Association Between Cycle Threshold Value and Vaccination Status Among Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Cases in Ontario, Canada, in December 2021.

Background: Increased immune evasion by emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and occurrence of breakthrough infections raise questions about whether coronavirus disease 2019 vaccination status affects SARS-CoV-2 viral load among those infected. This study examined the relationship between cycle threshold (Ct) value, which is inversely associated with viral load, and vaccination status at the onset of the Omicron wave onset in Ontario, Canada. Methods: Using linked provincial databases, we compared median Ct values across vaccination status among polymerase chain reaction-confirmed Omicron variant SARS-CoV-2 cases (sublineages B.1.1.529, BA.1, and BA.1.1) between 6 and 30 December 2021. Cases were presumed to be Omicron based on S-gene target failure. We estimated the relationship between vaccination status and Ct values using multiple linear regression, adjusting for age group, sex, and symptom status. Results: Of the 27 029 presumed Omicron cases in Ontario, the majority were in individuals who had received a complete vaccine series (87.7%), followed by unvaccinated individuals (8.1%), and those who had received a booster dose (4.2%). The median Ct value for post-booster dose individuals (18.3 [interquartile range, 15.4-22.3]) was significantly higher than that for unvaccinated (17.9 [15.2-21.6]; P = .02) and post-vaccine series individuals (17.8 [15.3-21.5]; P = .005). Post-booster dose cases remained associated with a significantly higher median Ct value than cases in unvaccinated individuals (P ≤ .001), after adjustment for covariates. Compared with values in persons aged 18-29 years, Ct values were significantly lower among most age groups >50 years. Conclusions: While slightly lower Ct values were observed among unvaccinated individuals infected with Omicron compared with post-booster dose cases, further research is required to determine whether a significant difference in secondary transmission exists between these groups.

Evaluation of the US Definitions for Coronavirus Disease 2019 Community Risk Levels.

The US Centers for Disease Control and Prevention (CDC) defines a county metric of coronavirus disease 2019 (COVID-19) community levels to inform public health measures. We find that the COVID-19 community levels vary frequently over time, which may not be optimal for decision making. Alternative metric formulations that do not compromise predictive ability are shown to reduce variability.

Universal healthcare as pandemic preparedness: The lives and costs that could have been saved during the COVID-19 pandemic.

The fragmented and inefficient healthcare system in the United States leads to many preventable deaths and unnecessary costs every year. During a pandemic, the lives saved and economic benefits of a single-payer universal healthcare system relative to the status quo would be even greater. For Americans who are uninsured and underinsured, financial barriers to COVID-19 care delayed diagnosis and exacerbated transmission. Concurrently, deaths beyond COVID-19 accrued from the background rate of uninsurance. Universal healthcare would alleviate the mortality caused by the confluence of these factors. To evaluate the repercussions of incomplete insurance coverage in 2020, we calculated the elevated mortality attributable to the loss of employer-sponsored insurance and to background rates of uninsurance, summing with the increased COVID-19 mortality due to low insurance coverage. Incorporating the demography of the uninsured with age-specific COVID-19 and nonpandemic mortality, we estimated that a single-payer universal healthcare system would have saved about 212,000 lives in 2020 alone. We also calculated that US$105.6 billion of medical expenses associated with COVID-19 hospitalization could have been averted by a single-payer universal healthcare system over the course of the pandemic. These economic benefits are in addition to US$438 billion expected to be saved by single-payer universal healthcare during a nonpandemic year.

Paradoxical psoriasis in pediatric patients: A systematic review.

