Program evaluation is a critical tool for understanding and improving organizational activities and systems. This report updates the 1999 CDC Framework for Program Evaluation in Public Health (CDC. Framework for program evaluation in public health. MMWR Recomm Rep 1999;48[No. RR-11];1-40) by integrating major advancements in the fields of evaluation and public health, lessons learned from practical applications of the original framework, and current Federal agency policies and practices. A practical, nonprescriptive tool, the updated 2024 framework is designed to summarize and organize essential elements of program evaluation, and can be applied at any level from individual programs to broader systems by novices and experts for planning and implementing an evaluation. Although many of the key aspects from the 1999 framework remain, certain key differences exist. For example, this updated framework also includes six steps that describe the general process of evaluation planning and implementation, but some content and step names have changed (e.g., the first step has been renamed Assess context). The standards for high-quality evaluation remain central to the framework, although they have been updated to the five Federal evaluation standards. The most substantial change from the 1999 framework is the addition of three cross-cutting actions that are core tenets to incorporate within each evaluation step: engage collaboratively, advance equity, and learn from and use insights. The 2024 framework provides a guide for designing and conducting evaluation across many topics within and outside of public health that anyone involved in program evaluation efforts can use alone or in conjunction with other evaluation approaches, tools, or methods to build evidence, understand programs, and refine evidence-based decision-making to improve all program outcomes.

OBJECTIVE: In April 2020, the US Centers for Disease Control and Prevention (CDC) recommended community masking to prevent the transmission of SARS-CoV-2. Since then, a total of 39 US states and DC issued mask mandates. Despite CDC recommendations and supporting evidence that masking reduces COVID-19 community transmission, from January to June 20, 2021 states lifted their mask mandates for all individuals. This study examined the association between lifting state-issued mask mandates and mask-wearing behavior in 2021. DESIGN: We estimated a difference-in-difference model, comparing changes in the likelihood for individuals to wear a mask in states that lifted their mask mandate relative to states that kept their mandates in place between February and June of 2021. SETTING: Individuals were surveyed from across the United States. PARTICIPANTS: We used masking behavior data collected by the Porter Novelli View 360 + national surveys (N = 3459), and data from state-issued mask mandates obtained by CDC and the University of Nevada, Las Vegas. MAIN OUTCOMES: The outcome variable of interest was self-reported mask use during the 30 days prior to the survey data collection. RESULTS: In the overall population, lifting mask mandates did not significantly influence mask-wearing behavior. Mask wearing did significantly decrease in response to the lifting of mask mandates among individuals living in rural counties and individuals who had not yet decided whether they would receive a COVID-19 vaccine. CONCLUSION: Policies around COVID-19 behavioral mitigation, specifically amongst those unsure about vaccination and in rural areas, may help reduce the transmission of COVID-19 and other respiratory viruses, especially in communities with low vaccination rates.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23-0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18-0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming.

BACKGROUND: Highly pathogenic avian influenza A(H5) human infections are a global concern, with many A(H5) human cases detected in Vietnam, including a case in October 2022. Using avian influenza virus surveillance from March 2017-September 2022, we described the percent of pooled samples that were positive for avian influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses in live bird markets (LBMs) in Vietnam. METHODS: Monthly at each LBM, 30 poultry oropharyngeal swab specimens and five environmental samples were collected. Samples were pooled in groups of five and tested for influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses by real-time reverse-transcription polymerase chain reaction. Trends in the percent of pooled samples that were positive for avian influenza were summarized by LBM characteristics and time and compared with the number of passively detected avian influenza outbreaks using Spearman's rank correlation. RESULTS: A total of 25,774 pooled samples were collected through active surveillance at 167 LBMs in 24 provinces; 36.9% of pooled samples were positive for influenza A, 3.6% A(H5), 1.9% A(H5N1), 1.1% A(H5N6), and 0.2% A(H5N8). Influenza A(H5) viruses were identified January-December and at least once in 91.7% of sampled provinces. In 246 A(H5) outbreaks in poultry; 20.3% were influenza A(H5N1), 60.2% A(H5N6), and 19.5% A(H5N8); outbreaks did not correlate with active surveillance. CONCLUSIONS: In Vietnam, influenza A(H5) viruses were detected by active surveillance in LBMs year-round and in most provinces sampled. In addition to outbreak reporting, active surveillance for A(H5) viruses in settings with high potential for animal-to-human spillover can provide situational awareness.

