Patient-care practices associated with an increased prevalence of hepatitis C virus infection among chronic hemodialysis patients.

OBJECTIVE: To identify patient-care practices related to an increased prevalence of hepatitis C virus (HCV) infection among chronic hemodialysis patients. DESIGN: Survey. SETTING: Chronic hemodialysis facilities in the United States. PARTICIPANTS: Equal-probability 2-stage cluster sampling was used to select 87 facilities from all Medicare-approved providers treating 30-150 patients; 53 facilities and 2,933 of 3,680 eligible patients agreed to participate. METHODS: Patients were tested for HCV antibody and HCV RNA. Data on patient-care practices were collected using direct observation. RESULTS: The overall prevalence of HCV infection was 9.9% (95% confidence interval [CI], 8.2%-11.6%); only 2 of 294 HCV-positive patients were detected solely by HCV RNA testing. After adjusting for non-dialysis-related HCV risk factors, patient-care practices independently associated with a higher prevalence of HCV infection included reusing priming receptacles without disinfection (odds ratio [OR], 2.3 [95% CI, 1.4-3.9]), handling blood specimens adjacent to medications and clean supplies (OR, 2.2 [95% CI, 1.3-3.6]), and using mobile carts to deliver injectable medications (OR, 1.7 [95% CI, 1.0-2.8]). Independently related facility covariates were at least 10% patient HCV infection prevalence (OR, 3.0 [95% CI, 1.8-5.2]), patient-to-staff ratio of at least 7 : 1 (OR, 2.4 [95% CI, 1.4-4.1]), and treatment duration of at least 2 years (OR, 2.4 [95% CI, 1.3-4.4]). CONCLUSIONS: This study provides the first epidemiologic evidence of associations between specific patient-care practices and higher HCV infection prevalence among hemodialysis patients. Staff should review practices to ensure that hemodialysis-specific infection control practices are being implemented, especially handling clean and contaminated items in separate areas, reusing items only if disinfected, and prohibiting mobile medication and clean supply carts within treatment areas.

End-point limiting-dilution real-time PCR assay for evaluation of hepatitis C virus quasispecies in serum: performance under optimal and suboptimal conditions.

An approach for determination of hepatitis C virus (HCV) quasispecies by end-point limiting-dilution real-time PCR (EPLD-PCR) is described. It involves isolation of individual coexisting sequence variants of the hypervariable region 1 (HVR1) of the HCV genome from serum specimens using a limiting-dilution protocol. EPLD-PCR applied to an HCV outbreak study provided insights into the epidemiological relationships between incident and chronic cases. When applied to samples from a longitudinal study of infected patients, HVR1 sequences from each sampling time-point were observed to group as distinct phylogenetic clusters. Melting peak analysis conducted on EPLD-PCR products generated from these patients could be used for evaluation of HVR1 sequence heterogeneity without recourse to clonal sequencing. Further, to better understand the mechanism of single-molecule PCR, experiments were conducted under optimal and suboptimal annealing temperatures. Under all temperature conditions tested, HVR1 variants from the major phylogenetic clusters of quasispecies could be amplified, revealing that successful HVR1 quasispecies analysis is not contingent to dilution of starting cDNA preparations to a single-molecule state. It was found that EPLD-PCR conducted at suboptimal annealing temperatures generated distributions of unique-sequence variants slightly different from the distribution obtained by PCR conducted at the optimal temperature. Hence, EPLD-PCR conditions can be manipulated to access different subpopulations of HCV HVR1 quasispecies, thus, improving the range of the quasispecies detection. Although EPLD-PCR conducted at different conditions detect slightly different quasispecies populations, as was shown in this study, the resulted samples of quasispecies are completely suitable for molecular epidemiological investigation in different clinical and epidemiological settings.

Hepatitis A vaccine versus immune globulin for postexposure prophylaxis.

