San Francisco's Citywide COVID-19 Response: Strategies to Reduce COVID-19 Severity and Health Disparities, March 2020 Through May 2022.

San Francisco implemented one of the most intensive, comprehensive, multipronged COVID-19 pandemic responses in the United States using 4 core strategies: (1) aggressive mitigation measures to protect populations at risk for severe disease, (2) prioritization of resources in neighborhoods highly affected by COVID-19, (3) timely and adaptive data-driven policy making, and (4) leveraging of partnerships and public trust. We collected data to describe programmatic and population-level outcomes. The excess all-cause mortality rate in 2020 in San Francisco was half that seen in 2019 in California as a whole (8% vs 16%). In almost all age and race and ethnicity groups, excess mortality from COVID-19 was lower in San Francisco than in California overall, with markedly diminished excess mortality among people aged >65 years. The COVID-19 response in San Francisco highlights crucial lessons, particularly the importance of community responsiveness, joint planning, and collective action, to inform future pandemic response and advance health equity.

Factors Influencing Parent and Guardian Decisions on Vaccinating Their Children Against SARS-CoV-2: A Qualitative Study.

This qualitative analysis sought to explore factors that influenced parent/guardian intentions to vaccinate their children against SARS-CoV-2 in San Francisco, California, USA in order to inform San Francisco Department of Public Health's (SFDPH) youth vaccine rollout program. 30-minute, semi-structured telephone interviews were conducted with parents and guardians in either Spanish or English. Respondents shared their perspectives on vaccinating their children against SARS-CoV-2. Interviews were conducted over the telephone and recorded on Zoom. Participants (n = 40) were parents/guardians responding on behalf of their adolescent children (age 13+) and parents/guardians identified from the SFDPH COVID-19 testing database who tested for SARS-CoV-2 within the last 2 weeks. Interviews were conducted, audio recorded, transcribed, translated into English as appropriate, and rapidly analyzed in REDCap according to matrix analysis methodology to develop parent study themes. Perspectives on child vaccination were then explored through thematic analysis. Three themes were identified from the thematic analysis: (1) parental desires for children to return to school safely, (2) unclear messaging and information on COVID-19 prevention and vaccination, and (3) consideration of child's desires or opinions on receiving the vaccine. This study highlights specific factors influencing parent/guardian decisions on whether to vaccinate their children against SARS-CoV-2. The analysis also illustrates a potential role for children to play in influencing household vaccine decision-making.

Outdoor Activities Associated with Lower Odds of SARS-CoV-2 Acquisition: A Case-Control Study.

Access to recreational physical activities, particularly in outdoor spaces, has been a crucial outlet for physical and mental health during the COVID-19 pandemic. There is a need to understand how conducting these activities modulates the risk of SARS-CoV-2 infection. In this case-control study of unvaccinated individuals conducted in San Francisco, California, the odds of testing positive to SARS-CoV-2 were lower for those who conducted physical activity in outdoor locations (adjusted odds ratio [aOR]: 0.16, 95% confidence interval [CI]: 0.05, 0.40) in the two weeks prior to testing than for those who conducted no activity or indoor physical activity only. Individuals who visited outdoor parks, beaches, or playgrounds also had lower odds of testing positive to SARS-CoV-2 (aOR: 0.28, 95% CI: 0.11, 0.68) as compared with those who did not visit outdoor parks, beaches, or playgrounds. These findings, albeit in an unvaccinated population, offer observational data to support pre-existing ecological studies that suggest that activity in outdoor spaces lowers COVID-19 risk.

Measles transmission during a large outbreak in California.

A large measles outbreak in 2014-2015, linked to Disneyland theme parks, attracted international attention, and led to changes in California vaccine policy. We use dates of symptom onset and known epidemic links for California cases in this outbreak to estimate time-varying transmission in the outbreak, and to estimate generation membership of cases probabilistically. We find that transmission declined significantly during the course of the outbreak (p = 0.012), despite also finding that estimates of transmission rate by day or by generation can overestimate temporal decline. We additionally find that the outbreak size and duration alone are sufficient in this case to distinguish temporal decline from time-invariant transmission (p = 0.014). As use of a single large outbreak can lead to underestimates of immunity, however, we urge caution in interpretation of quantities estimated from this outbreak alone. Further research is needed to distinguish causes of temporal decline in transmission rates.

