Viral clearance or persistence after acute hepatitis C infection: interim results from a prospective study.

OBJECTIVE: Hepatitis C virus infection (HCV) has a high rate of chronic evolution; however, the underlying mechanisms remain to be elucidated. We investigated natural clinical, virological, and immunological course of acute HCV infection in order to identify possible prognostic factors of spontaneous resolution and to gain more understanding of early characteristics responsible for viral clearance or persistence. MATERIALS AND METHODS: Eight patients with acute symptomatic hepatitis C were prospectively followed up for more than 6 months (range, 8-14 months). None of the individuals received antiviral therapy during the study period. We analyzed biochemical, virological, and immunological parameters of these patients detected at different time-points of the follow-up. Plasma HCV RNA was quantitated using TaqMan real-time polymerase chain reaction. Virus-specific CD4(+) T cells were enumerated by interferon-gamma (IFN-gamma) ELISpot assay. RESULTS: Two of eight individuals resolved HCV spontaneously, while the remaining patients developed chronic HCV infection. HCV RNA became undetectable within 14 days of the study, followed by a rapid alanine aminotransferase normalization in patients with resolved infection. On the contrary, chronically infected subjects demonstrated persistent viremia or intermittently undetectable HCV-RNA, accompanied by polyphasic alanine aminotransferase profile throughout the study. Patients with self-limited hepatitis C displayed the strongest virus-specific CD4(+) T (IFN-gamma) cell reactivity within the first weeks of the follow-up, while persistently infected subjects initially showed a weak antiviral CD4(+) T (IFN-gamma) cell response. CONCLUSIONS: In most cases, acute hepatitis C progresses to chronic disease. Viral clearance within the first month after clinical presentation accompanied by monophasic alanine aminotransferase profile could predict recovery. Early and strong CD4(+)/Th1 immune response against HCV might play an important role in the disease resolution.

Inhaled zanamivir versus placebo for the prevention of influenza outbreaks in an unvaccinated long-term care population.

BACKGROUND: Antiviral chemoprophylaxis effectiveness for influenza control has not been prospectively established for unvaccinated residents of long-term care facilities. This study evaluated the efficacy and tolerability of zanamivir against the standard of care (no intervention, ie, placebo) for influenza outbreak control in a largely unvaccinated institutionalized population. OBJECTIVE: To evaluate the efficacy and tolerability of zanamivir versus placebo for influenza outbreak control in long-term care facilities. METHODS: This double-blind, randomized, placebo-controlled study prospectively enrolled/followed residents of long-term care facilities (LTCF) at 12 centers for 1 to 3 influenza seasons (1997 to 2000). Following influenza outbreak declaration, asymptomatic subjects were randomized for prophylaxis to inhaled zanamivir 10 mg or inhaled placebo given once daily for 14 days. The proportion of randomized subjects who during prophylaxis developed symptomatic, laboratory-confirmed influenza (SLCI) was the primary end point. RESULTS: Influenza outbreaks were explosive. The attack rates varied from 9.5 to 14.8 per 100 residents. Of 1763 consents given and resulting in 494 randomizations, 49% received zanamivir and 51% placebo; 66% were elderly and 9% were vaccinated. SLCI occurred in 6% of zanamivir and 9% of placebo subjects (P = .355; protective efficacy for zanamivir = 29%, 95% confidence interval 31% to 62%), and symptomatic influenza confirmed by culture in 2% and 6%, respectively (P = .052; protective efficacy = 65%, 95% confidence interval 8.5% to 86%). Zanamivir use was also associated with a 70% (95% confidence interval 13% to 89%) reduction in laboratory-confirmed influenza with fever (2% vs 6%, P = .043). Influenza B was not detected. Zanamivir was well tolerated. No virus isolate demonstrated zanamivir resistance. CONCLUSIONS: The protective efficacy of zanamivir versus placebo for SLCI was marginal, for all laboratory confirmed illnesses, but significant against culture proven and febrile influenza, suggesting zanamivir can be effective for outbreak control and symptom reduction of unvaccinated institutionalized residents. Zanamivir had an acceptable safety profile in elderly, high-risk LTCF residents and was not associated with the emergence of resistant strains.