BACKGROUND: Vector-borne diseases cause morbidity and mortality globally. However, some areas are more impacted than others, especially with climate change. Controlling vectors remains the primary means to prevent these diseases, but new, more effective tools are needed. The World Health Organization (WHO) prioritized evaluating novel control methods, such as sterile insect technique (SIT) for control of Aedes-borne diseases. In response, a multiagency partnership between the U.S. Centers for Disease Control and Prevention (CDC), the Special Programme for Research and Training in Tropical Diseases (TDR), WHO, and the International Atomic Energy Agency (IAEA) supported the operational implementation and evaluation of SIT against Aedes aegypti and arboviral diseases in the Pacific through a consortium of regional partners (PAC-SIT Consortium). MAIN TEXT: A workshop was held from 2 to 6 May 2023, during which PAC-SIT country participants, researchers, and stakeholders in SIT, scientific advisory committee members, and organizational partners came together to review the principles and components of SIT, share experiences, visit field sites and the SIT facility, and officially launch the PAC-SIT project. Working in groups focused on entomology, epidemiology, and community engagement, participants addressed challenges, priorities, and needs for SIT implementation. CONCLUSIONS: The PAC-SIT workshop brought together researchers and stakeholders engaged in evaluating SIT for arboviral diseases in the Pacific region and globally. This training workshop highlighted that many countries are actively engaged in building operational capacities and phased testing of SIT. The workshop identified a key need for robust larger-scale studies tied with epidemiological endpoints to provide evidence for the scalability and impact on mosquito-borne diseases.

OBJECTIVES: In the United States, hepatitis C is the most commonly reported bloodborne infection. It is a leading cause of liver cancer and death from liver disease and imposes a substantial burden of hospitalization. We sought to describe regional differences in hepatitis C virus (HCV)-related hospitalizations during 2012 through 2019 to guide planning for hepatitis C elimination. METHODS: We analyzed discharge data from the National Inpatient Sample for 2012 through 2019. We considered hospitalizations to be HCV-related if (1) hepatitis C was the primary diagnosis or (2) hepatitis C was any secondary diagnosis and the primary diagnosis was a liver disease-related condition. We analyzed demographic and clinical characteristics of HCV-related hospitalizations and modeled the annual percentage change in HCV-related hospitalization rates, nationally and according to the 9 US Census Bureau geographic divisions. RESULTS: During 2012-2019, an estimated 553 900 HCV-related hospitalizations occurred in the United States. The highest hospitalization rate (34.7 per 100 000 population) was in the West South Central region, while the lowest (17.6 per 100 000 population) was in the West North Central region. During 2012-2019, annual hospitalization rates decreased in each region, with decreases ranging from 15.3% in the East South Central region to 48.8% in the Pacific region. By type of health insurance, Medicaid had the highest hospitalization rate nationally and in all but 1 geographic region. CONCLUSIONS: HCV-related hospitalization rates decreased nationally and in each geographic region during 2012-2019; however, decreases were not uniform. Expanded access to direct-acting antiviral treatment in early-stage hepatitis C would reduce future hospitalizations related to advanced liver disease and interrupt HCV transmission.

BACKGROUND: Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses. METHODS: Community-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017-2018 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016-2017) standard-dose vaccination. RESULTS: Mean fold rise (MFR) in antibody titers from day 0 to day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017-2018 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) versus without (range, 4.3-14.3) prior 2016-2017 vaccination. MFR was significantly reduced by about one-half to four-fifths for previously vaccinated recipients of standard-dose and all 3 enhanced vaccines (β range, .21-.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR versus standard-dose vaccine by microneutralization assay. CONCLUSIONS: In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination.

BACKGROUND: Hospitalization burden related to hepatitis C virus (HCV) infection is substantial. We sought to describe temporal trends in hospitalization rates before and after release of direct-acting antiviral (DAA) agents. METHODS: We analyzed 2000-2019 data from adults aged ≥18 years in the National Inpatient Sample. Hospitalizations were HCV-related if 1) hepatitis C was the primary diagnosis, or 2) hepatitis C was any secondary diagnosis with a liver-related primary diagnosis. We analyzed characteristics of HCV-related hospitalizations nationally, and examined trends in age-adjusted hospitalization rates. RESULTS: During 2000-2019, there were an estimated 1,286,397 HCV-related hospitalizations in the United States. The annual age-adjusted hospitalization rate was lowest in 2019 (18.7/100,000 population) and highest in 2012 (29.6/100,000 population). Most hospitalizations occurred among persons aged 45-64 (71.8%), males (67.1%), white non-Hispanic persons (60.5%), and Medicaid/Medicare recipients (64.0%). The national age-adjusted hospitalization rate increased during 2000-2003 (annual percent change [APC] 9.4%, P<.001) and 2003-2013 (APC 1.8%, P<.001) before decreasing during 2013-2019 (APC -7.6%, P<.001). Comparing 2000 to 2019, the largest increases in hospitalization rates occurred among persons aged 55-64 years (132.9%), Medicaid recipients (41.6%), and black non-Hispanic persons (22.3%). CONCLUSIONS: Although multiple factors likely contributed, overall HCV-related hospitalization rates declined steadily after 2013, coinciding with the release of DAAs. However, the declines were not observed equally among age, race/ethnicity, or insurance categories. Expanded access to DAA treatment is needed, particularly among Medicaid and Medicare recipients, to reduce disparities and morbidity, and eliminate hepatitis C as a public health threat.

Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1. inactivated vaccine with 2.8 μg hemagglutinin (HA)/dose + AS03(A); 2. inactivated vaccine with 5.75 μg HA/dose + AS03(A;) 3. inactivated vaccine with 11.5 μg HA/dose + MF59; and 4. recombinant virus like particle (VLP) vaccine with 15 μg HA/dose + ISCOMATRIX™. Vaccine group 1 had the highest antibody responses to the vaccine virus and the 3rd/5th wave drifted viruses. Notably, the relative levels of cross-reactivity to the drifted viruses as measured by the antibody GMT ratios to the 5th wave viruses were similar across all 4 vaccine groups. The 1st wave vaccines induced robust responses to the 3rd and Pearl River Delta lineage 5th wave viruses but lower cross-reactivity to the highly pathogenic 5th wave A(H7N9) virus. The population in the United States was largely immunologically naive to the A(H7N9) HA. Seasonal vaccination induced cross-reactive neuraminidase inhibition and binding antibodies to N9, but minimal cross-reactive antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies to A(H7N9).

PURPOSE: Metamodels are simplified approximations of more complex models that can be used as surrogates for the original models. Challenges in using metamodels for policy analysis arise when there are multiple correlated outputs of interest. We develop a framework for metamodeling with policy simulations to accommodate multivariate outcomes. METHODS: We combine 2 algorithm adaptation methods-multitarget stacking and regression chain with maximum correlation-with different base learners including linear regression (LR), elastic net (EE) with second-order terms, Gaussian process regression (GPR), random forests (RFs), and neural networks. We optimize integrated models using variable selection and hyperparameter tuning. We compare the accuracy, efficiency, and interpretability of different approaches. As an example application, we develop metamodels to emulate a microsimulation model of testing and treatment strategies for hepatitis C in correctional settings. RESULTS: Output variables from the simulation model were correlated (average ρ = 0.58). Without multioutput algorithm adaptation methods, in-sample fit (measured by R(2)) ranged from 0.881 for LR to 0.987 for GPR. The multioutput algorithm adaptation method increased R(2) by an average 0.002 across base learners. Variable selection and hyperparameter tuning increased R(2) by 0.009. Simpler models such as LR, EE, and RF required minimal training and prediction time. LR and EE had advantages in model interpretability, and we considered methods for improving the interpretability of other models. CONCLUSIONS: In our example application, the choice of base learner had the largest impact on R(2); multioutput algorithm adaptation and variable selection and hyperparameter tuning had a modest impact. Although advantages and disadvantages of specific learning algorithms may vary across different modeling applications, our framework for metamodeling in policy analyses with multivariate outcomes has broad applicability to decision analysis in health and medicine.

BACKGROUND: Syringe services programs (SSPs) are an important venue for reaching people who inject drugs (PWID) to offer preventive services; however, not all SSPs offer vaccinations. We aimed to describe barriers and opportunities for SSPs to offer vaccinations. METHODS: During June-August 2021, we conducted a descriptive, cross-sectional survey of SSP providers in the United States. SSPs were recruited from national listservs using purposive sampling to ensure geographic diversity. The survey included questions about SSP characteristics, client demographics, existing vaccination resources, resource needs, and staff perspectives on client vaccination barriers. Statistical comparisons were made using Pearson's chi-square test. RESULTS: In total, 105 SSPs from 34 states responded to the survey; 46 SSPs (43.8%) offered on-site vaccinations. SSPs without on-site vaccinations were more likely operated by community-based organizations (81.4% vs 30.4%, p < 0.001) in urban areas (71.4% vs 40.0%, p = 0.002) than SSPs offering on-site vaccinations. The most common staffing need was for personnel licensed to administer vaccines (74/98, 75.5%). Over half of SSPs reported vaccine supply, administration supplies, storage equipment, and systems to follow-up clients for multidose series as important resource needs. The most common resource need was for reminder/recall systems for vaccines with multidose series (75/92, 81.5%). Vaccine safety concerns (92/95, 96.8%) and competing priorities (92/96, 95.8%) were the most common staff-reported client barriers to vaccinations. CONCLUSIONS: Addressing missed opportunities for offering vaccinations to PWID who use SSPs will require increased numbers of on-site personnel licensed to administer vaccines and additional training, vaccination supplies, and storage and handling equipment.