Relapse of Juvenile Idiopathic Arthritis-Associated Uveitis after Discontinuation of Immunomodulatory Therapy.

Purpose: To assess treatment outcomes in juvenile idiopathic arthritis (JIA)-associated uveitis and relapse rates upon discontinuation of immunomodulatory therapy (IMT). Methods: Medical records of patients with JIA-associated uveitis seen at the University of Illinois at Chicago and the F.I. Proctor Foundation uveitis clinics from September 14, 1988 to January 5, 2011 were reviewed. The main outcome was time to relapse after attempting to discontinue IMT.Results: Of 66 patients with JIA-associated uveitis, 51 (77%) received IMT as either sole or combination therapy. Of a total of 51, 41 (80%) patients achieved corticosteroid-sparing control. Attempts were made to discontinue treatment in 19/51 (37%) patients. Of a total of 19 patients, 13 (68%) attempting to discontinue IMT relapsed, with a median time to relapse of 288 days from the time of attempted taper/discontinuation (IQR: 108-338).Conclusions: Corticosteroid-sparing control of inflammation was achieved in the majority of patients; however, attempts to stop IMT were often unsuccessful. Close follow-up of patients after discontinuation of therapy is warranted.

Genotype-Specific Measles Transmissibility: A Branching Process Analysis.

Background: Substantial heterogeneity in measles outbreak sizes may be due to genotype-specific transmissibility. Using a branching process analysis, we characterize differences in measles transmission by estimating the association between genotype and the reproduction number R among postelimination California measles cases during 2000-2015 (400 cases, 165 outbreaks). Methods: Assuming a negative binomial secondary case distribution, we fit a branching process model to the distribution of outbreak sizes using maximum likelihood and estimated the reproduction number R for a multigenotype model. Results: Genotype B3 is found to be significantly more transmissible than other genotypes (P = .01) with an R of 0.64 (95% confidence interval [CI], .48-.71), while the R for all other genotypes combined is 0.43 (95% CI, .28-.54). This result is robust to excluding the 2014-2015 outbreak linked to Disneyland theme parks (referred to as "outbreak A" for conciseness and clarity) (P = .04) and modeling genotype as a random effect (P = .004 including outbreak A and P = .02 excluding outbreak A). This result was not accounted for by season of introduction, age of index case, or vaccination of the index case. The R for outbreaks with a school-aged index case is 0.69 (95% CI, .52-.78), while the R for outbreaks with a non-school-aged index case is 0.28 (95% CI, .19-.35), but this cannot account for differences between genotypes. Conclusions: Variability in measles transmissibility may have important implications for measles control; the vaccination threshold required for elimination may not be the same for all genotypes or age groups.

The Effect of Contact Investigations and Public Health Interventions in the Control and Prevention of Measles Transmission: A Simulation Study.

BACKGROUND: Measles cases continue to occur despite its elimination status in the United States. To control transmission, public health officials confirm the measles diagnosis, identify close contacts of infectious cases, deliver public health interventions (i.e., post-exposure prophylaxis) among those who are eligible, and follow-up with the close contacts to determine overall health outcomes. A stochastic network simulation of measles contact tracing was conducted using existing agent-based modeling software and a synthetic population with high levels of immunity in order to estimate the impact of different interventions in controlling measles transmission. METHODS AND FINDINGS: The synthetic population was created to simulate California`s population in terms of population demographics, household, workplace, school, and neighborhood characteristics using California Department of Finance 2010 census data. Parameters for the model were obtained from a review of the literature, California measles case surveillance data, and expert opinion. Eight different scenarios defined by the use of three different public health interventions were evaluated: (a) post-exposure measles, mumps, and rubella (MMR) vaccine, (b) post-exposure immune globulin (IG), and (c) voluntary isolation and home quarantine in the presence or absence of public health response delays. Voluntary isolation and home quarantine coupled with one or two other interventions had the greatest reduction in the number of secondary cases infected by the index case and the probability of escape situations (i.e., the outbreak continues after 90 days). CONCLUSIONS: Interrupting contact patterns via voluntary isolation and home quarantine are particularly important in reducing the number of secondary cases infected by the index case and the probability of uncontrolled outbreaks.

