Managed Care - October 2008 - (Page IS6) Comparative efficacy against culture-confirmed, modified CDC-ILI (ATP population) TIV 10 9 8 7 6 5 4 3 2 1 0 Age group Attack rate (%) Number of cases 55.7% (P< .001) 7.2 9.8 54.4% (P< .001) n=1,852, 6–23 months n=2,084, 24–59 months n=1,834, 6–23 months n=2,082, 24–59 months LAIV 4.5 3.2 Solid bars = matched Hatched bars = mismatched 6–23 months 133 59 24–59 months 205 94 FIGURE 3 Study MI-CP111. Efficacy comparison by age: all strains SOURCE: Belshe 2007 ATP=according to protocol, CDC-ILI=influenza-like illness as defined by the Centers for Disease Control and Prevention, LAIV=live-attenuated influenza vaccine, TIV=trivalent inactivated vaccine. better outcomes with empiric therapy, and without the need to identify target virus, and to develop a vaccine aimed specifically at prevailing strains. Antiviral drugs Influenza-specific antiviral drugs are valuable adjuncts to vaccine in the management of influenza. Prophylactic or early (less than 48 hours after symptom initiation) treatment with these agents has been shown to reduce peak viral titers and limit the severity and duration of influenza-like illness. The agents available today target either the M2 ion channel of the viral envelope (amantadine or rimantadine) or the surface enzyme neuraminidase (oseltamivir or zanamivir). Neuraminidase is an enzyme that breaks down sialic acid on the host cell surface. In the natural history of the influenza virus, the cleavage of sialic acid enables entry of virus into the host cell, as well as the release of replicated virus from infected cells back into the environment. Thus, the neuraminidase inhibitors work both to prevent spread of influenza by blocking release of viral replicates and to reduce severity of illness in the treated patients by blocking virus uptake. The neuraminidase inhibitors have been reported to be 70 to 90 percent effective at preventing onset of both A and B viral influenza, depending on the population studied (Cooper 2003). Prophylactic treatment is cumbersome, however, necessitating daily intake for the duration of an epidemic, generally about 6 to 10 weeks. These agents have proven valuable for reducing the duration and severity of influenza symptoms, lessening the burden of pneumonia and otitis media, and reducing hospitalizations of infected patients (Cooper 2003). The drug must be given within 48 hours of the onset of illness — during which time culture-confirmed diagnosis, prescription, and fulfillment must all be completed — or viral replication will have peaked and the drugs will no longer provide a beneficial effect (oseltamivir phosphate 2008). The ion channel blockers also prevent the virus from penetrating the host cell. As a result, the virus does not replicate. These drugs are generally about 50 percent effective at preventing and 70 percent to 90 percent effective at reducing the intensity of influenza A but not B infection (Couch 1997). A problem occurs, however, when any of the amino acids lining the M2 ion channel mutate, which renders the drug ineffective. Changes in the amino acids are quite common, occurring in about 1 of 1,000 viral particles (Belshe 1989). In this case, when a patient is treated with an ion channel blocker, the stable viruses are eliminated, but resistant, or altered, viruses survive. As they are shed and begin to spread, there is a wave of resistant influenza, which has become a widespread problem limiting the use of these drugs. Conclusion Although influenza is a common and generally benign disease that has at one time or another affected every American in some way, it can in fact be quite devastating. Morbidity from influenza is a major public health concern, and flu pandemics that result from genetic reassortment or viral mutations have caused 6 MANAGED CARE / SUPPLEMENT
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