Recovery of Infectious Hepatitis C Virus From Injection Paraphernalia: Implications for Prevention Programs Serving People Who Inject Drugs.

Background: Controlling hepatitis C virus (HCV) transmission among people who inject drugs (PWID) has focused on preventing sharing syringes and drug preparation paraphernalia, but it is unclear whether HCV incidence linked to sharing paraphernalia reflects contamination of the paraphernalia or syringe-mediated contamination when drugs are shared. Methods: In experiments designed to replicate real-world injection practices when drugs are shared, the residual contents of HCV-contaminated syringes with detachable or fixed needled were passed through the "cookers" and filters used by PWID in preparing drugs for injection and then introduced into a second syringe. All items were tested for the presence of infectious HCV using a chimeric HCV with a luciferase gene. Results: Hepatitis C virus could not be recovered from cookers regardless of input syringe type or cooker design. Recovery was higher when comparing detachable needles to fixed needles for residue in input syringes (73.8% vs 0%), filters (15.4% vs 1.4%), and receptive syringes (93.8% vs 45.7%). Conclusions: Our results, consistent with the hypothesis that sharing paraphernalia does not directly result in HCV transmission but is a surrogate for transmissions resulting from sharing drugs, have important implications for HCV prevention efforts and programs that provide education and safe injection supplies for PWID populations.

Recovering Infectious HIV from Novel Syringe-Needle Combinations with Low Dead Space Volumes.

This study determines if detachable syringe-needle combinations redesigned to reduce their dead space volume may substantially reduce the burden of exposure to infectious HIV among people who inject drugs. Two novel, low dead space (LDS) syringe-needle designs-one added a piston to the plunger (LDS syringe) and the other added a filler to the needle (LDS needle) to reduce their dead space-were compared to standard detachable needle-syringe combinations and to syringes with fixed needles. LDS and standard syringes attached to LDS and standard needles of 23-, 25-, and 27-gauge size were contaminated with HIV-infected blood in the laboratory. The proportion of syringe-needle combinations containing infectious HIV was analyzed after syringes were (1) stored up to 7 days at 22°C or (2) rinsed with water. Detachable syringes attached to 25-gauge needles yielded comparable proportions of syringes with infectious HIV, whether the needle was standard or LDS. Among needles of greater diameter (23 gauge), LDS needles tended to reduce recoverable HIV to a greater extent than standard needles. Syringes with fixed needles showed superior results to LDS syringes attached to needles of equivalent diameter and were less likely to get clogged by blood. Detachable LDS syringe-needle designs must be recommended with caution since they still pose potential risk for HIV transmission. Distribution of LDS syringes and needles must be accompanied by recommendations and instructions for their proper rinsing and disinfection in order to reduce viral burden and chances of needle clogging.

Survival of Hepatitis C Virus in Syringes Is Dependent on the Design of the Syringe-Needle and Dead Space Volume.

BACKGROUND: Many people who inject drugs (PWID) use syringes with detachable needles, which have high dead space (HDS). Contaminated HDS blood may substantially contribute to the transmission of HIV, hepatitis C (HCV), and other blood-borne viruses within this population. Newly designed low dead space (LDS) syringe-needle combinations seek to reduce blood-borne virus transmission among PWID. We evaluated the infectivity of HCV-contaminated residual volumes recovered from two LDS syringe-needle combinations. METHODS: We tested two different design approaches to reducing the dead space. One added a piston to the plunger; the other reduced the dead space within the needle. The two approaches cannot be combined. Recovery of genotype-2a reporter HCV from LDS syringe-needle combinations was compared to recovery from insulin syringes with fixed needles and standard HDS syringe-needle combinations. Recovery of HCV from syringes was determined immediately following their contamination with HCV-spiked plasma, after storage at 22°C for up to 1 week, or after rinsing with water. RESULTS: Insulin syringes with fixed needles had the lowest proportion of HCV-positive syringes before and after storage. HCV recovery after immediate use ranged from 47%±4% HCV-positive 1 mL insulin syringes with 27-gauge ½ inch needles to 98%±1% HCV-positive HDS 2 mL syringes with 23-gauge 1» inch detachable needles. LDS combinations yielded recoveries ranging from 65%±5% to 93%±3%. Recovery was lower in combinations containing LDS needles than LDS syringes. After 3 days of storage, as much as 6-fold differences in virus recovery was observed, with HCV recovery being lower in combinations containing LDS needles. Most combinations with detachable needles required multiple rinses to reduce HCV infectivity to undetectable levels whereas a single rinse of insulin syringes was sufficient. CONCLUSIONS: Our study, the first to assess the infectivity of HCV in residual volumes of LDS syringes and needles available to PWID, demonstrates that LDS syringe-needle combination still has the greater potential for HCV transmission than insulin syringes with fixed needles. Improved LDS designs may be able to further reduce HCV recovery, but based on the designed tested, LDS needles and syringes remain intermediate between fixed-needle syringes and HDS combinations in reducing exposure to HCV.