BACKGROUND: Hepatitis A vaccine administered to persons after exposure to the hepatitis A virus has not been compared directly with immune globulin, which is known to be highly effective in preventing hepatitis A when given within 2 weeks after exposure to the virus. METHODS: We randomly assigned household and day-care contacts, 2 to 40 years of age, in Almaty, Kazakhstan, to receive one standard age-appropriate dose of hepatitis A vaccine or immune globulin within 14 days after exposure to patients with hepatitis A. Instances of laboratory-confirmed, symptomatic hepatitis A infection occurring between 15 and 56 days after exposure were then assessed during active follow-up of all susceptible contacts. RESULTS: Of 4524 contacts who underwent randomization, 1414 (31%) were susceptible to hepatitis A virus and 1090 were eligible for the per-protocol analysis. Among these contacts, 568 received hepatitis A vaccine and 522 received immune globulin. Most contacts were children (average age, 12 years), and most received prophylaxis during the second week after exposure (average interval after exposure, 10 days). The baseline characteristics of the contacts were similar in the two groups. Symptomatic infection with hepatitis A virus was confirmed in 25 contacts receiving vaccine (4.4%) and in 17 contacts receiving immune globulin (3.3%) (relative risk, 1.35; 95% confidence interval, 0.70 to 2.67). CONCLUSIONS: Low rates of hepatitis A in both groups indicate that hepatitis A vaccine and immune globulin provided good protection after exposure. Although the study's prespecified criterion for noninferiority was met, the slightly higher rates of hepatitis A among vaccine recipients may indicate a true modest difference in efficacy and might be clinically meaningful in some settings. Vaccine has other advantages, including long-term protection, and it may be a reasonable alternative to immune globulin for postexposure prophylaxis in many situations. (ClinicalTrials.gov number, NCT00139139 [ClinicalTrials.gov].).

Characterization of hepatitis E virus from outbreak and sporadic cases in Turkmenistan.

Large outbreaks and sporadic cases of hepatitis E have been reported in Central Asia. We assessed the genetic relatedness of hepatitis E virus (HEV) strains from outbreak and sporadic cases in Turkmenistan. Specimens from outbreak and sporadic cases of acute hepatitis non-A, non-B were tested by reverse transcription (RT)-polymerase chain reaction (PCR) to identify the presence of HEV RNA; nucleotide sequences were analyzed. HEV RNA was detected from 23/156 (15%) outbreak cases and 2/23 (9%) sporadic cases. The HEV outbreak isolates represented 14 unique sequences with genetic distances varying between 0.3% and 8.6%, 12 of which were closely related, with distances between 0.3% and 5.6%. Two unique sequences from outbreak cases 32 and 42 were closely related (99.7%) and shared 91.8-93.4% of sequence with the other 12 strains. The two strains were closely related to the previously published isolates from Burma (99.7-100%) and India-Madras (95.7-96.1%). The two 1994 sporadic HEV strains were 97.4% distinct, wile revealing 91.4-94.1% homology to 1985 strains, and 94.4-94.7% to HEV from the neighboring China and Pakistan. Genetic diversity of HEV that caused the hepatitis E outbreak in Turkmenistan in 1985 suggests heterogeneity of viral sources. Sporadic hepatitis E that occurred in 1994 was caused by viral strains genetically distinct from those causing the outbreak in 1985, yet closely related to HEV from neighboring countries. The study suggests that circulation of a broad variety of strains of HEV may occur in Central Asia, regardless of international borders, presenting a significant public health threat to the population of the region.

Hepatitis B-associated vasculitis in Alaska Natives: viral genotype, clinical and serologic outcome.

BACKGROUND: The highest incidence of hepatitis B virus (HBV)-associated vasculitis in the world has been reported in Alaska Natives. We examined the incidence of HBV-associated vasculitis before and after mass HBV vaccine immunization and the association between HBV genotype and vasculitis in a population-based cohort study in Alaska natives chronically infected with HBV. METHODS: Genotyping was performed in vasculitis cases and 644 hepatitis B-positive controls without vasculitis using polymerase chain reaction and sequencing of the S gene. Occurrence of HBV vasculitis from 1974 to 2004 was calculated. HBV vasculitis patients and controls were also tested for basal core promoter and precore mutations. RESULTS: Fifteen cases of HBV-associated vasculitis were identified: 13 (86%) had genotype D and one each genotype A and F. Genotype D was more commonly found in patients with vasculitis than controls [odd ratio (OR)=5.9, confidence interval (95% CI) 1.2, 21.8; P<0.015). CONCLUSIONS: HBV-associated vasculitis was associated with genotype D.

