The epidemiologic and genetic characteristics of mumps viruses detected in China from 1995 to 2010 were analyzed in this study. Mumps remains endemic in China with a high overall incidence rate. The incidence of mumps in Western China was higher than that in other regions of the country. Each year, most of mumps cases occurred between April and July, but a small peak also occurred in November and December. Mumps cases primarily affected the under 15 year old age group. Virologic data demonstrated that genotype F was the predominant circulating genotype throughout China for at least 15 years and no other genotype was detected between 1995 and 2010. Analysis of sequence data from the small hydrophobic (SH) gene indicated that multiple transmission chains of genotype F were found in various provinces of China, with no apparent chronologic and geographic restriction. This is the first report describing the epidemiology of mumps and genetic characterization of mumps viruses at the national level in China.

Immune imprinting is a driver known to shape the anti-hemagglutinin (HA) antibody landscape of individuals born within the same birth cohort. With the HA and neuraminidase (NA) proteins evolving at different rates under immune selection pressures, anti-HA and anti-NA antibody responses since childhood influenza infections have not been evaluated in parallel at the individual level. This is partly due to the limited knowledge of changes in NA antigenicity, as seasonal influenza vaccines have focused on generating neutralising anti-HA antibodies against HA antigenic variants. Here we systematically characterised the NA antigenic variants of seasonal A(H1N1) viruses from 1977 to 1991 and completed the antigenic profile of N1 NAs from 1977 to 2015. We identified that NA proteins of A/USSR/90/77, A/Singapore/06/86, and A/Texas/36/91 were antigenically distinct and mapped N386K as a key determinant of the NA antigenic change from A/USSR/90/77 to A/Singapore/06/86. With comprehensive panels of HA and NA antigenic variants of A(H1N1) and A(H1N1)pdm09 viruses, we determined hemagglutinin inhibition (HI) and neuraminidase inhibition (NI) antibodies from 130 subjects born between 1950-2015. Age-dependent imprinting was observed for both anti-HA and anti-NA antibodies, with the peak HI and NI titers predominantly detected from subjects at 4-12 years old during the year of initial virus isolation, except the age-independent anti-HA antibody response against A(H1N1)pdm09 viruses. More participants possessed antibodies that reacted to multiple antigenically distinct NA proteins than those with antibodies that reacted to multiple antigenically distinct HA proteins. Our results support the need to include NA proteins in seasonal influenza vaccine preparations.IMPORTANCE Seasonal influenza vaccines have aimed to generate neutralizing anti-HA antibodies for protection since licensure. More recently, anti-NA antibodies have been established as an additional correlate of protection. While HA and NA antigenic changes occurred discordantly, the anti-HA and anti-NA antibody profiles have rarely been analysed in parallel at the individual level, due to the limited knowledge on NA antigenic changes. By characterizing NA antigenic changes of A(H1N1) viruses, we determined the anti-HA and anti-NA antibody landscape against antigenically distinct A(H1N1) and A(H1N1)pdm09 viruses using sera of 130 subjects born between 1950-2015. We observed age-dependent imprinting of both anti-HA and anti-NA antibodies against strains circulated during the first decade of life. 67.7% (88/130) and 90% (117/130) of participants developed cross-reactive antibodies to multiple HA and NA antigens at titers ≥1:40. With slower NA antigenic changes and cross-reactive anti-NA antibody responses, including NA protein in influenza vaccine preparation may enhance vaccine efficacy. (150 words)

BACKGROUND: An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. OBJECTIVE: The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. METHODS: As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. RESULTS: The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. CONCLUSIONS: Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider.

BACKGROUND: Depression is common among breast cancer patients and can affect concordance with guideline-recommended treatment plans. Yet, the impact of depression on cancer treatment and survival is understudied, particularly in relation to the timing of the depression diagnosis. METHODS: The Kentucky Cancer Registry data was used to identify female patients diagnosed with primary invasive breast cancer who were 20 years of age or older in 2007-2011. Patients were classified as having no depression, depression pre-cancer diagnosis only, depression post- cancer diagnosis only, or persistent depression. The impact of depression on receiving guideline-recommended treatment and survival was examined using multivariable logistic regression and Cox regression, respectively. RESULTS: Of 6054 eligible patients, 4.1%, 3.7%, and 6.2% patients had persistent depression, depression pre-diagnosis only, and depression post-diagnosis only, respectively. A total of 1770 (29.2%) patients did not receive guideline-recommended cancer treatment. Compared to patients with no depression, the odds of receiving guideline-recommended treatment were decreased in patients with depression pre-diagnosis only (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.54-1.04) but not in patients with post-diagnosis only or persistent depression. Depression post-diagnosis only (hazard ratio, 1.51; 95% CI, 1.24-1.83) and depression pre-diagnosis only (hazard ratio, 1.26; 95% CI, 0.99-1.59) were associated with worse survival. No significant difference in survival was found between patients with persistent depression and patients with no depression (p > .05). CONCLUSIONS: Neglecting depression management after a breast cancer diagnosis may result in poorer cancer treatment concordance and worse survival. Early detection and consistent management of depression is critical in improving patient survival.