Individual and community-level COVID-19 mitigation policies can have effects beyond direct COVID-19 health outcomes, including social, behavioral, and economic outcomes. These social, behavioral, and economic outcomes can extend beyond the pandemic period and have disparate effects on populations. Public Health-Seattle & King County (PHSKC) built on the Centers for Disease Control and Prevention's community mitigation strategy framework to create a local project tracking near-real-time data to understand factors affected by mitigation approaches, inform decision-making, and monitor and evaluate community-level disparities during the pandemic. This case study describes the framework and lessons learned from PHSKC's collation, use, and dissemination of local data from 20 data sources to guide community and public health decision-making. Social, behavioral, economic, and health indicators were regularly updated and disseminated through interactive dashboards and products that examined data in the context of applicable policies. Data disaggregated by demographic characteristics and geography highlighted inequities, but not all datasets contained the same details; local surveys or qualitative data were used to fill gaps. Project outcomes included informing city and county emergency response planning related to implementation of financial and food assistance programs. Key lessons learned included the need to (1) build on existing processes and use automated processes and (2) partner with other sectors to use nontraditional public health data for active dissemination and data disaggregation and for real-time data contextualized by policy changes. This project provided programs and communities with timely, reliable data to understand where to invest recovery funding. A similar framework could position other health departments to examine social and economic effects during future public health emergencies.

INTRODUCTION: Dog-mediated rabies is enzootic in Vietnam, resulting in at least 70 reported human deaths and 500,000 human rabies exposures annually. In 2016, an integrated bite cases management (IBCM) based surveillance program was developed to improve knowledge of the dog-mediated rabies burden in Phu Tho Province of Vietnam. METHODS: The Vietnam Animal Rabies Surveillance Program (VARSP) was established in four stages: (1) Laboratory development, (2) Training of community One Health workers, (3) Paper-based-reporting (VARSP 1.0), and (4) Electronic case reporting (VARSP 2.0). Investigation and diagnostic data collected from March 2016 to December 2019 were compared with historical records of animal rabies cases dating back to January 2012. A risk analysis was conducted to evaluate the probability of a rabies exposure resulting in death after a dog bite, based on data collected over the course of an IBCM investigation. RESULTS: Prior to the implementation of VARSP, between 2012 and 2015, there was an average of one rabies investigation per year, resulting in two confirmed and two probable animal rabies cases. During the 46 months that VARSP was operational (2016 - 2019), 1048 animal investigations were conducted, which identified 79 (8%) laboratory-confirmed rabies cases and 233 (22%) clinically-confirmed(probable) cases. VARSP produced a 78-fold increase in annual animal rabies case detection (one cases detected per year pre-VARSP vs 78 cases per year under VARSP). The risk of succumbing to rabies for bite victims of apparently healthy dogs available for home quarantine, was three deaths for every 10,000 untreated exposures. DISCUSSION: A pilot IBCM model used in Phu Tho Province showed promising results for improving rabies surveillance, with a 26-fold increase in annual case detection after implementation of a One Health model. The risk for a person bitten by an apparently healthy dog to develop rabies in the absence of rabies PEP was very low, which supports the WHO recommendations to delay PEP for this category of bite victims, when trained animal assessors are available and routinely communicate with the medical sector. Recent adoption of an electronic IBCM system is likely to expedite adoption of VARSP 2.0 to other Provinces and improve accuracy of field decisions and data collection.

BACKGROUND: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure. METHODS: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively. RESULTS: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay. CONCLUSION: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families. IMPACT: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models.

OBJECTIVE: The Centers for Disease Control and Prevention's (CDC's) Evaluation Fellowship Program is a 2-year fellowship that includes training, placement with a CDC program, and professional development funds. We evaluated whether the program contributed to CDC's evaluation capacity, prepared fellows for evaluation work, and contributed to their career advancement during its first 10 years. METHODS: We used a mixed-methods approach, including conducting an online survey and telephone interviews. External evaluators sent surveys to all 152 alumni and all 123 mentors who participated in the program from 2011 through 2020 (first 8 cohorts) and interviewed 9 mentors and 15 alumni. RESULTS: A total of 110 alumni (72.4%) and 44 mentors (35.8%) completed surveys. Of 44 mentors, most agreed their fellow(s) contributed to their program's overall evaluation capacity (90.9%) and its ability to do more evaluation (88.6%). Most (84.2%-88.1%) alumni agreed that the Evaluation Fellowship Program prepared them to apply the 6 skill sets that aligned with CDC's Framework for Program Evaluation in Public Health. Support from the Fellowship office was significantly and positively correlated with performing evaluation tasks (β = 0.25; P = .004) and alumni obtaining their first job (β = 0.36; P < .001). Host program mentoring was significantly correlated with performing evaluation tasks (β = 0.27; P = .02) and alumni obtaining their first job (β = 0.34; P = .007). CONCLUSION: CDC's Evaluation Fellowship Program has made progress toward building CDC's evaluation capacity and preparing a public health workforce to use evaluation skills in various settings. A service-learning model that provides training and applied experiences could prepare a workforce to build evaluation capacity.

