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Recovery of Infectious Hepatitis C Virus From Injection Paraphernalia: Implications for Prevention Programs Serving People Who Inject Drugs
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The Journal of Infectious Diseases 17 January 2018
Robert Heimer,1 Mawuena Binka,1 Stephen Koester,2 Jean-Paul C. Grund,3 Amisha Patel,1 Elijah Paintsil,1,4 and Brett D. Lindenbach5
1Department of the Epidemiology Microbial Diseases, Yale University School of Public Health, New Haven, Connecticut; 2Department of Anthropology, University of Colorado, Denver; 3Addiction Research Centre, Utrecht, the Netherlands; Department of Addictology, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, the Czech Republic; Freudenthal Institute for Science and Mathematics Education, Utrecht, the Netherlands; Departments of 4Pediatrics and 5Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut

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.
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.
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%).
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.
Assignment of causality requires validating a set of assumptions; such a set of 9 criteria, set forth by Hill [40], includes biological gradient, plausibility, and experiment. Although the prior set of epidemiological studies [7-10] found strong correlations between the sharing of drug preparation paraphernalia and HCV incidence and established temporality and consistency, those studies could not differentiate between the 2 alternativeexplanations as to how sharing of paraphernalia other than needles or syringes produced HCV transmission. We have now provided biological evidence that the more compelling explanation for the association is that sharing of objects associated with the preparation but not the actual injection of drugs is a surrogate for shared injections in which the virus is introduced from a contaminated syringe. We have produced evidence that we can "follow the blood", and the HCV from a contaminated input syringe ends up in a second receptive syringe, leaving less virus behind in the input syringe and little or no virus in drug preparation paraphernalia.
The conclusion is reinforced if we focus our attention only on the data from syringes with fixed needles, syringes routinely used for the injection of insulin. This style of syringe is most commonly used by PWID in the United States and Canada and is the type overwhelmingly available in pharmacies and supplied by syringe exchange programs. The experimental procedures we describe in this report are equivalent to rinsing the input syringe with water, and, as past work has shown, a single rinse of this type of syringe can greatly reduce the HCV recovery [41]. So it is not surprising that our recovery of HCV from input syringes with fixed needles was negligible. Furthermore, work over the past decade by a group of researchers, including us, has highlighted the increased risk of bloodborne virus transmission that results from using syringes with detachable rather than fixed needles [25, 36, 37, 39, 42, 43].
Our findings on the retention of HCV in filters differ somewhat from that produced from similar laboratory simulations by Doerrbecker et al [44]. In their experiments, they passed 800 μL of fluid containing approximately 105 TCID50/mL through filters. This is far in excess of the 2 to 100 μL of HCV-contaminated fluid that might remain inside a used syringe that is being reused to prepare drugs for injection [25, 36-38]. Although we recovered an average of 23107 ± 13 870 RLU from receptive syringes using inputs from syringes with detachable needles, inputs of 105 TCID50/mL would yield >2 x 106 RLU in our microculture system [25]. Therefore, the experimental protocol of Doerrbecker et al [44] used HCV inputs that are 2 orders of magnitude higher than would occur under "real-world" conditions in which drugs are prepared, shared, and injected, whereas our experimental procedure more closely replicates those conditions.
Our findings on the stability of virus over time in the experiments pooling filters found rapid attenuation of infectivity in the input syringes and filters. This is consistent with our previous findings when titers of HCV are initially low and with findings on the duration of infectivity noted by Doerrbecker et al [25, 45]. A study by Ciesek et al [32], similar to that of Doerrrbecker et al [45], used an amount of HCV that was 10-fold higher than we did, so the results are not directly comparable.
As noted by Glass et al [46], once causality in the public health realm is firmly established, appropriate interventions can follow. In this case, it should lead us to reconsider policies, widely adapted by syringe exchange and other harm reduction programs, to provide clean cookers and filters along with sterile syringes when attempting to reduce the transmission of HCV. At a minimum, our findings should compel programs that serve PWID to focus more on the process of drug preparation and injection and less on the preparation paraphernalia. Going further, programs may want to reconsider expanding scarce resources to provide supplies that will do little or nothing to prevent HCV transmission. Given the usual situation of limited financial resources facing syringe exchange and related harm reduction programs, spending money on objects that can have little impact on disease transmission should come to be viewed as profligate. Money spent on cookers and filters would be better spent on giving away more syringes. Because HCV and HIV transmission are more likely if the syringe has a detachable rather than a fixed needle, efforts should focus on providing more syringes with fixed needles. An alternative for people who need syringes with detachable needles is to develop and market reduced dead space syringes [39, 43].
One additional way to improve bloodborne virus prevention efforts is providing guidance and materials to reduce the chances of using contaminated syringes to prepare or apportion drug. One such piece of drug preparation material could be syringes without accompanying needles that could be used to introduce water into cookers or apportion dissolved drugs. Lacking a needle, such a syringe is unlikely to become contaminated with HCV unless the water source itself was contaminated. Provision of sterile water supplies and training to minimize the commingling of water sources used to prepare drugs and rinse used syringes will do more than the provision of cookers and filters to prevent HCV transmission. There are 3 significant limitations to our work. First, we are using an in vitro system that is strongly parallel but not identical to the real-world situation, most notably in that it uses a chimeric virus derived from a genotype 2a virus that may not reflect survival and infectivity characteristics of the viruses passed among PWID or when patient-derived viruses are tested in culture. Second, the predominant genotypes among PWID worldwide are genotypes 1 and 3, so it would be useful to replicate our findings with viruses of these genotypes should they become available. If we were to validate our findings using genotype 1 and 3 viruses, it would strengthen the argument about refocusing prevention messaging and the provision of drug preparation and injection supplies more on needles and syringes and less on cookers and filters. Finally, our experiments are replications, reduced realities of real-world situations that are contingent on a host of interacting drug, set, and setting variables [47-50]. Although we have tried to select and replicate a worst-case scenario, we cannot describe the full range of HCV transmission risk that injectors experience.
Our studies reinforce the need for expanded education efforts and further environmental interventions, such as upscaling distribution of syringes with fixed needles or with reduced dead space to decrease the likelihood for HCV transmission among PWID. These syringes retain less fluid than syringes with detachable needles, and hence less HCV should the person using the syringe be actively infected, and, as previously shown, HCV infectivity persists for a shorter time [25]. Furthermore, as the current study demonstrates, there is less likelihood that shared drug preparation paraphernalia will harbor infectious virus. Given all these benefits, we would advise syringe access and harm reduction education programs to emphasize the distribution of insulin-type syringes with fixed needles and de-emphasize and not expend limited program resources on the distribution of cookers and filters.

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