Vaccinations in prison settings: A systematic review to assess the situation in EU/EEA countries and in other high income countries.

INTRODUCTION: In 2016, more than 600,000 persons were being held in EU/EEA correctional facilities on a given day. People in prison may be at risk of vaccine-preventable diseases. While vaccination recommendations for people in prison exist, little is known on coverage and implementation options. METHODS: We performed a systematic review on existing evidence on vaccination in prison settings in the EU/EEA. We searched peer-reviewed and grey literature following international methodology and reporting standards, to gather records published between 1980 and 2016 in all languages. We analysed quantitative (acceptance, uptake, cost-effectiveness) and qualitative (barriers) outcomes. RESULTS: Out of 7041 identified records, 19 full-text articles were included from peer-reviewed literature and two from grey literature. Of these, 18 reported on hepatitis A and/or B virus (HAV/HBV), two on influenza and one on MMR vaccination. Two studies on HAV vaccine reported varying acceptance (5-91%) and uptake rates (62.9-70.5%). Seven studies reported on HBV vaccination. A comparative study showed a significantly higher uptake of the third HBV vaccine dose with the very rapid (63%) compared to the standard schedule (20%). HBV vaccination was generally well accepted (54-100%), whereas uptake was variable (dose 1:23-100%, dose 2:48-92%, dose 3:19-80%). One study on the combined HAV/HBV vaccine reported an acceptance rate of 34%, and declining uptake following dose 1. One study on influenza vaccine showed an uptake of 42-46%, while another reported a MMR vaccine acceptance of 80% and an uptake of 74%. Overall, main reasons for non-vaccination included release from/or transfer between prisons, and refusal. CONCLUSIONS: This systematic review highlighted important knowledge gaps and operational challenges for vaccination in prison settings. Vaccination is an effective measure that warrants comprehensive and tailored implementation to reduce the preventable disease burden, avoid risks of large outbreaks of vaccine-preventable diseases, and contribute to health equity for people in prison.

A systematic review on models of care effectiveness and barriers to Hepatitis C treatment in prison settings in the EU/EEA.

Hepatitis C prevalence in prison populations is much higher than in the community. Effective hepatitis C treatment within this population does not only have a direct individual health benefit, but may lead to substantial community dividend. We reviewed available evidence on hepatitis C treatment in prison settings, with a focus on the European Union/European Economic Area. A systematic review of the literature (PubMed, EMBASE, Cochrane library) was performed and complemented with searches for conference abstracts and grey literature. Thirty-four publications were included reporting on the effectiveness, acceptability and economic aspects of hepatitis C virus treatment models of care to achieve treatment completion and sustained viral response in prison settings. Available evidence shows that hepatitis C treatment in prison settings is feasible and the introduction of direct-acting antivirals will most likely result in increased treatment completion and better clinical outcomes for the prison population, given the caveats of affordability and the need for increased funding for prison health, with the resulting benefits accruing mostly in the community.

Active Case Finding for Communicable Diseases in Prison Settings: Increasing Testing Coverage and Uptake Among the Prison Population in the European Union/European Economic Area.

Prison populations are disproportionally affected by communicable diseases when compared with the general community because of a complex mix of socioeconomic determinants and environmental factors. Tailored and adequate health care provision in prisons has the potential to reach vulnerable and underserved groups and address their complex needs. We investigated the available evidence on modalities and effectiveness of active case-finding interventions in prisons by searching PubMed, Embase, and the Cochrane Library for records on prison and active case finding with no language limit. Conference abstracts and unpublished research reports also were retrieved. We analyzed the findings by testing modality, outcomes, and study quality. The included 90 records-63 peer-reviewed, 26 from gray literature, and 1 systematic review-reported variously on viral hepatitis, human immunodeficiency virus, sexually transmitted infections, and tuberculosis. No records were retrieved for other communicable diseases. Provider-initiated opt-in testing was the most frequently investigated modality. Testing at entry and provider-initiated testing were reported to result in comparatively higher uptake ranges. However, no comparative studies were identified that reported statistically significant differences between testing modalities. Positivity rates among tested inmates ranged broadly but were generally high for all diseases. The evidence on active case finding in correctional facilities is limited, heterogeneous, and of low quality, making it challenging to draw conclusions on the effect of different testing modalities. Scale-up of provider-initiated testing in European correctional facilities could substantially reduce the undiagnosed fraction and, hence, prevent additional disease transmission in both prison settings and the community at large.

Management of HCV infection in the penitentiary setting in the direct-acting antivirals era: practical recommendations from an expert panel.