Patient-to-patient transmission of hepatitis B virus associated with oral surgery.

We used molecular epidemiologic techniques to document patient-to-patient transmission of hepatitis B virus (HBV) between 2 outpatient oral surgery patients operated on 161 min apart. Serological testing of 25 (93%) of 27 patients operated on after the source patient revealed that 19 (76%) of 25 were previously immune to HBV; no additional cases were identified. We found no deficiencies in infection control practices. Transmission may have been limited by the high prevalence (64%) of patients vaccinated against HBV. To our knowledge, this is the first documented case of patient-to-patient transmission of a bloodborne pathogen in a dental setting in the United States.

Recombinant hepatitis C virus in experimentally infected chimpanzees.

Genetic recombination between different strains of Hepatitis C virus (HCV) was investigated in three chimpanzees inoculated experimentally with factor VIII concentrate containing HCV subgenotypes 1a, 1b, 2b and 3a. A 750 bp long fragment from the HCV envelope region was amplified by RT-PCR and quasispecies were isolated by plasmid cloning. Nucleotide sequences derived from isolated quasispecies were screened for the presence of inter-subgenotypic recombination by using sequence analysis. Recombination between HCV subgenotype 1a and 1b was found in two animals; each recombinant variant differed by location of predicted crossover region or order of subgenotype 1a and 1b sequences.

Hepatitis C virus infections from a contaminated radiopharmaceutical used in myocardial perfusion studies.

CONTEXT: Nuclear pharmacies prepare radiopharmaceutical products for use in common diagnostic procedures, including myocardial perfusion studies. Hepatitis C virus (HCV) transmission has not been reported previously in the setting of nuclear imaging studies. OBJECTIVE: To investigate an outbreak of acute HCV infection identified among patients who underwent myocardial perfusion studies on October 15, 2004, using an injected radiopharmaceutical. DESIGN, SETTING, AND PATIENTS: Outbreak investigation including molecular epidemiology and pharmacy site investigation at outpatient cardiology clinics and a nuclear pharmacy in Maryland. Ninety patients who received injections drawn from select radiopharmaceutical vials prepared on October 14-15, 2004, at a single nuclear pharmacy were offered testing for bloodborne pathogens. Pharmacy procedures were reviewed and HCV quasi species analysis was performed. MAIN OUTCOME MEASURES: Hepatitis C virus infection and quasispecies sequence similarity. RESULTS: Sixteen patients with acute HCV infection were identified from 3 separate clinics. All patients received radiopharmaceutical injections drawn from a single pharmacy vial (vial 1). None of the 59 tested patients who received doses from 6 other vials had acute HCV infection. Blood from a potential source patient with HCV and human immunodeficiency virus (HIV) infection was processed for a radiolabeled white blood cell study in the pharmacy 12 hours before vial 1 was prepared. The HCV quasispecies sequences from this potential source patient were nearly identical to those from cases (97.8%-98.5% similarity). No acute HIV infections were identified. Pharmacy practices that could have led to blood cross-contamination included reuse of needles and syringes during dilutions and use of common flow hoods for some steps in the preparation of sterile and blood-derived products. CONCLUSIONS: Sixteen persons acquired HCV infection from a blood-contaminated radiopharmaceutical. The source and practices that could have facilitated breaks in aseptic technique were identified at the pharmacy. Nuclear pharmacies that handle biological products should follow appropriate aseptic technique to prevent contamination of sterile radiopharmaceuticals.

Hepatitis C virus genotypes and viral concentrations in participants of a general population survey in the United States.