Immune imprinting is a driver known to shape the anti-hemagglutinin (HA) antibody landscape of individuals born within the same birth cohort. With the HA and neuraminidase (NA) proteins evolving at different rates under immune selection pressures, anti-HA and anti-NA antibody responses since childhood influenza virus infections have not been evaluated in parallel at the individual level. This is partly due to the limited knowledge of changes in NA antigenicity, as seasonal influenza vaccines have focused on generating neutralizing anti-HA antibodies against HA antigenic variants. Here, we systematically characterized the NA antigenic variants of seasonal A(H1N1) viruses from 1977 to 1991 and completed the antigenic profile of N1 NAs from 1977 to 2015. We identified that NA proteins of A/USSR/90/77, A/Singapore/06/86, and A/Texas/36/91 were antigenically distinct and mapped N386K as a key determinant of the NA antigenic change from A/USSR/90/77 to A/Singapore/06/86. With comprehensive panels of HA and NA antigenic variants of A(H1N1) and A(H1N1)pdm09 viruses, we determined hemagglutinin inhibition (HI) and neuraminidase inhibition (NI) antibodies from 130 subjects born between 1950 and 2015. Age-dependent imprinting was observed for both anti-HA and anti-NA antibodies, with the peak HI and NI titers predominantly detected from subjects at 4 to 12 years old during the year of initial virus isolation, except the age-independent anti-HA antibody response against A(H1N1)pdm09 viruses. More participants possessed antibodies that reacted to multiple antigenically distinct NA proteins than those with antibodies that reacted to multiple antigenically distinct HA proteins. Our results support the need to include NA proteins in seasonal influenza vaccine preparations. IMPORTANCE Seasonal influenza vaccines have aimed to generate neutralizing anti-HA antibodies for protection since licensure. More recently, anti-NA antibodies have been established as an additional correlate of protection. While HA and NA antigenic changes occurred discordantly, the anti-HA and anti-NA antibody profiles have rarely been analyzed in parallel at the individual level, due to the limited knowledge on NA antigenic changes. By characterizing NA antigenic changes of A(H1N1) viruses, we determined the anti-HA and anti-NA antibody landscape against antigenically distinct A(H1N1) and A(H1N1)pdm09 viruses using sera of 130 subjects born between 1950 and 2015. We observed age-dependent imprinting of both anti-HA and anti-NA antibodies against strains circulated during the first decade of life. A total of 67.7% (88/130) and 90% (117/130) of participants developed cross-reactive antibodies to multiple HA and NA antigens at titers ≥1:40. With slower NA antigenic changes and cross-reactive anti-NA antibody responses, including NA protein in influenza vaccine preparation may enhance vaccine efficacy.

The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex.

BACKGROUND: Shoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, due to the difficulty of finding SIRVA cases in large health care databases, population-based studies are scarce. OBJECTIVE: The goal of the research was to develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes. METHODS: We conducted the study among members of a large integrated health care organization who were vaccinated between April 1, 2016, and December 31, 2017, and had subsequent diagnosis codes indicative of shoulder injury. Based on a training data set with a chart review reference standard of 164 cases, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified 3 groups of positive SIRVA cases (definite, probable, and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated cases. We then applied the final automated NLP algorithm to a broader cohort of vaccinated persons with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases. RESULTS: In the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 cases without SIRVA. In the broader cohort of 53,585 vaccinations, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.5% (278/291), 67.7% (84/124), and 17.3% (9/52), respectively. CONCLUSIONS: The algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE) underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed masks and respirators. We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus. DESIGN: The two arms of the study included: 1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment, and 2) PPE treatment with MBL for 5 cycles of decontamination (5CD) to determine maintenance of PPE performance. METHODS: MBL treatment was used to inactivate coronaviruses on three N95 filtering facepiece respirator (FFR) and two medical mask (MM) models. We inoculated FFR and MM materials with three coronaviruses, including SARS-CoV-2, and treated with 10 µM MB and exposed to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5CD using multiple US and international test methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. RESULTS: Overall, MBL robustly and consistently inactivated all three coronaviruses with 99.8 - to >99.9% virus inactivation across all FFRs and MMs tested. FFR and MM integrity was maintained after 5 cycles of MBL treatment, whereas one FFR model failed after 5 cycles of VHP+O3. CONCLUSIONS: MBL treatment decontaminated respirators and masks by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings.