BACKGROUND: Paradoxical psoriasis occurs in pediatric patients following treatment with biologic agents. These presentations are not well described, and optimal treatment strategies have not been established. OBJECTIVE: To describe the reported rates, demographic characteristics, clinical presentation, and treatment options for TNF-α inhibitor-induced psoriasis. METHODS: Systematic review of published cases and cohort studies of paradoxical psoriasis induced by biologic agents, with specific reference to TNF-α inhibitors. RESULTS: We identified 4564 pediatric patients treated with TNF-α inhibitors, of whom 210 (4.6%) developed paradoxical psoriasis. Infliximab was the drug most likely to induce psoriasis (8.3%), followed by adalimumab (3.3%). Individual-level data were acquired from 129 individuals with a mean age of 13.6 years (SD: 4.0); 45.0% were male. The scalp was the most commonly affected area (47.5%), followed by the ears (30.8%). Most (63.3%) patients were continued on TNF-α inhibitor therapy. Among those who switched TNF-α inhibitors, only 32.0% had complete clearance of their skin lesions. Among patients who were switched to a non-TNF-α inhibitor, 81% had complete clearance of their paradoxical psoriasis. LIMITATIONS: Data were acquired from retrospective studies including case reports and case series. CONCLUSION: TNF-α inhibitor-induced psoriasis is a common adverse effect; however, most patients can continue their original therapy and be managed with skin-directed topical or systemic medications. If a patient requires medication discontinuation, switching to a new TNF-α inhibitor is unlikely to lead to resolution of their skin lesions.

Racial disparities in COVID-19 mortality across Michigan, United States.

BACKGROUND: Black populations in the United States are being disproportionately affected by the COVID-19 pandemic, but the increased mortality burden after accounting for health and other demographic characteristics is not well understood. We examined characteristics of individuals who died from COVID-19 in Michigan by race stratified by their age, sex and comorbidity prevalence to illustrate and understand this disparity in mortality risk. METHODS: We evaluate COVID-19 mortality in Michigan by demographic and health characteristics, using individual-level linked death certificate and surveillance data collected by the Michigan Department of Health and Human Services from March 16 to October 26, 2020. We identified differences in demographics and comorbidity prevalence across race among individuals who died from COVID-19 and calculated mortality rates by age, sex, race, and number of comorbidities. FINDINGS: Among the 6,065 COVID-19 related deaths in Michigan, Black individuals are experiencing 3·6 times the mortality rate of White individuals (p<0.001), with a mortality rate for Black individuals under 65 years without comorbidities that is 12·6 times that of their White counterparts (p<0.001). After accounting for age, race, sex, and number of comorbidities, we find that Black individuals in all strata are at higher risk of COVID-19 mortality than their White counterparts. INTERPRETATION: Our findings demonstrate that Black populations are disproportionately burdened by COVID-19 mortality, even after accounting for demographic and underlying health characteristics. We highlight how disparities across race, which result from systemic racism, are compounded in crises. FUNDING: ASP, AP and APG were funded by NSF Expeditions grant 1918784, NIH grant 1R01AI151176-01, NSF Rapid Response Research for COVID-19 grant RAPID-2027755, and the Notsew Orm Sands Foundation. MCF was supported by NIH grant K01AI141576.

Improving the prognosis of health care in the USA.

Although health care expenditure per capita is higher in the USA than in any other country, more than 37 million Americans do not have health insurance, and 41 million more have inadequate access to care. Efforts are ongoing to repeal the Affordable Care Act which would exacerbate health-care inequities. By contrast, a universal system, such as that proposed in the Medicare for All Act, has the potential to transform the availability and efficiency of American health-care services. Taking into account both the costs of coverage expansion and the savings that would be achieved through the Medicare for All Act, we calculate that a single-payer, universal health-care system is likely to lead to a 13% savings in national health-care expenditure, equivalent to more than US$450 billion annually (based on the value of the US$ in 2017). The entire system could be funded with less financial outlay than is incurred by employers and households paying for health-care premiums combined with existing government allocations. This shift to single-payer health care would provide the greatest relief to lower-income households. Furthermore, we estimate that ensuring health-care access for all Americans would save more than 68 000 lives and 1·73 million life-years every year compared with the status quo.

Spatio-temporal dynamics of measles outbreaks in Cameroon.

