FEASIBILITY OF VACCINATION IN PREVENTING SECONDARY CASES OF HEPATITIS A VIRUS INFECTION

Although the secondary transmission of hepatitis A virus (HAV) infection is preventable through vaccination, it is not known whether the vaccination of household contacts is feasible. To this end, we conducted a prospective cohort study among the household contacts, 40 years of age or less, of all persons infected with primary HAV infection (index cases) and admitted to eight hospitals in southern Italy within 7 days of onset. Household contacts were vaccinated, and serum samples were taken at vaccination and after 14 and 45 days. Secondary cases were defined as those with IgM seroconversion occurring at least two weeks after enrolment. Coprimary cases were those assumed to have had the same exposure as the index case. Susceptible cases were those who were negative for both IgG and IgM. A total of 495 household contacts participated (acceptance rate of 65%); 65% were vaccinated within 4 days of admission of the index case and 95% within 7 days. At enrolment, 196 (39.6%) household contacts were immune (IgG-positive serum). During follow-up, 19 (3.8%) were IgM-positive: 13 (2.6%) were coprimary cases and 6 (1.2%; 95% CI: 0.2–3.2) secondary cases (5 identified at 14 days from vaccination and 1 at 45 days). Of the 241 susceptible cases, 192 (79.7%) had developed IgG antibodies at 14 days and only 3 (1.2%) did not develop IgG antibodies at 45 days. The 65% acceptance rate and the finding that 95% of the participating household contacts were vaccinated within 7 days of the index case’s hospitalization indicate that timely vaccination is indeed feasible. The necessity of returning for the collection of blood samples probably decreased the acceptance rate

Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans

Following binding to cannabinoid receptors, endocannabinoids regulate a variety of central nervous system processes including appetite and mood. Recent evidence suggests that the systemic release of these lipid metabolites can be altered by acute exercise and that their levels also vary across the 24-h sleep wake cycle. The present study utilized a within-subject design (involving 16 normal-weight men) to determine whether daytime circulating endocannabinoid concentrations differ following three nights of partial sleep deprivation (4.25-h sleep opportunity, 2:45-7 a.m. each night) vs. normal sleep (8.5-h sleep opportunity, 10:30 p.m.-7 a.m. each night), before and after an acute bout of ergometer cycling in the morning. In addition, subjective hunger and stress were measured. Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5 h after awakening (vs. normal sleep, p< 0.05) when participants were sleep-deprived. This coincided with increased hunger ratings (+25% vs. normal sleep, p < 0.05). Moreover, plasma 2AG was elevated 15 min post-exercise (+44%, p <0.05). Sleep duration did not however modulate this exercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (p < 0.05). Given that activation of the endocannabinoid system has been previously shown to acutely increase appetite and mood, our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway. In contrast, more pronounced exercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration

Long-term lymphoblastoid interferon-α therapy for non-cirrhotic chronic hepatitis C: An Italian multicentre study on dose and duration of IFNα treatment

The aims of the study were to evaluate the long-term efficacy and tolerability of different doses of interferon-α (IFNα) and different durations of treatment in chronic hepatitis C by comparing 3 or 6 mega units (MUs) three times weekly given for either 12 or 24 months, and the possibility of obtaining a response in non-responder patients by increasing the dose or by administering IFN daily. A total of 504 patients with non- cirrhotic chronic hepatitis C enrolled in a multicentre study were consecutively assigned to receive either 3 (255 patients) or 6 MU (249 patients) of lymphoblastoid IFNα 3 times a week (tiw). At the 12th month of therapy, patients with normal aminotransferase (AMT) in both groups were either given IFN for an additional 12 months with an unmodified or halved dose, or else discontinued therapy. For patients with unmodified AMT levels after 6 months of therapy, the IFN dose was doubled in the 3-MU group, while it was administered at 3 MU daily in the 6-MU group. When no improvement was achieved, therapy was discontinued; otherwise it was prolonged until the 18th month. Patients were followed up for 12 months after discontinuing IFN. Of the 255 patients enrolled at 3 MU, therapy was stopped during the first 6 months in 36 patients (14.1%) because of side effects, and in 24 (9.4%) because of lack of cooperation. Of the remaining 195 patients at the 6th month of therapy, 119 (61%) had normal and 76 (39%) unmodified AMT levels; 14 of the 76 normalized AMT after doubling the dose of IFN, but only 5 (6.6%) had a sustained response. Of the 119 patients with normal AMT, 40 discontinued IFN at the 12th month (schedule A), 39 remained at 3 MU tiw (schedule B) and 40 were given a dose of 1.5 MU tiw (schedule C) for an additional 12 months. At the end of follow-up, 23/40 (57.5%) patients in schedule A, 31/39 (79.5%) on schedule B and 29/40 (72.5%) on schedule C still had normal AMT (A vs. B p = 0.04). In an intention-to-treat analysis, the sustained response rate for patients enrolled at 3 MUs, including the 5 initial non-responders, was 34.5%. Of the 249 patients enrolled at 6 MU, therapy was discontinued during the first 6 months for 39 (15.7%) because of side effects, and for 27 (10.8%) because of lack of cooperation. Of the remaining 183 patients at the 6th month of therapy, 110 (60%) had normal and 73 (40%) unmodified AMT levels. Of the 73 patients, 55 accepted the daily regimen and 8 of them (14.5%) showed a sustained response. Of the 110 patients with normal AMT, 32 (29.1%), despite normalization of AMT, spontaneously discontinued IFN or reduced the dose because of a poor quality of life, while 78 continued with 6 MU until the 12th month, when therapy was discontinued for 28 (schedule A1); 24 patients were given an unmodified dose (schedule B1) and 26 a halved dose (schedule C1) for an additional 12 months. At the end of follow-up, 18/28 (64.3%) patients on schedule A1, 19/24 (79.2%) on schedule B1 and 19/26 (73.1%) on C1 still had normal AMT (p = NS). In an intention-to-treat evaluation, the sustained response rate for patients enrolled at 6 MU, including the 8 from the daily treatment, was 25.7% (64/249). HCV viraemia was undetectable 1 year after discontinuation of IFN in 72.6% of patients with a sustained response. Sustained response was observed in 36.4% of patients with minimal, 46.6% of those with mild, and 33.3% with moderate or severe histological activity (p = NS). The rate of sustained response was lower in patients with genotype 1b (23.6%) than in those with genotype 2a (67.8%, p = 0.002) or genotype 3 (50%, p = 0.03), irrespective of the histological activity. In conclusion, 6 MU IFNα are no more effective than 3 MU in inducing a sustained response in treatments of both 12 and 24 months. A 24-month treatment is more effective than a 12-month treatment in maintaining a biochemical response after discontinuation of IFN. In terms of efficacy, compliance and cost, 3 MU for 24 months appears to be the best treatment schedule. The benefit of doubling the dose of IFN for the 3 MU non-responders is slight, while the daily administration of 3 MU IFN seems to be more effective