On May 13, 2020, Chicago established a free community-based testing (CBT) initiative for SARS-CoV-2, the virus that causes COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR). The initiative focused on demographic groups and geographic areas that were underrepresented in testing by clinical providers and had experienced high COVID-19 incidence, including Hispanic persons and those who have been economically marginalized. To assess the CBT initiative, the Chicago Department of Public Health (CDPH) compared demographic characteristics, economic marginalization, and test positivity between persons tested at CBT sites and persons tested in all other testing settings in Chicago. During May 13-November 14, a total of 253,904 SARS-CoV-2 RT-PCR tests were conducted at CBT sites. Compared with those tested in all other testing settings in Chicago, persons tested at CBT sites were more likely to live in areas that are economically marginalized (38.6% versus 32.0%; p<0.001) and to be Hispanic (50.9% versus 20.7%; p<0.001). The cumulative percentage of positive test results at the CBT sites was higher than that at all other testing settings (11.1% versus 7.1%; p<0.001). These results demonstrate the ability of public health departments to establish community-based testing initiatives that reach communities with less access to testing in other settings and that experience disproportionately higher incidences of COVID-19.

Hearing loss due to high-level noise exposure remains a significant occupational health hazard that continues to increase in prevalence in industrial and military work environments despite government-mandated hearing conservation programs. The underlying assumption in current noise standards is that hearing loss over an 8-hour A-weighted equivalent continuous exposure level (often abbreviated as LAeq,8h) can be predicted by the equal energy hypothesis. This method assumes equivalent effects on hearing for a 3 dB increase or decrease in exposure intensity with a halving or doubling of exposure duration, respectively. In other words, equal amounts of hearing loss are expected regardless of how the noise exposure levels have occurred over time. The equal energy hypothesis is the basis of most noise standards and guidelines in the United States and internationally. Although this approach is generally considered appropriate for steady-state noise, it is not adequate for complex noise (Hamernik and Qiu, 2001). Some Background: Consensus has been lacking on the use of simple energy averaging to predict the effects of noise on hearing. In the United States, some government agencies use a modification consisting of a 5 dB trading relationship, whereas others use the internationally accepted 3 dB rule. Use of the 3 dB rule has been recommended by the National Institute of Occupational Safety and Health (NIOSH) since 1998, which recommendation has been validated based on additional, more recent research (Suter, 2017). Another issue with using a simple energy metric is the inability of sound energy averaging to account for the increased hazard of noise with impulsive components. Although intermittences in noise exposures may have been considered helpful to hearing in the past, this no longer seems to be the case with complex noise exposures, which are found frequently in manufacturing industries. Because the additional hazards from impulsive noise were already recognized, the earliest version of the International Standards Organization (ISO) 1999 standard (1971) suggested a 10 dB adjustment to the average exposure level when impulsive noise is superimposed on a background of continuous noise. At a 1981 meeting of noise experts in Southampton, UK, some participants proposed keeping the 10 dB adjustment, with others wanting to change it to 5 dB, and a third group proposing just using simple energy averaging (Personal Observation, Suter, 1981). The resulting report concluded that hearing conservation programs should be initiated at a 5 dB lower level as a precautionary measure whenever there are impulsive noise conditions (von Gierke et al., 1981). Consequently, the 1990 version of the standard contained a note suggesting a 5 dB correction but even that disappeared without explanation in later iterations of the ISO 1999 standard (2013). Since then, more evidence has emerged regarding the hazard to hearing from complex noise environments relative to continuous noise environments. Complex or Non-Gaussian Noise: A steady-state, continuous noise exposure typically has a normal or Gaussian amplitude distribution (see background in Figure 1). However, the temporal pattern of noise exposures often varies significantly in work environments. A complex noise environment may be described as Gaussian background noise punctuated by a series of high-level transient noises resulting in a non-Gaussian distribution (as shown in Figure 1). These transients can be brief, high-level noise bursts, impulses, or impacts with varying interpeak intervals, peak levels, and peak durations. Industrial workers are often exposed to complex noise environments. Examples include jobs involving maintenance work, metalworking, and power tools, such as impact wrenches and nail guns. Over the past several decades, a number of studies using animal models have shown that exposure to complex noise produces more hearing damage than an equivalent energy exposure to continuous Gaussian noise, in terms of both behavioral hearing loss and sensory cell loss (e.g., Lei et al., 1994). These results, along with similar findings from human data in industrial settings, have demonstrated that although acoustic energy and exposure duration are necessary metrics, they are not sufficient to evaluate the hearing loss from complex non-Gaussian noise exposure. Because many noise environments can be characterized by the same equivalent energy and spectra, a metric that describes the temporal structure of an exposure would be a useful adjunct to the equivalent sound pressure level metric. The kurtosis of a sample distribution is such a metric.

