To meet the educational, physical, social, and emotional needs of children, many U.S. schools opened for in-person learning during fall 2020 by implementing strategies to prevent transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). To date, there have been no U.S. studies comparing COVID-19 incidence in schools that varied in implementing recommended prevention strategies, including mask requirements and ventilation improvements* (2). Using data from Georgia kindergarten through grade 5 (K-5) schools that opened for in-person learning during fall 2020, CDC and the Georgia Department of Public Health (GDPH) assessed the impact of school-level prevention strategies on incidence of COVID-19 among students and staff members before the availability of COVID-19 vaccines.(†) Among 169 K-5 schools that participated in a survey on prevention strategies and reported COVID-19 cases during November 16-December 11, 2020, COVID-19 incidence was 3.08 cases among students and staff members per 500 enrolled students.(§) Adjusting for county-level incidence, COVID-19 incidence was 37% lower in schools that required teachers and staff members to use masks, and 39% lower in schools that improved ventilation, compared with schools that did not use these prevention strategies. Ventilation strategies associated with lower school incidence included methods to dilute airborne particles alone by opening windows, opening doors, or using fans (35% lower incidence), or in combination with methods to filter airborne particles with high-efficiency particulate absorbing (HEPA) filtration with or without purification with ultraviolet germicidal irradiation (UVGI) (48% lower incidence). Multiple strategies should be implemented to prevent transmission of SARS-CoV-2 in schools (2); mask requirements for teachers and staff members and improved ventilation are important strategies that elementary schools could implement as part of a multicomponent approach to provide safer, in-person learning environments. Universal and correct mask use is still recommended by CDC for adults and children in schools regardless of vaccination status (2).

Understanding the circumstances under which arboviruses emerge is critical for the development of targeted control and prevention strategies. This is highlighted by the emergence of chikungunya and Zika viruses in the New World. However, to comprehensively understand the ways in which viruses emerge and persist, factors influencing reductions in virus activity must also be understood. Western equine encephalitis virus (WEEV), which declined during the late 20th century in apparent enzootic circulation as well as equine and human disease incidence, provides a unique case study on how reductions in virus activity can be understood by studying evolutionary trends and mechanisms. Previously, we showed using phylogenetics that during this period of decline, six amino acid residues appeared to be positively selected. To assess more directly the effect of these mutations, we utilized reverse genetics and competition fitness assays in the enzootic host and vector (house sparrows and Culex tarsalis mosquitoes). We observed that the mutations contemporary with reductions in WEEV circulation and disease that were non-conserved with respect to amino acid properties had a positive effect on enzootic fitness. We also assessed the effects of these mutations on virulence in the Syrian-Golden hamster model in relation to a general trend of increased virulence in older isolates. However, no change effect on virulence was observed based on these mutations. Thus, while WEEV apparently underwent positive selection for infection of enzootic hosts, residues associated with mammalian virulence were likely eliminated from the population by genetic drift or negative selection. These findings suggest that ecologic factors rather than fitness for natural transmission likely caused decreased levels of enzootic WEEV circulation during the late 20th century.

Background: Cataracts are a major cause of visual impairment and blindness in the United States and worldwide. Introduction: Risk factors for cataracts include age over 40 years, smoking, diabetes, low socioeconomic status, female sex, steroid use, ocular trauma, genetic factors, and exposure to ultraviolet-B light. Community-based telemedicine vision screenings can be an efficient method for detecting cataracts in underserved populations. The Philadelphia Telemedicine Glaucoma Detection and Follow-Up Study reports the prevalence and risk factors for cataracts in individuals screened and examined for glaucoma and other eye diseases. Materials and Methods: A total of 906 high-risk individuals were screened for glaucoma using telemedicine in seven primary care practices and four Federally Qualified Health Centers in Philadelphia. Participants with suspicious nerves or other abnormalities on fundus photographs, unreadable images, and ocular hypertension returned for an eye examination with an ophthalmologist at the same community location. Results: Of the participants screened through telemedicine, 347 (38.3%) completed a follow-up eye examination by an ophthalmologist. Of these, 267 (76.9%) were diagnosed with cataracts, of which 38 (14.2%) had visually significant cataracts. Participants who were diagnosed with visually significant cataract were more likely to be older (p < 0.001), have diabetes (p = 0.003), and worse visual acuity (p < 0.001). Discussion: Our study successfully detected and confirmed cataracts in a targeted, underserved urban population at high risk for eye disease. Conclusions: Telemedicine programs offer an opportunity to identify and refer individuals who would benefit from continuous follow-up eye care and treatment to improve visual function and quality of life.

