Rapid Decline in HCV Incidence among People Who Inject Drugs Associated with National Scale-Up in Coverage of a Combination of Harm Reduction Interventions

Background

Government policy has precipitated recent changes in the provision of harm reduction interventions – injecting equipment provision (IEP) and opiate substitution therapy (OST) – for people who inject drugs (PWID) in Scotland. We sought to examine the potential impact of these changes on hepatitis C virus (HCV) transmission among PWID.

Methods and Findings

We used a framework to triangulate different types of evidence: ‘group-level/ecological’ and ‘individual-level’. Evidence was primarily generated from bio-behavioural cross-sectional surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1–2 months) where the virus is present, but antibodies have not yet been formed, were considered to have recent infection. The survey data were supplemented with service data on the provision of injecting equipment and OST. Ecological analyses examined changes in intervention provision, self-reported intervention uptake, self-reported risk behaviour and HCV incidence; individual-level analyses investigated relationships within the pooled survey data. Nearly 8,000 PWID were recruited in the surveys. We observed a decline in HCV incidence, per 100 person-years, from 13.6 (95% CI: 8.1–20.1) in 2008–09 to 7.3 (3.0–12.9) in 2011–12; a period during which increases in the coverage of OST and IEP, and decreases in the frequency of injecting and sharing of injecting equipment, were observed. Individual-level evidence demonstrated that combined high coverage of needles/syringes and OST were associated with reduced risk of recent HCV in analyses that were unweighted (AOR 0.29, 95%CI 0.11–0.74) and weighted for frequency of injecting (AOR_w 0.05, 95%CI 0.01–0.18). We estimate the combination of harm reduction interventions may have averted 1400 new HCV infections during 2008–2012.

Conclusions

This is the first study to demonstrate that impressive reductions in HCV incidence can be achieved among PWID over a relatively short time period through high coverage of a combination of interventions.     

Agent-Based Model Forecasts Aging of the Population of People Who Inject Drugs in Metropolitan Chicago and Changing Prevalence of Hepatitis C Infections

People who inject drugs (PWID) are at high risk for blood-borne pathogens transmitted during the sharing of contaminated injection equipment, particularly hepatitis C virus (HCV). HCV prevalence is influenced by a complex interplay of drug-use behaviors, social networks, and geography, as well as the availability of interventions, such as needle exchange programs. To adequately address this complexity in HCV epidemic forecasting, we have developed a computational model, the Agent-based Pathogen Kinetics model (APK). APK simulates the PWID population in metropolitan Chicago, including the social interactions that result in HCV infection. We used multiple empirical data sources on Chicago PWID to build a spatial distribution of an in silico PWID population and modeled networks among the PWID by considering the geography of the city and its suburbs. APK was validated against 2012 empirical data (the latest available) and shown to agree with network and epidemiological surveys to within 1%. For the period 2010–2020, APK forecasts a decline in HCV prevalence of 0.8% per year from 44(±2)% to 36(±5)%, although some sub-populations would continue to have relatively high prevalence, including Non-Hispanic Blacks, 48(±5)%. The rate of decline will be lowest in Non-Hispanic Whites and we find, in a reversal of historical trends, that incidence among non-Hispanic Whites would exceed incidence among Non-Hispanic Blacks (0.66 per 100 per years vs 0.17 per 100 person years). APK also forecasts an increase in PWID mean age from 35(±1) to 40(±2) with a corresponding increase from 59(±2)% to 80(±6)% in the proportion of the population >30 years old. Our studies highlight the importance of analyzing subpopulations in disease predictions, the utility of computer simulation for analyzing demographic and health trends among PWID and serve as a tool for guiding intervention and prevention strategies in Chicago, and other major cities.     

