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Background and Aims: In the United States, hepatitis C virus (HCV) infection occurs primarily through injection drug use (IDU), but transmission also occurs through other ways. This study examined HCV prevalence and disparities among US residents aged 12-59 years with no IDU history., Methods: We analysed 2013-March 2020 National Health and Nutrition Examination Survey data to calculate the HCV prevalence among people with no drug use history and only a non-IDU history, collectively referred to as no IDU history. These estimates were compared to those with an IDU history and stratified by sociodemographic and hepatitis A and hepatitis B serologic characteristics., Results: The current HCV infection prevalence among people aged 12-59 was .7% overall, and specifically 17.2% among people with an IDU history, .9% among people with a non-IDU history and .2% among people with no drug use history. These rates represented 1.4 million people with current HCV infection, of whom, 730 000 had an IDU history, 262 000 had a non-IDU history and 309 000 had no drug use history. Among people with no drug use history, current HCV infection prevalence was higher for people born during 1954-1965 versus after 1965, had completed high school or less versus at least some college and had past/present hepatitis B versus vaccinated for hepatitis B., Conclusion: While the HCV infection burden was highest among people with an IDU history, we found a sizeable burden among people without such a history. These findings support policies and practices aimed at addressing disparities among people needing treatment., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Hepatitis A is a vaccine-preventable disease that typically causes mild illness. Hepatitis A outbreaks associated with person-to-person transmission have been widespread in the United States since 2016. We used public-use US Multiple Cause of Death data to compare characteristics and listed comorbidities among decedents with hepatitis A-listed deaths during non-outbreak (2011-2015) and outbreak (2017-2021) periods and assessed the median age at death among decedents with and without hepatitis A-listed deaths during the outbreak period. From the non-outbreak period to the outbreak period, hepatitis A-listed deaths more than doubled (from 369 to 801), while the hepatitis A-listed age-adjusted mortality rate increased 150% (p < 0.001). When compared with the non-outbreak period, hepatitis A-listed decedents during the outbreak period were more frequently male, aged 18-49 years, non-Hispanic White, died in an inpatient setting, and had hepatitis A listed as their underlying cause of death. The median age at death for hepatitis A-listed decedents was significantly younger during the outbreak period overall and among females (62 and 66 years, respectively) compared with the non-outbreak period (64 and 72 years, respectively, p < 0.001). During the outbreak period, median age at death for hepatitis A-listed decedents was 14 years younger than decedents without hepatitis A listed. Compared with the general US population, decedents with hepatitis A listed on the death certificate died at younger ages during 2017-2021. Efforts are needed to improve hepatitis A vaccination coverage among adults recommended for hepatitis A vaccination to prevent additional premature hepatitis A deaths., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Injection drug use (IDU) is a major contributor to the syndemic of viral hepatitis, human immunodeficiency virus, and drug overdose. However, information on IDU is frequently missing in national viral hepatitis surveillance data, which limits our understanding of the full extent of IDU-associated infections. Multiple imputation by chained equations (MICE) has become a popular approach to address missing data, but its application for IDU imputation is less studied., Methods: Using the 2019-2021 National Notifiable Diseases Surveillance System acute hepatitis C case data and publicly available county-level measures, we evaluated listwise deletion (LD) and 3 models imputing missing IDU data through MICE: parametric logistic regression, semi-parametric predictive mean matching (PMM), and nonparametric random forest (RF) (both standard RF [sRF] and fast implementation of RF [fRF])., Results: The estimated IDU prevalence among acute hepatitis C cases increased from 63.5% by LD to 65.1% by logistic regression, 66.9% by PMM, 76.0% by sRF, and 85.1% by fRF. Evaluation studies showed that RF-based MICE imputation, especially fRF, has the highest accuracy (as measured by smallest raw bias, percent bias, and root mean square error) and highest efficiency (as measured by smallest 95% confidence interval width) compared to LD and other models. Sensitivity analyses indicated that fRF remained robust when data were missing not at random., Conclusion: Our analysis suggested that RF-based MICE imputation, especially fRF, could be a valuable approach for addressing missing IDU data in the context of population-based surveillance systems like National Notifiable Diseases Surveillance System. The inclusion of imputed IDU data may enhance the effectiveness of future surveillance and prevention efforts for the IDU-driven syndemic., Competing Interests: The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The authors have no conflicts of interest relevant to this article to disclose. The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The biological mechanisms that explain how adverse early life events influence adult disease risk are poorly understood. One proposed mechanism is via the induction of accelerated biological aging, for which telomere length is considered a biomarker. We aimed to determine if maternal depression pre- and post-partum was associated with telomere length in children at 4 years of age (n = 4299). Mothers completed structured questionnaires assessing depression during pregnancy (Edinburgh Depression Scale), at 9 months (Edinburgh Depression Scale), and at 54 months postpartum (Patient Health Questionnaire 9). Regression methods were used to investigate the relationship between telomere length (DNA from saliva) and maternal depression score recorded at each stage. Significant covariates included in the final model were: maternal age at pregnancy; child sex; child ethnicity; gestational age group, and rurality group. Child telomere length was found to be longer if their mother had a higher depression score at both postpartum time points tested (9 months of age; coefficient 0.003, SE = 0.001, P = 0.01, 54 months of age; coefficient 0.003, SE = 0.002, P = 0.02). Although these findings seem paradoxical, increased telomere length may be an adaptive response to early life stressors. We propose several testable hypotheses for these results and to determine if the positive association between depression and telomere length is a developmental adaptation or an indirect consequence of environmental factors., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Current US hepatitis B mortality rates remain three times higher than the national target. Mortality reduction will depend on addressing hepatitis B disparities influenced by social determinants of health., Objectives: This study aims to describe characteristics of hepatitis B-listed decedents, which included US birthplace status and county social vulnerability attributes and quantify premature mortality., Methods: We conducted a cross-sectional analysis of 17,483 hepatitis B-listed decedents using the 2010-2019 US Multiple-Cause-of-Death data merged with the county-level Social Vulnerability Index (SVI). Outcomes included the distribution of decedents according to US birthplace status and residence in higher versus lower death burden counties by sociodemographic characteristics, years of potential life lost (YPLL), and SVI quartiles., Results: Most hepatitis B-listed decedents were US-born, male, and born during 1945-1965. Median YPLL was 17.2; 90.0% died prematurely. US-born decedents were more frequently White, non-college graduates, unmarried, and had resided in a county with < 500,000 people; non-US-born decedents were more frequently Asian/Pacific Islander, college graduates, married, and had resided in a county with ≥ 1 million people. Higher death burden (≥ 20) counties were principally located in coastal states. US-born decedents more frequently resided in counties in the highest SVI quartile for "Household Characteristics" and "Uninsured," whereas non-US-born decedents more frequently resided in counties in the highest SVI quartile for "Racial/Ethnic Minority Status" and "Housing Type/Transportation.", Conclusion: This analysis found substantial premature hepatitis B mortality and residence in counties ranked high in social vulnerability. Successful interventions should be tailored to disproportionately affected populations and the social vulnerability features of their geographic areas., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: Hepatitis C virus (HCV) infection is the most common bloodborne infection in the United States. We assessed trends in HCV testing, infection, and surveillance cases among US adults., Methods: We used Quest Diagnostics data from 2013-2021 to assess trends in the numbers tested for HCV antibody and proportion of positivity for HCV antibody and HCV RNA. We also assessed National Notifiable Diseases Surveillance System 2013-2020 data for trends in the number and proportion of hepatitis C cases. We applied joinpoint regression for trends testing., Results: Annual HCV antibody testing increased from 1.7 million to 4.8 million from 2013 to 2021, and the positivity proportion declined (average, 0.2% per year) from 5.5% to 3.7%. The greatest percentage-point increase in HCV antibody testing occurred in hospitals and substance use disorder treatment facilities and among addiction medicine providers. HCV RNA positivity was stable at about 60% in 2013-2015 and declined to 41.0% in 2021 (2015-2021 average, -3.2% per year). Age-specific HCV RNA positivity was highest among people aged 40-59 years during 2013-2015 and among people aged 18-39 years during 2016-2021. The number of reported hepatitis C cases (acute and chronic) declined from 179 341 in 2015 to 105 504 in 2020 (average decline, -13 177 per year). The proportion of hepatitis C cases among those aged 18-39 years increased by an average of 1.4% per year during 2013-2020; among individuals aged 40-59 years, it decreased by an average of 2.3% per year during 2013-2018., Conclusions: HCV testing increased, suggesting improved universal screening. Various data sources are valuable for monitoring elimination progress., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Harvey W. Kaufman and Justin K. Niles are employees of, and William A. Meyer III serves as a consultant to, Quest Diagnostics. Harvey W. Kaufman and William A. Meyer III own stock in Quest Diagnostics.

