Yulin Lin

Hepatitis C Virus Infections from Unsafe Injection Practices at an Endoscopy Clinic in Las Vegas, Nevada, 2007–2008

BACKGROUND In January 2008, 3 persons with acute hepatitis C who all underwent endoscopy at a single facility in Nevada were identified. METHOD We reviewed clinical and laboratory data from initially detected cases of acute hepatitis C and reviewed infection control practices at the clinic where case patients underwent endoscopy. Persons who underwent procedures on days when the case patients underwent endoscopy were tested for hepatitis C virus (HCV) infection and other bloodborne pathogens. Quasispecies analysis determined the relatedness of HCV in persons infected. RESULTS In addition to the 3 initial cases, 5 additional cases of clinic-acquired HCV infection were identified from 2 procedure dates included in this initial field investigation. Quasispecies analysis revealed 2 distinct clusters of clinic-acquired HCV infections and a source patient related to each cluster, suggesting separate transmission events. Of 49 HCV-susceptible persons whose procedures followed that of the source patient on 25 July 2007, 1 (2%) was HCV infected. Among 38 HCV-susceptible persons whose procedures followed that of another source patient on 21 September 2007, 7 (18%) were HCV infected. Reuse of syringes on single patients in conjunction with use of single-use propofol vials for multiple patients was observed during normal clinic operations. CONCLUSIONS Patient-to-patient transmission of HCV likely resulted from contamination of single-use medication vials that were used for multiple patients during anesthesia administration. The resulting public health notification of approximately 50,000 persons was the largest of its kind in United States health care. This investigation highlighted breaches in aseptic technique, deficiencies in oversight of outpatient settings, and difficulties in detecting and investigating such outbreaks.

Multiple Clusters of Hepatitis Virus Infections Associated With Anesthesia for Outpatient Endoscopy Procedures

BACKGROUND & AIMS Hepatitis B virus (HBV) and hepatitis C virus (HCV) can be transmitted during administration of intravenous anesthesia when medication vials are used for multiple patients using incorrect technique. We investigated an outbreak of acute HBV and HCV infections among patients who received anesthesia during endoscopy procedures from the same anesthesiologist (anesthesiologist 1), in 2 different gastroenterology clinics. METHODS Chart reviews, patient interviews, clinic site visits and infection control assessments, and molecular sequencing of patient isolates were performed. Patients treated by anesthesiologist 1 on specific procedure days were offered testing for blood-borne pathogens. Endoscopy and anesthesia procedures were reviewed; HCV quasispecies analysis was performed. RESULTS Six cases of outbreak-associated HCV infection and 6 cases of outbreak-associated HBV infection were identified in clinic 1. One outbreak-associated HCV infection was identified in clinic 2. HCV quasispecies sequences from the patients were nearly identical (96.9%-100%) to those from source patients with chronic viral hepatitis. All affected patients in both clinics received propofol from anesthesiologist 1, who inappropriately used a single-patient-use vial of propofol for multiple patients. Reuse of syringes to redose patients, with resulting contamination of medication vials used for subsequent patients, likely resulted in viral transmission. CONCLUSIONS Twelve persons acquired HBV and HCV infections (6 hepatitis C, 5 hepatitis B, and 1 coinfection) in 2 separate offices as a result of receiving anesthesia from anesthesiologist 1. Gastroenterologists are urged to review carefully the injection, medication handling, and other infection control practices of all staff under their supervision, including providers of anesthesia services.

Accurate Genetic Detection of Hepatitis C Virus Transmissions in Outbreak Settings

Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections are associated with unsafe injection practices, drug diversion, and other exposures to blood and are difficult to detect and investigate. Here, we developed and validated a simple approach for molecular detection of HCV transmissions in outbreak settings. We obtained sequences from the HCV hypervariable region 1 (HVR1), using end-point limiting-dilution (EPLD) technique, from 127 cases involved in 32 epidemiologically defined HCV outbreaks and 193 individuals with unrelated HCV strains. We compared several types of genetic distances and calculated a threshold, using minimal Hamming distances, that identifies transmission clusters in all tested outbreaks with 100% accuracy. The approach was also validated on sequences obtained using next-generation sequencing from HCV strains recovered from 239 individuals, and findings showed the same accuracy as that for EPLD. On average, the nucleotide diversity of the intrahost population was 6.2 times greater in the source case than in any incident case, allowing the correct detection of transmission direction in 8 outbreaks for which source cases were known. A simple and accurate distance-based approach developed here for detecting HCV transmissions streamlines molecular investigation of outbreaks, thus improving the public health capacity for rapid and effective control of hepatitis C.