Feng Shuren, Mei Joanne, Yang Lu, Luo Ping, Wang Xiaonan, Wang Yuan, Yao Jingyi, Cui Lan, Pan Lei, Wang Zefang, Xin Li. International journal of neonatal screening 2020 Feb 6(1)

Ninhydrin-based fluorometric quantification of phenylalanine is one of the most widely used methods for hyperphenylalaninemia (HPA) screening in neonates due to its high sensitivity, high accuracy, and low cost. Here we report an increase of false positive cases in neonatal HPA screening with this method, caused by contamination of blood specimen collection devices during the printing process. Through multiple steps of verification, the contaminants were identified from ink circles printed on the collection devices to indicate the positions and sizes of blood drops. Blood specimens from HPA-negative persons collected on these contaminated collection devices showed positive results in the fluorometric tests, but negative results in tandem mass spectroscopy (MS/MS) experiments. Contaminants on the collection devices could be extracted by 80% ethanol and showed an absorption peak around 245 nm, suggesting that these contaminants may contain benzene derivatives with similar structure to phenylalanine. High-performance liquid chromatography (HPLC) analysis of the ethanol extracts from contaminated collection devices identified two prominent peaks specifically from the devices. Methyl-2-benzoylbenzoate (MBB, CAS#606-28-0) was found as one of the major chemicals from contaminated collection devices. This report aims to remind colleagues in the field of this potential contamination and call for tighter regulation and quality control of specimen collection devices.

The COVID-19 pandemic is currently causing a severe disruption and shortage in the global supply chain of necessary personal protective equipment (e.g., N95 respirators). The U.S. CDC has recommended use of household cloth by the general public to make cloth face coverings as a method of source control. We evaluated the filtration properties of natural and synthetic materials using a modified procedure for N95 respirator approval. Common fabrics of cotton, polyester, nylon, and silk had filtration efficiency of 5-25%, polypropylene spunbond had filtration efficiency 6-10%, and paper-based products had filtration efficiency of 10-20%. An advantage of polypropylene spunbond is that it can be simply triboelectrically charged to enhance the filtration efficiency (from 6 to >10%) without any increase in pressure (stable overnight and in humid environments). Using the filtration quality factor, fabric microstructure, and charging ability, we are able to provide an assessment of suggested fabric materials for homemade facial coverings.

BACKGROUND: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana. METHODS: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018. 15 communities were randomly assigned to receive HIV prevention and treatment interventions, including enhanced HIV testing, earlier antiretroviral therapy (ART), and strengthened male circumcision services, and 15 received standard of care. The first primary endpoint of HIV incidence has already been reported. In this Article, we report findings for the second primary endpoint of population uptake of HIV prevention services, as measured by proportion of people known to be HIV-positive or tested HIV-negative in the preceding 12 months; proportion of people living with HIV diagnosed and on ART; proportion of people living with HIV on ART with viral suppression; and proportion of HIV-negative men circumcised. A longitudinal cohort of residents aged 16-64 years from a random, approximately 20% sample of households across the 15 communities was enrolled to assess baseline uptake of study outcomes; we also administered an end-of-study survey to all residents not previously enrolled in the longitudinal cohort to provide study end coverage estimates. Differences in intervention uptake over time by randomisation group were tested via paired Student's t test. The study has been completed and is registered with ClinicalTrials.gov (NCT01965470). FINDINGS: In the six communities participating in the end-of-study survey, 2625 residents (n=1304 from standard-of-care communities, n=1321 from intervention communities) were enrolled into the 20% longitudinal cohort at baseline from Oct 30, 2013, to Nov 24, 2015. In the same communities, 10 791 (86%) of 12 489 eligible enumerated residents not previously enrolled in the longitudinal cohort participated in the end-of-study survey from March 30, 2017, to Feb 25, 2018 (5896 in intervention and 4895 in standard-of-care communities). At study end, in intervention communities, 1228 people living with HIV (91% of 1353) were on ART; 1166 people living with HIV (88% of 1321 with available viral load) were virally suppressed, and 673 HIV-negative men (40% of 1673) were circumcised in intervention communities. After accounting for baseline differences, at study end the proportion of people living with HIV who were diagnosed was significantly higher in intervention communities (absolute increase of 9% to 93%) compared with standard-of-care communities (absolute increase of 2% to 88%; prevalence ratio [PR] 1.08 [95% CI 1.02-1.14], p=0.032). Population levels of ART, viral suppression, and male circumcision increased from baseline in both groups, with greater increases in intervention communities (ART PR 1.12 [95% CI 1.07-1.17], p=0.018; viral suppression 1.13 [1.09-1.17], p=0.017; male circumcision 1.26 [1.17-1.35], p=0.029). INTERPRETATION: It is possible to achieve very high population levels of HIV testing and treatment in a high-prevalence setting. Maintaining these coverage levels over the next decade could substantially reduce HIV transmission and potentially eliminate the epidemic in these areas. FUNDING: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