The western black-legged tick (Ixodes pacificus) is the most frequently identified human-biting tick species in the western United States and the principal vector of at least three recognized bacterial pathogens of humans. A potentially pathogenic Rickettsia species, first described in 1978 and recently characterized as a novel transitional group agent designated as Rickettsia tillamookensis, also exists among populations of I. pacificus, although the distribution and frequency of this agent are poorly known. We evaluated DNA extracts from 348 host-seeking I. pacificus nymphs collected from 9 locations in five California counties, and from 916 I. pacificus adults collected from 24 locations in 13 counties, by using a real-time PCR designed specifically to detect DNA of R. tillamookensis. DNA of R. tillamookensis was detected in 10 (2.9%) nymphs (95% CI: 1.6-5.2%) and 17 (1.9%) adults (95% CI: 1.2-3.0%) from 11 counties of northern California. Although site-specific infection rates varied greatly, frequencies of infection remained consistently low when aggregated by stage, sex, habitat type, or geographical region. Four novel isolates of R. tillamookensis were cultivated in Vero E6 cells from individual adult ticks collected from Alameda, Nevada, and Yolo counties. Four historical isolates, serotyped previously as 'Tillamook-like' strains over 40 yr ago, were revived from long-term storage in liquid nitrogen and confirmed subsequently by molecular methods as isolates of R. tillamookensis. The potential public health impact of R. tillamookensis requires further investigation.

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5,773 HBV-infected persons with US cancer registries during 2006-2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (Standardized rate ratio [SRR] 30.79), gastric (SRR 7.95), neuroendocrine (SRR 5.88), cholangiocarcinoma (SRR 4.62), and ovarian (SRR 3.72) cancers, and non-Hodgkin lymphoma (SRR 2.52). Clinicians should be aware of a heightened potential for certain non-hepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.

BACKGROUND: Chlamydia trachomatis (Ct) infection ascending to the upper genital tract can cause infertility. Direct association of genetic variants as contributors is challenging because infertility may not be diagnosed until years after infection. Investigating the intermediate trait of ascension bridges this gap. METHODS: We identified infertility genome-wide association study (GWAS) loci using deoxyribonucleic acid from Ct-seropositive cisgender women in a tubal factor infertility study and Ct-infected cisgender women from a longitudinal pelvic inflammatory disease cohort with known fertility status. Deoxyribonucleic acid and blood messenger ribonucleic acid from 2 additional female cohorts with active Ct infection and known endometrial infection status were used to investigate the impact of infertility single-nucleotide polymorphisms (SNPs) on Ct ascension. A statistical mediation test examined whether multiple infertility SNPs jointly influenced ascension risk by modulating expression of mediator genes. RESULTS: We identified 112 candidate infertility GWAS loci, and 31 associated with Ct ascension. The SNPs altered chlamydial ascension by modulating expression of 40 mediator genes. Mediator genes identified are involved in innate immune responses including type I interferon production, T-cell function, fibrosis, female reproductive tract health, and protein synthesis and degradation. CONCLUSIONS: We identified Ct-related infertility loci and their potential functional effects on Ct ascension.

Introduction. Shigella sonnei, the cause of bacillary dysentery, belongs to Gram-negative enteropathogenic bacteria. S. sonnei contains a 210 kb virulence plasmid that encodes an O-antigen gene cluster of LPSs. However, this virulence plasmid is frequently lost during replication. It is well-documented that after losing the O-antigen and becoming rough strains, the Gram-negative bacteria may express an LPS core on its surface. Previous studies have suggested that by using the LPS core, Gram-negative bacteria can interact with several C-type lectin receptors that are expressed on antigen-presenting cells (APCs).Hypothesis/Gap Statement. S. sonnei by losing the virulence plasmid may hijack APCs via the interactions of LPS-CD209/CD207.Aim. This study aimed to investigate if the S. sonnei rough strain, by losing the virulence plasmid, interacted with APCs that express C-type lectins of human CD207, human CD209a and mouse CD209b.Methodology. SDS-PAGE silver staining was used to examine the O-antigen expression of S. sonnei WT and its rough strain. Invasion assays and inhibition assays were used to examine the ability of S. sonnei WT and its rough strain to invade APCs and investigate whether CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Animal assays were used to observe the dissemination of S. sonnei.Results. S. sonnei did not express O-antigens after losing the virulence plasmid. The S. sonnei rough strain invades with APCs, including human dendritic cells (DCs) and mouse macrophages. CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Expression of the O-antigen reduces the ability of the S. sonnei rough strain to be disseminated to mesenteric lymph nodes and spleens.Conclusion. This work demonstrated that S. sonnei rough strains - by losing the virulence plasmid - invaded APCs through interactions with CD209 and CD207 receptors.

Using electronic health records, we found that hepatitis C reporting on death certificates of 2,901 HCV-infected decedents from four U.S. healthcare organizations during 2011-2017 was documented in only 50% of decedents with hepatocellular carcinoma and less than half with decompensated cirrhosis. National figures likely underestimate the U.S. HCV mortality burden.