Malaria transmission-blocking vaccines (TBVs) are a critical tool for disease elimination. TBVs prevent completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen and structure-function studies have identified two Class II epitopes that induce potent transmission-blocking (T-B) antibodies. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ was immunogenic and immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity and establishing UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts.Competing Interest StatementThe authors have declared no competing interest.

Introduction: Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including bar work and transportation. However, data on changes in prevalence of untreated HIV infection and HIV incidence within occupations following rollout of antiretroviral therapy and voluntary medical male circumcision programs in 2004 are limited. Method(s): We evaluated 12 rounds of survey data collected between 1999-2016, from the Rakai Community Cohort Study, a population-based study of adolescents and adults 15-49 years in Uganda, to assess changes in the prevalence of untreated HIV infection and incidence by self-reported primary occupation. Adjusted prevalence risk ratios (adjPRR) for untreated HIV and incidence rate ratios for HIV incidence with 95% confidence intervals (CIs) were estimated using Poisson regression. Primary outcomes were stratified by gender and HIV incidence compared over three time periods (1999-2004; 2005-2011; 2011-2016) representing, respectively, the period prior to scale up of combined HIV prevention and treatment, the scale up period, and full implementation. Result(s): 33,866 individuals, including 19,113 (56%) women participated. Of these participants, 17,840 women and 14,244 men who were HIV-negative at their first study visit contributed 57,912 and 49,403 person-years of follow-up, respectively. Agriculture was the most common occupation at all study visits, though its prevalence declined from 39 to 29% among men and from 61 to 40% among women between 1999 and 2016. Untreated HIV infection substantially declined between 1999 and 2016 across most occupational subgroups, including by 70% among men (12 to 4.2%; adjPRR=0.30; 95%CI:0.23-0.41) and by 78% among women working in agriculture (14.7 to 4.0%; adjPRR=0.22; 95%CI:0.18-0.27), along with increasing antiretroviral therapy coverage. Exceptions included men working in transportation and women working in tailoring/laundry services. HIV incidence declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers or men working in transportation. Conclusion(s): Untreated HIV infection and HIV incidence have declined in most occupational sub-groups in Rakai, Uganda. However, women working in bars and restaurants and men working in transportation continue to have relatively high burden of untreated HIV and HIV incidence, and as such should be considered key priority populations for targeted HIV programming. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Background HIV testing and counseling is a key component of HIV prevention and the entry point into the treatment cascade, which improves for individual clinical outcomes and reduces onward HIV transmission. Current guidelines recommend at least annual testing for key populations. More frequent testing could provide health benefits, but these additional services increase the program the cost-effectiveness is not well-evaluated. Methods We used a compartmental mathematical model to simulate the health and economic impact of HIV testing one to four times per year for men who have sex with men, people who inject drugs, and female sex workers in Viet Nam. Model outcomes included costs, HIV infections, HIV-related deaths, and disability-adjusted life years (DALYs) associated with each scenario. We used an opportunity cost-based cost-effectiveness threshold of US $2,255 per DALY averted, discounted costs and health benefits at 3% annually, and used a time horizon from 2021 to 2030 to calculate incremental cost-effectiveness ratios (ICERs). Results Compared to the baseline scenario, more frequent HIV testing was estimated to incrementally avert 10.2%, 5.2%, 3.0%, and 1.6% discounted infections for one-, two-, three-, and four-tests per year, respectively. ICERs associated with each scenario ranged from $464, $1,190, $1,762, and $2,727 per DALY averted for one-, two-, three-, and four-tests per year, respectively. Conclusions Increased HIV testing frequency for key populations was projected to avert HIV incidence, mortality, and disability in Viet Nam and was cost-effective. Settings with a similar context should consider strategies on how to optimize retesting among key populations. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