Assessing the Long-Term Impact of Treating Hepatitis C Virus (HCV)-Infected People Who Inject Drugs in the UK and the Relationship between Treatment Uptake and Efficacy on Future Infections

ObjectiveThe prevalence of the hepatitis C virus (HCV) remains high amongst people who inject drugs (PWID) and accounts for the majority of newly acquired infections. This study aims to quantify the value of treatment amongst PWID with more efficacious treatments and at increased uptake rates, with respect to the avoidance of future infections and subsequent long-term complications of HCV.MethodsA dynamic HCV transmission and disease progression model was developed, incorporating acute and chronic infection and their long-term complications (decompensated cirrhosis, cancer, liver transplant and mortality), with the potential for HCV transmission to other PWID prior to successful treatment. The model was populated with prevalence and therapy data from a UK setting. Scenarios of current standard of care (SoC) treatment efficacy and uptake were compared to anticipated sustained virologic response (SVR) rates of 90–100% and increased uptake over varied horizons.ResultsSoC led to modest reductions in prevalence; >5% after 200 years. New treatments achieving 90% SVR could reduce prevalence below 5% within 60 years at current uptake rates or within 5 years if all patients are treated. Amongst 4,240 PWID, chronic HCV infections avoided as a result of increasing treatment uptake over the period 2015–2027 ranged from 20–580 and 34–912 with SoC and 90% SVR rates respectively. The reduction in downstream HCV infections due to increasing treatment uptake resulted in an approximate discounted gain of 300 life-years (from avoiding reduced life expectancy from HCV infection) and a gain of 1,700 QALYs (from avoiding the disutility of HCV infection and related complications), with a projected £5.4 million cost saving.ConclusionWhile improved SVR profiles led to reductions in modelled prevalence, increased treatment uptake was the key driver of future infections avoided. Increased treatment among PWID with new more efficacious therapies could significantly change the future dynamics, cost and health burden of HCV-related disease.     

Hepatitis C Virus Infection Epidemiology among People Who Inject Drugs in Europe: A Systematic Review of Data for Scaling Up Treatment and Prevention

Background

People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed.

Methods and Findings

We searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7–28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally ‘difficult to treat’ genotypes (G1+G4) showed large variation (median 53, IQR 43–62). Twelve countries reported on HCV chronicity (median 72, IQR 64–81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2–28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38–64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5–15). Burden of disease, where assessed, was high and will rise in the next decade.

Conclusion

Key data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID.     

Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago

Background/Aim

New direct-acting antivirals (DAAs) provide an opportunity to combat hepatitis C virus (HCV) infection in persons who inject drugs (PWID). Here we use a mathematical model to predict the impact of a DAA-treatment scale-up on HCV prevalence among PWID and the estimated cost in metropolitan Chicago.

Methods

To estimate the HCV antibody and HCV-RNA (chronic infection) prevalence among the metropolitan Chicago PWID population, we used empirical data from three large epidemiological studies. Cost of DAAs is assumed $50,000 per person.

Results

Approximately 32,000 PWID reside in metropolitan Chicago with an estimated HCV-RNA prevalence of 47% or 15,040 cases. Approximately 22,000 PWID (69% of the total PWID population) attend harm reduction (HR) programs, such as syringe exchange programs, and have an estimated HCV-RNA prevalence of 30%. There are about 11,000 young PWID (<30 years old) with an estimated HCV-RNA prevalence of 10% (PWID in these two subpopulations overlap). The model suggests that the following treatment scale-up is needed to reduce the baseline HCV-RNA prevalence by one-half over 10 years of treatment [cost per year, min-max in millions]: 35 per 1,000 [$50-$77] in the overall PWID population, 19 per 1,000 [$20-$26] for persons in HR programs, and 5 per 1,000 [$3-$4] for young PWID.

Conclusions

Treatment scale-up could dramatically reduce the prevalence of chronic HCV infection among PWID in Chicago, who are the main reservoir for on-going HCV transmission. Focusing treatment on PWID attending HR programs and/or young PWID could have a significant impact on HCV prevalence in these subpopulations at an attainable cost.     

The Impact of Contact Tracing in Clustered Populations

The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease.     

Estimating the Number of Persons Who Inject Drugs in the United States by Meta-Analysis to Calculate National Rates of HIV and Hepatitis C Virus Infections

Background

Injection drug use provides an efficient mechanism for transmitting bloodborne viruses, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Effective targeting of resources for prevention of HIV and HCV infection among persons who inject drugs (PWID) is based on knowledge of the population size and disparity in disease burden among PWID. This study estimated the number of PWID in the United States to calculate rates of HIV and HCV infection.