AIMS: We assessed prevalence and correlates for hepatitis C virus (HCV) infection in young adult people who inject drugs (PWID) in rural New Mexico, where opioid use has been historically problematic. METHODS: Participants were 18-29 years old with self-reported injection drug use in the past 90 days. We conducted testing for HCV antibodies (anti-HCV) and HCV ribonucleic acid (RNA) and assessed sociodemographic and risk exposures. We provided counseling and referrals to prevention services and drug treatment. We estimated prevalence ratios (PR) to assess bivariate associations with HCV infection; and adjusted PRs using modified Poisson regression methods. RESULTS: Among 256 participants tested for anti-HCV, 156 (60.9 %) had been exposed (anti-HCV positive), and of 230 tested for both anti-HCV and HCV RNA, 103 (44.8 %) had current infection (RNA-positive). The majority (87.6 %) of participants were Hispanic. Almost all (96.1 %) had ever injected heroin; 52.4 % and 52.0 % had ever injected methamphetamine or cocaine, respectively. Polysubstance injecting (heroin and any other drug) was associated with significantly higher prevalence of HCV infection (76.0 %) compared to injecting only heroin (24.0 %) (PR: 3.17 (95 % CI:1.93, 5.23)). Years of injecting, history of non-fatal opioid-involved overdose, polysubstance injecting, and stable housing were independently associated with HCV infection. CONCLUSIONS: HCV is highly prevalent among young adult PWID in rural NM. The high reported prevalence of polysubstance injecting and its association with HCV infection should be considered in prevention planning.

There are limited data examining the relationship between psychosocial factors and receipt of direct-acting antiviral (DAA) treatment among patients with hepatitis C in large health care organizations in the United States. We therefore sought to determine whether such factors were associated with DAA initiation. We analyzed data from an extensive psychological, behavioral, and social survey (that incorporated several health-related quality of life assessments) coupled with clinical data from electronic health records of patients with hepatitis C enrolled at four health care organizations during 2017-2018. Of 2,681 patients invited, 1,051 (39.2%) responded to the survey; of 894 respondents eligible for analysis, 690 (77.2%) initiated DAAs. Mean follow-up among respondents was 9.2 years. Compared with DAA recipients, nonrecipients had significantly poorer standardized scores for depression, anxiety, and life-related stressors as well as poorer scores related to physical and mental function. Lower odds of DAA initiation in multivariable analysis (adjusted by age, race, sex, study site, payment provider, cirrhosis status, comorbidity status, and duration of follow-up) included Black race (adjusted odds ratio [aOR], 0.59 vs. White race), perceived difficulty getting medical care in the preceding year (aOR, 0.48 vs. no difficulty), recent injection drug use (aOR, 0.11 vs. none), alcohol use disorder (aOR, 0.58 vs. no alcohol use disorder), severe depression (aOR, 0.42 vs. no depression), recent homelessness (aOR, 0.36 vs. no homelessness), and recent incarceration (aOR, 0.34 vs. no incarceration). Conclusion(s): In addition to racial differences, compared with respondents who initiated DAAs, those who did not were more likely to have several psychological, behavioral, and social impairments. Psychosocial barriers to DAA initiation among patients in care should also be addressed to reduce hepatitis C-related morbidity and mortality.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED).(†) These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.

Abscess is a common source of morbidity for people who inject drugs. We used data from the Study to Assess Hepatitis C Risk to measure prevalence of abscess and identify factors associated with the history of abscess. Of 541 participants, 388 (72%) were male and 149 (28%) were female. Almost half (n = 258, 48%) reported ever having an abscess. Persons who inject drugs with an abscess history were significantly more likely to have more injection partners (p = .01), inject heroin daily (p < .05), and share cookers (p = .001) and less likely to report using new syringes with each injection (p = .02). Most reported self-treating their last abscess and increasing drug use when having an abscess. High-risk injection-related activity was associated not only with infections such as HIV and hepatitis C virus but also with abscess. Nurses should screen patients presenting with abscess for high-risk practices and provide prevention education.

BACKGROUND: According to death certificates, approximately 1800 persons die from hepatitis B annually in the United States; however, this figure may underestimate true mortality from chronic hepatitis B (CHB). METHODS: We analyzed data from CHB patients seen in the Chronic Hepatitis Cohort Study (CHeCS) between 1 January 2006 and 31 December 2013. We compared overall and cause-specific death rates and mean ages at death between CHeCS CHB decedents and U.S. decedents from the Multiple Cause of Death (MCOD) file. RESULTS: Of 4389 CHB patients followed for a mean of 5.38 years, 492 (11%) CHB patients died after a mean follow-up of 3.00 years. Compared to survivors, decedents were older, more likely to be White (40.6%), African-American (27.1%), or male (74.2%); and more likely to have had cirrhosis (59.8%), diabetes (27.2%), alcohol abuse (17.7%), hepatocellular carcinoma (17.5%), or a liver transplant (5.7%); whereas survivors were more likely to be Asian (48.8%; all P < .001). CHB patients died at an average age of 59.8 years-14 years younger than the general U.S. population-and at higher rates for all causes (relative risk [RR] = 1.85, 95% confidence interval [CI], 1.851-1.857) and liver-related causes (RR = 15.91, 95% CI, 15.81-16.01). Only 19% of CHB decedents and 40% of those dying of liver disease had hepatitis B reported on their death certificates. CONCLUSIONS: Compared to the general population, CHB patients die at younger ages and higher rates from all causes and liver-related causes. Death certificates underrepresent the true mortality from CHB.