During the COVID-19 pandemic, renewal equation estimates of time-varying effective reproduction numbers were useful to policymakers in evaluating the need for and impact of mitigation measures. Our objective here is to illustrate the utility of mechanistic expressions for the basic and effective (or intrinsic and realized) reproduction numbers, [Formula: see text] and related quantities derived from a Susceptible-Exposed-Infectious-Removed (SEIR) model including features of COVID-19 that might affect transmission of SARS-CoV-2, including asymptomatic, pre-symptomatic, and symptomatic infections, with which people may be hospitalized. Expressions from homogeneous host population models can be analyzed to determine the effort needed to reduce [Formula: see text] from [Formula: see text] to 1 and contributions of modeled mitigation measures. Our model is stratified by age, 0-4, 5-9, …, 75+ years, and location, the 50 states plus District of Columbia. Expressions from such heterogeneous host population models include subpopulation reproduction numbers, contributions from the above-mentioned infectious states, metapopulation numbers, subpopulation contributions, and equilibrium prevalence. While the population-immunity at which [Formula: see text] has captured the popular imagination, the metapopulation [Formula: see text] could be attained in an infinite number of ways even if only one intervention (e.g., vaccination) were capable of reducing [Formula: see text] However, gradients of expressions derived from heterogeneous host population models,[Formula: see text] can be evaluated to identify optimal allocations of limited resources among subpopulations. We illustrate the utility of such analytical results by simulating two hypothetical vaccination strategies, one uniform and other indicated by [Formula: see text] as well as the actual program estimated from one of the CDC's nationwide seroprevalence surveys conducted from mid-summer 2020 through the end of 2021.

BACKGROUND: A major concern among healthcare experts is a shortage of N95 filtering facepiece respirators (FFRs) during a pandemic. If the supply of N95 FFRs becomes limited, reusable elastomeric half-mask respirators (EHMRs) may be used to protect healthcare workers. The focus of this study was to evaluate the effects on filter performance of wiping decontamination for EHMR P100 filter cartridges. METHODS: The filter cartridge exterior of EHMR Honeywell, Moldex, and MSA models was wiped using quaternary ammonium and sodium hypochlorite wipes. These filter cartridge properties were assessed including observational analysis and filter performance tests. These wiping and assessing procedures were repeated after each set of wiping cycles (50, 100, 150, 200, and 400 cycles) to determine the effects of wiping decontamination. RESULTS: For sodium hypochlorite wipes, Honeywell, Moldex, and MSA models passed the NIOSH liquid particulate penetration criteria for all wiping cycles from 50 to 400 (penetrations < 0.014%). For quaternary ammonium wipes, filter penetrations of Moldex failed (penetrations >0.03%) after 150 cycles, while the filter penetrations of Honeywell and MSA passed for all wiping cycles (penetrations ≤ 0.013%). CONCLUSIONS: Wiping decontamination methods using sodium hypochlorite and quaternary ammonium wipes could be considered as promising decontamination candidates for Honeywell, Moldex, and MSA reuse, except for the wiping number selection for Moldex (< 150 cycles) when using the quaternary ammonium wipe.

As authorities braced for the arrival of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infrastructure investments and government directives prompted action in central Viet Nam to establish capacity for genomic surveillance sequencing. From 17 November 2021 to 7 January 2022, the Pasteur Institute in Nha Trang sequenced 162 specimens from 98 150 confirmed SARS-CoV-2 cases in the region collected from 8 November to 31 December 2021. Of these, all 127 domestic cases were identified as the B.1.617.2 (Delta) variant, whereas 92% (32/35) of imported cases were identified as the B.1.1.529 (Omicron) variant, all among international flight passengers. Patients were successfully isolated, enabling health-care workers to prepare for additional cases. Most (78%) of the 32 Omicron cases were fully vaccinated, suggesting continued importance of public health and social measures to control the spread of new variants.