Methods

We conducted meta-analysis using data from 4 national probability surveys that measured lifetime (3 surveys) or past-year (3 surveys) injection drug use to estimate the proportion of the United States population that has injected drugs. We then applied these proportions to census data to produce population size estimates. To estimate the disease burden among PWID by calculating rates of disease we used lifetime population size estimates of PWID as denominators and estimates of HIV and HCV infection from national HIV surveillance and survey data, respectively, as numerators. We calculated rates of HIV among PWID by gender-, age-, and race/ethnicity.

Results

Lifetime PWID comprised 2.6% (95% confidence interval: 1.8%–3.3%) of the U.S. population aged 13 years or older, representing approximately 6,612,488 PWID (range: 4,583,188–8,641,788) in 2011. The population estimate of past-year PWID was 0.30% (95% confidence interval: 0.19 %–0.41%) or 774,434 PWID (range: 494,605–1,054,263). Among lifetime PWID, the 2011 HIV diagnosis rate was 55 per 100,000 PWID; the rate of persons living with a diagnosis of HIV infection in 2010 was 2,147 per 100,000 PWID; and the 2011 HCV infection rate was 43,126 per 100,000 PWID.

Conclusion

Estimates of the number of PWID and disease rates among PWID are important for program planning and addressing health inequities.     

Transitions from injection-drug-use-concentrated to self-sustaining heterosexual HIV epidemics: patterns in the international data

Background

Injecting drug use continues to be a primary driver of HIV epidemics in many parts of the world. Many people who inject drugs (PWID) are sexually active, so it is possible that high-seroprevalence HIV epidemics among PWID may initiate self-sustaining heterosexual transmission epidemics.

Methods

Fourteen countries that had experienced high seroprevalence (<20%) HIV epidemics among PWID and had reliable data for injection drug use (IDU) and heterosexual cases of HIV or AIDS were identified. Graphs of newly reported HIV or AIDS cases among PWID and heterosexuals were constructed to identify temporal relationships between the two types of epidemics. The year in which newly reported cases among heterosexuals surpassed newly reported cases among PWID, aspects of the epidemic curves, and epidemic case histories were analyzed to assess whether it was “plausible” or “highly unlikely” that the HIV epidemic among PWID might have initiated the heterosexual epidemic in each country.

Results

Transitions have occurred in 11 of the 14 countries. Two types of temporal relationships between IDU and heterosexual HIV epidemics were identified, rapid high incidence transitions vs. delayed, low incidence transitions. In six countries it appears “plausible” that the IDU epidemic initiated a heterosexual epidemic, and in five countries it appears “highly unlikely” that the IDU epidemic initiated a heterosexual epidemic. A rapid decline in incidence among PWID after the peak year of new cases and national income were the best predictors of the “highly unlikely” initiation of a heterosexual epidemic.

Discussion

Transitions from IDU concentrated epidemics to heterosexual epidemics are common in countries with high seroprevalence among PWID though there are distinct types of transitions. Interventions to immediately reduce HIV incidence among PWID may reduce the likelihood that an IDU epidemic may initiate a heterosexual epidemic.     

Contact Trees: Network Visualization beyond Nodes and Edges

Node-Link diagrams make it possible to take a quick glance at how nodes (or actors) in a network are connected by edges (or ties). A conventional network diagram of a “contact tree” maps out a root and branches that represent the structure of nodes and edges, often without further specifying leaves or fruits that would have grown from small branches. By furnishing such a network structure with leaves and fruits, we reveal details about “contacts” in our ContactTrees upon which ties and relationships are constructed. Our elegant design employs a bottom-up approach that resembles a recent attempt to understand subjective well-being by means of a series of emotions. Such a bottom-up approach to social-network studies decomposes each tie into a series of interactions or contacts, which can help deepen our understanding of the complexity embedded in a network structure. Unlike previous network visualizations, ContactTrees highlight how relationships form and change based upon interactions among actors, as well as how relationships and networks vary by contact attributes. Based on a botanical tree metaphor, the design is easy to construct and the resulting tree-like visualization can display many properties at both tie and contact levels, thus recapturing a key ingredient missing from conventional techniques of network visualization. We demonstrate ContactTrees using data sets consisting of up to three waves of 3-month contact diaries over the 2004-2012 period, and discuss how this design can be applied to other types of datasets.     

