Gregory L. Armstrong

The Prevalence of Hepatitis C Virus Infection in the United States, 1999 through 2002

Context The Third National Health and Nutrition Examination Survey (NHANES III), conducted between 1988 and 1994, indicated that 1.8% of people in the United States had been infected with hepatitis C virus (HCV), 70% of whom had chronic infection. Most anti-HCVpositive individuals were between 30 and 49 years of age. Contribution Data from the recent NHANES (19992002) show little change in anti-HCV prevalence, but peak prevalence has shifted to individuals between 40 and 49 years of age. More than 85% of HCV RNApositive individuals may be identified through targeted testing of 18% of adults between 20 and 59 years of age: persons with abnormal serum alanine aminotransferase levels, those who have used injection drugs, and those who received blood transfusions before 1992. Cautions Incarcerated and homeless people were not included in the survey. Implications Despite a decrease in new HCV infections, aging of chronically infected individuals may presage an imminent increase in complications. The Editors A decade ago, the Third National Health and Nutrition Examination Survey (NHANES III, 19881994) showed hepatitis C virus (HCV) to be the most common chronic bloodborne infection in the United States (1). An estimated 3.9 million people (1.8% of the population) tested positive for antibody to HCV (anti-HCV), and 2.7 million had chronic infection. Most (65%) anti-HCVpositive persons were 30 to 49 years of age and had been infected for fewer than 20 years. The genetic diversity of HCV circulating in the United States (2) and the pattern of age-specific prevalence (3, 4) both suggest that the incidence of infection increased substantially in the 1960s and 1970s and peaked in the 1980s. Identification of HCV-positive persons for appropriate counseling and management is the major focus of a national prevention program, and routine testing is recommended for persons most likely to have HCV infection (5). To determine the characteristics of HCV-infected persons in the general United States population today and to monitor trends in prevalence, we analyzed data on HCV infection from the most recent NHANES. Methods The National Center for Health Statistics has conducted NHANES periodically to compile nationally representative statistics on the health of the U.S. population (6). The most recent series was begun in 1999 and is designed to run continuously; data are released every 2 years. Our analysis includes data collected from 1999 through 2002. Participants were chosen according to a stratified, multistage algorithm to produce a representative sample of the civilian, noninstitutionalized population of all 50 states and the District of Columbia. Extensive efforts were made to ensure high participation rates, and all respondents were reimbursed for time and travel expenses (6). Initially, a questionnaire covering only nonsensitive topics was used to interview participants in person at home. Information on potentially sensitive subjects, such as sexual practices and illicit drug use, was obtained later at a mobile examination center by means of computer-assisted interviewing technology. The ethnicity of each participant was categorized as non-Hispanic white, non-Hispanic black, and Mexican American. Persons not fitting these categories were classified as other and were included in the total population. Blood samples were obtained at the mobile examination center (7). Only participants who were 6 years of age or older were eligible for HCV testing because of low sample volume in younger children. Laboratory Methods Serum specimens were sent to the Centers for Disease Control and Prevention, where they were tested for anti-HCV by using Ortho HCV enzyme-linked immunosorbent assay (ELISA), version 3.0 (Ortho-Clinical Diagnostics, Raritan, New Jersey). Supplemental recombinant immunoblot assays (RIBA) (Chiron RIBA HCV Strip Immunoblot Assay, version 3.0, Chiron Corp., Emeryville, California) were performed on all specimens that were repeatedly reactive by ELISA testing. For those specimens classified as positive or indeterminate by RIBA, separate, archived aliquots stored at 70C and suitable for nucleic acid amplification testing were submitted for quantitative HCV RNA testing using Cobas Amplicor HCV Monitor Test, version 2.0 (Roche Molecular Diagnostics, Pleasanton, California). If that result was below the level of detection, a qualitative assay (Amplicor HCV Test, version 2.0, Roche Molecular Diagnostics) was performed. Samples found to be reactive by enzyme immunoassay and confirmed by RIBA or Amplicor were considered to be anti-HCVpositive. Alanine aminotransferase (ALT) levels (reference range, 0 to 39 U/L) were measured in specimens that had been stored and shipped under appropriate refrigeration conditions (4C to 8C). Statistical Analysis All statistical analyses were performed with SUDAAN software (RTI International, Research Triangle Park, North Carolina) according