Seroprevalence studies can estimate proportions of the population that have been infected or vaccinated, including infections that were not reported because of the lack of symptoms or testing. Based on information from studies in the United States from mid-summer 2020 through the end of 2021, we describe proportions of the population with antibodies to SARS-CoV-2 as functions of age and time. Slices through these surfaces at arbitrary times provide initial and target conditions for simulation modeling. They also provide the information needed to calculate age-specific forces of infection, attack rates, and - together with contact rates - age-specific probabilities of infection on contact between susceptible and infectious people. We modified the familiar Susceptible-Exposed-Infectious-Removed (SEIR) model to include features of the biology of COVID-19 that might affect transmission of SARS-CoV-2 and stratified by age and location. We consulted the primary literature or subject matter experts for contact rates and other parameter values. Using time-varying Oxford COVID-19 Government Response Tracker assessments of US state and DC efforts to mitigate the pandemic and compliance with non-pharmaceutical interventions (NPIs) from a YouGov survey fielded in the US during 2020, we estimate that the efficacy of social-distancing when possible and mask-wearing otherwise at reducing susceptibility or infectiousness was 31% during the fall of 2020. Initialized from seroprevalence among people having commercial laboratory tests for purposes other than SARS-CoV-2 infection assessments on 7 September 2020, our age- and location-stratified SEIR population model reproduces seroprevalence among members of the same population on 25 December 2020 quite well. Introducing vaccination mid-December 2020, first of healthcare and other essential workers, followed by older adults, people who were otherwise immunocompromised, and then progressively younger people, our metapopulation model reproduces seroprevalence among blood donors on 4 April 2021 less well, but we believe that the discrepancy is due to vaccinations being under-reported or blood donors being disproportionately vaccinated, if not both. As experimenting with reliable transmission models is the best way to assess the indirect effects of mitigation measures, we determined the impact of vaccination, conditional on NPIs. Results indicate that, during this period, vaccination substantially reduced infections, hospitalizations and deaths. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics."

OBJECTIVE: State-issued behavioral policy interventions (BPIs) can limit community spread of COVID-19, but their effects on COVID-19 transmission may vary by level of social vulnerability in the community. We examined the association between the duration of BPIs and the incidence of COVID-19 across levels of social vulnerability in US counties. METHODS: We used COVID-19 case counts from USAFacts and policy data on BPIs (face mask mandates, stay-at-home orders, gathering bans) in place from April through December 2020 and the 2018 Social Vulnerability Index (SVI) from the Centers for Disease Control and Prevention. We conducted multilevel linear regression to estimate the associations between duration of each BPI and monthly incidence of COVID-19 (cases per 100000 population) by SVI quartiles (grouped as low, moderate low, moderate high, and high social vulnerability) for 3141 US counties. RESULTS: Having a BPI in place for longer durations (ie, 2 months) was associated with lower incidence of COVID-19 compared with having a BPI in place for <1 month. Compared with having no BPI in place or a BPI in place for <1 month, differences in marginal mean monthly incidence of COVID-19 per 100000 population for a BPI in place for 2 months ranged from -4 cases in counties with low SVI to -401 cases in counties with high SVI for face mask mandates, from -31 cases in counties with low SVI to -208 cases in counties with high SVI for stay-at-home orders, and from -227 cases in counties with low SVI to -628 cases in counties with high SVI for gathering bans. CONCLUSIONS: Establishing COVID-19 prevention measures for longer durations may help reduce COVID-19 transmission, especially in communities with high levels of social vulnerability.

Human papillomavirus (HPV) causes cervical cancer among women and is associated with other anogenital cancers in men and women. Prophylactic particulate vaccines that are affordable, self-administered and efficacious could improve uptake of HPV vaccines world-wide. The goal of this research is to develop a microparticulate HPV16 vaccine for transdermal administration using AdminPatch(®) and assess its immunogenicity in a pre-clinical mouse model. HPV16 microparticles were prepared using a biocompatible polymer and characterized in terms of size, zeta potential, encapsulation efficiency and microparticle yield. Scanning and transmission electron microscopy were conducted to confirm particle image and to visualize the conformation of HPV16 vaccine particles released from microparticle formulation. In vivo studies performed to evaluate the potential of the microparticulate vaccine initiated a robust and sustained immune response. HPV16 IgG antibodies were significantly elevated in the microparticle group compared to antigen solutions administered by the transdermal route. Results show significant expansion of CD4+, CD45R, CD27 and CD62L cell populations in the vaccinated mice group, indicating the high efficacy of the microparticulate vaccine when administered via transdermal route. The findings of this study call attention to the use of minimally invasive, pain-free routes to deliver vaccine.

