Modeling local coronavirus outbreaks.

This article presents an overview of methods developed for the modeling and control of local coronavirus outbreaks. The article reviews early transmission dynamics featuring exponential growth in infections, and links this to a renewal epidemic model where the current incidence of infection depends upon the expected value of incidence randomly lagged into the past. This leads directly to simple formulas for the fraction of the population infected in an unmitigated outbreak, and reveals herd immunity as the solution to an optimization problem. The model also leads to direct and easy-to-understand formulas for aligning observable epidemic indicators such as cases, hospitalizations and deaths with the unobservable incidence of infection, and as a byproduct leads to a simple first-order approach for estimating the effective reproduction number R t . The model also leads naturally to direct assessments of the effectiveness of isolation in preventing the spread of infection. This is illustrated with application to repeat asymptomatic screening programs of the sort utilized by universities, sports teams and businesses to prevent the spread of infection.

Repeat SARS-CoV-2 testing models for residential college populations.

Residential colleges are considering re-opening under uncertain futures regarding the COVID-19 pandemic. We consider repeat SARS-CoV-2 testing models for the purpose of containing outbreaks in the residential campus community. The goal of repeat testing is to detect and isolate new infections rapidly to block transmission that would otherwise occur both on and off campus. The models allow for specification of aspects including scheduled on-campus resident screening at a given frequency, test sensitivity that can depend on the time since infection, imported infections from off campus throughout the school term, and a lag from testing until student isolation due to laboratory turnaround and student relocation delay. For early- (late-) transmission of SARS-CoV-2 by age of infection, we find that weekly screening cannot reliably contain outbreaks with reproductive numbers above 1.4 (1.6) if more than one imported exposure per 10,000 students occurs daily. Screening every three days can contain outbreaks providing the reproductive number remains below 1.75 (2.3) if transmission happens earlier (later) with time from infection, but at the cost of increased false positive rates requiring more isolation quarters for students testing positive. Testing frequently while minimizing the delay from testing until isolation for those found positive are the most controllable levers for preventing large residential college outbreaks. A web app that implements model calculations is available to facilitate exploration and consideration of a variety of scenarios.

Aligning SARS-CoV-2 indicators via an epidemic model: application to hospital admissions and RNA detection in sewage sludge.

Ascertaining the state of coronavirus outbreaks is crucial for public health decision-making. Absent repeated representative viral test samples in the population, public health officials and researchers alike have relied on lagging indicators of infection to make inferences about the direction of the outbreak and attendant policy decisions. Recently researchers have shown that SARS-CoV-2 RNA can be detected in municipal sewage sludge with measured RNA concentrations rising and falling suggestively in the shape of an epidemic curve while providing an earlier signal of infection than hospital admissions data. The present paper presents a SARS-CoV-2 epidemic model to serve as a basis for estimating the incidence of infection, and shows mathematically how modeled transmission dynamics translate into infection indicators by incorporating probability distributions for indicator-specific time lags from infection. Hospital admissions and SARS-CoV-2 RNA in municipal sewage sludge are simultaneously modeled via maximum likelihood scaling to the underlying transmission model. The results demonstrate that both data series plausibly follow from the transmission model specified and provide a 95% confidence interval estimate of the reproductive number R0 ≈ 2.4 ± 0.2. Sensitivity analysis accounting for alternative lag distributions from infection until hospitalization and sludge RNA concentration respectively suggests that the detection of viral RNA in sewage sludge leads hospital admissions by 3 to 5 days on average. The analysis suggests that stay-at-home restrictions plausibly removed 89% of the population from the risk of infection with the remaining 11% exposed to an unmitigated outbreak that infected 9.3% of the total population.

Snapshot Models of Undocumented Immigration.