BACKGROUND: The prevalence of HCV infection is higher among prisoners than in the general population. The introduction of HCV direct-acting antivirals (DAA) holds the potential to improve clinical outcomes also in inmates. However, treatment of hepatitis C in inmates has to face several clinical and logistical issues which are peculiar of prison environment. Recommendations on the management of HCV infection specific for the penitentiary setting in the DAA era remain scant. The Italian Society for Penitentiary Medicine and Healthcare has, therefore, issued these recommendations, to provide clinicians with a guide for the comprehensive management of HCV infection in the restriction setting, taking into account its peculiar characteristics. RESULTS: Dedicated diagnostic and treatment procedures should be established in each prison. In particular, the use of DAAs appears crucial to provide patients with an effective therapeutic option, able to overcome the limitations of IFN-based regimens with a short period of treatment. DAA treatment should be initiated as soon as possible in all eligible subjects with the aim to cure the patient, as well as to limit the transmission of HCV infection both inside the penitentiary system and to the free community, once the inmates ends his/her release. Importantly, efforts should be made to open a discussion with regulatory bodies, to define specific regulations aimed to guarantee wide access to effective therapies of all eligible patients, to optimize the management of and the adherence to the HCV treatment, and to ensure the therapeutic continuity after discharge from prison.

Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study.

Coinfection of blood-borne hepatitis B and hepatitis C viruses (HBV and HCV, respectively) in human immunodeficiency virus type 1 (HIV-1)-positive individuals frequently occurs in inmate population and peculiar viral strains and patterns of virological markers may be observed.Plasma from 69 HIV-1-positive inmates was obtained from 7 clinical centers connected with correctional centers in different towns in Italy. HIV, HBV, and HCV markers were tested by commercial assays. Virus genotyping was carried out by sequencing the protease and reverse transcriptase-encoding region (PR-RT region) for HIV and a region encompassing the NS5B gene for HCV and subsequent phylogenetic analysis.Twelve over 14 HIV-subtyped inmates were infected with HIV-1 subtype B strains. The 2 non-B strains belonged to subtype G and CRF02_AG, in an Italian and a Gambian patient, respectively. Variants carrying the K103N and Y181C resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were found in 2 out of 9 patients naive for combined antiretroviral therapy (cART) (22.2%). Most HIV-positive patients (92.8%) showed evidence of past or present HBV and/or HCV infection. Prevalence of HBV and HCV was 81.2% for both viruses, whereas prevalence of HBV/HCV coinfection was 69.6%. A significantly higher presence of HCV infection was found in Italians [odds ratio (OR) 11.0; interval 1.7-80.9] and in drug users (OR 27.8; interval 4.9-186.0). HCV subtypes were determined in 42 HCV or HBV/HCV-coinfected individuals. HCV subtypes 1a, 3a, 4d, and 1b were found in 42.9%, 40.5%, 14.3%, and 2.4% of inmates, respectively. Low titers of HBV DNA in HBV DNA positive subjects precluded HBV subtyping.The high prevalence of HBV and HCV coinfections in HIV-infected inmates, as well as the heterogeneity of HIV and HCV subtypes suggest the need to adopt systematic controls in prisons to monitor both the burden and the genetic forms of blood-borne viral infections, in order to apply targeted therapeutic interventions.

Boceprevir or telaprevir in hepatitis C virus chronic infection: The Italian real life experience.

AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.

May some HCV genotype 1 patients still benefit from dual therapy? The role of very early HCV kinetics.

When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.

HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b.

BACKGROUND: The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin. METHODS: For 48 weeks, 388 "naïve"genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000-1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR). RESULTS: The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR. CONCLUSION: Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01342003.

Targeting candidates for directly administered highly active antiretroviral therapy: benefits observed in HIV-infected injecting drug users in residential drug-rehabilitation facilities.

The purpose of this study was to evaluate retrospectively the potential benefits of directly administered antiretroviral therapy (DAART) in HIV-infected former injecting drug users (ex-IDUs) admitted to residential drug rehabilitation facilities. We compared 106 of these patients consecutively admitted in 12 communities where DAART was administered (DAART group) to two matched control groups of ex-IDUs undergoing self-administered ART: 106 subjects in other 10 communities (SAT group) and 106 outpatients at hospital infectious-disease wards where community patients were referred after discharge (OUT group). We estimated the proportion of patients with high adherence and the hazard ratio (HR) of 20% or more increase in the CD4(+) cell count and of reaching an undetectable viral load. The proportion of patients with high adherence to treatment was highest in the DAART group. The probability of 20% or more increase in the CD4(+) cell count was significantly lower in the two control groups versus the DAART group (SAT group HR=0.32; OUT group HR=0.43). The HR of observing an undetectable HIV-RNA level versus DAART was significantly lower in the OUT group (HR: 0.71; 95% confidence interval [CI]: 0.52-0.97) but did not reach statistical significance for the SAT group (HR: 0.99; 95% CI: 0.74-1.33). Our findings after a 24-month follow-up, suggest that DAART in HIV-infected patients of drug-rehabilitation communities improves adherence, immunologic, and virologic outcome toward free outpatients. Even if our retrospective 36-month data do not show a prolonged viral suppression in these patients, DAART may be considered a valuable therapeutic and educational strategy in this particular target group.