To characterize bat influenza H18N11 virus, we propagated a reverse genetics-generated H18N11 virus in MDCK II cells and detected two adapting mutations in the neuraminidase (NA)-like protein (NA-F144C and NA-T342A, N2 numbering) that increased virus titers in three mammalian cell lines (i.e., Madin-Darby canine kidney, Madin-Darby canine kidney II, and human lung adenocarcinoma Calu-3 cells). In mice, wild-type H18N11 virus replicated only in the lungs of the infected animals, whereas the NA-T342A and NA-F144C/T342A mutant viruses were detected in the nasal turbinates in addition to the lungs. Bat influenza viruses have not been tested for their virulence and organ tropism in ferrets. We detected wild-type and single mutant viruses each possessing NA-F144C or NA-T342A in the nasal turbinates of one or several infected ferret(s), respectively. A mutant virus possessing both NA-F144C and T342A was isolated from both the lung and trachea, suggesting broader organ tropism compared with wild-type virus. However, none of the H18N11 viruses caused symptoms in mice or ferrets. The NA-F144C/T342A double mutation did not substantially affect virion morphology or the release of virions from cells. Collectively, our data demonstrate that propagation of bat influenza H18N11 virus in mammalian cells can result in mammalian-adapting mutations that could increase virus replicative ability and/or organ tropism; overall, however, these viruses did not replicate to high titers throughout the respiratory tract of mice and ferrets.IMPORTANCE Bats are reservoirs for several severe zoonotic pathogens. The genomes of influenza A viruses of the H17N10 and H18N11 subtypes were identified in bats, but no live virus has been isolated. The characterization of artificially generated bat influenza H18N11 virus in mammalian cell lines and animal models revealed that this virus can acquire mammalian-adapting mutations that could increase its zoonotic potential; however, the wild-type and mutant viruses did not replicate in the lungs of all infected animals.

Human infections caused by avian influenza A(H7N9) viruses have raised concerns of a pandemic. The capability of the current stockpiled A(H7N9) vaccines to induce cross-protective, non-neutralizing functional antibodies against antigenically drifted A(H7N9) viruses has not been evaluated before. Here we show that vaccination with either MF59- or AS03-adjuvanted inactivated A(H7N9) vaccines elicited robust, cross-reactive ADCC-mediating and neuraminidase-inhibiting functional antibodies against the antigenically drifted A(H7N9) viruses that emerged recently during the 5th wave outbreak in China, including a highly pathogenic A(H7N9) human isolate. Such cross-reactive humoral immunity may provide vital first-line defense against fatal outcomes in case of a A(H7N9) pandemic.

BACKGROUND: Six-monthly hepatocellular carcinoma (HCC) screening in cirrhotic patients has been recommended since 2011. HCC prognosis is associated with diagnosis at an early stage. We examined the prevalence and correlates of 6-monthly HCC surveillance in a cohort of HCV-infected cirrhotic patients. METHODS: Data were obtained from the medical records of patients receiving care from four hospitals between January 2011 and December 2016. Frequencies and logistic regression were conducted. RESULTS: Of 2,933 HCV-infected cirrhotic patients, most were >/= 60 years old (68.5%), male (62.2%), White (65.8%), and had compensated cirrhosis (74.2%). The median follow-up period was 3.5 years. Among these patients, 10.9% were consistently screened 6 monthly and 21.4% were never screened. Patients with a longer history of cirrhosis (AOR = 0.86, 95% CI = 0.80-0.93) were less likely to be screened 6 monthly while decompensated cirrhotic patients (AOR = 1.39, 95% CI = 1.06-1.81) and cirrhotic patients between 18 and 44 years (AOR = 2.01, 95% CI = 1.07-3.74) were more likely to be screened 6 monthly compared to compensated cirrhotic patients and patients 60 years and older respectively. There were no significant differences by race, gender, or insurance type. CONCLUSION: The prevalence of consistent HCC surveillance remains low despite formalized recommendations. One in five patients was never surveilled. Patients with a longer history of cirrhosis were less likely to be surveilled consistently despite their greater HCC risk. Improving providers' knowledge about current HCC surveillance guidelines, educating patients about the benefits of consistent HCC surveillance, and systemic interventions like clinical reminders and standing HCC surveillance protocols can improve guideline-concordant surveillance in clinical practice.

