Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis.

Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.

Levels of HIV Testing Among Young Men Who Have Sex with Men in Bulgaria: Very Low Testing by Ethnic Minority Roma (Gypsy) Men.

Little is known about HIV testing among young men who have sex with men (MSM) in Southeastern European countries, nor about differences in testing by young ethnic majority and young Roma MSM, the region's most disadvantaged minority population. 271 young MSM (153 non-Roma and 118 Roma) were recruited in Sofia, Bulgaria and completed measures of HIV testing, psychosocial characteristics related to testing, sexual behavior, and substance use. While 74% of ethnic majority MSM had an HIV test (and 56% had multiple prior tests), only 4% of Roma MSM had ever been tested. Roma MSM had lower knowledge about HIV testing, perceived greater barriers and weaker social norms for testing, and held more negative testing attitudes and intentions. Although all had male partners, no Roma MSM self-identified as gay and most reported transactional sex. Efforts are urgently needed to increase HIV testing uptake by young Roma MSM.

Prevalence of hepatitis C in the adult population of Bulgaria: a pilot study.

OBJECTIVE: This study piloted a European technical protocol for conducting chronic hepatitis C prevalence surveys in the general population. The pilot study took place in the Bulgarian city of Stara Zagora in 2018, and results of setting up, conducting and evaluating the survey are presented. RESULTS: A probability-based sample of the general adult population was drawn from the local population registry, stratified by age and sex. A sample size of 999 was calculated, and accounting for 50% non-response, 1998 registered invitation letters were sent. Venous blood samples and questionnaire data were collected by the Regional Health Inspectorate in Stara Zagora. Blood samples were tested for anti-HCV, and if reactive for RNA. 252 (21.6%) of the participants were included in the study. Mean age and sex distribution differed between the participants (55.9 years, 60.3% females) and the total sample (48.9 years, 53.4%). The weighted chronic HCV prevalence among participants was 0.9% [95% CI 0.2-4.2%]. The approach of only sending registered letters contributed to a low response rate, and more efforts are needed to reduce non-response, especially among men and younger age groups. Results of the evaluation were integrated in the final technical protocol.

HIV-1 genetic diversity and demographic characteristics in Bulgaria.

HIV-1 strain diversity in Bulgaria is extensive and includes contributions from nearly all major subtypes and the Circulating Recombinant Forms (CRF): 01_AE, 02_AG, and 05_DF. Prior to this study, HIV-1 sequence information from Bulgaria has been based solely on the pro-RT gene, which represent less than 15% of the viral genome. To further characterize HIV-1 in Bulgaria, assess participant risk behaviors, and strengthen knowledge of circulating strains in the region, the study "Genetic Subtypes of HIV-1 in Bulgaria (RV240)" was conducted. This study employed the real time-PCR based Multi-region Hybridization Assay (MHA) B/non-B and HIV-1 sequencing to survey 215 of the approximately 1100 known HIV-1 infected Bulgarian adults (2008-2009) and determine if they were infected with subtype B HIV-1. The results indicated a subtype B prevalence of 40% and demonstrate the application of the MHA B/non-B in an area containing broad HIV-1 strain diversity. Within the assessed risk behaviors, the proportion of subtype B infection was greatest in men who have sex with men and lowest among those with drug use risk factors. During this study, 15 near full-length genomes and 22 envelope sequences were isolated from study participants. Phylogenetic analysis shows the presence of subtypes A1, B, C, F1, and G, CRF01_AE, CRF02_AG, CRF05_DF, and one unique recombinant form (URF). These sequences also show the presence of two strain groups containing participants with similar risk factors. Previous studies in African and Asian cohorts have shown that co-circulation of multiple subtypes can lead to viral recombination within super-infected individuals and the emergence of new URFs. The low prevalence of URFs in the presence of high subtype diversity in this study, may be the result of successful infection prevention and control programs. Continued epidemiological monitoring and support of infection prevention programs will help maintain control of the HIV-1 epidemic in Bulgaria.

Health system factors influencing management of multidrug-resistant tuberculosis in four European Union countries - learning from country experiences.