Background: Many tobacco dependent cancer survivors continue to smoke after diagnosis and treatment. This study investigated the extent to which hospital-based cancer registries could be used to identify smokers in order to offer them assistance in quitting. The concordance of tobacco use coded in the registry was compared with tobacco use as coded in the accompanying Electronic Health Records (EHRs). Methods: We gathered data from three hospital-based cancer registries in New York City during June 2014 to December 2016. For each patient identified as a current combustible tobacco user in the cancer registries, we abstracted tobacco use data from their EHR to independently code and corroborate smoking status. We calculated the proportion of current smokers, former smokers, and never smokers as indicated in the EHR for the hospitals, cancer site, cancer stage, and sex. We used a logistic regression model to estimate the log odds of the registry-based smoking status correctly predicting the EHR-based smoking status. Results: Agreement in current smoking status between the registry-based smoking status and the EHR-based smoking status was 65%, 71%, and 90% at the three participating hospitals. Logistic regression results indicated that agreement in smoking status between the registry and the EHRs varied by hospital, cancer type, and stage, but not by age and sex. Conclusions: The utility of using tobacco use data in cancer registries for population-based tobacco treatment interventions is dependent on multiple factors including accurate entry into EHR systems, updated data, and consistent smoking status definitions and registry coding protocols. Our study found that accuracy varied across the three hospitals and may not be able to inform interventions at these hospitals at this time. Several changes may be needed to improve the coding of tobacco use status in EHRs and registries.

Loose-fitting powered air-purifying respirators (PAPRs) are used in healthcare settings to reduce exposure to high-risk respiratory pathogens. Innovative computational fluid dynamics (CFD) models were developed for evaluating loose-fitting PAPR performance. However, the computational results of the CFD models have not been validated using actual experimental data. Experimental testing to evaluate particle facepiece leakage was performed in a test laboratory using two models of loose-fitting PAPRs. Each model was mounted on a static (non-moving) advanced headform placed in a sodium chloride (NaCl) aerosol test chamber. The headform performed cyclic breathing via connection to a breathing machine. High-efficiency particulate air (HEPA)-filtered air was supplied directly to the PAPR facepiece using laboratory compressed supplied-air regulated with a mass-flow controller. One model was evaluated with six supplied-air flowrates from 50-215 L/min (Lpm) and the other model with six flowrates from 50-205 Lpm. Three different workrates (minute volumes) were evaluated: low (25 Lpm), moderate 46 (Lpm), and high 88 (Lpm). Manikin penetration factor (mPF) was calculated as the ratio of chamber particle concentration to the in-facepiece concentration. Overall, data analyses indicated that the mPF results from the simulations were well correlated with the experimental laboratory data for all data combined (r = 0.88). For data at the three different workrates (high, moderate, low) for both models combined, the r-values were 0.96, 0.97, and 0.77, respectively. The CFD models of the two PAPR models were validated and may be utilized for further research.

In surgical settings, infectious particulate wound contamination is a recognized cause of post-operative infections. Powered air purifying respirators (PAPRs) are worn by healthcare workers for personal protection against contaminated aerosols. Healthcare infection preventionists have expressed concern about the possibility that infectious particles expelled from PAPR exhalation channels could lead to healthcare-associated disease, especially in operative settings where sterile procedural technique is essential. This study used computational fluid dynamics (CFD) modeling to simulate and visualize the distribution of particles exhaled by PAPR wearers. Using CFD simulations, the PAPR inside to outside ratio of particle concentrations was estimated. Also, the effects of particle sizes, supplied-air flow rates, and breathing work rates on outward leakage were evaluated. This simulation study reconstructed a geometrical model of a static median headform wearing a loose-fitting PAPR by capturing a 3D image. We defined a mathematical model for the headform and PAPR system and ran simulations with four particle sizes, three breathing workloads and two supplied-air flow rates (a total 24 configurations; 4×3×2=24) applied on the digital model of the headform and PAPR system. This model accounts for exhaled particles, but not ambient particles. Computed distributions of particles inside and outside the PAPR are displayed. The outward concentration leakage was low at surgical setting, e.g., it was about 9% for a particle size of 0.1 and 1 μm at light breathing and a 205 L/min supplied-air flow rate. The supplied-air flow rates, particle sizes, and breathing workloads had effects on the outward concentration leakage, as the outward concentration leakage increased as particle size decreased, breathing workload increased, and the supplied-air flow rate decreased. The CFD simulations can help to optimize the supplied-air flow rates. When the loose-fitting PAPR is used, exhaled particles with small size (below 1μm), or heavy breathing workloads, may generate a great risk to the sterile field and should be avoided.

BACKGROUND: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown. METHODS: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals. RESULTS: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35). CONCLUSIONS: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.).