The application of a care continuum model (CCM) can identify gaps in diagnosis, care, and treatment of populations with a common condition, but challenges are inherent in developing a CCM for chronic hepatitis B. In contrast with treatment for HIV or hepatitis C, treatment is not indicated for all people with chronic hepatitis B, clinical endpoints are not clear for those receiving treatment, and those for whom treatment is not indicated remain at risk for complications. This topical review examines the data elements necessary to develop and apply chronic hepatitis B CCMs at the jurisdictional health department level. We conducted a nonsystematic review of US-based publications in Ovid MEDLINE (1946-present), Ovid Embase (1974-present), and Scopus (not date limited) databases, which yielded 724 publications for review. Jurisdictional health departments, if properly supported, could develop locale-specific focused CCMs using person-level chronic hepatitis B registries, updated longitudinally using electronic laboratory reporting data and case reporting data. These CCMs could be applied to identify disparities and improve rates in testing and access to care and treatment, which are necessary to reduce liver disease and chronic hepatitis B mortality. Investments in public health surveillance infrastructure, including substantial enhancements in electronic laboratory reporting and case reporting and the use of supplementary data sources, could enable jurisdictional health departments to develop modified CCMs for chronic hepatitis B that focus, at least initially, on "early" CCM steps, which emphasize optimization of hepatitis B diagnosis, linkage to care, and ongoing clinical follow-up of diagnosed people, all of which can lead to improved outcomes., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities., Methods: This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls less than 18 years old frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression., Results: We compared 241 MIS-C cases with 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children [adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48]. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28)., Conclusions: In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted., Competing Interests: The authors have no conflicts of interest to disclose. Individual ICMJE disclosure forms from authors will be provided., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: US hepatitis B mortality has been described nationally, but examination subnationally may identify differences in mortality rates and decedent characteristics, including birthplace., Objective: To examine characteristics of decedents with hepatitis B-listed deaths during 2010 to 2019 and compare age-adjusted hepatitis B-listed death rates during 2010 to 2019 vs 2000 to 2009., Design, Setting, and Participants: This cross-sectional study used Multiple Cause of Death data from 50 US states and the District of Columbia (DC) from 2000 to 2019 to assess characteristics of US residents with hepatitis B listed as an underlying cause of death (UCOD) or contributing cause of death on death certificates. Data were analyzed from September 2019 to May 2022., Exposures: Hepatitis B listed as underlying or contributing cause of death., Main Outcomes and Measures: Outcomes of interest were hepatitis B-listed death counts, age-adjusted rates, and characteristics of decedents during 2000 to 2019. The distribution of hepatitis B-listed deaths according to sociodemographic characteristics and UCOD among US- and non-US-born decedents were also examined., Results: A total of 35 280 decedents with hepatitis B listed as the cause of death were identified, including 17 483 deaths during 2010 to 2019. Decedents were 63.3% US-born, and 25.8% of decedents were Asian or Pacific Islander and 46.5% of decedents were White; 28.4% of decedents were listed as having hepatitis C virus (HCV) or HIV coinfection. State-level rates significantly surpassed the overall US rate (0.47 deaths per 100 000 population) in DC (high, 1.78 deaths per 100 000 population), Hawaii, Oklahoma, California, Tennessee, West Virginia, Mississippi, Oregon, Washington, Louisiana, Kentucky, and New York (low, 0.61 deaths per 100 000 population). Median (IQR) age at hepatitis B death was significantly younger in Kentucky (54.0 [46.0-64.0] years), West Virginia (56.0 [47.0-65.0] years), Tennessee (57.0 [50.0-65.0] years), Mississippi (58.0 [50.0-65.0] years), and Ohio (59.0 [50.0-66.0] years) than the national median (60.0 [53.0-69.0] years), which itself was significantly younger than nonhepatitis B-listed deaths (77 [63.0-87.0] years; P < .001). Hepatitis B was the UCOD among approximately 30% of US- and non-US-born decedents with hepatitis B COD. Irrespective of birthplace, most decedents had liver-related UCOD. Compared with non-US-born decedents, US-born decedents more frequently had nonliver conditions listed as UCOD. Liver cancer was the predominant UCOD among non-US-born decedents (37.9% of decedents). From 2000 to 2009 compared with 2010 to 2019, the hepatitis B-listed mortality rate significantly decreased nationally (change, -18.97%) and in 14 states; significant increases were observed in West Virginia (change, 83.78%) and Kentucky (change, 69.44%)., Conclusions and Relevance: These findings suggest that US-born decedents constituted two-thirds of all hepatitis B-listed deaths and median age at death was youngest in Appalachian states. Irrespective of birthplace, most decedents had liver-related UCOD; however, US-born decedents more frequently had nonliver UCOD than non-US-born decedents. In addition to addressing liver-related complications, US-born persons with chronic infection may also require diagnosis and management of multiple comorbidities.