BACKGROUND & AIMS: Estimates of the long-term benefits of antiviral therapies for chronic hepatitis C are influenced by the frequency of characteristics that affect response in the population treated. This study determined hepatitis C virus (HCV) genotypes and RNA titers among HCV-infected persons in the general population of the United States. METHODS: Genotypes were determined from the NS5b region, and HCV RNA was quantified by using Amplicor Monitor (Roche Diagnostic Systems, Inc, Branchburg, NJ) from 275 HCV RNA-positive participants in the Third National Health and Nutrition Examination Survey conducted during 1988 to 1994. RESULTS: The HCV genotypes identified included 1a (n = 142), 1b (n = 73), 2a (n = 8), 2b (n = 27), 3a (n = 17), 4 (n = 3), and 6 (n = 5). Based on weighted analysis of persons infected with genotypes 1, 2, and 3, genotype 1 predominated in all age groups (75.3%). By racial/ethnic group, genotype 1 was found in 90.9% of non-Hispanic blacks, 69.6% of non-Hispanic whites, and 71.2% of Mexican Americans. After adjusting for age and gender, only non-Hispanic black race/ethnicity was independently associated with genotype 1 infection (adjusted odds ratio 4.9; 95% confidence interval, 1.9-12.8). The overall geometric mean concentration of HCV RNA was 2.1 x 10(6) IU/mL; concentrations > 2 million IU/mL were found in 53.0% overall and 50.3% of persons with genotype 1. CONCLUSIONS: Persons with chronic hepatitis C in the United States who may require treatment in the foreseeable future are predominantly infected with genotype 1, including a disproportionate number of non-Hispanic blacks. These features emphasize the need for improved therapies that reduce or eliminate complications from genotype 1 infections.

Diagnosis of hepatitis a virus infection: a molecular approach.

Current serologic tests provide the foundation for diagnosis of hepatitis A and hepatitis A virus (HAV) infection. Recent advances in methods to identify and characterize nucleic acid markers of viral infections have provided the foundation for the field of molecular epidemiology and increased our knowledge of the molecular biology and epidemiology of HAV. Although HAV is primarily shed in feces, there is a strong viremic phase during infection which has allowed easy access to virus isolates and the use of molecular markers to determine their genetic relatedness. Molecular epidemiologic studies have provided new information on the types and extent of HAV infection and transmission in the United States. In addition, these new diagnostic methods have provided tools for the rapid detection of food-borne HAV transmission and identification of the potential source of the food contamination.

Selective transmission of hepatitis C virus genotypes and quasispecies in humans and experimentally infected chimpanzees.

This study determined whether selective transmission of hepatitis C virus (HCV) species occurred among human and chimpanzee recipients of contaminated blood products or plasma containing multiple genotypes, subgenotypes and quasispecies. Commercially prepared factor VIII concentrate (lot DO56), produced prior to HCV testing and inactivation, was subsequently found by direct cloning to contain the following subgenotypes: 1a and 1b (73 % of clones), 2a (13 % of clones), 2b (11 % of clones) and 3a (4 % of clones). A patient transfused with factor VIII concentrate DO56 was diagnosed with clinical non-A, non-B hepatitis and subsequently found to be infected with HCV subgenotype 1b. Among five chimpanzees inoculated experimentally with the same factor VIII concentrate, two were infected only with HCV subgenotype 1a and three were infected with approximately equivalent clonal proportions of subgenotypes 1a and 1b. HCV hypervariable region 1 (HVR1) quasispecies analysis of the DO56 factor VIII concentrate and a serum specimen from the single chimpanzee that developed a chronic HCV infection following inoculation with DO56 showed 0-56 % nucleotide variation. However, specimens from chimpanzees infected in the second to fourth passages of the DO56 inoculum had 0-8 % HVR1 quasispecies nucleotide variation. The high HVR1 quasispecies variation in the factor VIII concentrate and its first passage in chimpanzees indicates the presence of multiple HCV isolates, whereas the low variation in the second to fourth chimpanzee passages suggests transmission of a single HCV isolate. These findings strongly suggest selective transmission of HCV isolates during experimental chimpanzee infection and among humans exposed to multiple HCV species.

[The incidence rate of hepatitis B virus surface gene variants in Korean children with immunoprophylaxis failure of perinatal infection].