Comparison of Surgical Outcome After Ahmed Valve Implantation for Patients With and Without Fluocinolone Intravitreal Implant (Retisert).

PURPOSE: To determine whether long-term, slow-release exposure to corticosteroids with Retisert promotes better surgical outcomes after Ahmed valve implantation. PATIENTS: This comparative retrospective cohort study included 17 study eyes (10 patients) with uncontrolled uveitis requiring Retisert and Ahmed implantation, and 55 control eyes (51 patients) with other types of medically uncontrolled glaucoma that only received Ahmed. MATERIALS AND METHODS: Main outcome measures were intraocular pressure (IOP), glaucoma eye drops per day, best-corrected visual acuity, early complications, and late complications at 1, 3, 6, and 12 months. Linear mixed effects models were used to model IOP, glaucoma drops per day, and visual acuity at 1 year after surgery. RESULTS: At 1 year, the study eyes had a mean IOP of 12.24, which was lower than that for control eyes at 15.17 (P=0.04). At 1 year, the average number of glaucoma eye drops used per day for study eyes was 1.4, which was lower than that for control eyes at 2.3 (P=0.03). At 1 year, there were no statistically significant differences in change in visual acuity, early complications, and late complications between study and control eyes. CONCLUSIONS: Patients who received a Retisert implantation had lower IOP and used fewer glaucoma eye drops compared with control eyes at 1-year post-Ahmed valve surgery. This study suggests that long-term, slow-release corticosteroid medication from Retisert (fluocinolone acetonide) may improve the surgical outcome for patients with an Ahmed valve implantation and/or Retisert helps control uveitis in patients with uveitic glaucoma receiving Ahmed valves.

Correction: Evaluating Subcriticality during the Ebola Epidemic in West Africa.

[This corrects the article DOI: 10.1371/journal.pone.0140651.].

The permuted locus trial--Well suited for emerging pathogens?

The recent Ebola virus epidemic was waning by the time stakeholders were ready to field vaccines for testing but an evidence-based response to a novel pathogen will surely be required again. Here, we present a design for such a randomized controlled trial. The permuted locus trial was originally intended for studying the influence of water wells on trachoma. While outcomes can be measured in individuals, neither individuals nor groups are themselves randomized to arms, just potential well-sites, or in the case of an epidemic, index cases. The permuted locus trial may be used when classic individual and cluster-randomized trial design and analyses may not be optimal.

Evaluating Subcriticality during the Ebola Epidemic in West Africa.

The 2014-2015 Ebola outbreak is the largest and most widespread to date. In order to estimate ongoing transmission in the affected countries, we estimated the weekly average number of secondary cases caused by one individual infected with Ebola throughout the infectious period for each affected West African country using a stochastic hidden Markov model fitted to case data from the World Health Organization. If the average number of infections caused by one Ebola infection is less than 1.0, the epidemic is subcritical and cannot sustain itself. The epidemics in Liberia and Sierra Leone have approached subcriticality at some point during the epidemic; the epidemic in Guinea is ongoing with no evidence that it is subcritical. Response efforts to control the epidemic should continue in order to eliminate Ebola cases in West Africa.

The role of vaccination coverage, individual behaviors, and the public health response in the control of measles epidemics: an agent-based simulation for California.