Persons with isolated antibody to hepatits B virus (HBV) core antigen (IAHBc) may have occult HBV infection (OBI), which is associated with reactivation and potential risk for hepatocellular carcinoma and HBV transmission. We used National Health and Nutrition Examination Survey data to estimate US IAHBc prevalence and published studies of IAHBc-associated OBI prevalence to estimate OBI burden. During 2001-2018, the prevalence of IAHBc was 0.8% (approximately 2.1 million persons), and the OBI burden range was 35 500-83 600 persons. These data support the need for more robust estimates of IAHBc-associated OBI prevalence in the general US population., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background and Aims: In the USA, HBV is one of the leading causes of chronic liver disease and cirrhosis and is a major cause of liver cancer. We aimed to estimate the prevalence of past and present HBV infection, susceptibility to HBV infection, and vaccine-induced immunity to hepatitis B among the US population during 2013-2018., Approach and Results: Prevalence estimates and 95% CIs were analyzed using 2013-2018 data from the National Health and Nutrition Examination Survey. Serologic testing among noninstitutionalized persons aged ≥ 6 years was used for classifying persons as total hepatitis B core antibody (anti-HBc), indicative of current or previous (ever having had) HBV infection; HBsAg, indicative of current HBV infection; and antibody to ABsAg (anti-HBs), indicative of immunity attributable to hepatitis B vaccination. Persons who tested negative for anti-HBc, HBsAg, and anti-HBs were considered susceptible to HBV infection. Non-US-born residents accounted for 69.1% of the population with chronic HBV infection and were 9.1 times more likely to be living with chronic hepatitis B, compared with US-born persons. Among adults aged ≥ 25 years who resided in US households, an estimated 155.8 million persons (or 73.4%) were susceptible to HBV infection, and an estimated 45.4 million had vaccine-induced immunity to hepatitis B. Men who have sex with men (MSM) were 3.6 times more likely to have ever been infected with HBV; however, MSM were just as likely to have vaccine-induced immunity to hepatitis B as non-MSM., Conclusion: Despite increasing immune protection among young persons vaccinated after birth, the estimated prevalence of persons living with chronic hepatitis B in the USA has remained unchanged at 0.3% since 1999., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Background: After decades of decline, US acute hepatitis B incidence flattened since 2011. In persons aged ≥40 years and in jurisdictions affected by the opioid crisis, there is an increase in new cases. Data suggest new infections are occurring among US-born persons., Methods: We used National Health and Nutrition Examination Survey data during 2001-2018 to examine changes in total antibody to hepatitis B virus core antigen (anti-HBc) prevalence in US-born persons. During 2013-2018, the distribution of characteristics was examined., Results: During 2001-2006, 2007-2012, and 2013-2018, anti-HBc prevalence was 3.5%, 2.5%, and 2.6% among US-born persons, respectively. This corresponded to 5.7 (range, 4.8-6.6) million US-born persons with resolved or current HBV infection during 2013-2018, including 344 600 persons aged 6-29 years. The largest increase and highest prevalence was among persons who reported injection drug use (IDU), which increased from 35.3% during 2001-2006 to 58.4% during 2013-2018 (P = .07)., Conclusions: Anti-HBc prevalence among US-born persons remained flat during the most recent period, coinciding with a doubling of prevalence among persons reporting IDU. These data are consistent with acute hepatitis B surveillance trends, showing increasing incidence in subpopulations where prevention could be strengthened.Anti-HBc prevalence among US-born persons decreased from 2001-2006 to 2007-2012 and remained flat during 2013-2018, coinciding with a near doubling of prevalence among US-born persons reporting a history of injection drug use., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: Despite national immunization efforts, including universal childhood hepatitis A (HepA) vaccination recommendations in 2006, hepatitis A virus (HAV)-associated outbreaks have increased in the United States. Unvaccinated or previously uninfected persons are susceptible to HAV infection, yet the susceptibility in the US population is not well known., Methods: Using National Health and Nutrition Examination Survey 2007-2016 data, we estimated HAV susceptibility prevalence (total HAV antibody negative) among persons aged ≥2 years. Among US-born adults aged ≥20 years, we examined prevalence, predictors, and age-adjusted trends of HAV susceptibility by sociodemographic characteristics. We assessed HAV susceptibility and self-reported nonvaccination to HepA among risk groups and the "immunization cohort" (those born in or after 2004)., Results: Among US-born adults aged ≥20 years, HAV susceptibility prevalence was 74.1% (95% confidence interval, 72.9-75.3%) during 2007-2016. Predictors of HAV susceptibility were age group 30-49 years, non-Hispanic white/black, 130% above the poverty level, and no health insurance. Prevalences of HAV susceptibility and nonvaccination to HepA, respectively, were 72.9% and 73.1% among persons who reported injection drug use, 67.5% and 65.2% among men who had sex with men, 55.2% and 75.1% among persons with hepatitis B or hepatitis C, and 22.6% and 25.9% among the immunization cohort. Susceptibility and nonvaccination decreased over time among the immunization cohort but remained stable among risk groups., Conclusions: During 2007-2016, approximately three-fourths of US-born adults remained HAV susceptible. Enhanced vaccination efforts are critically needed, particularly targeting adults at highest risk for HAV infection, to mitigate the current outbreaks., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Mortality associated with hepatitis C virus (HCV) has been well-documented nationally, but an examination across regions and jurisdictions may inform health-care planning., Methods: To document HCV-associated deaths sub-nationally, we calculated age-adjusted, HCV-associated death rates and compared death rate ratios (DRRs) for 10 US regions, 50 states, and Washington, D.C., using the national rate and described rate changes between 2016 and 2017 to determine variability. We examined the mean age at HCV-associated death, and rates and proportions by sex, race/ethnicity, and birth year., Results: In 2017, there were 17 253 HCV-associated deaths, representing 4.13 (95% confidence interval [CI], 4.07-4.20) deaths/100 000 standard population, in a significant, 6.56% rate decline from 4.42 in 2016. Age-adjusted death rates significantly surpassed the US rate for the following jurisdictions: Oklahoma; Washington, D.C.; Oregon; New Mexico; Louisiana; Texas; Colorado; California; Kentucky; Tennessee; Arizona; and Washington (DRRs, 2.87, 2.77, 2.24, 1.62, 1.57, 1.46, 1.36, 1.35, 1.35, 1.35, 1.32, and 1.32, respectively; P < .05). Death rates ranged from a low of 1.60 (95% CI, 1.07-2.29) in Maine to a high of 11.84 (95% CI, 10.82-12.85) in Oklahoma. Death rates were highest among non-Hispanic (non-H) American Indians/Alaska Natives and non-H Blacks, both nationally and regionally. The mean age at death was 61.4 years (range, 56.6 years in West Virginia to 64.1 years in Washington, D.C.), and 78.6% of those who died were born during 1945-1965., Conclusions: In 2016-2017, the national HCV-associated mortality declined but rates remained high in the Western and Southern regions and Washington, D.C., and among non-H American Indians/Alaska Natives, non-H Blacks, and Baby Boomers. These data can inform local prevention and control programs to reduce the HCV mortality burden., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: Hepatitis B virus (HBV) can transmit through needle sharing. The national HBV infection prevalence in persons who inject drugs remains ill-defined. We estimated the prevalence of total HBV core antibody (anti-HBc) positivity, indicating a previous or ongoing HBV infection, among adults aged 20-59 years with an injection drug use (IDU) history. We compared select characteristics by anti-HBc status., Methods: Using 2001-2016 National Health and Nutrition Examination Survey data, we calculated the anti-HBc positivity prevalence among adults with IDU histories and among the general US population. For adults with IDU histories, we compared sex, age group, birth cohort, race/ethnicity, health insurance coverage, and hepatitis A immunity by anti-HBc status. Using marginal structural models, we calculated model-adjusted prevalence rates and ratios to determine the characteristics associated with anti-HBc positivity among adults with IDU histories., Results: From 2001-2016, the anti-HBc positivity prevalence was 19.7% (95% confidence interval [CI] 16.0-24.0%) among those with IDU histories, compared with 4.6% (95% CI 4.3-5.0%) in the general population. The HBV surface antigen positivity prevalence was 0.4% (95% CI 0.3-0.5%) in the general population. Among adults with IDU histories, 19.8% reported prior-year IDU and 28.5% had a hepatitis A immunity., Conclusions: One-fifth of adults with IDU histories had a previous or ongoing HBV infection: a rate over 4 times higher than the prevalence in the general population. One-fifth of adults with IDU histories reported prior-year use. Programs promoting safe IDU practices, drug treatment, and hepatitis A and B vaccinations should be key components of viral hepatitis prevention., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (Published by Oxford University Press for the Infectious Diseases Society of America 2018.)