Incarceration is associated with used syringe lending among active injection drug users with detectable plasma HIV-1 RNA: a longitudinal analysis.

BACKGROUND: Informed by recent studies demonstrating the central role of plasma HIV-1 RNA viral load (VL) on HIV transmission, interventions to employ HIV antiretroviral treatment as prevention (TasP) are underway. To optimize these efforts, evidence is needed to identify factors associated with both non-suppressed VL and HIV risk behaviours. Thus, we sought to assess the possible role played by exposure to correctional facilities on VL non-suppression and used syringe lending among HIV-seropositive people who use injection drugs (PWID). METHODS: We used data from the ACCESS study, a community-recruited prospective cohort. We used longitudinal multivariate mixed-effects analyses to estimate the relationship between incarceration and plasma HIV-1 RNA > 500 copies/mL among antiretroviral therapy (ART)-exposed active PWID and, during periods of non-suppression, the relationship between incarceration and used syringe lending. RESULTS: Between May 1996 and March 2012, 657 ART-exposed PWID were recruited. Incarceration was independently associated with higher odds of VL non-suppression (Adjusted Odds Ratio [AOR] = 1.54, 95% Confidence Interval [95% CI]: 1.10, 2.16). In a separate multivariate model restricted to periods of VL non-suppression, incarceration was independently associated with lending used syringes (AOR = 1.81, 95% CI: 1.03, 3.18). CONCLUSIONS: The current findings demonstrate that incarceration is associated with used syringe lending among active PWID with detectable plasma HIV-1 RNA. Our results provide a possible pathway for the commonly observed association between incarceration and increased risk of HIV transmission. Our results suggest that alternatives to incarceration of non-violent PWID and evidence-based combination HIV prevention interventions for PWID within correctional facilities are urgently needed.

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.

"Injection first": a unique group of injection drug users in Tijuana, Mexico.

Using baseline data from a study of injection drug users (IDUs) in Tijuana, Mexico (N = 1,052), we identified social and behavioral factors associated with injecting at the same age or earlier than other administration routes of illicit drug use (eg, "injection first") and examined whether this IDU subgroup had riskier drug using and sexual behaviors than other IDUs. Twelve-percent "injected first." Characteristics independently associated with a higher odds of "injection first" included being younger at first injection, injecting heroin as their first drug, being alone at the first injection episode, and having a sexual debut at the same age or earlier as when they initiated drug use; family members' illicit drug use was associated with lower odds of injecting first. When adjusting for age at first injection and number of years injecting, "injection first" IDUs had lower odds of ever overdosing, and ever trading sex. On the other hand, they were less likely to have ever been enrolled in drug treatment, and more commonly obtained their syringes from potentially unsafe sources. In conclusion, a sizable proportion of IDUs in Tijuana injected as their first drug using experience, although evidence that this was a riskier subgroup of IDUs was inconclusive.

Hepatitis C transmission in injection drug users: could swabs be the main culprit?

