Golgi network (TGN), and into the endoplasmic reticulum. A fraction of toxin also moves from endosomes across the cell to the basolateral plasma membrane by transcytosis, thus breeching the intestinal barrier. Here we find that sorting of cholera toxin into this transcytotic pathway bypasses retrograde transport to the TGN. We also find that GM1 sphingolipids can traffic from apical to basolateral membranes by transcytosis in the absence of toxin binding but only if the GM1 species contain cis-unsaturated or short acyl chains in the ceramide domain. We found previously that the same GM1 species are needed to efficiently traffic retrograde into the TGN and endoplasmic reticulum and into the recycling endosome, implicating a shared mechanism of action for sorting by lipid shape among these pathways.

Declines in student obesity prevalence associated with a prevention initiative - King County, Washington, 2012.

The United States has invested heavily, through public and private sector initiatives, in actions to prevent youth obesity by promoting healthy eating and physical activity. This report documents recent trends in youth obesity in King County, Washington, which implemented a Communities Putting Prevention to Work (CPPW) obesity prevention initiative during 2010-2012, including a school-based component. Similar large-scale obesity prevention initiatives did not occur elsewhere in Washington. Beginning in 2004, the Washington State Department of Health began monitoring youth obesity through the biennially administered Washington State Healthy Youth Survey (HYS). Based on data from this survey, neither King County nor the rest of Washington showed statistically significant changes in obesity prevalence in 2006, 2008, and 2010, relative to 2004. In 2012, however, King County youth obesity prevalence showed a statistically significant decrease, while no change occurred in the remainder of the state. Within King County, CPPW was implemented only in low-income school districts to address geographic inequities in obesity rates. Analysis within King County comparing CPPW and non-CPPW school districts before and after the intervention (2010 versus 2012) revealed a statistically significant decline in obesity prevalence in CPPW schools yet no change in non-CPPW schools. This decline in CPPW schools was significantly different than in non-CPPW schools. These findings suggest that school-based policy, systems, and environment changes might help reduce youth obesity, warranting further evaluation of short- and long-term impacts on population health.

Care-seeking and appropriate treatment for childhood acute respiratory illness: an analysis of Demographic and Health Survey and Multiple Indicators Cluster Survey datasets for high-mortality countries.

BACKGROUND: Acute lower respiratory illness (ALRI) is a major global cause of morbidity and mortality among children under 5. Antibiotic treatment for ALRI is inexpensive and decreases case fatality, but care-seeking patterns and appropriate treatment vary widely across countries. This study sought to examine patterns of appropriate treatment and estimate the burden of cases of untreated ALRI in high mortality countries. METHODS: This study used cross-sectional survey data from the Phase 5/Phase 6 DHS and MIC3/MICS4 for 39 countries. We analyzed care-seeking patterns and antibiotic treatment based on country-level trends, and estimated the burden of untreated cases using country-level predictors in a general linear model. RESULTS: According to this analysis, over 66 million children were not treated with antibiotics for ALRI in 2010. Overall, African countries had a lower proportion of mothers who sought care for a recent episode of ALRI (41% to 86%) relative to Asian countries (75% to 87%). Seeking any care for ALRI was inversely related to seeking public sector care. Treatment with antibiotics ranged from 8% in Nepal to 87% in Jordan, and was significantly associated with urban residence. CONCLUSIONS: Untreated ALRI remains a substantial problem in high mortality countries. In Asia, the large population numbers lead to a high burden of children with untreated ALRI. In Africa, care-seeking behaviors and access to care issues may lead to missed opportunities to treat children with antibiotics.

Provision of bednets and water filters to delay HIV-1 progression: cost-effectiveness analysis of a Kenyan multisite study.

OBJECTIVE: To estimate the effectiveness, costs and cost-effectiveness of providing long-lasting insecticide-treated nets (LLINs) and point-of-use water filters to antiretroviral therapy (ART)-naïve HIV-infected adults and their family members, in the context of a multisite study in Kenya of 589 HIV-positive adults followed on average for 1.7 years. METHODS: The effectiveness, costs and cost-effectiveness of the intervention were estimated using an epidemiologic-cost model. Model epidemiologic inputs were derived from the Kenya multisite study data, local epidemiological data and from the published literature. Model cost inputs were derived from published literature specific to Kenya. Uncertainty in the model estimates was assessed through univariate and multivariate sensitivity analyses. RESULTS: We estimated net cost savings of about US$ 26 000 for the intervention, over 1.7 years. Even when ignoring net cost savings, the intervention was found to be very cost-effective at a cost of US$ 3100 per death averted or US$ 99 per disability-adjusted life year (DALY) averted. The findings were robust to the sensitivity analysis and remained most sensitive to both the duration of ART use and the cost of ART per person-year. CONCLUSIONS: The provision of LLINs and water filters to ART-naïve HIV-infected adults in the Kenyan study resulted in substantial net cost savings, due to the delay in the initiation of ART. The addition of an LLIN and a point-of-use water filter to the existing package of care provided to ART-naïve HIV-infected adults could bring substantial cost savings to resource-constrained health systems in low- and middle-income countries.