AIMS: To evaluate agreement between ocular findings of a telemedicine eye screening (visit 1) with diagnoses of a comprehensive eye examination (visit 2). METHODS: A primary care practice (PCP)-based telemedicine screening programme incorporating fundus photography, intraocular pressure (IOP) and clinical information was conducted. Eligible individuals were African American, Hispanic/Latino or Asian over the age of 40; Caucasian individuals over age 65; and adults of any ethnicity over age 40 with a family history of glaucoma or diabetes. Participants with abnormal images or elevated IOP were invited back for a complete eye examination. Both visit 1 and visit 2 were conducted at participants' local PCP. Ocular findings at visit 1 and eye examination diagnoses at visit 2 are presented, including a cost analysis. RESULTS: Of 906 participants who attended visit 1, 536 were invited to visit 2 due to ocular findings or unreadable images. Among the 347 (64.9%) who attended visit 2, 280 (80.7%) were diagnosed with at least one ocular condition. Participants were predominately women (59.9%) and African American (65.6%), with a mean age (+/-SD) of 60.6+/-11.0 years. A high diagnostic confirmation rate (86.0%) was found between visit 1 and visit 2 for any ocular finding. Of 183 with suspicious nerves at visit 1, 143 (78.1%) were diagnosed as glaucoma or glaucoma suspects at visit 2. CONCLUSIONS: This screening model may be adapted and scaled nationally and internationally. Referral to an ophthalmologist is warranted if abnormal or unreadable fundus images are detected or IOP is >21 mm Hg. TRIAL REGISTRATION NUMBER: NCT02390245.

PURPOSE: To describe methodology and screening results from the Philadelphia Telemedicine Glaucoma Detection and Follow-up Study. DESIGN: Screening program results for a prospective, randomized clinical trial. MATERIALS AND METHODS: Individuals were recruited who were African-American, Hispanic/Latino, or Asian over age 40 years; Caucasian individuals over age 65 years; any ethnicity over age 40 years with a family history of glaucoma or diabetes. Primary care offices and Federally Qualified Health Centers were used for telemedicine (Visit 1). Two posterior fundus photographs and 1 anterior segment photograph were captured per eye in each participant, using a non-mydriatic, auto-focus, hand-held fundus camera (Volk Optical, Mentor, Ohio, USA). Medical and ocular history, family history of glaucoma, visual acuity, and intraocular pressure measurements using the ICarerebound tonometer (ICare, Helsinki, Finland) were obtained. Images were read remotely by a trained retina reader and a glaucoma specialist. RESULTS: From 4/1/15, to 2/6/17, 906 individuals consented and attended Visit 1. Of these, 553 participants were female (61.0%) and 550 were African American (60.7%), with a mean age of 58.7 years. A total of 532 (58.7%) participants had diabetes, and 616 (68%) had a history of hypertension. During Visit 1, 356 (39.3%) participants were graded with a normal image. Using image data from the worse eye, 333 (36.8%) were abnormal and 155 (17.1%) were unreadable. A total of 258 (28.5%) had a suspicious nerve; 62 (6.8%) had ocular hypertension, 102 (11.3%) had diabetic retinopathy; and 68 (7.5%) had other retinal abnormalities. CONCLUSION: An integrated telemedicine screening intervention in primary care offices and Federally Qualified Health Centers detected high rate of suspicious optic nerves, ocular hypertension, and retinal pathology.