to National Center for Health Statistics guidelines. We used appropriate study design variables and published weights that were further adjusted to compensate for missing anti-HCV values (8). These weights accounted for oversampling of certain demographic groups (6) and for nonparticipation such that the sum of the weights for persons with anti-HCV results equaled the U.S. civilian, noninstitutionalized population 6 years of age and older. To estimate the number of HCV RNApositive persons, these weights were further adjusted to compensate for the RIBA-positive and RIBA-indeterminate specimens that were unavailable for RNA testing because of inadequate specimen volumes. Proportions from univariable analyses were compared by using chi-square tests (as implemented in SUDAAN). The P values presented were not corrected for multiple comparisons; P values less than 0.05 were considered statistically significant. Two logistic regression models were used for multivariable analysis; 1 model was used for persons 20 to 59 years of age whose drug use and sexual practices data were available, and the other model was used for persons 60 years of age or older. Two variables, history of blood transfusion (both models) and injection drug use (persons 20 to 59 years of age), were forced into the models on the basis of substantial published data that has established them as risk factors for HCV infection. We sought the most parsimonious model by using these and all other variables that were significant at a P value less than 0.20 on univariable analysis. With the resulting model, we then examined the effect of adding other variables of interest, including those variables that had been excluded at earlier steps in the modeling process. In the final models, all first-order interactions were examined for statistical significance, epidemiologic plausibility, and the impact of their inclusion on the other model parameters. Role of the Funding Source No external funding was received for this study. Results Of 21509 participants 6 years of age or older, 17548 were interviewed and 15079 gave a blood sample suitable for anti-HCV testing (final response rate for testing, 70.1%). Among those who completed home interviews, participation rates did not differ significantly between those with and without risk factors for HCV infection. The weighted prevalence of anti-HCV in the United States was 1.6% (95% CI, 1.3% to 1.9%), corresponding to 4.1 million (CI, 3.4 million to 4.9 million) anti-HCVpositive persons (Table 1). Of anti-HCVpositive participants, 78.8% had specimens suitable for HCV RNA testing; 79.7% (CI, 70.4% to 86.6%) of these tested positive for HCV RNA. After we accounted for untested specimens, the nationwide prevalence of HCV RNA among all participants was 1.3% (CI, 1.0% to 1.5%), equating to 3.2 million (CI, 2.7 million to 3.9 million) HCV RNApositive persons. Table 1. Prevalence of Antibody to Hepatitis C Virus by Demographic Characteristics and Potential Risk Factors Demographic Characteristics Associated with HCV Infection Anti-HCV prevalence was significantly higher in men than in women (Table 1). Prevalence was also higher in non-Hispanic black participants than in either of the other 2 ethnic groups. Among persons younger than 50 years of age, prevalence of anti-HCV increased with age from 1.0% in those 20 to 29 years of age to a peak of 4.3% in those 40 to 49 years of age (Figure 1). Among older persons, anti-HCV prevalence decreased to 1.6% in persons 50 to 59 years of age and to 0.9% in persons 60 years of age and older. Prevalence was higher in men than in women in most age groups (Figure 1). The higher overall prevalence among non-Hispanic black persons compared with non-Hispanic white persons was almost entirely attributable to differences among older participants. Among participants 40 to 49 years of age, 9.4% of non-Hispanic black persons had positive results for anti-HCV compared with 3.8% of non-Hispanic white persons (P< 0.001); of participants 50 years of age or older, 3.3% of non-Hispanic black persons had positive results compared with 0.9% of non-Hispanic white persons (P= 0.002). The demographic group with the highest prevalence was non-Hispanic black men between 40 and 49 years of age (13.6% [CI, 10.0% to 18.2%]). Prevalence was not significantly different between non-Hispanic black and non-Hispanic white persons who were younger than 40 years of age (1.2% vs. 1.1%; P= 0.73). Participants who were born in the United States had a higher prevalence of anti-HCV than those who were not, and prevalence increased with decreasing family income and level of education (Table 1). Among men, prevalence did not vary according to service in the military (Table 1). The sample of women who had served in the military was too small to analyze. Figure 1. Prevalence of antibodies to hepatitis C virus ( HCV ) by ethnicity, age, and sex. The overall prevalence of anti-HCV in the current survey was similar to that observed in NHANES III, but the peak in age-specific prevale