Quantitative knowledge about which natural and anthropogenic factors influence the global spread of plague remains sparse. We estimated the worldwide spreading velocity of plague during the Third Pandemic, using more than 200 years of extensive human plague case records and genomic data, and analyzed the association of spatiotemporal environmental factors with spreading velocity. Here, we show that two lineages, 2.MED and 1.ORI3, spread significantly faster than others, possibly reflecting differences among strains in transmission mechanisms and virulence. Plague spread fastest in regions with low population density and high proportion of pasture- or forestland, findings that should be taken into account for effective plague monitoring and control. Temperature exhibited a nonlinear, U-shaped association with spread speed, with a minimum around 20 degrees C, while precipitation showed a positive association. Our results suggest that global warming may accelerate plague spread in warm, tropical regions and that the projected increased precipitation in the Northern Hemisphere may increase plague spread in relevant regions.

In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. PATIENT: The isolate harbored four known beta-lactamase genes, including plasmid-mediated blaNDM-1 and blaCMY-6, as well as chromosomal blaCTX-M-15 and blaSHV-28, which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U.S. PATIENT: Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread.

Few studies have been conducted on the distribution of Enterocytozoon bieneusi genotypes in Tibetan sheep and yaks, which live outdoors in extreme climate with high altitude. In this study, fecal specimens from 312 Tibetan sheep and 554 yaks in Qinghai, China, were collected and examined for E. bieneusi by PCR-sequence analysis of the ribosomal internal transcribed spacer. Among them, 73 (23.4%) specimens from Tibetan sheep and 40 (7.2%) from yaks were positive for E. bieneusi. There were eight E. bieneusi genotypes in Tibetan sheep, including three known ones (BEB6, COS-I, and NESH5) and five novel ones (named as CHS13-CHS17). Similarly, seven E. bieneusi genotypes were found in yaks, including five known ones (J, BEB4, BEB6, COS-I, and NESH5) and two novel ones (named as CHN13 and CHN14). Most of the E. bieneusi genotypes and all frequent ones identified in the study belonged to group 2. One new subgroup of genotypes was identified within group 1. The distribution of E. bieneusi genotypes was different between Tibetan sheep and yaks, with BEB6 as the dominant one (42.5%) in Tibetan sheep and J as the dominant one (47.5%) in yaks. These data support the occurrence of host adaptation among E. bieneusi genotypes within group 2.

Reporting of adverse events following immunization (AEFI) is a key component for functional vaccine safety monitoring system. The aim of our study is to document trends in the AEFI reporting ratio globally and across the six World Health Organization (WHO) regions. We describe the number of AEFI reports communicated each year through the World Health Organization/United Nations Children's Fund Joint Reporting Form on Immunization from 2000 to 2015. The AEFI reporting ratios (annual AEFI reports per 100,000 surviving infants) were calculated to identify WHO countries (n=191 in 2000 and n=194 by 2015) that met a minimal reporting ratio of 10, a target set by the Global Vaccine Action Plan for vaccine safety monitoring as a proxy measure for a functional AEFI reporting system. The number of countries reporting any AEFI fluctuated over time but with progress from 32 (17%) in 2000 to 124 (64%) in 2015. In 2015, the global average AEFI reporting ratio was 549 AEFI reports per 100,000 surviving infants. The number of countries with AEFI reporting ratiosgreater than10 increased from 8 (4%) in 2000 to 81 (42%) in 2015. In 2015, 60% of countries in the WHO Region of the Americas reported at least 10 AEFI per 100,000 surviving infants, followed by 55% in European Region, 43% in Eastern Mediterranean Region, 33% in Western Pacific Region, 27% in South-East Asia Region and 21% in African Region. Overall, AEFI reporting has increased over the past sixteen years worldwide, but requires strengthening in a majority of low- and middle- income countries. The AEFI reporting ratio is useful for benchmarking and following trends over time; but does not provide information on the quality of the reporting system and does not guarantee capacity to detect and manage a vaccine safety problem at a national level. Additional efforts are required to ensure and improve data quality, AEFI reporting and surveillance of immunization safety in every country.

PURPOSE: The objective of our study was to conduct a data mining analysis to identify potential adverse events (AEs) following MENACWY-D using the tree-temporal scan statistic in the Vaccine Safety Datalink population and demonstrate the feasibility of this method in a large distributed safety data setting. METHODS: Traditional pharmacovigilance techniques used in vaccine safety are generally geared to detecting AEs based on pre-defined sets of conditions or diagnoses. Using a newly developed tree-temporal scan statistic data mining method, we performed a pilot study to evaluate the safety profile of the meningococcal conjugate vaccine Menactra(R) (MenACWY-D), screening thousands of potential AE diagnoses and diagnosis groupings. The study cohort included enrolled participants in the Vaccine Safety Datalink aged 11 to 18 years who had received MenACWY-D vaccination(s) between 2005 and 2014. The tree-temporal scan statistic was employed to identify statistical associations (signals) of AEs following MENACWY-D at a 0.05 level of significance, adjusted for multiple testing. RESULTS: We detected signals for 2 groups of outcomes: diseases of the skin and subcutaneous tissue, fever, and urticaria. Both groups are known AEs following MENACWY-D vaccination. We also identified a statistical signal for pleurisy, but further examination suggested it was likely a false signal. No new MENACWY-D safety concerns were raised. CONCLUSIONS: As a pilot study, we demonstrated that the tree-temporal scan statistic data mining method can be successfully applied to screen broadly for a wide range of vaccine-AE associations within a large health care data network.