Background: Mother-to-child transmission of hepatitis B can be prevented with vaccination and screening. Foreign-born women living in the United States may have lower vaccination coverage and greater lifetime exposure to hepatitis B virus than US-born women. This study compares self-reported hepatitis B vaccination and screening between US-born and foreign-born women of reproductive age and examines predictors., Methods: National Health Interview Survey data from 2013-2015 were pooled to estimate the prevalence of lifetime history of hepatitis B vaccination and screening self-reported by women aged 18-44 years who were born in the United States or elsewhere (foreign born). The significance of world region of birth, birth-year cohort, and immigration-related characteristics was considered., Results: Among women of reproductive age (n = 24216), the reported hepatitis B vaccination coverage rate was 33% lower for foreign-born (27.3%) than for US-born (40.9%) women (t test, P < .05). Vaccination coverage was low for women who were born in Mexico/Central America/Caribbean islands (18.4%), South America (25.3%), and the Indian subcontinent (31.7%). Education, income, and insurance coverage were associated with vaccination in both groups. Screening was reported by 28.5% of foreign-born versus 31.9% of US-born women (t test, P < .05). The lowest reported screening prevalence occurred among foreign-born Hispanic or Latina Mexican (21.0%) and Puerto Rican (21.9%) women. Factors associated with screening prevalence among foreign-born women included English fluency, recent US residency, and citizenship., Conclusions: Foreign-born women of reproductive age had lower hepatitis B vaccination and screening coverage than US-born women of reproductive age.