BACKGROUND: Measles cases continue to occur among susceptible individuals despite the elimination of endemic measles transmission in the United States. Clustering of disease susceptibility can threaten herd immunity and impact the likelihood of disease outbreaks in a highly vaccinated population. Previous studies have examined the role of contact tracing to control infectious diseases among clustered populations, but have not explicitly modeled the public health response using an agent-based model. METHODS: We developed an agent-based simulation model of measles transmission using the Framework for Reconstructing Epidemiological Dynamics (FRED) and the Synthetic Population Database maintained by RTI International. The simulation of measles transmission was based on interactions among individuals in different places: households, schools, daycares, workplaces, and neighborhoods. The model simulated different levels of immunity clustering, vaccination coverage, and contact investigations with delays caused by individuals' behaviors and/or the delay in a health department's response. We examined the effects of these characteristics on the probability of uncontrolled measles outbreaks and the outbreak size in 365 days after the introduction of one index case into a synthetic population. RESULTS: We found that large measles outbreaks can be prevented with contact investigations and moderate contact rates by having (1) a very high vaccination coverage (≥ 95%) with a moderate to low level of immunity clustering (≤ 0.5) for individuals aged less than or equal to 18 years, or (2) a moderate vaccination coverage (85% or 90%) with no immunity clustering for individuals (≤ 18 years of age), a short intervention delay, and a high probability that a contact can be traced. Without contact investigations, measles outbreaks may be prevented by the highest vaccination coverage with no immunity clustering for individuals (≤ 18 years of age) with moderate contact rates; but for the highest contact rates, even the highest coverage with no immunity clustering for individuals (≤ 18 years of age) cannot completely prevent measles outbreaks. CONCLUSIONS: The simulation results demonstrated the importance of vaccination coverage, clustering of immunity, and contact investigations in preventing uncontrolled measles outbreaks.

The epidemiology and surveillance workforce among local health departments in California: mutual aid and surge capacity for routine and emergency infectious disease situations.

OBJECTIVE: Public health surveillance and epidemiologic investigations are critical public health functions for identifying threats to the health of a community. We conducted a survey of local health departments (LHDs) in California to describe the workforce that supports public health surveillance and epidemiologic functions during routine and emergency infectious disease situations. METHODS: The target population consisted of the 61 LHDs in California. The online survey instrument was designed to collect information about the workforce involved in key epidemiologic functions. We also examined how the public health workforce increases its epidemiologic capacity during infectious disease emergencies. RESULTS: Of 61 LHDs in California, 31 (51%) completed the survey. A wide range of job classifications contribute to epidemiologic functions routinely, and LHDs rely on both internal and external sources of epidemiologic surge capacity during infectious disease emergencies. This study found that while 17 (55%) LHDs reported having a mutual aid agreement with at least one other organization for emergency response, only nine (29%) LHDs have a mutual aid agreement specifically for epidemiology and surveillance functions. CONCLUSIONS: LHDs rely on a diverse workforce to conduct epidemiology and public health surveillance functions, emphasizing the need to identify and describe the types of staff positions that could benefit from public health surveillance and epidemiology training. While some organizations collaborate with external partners to support these functions during an emergency, many LHDs do not rely on mutual aid agreements for epidemiology and surveillance activities.

A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

OBJECTIVE: To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Multicenter, block-randomized, observer-masked clinical trial. PARTICIPANTS: Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. INTERVENTION: Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. MAIN OUTCOME MEASURES: Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. RESULTS: Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). CONCLUSIONS: There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

Identifying postelimination trends for the introduction and transmissibility of measles in the United States.

The continued elimination of measles requires accurate assessment of its epidemiology and a critical evaluation of how its incidence is changing with time. National surveillance of measles in the United States between 2001 and 2011 provides data on the number of measles introductions and the size of the resulting transmission chains. These data allow inference of the effective reproduction number, Reff, and the probability of an outbreak occurring. Our estimate of 0.52 (95% confidence interval: 0.44, 0.60) for Reff is smaller than prior results. Our findings are relatively insensitive to the possibility that as few as 75% of cases were detected. Although we confirm that measles remains eliminated, we identify an increasing trend in the number of measles cases with time. We show that this trend is likely attributable to an increase in the number of disease introductions rather than a change in the transmissibility of measles. However, we find that transmissibility may increase substantially if vaccine coverage drops by as little as 1%. Our general approach of characterizing the case burden of measles is applicable to the epidemiologic assessment of other weakly transmitting or vaccine-controlled pathogens that are either at risk of emerging or on the brink of elimination.

Antibiotic use as a tragedy of the commons: a cross-sectional survey.