An outbreak of hepatitis a associated with green onions

BACKGROUND In November 2003, a large hepatitis A outbreak was identified among patrons of a single Pennsylvania restaurant. We investigated the cause of the outbreak and factors that contributed to its unprecedented size. METHODS Demographic and clinical outcome data were collected from patients with laboratory confirmation of hepatitis A, and restaurant workers were tested for hepatitis A. A case-control study was conducted among patrons who dined at the restaurant between October 3 and October 6, 2003. Sequence analysis was performed on a 315-nucleotide region of viral RNA extracted from serum specimens. RESULTS Of 601 patients identified, 3 died; at least 124 were hospitalized. Of 425 patients who recalled a single dining date at the restaurant, 356 (84 percent) had dined there between October 3 and October 6. Among 240 patients in the case-control study, 218 had eaten mild salsa (91 percent), as compared with 45 of 130 controls (35 percent) (odds ratio, 19.6; 95 percent confidence interval, 11.0 to 34.9) for whom data were available. A total of 98 percent of patients and 58 percent of controls reported having eaten a menu item containing green onions (odds ratio, 33.3; 95 percent confidence interval, 12.8 to 86.2). All restaurant workers were tested, but none were identified who could have been the source of the outbreak. Sequences of hepatitis A virus from all 170 patients who were tested were identical. Mild salsa, which contained green onions grown in Mexico, was prepared in large batches at the restaurant and provided to all patrons. CONCLUSIONS Green onions that were apparently contaminated before arrival at the restaurant caused this unusually large foodborne outbreak of hepatitis A. The inclusion of contaminated green onions in large batches that were served to all customers contributed to the size of the outbreak.

The global burden of disease attributable to contaminated injections given in health care settings

As part of the 2000 Global Burden of Disease study, we quantified the death and disability from injection-associated infections with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). We modelled the fraction of incident infections attributable to health care injections in the year 2000 on the basis of the annual number of injections, the proportion of injections administered with reused equipment, the probability of transmission following percutaneous exposure, the prevalence of active infection, the prevalence of immunity and the total incidence. Infections in 2000 were converted into disability-adjusted life years (DALYs) in 2000–2030 using natural history parameters, background mortality, duration of disease, disability weights, age weights and a 3% discount rate. Four Global Burden of Disease regions where reuse of injection equipment in the absence of sterilization was negligible were excluded from the analysis. In the remaining 10 regions, in 2000, persons received an average of 3.4 injections per year, 39.3% of which were given with reused equipment. In 2000, contaminated injections caused an estimated 21 million HBV infections, two million HCV infections and 260,000 HIV infections, accounting for 32%, 40% and 5%, respectively, of new infections for a burden of 9,177,679 DALYs between 2000 and 2030. Injection overuse and unsafe practices account for a substantial burden of death and disability worldwide. There is a need for policies and plans for the safe and appropriate use of injections in countries where practices are poor.

Use of injections in healthcare settings worldwide, 2000: literature review and regional estimates

Abstract Objective To describe injection practices worldwide in terms of frequency and safety. Design Literature review. The global burden of disease project of the World Health Organization defined 14 regions on the basis of geography and mortality patterns. Data sources included published studies and unpublished WHO reports. Studies were reviewed by using a standardised decision making algorithm to generate region specific estimates. Setting Healthcare facilities, both formal and informal. Data sources: General population and users of healthcare facilities. Main outcome measure Annual number of injections per person and proportion of injections administered with syringes or needles, or both, reused in the absence of sterilisation. Results The analysis excluded four regions (predominantly affluent, developed nations) where reuse of injection equipment in the absence of sterilisation was assumed to be negligible. In the 10 other regions, the annual ratio of injections per person ranged from 1.7 to 11.3. Of these, the proportion administered with equipment reused in the absence of sterilisation ranged from 1.2% to 75.0%. Reuse was highest in the South East Asia region “D” (seven countries, mostly located in South Asia), the eastern Mediterranean region “D” (nine countries, mostly located in the Middle East crescent), and the western Pacific region “B” (22 countries). No information regarding injection safety was available for Latin America. Conclusions Overuse of injections and unsafe practices are still common in developing and transitional countries. An urgent need exists to use injections safely and appropriately, to prevent healthcare associated infections with HIV and other bloodborne pathogens.