OBJECTIVES: Key populations, including sex workers, men who have sex with men, and people who inject drugs, have a high risk of HIV and sexually transmitted infections. We assessed the health and economic impacts of different HIV and syphilis testing strategies among three key populations in Viet Nam using a dual HIV/syphilis rapid diagnostic test (RDT). SETTING: We used the spectrum AIDS impact model to simulate the HIV epidemic in Viet Nam and evaluated five testing scenarios among key populations. We used a 15-year time horizon and a provider perspective for costs. PARTICIPANTS: We simulate the entire population of Viet Nam in the model. INTERVENTIONS: We modelled five testing scenarios among key populations: (1) annual testing with an HIV RDT, (2) annual testing with a dual RDT, (3) biannual testing using dual RDT and HIV RDT, (4) biannual testing using HIV RDT and (5) biannual testing using dual RDT. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is incremental cost-effectiveness ratios. Secondary outcomes include HIV and syphilis cases. RESULTS: Annual testing using a dual HIV/syphilis RDT was cost-effective (US$10 per disability-adjusted life year (DALY)) and averted 3206 HIV cases and treated 27727 syphilis cases compared with baseline over 15 years. Biannual testing using one dual test and one HIV RDT (US$1166 per DALY), or two dual tests (US$5672 per DALY) both averted an additional 875 HIV cases, although only the former scenario was cost-effective. Annual or biannual HIV testing using HIV RDTs and separate syphilis tests were more costly and less effective than using one or two dual RDTs. CONCLUSIONS: Annual HIV and syphilis testing using dual RDT among key populations is cost-effective in Vietnam and similar settings to reach global reduction goals for HIV and syphilis.

During the Centers for Disease Control and Prevention's Zika Virus Response, birth defects surveillance programs adapted to monitor birth defects potentially related to Zika virus (ZIKV) infection during pregnancy. Pregnancy outcomes occurring during January 2016 to June 2017 in 22 U.S. states and territories were used to estimate the prevalence of those brain and eye defects potentially related to ZIKV. Jurisdictions were divided into three groups: areas with widespread ZIKV transmission, areas with limited local ZIKV transmission, and areas without local ZIKV transmission. Prevalence estimates for selected brain and eye defects and microcephaly per 10,000 live births were estimated. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression for areas with widespread and limited ZIKV transmission compared with areas without local ZIKV transmission. Defects with significantly higher prevalence in areas of widespread transmission were pooled, and PRs were calculated by quarter, comparing subsequent quarters to the first quarter (January-March 2016). Nine defects had significantly higher prevalence in areas of widespread transmission. The highest PRs were seen in intracranial calcifications (PR = 12.6, 95% CI [7.4, 21.3]), chorioretinal abnormalities (12.5 [7.1, 22.3]), brainstem abnormalities (9.3 [4.7, 18.4]), and cerebral/cortical atrophy (6.7 [4.2, 10.8]). The PR of the nine pooled defects was significantly higher in three quarters in areas with widespread transmission. The largest difference in prevalence was observed for defects consistently reported in infants with congenital ZIKV infection. Birth defects surveillance programs could consider monitoring a subset of birth defects potentially related to ZIKV in pregnancy.

This study aimed to determine the interactive physiological effect of backpack load carriage and slope during walking in professional mountain rescuers. Sixteen mountain rescuers walked on a treadmill at 3.6 km/h for 5 min in each combination of three slopes (1%, 10%, 20%) and five backpack loads (0%, 10%, 20%, 30%, and 40% body weight). Relative heart rate (%HRmax), relative oxygen consumption (%VO(2)max), and rating of perceived exertion (RPE, Borg 1-10 scale) were compared across conditions using two-way ANOVA. Significant differences in %VO(2)max, %HRmax, and RPE across slopes and loads were found where burden increased directly with slope and load (main effect of slope, p < 0.001 for all; main effect of load, p < 0.001 for all). Additionally, significant slope by load interactions were found for all parameters, indicating an additive effect (p < 0.001 for all). Mountain rescuers should consider the physiological interaction between slope and load when determining safe occupational walking capacity.