Accurately estimating the size of the undocumented immigrant population is a critical component of assessing the health and security risks of undocumented immigration to the United States. To provide one such estimate, we use data from the Mexican Migration Project (MMP), a study that includes samples of undocumented Mexican immigrants to the United States after their return to Mexico. Of particular interest are the departure and return dates of a sampled migrant's most recent sojourn in the United States, and the total number of such journeys undertaken by that migrant household, for these data enable the construction of data-driven undocumented immigration models. However, such data are subject to an extreme physical bias, for to be included in such a sample, a migrant must have returned to Mexico by the time of the survey, excluding those undocumented immigrants still in the United States. In our analysis, we account for this bias by jointly modeling trip timing and duration to produce the likelihood of observing the data in such a "snapshot" sample. Our analysis characterizes undocumented migration flows including single-visit migrants, repeat visitors, and "retirement" from circular migration. Starting with 1987, we apply our models to 30 annual random snapshot surveys of returned undocumented Mexican migrants accounting for undocumented Mexican migration from 1980 to 2016. Scaling to population quantities and supplementing our analysis of southern border crossings with estimates of visa overstays, we produce lower bounds on the total number of undocumented immigrants that are much larger than conventional estimates based on U.S.-based census-linked surveys, and broadly consistent with the more recent estimates reported by Fazel-Zarandi, Feinstein, and Kaplan.

Contributions of Persons Living With Dementia to Scientific Research Meetings. Results From the National Research Summit on Care, Services, and Supports for Persons With Dementia and Their Caregivers.

OBJECTIVE: Inclusion of patients in research activities has increased in the United States but no guidelines for inclusion of individuals with cognitive impairment exist. The experiences from the Persons Living with Dementia (PLWD) Stakeholder Group that formed to support the first National Research Summit on Care, Services, and Supports for Persons with Dementia and Their Caregivers provided a test of feasibility of this type of participation for a major research meeting and an opportunity to understand specific contributions of the Group. METHODS: The PLWD Stakeholder Group was formed by Summit co-chairs as one of six stakeholder groups charged with providing input into the Summit agenda and meeting recommendations. Members were recruited through clinician/researchers with personal knowledge of potential members. Following the Summit, Group members convened to review Group contributions to the Summit agenda, list of speakers, and Summit research recommendations. RESULTS: The PLWD Group influenced the content of the Summit agenda and some Group members were invited to contribute through Summit presentations. The Group influenced Summit outcomes: of the 58 research recommendations that emerged, 30 express ideas contributed by the PLWD. CONCLUSIONS: The Stakeholder Group for PLWD proved feasible to implement and impacted the agenda and output of a major national research meeting on dementia.

The Experiences of Persons Living with Dementia Planning for a Dementia Research Meeting. Lessons Learned From the National Research Summit on Care, Services, and Supports for Persons With Dementia and Their Caregivers.

OBJECTIVE: A stakeholder group for persons living with dementia (PLWD) was convened to support the work of a major US dementia research meeting. The objectives of this examination are to present the steps used to implement the Group and guidance for both PLWD and researchers for partnering on research conference planning and participation. METHODS: PLWD met monthly to provide input into the agenda for the 2017 Research Summit on Dementia Care and some Group members also presented at the Summit. Following the Summit, the Group reviewed their contributions and completed an evaluation of the Group process, identifying best practices to support future efforts. RESULTS: Group members were initially unsure about participating due to concerns about ability to contribute and concerns about disease progression. Members reported that participation was a positive experience, however, identifying Group-led governance and attention to Group work process as important contributors. In addition to giving input to the Summit and having the opportunity to interact with researchers, sharing personal experiences with each other was part of the value of the Group to members. Careful Group selection and attention to governance were among the Best Practices members. CONCLUSION: Despite initial uncertainty among members about participating as a Stakeholder Group to inform a national research meeting, members developed a successful process for governance, convening, and providing input to a major national research meeting. Group's self-evaluation yielded specific strategies likely to be useful in formation and implementation of future partnerships between researchers and persons living with dementia.

Containing 2019-nCoV (Wuhan) coronavirus.