Intimate Injection Partnerships Are at Elevated Risk of High-Risk Injecting: A Multi-Level Longitudinal Study of HCV-Serodiscordant Injection Partnerships in San Francisco,CA

Background

It is increasingly recognized that the risk for HIV and hepatitis C (HCV) transmission among people who inject drugs (PWID), such as syringe sharing, occurs in the context of relationships between (at least) two people. Evidence suggests that the risk associated with injection behavior varies with injection partner types.

Methods

We utilized longitudinal dyad-level data from a study of young PWID from San Francisco (2006 to 2013) to investigate the relationship-level factors influencing high-risk injecting within HCV-serodiscordant injection partners (i.e., individuals who injected together ≥5 times in the prior month). Utilizing data from 70 HCV-serodiscordant injection partnerships, we used generalized linear models to examine relationship-level predictors (i.e., partnership composition, partnership closeness, and partnership dynamics) of: (1) receptive syringe sharing (RSS); and (2) receptive cooker use (RCU), as reported by the HCV-negative injection partner.

Results

As reported by the “at-risk” HCV-negative injection partner, receptive syringe sharing (RSS) and receptive cooker use (RCU) were 19% and 33% at enrollment, and 11% and 12% over all visits (total follow-up time 55 person-years) resulting in 13 new HCV-infections (incidence rate: 23.8/100 person-years). Person-level factors, injection partnership composition, and partnership dynamics were not significantly associated with either RSS or RCU. Instead, intimate injection partnerships (those who lived together and were also in a sexual relationship) were independently associated with a 5-times greater risk of both RSS and a 7-times greater risk of RCU when compared to injecting only partnerships.

Conclusion

Our findings suggest a positive, and amplified effect of relationship factors on injecting drug risk behaviors among young PWID injection partnerships. The majority of interventions to reduce injection drug use related harms focus on individual-based education to increase drug use knowledge. Our findings support the need to expand harm reduction strategies to relationship-based messaging and interventions.     

A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models

We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.     

HIV,HBV and HCV Coinfection Prevalence in Iran - A Systematic Review and Meta-Analysis

Background

worldwide, hepatitis C and B virus infections (HCV and HCV), are the two most common coinfections with human immunodeficiency virus (HIV) and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran.

Method

Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals.

Findings

HIV prevalence varied from %0.00 (95% CI: 0.00–0.003) in the general population to %17.25 (95% CI: 2.94–31.57) in people who inject drugs (PWID). HBV prevalence ranged from % 0.00 (95% CI: 0.00–7.87) in health care workers to % 30.9 (95% CI: 27.88–33.92) in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00–0.66) in health care workers to %51.46 (95% CI: 34.30–68.62) in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple infections (1.25%) in PWID.

Conclusions

We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others.     

Is Early Tuberculosis Death Associated with Increased Tuberculosis Transmission?

Introduction

Tuberculosis (TB) is now a relatively uncommon disease in high income countries. As such, its diagnosis may be missed or delayed resulting in death before or shortly after the introduction of treatment. Whether early TB death is associated with increased TB transmission is unknown. To determine the transmission risk attributable to early TB death we undertook a case-control study.

Methods

All adults who were: (1) diagnosed with culture-positive pulmonary TB in the Province of Alberta, Canada between 1996 and 2012, and (2) died a TB-related death before or within the first 60 days of treatment, were identified. For each of these “cases” two sets of “controls” were randomly selected from among culture-positive pulmonary TB cases that survived beyond 60 days of treatment. “Controls” were matched by age, sex, population group, +/- smear status. Secondary cases of “cases” and “controls” were identified using conventional and molecular epidemiologic tools and compared. In addition, new infections were identified and compared in contacts of “cases” that died before treatment and contacts of their smear-matched “controls”. Conditional logistic regression was used to find associations in both univariate and multivariate analysis.

Results

“Cases” were as, but not more, likely than “controls” to transmit. This was so whether transmission was measured in terms of the number of “cases” and smear-unmatched or -matched “controls” that had a secondary case, the number of secondary cases that they had or the number of new infections found in contacts of “cases” that died before treatment and their smear-matched “controls”.