The emergence of birth defects programs in the United States accelerated in the 1970s and 1980s due to recognition that the use of the drug thalidomide during pregnancy resulted in fetal abnormalities (McBride, 1961; Smithells, 1962) and concerns around environmental exposures, such as Agent Orange exposure during the Vietnam War (Erickson et al., 1984). These experiences shaped the mission of many birth defect programs to focus on the surveillance of fetuses/infants affected by birth defects to monitor prevalence, identify and respond to clusters, and explore the epidemiology of birth defects as early warning systems to identify potential teratogens. This work helped identify additional risk factors for birth defects, support primary prevention opportunities, such as folic acid fortification and supplementation for neural tube defect prevention, and enabled evaluations of the success of those efforts (Harris et al., 2017).

CONTEXT: In response to the COVID-19 pandemic, states across the United States implemented various strategies to mitigate transmission of SARS-CoV-2 (the virus that causes COVID-19). OBJECTIVE: To examine the effect of COVID-19-related state closures on consumer spending, business revenue, and employment, while controlling for changes in COVID-19 incidence and death. DESIGN: The analysis estimated a difference-in-difference model, utilizing temporal and geographic variation in state closure orders to analyze their impact on the economy, while controlling for COVID-19 incidence and death. PARTICIPANTS: State-level data on economic outcomes from the Opportunity Insights data tracker and COVID-19 cases and death data from usafacts.org. INTERVENTIONS: The mitigation strategy analyzed within this study was COVID-19-related state closure orders. Data on these orders were obtained from state government Web sites containing executive or administrative orders. MAIN OUTCOME MEASURES: Outcomes include state-level estimates of consumer spending, business revenue, and employment levels. RESULTS: Analyses showed that although state closures led to a decrease in consumer spending, business revenue, and employment, they accounted for only a small portion of the observed decreases in these outcomes over the first wave of COVID-19. CONCLUSIONS: The impact of COVID-19 on economic activity likely reflects a combination of factors, in addition to state closures, such as individuals' perceptions of risk related to COVID-19 incidence, which may play significant roles in impacting economic activity.

Firefighters' protective clothing (FPC) can limit human thermoregulation due to limited water vapor permeability and insulation. This study investigated the effect of cooling on the physiological responses and probability of hyperthermia in subjects wearing FPC during exercise in a hot environment. Twelve males participated in this study. A maximal graded treadmill exercise test was performed to measure maximal oxygen uptake (V̇O(2max)) and to assess subjects' capacity to perform the assigned exercise. Exercise included treadmill walking at 40% V̇O(2max) in warm (30 °C) and humid (70% RH) conditions for 40 min while wearing FPC. Subjects participated in two randomly counterbalanced assigned experimental protocols: control (no cooling) and intervention (cooling). The experimental intervention consisted of a cooling garment infused with cooled water (18 °C) through silastic tubing sewn into the fabric and worn underneath FPC. Each subject served as their own control and, therefore, completed both the control and intervention of the protocol. A logistic regression model was used to analyze the interaction effect of cooling on the probability of progression to hyperthermia (T(c) ≥ 38 °C). Subjects' physiological responses increased during exercise in a warm and humid environment. Active cooling decreased (p < 0.05) the thermal stress thereby reducing the probability of hyperthermia while exercising in hot and humid conditions. The results indicate that when cooling was used each subject, on average, was 91% less likely to reach the lower threshold limit of hyperthermia. Exercise in hot environments while wearing FPC results in significant physiological strain, which may lead to hyperthermia. Utilization of a cooling garment reduced physiological strain and the probability of hyperthermia.

Malaria transmission-blocking vaccines (TBVs) prevent the completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen. Structure-function studies identified two Class II epitopes that can induce potent transmission-blocking (T-B) antibodies, informing the design of the next-generation AnAPN1. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We then established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ effectively immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity, underscoring UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts.

BACKGROUND: A major concern among health care experts is a shortage of N95 filtering facepiece respirators (FFRs) during a pandemic. One option for mitigating an FFR shortage is to decontaminate and reuse the devices. The focus of this study was to develop a new evaluation technique based on three major decontamination requirements: 1) inactivating viruses, 2) not altering the respirator properties, and 3) not leaving any toxic byproduct on the FFR. METHODS: Hydrophilic and hydrophobic FFRs were contaminated with MS2 virus. In the solution-based deposition, the virus-containing liquid droplets were spiked directly onto FFRs, while in the vapor-based and aerosol-based depositions, the viral particles were loaded onto FFRs using a bio-aerosol testing system. Ultraviolet germicidal irradiation (UVGI) and moist heat (MH) decontamination methods were used for inactivation of viruses applied to FFRs. RESULTS: Both UVGI and MH methods inactivated viruses (> 5-log reduction of MS2 virus; in 92% of both method experiments, the virus was reduced to levels below the detection limit), did not alter the respirator properties, and did not leave any toxic byproduct on the FFRs. CONCLUSIONS: Both UVGI and MH methods could be considered as promising decontamination candidates for inactivation of viruses for respirator reuse during shortages.