Objective: Although severe hypoglycaemia (SH) can lead to adverse health outcomes, little is known about its occurrence and re-occurrence among youth with type 1 or type 2 diabetes. Methods: This study included 2740 participants aged <20 years at diabetes diagnosis and 5-14 years diabetes duration from the SEARCH for Diabetes in Youth Cohort Study. Participants reported SH events in the past 6 months. Differences in SH events by demographic and clinical factors were tested using logistic regression models. Results: Severe hypoglycaemia in the past 6 months was more common among youth with type 1 (7.0%, 168 of 2399) than with type 2 diabetes (2.6%, nine of 341) (P < 0.002). The median number of SH events per youth who had at least one SH event in the past 6 months was 1 for both type 1 type 2 diabetes. For youth with type 1 diabetes, those who reported SH events were older, were more likely to have obesity or to be physically active, and had lower HbA1c. After adjustments, one unit increase in HbA1c was associated with 16% lower likelihood (OR 0.84, 95% CI 0.75, 0.94) and being physically active was associated with an 87% higher likelihood (OR 1.87, 95% CI 1.23, 2.86) of reporting a SH event. There were too few SH events among youth with type 2 diabetes to analyse further. Conclusions: In youth with diabetes, SH was common even within a short 6-month window. Better understanding the causes of SH may help prevent them from occurring.

BACKGROUND/OBJECTIVES: The waist-to-height ratio (WHtR) estimates cardiometabolic risk in youth without need for growth charts by sex and age. Questions remain about whether waist circumference measured per protocol of the National Health and Nutrition Examination Survey (WNHAHtR) or World Health Organization (WWHOHtR) can better predict blood pressures and lipid parameters in youth. PARTICIPANTS/METHODS: WHtR was measured under both anthropometric protocols among participants in the SEARCH Study, who were recently diagnosed with diabetes (ages 5-19 years; N = 2 773). Biomarkers were documented concurrently with baseline anthropometry and again ~7 years later (ages 10-30 years; N = 1 712). For prediction of continuous biomarker outcomes, baseline WNHAHtR or WWHOHtR entered semiparametric regression models employing restricted cubic splines. To predict binary biomarkers (high-risk group defined as the most adverse quartile) linear WNHAHtR or WWHOHtR terms entered logistic models. Model covariates included demographic characteristics, pertinent medication use, and (for prospective predictions) the follow-up time since baseline. We used measures of model fit, including the adjusted-R(2) and the area under the receiver operator curves (AUC) to compare WNHAHtR and WWHOHtR. RESULTS: For the concurrent biomarkers, the proportion of variation in each outcome explained by full regression models ranged from 23 to 46%; for the prospective biomarkers, the proportions varied from 11 to 30%. Nonlinear relationships were recognized with the lipid outcomes, both at baseline and at follow-up. In full logistic models, the AUCs ranged from 0.75 (diastolic pressure) to 0.85 (systolic pressure) at baseline, and from 0.69 (triglycerides) to 0.78 (systolic pressure) at the prospective follow-up. To predict baseline elevations of the triglycerides/HDL cholesterol ratio, the AUC was 0.816 for WWHOHtR compared with 0.810 for WNHAHtR (p = 0.003), but otherwise comparisons between alternative WHtR protocols were not significantly different. CONCLUSIONS: Among youth with recently diagnosed diabetes, measurements of WHtR by either waist circumference protocol similarly helped estimate current and prospective cardiometabolic risk biomarkers.

IMPORTANCE: Health disparities in the clinical presentation and outcomes among youth with type 1 diabetes exist. Long-term glycemic control patterns in racially/ethnically diverse youth are not well described. OBJECTIVES: To model common trajectories of hemoglobin A1c (HbA1c) among youth with type 1 diabetes and test how trajectory group membership varies by race/ethnicity. DESIGN SETTING AND PARTICIPANTS: Longitudinal cohort study conducted in 5 US locations. The analysis included data from 1313 youths (aged <20 years) newly diagnosed in 2002 through 2005 with type 1 diabetes in the SEARCH for Diabetes in Youth study (mean [SD] age at diabetes onset, 8.9 [4.2] years) who had 3 or more HbA1c study measures during 6.1 to 13.3 years of follow-up. Data were analyzed in 2017. EXPOSURES: Self-reported race/ethnicity. MAIN OUTCOMES AND MEASURES: Hemoglobin A1c trajectories identified through group-based trajectory modeling over a mean (SD) of 9.0 (1.4) years of diabetes duration. Multinomial models studied the association of race/ethnicity with HbA1c trajectory group membership, adjusting for demographic characteristics, clinical factors, and socioeconomic position. RESULTS: The final study sample of 1313 patients was 49.3% female (647 patients) with mean (SD) age 9.7 (4.3) years and mean (SD) disease duration of 9.2 (6.3) months at baseline. The racial/ethnic composition was 77.0% non-Hispanic white (1011 patients), 10.7% Hispanic (140 patients), 9.8% non-Hispanic black (128 patients), and 2.6% other race/ethnicity (34 patients). Three HbA1c trajectories were identified: group 1, low baseline and mild increases (50.7% [666 patients]); group 2, moderate baseline and moderate increases (41.7% [548 patients]); and group 3, moderate baseline and major increases (7.5% [99 patients]). Group 3 was composed of 47.5% nonwhite youths (47 patients). Non-Hispanic black youth had 7.98 higher unadjusted odds (95% CI, 4.42-14.38) than non-Hispanic white youth of being in the highest HbA1c trajectory group relative to the lowest HbA1c trajectory group; the association remained significant after full adjustment (adjusted odds ratio of non-Hispanic black race in group 3 vs group 1, 4.54; 95% CI, 2.08-9.89). Hispanic youth had 3.29 higher unadjusted odds (95% CI, 1.78-6.08) than non-Hispanic white youth of being in the highest HbA1c trajectory group relative to the lowest HbA1c trajectory group; the association remained significant after adjustment (adjusted odds ratio of Hispanic ethnicity in group 3 vs group 1, 2.24; 95% CI, 1.02-4.92). In stratified analyses, the adjusted odds of nonwhite membership in the highest HbA1c trajectory remained significant among male patients and youth diagnosed at age 9 years or younger, but not female patients and youth who were older than 9 years when they were diagnosed (P for interaction = .04 [sex] and .02 [age at diagnosis]). CONCLUSIONS AND RELEVANCE: There are racial/ethnic differences in long-term glycemic control among youth with type 1 diabetes, particularly among nonwhite male patients and nonwhite youth diagnosed earlier in life.