Prevention programs for intravenous drug users have proven their efficacy in decreasing human immunodeficiency virus transmission but have limited effect on hepatitis C virus (HCV) contamination. A study was conducted to document the presence of HCV genome (HCV RNA) in 620 items of used injecting paraphernalia collected from representative sites. Using sensitive molecular techniques, HCV RNA was not detected on used filters or water vials and was seldom detected on cups (9%). However, HCV RNA was frequently found on syringe pools (38%) and on swabs (82%) at high titers. Our investigation, which was conducted in real injecting settings, highlights swabs as a potential source for HCV transmission.

[Nosocomial transmission of hepatitis C associated with anesthesia procedures: a case-control study]. / Transmisión nosocomial de la hepatitis C asociada a procedimientos anestésicos: un estudio de casos y controles.

OBJECTIVE: Nosocomial transmission of hepatitis C virus (HCV) infection had been related with anesthesia procedures. The study aim was to measure the association between anesthesia procedures in cases with previous surgery and HCV infection. MATERIAL AND METHODS: In a case-control study were included subjects that attended to the Central Blood Bank of the West Medical National Center, Mexican Institute of the Social Security in Guadalajara, Jalisco between july 2005 and september 2007. Cases were patients with positive hepatitis C antibody (anti-HCV) confirmed by recombinant immunoblot assay (RIBA) and/or nucleic acid test (HCV RNA); the control group was blood donors with negative antibody. An exhaustive questionnaire about risk factors for hepatitis C, was applied. The risk of HCV infection was determined with the Odds Ratio (OR) and multivariate analysis was made by logistic regression. RESULTS: We included 362 subjects, 211 cases and 151 controls; in 70 (33.2%) cases were found significant association between the anesthesia procedures and HCV infection in patients with previous surgery (OR adjusted 2.44, CI 95% 1.44 - 4.11) CONCLUSION: This is the first study in México that demonstrate association between history of anesthesia procedures and HCV infection in cases with previous surgery.

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.

An outbreak of hepatitis B with high mortality in India: association with precore, basal core promoter mutants and improperly sterilized syringes.

In 2009, an outbreak of hepatitis B with high mortality was observed in Sabarkantha district, Gujarat state, India with 456 cases and 89 deaths. Hospitalized patients with self-limiting disease (152, AVH)) and fulminant hepatic failure (39, FHF including 27 fatal and 12 survivals) were investigated. These were screened for diagnostic markers for hepatitis viruses, hepatitis B virus (HBV) genotyping and mutant analysis. Complete HBV genomes from 22 FHF and 17 AVH cases were sequenced. Serosurveys were carried out in the most and least affected blocks for the prevalence of HBV and identification of mutants. History of injection from a physician was associated with FHF and AVH cases. Co-infection with other hepatitis viruses or higher HBV DNA load was not responsible for mortality. Four blocks contributed to 85.7% (391/456) of the cases and 95.5% (85/89) mortality while two adjacent blocks had negligible mortality. Sequence analysis showed the presence of pre-core and basal core promoter mutants and 4 amino acid substitutions exclusively among FHF cases. None of the self-limiting patients exhibited these dual mutations. Genotype D was predominant, D1 being present in all FHF cases while D2 was most prevalent in AVH cases. Probably due to violation of accepted infection control procedures by the qualified medical practitioners, HBV prevalence was higher in the affected blocks before the outbreak. Gross and continued use of HBV contaminated (mutant and wild viruses) injection devices led to an explosive outbreak with high mortality with a striking association with pre-C/BCP mutants and D1 genotype.

Transmisión nosocomial de la hepatitis C asociada a procedimientos anestésicos: un estudio de casos y controles

OBJETIVO: Medir la asociación entre el antecedente de procedimientos anestésicos y el riesgo de infección por el virus de la hepatitis C (VHC) en pacientes con cirugía previa. MATERIAL Y MÉTODOS: Diseño de casos y controles; los casos fueron pacientes con anticuerpo (anti-VHC) positivo confirmado por RIBA y/o RNA VHC y los controles fueron sujetos con el anti-VHC negativo. El riesgo de infección se estimó por razón de momios (RM) y análisis multivariado con regresión logística. RESULTADOS: Se incluyeron 362 sujetos, 211 casos y 151 controles; en 70 casos (33.2 por ciento), con cirugía previa, los procedimientos anestésicos se identificaron como único factor de riesgo significativo para la infección por el VHC (RM ajustada 2.44, IC 95 por ciento 1.44 - 4.11). CONCLUSIONES: Este es el primer estudio en México que demuestra asociación de riesgo significativa con el antecedente de procedimientos anestésicos por cirugía previa, en uno de cada tres enfermos con hepatitis C.