HIV-1 diversity among inmates of Italian prisons.

In Italy, the prevalence of non-B HIV-1 subtypes ranges reportedly from 5.4% to 12.6%, yet there are no data on their circulation in prisons, where the prevalence of HIV infection is high. A retrospective study was conducted to evaluate the circulation of non-B subtypes and to characterize their determinants in five Italian prisons. To this end an aliquot of samples of blood was taken in the period 2001-2006 from all 262 HIV-positive inmates in whom antiretroviral treatment had failed. Complete HIV-1 PR and RT regions were sequenced for all samples and subjected to phylogenetic analysis; 250 (95.4%) sequences clustered with subtype B. The non-B subtype was found in 4% of Italian prison inmates and 16.7% of non-Italian prison inmates; the overall percentage increased from 1.8% for inmates infected in 1982-1990 to 4.4% in 1991-1999 and 21.9% in 2000-2006. Factors significantly associated with non-B subtypes were an exposure to other than injecting drug use and a first positive HIV test in 2000-2006. Non-B subtypes were distributed within five monophyletic clades. In all cases but one, it was possible to correlate the history of HIV-exposure to the origin of the clade, with high bootstrap values. In conclusion, although the sample may not be representative of the prison inmate population in Italy, the data suggest strongly that the circulation of non-B subtypes has apparently increased. Non-B subtypes were found to have been associated with heterosexual contact and time of the first HIV-positive test. Knowledge of the different subtypes circulating in prisons may be useful for tracking the epidemiology of HIV infection and for choosing antiretroviral therapy.

Effectiveness of a multi-disciplinary standardized management model in the treatment of chronic hepatitis C in drug addicts engaged in detoxification programmes.

AIM: To evaluate the effect of a multi-disciplinary standardized management model on the efficacy of pegylated (Peg)-interferon alpha-2b plus ribavirin treatment of chronic hepatitis C in drug addicts undergoing substitutive or antagonist therapy. DESIGN: Observational prospective multi-centre study. SETTING: Six clinical infectious disease centres in collaboration with 11 drug dependency units (DDU) in five Italian regions. PARTICIPANTS: Intravenous drug users affected by chronic hepatitis C engaged in detoxification programmes. METHODS: Application of a multi-disciplinary standardized management model for HCV treatment involving DDU operators, psychologists or psychiatrists and infectious disease specialists. MEASUREMENTS: Very early, early, end-of-treatment and sustained virological response to Peg-interferon alpha-2b plus ribavirin. FINDINGS: Fifty-three subjects were studied [43.4% with hepatitis C virus (HCV) genotypes 1 or 4]. Intent-to-treat analysis showed an end-of-treatment virological response in 58.5% of patients (39.1% genotypes 1 or 4; 73.4% genotype 3) and a sustained virological response in 54.7% (34.8% genotypes 1 or 4; 70.0% genotype 3). There were 19 (35.8%) dropouts and three (5.7%) non-responders: one genotype 1 and two genotype 4. Two (3.8%) patients relapsed: genotypes 1 and 3. On-treatment analysis showed negative HCV-RNA in 40 (93.1%) of 43 subjects who completed the first 12 treatment weeks and in 35 who completed the first 24 treatment weeks. All subjects with an end-of-treatment response, except one with genotype 3 infection, had a sustained response. CONCLUSIONS: Our data show that antiviral treatment in the context of a multi-disciplinary standardized management model helps many HCV-positive drug addicts achieve a good virological response.

[HIV and related infections in Italian penal institutions: epidemiological and health organization note]. / HIV e infezioni correlate negli Istituti Penitenziari Italiani: note di epidemiologia e di organizzazione sanitaria.

HIV and other infections represent an important health problem in Italian jails. In particular, HIV prevalence is high, due to the characteristics of the prison population, which is constituted by a large proportion of injecting drug users and foreigners. In addition, data from other countries suggest that risky behaviour are not uncommon during imprisonment, and transmission of HIV and other infection in this setting may also occur. Data from surveys conducted by the Penitentiary Authority in Italian jails show a decline of HIV seroprevalence from 9.7% in 1990 to 2.6% in 2001. However, these data are largely incomplete and do not account for possible biases due to self-selection of inmates toward HIV serological testing or to variations in the access to screening activities. More accurate data, possibly obtained through anonymous unlinked surveys, are needed in order to better plan health services and preventive measures.