Conclusion

In a low TB incidence/low HIV prevalence country, pulmonary TB patients that die a TB-related death before or in the initial phase of treatment and pulmonary TB patients that survive beyond the initial phase of treatment are equally likely to transmit.     

Estimates of Social Contact in a Middle School Based on Self-Report and Wireless Sensor Data

Estimates of contact among children, used for infectious disease transmission models and understanding social patterns, historically rely on self-report logs. Recently, wireless sensor technology has enabled objective measurement of proximal contact and comparison of data from the two methods. These are mostly small-scale studies, and knowledge gaps remain in understanding contact and mixing patterns and also in the advantages and disadvantages of data collection methods. We collected contact data from a middle school, with 7th and 8th grades, for one day using self-report contact logs and wireless sensors. The data were linked for students with unique initials, gender, and grade within the school. This paper presents the results of a comparison of two approaches to characterize school contact networks, wireless proximity sensors and self-report logs. Accounting for incomplete capture and lack of participation, we estimate that “sensor-detectable”, proximal contacts longer than 20 seconds during lunch and class-time occurred at 2 fold higher frequency than “self-reportable” talk/touch contacts. Overall, 55% of estimated talk-touch contacts were also sensor-detectable whereas only 15% of estimated sensor-detectable contacts were also talk-touch. Contacts detected by sensors and also in self-report logs had longer mean duration than contacts detected only by sensors (6.3 vs 2.4 minutes). During both lunch and class-time, sensor-detectable contacts demonstrated substantially less gender and grade assortativity than talk-touch contacts. Hallway contacts, which were ascertainable only by proximity sensors, were characterized by extremely high degree and short duration. We conclude that the use of wireless sensors and self-report logs provide complementary insight on in-school mixing patterns and contact frequency.     

HIV among People Who Inject Drugs in the Middle East and North Africa: Systematic Review and Data Synthesis

Background

It is perceived that little is known about the epidemiology of HIV infection among people who inject drugs (PWID) in the Middle East and North Africa (MENA). The primary objective of this study was to assess the status of the HIV epidemic among PWID in MENA by describing HIV prevalence and incidence. Secondary objectives were to describe the risk behavior environment and the HIV epidemic potential among PWID, and to estimate the prevalence of injecting drug use in MENA.

Methods and Findings

This was a systematic review following the PRISMA guidelines and covering 23 MENA countries. PubMed, Embase, regional and international databases, as well as country-level reports were searched up to December 16, 2013. Primary studies reporting (1) the prevalence/incidence of HIV, other sexually transmitted infections, or hepatitis C virus (HCV) among PWIDs; or (2) the prevalence of injecting or sexual risk behaviors, or HIV knowledge among PWID; or (3) the number/proportion of PWID in MENA countries, were eligible for inclusion. The quality, quantity, and geographic coverage of the data were assessed at country level. Risk of bias in predefined quality domains was described to assess the quality of available HIV prevalence measures. After multiple level screening, 192 eligible reports were included in the review. There were 197 HIV prevalence measures on a total of 58,241 PWID extracted from reports, and an additional 226 HIV prevalence measures extracted from the databases.We estimated that there are 626,000 PWID in MENA (range: 335,000–1,635,000, prevalence of 0.24 per 100 adults). We found evidence of HIV epidemics among PWID in at least one-third of MENA countries, most of which are emerging concentrated epidemics and with HIV prevalence overall in the range of 10%–15%. Some of the epidemics have however already reached considerable levels including some of the highest HIV prevalence among PWID globally (87.1% in Tripoli, Libya). The relatively high prevalence of sharing needles/syringes (18%–28% in the last injection), the low levels of condom use (20%–54% ever condom use), the high levels of having sex with sex workers and of men having sex with men (15%–30% and 2%–10% in the last year, respectively), and of selling sex (5%–29% in the last year), indicate a high injecting and sexual risk environment. The prevalence of HCV (31%–64%) and of sexually transmitted infections suggest high levels of risk behavior indicative of the potential for more and larger HIV epidemics.