The novel coronavirus 2019-nCoV first appeared in December 2019 in Wuhan, China. While most of the initial cases were linked to the Huanan Seafood Wholesale Market, person-to-person transmission has been verified. Given that a vaccine cannot be developed and deployed for at least a year, preventing further transmission relies upon standard principles of containment, two of which are the isolation of known cases and the quarantine of persons believed at high risk of exposure. This note presents probability models for assessing the effectiveness of case isolation and quarantine within a community during the initial phase of an outbreak with illustrations based on early observations from Wuhan.

Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association.

BACKGROUND: Acute rheumatic fever remains a serious healthcare concern for the majority of the world's population despite its decline in incidence in Europe and North America. The goal of this statement was to review the historic Jones criteria used to diagnose acute rheumatic fever in the context of the current epidemiology of the disease and to update those criteria to also take into account recent evidence supporting the use of Doppler echocardiography in the diagnosis of carditis as a major manifestation of acute rheumatic fever. METHODS AND RESULTS: To achieve this goal, the American Heart Association's Council on Cardiovascular Disease in the Young and its Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee organized a writing group to comprehensively review and evaluate the impact of population-specific differences in acute rheumatic fever presentation and changes in presentation that can result from the now worldwide availability of nonsteroidal anti-inflammatory drugs. In addition, a methodological assessment of the numerous published studies that support the use of Doppler echocardiography as a means to diagnose cardiac involvement in acute rheumatic fever, even when overt clinical findings are not apparent, was undertaken to determine the evidence basis for defining subclinical carditis and including it as a major criterion of the Jones criteria. This effort has resulted in the first substantial revision to the Jones criteria by the American Heart Association since 1992 and the first application of the Classification of Recommendations and Levels of Evidence categories developed by the American College of Cardiology/American Heart Association to the Jones criteria. CONCLUSIONS: This revision of the Jones criteria now brings them into closer alignment with other international guidelines for the diagnosis of acute rheumatic fever by defining high-risk populations, recognizing variability in clinical presentation in these high-risk populations, and including Doppler echocardiography as a tool to diagnose cardiac involvement.

Clinical Perineal Streptococcal Infection in Children: Epidemiologic Features, Low Symptomatic Recurrence Rate after Treatment, and Risk Factors for Recurrence.

OBJECTIVES: To evaluate the epidemiology of perineal streptococcal infection and recurrence rates following amoxicillin treatment. STUDY DESIGN: We used laboratory logs in a single pediatric practice to identify patients 0-18 years of age with perineal cultures positive for group A Streptococcus (GAS) and reviewed their medical charts. We described epidemiologic features, determined recurrence rates following antibiotic treatment, and performed a case-control study to identify possible risk factors for recurrence in patients treated with amoxicillin. RESULTS: We found a perineal streptococcal infection rate of 4.6 per 10,000 patient encounters and a recurrence rate in 157 patients with perineal streptococcal infection of 12.4% after amoxicillin. In male patients, the predominant site of involvement was the perianal region (86%), and for female patients, the perivaginal area (62%). Nearly 80% of patients were 2-7 years of age (range 18 days-12.5 years). Perineal streptococcal infection and GAS pharyngitis followed a similar seasonal pattern of occurrence with 65% of perineal streptococcal infection occurring October through March. In patients with perineal streptococcal infection, 95% had a concomitant pharyngeal culture positive for GAS. Best predictive factors for recurrence after amoxicillin were longer duration of symptoms prior to diagnosis and having a sibling with perineal streptococcal infection at some time before or after the initial episode. CONCLUSIONS: Following treatment with amoxicillin, we found a low recurrence rate of 12.4%. Amoxicillin can be expected to be reliable first-line therapy for perineal streptococcal infection.

A population pharmacokinetic modeling approach shows that serum penicillin G concentrations are below inhibitory concentrations by two weeks after benzathine penicillin G injection in the majority of young adults.

Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of >0.02 mg/liter, a proposed protective threshold against group A Streptococcus pyogenes (GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of >0.02 mg/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of >0.02 mg/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks.

Clinical management of the most common group A ß-hemolytic streptococcal infections.