Chronic Hepatitis Cohort Study (CHeCS) publications using data from "real-world" patients with hepatitis C virus (HCV) have described demographic disparities in access to care; rates of advanced liver disease, morbidity, and mortality (2.5%-3.5% per year during 2006-10, although only 19% of all CHeCS decedents, and just 30% of those with deaths attributed to liver disease, had HCV listed on death certificate); substantial comorbidities, such as diabetes, advanced liver fibrosis (29% prevalence), renal disease, and depression, and partial reversal of all these with successful antiviral therapy; patient risk behaviors; and use of noninvasive markers to assess liver disease.

Surveillance of chronic hepatitis C virus (HCV) cases faces limitations that result in delays and underreporting. With increasing use of electronic health records (EHRs), the authors evaluated the predictive value of using International Classification of Diseases, Ninth Revision (ICD-9) codes to identify chronic HCV cases from EHR data. Longitudinal EHR data from 4 health care systems during 2006-2012 were evaluated. Using chart abstraction and review to confirm chronic HCV cases ("gold standard" definition), the authors calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 2 case definitions: (1) >/=2 ICD-9 codes separated by >/= 6 months and (2) >/=1 positive HCV RNA (ribonucleic acid) test. Among 2,718,995 patients, 20,779 (0.8%) with ICD-9 codes indicating a likely diagnosis of chronic HCV infection were identified; 13,595 (65.4%) of these were randomly selected for review. Case definition 1 (>/= 2 ICD-9 codes separated by >/= 6 months) had 70.3% sensitivity, 91.9% PPV, 99.9% specificity, and 99.9% NPV while case definition 2 (>/= 1 positive HCV RNA test) had 74.1% sensitivity, 97.4% PPV, 99.9% specificity, and 99.9% NPV. The predictive values of these alternate EHR-derived ICD-9 code-based case definitions suggest that these measures may be useful in capturing the burden of diagnosed chronic HCV infections. Their use can augment current chronic HCV case surveillance efforts; however, their accuracy may vary by length of observation and completeness of EHR data.

Multiple clusters of human infections with novel avian influenza A(H7N9) virus have occurred since the virus was first identified in spring 2013. However, in many situations it is unclear whether these clusters result from person-to-person transmission or exposure to a common infectious source. We analyzed the possibility of person-to-person transmission in each cluster and developed a framework to assess the likelihood that person-to-person transmission had occurred. We described 21 clusters with 22 infected contact cases that were identified by the Chinese Center for Disease Control and Prevention from March 2013 through June 2015. Based on detailed epidemiological information and the timing of the contact case patients' exposures to infected persons and to poultry during their potential incubation period, we graded the likelihood of person-to-person transmission as probable, possible, or unlikely. We found that person-to-person transmission probably occurred 12 times and possibly occurred 4 times; it was unlikely in 6 clusters. Probable nosocomial transmission is likely to have occurred in 2 clusters. Limited person-to-person transmission is likely to have occurred on multiple occasions since the H7N9 virus was first identified. However, these transmission events represented a small fraction of all identified cases of H7N9 human infection, and sustained person-to-person transmission was not documented.

BACKGROUND: Research suggests depression and alcohol misuse are highly prevalent among chronic hepatitis C (CHC) patients, which is of clinical concern. AIMS: To compare ICD-9 codes for depression and alcohol misuse to validated survey instruments. METHODS: Among CHC patients, we assessed how well electronic ICD-9 codes for depression and alcohol misuse predicted these disorders using validated instruments. RESULTS: Of 4874 patients surveyed, 56% were male and 52% had a history of injection drug use. Based on the PHQ-8, the prevalence of depression was 30% compared to 14% based on ICD-9 codes within 12 months of survey, 37% from ICD-9 codes any time before or within 12 months after survey, and 48% from ICD-9 codes any time before or within 24 months after survey. ICD-9 codes predicting PHQ-8 depression had a sensitivity ranging from 59 to 88% and a specificity ranging from 33 to 65%. Based on the AUDIT-C, the prevalence of alcohol misuse was 21% compared to 3-23% using ICD-9 codes. The sensitivity of ICD-9 codes to predict AUDIT-C score ranged from 9 to 35% and specificity from 80 to 98%. Overall 39% of patients reported ever binge drinking, with a sensitivity of ICD-9 to predict binge drinking ranging from 7 to 33% and a specificity from 84 to 98%. More than half of patients had either an ICD-9 code for depression, a survey score indicating depression, or both (59%); more than one-third had the same patterns for alcohol misuse (36%). CONCLUSIONS: ICD-9 codes were limited in predicting current depression and alcohol misuse, suggesting that caution should be exercised when using ICD-9 codes to assess depression or alcohol misuse among CHC patients.