BACKGROUND/AIMS: Perinatal infection with hepatitis B virus (HBV) may occur despite immunoprophylaxis. One of the important mechanisms for perinatal prophylaxis failure, might include HBV surface gene variants. Therefore, we screened Korean children, in whom perinatal prophylaxis failed, for HBV surface gene variants. METHODS: Thirty-one children with perinatal HBV prophylaxis failure were selected. To amplify the major hydrophilic region of the HBV surface gene, nested PCR with primers targeted to nucleotides 237 to 706 was performed, and then sequencing was done. RESULTS: All cases were shown to be PCR positive for HBV-DNA and genotype C. Nine out of 31 (29%) with perinatal prophylaxis failure had a nucleotide substitution at the major hydrophilic region of the gene; but only two cases (6.5%) had an amino acid substitution. One case was infected by wild type and variants of I126S, and the other by wild type and S114A+I126S, respectively. CONCLUSIONS: In Korea, compared to the previous studies of other nations, gene surface variants such as G145R do not appear to play an important role in perinatal immunoprophylaxis failure.

Transmission of hepatitis C virus to several organ and tissue recipients from an antibody-negative donor.

BACKGROUND: Although hepatitis C virus (HCV) transmission through tissue transplantation has been rarely reported, a donor with undetected viremia may infect several recipients. A patient developed acute hepatitis C shortly after tissue transplantation. Ninety-one tissues or organs had been recovered from the donor. OBJECTIVE: To determine whether the donor was the source of infection and the extent of transmission to other organ and tissue recipients. DESIGN: Descriptive epidemiologic study; serum testing for HCV infection. SETTING: Recipients were located in 16 states and 2 other countries. PARTICIPANTS: Donor and graft recipients. MEASUREMENTS: Hepatitis C virus infection was defined as the presence of anti-HCV or HCV RNA. The authors determined the genetic relatedness of viral isolates from the donor and recipients by genotype comparison and quasi-species analysis. RESULTS: The donor was anti-HCV-negative but was HCV RNA-positive (genotype 1a). Forty persons received transplants during 22 months. Five persons were HCV-infected before transplantation or had a genotype other than 1a, and 5 persons had no post-transplantation serum specimens available. Of the remaining 30 recipients, HCV infection occurred in 8 recipients: 3 of 3 organ recipients, 1 of 2 saphenous vein recipients, 1 of 3 tendon recipients, and 3 of 3 tendon with bone recipients. These 8 recipients had viral isolates genetically related to those of the donor. No cases occurred in recipients of skin (n = 2), cornea (n = 1), or irradiated bone (n = 16). LIMITATIONS: Post-transplantation serum specimens were unavailable for 5 recipients. CONCLUSIONS: An anti-HCV-negative donor was the source of HCV infection for 8 recipients of organs or tissues. Although HCV transmission from anti-HCV-negative donors is probably uncommon, changes in donor screening to include routine testing for HCV RNA merit further consideration to improve the safety of transplantation.

Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy.

BACKGROUND: The goal of the present study was to assess risk factors for perinatal hepatitis C virus (HCV) transmission and the natural history of infection among HCV-infected infants. METHODS: In a cohort study, 244 infants born to HCV-positive mothers were followed from birth until age > or =12 months. Maternal serum was collected at enrollment and delivery; infant serum was collected at birth and at 8 well-child visits. Testing included detection of antibody to HCV, detection of HCV RNA (qualitative and quantitative), and genotyping. HCV-infected infants were followed annually until age 5 years. RESULTS: Overall, 9 of 190 (4.7% [95% confidence interval (CI), 2.3%-9.1%]) infants born to mothers who were HCV RNA positive at delivery became infected, compared with 0 of 54 infants born to HCV RNA-negative mothers (P=.10). Among HCV RNA-positive mothers, the rate of transmission was 3.8% (95% CI, 1.7%-8.1%) from the 182 who were human immunodeficiency virus (HIV) negative, compared with 25.0% (95% CI, 4.5%-64.4%) from the 8 who were HIV positive (P<.05). Three infected infants resolved their infection (i.e., became HCV RNA negative). In multivariate analysis restricted to HCV RNA-positive mothers, membrane rupture > or =6 h (odds ratio [OR], 9.3 [95% CI, 1.5-179.7]) and internal fetal monitoring (OR, 6.7 [95% CI, 1.1-35.9]) were associated with transmission of HCV to infants. CONCLUSION: If duration of membrane rupture and internal fetal monitoring are confirmed to be associated with transmission, interventions may be possible to decrease the risk of transmission.