Mumps incidence in mainland China remains at a high level. Genotype F has been the predominant genotype of mumps virus (MuV) in the last 20 years in mainland China. To better understand the genetic characteristics of MuV in China, the sequences of the Small Hydrophobic (SH), Hemagglutinin-Neuraminidase (HN) and Fusion (F) genes of MuVs of genotype F collected during 2001-2015 were determined. The evolutionary rates of the HN and F genes were similar (0.5 x 10(-3) substitutions/site/year) whereas the SH gene evolutionary rate was three times faster. The most recent common ancestor of genotype F was traced back to 1980. Four lineages were identified within HN and F MuV sequences. A phylogeographic analysis indicated that the genotype F viruses originally spread from the Liaoning and Shandong provinces followed by a spread to the South and East of China. This study provides important genetic baseline data for the development of prevention and control measures of mumps.

OBJECTIVE: Loose-fitting powered air-purifying respirators (PAPRs) are increasingly being used in healthcare. NIOSH has previously used advanced manikin headforms to develop methods to evaluate filtering facepiece respirator fit; research has now begun to develop methods to evaluate PAPR performance using headforms. This preliminary study investigated the performance of PAPRs at different work rates to support development of a manikin-based test method. METHODS: Manikin penetration factors (mPF) of three models of loose-fitting PAPRs were measured at four different work rates (REST: 11 Lpm, LOW: 25 Lpm, MODERATE: 48 Lpm, and HIGH: 88 Lpm) using a medium-sized NIOSH static advanced headform mounted onto a torso. In-mask differential pressure was monitored throughout each test. Two condensation particle counters were used to measure the sodium chloride aerosol concentrations in the test chamber and also inside the PAPR facepiece over a 2-minute sample period. Two test system configurations were evaluated for returning air to the headform in the exhalation cycle (filtered and unfiltered). Geometric mean (GM) and 5th percentile mPFs for each model/work rate combination were computed. Analysis of variance tests were used to assess the variables affecting mPF. RESULTS: PAPR model, work rate, and test configuration significantly affected PAPR performance. PAPR airflow rates for the three models were approximately 185, 210, and 235 Lpm. All models achieved GM mPFs and 5(th) percentile mPFs greater than their designated Occupational Safety and Health Administration assigned protection factors despite negative minimum pressures observed for some work rate/model combinations. CONCLUSIONS: PAPR model, work rate, and test configuration affect PAPR performance. Advanced headforms have potential for assessing PAPR performance once test methods can be matured. A manikin-based inward leakage test method for PAPRs can be further developed using the knowledge gained from this study. Future studies should vary PAPR airflow rate to better understand the effects on performance. Additional future research is needed to evaluate the correlation of PAPR performance using advanced headforms to the performance measured with human subjects.

Long term storage of personal protective equipment (PPE) in stockpiles is increasingly common in preparation for use during public health emergency responses. Confidence in PPE requires an understanding of the impact of time in storage on all aspects of PPE effectiveness, including protection against inward leakage. Disposable N95 filtering facepiece respirators (FFR) typically rely upon inexpensive elastomeric head straps to provide an effective seal between the filter body and the wearer's face. Annual fit testing provides a measure of assurance that a model fresh from the manufacturer will prove effective, but seal quality may degrade during long term storage. This study examines the stability of a s election of polyisoprene elastomer straps taken from various ages of common N95 FFRs. The tension of the straps at a predetermined strain of 150% was found to differ according to age for one respirator model, though whether due to age or due to manufacturing variations could not be determined. The straps from one manufacturer were found to have notable variation in length, indicating that minor variations in strap tensile properties may not result in significant differences in respirator seal quality. Based on our observations, prolonged storage may affect the tensile properties of headstraps for some models of N95.