OBJECTIVE: New cholesterol treatment guidelines from American College of Cardiology/American Heart Association recommend statin treatment for more of US population to prevent atherosclerotic cardiovascular disease (ASCVD). It is important to assess how new guidelines may affect population-level health. This study assessed the impact of statin use for primary prevention of ASCVD under the new guidelines. METHODS: We used data from 2010 US Multiple Cause Mortality, Third National Health and Nutrition Examination Survey (NHANES III) Linked Mortality File (1988-2006, n=8941) and NHANES 2005-2010 (n=3178) participants 40-75 years of age for the present study. RESULTS: Among 33.0 million adults meeting new guidelines for primary prevention of ASCVD, 8.8 million were taking statins; 24.2 million, including 7.7 million with diabetes, are eligible for statin treatment. If all those with diabetes used a statin, 2514 (95% CI 592 to 4142) predicted ASCVD deaths would be prevented annually with 482 (0 to 2239) predicted annual additional cases of myopathy based on randomised clinical trials (RCTs), and 11 801 (9251 to 14 916) using population-based study. Among 16.5 million without diabetes, 5425 (1276 to 8935) ASCVD deaths would be prevented annually with 16 406 (4922 to 26 250) predicted annual additional cases of diabetes and between 1030 (0 to 4791) and 24 302 (19 363 to 30 292) additional cases of myopathy based on RCTs and population-based study. Assuming 80% eligible population take statins with 80% medication adherence, among those without diabetes, the corresponding numbers were 3472 (817 to 5718) deaths, 10 500 (3150 to 16 800) diabetes, 660 (0 to 3066) myopathy (RCTs), and 15 554 (12 392 to 19 387) myopathy (population-based). The estimated total annual cost of statins use ranged from US$1.65 to US$6.5 billion if 100% of eligible population take statins. CONCLUSIONS: This population-based modelling study focused on impact of statin use on ASCVD mortality. Under the new guidelines, if all those eligible for primary prevention of ASCVD take statins, up to 12.6% of annual ASCVD deaths might be prevented, though additional cases of diabetes and myopathy likely occur. DISCLAIMER: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

PURPOSE: The development of a sustainable pediatric diabetes surveillance system for the United States requires a better understanding of issues related to case ascertainment. METHODS: Using the SEARCH for Diabetes in Youth registry, we examined whether time from diabetes diagnosis to case registration differed by diabetes type, patient demographics, and the type of provider reporting the case to the study. Plots for time from diagnosis to registration were developed, and differences by key variables were examined using the log-rank test. RESULTS: Compared with time to registration for type 1 cases, it took 2.6 (95% confidence interval [CI], 2.5-2.6) times longer to register 50% of type 2 diabetes cases, and 2.3 (95% CI, 2.0-2.5) times longer to register 90% of type 2 cases. For type 1 diabetes cases, a longer time to registration was associated with older age, minority race/ethnicity, and cases, where the referring provider was not an endocrinologist. For type 2 diabetes cases, older age, non-Hispanic white race/ethnicity, and cases reported by providers other than an endocrinologist took longer to identify and register. CONCLUSIONS: These findings highlight the need for continued childhood diabetes surveillance to identify future trends and influences on changes in prevalence and incidence.

Background. Detection of neutralizing antibodies (nAbs) to influenza A virus hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However, current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred. Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection. Methods. Virus neutralization and ADCC activities of serum samples from individuals who received either seasonal or a stock-piled H5N1 avian influenza vaccine were evaluated by hemagglutination inhibition assay, microneutralization assay, and an improved ADCC natural killer (NK) cell activation assay. Results. Immunization with inactivated seasonal influenza vaccine led to strong expansion of both nAbs and ADCC-mediating antibodies (adccAbs) to H3 antigen of the vaccine virus in 24 postvaccination human sera. In sharp contrast, 18 individuals vaccinated with the adjuvanted H5N1 avian influenza vaccine mounted H5-specific antibodies with strong ADCC activities despite moderate virus neutralization capacity. Strength of HA-specific ADCC activities is largely associated with the titers of HA-binding antibodies and not with the fine antigenic specificity of anti-HA nAbs. Conclusions. Detection of both nAbs and adccAbs may better reflect protective capacity of HA-specific antibodies induced by avian influenza vaccines.