BACKGROUND: Many believe antibiotic use results in a tragedy of the commons, since overuse may lead to antibiotic resistance and limiting use would benefit society. In contrast, mass antibiotic treatment programs are thought to result in community-wide benefits. A survey was conducted to learn the views of infectious disease experts on the individual- and societal-level consequences of antibiotic use. METHODS: The survey instrument was designed to elicit opinions on antibiotic use and resistance. It was sent via SurveyMonkey to infectious disease professionals identified through literature searches. Descriptive statistics were used to analyze the data. RESULTS: A total of 1,530 responses were received for a response rate of 9.9%. Nearly all participants believed antibiotic use could result in a tragedy of the commons, at least in certain circumstances (96.0%). Most participants did not believe mass antibiotic treatment programs could produce societal benefits in an antibiotic-free society (91.4%) or in the United States (94.2%), though more believed such programs would benefit antibiotic-free societies compared to the United States (P < 0.001). CONCLUSIONS: The experts surveyed believe that antibiotic use can result in a tragedy of the commons and do not believe that mass treatment programs benefit individuals or society.

Effect of the one-child policy on influenza transmission in China: a stochastic transmission model.

BACKGROUND: China's one-child-per-couple policy, introduced in 1979, led to profound demographic changes for nearly a quarter of the world's population. Several decades later, the consequences include decreased fertility rates, population aging, decreased household sizes, changes in family structure, and imbalanced sex ratios. The epidemiology of communicable diseases may have been affected by these changes since the transmission dynamics of infectious diseases depend on demographic characteristics of the population. Of particular interest is influenza because China and Southeast Asia lie at the center of a global transmission network of influenza. Moreover, changes in household structure may affect influenza transmission. Is it possible that the pronounced demographic changes that have occurred in China have affected influenza transmission? METHODS AND FINDINGS: To address this question, we developed a continuous-time, stochastic, individual-based simulation model for influenza transmission. With this model, we simulated 30 years of influenza transmission and compared influenza transmission rates in populations with and without the one-child policy control. We found that the average annual attack rate is reduced by 6.08% (SD 2.21%) in the presence of the one-child policy compared to a population in which no demographic changes occurred. There was no discernible difference in the secondary attack rate, -0.15% (SD 1.85%), between the populations with and without a one-child policy. We also forecasted influenza transmission over a ten-year time period in a population with a two-child policy under a hypothesis that a two-child-per-couple policy will be carried out in 2015, and found a negligible difference in the average annual attack rate compared to the population with the one-child policy. CONCLUSIONS: This study found that the average annual attack rate is slightly lowered in a population with a one-child policy, which may have resulted from a decrease in household size and the proportion of children in the population.

Incidence of scleritis and episcleritis: results from the Pacific Ocular Inflammation Study.

PURPOSE: To ascertain the incidence of scleritis and episcleritis in a Hawaiian population and describe variations by age, sex, and race. DESIGN: Retrospective, population-based cohort study. METHODS: All electronic medical records for enrollees in Kaiser Permanente Hawaii (n = 217,061) from January 1, 2006 to December 31, 2007 were searched for International Classification of Diseases, 9th Edition (ICD-9) codes associated with ocular inflammation. Chart review was conducted to verify a clinical diagnosis of scleritis or episcleritis. Confirmed cases were used to calculate incidence rates per 100,000 person-years. Ninety-five percent confidence intervals (CI) were calculated for each incidence rate, including age-, sex-, and race-specific rates, using bias-corrected Poisson regression. To assess for confounding, a multivariate analysis adjusting for age, sex, and race was also performed. RESULTS: Of 217,061 eligible patients, 17 incident scleritis cases and 93 incident episcleritis cases were confirmed. The overall incidence rates of scleritis and episcleritis were 4.1 (95% CI: 2.6-6.6) and 21.7 (95% CI: 17.7-26.5) cases per 100,000 person-years, respectively. Women were overrepresented among scleritis patients (P = .049). Pacific Islanders were the most underrepresented racial group among cases of scleritis and episcleritis (P = .006, P = .001). Blacks had the highest incidence of scleritis (P = .004). CONCLUSIONS: These results provide a population-based estimate of the incidence of scleritis and episcleritis in a diverse population and highlight differences in patients' demographic characteristics. Differences in incidence by sex and race raise questions about genetic and environmental influences on the development of these conditions.