Increasing incidence of HIV- associated tuberculosis in Romanian injecting drug users.

BACKGROUND: A high prevalence of tuberculosis (TB) among HIV-positive injecting drug users (IDUs) may fuel the TB epidemic in the general population of Romania. We determined the frequency and characteristics of TB in HIV-infected IDUs referred to a national centre. METHODS: Prospective observational cohort study of all newly-diagnosed HIV-positive IDUs admitted to Victor Babes Hospital, Bucharest, between January 2009 and December 2014. Socio-demographics, clinical characteristics and outcomes of HIV/TB co-infected IDUs were compared to HIV-positive IDUs without TB. RESULTS: 170/598 (28.5%) HIV-infected IDUs were diagnosed with TB. The prevalence increased from 12.5% in 2009 to 32.1% in 2014 (P < 0.001). HIV/TB co-infected individuals had lower median CD4 cell counts 75 (vs. 450/mm3 , P < 0.0001) and higher median HIV viral loads 5.6 log10 (vs. 4.9 log10 , P < 0.0001) when presenting to healthcare services. 103/170 (60.6%) HIV/TB co-infected IDUs were diagnosed with pulmonary TB. Resistant Mycobacterium tuberculosis strains were common, with 18/105 (17.1%) of patients having Multi-Drug Resistant (MDR) disease. Higher mortality rate was associated with TB co-infection (P < 0.0001), extra-pulmonary TB (P = 0.0026) and extensively drug resistant TB (P = 0.024). CONCLUSIONS: Tuberculosis (TB) is an increasing problem in HIV-infected IDUs in Romania. Presentation is often with advanced HIV, significant TB drug resistance and consequent outcomes are poor.

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. AIM: To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.

Alisporivir with peginterferon/ribavirin in patients with chronic hepatitis C genotype 1 infection who failed to respond to or relapsed after prior interferon-based therapy: FUNDAMENTAL, a Phase II trial.

Alisporivir (ALV) is an oral, investigational host-targeting agent, with pangenotypic activity against hepatitis C virus (HCV). This randomized, double-blind, placebo-controlled, Phase II study explored the efficacy and safety of ALV with peginterferon-α2a/ribavirin (PR) in patients with chronic HCV genotype 1 infection in whom prior PR had failed (43% relapsers, 34% null responders and 23% partial responders). Four-hundred-and-fifty-nine patients were randomized (1:1:1:1) to ALV 600 mg once daily (QD), ALV 800 mg QD, ALV 400 twice daily (BID) or placebo plus PR for 48 weeks. When the global ALV trial programme was put on clinical hold, all patients in this study had received ≥31 weeks of randomized treatment; patients completed 48 weeks on PR alone. All ALV groups demonstrated superior rates of complete early virologic response (cEVR; primary endpoint) vs PR alone (P ≤ 0.0131), with highest cEVR rate seen with ALV 400 mg BID (74% vs 36% with PR alone; P < 0.0001). Respective SVR12 rates (key secondary endpoint) were 65% vs 26% in prior relapsers, 63% vs 5% in partial responders and 68% vs 3% in null responders. In patients who received >40 weeks of randomized treatment, the SVR12 rate was 89% for ALV 400 mg BID vs 30% for PR alone (P = 0.0053). Rates of viral breakthrough and relapse were lowest with ALV 400 mg BID. One case of pancreatitis (fully recovered) occurred with ALV/PR. Common AEs were headache, fatigue, anaemia, neutropenia and nausea. Hypertension was infrequent, but more common with ALV. ALV merits further investigation in interferon-free regimens in combination with direct-acting antiviral agents.

Plasmodium vivax malaria in a Romanian traveller returning from Greece, August 2011.

In August 2011, a Plasmodium vivax malaria infection was diagnosed in a Romanian traveller returning from Greece. This case together with several reports over the past decade of autochthonous cases in Greece highlight that malaria should be considered as differential diagnosis in symptomatic travellers returning from this country. Travellers may serve as sentinels of emerging vector-borne diseases.

Clinical effects of erdosteine in the treatment of acute respiratory tract diseases in children.

Erdosteine has positive effects on mucus rheology and transport due to the active metabolite (Metabolite I) which contains a free thiol group. Erdosteine inhibits bacterial adhesiveness and has antioxidant properties. A synergistic effect of erdosteine with various antibiotics has been demonstrated in pharmacological and clinical studies. The present study was multicenter, randomized, double-blind and placebo-controlled. The aims of the study were to compare a combination of erdosteine with amoxicillin against an amoxicillin-placebo combination in pediatric patients with acute lower respiratory tract disease. A total of 158 patients (78 in the erdosteine group and 80 in the placebo group) were treated for 7 +/- 2 days. The efficacy parameters were cough (primary), polypnea, rhonchi, rales and body temperature (all measured at baseline, on Day 3 and at the end of treatment). Safety was assessed by strictly monitoring the occurrence of adverse events and using standard laboratory parameters. The results of the intention-to-treat analysis showed that the severity of cough was decreased by 47% at Day 3 in the erdosteine group with a statistically significant difference compared to placebo, the difference was still significant at the final visit. The decrease in the severity of rales was significantly greater at Day 3 in the erdosteine group than in the placebo group. The incidence of polypnea and rhonchi in the two groups showed similar decreases, an improvement mainly due to the antibiotic. No adverse events occurred and no adverse changes in laboratory parameters were observed. It is concluded that the combination of erdosteine and amoxicillin is a safe medication which is clinically superior to that of the antibiotic combined with placebo, especially in regard to the effects on cough.

Clinical manifestations in the West Nile virus outbreak.

During the summer of 1996 an unusual clustering of meningoencephalitis cases was recorded in the Capital City, Bucharest, and in some areas from South-East Romania. After an initial suspicion of an enteroviral etiology was discarded, the West Nile etiology was confirmed by specific antibodies demonstration through hemagglutination-inhibition and ELISA tests. This study included 251 patients with the diagnoses of West Nile acute encephalitis (166 cases), acute meningitis (57 cases) and acute febrile disease (33 cases). The patients' age ranged from 1 to 89 years (mean 51.1 years). The most frequent clinical manifestations were: fever (95.7% of cases), cephalalgia (92.6%), stiffness of the neck (89.1%), vomiting (62.5%), marked asthenia (46.5%), myalgia (28.9%). In addition, patients with encephalitis exhibited: alteration of consciousness (89.2% of cases), tremor of extremities (40.4%), ataxia (44%), paralysis (15.1%). The fatality rate was 15.1% in acute encephalitis, 1.8% in acute meningitis and 0% in the acute febrile disease.