Prevalence of Hepatitis C Virus Infection among Injection Drug Users in the United States, 1994–2004

OBJECTIVE To examine hepatitis C virus (HCV) seroprevalence among injection drug users in 4 US cities from 1994 through 2004. METHODS Demographic characteristics, behaviors, and prevalence of HCV antibody among 5088 injection drug users aged 18-40 years from Baltimore, Maryland; Chicago, Illinois; Los Angeles, California; and New York, New York, enrolled in 3 related studies--Collaborative Injection Drug User Study (CIDUS) I (1994-1996), CIDUS II (1997-1999), and CIDUS III/Drug User Intervention Trial (2002-2004)--were compared using the chi(2) and Mantel-Haenszel tests of significance. Trends over time were assessed by logistic regression. RESULTS Prevalence of HCV infection was 65%, 35%, and 35% in CIDUS I, CIDUS II, and CIDUS III, respectively. The adjusted prevalence odds ratio (OR) of being HCV antibody positive increased with the number of years of injection drug use (OR, 1.93 [95% confidence interval {CI}, 1.68-2.21] for each year of injecting within the first 2 years; OR, 1.09 [95% CI, 1.07-1.11] for each year of injecting beyond the first 2 years). Significant decreases were observed in the prevalence of HCV antibody between CIDUS I and CIDUS III in Baltimore (OR, 0.30; 95% CI, 0.20-0.43) and Los Angeles (OR, 0.17; 95% CI, 0.09-0.31) and among people of races other than black in Chicago (OR, 0.12; 95% CI, 0.08-0.17). No decrease in prevalence was seen in New York (OR, 1.04; 95% CI, 0.69-1.58) or among blacks in Chicago (OR, 0.55; 95% CI, 0.16-1.90). CONCLUSION Although regional differences exist, our data suggest that the incidence of HCV infection among injection drug users in the United States decreased from 1994 through 2004.

Health Care–Associated Measles Outbreak in the United States After an Importation: Challenges and Economic Impact

BACKGROUND On 12 February 2008, an infected Swiss traveler visited hospital A in Tucson, Arizona, and initiated a predominantly health care-associated measles outbreak involving 14 cases. We investigated risk factors that might have contributed to health care-associated transmission and assessed outbreak-associated hospital costs. METHODS Epidemiologic data were obtained by case interviews and review of medical records. Health care personnel (HCP) immunization records were reviewed to identify non-measles-immune HCP. Outbreak-associated costs were estimated from 2 hospitals. RESULTS Of 14 patients with confirmed cases, 7 (50%) were aged ≥ 18 years, 4 (29%) were hospitalized, 7 (50%) acquired measles in health care settings, and all (100%) were unvaccinated or had unknown vaccination status. Of the 11 patients (79%) who had accessed health care services while infectious, 1 (9%) was masked and isolated promptly after rash onset. HCP measles immunity data from 2 hospitals confirmed that 1776 (25%) of 7195 HCP lacked evidence of measles immunity. Among these HCPs, 139 (9%) of 1583 tested seronegative for measles immunoglobulin G, including 1 person who acquired measles. The 2 hospitals spent US

National seroprevalence and trends in herpes simplex virus type 1 in the United States, 1976-1994.

799,136 responding to and containing 7 cases in these facilities. CONCLUSIONS Suspecting measles as a diagnosis, instituting immediate airborne isolation, and ensuring rapidly retrievable measles immunity records for HCPs are paramount in preventing health care-associated spread and in minimizing hospital outbreak-response costs.