Brain dopamine-serotonin vesicular transport disease is a rare disease caused by autosomal recessive mutations in the SLC18A2 gene, which encodes the VMAT2 protein. VMAT2 is a membrane protein responsible for vesicular transport of monoamines, and its disruption negatively affects neurotransmission. This results in a severe neurodevelopmental disorder affecting motor skills and development, and causes muscular hypotonia. The condition was initially described in a consanguineous Saudi Arabian family with affected siblings homozygous for a P387L mutation. We subsequently found a second mutation in a New Zealand family (homozygous P237H), which was later also identified in an Iraqi family. Pramipexole has been shown to have some therapeutic benefit. Transgenic Caenorhabditis elegans were developed to model the P237H and P387L mutations. Investigations into dopamine- and serotonin-related C. elegans phenotypes, including pharyngeal pumping and grazing, showed that both mutations cause significant impairment of these processes when compared with a non-transgenic N2 strain and a transgenic containing the wild-type human SLC18A2 gene. Preliminary experiments investigating the therapeutic effects of serotonin and pramipexole demonstrated that serotonin could successfully restore the pharyngeal pumping phenotype. These analyses provide further support for the role of these mutations in this disease., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

The prevalence of hepatitis C virus (HCV) infection in the Kenyan population has not been previously determined. We estimated the Kenyan HCV prevalence in HIV-negative persons aged 15-64 years. This is a retrospective cross-sectional study using data from the 2007 Kenya AIDS Indicator Survey-a nationally representative sample of 15,853 persons aged 15-64 years who completed a health interview and provided a blood specimen. Of the 1,091 randomly selected participants, 50 tested positive for HCV antibody using the automated chemiluminescence immunoassay, corresponding to a weighted HCV antibody positivity rate of 4.4% (95% confidence interval: 3.3-5.9%) or 848,000 (range: 634,000-1,100,000) persons. Hepatitis C virus RNA, a marker for current infection, was not detected in any of the tested antibody-positive specimens. The high HCV antibody prevalence together with no current infection suggests that some HCV antibody serologic testing in Kenya may result in false positives whereas others may be because of spontaneous viral clearance.

Background: In the United States, hepatitis C virus (HCV) infection has increased among young persons who inject drugs, but the extent of this epidemic among reproductive-aged women and their children is unknown., Objective: To estimate numbers and describe characteristics of reproductive-aged women with HCV infection and of their offspring., Design: Analysis of the National Notifiable Diseases Surveillance System (NNDSS) from 2006 to 2014 and the Quest Diagnostics Health Trends national database from 2011 to 2014., Setting: United States., Participants: 171 801 women (aged 15 to 44 years) and 1859 children (aged 2 to 13 years) with HCV infection reported to the NNDSS; 2.1 million reproductive-aged women and 56 684 children who had HCV testing by Quest Diagnostics., Measurements: NNDSS HCV case reports and Quest laboratory data regarding unique reproductive-aged women and children who were tested for HCV infection., Results: The number of reproductive-aged women with acute and past or present HCV infection in the NNDSS doubled, from 15 550 in 2006 to 31 039 in 2014. Of 581 255 pregnant women tested by Quest from 2011 to 2014, 4232 (0.73% [95% CI, 0.71% to 0.75%]) had HCV infection. Of children tested by Quest, 0.76% (CI, 0.69% to 0.83%) had HCV infection, but the percentage was 3.2-fold higher among children aged 2 to 3 years (1.62% [CI, 1.34% to 1.96%]) than those aged 12 to 13 years (0.50% [CI, 0.41% to 0.62%]). Applying the Quest HCV infection rate to annual live births from 2011 to 2014 resulted in an estimated average of 29 000 women (CI, 27 400 to 30 900 women) with HCV infection, who gave birth to 1700 infants (CI, 1200 to 2200 infants) with the infection each year., Limitations: Only a fraction of HCV infections is detected and reported to the NNDSS. Quest data are potentially biased, because women who are asymptomatic, do not access health care, or have unreported risks may be less likely to be tested for HCV infection., Conclusion: These data suggest a recent increase in HCV infection among reproductive-aged women and may inform deliberations regarding a role for routine HCV screening during pregnancy., Primary Funding Source: Centers for Disease Control and Prevention.