BACKGROUND: In the European Union and European Economic Area only 38% of multidrug-resistant tuberculosis patients notified in 2011 completed treatment successfully at 24 months' evaluation. Socio-economic factors and patient factors such as demographic characteristics, behaviour and attitudes are associated with treatment outcomes. Characteristics of healthcare systems also affect health outcomes. This study was conducted to identify and better understand the contribution of health system components to successful treatment of multidrug-resistant tuberculosis. METHODS: We selected four European Union countries to provide for a broad range of geographical locations and levels of treatment success rates of the multidrug-resistant tuberculosis cohort in 2009. We conducted semi-structured interviews following a conceptual framework with representatives from policy and planning authorities, healthcare providers and civil society organisations. Responses were organised according to the six building blocks of the World Health Organization health systems framework. RESULTS: In the four included countries, Austria, Bulgaria, Spain, and the United Kingdom, the following healthcare system factors were perceived as key to achieving good treatment results for patients with multidrug-resistant tuberculosis: timely diagnosis of drug-resistant tuberculosis; financial systems that ensure access to a full course of treatment and support for multidrug-resistant tuberculosis patients; patient-centred approaches with strong intersectoral collaboration that address patients' emotional and social needs; motivated and dedicated healthcare workers with sufficient mandate and means to support patients; and cross-border management of multidrug-resistant tuberculosis to secure continuum of care between countries. CONCLUSION: We suggest that the following actions may improve the success of treatment for multidrug-resistant tuberculosis patients: deployment of rapid molecular diagnostic tests; development of context-specific treatment guidance and criteria for hospital admission and discharge in the European context; strengthening patient-centred approaches; development of collaborative mechanisms to ensure cross-border care, and development of long-term sustainable financing strategies.

High Rate of Hepatitis B and C Coinfections Among People Living with HIV-1 in Bulgaria: 2010-2014.

In a representative nationwide study, we have determined the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfections among HIV-positive patients diagnosed during the period 2010-2014 in Bulgaria. Despite a relatively low rate of new HIV diagnoses, the rates of hepatitis B and C coinfections among these patients fell within the upper range reported in Europe. HBsAg and HCV antibodies (Ab) were found in 10.4% and 25.6% of the tested individuals, respectively. Importantly, high rates of active hepatitis infections were confirmed by detection of HBV DNA in 51.1% and HCV RNA in 78.1% of the tested individuals. Hepatitis coinfections affected mostly high risk groups and persons with multiple risk behavior, including people who inject drugs, men who have sex with men, prisoners, and Roma people.

Origin and spread of HIV-1 in persons who inject drugs in Bulgaria.

Increased HIV transmission in persons who inject drugs (PWIDs) has led to subepidemics and outbreaks in several countries in Europe, including Bulgaria. In this study in Bulgaria, we investigate the origin and spatiotemporal evolutionary history of HIV-1 infections in PWIDs and the distribution of antiretroviral resistance mutations and hepatitis co-infections in these populations. We analyzed HIV-1 polymerase sequences available from 117 of 359 PWIDs diagnosed with HIV/AIDS from 1999 to 2011. Of these, 50 (42.7%) were classified as CRF02_AG, 41 (35.0%) CRF01_AE, 12 (10.3%) URFs, ten (8.5%) subtype B, two (1.7%) subtype F1 and two (1.7%) CRF14_BG. Most recent common ancestor dating suggests that CRF01_AE was likely first introduced from Southeast Asia into persons reporting heterosexual infection in Bulgaria in 1992 and spread subsequently to PWIDs in the capital city of Sofia around 2003. Conversely, CRF02_AG in Bulgaria was likely first introduced into PWID from Germany in 2000 and later entered heterosexual populations around 2009. The overall prevalence of resistance mutations was 6.8% (8/117), of which 5.1% (5/117) was observed in patients on antiretroviral therapy and 1.7% (2/117) was from transmitted drug resistance mutations in drug-naïve individuals. 189/204 (92.6%) PWIDs were also co-infected with hepatitis C (HCV) and 31/183 (16.9%) were co-infected with hepatitis B (HBV). Our study provides valuable molecular epidemiological information on the introduction and distribution of the main HIV-1 subtypes, resistance mutations and hepatitis co-infections among PWIDs with HIV-1 in Bulgaria which can be used to target prevention efforts.

Factors associated with treatment success and death in cases with multidrug-resistant tuberculosis in Bulgaria, 2009-2010.