Behavioral Health Integration in Community Health Centers and Emergency Department Use.

Medicaid enrollees with behavioral health disorders often experience fragmented care, leading to high rates of preventable use of emergency departments (EDs). As part of its Medicaid Transformation Program, the Washington Health Care Authority partnered with regional accountable communities of health to collect data on behavioral health integration in community health centers. Clinics who participated in the integrated care demonstration received technical and financial support to increase capacity for integration. This column describes results from an analysis that linked clinic surveys to Medicaid claims to explore characteristics of highly integrated clinics and assess whether clinic capacity for behavioral health integration is associated with ED visit frequency.

A retrospective cohort study of lung cancer incidence in nylon flock workers, 1998-2008.

During an investigation of a novel interstitial lung disease in a cohort of nylon flock workers, a former worker was found to have developed bilateral synchronous pulmonary adenocarcinomas three decades after he quit smoking, suggesting that exposures in this industry might pose excessive risk of lung cancer. We conducted a retrospective cohort study of lung cancer incidence in the original study cohort (n=162) from August 15, 1998, to August 14, 2008. The Rhode Island Cancer Registry identified cohort members with lung cancer and provided age-gender-era-specific rates of lung cancer in Rhode Island. Five cases of lung cancer occurred among cohort members versus 1.61 cases expected for a standardized incidence ratio of 3.1 (95% CI, 1.01-7.23). The observed threefold increase in lung cancer incidence could not be readily ascribed to chance, study bias, or uncontrolled confounding. Workers in this industry should be notified of their potentially increased risk of lung cancer.

Implementation Science to Respond to the COVID-19 Pandemic.

The COVID-19 pandemic continues to expand globally, requiring massive public health responses from national and local governments. These bodies have taken heterogeneous approaches to their responses, including when and how to introduce and enforce evidence-based interventions-such as social distancing, hand-washing, personal protective equipment (PPE), and testing. In this commentary, we reflect on opportunities for implementation science to contribute meaningfully to the COVID-19 pandemic response. We reflect backwards on missed opportunities in emergency preparedness planning, using the example of PPE stockpiling and supply management; this planning could have been strengthened through process mapping with consensus-building, microplanning with simulation, and stakeholder engagement. We propose current opportunities for action, focusing on enhancing the adoption, fidelity, and sustainment of hand washing and social distancing; we can combine qualitative data, policy analysis, and dissemination science to inform agile and rapid adjustment to social marketing strategies to enhance their penetration. We look to future opportunities to enhance the integration of new evidence in decision-making, focusing on serologic and virologic testing systems; we can leverage simulation and other systems engineering modeling to identify ideal system structures. Finally, we discuss the ways in which the COVID-19 pandemic challenges implementation science to become more rapid, rigorous, and nimble in its approach, and integrate with public health practice. In summary, we articulate the ways in which implementation science can inform, and be informed by, the COVID-19 pandemic, looking backwards, proposing actions for the moment, and approaches for the future.

Attenuated endocytosis and toxicity of a mutant cholera toxin with decreased ability to cluster ganglioside GM1 molecules.

Cholera toxin (CT) moves from the plasma membrane (PM) of host cells to the endoplasmic reticulum (ER) by binding to the lipid raft ganglioside GM(1). The homopentomeric B-subunit of the toxin can bind up to five GM(1) molecules at once. Here, we examined the role of polyvalent binding of GM(1) in CT action by producing chimeric CTs that had B-subunits with only one or two normal binding pockets for GM(1). The chimeric toxins had attenuated affinity for binding to host cell PM, as expected. Nevertheless, like wild-type (wt) CT, the CT chimeras induced toxicity, fractionated with detergent-resistant membranes extracted from toxin-treated cells, displayed restricted diffusion in the plane of the PM in intact cells, and remained bound to GM(1) when they were immunoprecipitated. Thus, binding normally to two or perhaps only one GM(1) molecule is sufficient for association with lipid rafts in the PM and toxin action. The chimeric toxins, however, were much less potent than wt toxin, and they entered the cell by endocytosis more slowly, suggesting that clustering of GM(1) molecules by the B-subunit enhances the efficiency of toxin uptake and perhaps also trafficking to the ER.

Variation in life expectancy and mortality by cause among neighbourhoods in King County, WA, USA, 1990-2014: a census tract-level analysis for the Global Burden of Disease Study 2015.