Current estimates put the prevalence of hepatitis B virus (HBV) infection in Kenya at 5-8%. We determined the HBV infection prevalence in the human immunodeficiency virus (HIV)-negative Kenyan adult and adolescent population based on samples collected from a national survey. We analyzed data from HIV-negative participants in the 2007 Kenya AIDS Indicator Survey to estimate the HBV infection prevalence. We defined past or present HBV infection as presence of total hepatitis B core antibody (HBcAb), and chronic HBV infection (CHBI) as presence of both total HBcAb and hepatitis B surface antigen (HBsAg). We calculated crude and adjusted odds of HBV infection by demographic characteristics and risk factors using logistic regression analyses. Of 1,091 participants aged 15-64 years, approximately 31.5% (95% confidence interval [CI] = 28.0-35.3%) had exposure to HBV, corresponding to approximately 6.1 million (CI = 5.4-6.8 million) with past or present HBV infection. The estimated prevalence of CHBI was 2.1% (95% CI = 1.4-3.1%), corresponding to approximately 398,000 (CI = 261,000-602,000) with CHBI. CHBI is a major public health problem in Kenya, affecting approximately 400,000 persons. Knowing the HBV infection prevalence at baseline is important for planning and public health policy decision making and for monitoring the impact of viral hepatitis prevention programs., (© The American Society of Tropical Medicine and Hygiene.)

In the United States, hepatitis C virus (HCV)-associated mortality is increasing. From 2003-2013, the number of deaths associated with HCV has now surpassed 60 other nationally notifiable infectious conditions combined. The increasing HCV-associated mortality trend underscores the urgency in finding, evaluating, and treating HCV-infected persons., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers., Methods: Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2012 and mortality for 1975-2012) and short-term trends (2008-2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013., Results: Among men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence rates were higher for persons born after the 1938 to 1947 birth cohort. In contrast, there was a minimal birth cohort effect for NH Asian and Pacific Islanders (APIs). NH black men and Hispanic men had the lowest median age at death (60 and 62 years, respectively) and the highest average person-years of life lost per death (21 and 20 years, respectively) from liver cancer. HCV and liver cancer-associated death rates were highest among decedents who were born during 1945 through 1965., Conclusions: Overall, cancer incidence and mortality declined among men; and, although cancer incidence was stable among women, mortality declined. The burden of liver cancer is growing and is not equally distributed throughout the population. Efforts to vaccinate populations that are vulnerable to hepatitis B virus (HBV) infection and to identify and treat those living with HCV or HBV infection, metabolic conditions, alcoholic liver disease, or other causes of cirrhosis can be effective in reducing the incidence and mortality of liver cancer. Cancer 2016;122:1312-1337. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Unlabelled: The number of persons with chronic hepatitis B virus (HBV) infection in the United States is affected by diminishing numbers of young persons who are susceptible because of universal infant vaccination since 1991, offset by numbers of HBV-infected persons migrating to the United States from endemic countries. The prevalence of HBV infection was determined by serological testing and analysis among noninstitutionalized persons age 6 years and older for: antibody to hepatitis B core antigen (anti-HBc), indicative of previous HBV infection; hepatitis B surface antigen (HBsAg), indicative of chronic (current) infection; and antibody to hepatitis B surface antigen (anti-HBs), indicative of immunity from vaccination. These prevalence estimates were analyzed in three periods of the National Health and Nutrition Examination Survey (NHANES): 1988-1994 (21,260 persons); 1999-2008 (29,828); and 2007-2012 (22,358). In 2011-2012, for the first time, non-Hispanic Asians were oversampled in NHANES. For the most recent period (2007-2012), 3.9% had anti-HBc, indicating approximately 10.8 (95% confidence interval [CI]: 9.4-12.2) million noninstitutionalized U.S. residents having ever been infected with HBV. The overall prevalence of chronic HBV infection has remained constant since 1999: 0.3% (95% CI: 0.2-0.4), and since 1999, prevalence of chronic HBV infection among non-Hispanic blacks has been 2- to 3-fold greater than the general population. An estimated 3.1% (1.8%-5.2%) of non-Hispanic Asians were chronically infected with HBV during 2011-2012, which reflects a 10-fold greater prevalence than the general population. Adjusted prevalence of vaccine-induced immunity increased 16% since 1999, and the number of persons (mainly young) with serological evidence of vaccine protection from HBV infection rose from 57.8 (95% CI: 55.4-60.1) million to 68.5 (95% CI: 65.4-71.2) million., Conclusion: Despite increasing immune protection in young persons vaccinated in infancy, an analysis of chronic hepatitis B prevalence in racial and ethnic populations indicates that during 2011-2012, there were 847,000 HBV infections (which included ~400,000 non-Hispanic Asians) in the noninstitutionalized U.S. POPULATION., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)