A large outbreak of hepatitis B virus infections associated with frequent injections at a physician's office.

OBJECTIVES: To determine whether hepatitis B virus (HBV) transmission occurred among patients visiting a physician's office and to evaluate potential transmission mechanisms. DESIGN: Serologic survey, retrospective cohort study, and observation of infection control practices. SETTING: Private medical office. PATIENTS: Those visiting the office between March 1 and December 26, 2001. RESULTS: We identified 38 patients with acute HBV infection occurring between February 2000 and February 2002. The cohort study, limited to the 10 months before outbreak detection, included 91 patients with serologic test results and available charts representing 18 case-patients and 73 susceptible patients. Overall, 67 patients (74%) received at least one injection during the observation period. Case-patients received a median of 14 injections (range, 2-25) versus 2 injections (range, 0-17) for susceptible patients (P < .001). Acute infections occurred among 18 (27%) of 67 who received at least one injection versus none of 24 who received no injections (RR, 13.6; CI95, 2.4-undefined). Risk of infection increased 5.2-fold (CI95, 0.6-47.3) for those with 3 to 6 injections and 20.0-fold (CI95, 2.8-143.5) for those with more than 6 injections. Typically, injections consisted of doses of atropine, dexamethasone, vitamin B12, or a combination of these mixed in one syringe. HBV DNA genetic sequences of 24 patients with acute infection and 4 patients with chronic infection were identical in the 1,500-bp region examined. Medical staff were seronegative for HBV infection markers. The same surface was used for storing multidose vials, preparing injections, and dismantling used injection equipment. CONCLUSION: Administration of unnecessary injections combined with failure to separate clean from contaminated areas and follow safe injection practices likely resulted in patient-to-patient HBV transmission in a private physician's office.

Ongoing transmission of hepatitis B virus infection among inmates at a state correctional facility.

OBJECTIVES: We sought to determine hepatitis B virus (HBV) infection prevalence, associated exposures, and incidence among male inmates at a state correctional facility. METHODS: A cross-sectional serological survey was conducted in June 2000, and susceptible inmates were retested in June 2001. RESULTS: At baseline, 230 inmates (20.5%; 95% confidence interval [CI]=18.2%, 22.9%) exhibited evidence of HBV infection, including 11 acute and 11 chronic infections. Inmates with HBV infection were more likely than susceptible inmates to have injected drugs (38.8% vs 18.0%; adjusted prevalence odds ratio [OR]=3.0; 95% CI=1.9, 4.9), to have had more than 25 female sex partners (27.7% vs 17.5%; adjusted prevalence OR=2.0; 95% CI=1.4, 3.0), and to have been incarcerated for more than 14 years (38.4% vs 17.6%; adjusted prevalence OR=1.7; 95% CI=1.1, 2.6). One year later, 18 (3.6%) showed evidence of new HBV infection. Among 19 individuals with infections, molecular analysis identified 2 clusters involving 10 inmates, each with a unique HBV sequence. CONCLUSIONS: We documented ongoing HBV transmission at a state correctional facility. Similar transmission may occur at other US correctional facilities and could be prevented by vaccination of inmates.

Molecular epidemiology of foodborne hepatitis a outbreaks in the United States, 2003.