Transmission of Hepatitis C Virus During Myocardial Perfusion Imaging in an Outpatient Clinic

Reports of health care--associated viral hepatitis transmission have been increasing in the United States. Transmission due to poor infection control practices during myocardial perfusion imaging (MPI) has not previously been reported. The aim of this study was to identify the source of incident hepatitis C virus (HCV) infection in a patient without identified risk factors who had undergone MPI 6 weeks before diagnosis. Practices at the cardiology clinic and nuclear pharmacy were evaluated, and HCV testing was performed in patients with shared potential exposures. Clinical and epidemiologic information was obtained for patients with HCV infection, and molecular testing was performed to assess viral relatedness. Evidence of HCV transmission among patients who had undergone MPI at the cardiology clinic on 2 separate dates was found, involving 2 potential source patients and a total of 5 newly infected patients. Molecular testing identified a high degree of genetic homology among viruses from patients with common procedure dates. The nuclear medicine technologist routinely drew up flush from multidose vials of saline solution using the same needle and syringe that had been used to administer radiopharmaceutical doses. Multipatient use of vials was not observed, but a review of purchasing invoices and interviews with staff members suggested that this had occurred. No evidence of transmission via contamination of radiopharmaceuticals at the nuclear pharmacy was found. In conclusion, transmission of HCV occurred because of unsafe injection practices during MPI. Cardiologists should carefully review their infection control practices and the practices of other staff members involved with these procedures.

Health Care–Associated Hepatitis C Virus Infections Attributed to Narcotic Diversion

BACKGROUND Three cases of genetically related hepatitis C virus (HCV) infection that were unattributable to infection control breaches were identified at a health care facility. OBJECTIVE To investigate HCV transmission from an HCV-infected health care worker to patients through drug diversion. DESIGN Cluster and look-back investigations. SETTING Acute care hospital and affiliated multispecialty clinic. PATIENTS Inpatients and outpatients during the period of HCV transmission. MEASUREMENTS Employee work and narcotic dispensing records, blood testing for HCV antibody and RNA, and sequencing of the NS5B gene and the hypervariable region 1 of the E2 gene. RESULTS 21 employees were recorded as being at work or as retrieving a narcotic from an automated dispensing cabinet in an area where a narcotic was administered to each of the 3 case patients; all employees provided blood samples for HCV testing. One employee was infected with HCV that had more than 95% NS5B sequence homology with the HCV strains of the 3 case patients. Quasi-species analysis showed close genetic relatedness with variants from each of the case patients and more than 97.9% nucleotide identity. The employee acknowledged parenteral opiate diversion. An investigation identified 6132 patients at risk for exposure to HCV because of the drug diversion. Of the 3929 living patients, 3444 (87.7%) were screened for infection. Two additional cases of genetically related HCV infection attributable to the employee were identified. LIMITATION Of the living patients at risk for HCV exposure, 12.3% were not tested. CONCLUSION Five cases of HCV infection occurring over 3 to 4 years were attributed to drug diversion by an HCV-infected health care worker. Studies of drug diversion and assessments of strategies to prevent narcotics tampering in all health care settings are needed. PRIMARY FUNDING SOURCE None.

Outbreak of hepatitis C virus infection associated with narcotics diversion by an hepatitis C virus–infected surgical technician

BACKGROUND Drug diversion by health care personnel poses a risk for serious patient harm. Public health identified 2 patients diagnosed with acute hepatitis C virus (HCV) infection who shared a common link with a hospital. Further investigation implicated a drug-diverting, HCV-infected surgical technician who was subsequently employed at an ambulatory surgical center. METHODS Patients at the 2 facilities were offered testing for HCV infection if they were potentially exposed. Serum from the surgical technician and patients testing positive for HCV but without evidence of infection before their surgical procedure was further tested to determine HCV genotype and quasi-species sequences. Parenteral medication handling practices at the 2 facilities were evaluated. RESULTS The 2 facilities notified 5970 patients of their possible exposure to HCV, 88% of whom were tested and had results reported to the state public health departments. Eighteen patients had HCV highly related to the surgical technicians virus. The surgical technician gained unauthorized access to fentanyl owing to limitations in procedures for securing controlled substances. CONCLUSIONS Public health surveillance identified an outbreak of HCV infection due to an infected health care provider engaged in diversion of injectable narcotics. The investigation highlights the value of public health surveillance in identifying HCV outbreaks and uncovering a method of drug diversion and its impacts on patients.