Background & Aims: Persons chronically infected with the hepatitis C virus (HCV) may be at higher risk for developing and dying from non-liver cancers than the general population., Methods: 12,126 chronic HCV-infected persons in the Chronic Hepatitis Cohort Study (CHeCS) contributed 39,984 person-years of follow-up from 2006 to 2010 and were compared to 133,795,010 records from 13 Surveillance, Epidemiology and End Results Program (SEER) cancer registries, and approximately 12 million U.S. death certificates from Multiple Cause of Death (MCOD) data. Measurements included standardized rate ratios (SRR) and relative risk (RR)., Results: The incidence of the following cancers was significantly higher among patients with chronic HCV infection: liver (SRR, 48.6 [95% CI, 44.4-52.7]), pancreas (2.5 [1.7-3.2]), rectum (2.1 [1.3-2.8]), kidney (1.7 [1.1-2.2]), non-Hodgkin lymphoma (NHL) (1.6 [1.2-2.1]), and lung (1.6 [1.3-1.9]). Age-adjusted mortality was significantly higher among patients with: liver (RR, 29.6 [95% CI, 29.1-30.1]), oral (5.2 [5.1-5.4]), rectum (2.6 [2.5-2.7]), NHL (2.3 [2.2-2.31]), and pancreatic (1.63 [1.6-1.7]) cancers. The mean ages of cancer diagnosis and cancer-related death were significantly younger among CHeCS HCV cohort patients compared to the general population for many cancers., Conclusions: Incidence and mortality of many types of non-liver cancers were higher, and age at diagnosis and death younger, in patients with chronic HCV infection compared to the general population., (Published by Elsevier B.V.)

Aim: Chronic liver disease (CLD) is a leading cause of death and is defined based on a specific set of underlying cause-of-death codes on death certificates. This conventional approach to measuring CLD mortality underestimates the true mortality burden because it does not consider certain CLD conditions like viral hepatitis and hepatocellular carcinoma. We measured how much the conventional CLD mortality case definition will underestimate CLD mortality and described the distribution of CLD etiologies in Connecticut., Methods: We used 2004 Connecticut death certificates to estimate CLD mortality two ways. One way used the conventional definition and the other used an expanded definition that included more conditions suggestive of CLD. We compared the number of deaths identified using this expanded definition with the number identified using the conventional definition. Medical records were reviewed to confirm CLD deaths., Results: Connecticut had 29 314 registered deaths in 2004. Of these, 282 (1.0%) were CLD deaths identified by the conventional CLD definition while 616 (2.1%) were CLD deaths defined by the expanded definition. Medical record review confirmed that most deaths identified by the expanded definition were CLD-related (550/616); this suggested a 15.8 deaths/100 000 population mortality rate. Among deaths for which hepatitis B, hepatitis C and alcoholic liver disease were identified during medical record review, only 8.6%, 45.4% and 36.5%, respectively, had that specific cause-of-death code cited on the death certificate., Conclusion: An expanded CLD mortality case definition that incorporates multiple causes of death and additional CLD-related conditions will better estimate CLD mortality., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

Background: In recent years, few US adults have had exposure and resultant immunity to hepatitis A virus (HAV). Further, persons with liver disease have an increased risk of adverse consequences if they are infected with HAV., Methods: This study used 1999-2011 National Notifiable Diseases Surveillance System and Multiple Cause of Death data to assess trends in the incidence of HAV infection, HAV-related hospitalization, and HAV-related mortality., Results: During 1999-2011, the incidence of HAV infection declined from 6.0 cases/100 000 to 0.4 cases/100 000. Similar declines were seen by sex and age, but persons aged ≥80 years had the highest incidence of HAV infection in 2011 (0.8 cases/100 000). HAV-related hospitalizations increased from 7.3% in 1999 to 24.5% in 2011. The mean age of hospitalized cases increased from 36.0 years in 1999 to 45.1 years in 2011. While HAV-related mortality declined, the mean age at death among decedents with HAV infection increased from 48.0 years in 1999 to 76.2 years in 2011. The median age range of decedents who had HAV infection and a liver-related condition was 51.0 to 68.0 years., Conclusions: Although vaccine-preventable, HAV-related hospitalizations increased greatly, mostly among adults, and liver-related conditions were frequently reported among HAV-infected individuals who died. Public health efforts should focus on the need to assess protection from hepatitis A among adults, including those with liver disease., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

American Samoa does not have a hepatitis B vaccination policy for healthcare personnel (HCP). Consequently, hepatitis B has remained a health threat to HCP. In this study, we performed a cross-sectional study and examined demographic and risk information and hepatitis B vaccination, testing, and serostatus in hospital employees in American Samoa. Of 604 hospital employees, 231 (38·2%) participated, and of these, 158 (68·4%) were HCP. Of HCP participants, 1·9% had chronic hepatitis B infection, 36·1% were susceptible, and 60·8% were immune. Nearly half of HCP participants reported history of needlestick injury. Overall, participants' knowledge of their hepatitis B infection and vaccination status was low. These data support the adoption of a hepatitis B vaccination policy for HCP by American Samoa, as currently recommended by the World Health Organization and the US Centers for Disease Control and Prevention. Adherence to the policy could be monitored as a way to measure protection.