BACKGROUND: Molecular epidemiologic investigations can link geographically separate foodborne hepatitis A outbreaks but have not been used while field investigations are in progress. In 2003, outbreaks of foodborne hepatitis A were reported in multiple states. METHODS: Case-control studies were conducted in 3 states. Hepatitis A virus was sequenced from serologic specimens from individuals associated with outbreaks and from individuals concurrently ill with hepatitis A in non-outbreak settings in the United States and Mexico. RESULTS: Case-control studies in Tennessee (TN), North Carolina (NC), and Georgia (GA) found green onions to be associated with illness among restaurant patrons (TN: odds ratio [OR], 65.5 [95% confidence interval {CI}, 8.9-482.5; NC: OR, 2.4 [95% CI, 0.3-21.9]; GA: OR, 20.9 [95% CI, 3.9-110.3]). Viral sequences from TN case patients differed by 2 nt, compared with those from case patients in NC and GA. A third sequence, differing from the TN and GA/NC sequences by 1 nt, was identified among case patients in a subsequent outbreak in Pennsylvania. Each outbreak sequence was identical to > or =1 sequence isolated from northern Mexican resident(s) with hepatitis A. The sources of green onions served in restaurants in TN and GA were 3 farms in northern Mexico. CONCLUSIONS: Ongoing viral strain surveillance facilitated the rapid implementation of control measures. Incorporation of molecular epidemiologic methods into routine hepatitis A surveillance would improve the detection of hepatitis A outbreaks and increase our understanding of hepatitis A epidemiology in the United States.

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.

Persistence of antibody to hepatitis B and protection from disease among Alaska natives immunized at birth.

BACKGROUND: Alaska Native (AN) children were at high risk of acquiring hepatitis B virus (HBV) infection before vaccination began in 1983. We evaluated the long-term protection from hepatitis B (HB) vaccination among AN children immunized when infants. METHODS: During 1984-1995, we recruited a convenience sample of AN children who had received a three dose series of HB vaccine starting at birth and had serum antibody to hepatitis B (anti-HBs) concentrations of >/= 10 mIU/mL at 7-26 months of age. We evaluated anti-HBs concentrations and the presence of anti-HBc in participants' sera every other year up to age 16 years. Anti-HB core antigen (anti-HBc)-positive specimens were tested for hepatitis B surface antigen and for HBV DNA. RESULTS: We followed 334 children for 3151 person-years (median, 10 years per child) with 1610 specimens collected. Anti-HBs concentrations dropped rapidly among all participants. Among children 2, 5 and 10 years of age, 37 of 79 (47%), 33 of 176 (19%) and 8 of 95 (8%), respectively, had anti-HBs concentrations of >/= 10 mIU/mL. Receipt of recombinant vaccine was significantly associated with a more rapid antibody decline (P < 0.001). Six (1.8%) children acquired anti-HBc, 3 of whom had definite breakthrough infections (at least 2 consecutive anti-HBc-positive specimens or at least 1 anti-HBc-positive specimen and HBV DNA detection by PCR). None of these children had detectable hepatitis B surface antigen, and none had symptoms of hepatitis. CONCLUSIONS: Anti-HBs concentrations declined over time among AN infants successfully immunized with HB vaccine starting at birth. Transient anti-HBc appeared in a small percentage of children; however, none developed clinical signs of hepatitis or chronic HBV infection.

Risk factors for hepatitis B in an outbreak of hepatitis B and D among injection drug users.

During January-April, 2000, 12 cases of acute hepatitis B were reported in Pierce County, Washington, compared with seven in all of 1999. Seven (58.3%) case patients were injection drug users (IDUs), three of whom were coinfected with hepatitis D virus (HDV) and died of fulminant hepatitis. Vaccination clinics were implemented at the local health department and needle exchange program to control the outbreak. We investigated this outbreak to determine risk factors for hepatitis B virus (HBV) transmission among IDUs. Hepatitis B cases were ascertained through routine surveillance and prevaccination testing at vaccination clinics. We conducted a case-control study comparing IDU case patients with HBV-susceptible IDUs identified at the vaccination clinics. Fifty-eight case patients were identified during January-December, 2000, 20 (34.5%) of whom were coinfected with HDV. Thirty-eight case patients (65.5%) reported current IDU. In the case-control study, the 17 case patients were more likely than the 141 controls to report having more than one sex partner [odds ratio (OR) =4.8, 95% confidence interval (CI) =1.5-15.0], injecting more than four times a day (OR = 4.5, 95% CI =1.2-15.6) and sharing drug cookers with more than two people (58.8% vs. 14.0%, OR =14.0, 95% CI =2.4-81.5). Results were similar after controlling for syringe sharing in multivariable analysis. IDUs should be vaccinated against hepatitis B and should be advised against sharing drug injection equipment.