OBJECTIVE: Nosocomial transmission of hepatitis C virus (HCV) infection had been related with anesthesia procedures. The study aim was to measure the association between anesthesia procedures in cases with previous surgery and HCV infection. MATERIAL AND METHODS: In a case-control study were included subjects that attended to the Central Blood Bank of the West Medical National Center, Mexican Institute of the Social Security in Guadalajara, Jalisco between july 2005 and september 2007. Cases were patients with positive hepatitis C antibody (anti-HCV) confirmed by recombinant immunoblot assay (RIBA) and/or nucleic acid test (HCV RNA); the control group was blood donors with negative antibody. An exhaustive questionnaire about risk factors for hepatitis C, was applied. The risk of HCV infection was determined with the Odds Ratio (OR) and multivariate analysis was made by logistic regression. RESULTS: We included 362 subjects, 211 cases and 151 controls; in 70 (33.2 percent) cases were found significant association between the anesthesia procedures and HCV infection in patients with previous surgery (OR adjusted 2.44, CI 95 percent 1.44 - 4.11) CONCLUSION: This is the first study in México that demonstrate association between history of anesthesia procedures and HCV infection in cases with previous surgery.

Survival of hepatitis C virus in syringes: implication for transmission among injection drug users.

BACKGROUND: We hypothesized that the high prevalence of hepatitis C virus (HCV) among injection drug users might be due to prolonged virus survival in contaminated syringes. METHODS: We developed a microculture assay to examine the viability of HCV. Syringes were loaded with blood spiked with HCV reporter virus (Jc1/GLuc2A) to simulate 2 scenarios of residual volumes: low void volume (2 microL) for 1-mL insulin syringes and high void volume (32 microL) for 1-mL tuberculin syringes. Syringes were stored at 4 degrees C, 22 degrees C, and 37 degrees C for up to 63 days before testing for HCV infectivity by using luciferase activity. RESULTS: The virus decay rate was biphasic (t1/2alpha= 0.4 h and t1/2beta = 28 hh). Insulin syringes failed to yield viable HCV beyond day 1 at all storage temperatures except 4 degrees , in which 5% of syringes yielded viable virus on day 7. Tuberculin syringes yielded viable virus from 96%, 71%, and 52% of syringes after storage at 4 degrees, 22 degrees, and 37 degrees for 7 days, respectively, and yielded viable virus up to day 63. CONCLUSIONS: The high prevalence of HCV among injection drug users may be partly due to the resilience of the virus and the syringe type. Our findings may be used to guide prevention strategies.

Modeling the effect of high dead-space syringes on the human immunodeficiency virus (HIV) epidemic among injecting drug users.

AIMS: To illustrate the impact of different proportions of injecting drug users (IDUs) sharing high dead-space syringes (HDSS) or low dead-space syringes (LDSS) on the probability of human immunodeficiency virus (HIV) transmission; and thus the impact on injection-related HIV prevalence and incidence. DESIGN: A stochastic mathematical model was used to evaluate the impact of HDSS use in high- and low-risk IDU populations. Model parameters were obtained from peer-reviewed publications. Analytical solutions of a simplified deterministic model were obtained to explain the effect of HDSS on HIV endemic states. FINDINGS: Simulation analysis shows that the HIV epidemic could be sustained even when a small percentage of sharing (10%) involved HDSS. The effect is much stronger in high-risk compared with low-risk populations. Steady state HIV prevalence increases with the proportion of HDSS, and for high- and low-risk populations reaches around 80% and 20%, respectively. For low-risk populations, the use of LDSS could result in the virtual elimination of HIV. These results are dependent upon an evidence-supported assumption of a significant difference in HIV transmission risk associated with HDSS versus LDSS. CONCLUSIONS: Our models suggest that injection-related HIV epidemics may not occur when most (e.g. 95% or more) IDUs use LDSS. While these results are based on indirect risk measures and a number of simplifying assumptions, the effect of blood retained in high dead-space syringes on HIV prevalence seems to be very strong, even using relatively conservative assumptions. The findings have potential implications for needle exchange programs and the types of syringes produced and distributed world-wide.