PURPOSE: In 2012, Cameroon experienced a large measles outbreak of over 14,000 cases. To determine the spatio-temporal dynamics of measles transmission in Cameroon, we analyzed weekly case data collected by the Ministry of Health. METHODS: We compared several multivariate time-series models of population movement to characterize the spatial spread of measles in Cameroon. Using the best model, we evaluated the contribution of population mobility to disease transmission at increasing geographic resolutions: region, department, and health district. RESULTS: Our spatio-temporal analysis showed that the power law model, which accounts for long-distance population movement, best represents the spatial spread of measles in Cameroon. Population movement between health districts within departments contributed to 7.6% (range: 0.4%-13.4%) of cases at the district level, whereas movement between departments within regions contributed to 16.0% (range: 1.3%-23.2%) of cases. Long-distance movement between regions contributed to 16.7% (range: 0.1%-59.0%) of cases at the region level, 20.1% (range: 7.1%-30.0%) at the department level, and 29.7% (range: 15.3%-47.6%) at the health district level. CONCLUSIONS: Population long-distance mobility is an important driver of measles dynamics in Cameroon. These findings demonstrate the need to improve our understanding of the roles of population mobility and local heterogeneity of vaccination coverage in the spread and control of measles in Cameroon.

Ebola vaccination in the Democratic Republic of the Congo.

Following the April 2018 reemergence of Ebola in a rural region of the Democratic Republic of the Congo (DRC), the virus spread to an urban center by early May. Within 2 wk of the first case confirmation, a vaccination campaign was initiated in which 3,017 doses were administered to contacts of cases and frontline healthcare workers. To evaluate the spatial dynamics of Ebola transmission and quantify the impact of vaccination, we developed a geographically explicit model that incorporates high-resolution data on poverty and population density. We found that while Ebola risk was concentrated around sites initially reporting infections, longer-range dissemination also posed a risk to areas with high population density and poverty. We estimate that the vaccination program contracted the geographical area at risk for Ebola by up to 70.4% and reduced the level of risk within that region by up to 70.1%. The early implementation of vaccination was critical. A delay of even 1 wk would have reduced these effects to 33.3 and 44.8%, respectively. These results underscore the importance of the rapid deployment of Ebola vaccines during emerging outbreaks to containing transmission and preventing global spread. The spatiotemporal framework developed here provides a tool for identifying high-risk regions, in which surveillance can be intensified and preemptive control can be implemented during future outbreaks.

Evaluating Vaccination Strategies for Zika Virus in the Americas.

Background: Mosquito-borne and sexually transmitted Zika virus has become widespread across Central and South America and the Caribbean. Many Zika vaccine candidates are under active development. Objective: To quantify the effect of Zika vaccine prioritization of females aged 9 to 49 years, followed by males aged 9 to 49 years, on incidence of prenatal Zika infections. Design: A compartmental model of Zika transmission between mosquitoes and humans was developed and calibrated to empirical estimates of country-specific mosquito density. Mosquitoes were stratified into susceptible, exposed, and infected groups; humans were stratified into susceptible, exposed, infected, recovered, and vaccinated groups. Age-specific fertility rates, Zika sexual transmission, and country-specific demographics were incorporated. Setting: 34 countries and territories in the Americas with documented Zika outbreaks. Target Population: Males and females aged 9 to 49 years. Intervention: Age- and sex-targeted immunization using a Zika vaccine with 75% efficacy. Measurements: Annual prenatal Zika infections. Results: For a base-case vaccine efficacy of 75% and vaccination coverage of 90%, immunizing females aged 9 to 49 years (the World Health Organization target population) would reduce the incidence of prenatal infections by at least 94%, depending on the country-specific Zika attack rate. In regions where an outbreak is not expected for at least 10 years, vaccination of women aged 15 to 29 years is more efficient than that of women aged 30 years or older. Limitation: Population-level modeling may not capture all local and neighborhood-level heterogeneity in mosquito abundance or Zika incidence. Conclusion: A Zika vaccine of moderate to high efficacy may virtually eliminate prenatal infections through a combination of direct protection and transmission reduction. Efficiency of age-specific targeting of Zika vaccination depends on the timing of future outbreaks. Primary Funding Source: National Institutes of Health.

Later school start times for supporting the education, health, and well-being of high school students.

