Simona Ruta

Ongoing outbreak of multiple blood-borne infections in injecting drug users in Romania.

In the recently published 2012 annual report on the state of the drugs problem in Europe, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) underlined the continuous increase in the drug-related infectious diseases, with a special mention for human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV). According to the last data released from the EMCDDA, Romania has experienced an increase in the lifetime use for all types of illicit drugs among subjects aged 15e64 years old, from 1.7% in 2007 to 4.3% in 2010. Central estimates for the capital city, Bucharest, show an increase with 5.37% in the number of problem drug users, in the 18e49-year old age group only: from 17 387 in 2008 to 18 316 in 2010, with a low number of treatment demands (between 10 and 15%); at the country level, these data are largely unknown. There are few published data on the prevalence of drug-related infectious diseases. Surveys using respondent-driven sampling or testing among those looking for medical assistance (both consisting on rather small samples of 200e500 drug users) reported high, although slightly decreasing levels, of HCV infection (from 72.6% in 2008 to 68.5% in 2011, with higher levels among those >34 years old); increasing rates of hepatitis B virus (HBV)

Serum iron markers in patients with chronic hepatitis C infection.

Background Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury. Objectives The aim of this study was to investigate the possible correlations between iron metabolism serum markers, HCV viral load, and liver disease severity in treatment-naive patients with chronic hepatitis C infection. Patients and Methods Eighty five patients with untreated hepatitis C chronic infection were investigated. Results Twenty one patients (24.7%) had elevated serum iron levels, and 29 subjects (34.1%) had severe liver fibrosis. Significantly elevated levels of serum iron (P < 0.05) and ferritin (P < 0.001), associated with lower levels of TIBC (P < 0.05) were detected in patients with severe fibrosis compared to no/mild fibrosis. Severe necroinflammatory activity was also significantly correlated with serum iron (P < 0.001), TIBC (P < 0.05), and ferritin levels (P < 0.001). Using multiple linear regression analysis, serum levels of ferritin and transferrin were the independent variables selected as being good predictors for advanced fibrosis and severe necroinflammatory activity. No significant correlations were detected between HCV viral load and iron markers. Conclusions This study revealed that serum iron markers (especially ferritin and transferrin) might be used as surrogate markers for both liver fibrosis and necroinflammatory activity.Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.

Transmitted HIV drug resistance in treatment-naive Romanian patients.

Transmitted HIV drug resistance (TDR) remains an important concern for individuals unexposed to antiretroviral treatment. Data on the prevalence of TDR, available mainly for HIV‐1 subtype B, are now also emerging for other subtypes. In Romania, a steady predominance of subtype F was reported among both long‐term survivor children and newly infected adults. The pol gene of 61 drug‐naïve patients infected with HIV, diagnosed between 1997 and 2011 was sequenced in order to analyze the prevalence of primary resistance mutations and to correlate these with the infecting genotype. Only 5/61 specimens were classified as infected recently using the BED‐Capture Enzyme Immunoassay. Subtype F1 was prevalent (80.3%), however, other HIV‐1 clades are increasingly identified, especially in the group of subjects infected recently. An HIV transmission cluster, associated to injecting drug use was identified by phylogenetic analysis. The overall prevalence of TDR was 14.75%, mainly associated with NRTI resistance (13.11%), TAMs and M184V being the most common mutations. A declining trend of TDR was recorded from 26.08% in 1997–2004 to 7.89% in 2005–2011. No primary resistance was identified among recent seroconvertors. All HIV‐1 strains had minor mutations in the protease and RT genes, often detected at polymorphic positions. The declining rates of TDR might be related to the high efficacy of HAART and to the increasing number of treated patients with virological success who have a low risk of transmission. The recent increase of HIV‐1 infections which involve other subtypes impose a continuous surveillance of the genetic composition of the epidemic. J. Med. Virol. 85:1139–1147, 2013.

miR-29a associates with viro-immunological markers of HIV infection in treatment experienced patients.

MicroRNAs (miRNAs) are small, non‐coding RNA species essential for the post‐translational regulation of gene expression. Several miRNA have been proposed to contribute to Human immunodeficiency virus‐1 (HIV‐1) infection establishment, progression and latency. Among them, miR‐29a seems to be of particular interest. The aim of this study was to investigate the association between miR‐29a expression and immunologic and virologic markers of HIV infection progression in long‐term antiretroviral‐treated individuals. In a homogenous group of 165 young adults, with chronic HIV infection, parenterally acquired during childhood, the expression level of miR‐29a was found to be inversely correlated with HIV viral load and the degree of immunosuppression, expressed by both CD4 cell count and the CD4/CD8 ratio. There was a significant difference in miR‐29a expression according to the patients response to treatment, with the lowest levels expressed by patients with treatment failure, defined as detectable viremia and CD4 < 350 cells/mm3. No significant correlation was found between miRNA level and the nadir CD4 count or zenith HIV viral load. This study establishes the association between miR‐29a expression and markers of HIV infection in long‐term survivors, treatment‐experienced patients, suggesting its potential use as an indicator for the on‐treatment disease evolution. J. Med. Virol. 88:2132–2137, 2016.