Background: The number of deaths in hepatitis C virus (HCV)-infected persons recorded on US death certificates has been increasing, but actual rates and causes of death in these individuals have not been well elucidated., Methods: Disease-specific, liver-related, and non-liver-related mortality data for HCV-infected patients in an observational cohort study, the Chronic Hepatitis Cohort Study (CHeCS) at 4 US healthcare systems, were compared with multiple cause of death (MCOD) data in 12 million death certificates in 2006-2010. Premortem diagnoses, liver biopsies, and FIB-4 scores (a noninvasive measure of liver damage) were examined., Results: Of 2 143 369 adult patients seen at CHeCS sites in 2006-2010, 11 703 (0.5%) had diagnosed chronic HCV infection, and 1590 (14%) died. The majority of CHeCS decedents were born from 1945 to 1965 (75%), white (50%), and male (68%); mean age of death was 59 years, 15 years younger than MCOD deaths. The age-adjusted mortality rate for liver disease in CHeCS was 12 times higher than the MCOD rate. Before death, 63% of decedents had medical record evidence of chronic liver disease, 76% had elevated FIB-4 scores, and, among those biopsied, 70% had moderate or worse liver fibrosis. However, only 19% of all CHeCS decedents and only 30% of those with recorded liver disease had HCV listed on their death certificates., Conclusions: HCV infection is greatly underdocumented on death certificates. The 16 622 persons with HCV listed in 2010 may represent only one-fifth of about 80 000 HCV-infected persons dying that year, at least two-thirds of whom (53 000 patients) would have had premortem indications of chronic liver disease.

Background and Purpose: Receptor activity-modifying proteins (RAMPs) define the pharmacology of the calcitonin receptor-like receptor (CLR). The interactions of the different RAMPs with this class B GPCR yield high-affinity calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors. However, the mechanism for this is unclear., Experimental Approach: Guided by receptor models, we mutated residues in the N-terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions. These were assayed for cAMP production with AM, AM2 and CGRP together with their cell surface expression. Binding studies were also conducted for selected mutants., Key Results: An important domain for peptide interactions on CLR from I32 to I52 was defined. Although I41 was universally important for binding and receptor function, the role of other residues depended on both ligand and RAMP. Peptide binding to CLR/RAMP3 involved a more restricted range of residues than that to CLR/RAMP1 or CLR/RAMP2. E101 of RAMP2 had a major role in AM interactions, and F111/W84 of RAMP2/3 was important with each peptide., Conclusions and Implications: RAMP-dependent effects of CLR mutations suggest that the different RAMPs control accessibility of peptides to binding residues situated on the CLR N-terminus. RAMP3 appears to alter the role of specific residues at the CLR-RAMP interface compared with RAMP1 and RAMP2., (© 2013 The Authors. British Journal of Pharmacology published by John Wiley &. Sons Ltd on behalf of The British Pharmacological Society.)

Background: Previous research indicates that the mortality burden from viral hepatitis is growing, particularly among middle-aged persons. To monitor progress toward prevention goals, it is important to continue to document characteristics and comortalities of these deaths. This study sought to examine demographic characteristics and the most frequent causes of death among decedents with a viral hepatitis-related death., Methods: A cross-sectional study was performed on approximately 2.4 million death records from 2010. We calculated mortality rates for decedents with and without hepatitis A, B, and C virus (HAV, HBV, and HCV) and relative risks for the most frequently cited conditions in decedents with and without HBV and HCV., Results: In 2010, there were 18 473 (0.7%) deaths with HAV, HBV, and HCV listed among causes of death, disproportionately in those aged 45-64 years. Among the 10 frequent causes of death, decedents listing HBV or HCV died, on average, 22-23 years earlier than decedents not listing these infections. HBV- and HCV-infected decedents aged 45-64 years had an increased risk of having the following conditions reported than decedents without these infections: cancer of liver and intrahepatic bile duct; fibrosis, cirrhosis, and other liver diseases; alcohol-related liver disease; gastrointestinal hemorrhage; human immunodeficiency infection; acute and unspecified renal failure; and septicemia (HCV only)., Conclusions: Decedents with other causes of death that include HBV or HCV died 22-23 years earlier than decedents not listing these infections. These data suggest and support the need for prevention, early identification, and treatment of HBV and HCV.

Background: The increasing health burden and mortality from hepatitis B virus (HBV) and hepatitis C virus (HCV) in the United States are underappreciated., Objective: To examine mortality from HBV; HCV; and, for comparison, HIV., Design: Analysis of U.S. multiple-cause mortality data from 1999 to 2007 from the National Center for Health Statistics., Setting: All U.S. states and the District of Columbia., Participants: Approximately 22 million decedents., Measurements: Age-adjusted mortality rates from HBV, HCV, and HIV. Logistic regression analyses of 2007 data generated 4 independent models per outcome (HCV- or HBV-related deaths) that each included 1 of 4 comorbid conditions and all sociodemographic characteristics., Results: Between 1999 and 2007, recorded deaths from HCV [corrected] increased significantly to 15,106, whereas deaths from HIV declined to 12,734 by 2007. Factors associated with HCV-related deaths included chronic liver disease, HBV co-infection, alcohol-related conditions, minority status, and HIV co-infection. Factors that increased odds of HBV-related death included chronic liver disease, HCV co-infection, Asian or Pacific Islander descent, HIV co-infection, and alcohol-related conditions. Most deaths from HBV and HCV occurred in middle-aged persons., Limitation: A person other than the primary physician of the decedent frequently completed the death certificate, and HCV and HBV often were not detected and thus not reported as causes of death., Conclusion: By 2007, HCV had superseded HIV as a cause of death in the United States, and deaths from HCV and HBV disproportionately occurred in middle-aged persons. To achieve decreases in mortality similar to those seen with HIV requires new policy initiatives to detect patients with chronic hepatitis and link them to care and treatment., Primary Funding Source: Centers for Disease Control and Prevention.