Evaluation of viral heterogeneity using next-generation sequencing, end-point limiting-dilution and mass spectrometry

Hepatitis C Virus sequence studies mainly focus on the viral amplicon containing the Hypervariable region 1 (HVR1) to obtain a sample of sequences from which several population genetics parameters can be calculated. Recent advances in sequencing methods allow for analyzing an unprecedented number of viral variants from infected patients and present a novel opportunity for understanding viral evolution, drug resistance and immune escape. In the present paper, we compared three recent technologies for amplicon analysis: (i) Next-Generation Sequencing; (ii) Clonal sequencing using End-point Limiting-dilution for isolation of individual sequence variants followed by Real-Time PCR and sequencing; and (iii) Mass spectrometry of base-specific cleavage reactions of a target sequence. These three technologies were used to assess intra-host diversity and inter-host genetic relatedness in HVR1 amplicons obtained from 38 patients (subgenotypes 1a and 1b). Assessments of intra-host diversity varied greatly between sequence-based and mass-spectrometry-based data. However, assessments of inter-host variability by all three technologies were equally accurate in identification of genetic relatedness among viral strains. These results support the application of all three technologies for molecular epidemiology and population genetics studies. Mass spectrometry is especially promising given its high throughput, low cost and comparable results with sequence-based methods.

Detection of Hepatitis C Virus Transmission by Use of DNA Mass Spectrometry

The molecular detection of transmission of rapidly mutating pathogens such as hepatitis C virus (HCV) is commonly achieved by assessing the genetic relatedness of strains among infected patients. We describe the development of a novel mass spectrometry (MS)-based approach to identify HCV transmission. MS was used to detect products of base-specific cleavage of RNA molecules obtained from HCV polymerase chain reaction fragments. The MS-peak profiles were found to reflect variation in the HCV genomic sequence and the intrahost composition of the HCV population. Serum specimens originating from 60 case patients from 14 epidemiologically confirmed outbreaks and 25 unrelated controls were tested. Neighbor-joining trees constructed using MS-peak profile-based Hamming distances showed 100% accuracy, and linkage networks constructed using a threshold established from the Hamming distances between epidemiologically unrelated cases showed 100% sensitivity and 99.93% specificity in transmission detection. This MS-based approach is rapid, robust, reproducible, cost-effective, and applicable to investigating transmissions of other pathogens.

Automated quality control for a molecular surveillance system

BackgroundMolecular surveillance and outbreak investigation are important for elimination of hepatitis C virus (HCV) infection in the United States. A web-based system, Global Hepatitis Outbreak and Surveillance Technology (GHOST), has been developed using Illumina MiSeq-based amplicon sequence data derived from the HCV E1/E2-junction genomic region to enable public health institutions to conduct cost-effective and accurate molecular surveillance, outbreak detection and strain characterization. However, as there are many factors that could impact input data quality to which the GHOST system is not completely immune, accuracy of epidemiological inferences generated by GHOST may be affected. Here, we analyze the data submitted to the GHOST system during its pilot phase to assess the nature of the data and to identify common quality concerns that can be detected and corrected automatically.ResultsThe GHOST quality control filters were individually examined, and quality failure rates were measured for all samples, including negative controls. New filters were developed and introduced to detect primer dimers, loss of specimen-specific product, or short products. The genotyping tool was adjusted to improve the accuracy of subtype calls. The identification of “chordless” cycles in a transmission network from data generated with known laboratory-based quality concerns allowed for further improvement of transmission detection by GHOST in surveillance settings. Parameters derived to detect actionable common quality control anomalies were incorporated into the automatic quality control module that rejects data depending on the magnitude of a quality problem, and warns and guides users in performing correctional actions. The guiding responses generated by the system are tailored to the GHOST laboratory protocol.ConclusionsSeveral new quality control problems were identified in MiSeq data submitted to GHOST and used to improve protection of the system from erroneous data and users from erroneous inferences. The GHOST system was upgraded to include identification of causes of erroneous data and recommendation of corrective actions to laboratory users.