HEPATITIS C VIRUS GENOTYPES IN INJECTING DRUG USERS FROM ROMANIA.

Due to the increasing number of infections related to injecting drug use, both the pattern of hepatitis C virus (HCV) transmission, and the circulating genotypes in Europe have changed. As there are little available data in this respect for Romania, the aim of our study was a preliminary analysis of the distribution of HCV genotypes circulating among injecting drug users (IDUs). Of the 45 IDUs evaluated (86.7% men, mean age − 27.6 ± 3.7 years, mean age at first drug use − 17.5 ± 3.9 years), 88.9% presented anti-HCV antibodies, with higher rates in those with an injecting history of more than 10 years; 57.8% of the subjects had detectable HCV viral load. Only 6.7% had markers of chronic hepatitis B infection, and none had anti-HIV antibodies. While HCV subtype 1b is still prevalent (in 50% of the viraemic subjects), other subtypes begin to emerge, especially in younger patients (1a — in 23.1%, 4 — in 11.5%, 3a — in 7.7% of the cases). These data indicate the possibility of major shifts in the distribution of the dominant subtype, underlining the need for close surveillance of HCV infections in IDUs, who can act as a bridging group toward the general population.

Hepatitis B virus compartmentalization in the cerebrospinal fluid of HIV-infected patients

We detected hepatitis B virus (HBV) DNA in the cerebrospinal fluid (CSF) of 26 adolescents co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) with neurological disease and studied compartmentalization of HBV in the CSF. More than half of the subjects with positive HBV DNA plasma also had CSF positive for HBV. CSF HBV DNA was found in subjects with preserved blood-brain barrier integrity. In a subgroup of these subjects, compartmentalized evolution of HBV was demonstrated by distinct profiles of resistance mutations. Future studies are warranted to determine the clinical significance of HBV presence in the CSF and its contribution to HIV-associated neurological disease.

Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe

The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1-5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries.

Neurologic Complications of Influenza B Virus Infection in Adults, Romania

Infection with this virus should be considered as an etiologic factor for encephalitis.

Complications of Varicella in Unvaccinated Children From Romania, 2002-2013: A Retrospective Study.

The epidemiologic and clinical pattern of varicella-related hospitalizations recorded during 2002–2013 in Romania showed the highest hospitalization rate in the 0–1 year age group. Younger age and diagnosis after 2007 were independent predictors of varicella-related complications, recorded in half of the hospitalized cases.

Predictors of Chronic Hepatitis C Evolution in HIV Co-Infected Patients From Romania

Background Due to a recent alarming increase in the number of HIV-HCV co-infected patients in Romania. Objectives A cross sectional study was conducted to assess the baseline predictors of liver disease evolution. Patients and Methods 83 HIV-HCV co-infected patients, untreated for HCV infection, were evaluated for viral replication, liver fibrosis (estimated by a noninvasive marker - FIB4), and plasma levels of IP-10 (interferon-gamma inducible protein 10) - a cytokine associated with an unfavorable outcome of HCV infection. Results The median value for HCV viral load was high (6.3 log10 IU/mL), 98.8% of the patients were infected with HCV genotype 1. Although 53% of the patients received antiretroviral therapy (cART), only 31.8% of these achieved undetectable HIV levels. HCV viral load was significantly higher in patients with AIDS (6.4 vs. 6.1 log10IU/mL; P = 0.04), and in those naïve for cART (6.5 vs. 5.9 log10 IU/mL; P = 0.04). Severe fibrosis was directly correlated with immunosupression (56% vs. 17.4%, P = 0.03), HCV replication (6.1 vs. 4.9 log10IU/mL P = 0.008), and IP-10 median values (312 vs. 139 pg/ml, P=0.008). A serum IP-10 level higher than 400 pg/mL was significantly associated with FIB-4 median values (4.09 vs. 1.7, P = 0.004), HCV viral load (6.4 vs. 6.1 log10 IU/mL, P = 0.02) and ALT level (206.8 vs. 112.4 IU/L, P = 0.05). Conclusions An important part of the HIV-HCV co-infected patients had negative baseline predictors for the evolution of HCV infection; their therapeutical management must be conducted with special attention towards adherence and potential overlapping drug toxicities. High concentrations of plasma IP-10 are reliable markers for the severity of liver disease.