BACKGROUND: Our medical center laboratory recently adapted its 24/7, two-hourly testing program to use an ARCHITECT-Multispot-viral load (AR-MS-VL) algorithm in place of a previous rapid test-immunofluorescence (RT-IF) algorithm. OBJECTIVES: We evaluated screening test performance, acute case detection, turnaround time and ability to resolve HIV status under the new algorithm. STUDY DESIGN: We considered consecutive HIV tests from January to November 2015. AR-MS-VL results at Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG) were compared with RT-IF results at ZSFG and also with AR-MS-VL results in the recently completed CDC Screening Targeted Populations to Interrupt On-going Chains of HIV Transmission with Enhanced Partner Notification (STOP) Study for targeted testing of MSM at publicly funded testing sites in San Francisco. RESULTS: Among 21,985 HIV tests performed at ZSFG, 16,467 were tested by RT-IF and 5518 by AR-MS-VL. There were 321 HIV infections detected, of which 274 (84%) were known HIV+ cases, and 47 were newly identified HIV infections. Considering only patients of HIV-negative or -unknown status, prevalence was 0.22%. Under the AR-MS-VL algorithm, turnaround times for screening results and full algorithm results were 3 and 21h; status-unresolved cases were reduced (from 47% to 22%) compared with the RT-IF algorithm. The positive predictive value (PPV) of a new-positive AR screening test was low (0.44) at ZSFG, where no acute infections were detected. At STOP Study sites where HIV prevalence was higher and acute infection was more common, the AR PPV was higher (0.93). All 24 false-positive AR screening tests at ZSFG had a signal/cutoff (S/CO) ratio of <15 and all 88 true-positive tests had S/CO ratio >15. Of 62 acute infections in the STOP Study, 23 (37%) had an S/CO<15. DISCUSSION: An AR-MS-VL algorithm is feasible and can return rapid results in a large medical center. In this setting, reactive 4th generation assay tests that are negative for HIV antibodies are typically false-positive with low S/CO ratios.

PURPOSE: Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years within the United States. The Innovative Network for Sight Research group (INSIGHT) designed the Diabetic Eye Screening Study (DESS) to examine the feasibility and short-term effectiveness of non-mydriatic diabetic retinopathy (DR) screening for adults with diabetes in community-based settings. METHODS: Study enrollment began in December 2011 at four sites: an internal medicine clinic at a county hospital in Birmingham, Alabama; a Federally-qualified community healthcare center in Miami-Dade County, Florida; a university-affiliated outpatient pharmacy in Philadelphia, Pennsylvania; and a medical home in Winston-Salem, North Carolina. People 18 years or older with previously diagnosed diabetes were offered free DR screening using non-mydriatic retinal photography that was preceded by a brief questionnaire addressing demographic information and previous eye care use. Visual acuity was also measured for each eye. Images were evaluated at a telemedicine reading center by trained evaluators using the National Health System DR grading classification. Participants and their physicians were sent screening report results and telephoned for a follow-up survey 3 months post-screening to determine whether participants had sought follow-up comprehensive eye care and their experiences with the screening process. RESULTS: Target enrollment at each site was a minimum of 500 persons. Three of the four sites met this enrollment goal. CONCLUSION: The INSIGHT/DESS is intended to establish the feasibility and short-term effectiveness of DR screening using non-mydriatic retinal photography in persons with diabetes who seek services in community-based clinic and pharmacy settings.

BACKGROUND: Dengue viruses (DENV) infect over 300 million people annually causing 96 million cases of dengue disease and 22,000 deaths. A safe vaccine which protects against DENV disease is a global health priority. METHODS: We enrolled 72 flavivirus-naive healthy adults in a Phase I double-blind randomized placebo-controlled dose escalation trial (low and high dose) of a live attenuated recombinant tetravalent dengue vaccine candidate (TDV) given in two doses 90 days apart. Volunteers were followed for safety, vaccine component viremia, and development of neutralizing antibodies to the four DENV. RESULTS: The majority of adverse events were mild, with no vaccine-related serious adverse events (SAE). Vaccinees reported injection site pain (52% vs. 17%) or erythema (73% vs. 25%) more frequently than placebo recipients. Low levels of TDV-2, -3, and -4 viremia were observed after the first but not second administration. Overall seroconversion rates and geometric mean neutralization titers after two doses were: DENV-1 (84.2%, 54.1), DENV-2 (92.1%, 292.8), DENV-3 (86.8%, 32.3), and DENV-4 (71.1%, 15.0) and>90.0% of high dose recipients had trivalent or broader responses. CONCLUSIONS: TDV was generally well-tolerated, induced trivalent or broader neutralizing antibodies to DENV in most flavivirus-naive vaccinees, and is undergoing further development.