BACKGROUND: A number of school systems worldwide have proposed and implemented later school start times as a means of avoiding the potentially negative impacts that early morning schedules can have on adolescent students. Even mild sleep deprivation has been associated with significant health and educational concerns: increased risk for accidents and injuries, impaired learning, aggression, memory loss, poor self-esteem, and changes in metabolism. Although researchers have begun to explore the effects of delayed school start time, no one has conducted a rigorous review of evidence to determine whether later school start times support adolescent health, education, and well-being. OBJECTIVES: We aimed to assess the effects of a later school start time for supporting health, education, and well-being in high school students.Secondary objectives were to explore possible differential effects of later school start times in student subgroups and in different types of schools; to identify implementation practices, contextual factors, and delivery modes associated with positive and negative effects of later start times; and to assess the effects of later school start times on the broader community (high school faculty and staff, neighborhood, and families). SEARCH METHODS: We conducted the main search for this review on 28 October 2014 and updated it on 8 February 2016. We searched CENTRAL as well as 17 key electronic databases (including MEDLINE, Embase, ERIC, PsycINFO, and Sociological Abstracts), current editions of relevant journals and organizational websites, trial registries, and Google Scholar. SELECTION CRITERIA: We included any randomized controlled trials, controlled before-and-after studies, and interrupted time series studies with sufficient data points that pertained to students aged 13 to 19 years and that compared different school start times. Studies that reported either primary outcomes of interest (academic outcomes, amount or quality of sleep, mental health indicators, attendance, or alertness) or secondary outcomes (health behaviors, health and safety indicators, social outcomes, family outcomes, school outcomes, or community outcomes) were eligible. DATA COLLECTION AND ANALYSIS: At least two review authors independently determined inclusion and exclusion decisions through screening titles, abstracts, and full-text reports. Two review authors independently extracted data for all eligible studies. We presented findings through a narrative synthesis across all studies. When two or more study samples provided sufficient information to permit effect size calculations, we conducted random-effects meta-analyses to synthesize effects across studies. MAIN RESULTS: Our search located 17 eligible records reporting on 11 unique studies with 297,994 participants; the studies examined academic outcomes, amount and quality of sleep, mental health indicators, attendance, and student alertness. Overall, the quality of the body of evidence was very low, as we rated most studies as being at high or unclear risk of bias with respect to allocation, attrition, absence of randomization, and the collection of baseline data. Therefore, we cannot be confident about the effects of later school start times.Preliminary evidence from the included studies indicated a potential association between later school start times and academic and psychosocial outcomes, but quality and comparability of these data were low and often precluded quantitative synthesis. Four studies examined the association between later school start times and academic outcomes, reporting mixed results. Six studies examined effects on total amount of sleep and reported significant, positive relationships between later school start times and amount of sleep. One study provided information concerning mental health outcomes, reporting an association between decreased depressive symptoms and later school start times. There were mixed results for the association between later school start times and absenteeism. Three studies reported mixed results concerning the association between later school start times and student alertness. There was limited indication of potential adverse effects on logistics, as the qualitative portions of one study reported less interaction between parents and children, and another reported staffing and scheduling difficulties. Because of the insufficient evidence, we cannot draw firm conclusions concerning adverse effects at this time.It is important to note the limitations of this evidence, especially as randomized controlled trials and high-quality primary studies are difficult to conduct; school systems are often unwilling or unable to allow researchers the necessary control over scheduling and data collection. Moreover, this evidence does not speak to the process of implementing later school starts, as the included studies focused on reporting the effects rather than exploring the process. AUTHORS' CONCLUSIONS: This systematic review on later school start times suggests several potential benefits for this intervention and points to the need for higher quality primary studies. However, as a result of the limited evidence base, we could not determine the effects of later school start times with any confidence.

The potential economic burden of Zika in the continental United States.