The drivers and patterns of zoonotic virus emergence in the human population are poorly understood. The mosquito Aedes aegypti is a major arbovirus vector native to Africa that invaded most of the world's tropical belt over the past four centuries, after the evolution of a "domestic" form that specialized in biting humans and breeding in water storage containers. Here, we show that human specialization and subsequent spread of A. aegypti out of Africa were accompanied by an increase in its intrinsic ability to acquire and transmit the emerging human pathogen Zika virus. Thus, the recent evolution and global expansion of A. aegypti promoted arbovirus emergence not solely through increased vector-host contact but also as a result of enhanced vector susceptibility.

As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION's potential for low-cost, high volume sequencing of pathogens in locations with limited resources.

BACKGROUND: Merely having the tools to end HIV is insufficient. Effectively ending the epidemic necessitates addressing barriers that impede engagement in biomedical and behavioral prevention and wide scale implementation and utilization of existing interventions. This qualitative study identifies suggestions for increasing access to, engagement in, and impact of HIV prevention among women living in cities in high HIV burden counties in the eastern US. METHODS: Data analyzed for the current study were collected via a qualitative sub-study within the HIV Prevention Trials Network Study 064 (HPTN 064), a multisite observational cohort study designed to estimate HIV incidence among women residing in communities with elevated HIV prevalence who also reported personal or partner characteristics associated with increased risk of HIV acquisition. Focus group and interview participants in the qualitative sub-study (N = 288) were from four cities in the eastern US. RESULTS: Thematic analyses revealed four themes describing women's most frequently stated ideas for improving prevention efforts: 1) Promote Multilevel Empowerment, 2) Create Engaging Program Content, 3) Build "Market Demand", and 4) Ensure Accessibility. We conducted additional analyses to identify contradictory patterns in the data, which revealed an additional three themes: 1) Address Structural Risk Factors, 2) Increase Engagement via Pleasure Promotion, 3) Expand Awareness of and Access to Prevention Resources. CONCLUSIONS: Findings may be useful for enhancing women's engagement in and uptake of behavioral and biomedical HIV prevention resources, improving policy, and addressing multilevel risk factors. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00995176 , prospectively registered.

The aim of this study was to develop a new method to measure respirator protection factors for aerosol particles using portable instruments while workers conduct their normal work. The portable instruments, including a set of two handheld condensation particle counters (CPCs) and two portable aerosol mobility spectrometers (PAMSs), were evaluated with a set of two reference scanning mobility particle sizers (SMPSs). The portable instruments were mounted to a tactical load-bearing vest or backpack and worn by the test subject while conducting their simulated workplace activities. Simulated workplace protection factors (SWPFs) were measured using human subjects exposed to sodium chloride aerosols at three different steady state concentration levels: low (8x10(3) particles/cm(3)), medium (5x10(4) particles/cm(3)), and high (1x10(5) particles/cm(3)). Eight subjects were required to pass a quantitative fit test before beginning a SWPF test for the respirators. Each SWPF test was performed using a protocol of five exercises for 3 min each: (1) normal breathing while standing; (2) bending at the waist; (3) a simulated laboratory-vessel cleaning motion; (4) slow walking in place; and (5) deep breathing. Two instrument sets (one portable instrument {CPC or PAMS} and one reference SMPS for each set) were used to simultaneously measure the aerosol concentrations outside and inside the respirator. The SWPF was calculated as a ratio of the outside and inside particles. Generally, the overall SWPFs measured with the handheld CPCs had a relatively good agreement with those measured with the reference SMPSs, followed by the PAMSs. Under simulated workplace activities, all handheld CPCs, PAMSs, and the reference SMPSs showed a similar GM SWPF trend, and their GM SWPFs decreased when simulated workplace movements increased. This study demonstrated that the new design of mounting two handheld CPCs in the tactical load-bearing vest or mounting one PAMS unit in the backpack permitted subjects to wear it while performing the simulated workplace activities. The CPC shows potential for measuring SWPFs based on its light weight and lack of major instrument malfunctions.