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 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.

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.

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.

The epidemiology and surveillance response to pandemic influenza A (H1N1) among local health departments in the San Francisco Bay Area.

BACKGROUND: Public health surveillance and epidemiologic investigations are critical public health functions for identifying threats to the health of a community. Very little is known about how these functions are conducted at the local level. The purpose of the Epidemiology Networks in Action (EpiNet) Study was to describe the epidemiology and surveillance response to the 2009 pandemic influenza A (H1N1) by city and county health departments in the San Francisco Bay Area in California. The study also documented lessons learned from the response in order to strengthen future public health preparedness and response planning efforts in the region. METHODS: In order to characterize the epidemiology and surveillance response, we conducted key informant interviews with public health professionals from twelve local health departments in the San Francisco Bay Area. In order to contextualize aspects of organizational response and performance, we recruited two types of key informants: public health professionals who were involved with the epidemiology and surveillance response for each jurisdiction, as well as the health officer or his/her designee responsible for H1N1 response activities. Information about the organization, data sources for situation awareness, decision-making, and issues related to surge capacity, continuity of operations, and sustainability were collected during the key informant interviews. Content and interpretive analyses were conducted using ATLAS.ti software. RESULTS: The study found that disease investigations were important in the first months of the pandemic, often requiring additional staff support and sometimes forcing other public health activities to be put on hold. We also found that while the Incident Command System (ICS) was used by all participating agencies to manage the response, the manner in which it was implemented and utilized varied. Each local health department (LHD) in the study collected epidemiologic data from a variety of sources, but only case reports (including hospitalized and fatal cases) and laboratory testing data were used by all organizations. While almost every LHD attempted to collect school absenteeism data, many respondents reported problems in collecting and analyzing these data. Laboratory capacity to test influenza specimens often aided an LHD's ability to conduct disease investigations and implement control measures, but the ability to test specimens varied across the region and even well-equipped laboratories exceeded their capacity. As a whole, the health jurisdictions in the region communicated regularly about key decision-making (continued on next page) (continued from previous page) related to the response, and prior regional collaboration on pandemic influenza planning helped to prepare the region for the novel H1N1 influenza pandemic. The study did find, however, that many respondents (including the majority of epidemiologists interviewed) desired an increase in regional communication about epidemiology and surveillance issues. CONCLUSION: The study collected information about the epidemiology and surveillance response among LHDs in the San Francisco Bay Area that has implications for public health preparedness and emergency response training, public health best practices, regional public health collaboration, and a perceived need for information sharing.

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.

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.

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.

Effectiveness of the polysaccharide pneumococcal vaccine among HIV-infected persons in Brazil: a case control study.

BACKGROUND: Polysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil but there is uncertainty about its effectiveness in this patient population. The main objective of this study was to assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal infection among HIV-infected adult patients in São Paulo, Brazil. METHODS: A case-control study of 79 cases and 242 controls matched on CD4+ cell count and health care setting was conducted. Among HIV-infected adults in São Paulo, Brazil, with and without S. pneumoniae recovered from a normally sterile site; prior receipt of 23 valent polysaccharide pneumococcal vaccine was determined by review of medical records and patient interview. RESULTS: After adjustment for confounding factors, the point estimate for the effectiveness of 23 valent polysaccharide vaccine among HIV-infected adults against all invasive pneumococcal infection was 18% (95% CI: <0 to 62%). CONCLUSION: We were unable to demonstrate a statistically significant protective effect of 23 valent polysaccharide against invasive pneumococcal infection vaccine among HIV-infected adults in Brazil.While the vaccine is relatively inexpensive and safe, its effectiveness among HIV-infected adults in Brazil is uncertain.

Early prediction of median survival among a large AIDS surveillance cohort.

BACKGROUND: For individuals with AIDS, data exist relatively soon after diagnosis to allow estimation of "early" survival quantiles (e.g., the 0.10, 0.15, 0.20 and 0.30 quantiles, etc.). Many years of additional observation must elapse before median survival, a summary measure of survival, can be estimated accurately. In this study, a new approach to predict AIDS median survival is presented and its accuracy tested using AIDS surveillance data. METHODS: The data consisted of 96,373 individuals who were reported to the HIV/AIDS Reporting System of the California Department of Health Services Office of AIDS as of December 31, 1996. We defined cohorts based on quarter year of diagnosis (e.g., the "931" cohort consists of individuals diagnosed with AIDS in the first quarter of 1993). We used early quantiles (estimated using the Inverse Probability of Censoring Weighted estimator) of the survival distribution to estimate median survival by assuming a linear relationship between the earlier quantiles and median survival. From this model, median survival was predicted for cohorts for which a median could not be estimated empirically from the available data. This prediction was compared with the actual medians observed when using updated survival data reported at least five years later. RESULTS: Using the 0.15 quantile as the predictor and the data available as of December 31, 1996, we were able to predict the median survival of four cohorts (933, 934, 941, and 942) to be 34, 34, 31, and 29 months. Without this approach, there were insufficient data with which to make any estimate of median survival. The actual median survival of these four cohorts (using data as of December 31, 2001) was found to be 32, 40, 46, and 80 months, suggesting that the accuracy for this approach requires a minimum of three years to elapse from diagnosis to the time an accurate prediction can be made. CONCLUSION: The results of this study suggest that early and accurate prediction of median survival time after AIDS diagnosis may be possible using early quantiles of the survival distribution. The methodology did not seem to work well during a period of significant change in survival as observed with highly active antiretroviral treatment, but results suggest that it may work well in a time of more gradual improvement in survival.

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.

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

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

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.

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.

Treatment outcomes after highly active antiretroviral therapy: a meta-analysis of randomised controlled trials.

This systematic review summarises the evidence for treatment efficacy and tolerability of highly active antiretroviral therapies containing two nucleoside reverse transcriptase inhibitors (NRTI) with a protease inhibitor (PI), compared with two NRTIs alone for the treatment of HIV-1 infection in randomised controlled trials. Three electronic databases (Medline, Embase, and the Cochrane Library) were searched up to December 2003. 16 randomised controlled trials met the inclusion criteria and were included in the analysis from 328 articles screened. The pooled analysis indicated that treatment with two NRTIs with a PI is more effective in achieving viral suppression than two NRTIs alone (relative risk [RR] 3.44, 95% confidence interval [CI] 2.43-4.87). However, the RR for discontinuation of treatment due to adverse events of treatment with two NRTIs with a PI compared with two NRTIs alone was 1.81 (95% CI 1.17-2.79). The benefits of treatment with two NRTIs and a PI are substantial among those who can tolerate the regimen in comparison with treatment with two NRTIs alone.

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.