BACKGROUND: As the Zika virus epidemic continues to spread internationally, countries such as the United States must determine how much to invest in prevention, control, and response. Fundamental to these decisions is quantifying the potential economic burden of Zika under different scenarios. METHODOLOGY/PRINCIPLE FINDINGS: To inform such decision making, our team developed a computational model to forecast the potential economic burden of Zika across six states in the US (Alabama, Florida, Georgia, Louisiana, Mississippi, and Texas) which are at greatest risk of Zika emergence, under a wide range of attack rates, scenarios and circumstances. In order to accommodate a wide range of possibilities, different scenarios explored the effects of varying the attack rate from 0.01% to 10%. Across the six states, an attack rate of 0.01% is estimated to cost $183.4 million to society ($117.1 million in direct medical costs and $66.3 million in productivity losses), 0.025% would result in $198.6 million ($119.4 million and $79.2 million), 0.10% would result in $274.6 million ($130.8 million and $143.8 million) and 1% would result in $1.2 billion ($268.0 million and $919.2 million). CONCLUSIONS: Our model and study show how direct medical costs, Medicaid costs, productivity losses, and total costs to society may vary with different attack rates across the six states and the circumstances at which they may exceed certain thresholds (e.g., Zika prevention and control funding allocations that are being debated by the US government). A Zika attack rate of 0.3% across the six states at greatest risk of Zika infection, would result in total costs that exceed $0.5 billion, an attack rate of 1% would exceed $1 billion, and an attack rate of 2% would exceed $2 billion.

Effectiveness of UNAIDS targets and HIV vaccination across 127 countries.

The HIV pandemic continues to impose enormous morbidity, mortality, and economic burdens across the globe. Simultaneously, innovations in antiretroviral therapy, diagnostic approaches, and vaccine development are providing novel tools for treatment-as-prevention and prophylaxis. We developed a mathematical model to evaluate the added benefit of an HIV vaccine in the context of goals to increase rates of diagnosis, treatment, and viral suppression in 127 countries. Under status quo interventions, we predict a median of 49 million [first and third quartiles 44M, 58M] incident cases globally from 2015 to 2035. Achieving the Joint United Nations Program on HIV/AIDS 95-95-95 target was estimated to avert 25 million [20M, 33M] of these new infections, and an additional 6.3 million [4.8M, 8.7M] reduction was projected with the 2020 introduction of a 50%-efficacy vaccine gradually scaled up to 70% coverage. This added benefit of prevention through vaccination motivates imminent and ongoing clinical trials of viable candidates to realize the goal of HIV control.

Mitigating Prenatal Zika Virus Infection in the Americas.

BACKGROUND: Because of the risk for Zika virus infection in the Americas and the links between infection and microcephaly, other serious neurologic conditions, and fetal death, health ministries across the region have advised women to delay pregnancy. However, the effectiveness of this policy in reducing prenatal Zika virus infection has yet to be quantified. OBJECTIVE: To evaluate the effectiveness of pregnancy-delay policies on the incidence and prevalence of prenatal Zika virus infection. DESIGN: Vector-borne Zika virus transmission model fitted to epidemiologic data from 2015 to 2016 on Zika virus infection in Colombia. SETTING: Colombia, August 2015 to July 2017. PATIENTS: Population of Colombia, stratified by sex, age, and pregnancy status. INTERVENTION: Recommendations to delay pregnancy by 3, 6, 9, 12, or 24 months, at different levels of adherence. MEASUREMENTS: Weekly and cumulative incidence of prenatal infections and microcephaly cases. RESULTS: With 50% adherence to recommendations to delay pregnancy by 9 to 24 months, the cumulative incidence of prenatal Zika virus infections is likely to decrease by 17% to 44%, whereas recommendations to delay pregnancy by 6 or fewer months are likely to increase prenatal infections by 2% to 7%. This paradoxical exacerbation of prenatal Zika virus exposure is due to an elevated risk for pregnancies to shift toward the peak of the outbreak. LIMITATION: Sexual transmission was not explicitly accounted for in the model because of limited data but was implicitly subsumed within the overall transmission rate, which was calibrated to observed incidence. CONCLUSION: Pregnancy delays can have a substantial effect on reducing cases of microcephaly but risks exacerbating the Zika virus outbreak if the duration is not sufficient. Duration of the delay, population adherence, and the timing of initiation of the intervention must be carefully considered. PRIMARY FUNDING SOURCE: National Institutes of Health.