This study assessed key test parameters and pass/fail criteria options for developing a respirator fit capability (RFC) test for half-mask air-purifying particulate respirators. Using a 25-subject test panel, benchmark RFC data were collected for 101 National Institute for Occupational Safety and Health-certified respirator models. These models were further grouped into 61 one-, two- or three-size families. Fit testing was done using a PortaCount Plus with N95-Companion accessory and an Occupational Safety and Health Administration-accepted quantitative fit test protocol. Three repeated tests (donnings) per subject/respirator model combination were performed. The panel passing rate (PPR) (number or percentage of the 25-subject panel achieving acceptable fit) was determined for each model using five different alternative criteria for determining acceptable fit.When the 101 models are evaluated individually (i.e., not grouped by families), the percentages of models capable of fitting > 75% (19/25 subjects) of the panel were 29% and 32% for subjects achieving a fit factor ≥ 100 for at least one of the first two donnings and at least one of three donnings, respectively. When the models are evaluated grouped into families and using > 75% of panel subjects achieving a fit factor ≥ 100 for at least one of two donnings as the PPR pass/fail criterion, 48% of all models can pass. When > 50% (13/25 subjects) of panel subjects was the PPR criterion, the percentage of passing models increased to 70%.Testing respirators grouped into families and evaluating the first two donnings for each of two respirator sizes provided the best balance between meeting end user expectations and creating a performance bar for manufacturers. Specifying the test criterion for a subject obtaining acceptable fit as achieving a fit factor ≥ 100 on at least one out of the two donnings is reasonable because a majority of existing respirator families can achieve an PPR of > 50% using this criterion. The different test criteria can be considered by standards development organizations when developing standards.

BACKGROUND: Human noroviruses are a major cause of viral gastroenteritis and are the main etiological agents of acute gastroenteritis outbreaks. An increasing number of outbreaks and sporadic cases of norovirus have been reported in China in recent years. There was a large acute gastroenteritis outbreak at a university in Henan Province, China in the past five years. We want to identify the source, transmission routes of the outbreak by epidemiological investigation and laboratory testing in order to provide the effective control measures. METHODS: The clinical cases were investigated, and analysed by descriptive epidemiological methods according to factors such as time, department, grade and so on. Samples were collected from clinical cases, healthy persons, the environment, water, and food at the university. These samples were tested for potential bacteria and viruses. The samples that tested positive for norovirus were selected for whole genome sequencing and the sequences were then analysed. RESULTS: From 4 March to 3 April 2015, a total of 753 acute diarrhoea cases were reported at the university; the attack rate was 3.29%. The epidemic curve showed two peaks, with the main peak occurring between 10 and 20 March, accounting for 85.26% of reported cases. The rates of norovirus detection in samples from confirmed cases, people without symptoms, and environmental samples were 32.72%, 17.39%, and 9.17%, respectively. The phylogenetic analysis showed that the norovirus belonged to the genotype GII.17. CONCLUSIONS: This is the largest and most severe outbreak caused by genotype GII.17 norovirus in recent years in China. The GII.17 viruses displayed high epidemic activity and have become a dominant strain in China since the winter of 2014, having replaced the previously dominant GII.4 Sydney 2012 strain.

BACKGROUND: HIV programmes face challenges achieving high rates of HIV testing and treatment needed to optimise health and to reduce transmission. We used data from the Botswana Combination Prevention Project study survey to assess Botswana's progress toward achieving UNAIDS targets for 2020: 90% of all people living with HIV knowing their status, 90% of these receiving sustained antiretroviral therapy (ART), and 90% of those having virological suppression (90-90-90). METHODS: A population-based sample of individuals was recruited and interviewed in 30 rural and periurban communities from Oct 30, 2013, to Nov 24, 2015, as part of a large, ongoing community-randomised trial designed to assess the effect of a combination prevention package on HIV incidence. A random sample of about 20% of households in each community was selected. Consenting household residents aged 16-64 years who were Botswana citizens or spouses of citizens responded to a questionnaire and had blood drawn for HIV testing in the absence of documentation of positive HIV status. Viral load testing was done in all HIV-infected participants, irrespective of treatment status. We used modified Poisson generalised estimating equations to obtain prevalence ratios, corresponding Huber robust SEs, and 95% Wald CIs to examine associations between individual sociodemographic factors and a binary outcome indicating achievement of the three individual and combined overall 90-90-90 targets. The study is registered at ClinicalTrials.gov, number NCT01965470. FINDINGS: 81% of enumerated eligible household members took part in the survey (10% refused and 9% were absent). Among 12 610 participants surveyed, 3596 (29%) were infected with HIV, and 2995 (83.3%, 95% CI 81.4-85.2) of these individuals already knew their HIV status. Among those who knew their HIV status, 2617 (87.4%, 95% CI 85.8-89.0) were receiving ART (95% of those eligible by national guidelines, and 73% of all infected people). Of the 2609 individuals receiving ART with a viral load measurement, 2517 (96.5%, 95% CI 96.0-97.0) had viral load of 400 copies per mL or less. Overall, 70.2% (95% CI 67.5-73.0) of HIV-infected people had virological suppression, close to the UNAIDS target of 73%. INTERPRETATION: UNAIDS 90-90-90 targets are achievable even in resource-constrained settings with high HIV burden. FUNDING: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.