Elimination of Endemic Measles, Rubella, and Congenital Rubella Syndrome From the Western Hemisphere The US Experience

Objectives: The objectives of this study were to estimate national seroprevalence of herpes simplex virus type 1 (HSV-1), describe trends in seroprevalence, and examine correlates of infection. Goal: The goal of this study was to measure the burden of HSV-1 infection in the U.S. population. Study: We tested serum samples for HSV-1 antibody and analyzed questionnaire data collected for the second and third National Health and Nutrition Surveys (NHANES II, 1976–80; NHANES III, 1988—94). Seroprevalence estimates were weighted to represent the total U.S. population. Results: At the time of NHANES III, two thirds (68%) of the U.S. population 12 years and older had HSV-1 antibody. Prevalence increased with age and varied by race/ethnicity; the majority of persons in all race/ethnic groups were HSV-1-seropositive by age 30. Overall, the national seroprevalence of HSV-1 decreased nonsignificantly by 2% in the years between NHANES II and III; decreases in HSV-1 seroprevalence in some population subgroups were balanced by increases in other groups. Conclusions: There was no overall change in the seroprevalence of HSV-1 in the U.S. population between NHANES II and III.

Hepatitis B vaccination of newborn infants in rural China: evaluation of a village-based, out-of-cold-chain delivery strategy

IMPORTANCE To verify the elimination of endemic measles, rubella, and congenital rubella syndrome (CRS) from the Western hemisphere, the Pan American Health Organization requested each member country to compile a national elimination report. The United States documented the elimination of endemic measles in 2000 and of endemic rubella and CRS in 2004. In December 2011, the Centers for Disease Control and Prevention convened an external expert panel to review the evidence and determine whether elimination of endemic measles, rubella, and CRS had been sustained. OBJECTIVE To review the evidence for sustained elimination of endemic measles, rubella, and CRS from the United States through 2011. DESIGN, SETTING, AND PARTICIPANTS Review of data for measles from 2001 to 2011 and for rubella and CRS from 2004 to 2011 covering the US resident population and international visitors, including disease epidemiology, importation status of cases, molecular epidemiology, adequacy of surveillance, and population immunity as estimated by national vaccination coverage and serologic surveys. MAIN OUTCOMES AND MEASURES Annual numbers of measles, rubella, and CRS cases, by importation status, outbreak size, and distribution; proportions of US population seropositive for measles and rubella; and measles-mumps-rubella vaccination coverage levels. RESULTS Since 2001, US reported measles incidence has remained below 1 case per 1,000,000 population. Since 2004, rubella incidence has been below 1 case per 10,000,000 population, and CRS incidence has been below 1 case per 5,000,000 births. Eighty-eight percent of measles cases and 54% of rubella cases were internationally imported or epidemiologically or virologically linked to importation. The few cases not linked to importation were insufficient to represent endemic transmission. Molecular epidemiology indicated no endemic genotypes. The US surveillance system is adequate to detect endemic measles or rubella. Seroprevalence and vaccination coverage data indicate high levels of population immunity to measles and rubella. CONCLUSIONS AND RELEVANCE The external expert panel concluded that the elimination of endemic measles, rubella, and CRS from the United States was sustained through 2011. However, international importation continues, and health care providers should suspect measles or rubella in patients with febrile rash illness, especially when associated with international travel or international visitors, and should report suspected cases to the local health department.

Hepatitis A Molecular Epidemiology in the United States, 1996–1997: Sources of Infection and Implications of Vaccination Policy

OBJECTIVE To prevent perinatal transmission of hepatitis B virus (HBV), WHO recommends that the first dose of hepatitis B (HepB) vaccine be given within 24 hours after birth. This presents a challenge in remote areas with limited cold-chain infrastructure and where many children are born at home. METHODS Rural townships in three counties in Chinas Hunan Province were randomized into three groups with different strategies for delivery of the first dose of HepB vaccine. In group 1, vaccine was stored within the cold chain and administered in township hospitals. In group 2, vaccine was stored out of the cold chain in villages and administered by village-based health workers to infants at home. Group 3 used the same strategy as group 2, but vaccine was packaged in a prefilled injection device. Training of immunization providers and public communication conveying the importance of the birth dose was performed for all groups. FINDINGS Among children born at home, timely administration (within 24 hours after birth) of the first dose of HepB vaccine increased in all groups after the study: group 1, from 2.4% to 25.2%; group 2, from 2.6% to 51.8%; and group 3, from 0.6% to 66.7%; P < 0.001 in each case. No significant difference in antibody response to vaccine was observed between the groups. CONCLUSION Timely administration of the first dose of HepB vaccine was improved by communication and training activities, and by out-of-cold-chain storage of vaccine and administration at the village level, especially among children born at home.