Conclusions

Our study identified a large volume of HIV-related biological and behavioral data among PWID in the MENA region. The coverage and quality of the data varied between countries. There is robust evidence for HIV epidemics among PWID in multiple countries, most of which have emerged within the last decade and continue to grow. The lack of sufficient evidence in some MENA countries does not preclude the possibility of hidden epidemics among PWID in these settings. With the HIV epidemic among PWID in overall a relatively early phase, there is a window of opportunity for prevention that should not be missed through the provision of comprehensive programs, including scale-up of harm reduction services and expansion of surveillance systems. Please see later in the article for the Editors'' Summary     

The Epidemiology of Hepatitis C Virus in the Fertile Crescent: Systematic Review and Meta-Analysis

Objective

To characterize hepatitis C virus (HCV) epidemiology in countries of the Fertile Crescent region of the Middle East and North Africa (MENA), namely Iraq, Jordan, Lebanon, Palestine, and Syria.

Methods

We systematically reviewed and synthesized available records of HCV incidence and prevalence following PRISMA guidelines. Meta-analyses were implemented using a DerSimonian-Laird random effects model with inverse weighting to estimate the country-specific HCV prevalence among the various at risk population groups.

Results

We identified eight HCV incidence and 240 HCV prevalence measures in the Fertile Crescent. HCV sero-conversion risk among hemodialysis patients was 9.2% in Jordan and 40.3% in Iraq, and ranged between 0% and 3.5% among other populations in Iraq over different follow-up times. Our meta-analyses estimated HCV prevalence among the general population at 0.2% in Iraq (range: 0–7.2%; 95% CI: 0.1–0.3%), 0.3% in Jordan (range: 0–2.0%; 95% CI: 0.1–0.5%), 0.2% in Lebanon (range: 0–3.4%; 95% CI: 0.1–0.3%), 0.2% in Palestine (range: 0–9.0%; 95% CI: 0.2–0.3%), and 0.4% in Syria (range: 0.3–0.9%; 95% CI: 0.4–0.5%). Among populations at high risk, HCV prevalence was estimated at 19.5% in Iraq (range: 0–67.3%; 95% CI: 14.9–24.5%), 37.0% in Jordan (range: 21–59.5%; 95% CI: 29.3–45.0%), 14.5% in Lebanon (range: 0–52.8%; 95% CI: 5.6–26.5%), and 47.4% in Syria (range: 21.0–75.0%; 95% CI: 32.5–62.5%). Genotypes 4 and 1 appear to be the dominant circulating strains.

Conclusions

HCV prevalence in the population at large appears to be below 1%, lower than that in other MENA sub-regions, and tending towards the lower end of the global range. However, there is evidence for ongoing HCV transmission within medical facilities and among people who inject drugs (PWID). Migration dynamics appear to have played a role in determining the circulating genotypes. HCV prevention efforts should be targeted, and focus on infection control in clinical settings and harm reduction among PWID.     

Individual and Population Level Effects of Partner Notification for Chlamydia trachomatis

Partner notification (PN or contact tracing) is an important aspect of treating bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis. It facilitates the identification of new infected cases that can be treated through individual case management. PN also acts indirectly by limiting onward transmission in the general population. However, the impact of PN, both at the level of individuals and the population, remains unclear. Since it is difficult to study the effects of PN empirically, mathematical and computational models are useful tools for investigating its potential as a public health intervention. To this end, we developed an individual-based modeling framework called Rstisim. It allows the implementation of different models of STI transmission with various levels of complexity and the reconstruction of the complete dynamic sexual partnership network over any time period. A key feature of this framework is that we can trace an individual’s partnership history in detail and investigate the outcome of different PN strategies for C. trachomatis. For individual case management, the results suggest that notifying three or more partners from the preceding 18 months yields substantial numbers of new cases. In contrast, the successful treatment of current partners is most important for preventing re-infection of index cases and reducing further transmission of C. trachomatis at the population level. The findings of this study demonstrate the difference between individual and population level outcomes of public health interventions for STIs.     