A Cost-Effectiveness Tool for Informing Policies on Zika Virus Control.

BACKGROUND: As Zika virus continues to spread, decisions regarding resource allocations to control the outbreak underscore the need for a tool to weigh policies according to their cost and the health burden they could avert. For example, to combat the current Zika outbreak the US President requested the allocation of $1.8 billion from Congress in February 2016. METHODOLOGY/PRINCIPAL FINDINGS: Illustrated through an interactive tool, we evaluated how the number of Zika cases averted, the period during pregnancy in which Zika infection poses a risk of microcephaly, and probabilities of microcephaly and Guillain-Barré Syndrome (GBS) impact the cost at which an intervention is cost-effective. From Northeast Brazilian microcephaly incidence data, we estimated the probability of microcephaly in infants born to Zika-infected women (0.49% to 2.10%). We also estimated the probability of GBS arising from Zika infections in Brazil (0.02% to 0.06%) and Colombia (0.08%). We calculated that each microcephaly and GBS case incurs the loss of 29.95 DALYs and 1.25 DALYs per case, as well as direct medical costs for Latin America and the Caribbean of $91,102 and $28,818, respectively. We demonstrated the utility of our cost-effectiveness tool with examples evaluating funding commitments by Costa Rica and Brazil, the US presidential proposal, and the novel approach of genetically modified mosquitoes. Our analyses indicate that the commitments and the proposal are likely to be cost-effective, whereas the cost-effectiveness of genetically modified mosquitoes depends on the country of implementation. CONCLUSIONS/SIGNIFICANCE: Current estimates from our tool suggest that the health burden from microcephaly and GBS warrants substantial expenditures focused on Zika virus control. Our results justify the funding committed in Costa Rica and Brazil and many aspects of the budget outlined in the US president's proposal. As data continue to be collected, new parameter estimates can be customized in real-time within our user-friendly tool to provide updated estimates on cost-effectiveness of interventions and inform policy decisions in country-specific settings.

Encephalitis, Ontario, Canada, 2002-2013.

Encephalitis, a brain inflammation leading to severe illness and often death, is caused by >100 pathogens. To assess the incidence and trends of encephalitis in Ontario, Canada, we obtained data on 6,463 Ontario encephalitis hospitalizations from the hospital Discharge Abstract Database for April 2002-December 2013 and analyzed these data using multiple negative binomial regression. The estimated crude incidence of all-cause encephalitis in Ontario was ≈4.3 cases/100,000 persons/year. Incidence rates for infants <1 year of age and adults >65 years were 3.9 and 3.0 times that of adults 20-44 years of age, respectively. Incidence peaks during August-September in 2002 and 2012 resulted primarily from encephalitis of unknown cause and viral encephalitis. Encephalitis occurred more frequently in older age groups and less frequently in women in Ontario when compared to England, but despite differences in population, vector-borne diseases, climate, and geography, the epidemiology was overall remarkably similar in the two regions.

Effects of Response to 2014-2015 Ebola Outbreak on Deaths from Malaria, HIV/AIDS, and Tuberculosis, West Africa.

Response to the 2014-2015 Ebola outbreak in West Africa overwhelmed the healthcare systems of Guinea, Liberia, and Sierra Leone, reducing access to health services for diagnosis and treatment for the major diseases that are endemic to the region: malaria, HIV/AIDS, and tuberculosis. To estimate the repercussions of the Ebola outbreak on the populations at risk for these diseases, we developed computational models for disease transmission and infection progression. We estimated that a 50% reduction in access to healthcare services during the Ebola outbreak exacerbated malaria, HIV/AIDS, and tuberculosis mortality rates by additional death counts of 6,269 (2,564-12,407) in Guinea; 1,535 (522-2,8780) in Liberia; and 2,819 (844-4,844) in Sierra Leone. The 2014-2015 Ebola outbreak was catastrophic in these countries, and its indirect impact of increasing the mortality rates of other diseases was also substantial.