Population risk of syringe reuse: estimating the probability of transmitting bloodborne disease.

BACKGROUND: In 2008, the Medical Officer of Health at Alberta Health Services (Edmonton, Canada) was notified that, in some practice settings, a syringe was used to administer medication through the side port of an intravenous circuit and then the syringe, with residual drug, was used to administer medication to other patients in the same manner. This practice has been implicated in several outbreaks of bloodborne infection in hospital and clinic settings. METHODS: A risk assessment model was developed to predict the risk of a patient contracting a bloodborne viral infection from the practice. The risk of transmission was defined as the product of 5 factors: (1) the population prevalence of a specific bloodborne pathogen, (2) the probability of finding a viral bloodborne pathogen in an intravenous circuit, (3) the rate of syringe reuse, (4) the probability of causing disease given a bloodborne pathogen exposure, and (5) the susceptibility of the exposed person. RESULTS: The risk was modeled first with consistent use of the proximal port of the intravenous circuit. The risk of transmission of hepatitis B virus was approximately 12-53 transmission events per 1,000,000 exposure events for a range of practice probabilities (ie, frequency of the risk practice) from 20% to 80%, respectively. The risk of transmission of hepatitis C virus was approximately 1.0-4.3 transmission events per 1,000,000 exposure events for the same practice probability range, and the risk of transmission of human immunodeficiency virus was approximately 0.03-0.15 transmission events per 1,000,000 exposure events for the same practice probability range. The use of the distal port was associated with a 10-fold decrease in the risk. CONCLUSIONS: Practitioners must practice safe, aseptic injection techniques. The model presented here can be used to estimate the risk of disease transmission in situations where reuse has occurred and can serve as a framework for informing public health action.

US outbreak investigations highlight the need for safe injection practices and basic infection control.

Current understanding of viral hepatitis transmission in United States health care settings indicates progress over the past several decades with respect to the risks from transfusions or blood products. Likewise, risks to health care providers from sharps injuries and other blood and body fluid exposures have been reduced as a consequence of widespread hepatitis B vaccination and the adoption of safer work practices. Increasing recognition of outbreaks involving patient-to-patient spread of hepatitis B and hepatitis C virus infections, however, has uncovered a disturbing trend. This article highlights the importance of basic infection control and the need for increased awareness of safe injection practices.

Statistical design for a small serial dilution series.

We describe statistical plans for a serial dilution series designed to detect and estimate the number of viral particles in a solution. The design addresses a problem when a very limited number of aliquots are available for proliferation. A gamma prior distribution on the number of viral particles allows us to describe the marginal probability distribution of all experimental outcomes. We examine a design that minimizes the expected reciprocal information and compare this with the maximum entropy design. We argue that the maximum entropy design is more useful from the point of view of the laboratory technician. The problem and design are motivated by our study of the viability of human immunodeficiency virus in syringes and other equipment that might mediate blood-borne viral transmission.

Presence of hepatitis C virus in syringes confiscated in prisons in Australia.

BACKGROUND AND AIMS: Needlestick injuries are an occupational hazard for prison officers. This study aimed to assess the presence of hepatitis C virus (HCV) in syringes found in prisons. METHODS: Sixty-nine syringes found in prisons were tested for HCV RNA using previously published methods. RESULTS: Three syringes tested positive for HCV RNA. CONCLUSION: Compared to the prevalence of HCV among injecting drug users in prisons, few syringes were found to contain HCV RNA. It is likely that conditions under which syringes are kept in prisons are not favorable for survival of detectable HCV RNA. Further work is needed to establish the risk of HCV transmission posed by needlestick injuries in prison settings.