Sheep Movement Networks and the Transmission of Infectious Diseases

Background and Methodology

Various approaches have been used to investigate how properties of farm contact networks impact on the transmission of infectious diseases. The potential for transmission of an infection through a contact network can be evaluated in terms of the basic reproduction number, R ₀. The magnitude of R ₀ is related to the mean contact rate of a host, in this case a farm, and is further influenced by heterogeneities in contact rates of individual hosts. The latter can be evaluated as the second order moments of the contact matrix (variances in contact rates, and co-variance between contacts to and from individual hosts). Here we calculate these quantities for the farms in a country-wide livestock network: >15,000 Scottish sheep farms in each of 4 years from July 2003 to June 2007. The analysis is relevant to endemic and chronic infections with prolonged periods of infectivity of affected animals, and uses different weightings of contacts to address disease scenarios of low, intermediate and high animal-level prevalence.

Principal Findings and Conclusions

Analysis of networks of Scottish farms via sheep movements from July 2003 to June 2007 suggests that heterogeneities in movement patterns (variances and covariances of rates of movement on and off the farms) make a substantial contribution to the potential for the transmission of infectious diseases, quantified as R ₀, within the farm population. A small percentage of farms (<20%) contribute the bulk of the transmission potential (>80%) and these farms could be efficiently targeted by interventions aimed at reducing spread of diseases via animal movement.     

Diffusion of Information throughout the Host Interactome Reveals Gene Expression Variations in Network Proximity to Target Proteins of Hepatitis C Virus

Hepatitis C virus infection is one of the most common and chronic in the world, and hepatitis associated with HCV infection is a major risk factor for the development of cirrhosis and hepatocellular carcinoma (HCC). The rapidly growing number of viral-host and host protein-protein interactions is enabling more and more reliable network-based analyses of viral infection supported by omics data. The study of molecular interaction networks helps to elucidate the mechanistic pathways linking HCV molecular activities and the host response that modulates the stepwise hepatocarcinogenic process from preneoplastic lesions (cirrhosis and dysplasia) to HCC. Simulating the impact of HCV-host molecular interactions throughout the host protein-protein interaction (PPI) network, we ranked the host proteins in relation to their network proximity to viral targets. We observed that the set of proteins in the neighborhood of HCV targets in the host interactome is enriched in key players of the host response to HCV infection. In opposition to HCV targets, subnetworks of proteins in network proximity to HCV targets are significantly enriched in proteins reported as differentially expressed in preneoplastic and neoplastic liver samples by two independent studies. Using multi-objective optimization, we extracted subnetworks that are simultaneously “guilt-by-association” with HCV proteins and enriched in proteins differentially expressed. These subnetworks contain established, recently proposed and novel candidate proteins for the regulation of the mechanisms of liver cells response to chronic HCV infection.     

Effectiveness of realistic vaccination strategies for contact networks of various degree distributions

A "contact network" that models infection transmission comprises nodes (or individuals) that are linked when they are in contact and can potentially transmit an infection. Through analysis and simulation, we studied the influence of the distribution of the number of contacts per node, defined as degree, on infection spreading and its control by vaccination. Three random contact networks of various degree distributions were examined. In a scale-free network, the frequency of high-degree nodes decreases as the power of the degree (the case of the third power is studied here); the decrease is exponential in an exponential network, whereas all nodes have the same degree in a constant network. Aiming for containment at a very early stage of an epidemic, we measured the sustainability of a specific network under a vaccination strategy by employing the critical transmissibility larger than which the epidemic would occur. We examined three vaccination strategies: mass, ring, and acquaintance. Irrespective of the networks, mass preventive vaccination increased the critical transmissibility inversely proportional to the unvaccinated rate of the population. Ring post-outbreak vaccination increased the critical transmissibility inversely proportional to the unvaccinated rate, which is the rate confined to the targeted ring comprising the neighbors of an infected node; however, the total number of vaccinated nodes could mostly be fewer than 100 nodes at the critical transmissibility. In combination, mass and ring vaccinations decreased the pathogen's "effective" transmissibility each by the factor of the unvaccinated rate. The amount of vaccination used in acquaintance preventive vaccination was lesser than the mass vaccination, particularly under a highly heterogeneous degree distribution; however, it was not as less as that used in ring vaccination. Consequently, our results yielded a quantitative assessment of the amount of vaccination necessary for infection containment, which is universally applicable to contact networks of various degree distributions.