Group A streptococcal (Streptococcus pyogenes) infections remain important causes of medical and public health morbidity and mortality even during the early twenty-first century. Although most often concentrated in socially/economically disadvantaged populations, the problems remain significant in both industrializing and industrialized countries. The many M/emm types of GAS contribute to herd immunity in populations and also affect the control of streptococcal infections in these populations. Although this bacterium remains among the most susceptible to most antibiotics, it is evident that antibiotics alone have not solved the group A streptococcal medical and public health problems, even in those places where access to medical care is readily available. It is likely that the current streptococcal problems will remain difficult to manage and will remain essentially unchanged until the broad implementation of a cost-effective group A streptococcal vaccine, likely some years in the future.

Foodborne outbreak of group a streptococcus pharyngitis associated with a high school dance team banquet--Minnesota, 2012.

BACKGROUND: On 20 March 2012, the Minnesota Department of Health (MDH) was notified of multiple Facebook postings suggestive of a foodborne outbreak of Group A Streptococcus (GAS) pharyngitis occurring among attendees of a high school dance team banquet. An investigation was initiated. METHODS: Associations between GAS pharyngitis and specific food items were assessed among banquet attendees. Pharyngeal swabs were performed on attendees, household contacts, and food workers. Patient GAS isolates from clinical laboratories were also obtained. Pharyngeal and food specimens were cultured for GAS by the MDH Public Health Laboratory. Isolates were further characterized by pulsed-field gel electrophoresis (PFGE) and emm typing. RESULTS: Among 63 persons who consumed banquet food, 18 primary illnesses occurred, yielding an attack rate of 29%. Although no food or beverage items were significantly associated with illness, pasta consumption yielded the highest relative risk (risk ratio, 3.56; 95% confidence interval, .25-50.6). GAS colonies with indistinguishable PFGE patterns corresponding to emm subtype 1.0 were isolated from 5 patients and from leftover pasta. The pasta was prepared at home by a dance team member parent; both parent and child reported GAS pharyngitis episodes 3 weeks before the banquet. CONCLUSIONS: In this foodborne outbreak of GAS pharyngitis, pasta was implicated as the vehicle. Recognition of foodborne GAS illness is challenging because transmission is typically assumed to occur by respiratory spread; foodborne transmission should be considered when clusters of GAS pharyngitis patients are encountered. DNA-based typing can reveal potentially epidemiologically related isolates during GAS disease outbreaks and facilitate understanding and control of GAS disease.

Tracing the evolutionary history of the pandemic group A streptococcal M1T1 clone.

The past 50 years has witnessed the emergence of new viral and bacterial pathogens with global effect on human health. The hyperinvasive group A Streptococcus (GAS) M1T1 clone, first detected in the mid-1980s in the United States, has since disseminated worldwide and remains a major cause of severe invasive human infections. Although much is understood regarding the capacity of this pathogen to cause disease, much less is known of the precise evolutionary events selecting for its emergence. We used high-throughput technologies to sequence a World Health Organization strain collection of serotype M1 GAS and reconstructed its phylogeny based on the analysis of core genome single-nucleotide polymorphisms. We demonstrate that acquisition of a 36-kb genome segment from serotype M12 GAS and the bacteriophage-encoded DNase Sda1 led to increased virulence of the M1T1 precursor and occurred relatively early in the molecular evolutionary history of this strain. The more recent acquisition of the phage-encoded superantigen SpeA is likely to have provided selection advantage for the global dissemination of the M1T1 clone. This study provides an exemplar for the evolution and emergence of virulent clones from microbial populations existing commensally or causing only superficial infection.

Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America.

The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America.

The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

Scaling SARS-CoV-2 wastewater concentrations to population estimates of infection.

Monitoring the progression of SARS-CoV-2 outbreaks requires accurate estimation of the unobservable fraction of the population infected over time in addition to the observed numbers of COVID-19 cases, as the latter present a distorted view of the pandemic due to changes in test frequency and coverage over time. The objective of this report is to describe and illustrate an approach that produces representative estimates of the unobservable cumulative incidence of infection by scaling the daily concentrations of SARS-CoV-2 RNA in wastewater from the consistent population contribution of fecal material to the sewage collection system.