BACKGROUND: Health outcomes are known to vary at both the country and local levels, but trends in mortality across a detailed and comprehensive set of causes have not been previously described at a very local level. Life expectancy in King County, WA, USA, is in the 95th percentile among all counties in the USA. However, little is known about how life expectancy and mortality from different causes of death vary at a local, neighbourhood level within this county. In this analysis, we estimated life expectancy and cause-specific mortality within King County to describe spatial trends, quantify disparities in mortality, and assess the contribution of each cause of death to overall disparities in all-cause mortality. METHODS: We applied established so-called garbage code redistribution algorithms and small area estimation methods to death registration data for King County to estimate life expectancy, cause-specific mortality rates, and years of life lost (YLL) rates from 152 causes of death for 397 census tracts from Jan 1, 1990, to Dec 31, 2014. We used the cause list developed for the Global Burden of Disease 2015 study for this analysis. Deaths were tabulated by age group, sex, census tract, and cause of death. We used Bayesian mixed-effects regression models to estimate mortality overall and from each cause. FINDINGS: Between 1990 and 2014, life expectancy in King County increased by 5·4 years (95% uncertainty interval [UI] 5·0-5·7) among men (from 74·0 years [73·7-74·3] to 79·3 years [79·1-79·6]) and by 3·4 years (3·0-3·7) among women (from 80·0 years [79·7-80·2] to 83·3 years [83·1-83·5]). In 2014, life expectancy ranged from 68·4 years (95% UI 66·9-70·1) to 86·7 years (85·0-88·2) for men and from 73·6 years (71·6-75·5) to 88·4 years (86·9-89·9) for women among census tracts within King County. Rates of YLL by cause also varied substantially among census tracts for each cause of death. Geographical areas with relatively high and relatively low YLL rates differed by cause. In general, causes of death responsible for more YLLs overall also contributed more significantly to geographical inequality within King County. However, certain causes contributed more to inequality than to overall YLLs. INTERPRETATION: This census tract-level analysis of life expectancy and cause-specific YLL rates highlights important differences in health among neighbourhoods in King County that are masked by county-level estimates. Efforts to improve population health in King County should focus on reducing geographical inequality, by targeting those health conditions that contribute the most to overall YLLs and to inequality. This analysis should be replicated in other locations to more fully describe fine-grained local-level variation in population health and contribute to efforts to improve health while reducing inequalities. FUNDING: John W Stanton and Theresa E Gillespie.

Are long-lasting insecticide-treated bednets and water filters cost-effective tools for delaying HIV disease progression in Kenya?

BACKGROUND: Co-infection with malaria and other infectious diseases has been shown to increase viral load and accelerate HIV disease progression. A recent study in Kenya demonstrated that providing long-lasting insecticide-treated bednets (LLIN) and water filters (WF) to HIV-positive adults with CD4 >350 cells/mm(3) significantly reduced HIV progression. DESIGN: We conducted a cost analysis to estimate the potential net financial savings gained by delaying HIV progression and increasing the time to antiretroviral therapy (ART) eligibility through delivering LLIN and WF to 10% of HIV-positive adults with CD4 >350 cells/mm(3) in Kenya. RESULTS: Given a 3-year duration of intervention benefit, intervention unit cost of US$32 and patient-year ART cost of US$757 (2011 US$), over the lifetime of ART patients, in Kenya, we estimated the intervention could yield a return on investment (ROI) of 11 (95% uncertainty range [UR]: 5-23), based on a cost of about US$2 million and savings in ART costs of about US$26 million (95% UR: 8-50) (discounted at 3%). Our findings were subjected to a number of sensitivity analyses. Of note, deferral of time to ART eligibility could potentially result in 3,000 new HIV infections not averted by ART and thus decrease ART cost savings to US$14 million, decreasing the ROI to 6. CONCLUSIONS: Provision of LLIN and WF could be a cost-saving and practical method to defer time to ART eligibility in the context of highly resource-constrained environments experiencing donor fatigue for HIV/AIDS programs.

Role of p97 AAA-ATPase in the retrotranslocation of the cholera toxin A1 chain, a non-ubiquitinated substrate.

The enzymatic A1 chain of cholera toxin retrotranslocates across the endoplasmic reticulum membrane into the cytosol, where it induces toxicity. Almost all other retrotranslocation substrates are modified by the attachment of polyubiquitin chains and moved into the cytosol by the ubiquitin-interacting p97 ATPase complex. The cholera toxin A1 chain, however, can induce toxicity in the absence of ubiquitination, and the motive force that drives retrotranslocation is not known. Here, we use adenovirus expressing dominant-negative mutants of p97 to test whether p97 is required for toxin action. We find that cholera toxin still functions with only a small decrease in potency in cells that cannot retrotranslocate other substrates at all. These results suggest that p97 does not provide the primary driving force for extracting the A1 chain from the endoplasmic reticulum, a finding that is consistent with a requirement for polyubiquitination in p97 function.