OBJECTIVE: To analyze determinants of success and death in multidrug-resistant tuberculosis patients (MDR-TB; resistance to, at least, isoniazid and rifampicin) placed on treatment in Bulgaria during the period September 2009 to March 2010 using logistic regression. RESULTS: Fifty MDR-TB patients started treatment. Male:Female ratio was 2.3:1; mean age 43 years (range: 18-77); 19 patients (38%) were new; median duration of disease before treatment was 5 years (range: 1-13). All patients tested negative for HIV. Eight cases had XDR-TB (MDR-TB plus resistance to any fluoroquinolone and any second-line injectable). Twenty-four months after starting treatment, 24 patients (48%) had a successful outcome, in 6 (12%) treatment failed, 19 (38%) died, and one (2%) interrupted treatment. XDR-TB cases experienced higher mortality than others (75% vs. 30.9%, respectively, P<0.05). Sputum smear positivity at start of treatment and weight loss or no weight gain were positively associated with death (adjusted Odds ratio: 5.16; 95% confidence interval: 1.16-22.84 and 5.61; 1.48-21.20, respectively) and negatively with success (0.13; 0.02-0.94 and 0.02; 0.00-0.19). No previous TB treatment increased likelihood of success (7.82; 1.09-56.15). DISCUSSION AND CONCLUSIONS: Most MDR-TB patients in this first treatment cohort using WHO-recommended norms had advanced disease explaining the high mortality and low success. Early, adequate treatment of MDR-TB patients can improve outcomes and avert transmission.

Detailed molecular epidemiologic characterization of HIV-1 infection in Bulgaria reveals broad diversity and evolving phylodynamics.

Limited information is available to describe the molecular epidemiology of HIV-1 in Bulgaria. To better understand the genetic diversity and the epidemiologic dynamics of HIV-1 we analyzed 125 new polymerase (pol) sequences from Bulgarians diagnosed through 2009 and 77 pol sequences available from our previous study from persons infected prior to 2007. Epidemiologic and demographic information was obtained from each participant and phylogenetic analysis was used to infer HIV-1 evolutionary histories. 120 (59.5%) persons were infected with one of five different HIV-1 subtypes (A1, B, C, F1 and H) and 63 (31.2%) persons were infected with one of six different circulating recombinant forms (CRFs; 01_AE, 02_AG, 04_cpx, 05_DF, 14_BG, and 36_cpx). We also for the first time identified infection with two different clusters of unique A-like and F-like sub-subtype variants in 12 persons (5.9%) and seven unique recombinant forms (3.5%), including a novel J/C recombinant. While subtype B was the major genotype identified and was more prevalent in MSM and increased between 2000-2005, most non-B subtypes were present in persons ≥45 years old. CRF01_AE was the most common non-B subtype and was higher in women and IDUs relative to other risk groups combined. Our results show that HIV-1 infection in Bulgaria reflects the shifting distribution of genotypes coincident with the changing epidemiology of the HIV-1 epidemic among different risk groups. Our data support increased public health interventions targeting IDUs and MSM. Furthermore, the substantial and increasing HIV-1 genetic heterogeneity, combined with fluctuating infection dynamics, highlights the importance of sustained and expanded surveillance to prevent and control HIV-1 infection in Bulgaria.

The HIV type 1 epidemic in Bulgaria involves multiple subtypes and is sustained by continuous viral inflow from West and East European countries.

Little is known about the HIV-1 epidemic in Balkan countries. To fill the gap, we investigated the viral genetic diversity in Bulgaria, by sequencing and phylogenetic characterization of 86 plasma samples collected between 2002 and 2006 from seropositive individuals diagnosed within 1986-2006. Analysis of pol gene sequences assigned 51% of the samples to HIV-1 subtype B and 27% to subtype A1. HIV-1 subtype C, F, G, H, and a few putative recombinant forms were also found. Phylogenetic and molecular clock analysis showed a continuous exchange of subtype A and B between Bulgaria and Western as well as other Eastern European countries. At least three separate introductions of HIV-1 subtype A and four of HIV-1 subtype B have occurred within the past 25 years in Bulgaria. The central geographic location of Bulgaria, the substantial genetic heterogeneity of the epidemic with multiple subtypes, and the significant viral flow observed to and from the Balkan countries have the potential to modify the current HIV-1 epidemiological structure in Europe and highlight the importance of more extensive and continuous monitoring of the epidemic in the Balkans.