HCV treatment in Sardinian HIV-HCV coinfected patients: a real-life perspective study on safety, efficacy, and immune reconstitution.

BACKGROUND: HIV-HCV co-infected patients have long been considered difficult-to-treat. The introduction of direct-acting antivirals (DAAs) changed this paradigm.We evaluated the efficacy and safety of DAA-based regimens and the impact of DAAs-induced HCV clearance on the immunological status in HIV-HCV co-infected patients. RESEARCH DESIGN AND METHODS: HIV patients starting HCV treatment with DAAs were included. Sustained virological response at 12 weeks after DAAs treatment (SVR12) was assessed. CD4+ and CD8+ blood cell count and CD4+/CD8+ ratio were recorded at baseline and six months post DAA treatment. We enrolled 201 patients, 76.1% males, median age 54 years, the most common genotypes 3 (29.8%) and 1a (29.4%), 40.3% with cirrhosis, 32.3% with prior interferon-based treatment. All patients were on antiretroviral treatment, 24.4% on methadone maintenance therapy and 22.6% on psychotropic drugs. RESULTS: SVR12 was 98.4%, the most common side effects were pruritus (8.4%), headache (7.4%) and fatigue (5.9%). An increase in CD4+ and CD8+ cell count was observed six months after completion of DAAs treatment, in particular in patients with low CD4+ cell count at baseline. CONCLUSIONS: DAAs treatment resulted in high SVR12 rates, was well tolerated and Increased CD4+ and CD8+, especially in patients with low CD4+ cell count at baseline.

Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection.

BACKGROUND: The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study's focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. METHODS: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. RESULTS: Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1-2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3-0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3-0.7), PM = 0.0005, PMC = 0.005]. CONCLUSIONS: The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection.

[The key role of public health medical resident education for future public health challenges]. / La formazione del giovane igienista per le nuove sfide della sanità pubblica.

INTRODUCTION: The Italian Committee of medical residents in Hygiene, Preventive Medicine and Public Health is a member of the Italian Society of Hygiene, Preventive Medicine and Public Health with the aim of developing a network among Italian resident in public health and promoting the educational path improvement through comparisons and debates between postgraduate medical schools. In this perspective, during last years account has been taken of some essential topics concerning education of public health medical residents, which represent future health-care and public health experts. METHODS: Cross-sectional researches were conducted among Italian public health medical residents (PHMRs) through self-administered and web-based questionnaires. Each questionnaire was previously validated by pilot studies conducted during the 46th National Conference of the Italian Society of Hygiene, Preventive Medicine and Public Health. RESULTS: Seventy percent of Italian PHMRs considered the actual length of Public Health postgraduate medical school excessively long, with regard to predetermined educational goals. Confirming this statement, 90% of respondents were inclined to a reduction from 5 to 4 years of postgraduate medical school length, established by Law Decree 104/2013. Seventy seven percent of surveyed PHMRs stand up for a rearrangement on a national setting of the access contest to postgraduate medical schools. Moreover 1/3 of Italian schools performed less than 75%of learning and qualifying activities specified in Ministerial Decree of August 2005. In particular, data analysis showed considerable differences among Italian postgraduate schools. Finally, in 2015 only four Italian Universities (Napoli Federico II, Palermo, Pavia, Roma Tor Vergata) provide for the Second Level Master qualify for the functions of occupational doctor. This offer makes available 60 positions against a request of over 200 future Public Health medical doctors who have shown interest in the Master. CONCLUSIONS: In Italy, after the introduction of Ministerial Decree 285/2005, the educational course of PHMRs was significantly improved. The standardization of learning and qualifying activities allowed for the first time the attendance at medical directions or Local Health Units. Nevertheless, the excessive lenght of postgradute schools and the differences about training among Italian Universities are critical and actual issue. Moreover, the remarkable interest shown by PHMRs in the Master could suggest a poor job replacement prospect for young medical specialist in Hygiene, Preventive Medicine and Public Health.

Epidemiological impact of mandatory vaccination against hepatitis B in Italian young adults.

BACKGROUND: Viral hepatitis caused by hepatitis B virus (HBV) is a leading cause of acute and chronic liver diseases worldwide. OBJECTIVES: In Italy, a mandatory vaccination policy was introduced in 1991 and was established for all newborns and 12-year-old individuals. In 2004, vaccination of 12-year old adolescents was discontinued, and that of infants was maintained. PATIENTS AND METHODS: We evaluated the seroprevalence of HBV markers in 806 individuals, who were vaccinated at birth or at 12 years of age, to assess the effectiveness of the national policy against HBV. RESULTS: The overall prevalence of anti-HBs antibodies was 90.32% (95% confidence interval [CI]: 88.28-92.36%); 2.23% (95% CI: 1.21-3.25%) of the subjects were positive for both antibodies to HBsAg (anti-HBs) and antibodies to hepatitis B core antigen (anti-HBc), whereas 5.83% (95% CI 4.21-7.45) of the subjects were negative for all markers tested. Further, 1.61% (95% CI: 0.74-2.48%) of the subjects were positive for hepatitis B surface antigen (HBsAg). CONCLUSIONS: Our data provide additional evidence that HBV vaccination can confer long-term immunity when performed at birth and when performed for healthy adolescents; moreover, the results show the effectiveness of the application of a national vaccination strategy.