IMPORTANCE: The use of a nonmydriatic camera for retinal imaging combined with the remote evaluation of images at a telemedicine reading center has been advanced as a strategy for diabetic retinopathy (DR) screening, particularly among patients with diabetes mellitus from ethnic/racial minority populations with low utilization of eye care. OBJECTIVE: To examine the rate and types of DR identified through a telemedicine screening program using a nonmydriatic camera, as well as the rate of other ocular findings. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study (Innovative Network for Sight [INSIGHT]) was conducted at 4 urban clinic or pharmacy settings in the United States serving predominantly ethnic/racial minority and uninsured persons with diabetes. Participants included persons aged 18 years or older who had type 1 or 2 diabetes mellitus and presented to the community-based settings. MAIN OUTCOMES AND MEASURES: The percentage of DR detection, including type of DR, and the percentage of detection of other ocular findings. RESULTS: A total of 1894 persons participated in the INSIGHT screening program across sites, with 21.7% having DR in at least 1 eye. The most common type of DR was background DR, which was present in 94.1% of all participants with DR. Almost half (44.2%) of the sample screened had ocular findings other than DR; 30.7% of the other ocular findings were cataract. CONCLUSIONS AND RELEVANCE: In a DR telemedicine screening program in urban clinic or pharmacy settings in the United States serving predominantly ethnic/racial minority populations, DR was identified on screening in approximately 1 in 5 persons with diabetes. The vast majority of DR was background, indicating high public health potential for intervention in the earliest phases of DR when treatment can prevent vision loss. Other ocular conditions were detected at a high rate, a collateral benefit of DR screening programs that may be underappreciated.

BACKGROUND: Dengue virus is the most serious mosquito-borne viral threat to public health and no vaccines or antiviral therapies are approved for dengue fever. The tetravalent DENVax vaccine contains a molecularly characterised live attenuated dengue serotype-2 virus (DENVax-2) and three recombinant vaccine viruses expressing the prM and E structural genes for serotypes 1, 3, and 4 in the DENVax-2 genetic backbone. We aimed to assess the safety and immunogenicity of tetravalent DENVax formulations. METHODS: We undertook a randomised, double-blind, phase 1, dose-escalation trial between Oct 11, 2011, and Nov 9, 2011, in the Rionegro, Antioquia, Colombia. The first cohort of participants (aged 18-45 years) were randomly assigned centrally, via block randomisation, to receive a low-dose formulation of DENvax, or placebo, by either subcutaneous or intradermal administration. After a safety assessment, participants were randomly assigned to receive a high-dose DENVax formulation, or placebo, by subcutaneous or intradermal administration. Group assignment was not masked from study pharmacists, but allocation was concealed from participants, nurses, and investigators. Primary endpoints were frequency and severity of injection-site and systemic reactions within 28 days of each vaccination. Secondary endpoints were the immunogenicity of DENVax against all four dengue virus serotypes, and the viraemia due to each of the four vaccine components after immunisation. Analysis was by intention to treat for safety and per protocol for immunogenicity. Because of the small sample size, no detailed comparison of adverse event rates were warranted. The trial is registered with ClinicalTrials.gov, number NCT01224639. FINDINGS: We randomly assigned 96 patients to one of the four study groups: 40 participants (42%) received low-dose vaccine and eight participants (8%) received placebo in the low-dose groups; 39 participants (41%) received high-dose vaccine, with nine (9%) participants assigned to receive placebo. Both formulations were well tolerated with mostly mild and transient local or systemic reactions. No clinically meaningful differences were recorded in the overall incidence of local and systemic adverse events between patients in the vaccine and placebo groups; 68 (86%) of 79 participants in the vaccine groups had solicited systemic adverse events compared with 13 (76%) of 17 of those in the placebo groups. By contrast, 67 participants (85%) in the vaccine group had local solicited reactions compared with five (29%) participants in the placebo group. Immunisation with either high-dose or low-dose DENVax formulations induced neutralising antibody responses to all four dengue virus serotypes; 30 days after the second dose, 47 (62%) of 76 participants given vaccine seroconverted to all four serotypes and 73 (96%) participants seroconverted to three or more dengue viruses. Infectious DENVax viruses were detected in only ten (25%) of 40 participants in the low-dose group and 13 (33%) of 39 participants in the high-dose group. INTERPRETATION: Our findings emphasise the acceptable tolerability and immunogenicity of the tetravalent DENVax formulations in healthy, flavivirus-naive adults. Further clinical testing of DENVax in different age groups and in dengue-endemic areas is warranted. FUNDING: Takeda Vaccines.

Dengue viruses (DENVs) cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine tetravalent dengue vaccine (TDV) that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3, and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS) is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0) at two different anatomical locations with a needle-free disposable syringe jet injection delivery devices (PharmaJet) in non-human primates. This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (2 months later) vaccination schedule. In addition, the vaccine induced CD4(+) and CD8(+) T cells producing IFN-gamma, IL-2, and TNF-alpha, and targeting the DENV-2 NS1, NS3, and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post-challenge). RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas.