Viral Sepsis in Children

Gupta, Neha; Richter, Robert; Robert, Stephen; Kong, Michele

Unlike RSV, seasonal vaccines and several antiviral therapies are available to treat influenza viral infections. The seasonal influenza vaccine has demonstrated reasonable efficacy at attenuating influenza A and B viral disease (143) . Currently, two forms of the influenza vaccine are available for use in children: a live attenuated vaccine in the form of a nasal spray and an inactivated vaccine in an injectable form. Antiviral agents used in the treatment and post-exposure prophylaxis of influenza infections include neuraminidase inhibitors (oseltamivir and zanamivir) and the adamantanes (amantadine and rimantadine). Oseltamivir is the most commonly used medication due to high prevalence of adamantane resistance. Oseltamivir has shown to be beneficial and tolerable in children with influenza if received within first 48 h of illness (144, 145) . However, in cases of severe infection, initiation of oseltamivir beyond 48 h of symptom onset may still provide benefit (146) . Nanotechnology-based vaccines are also being developed for influenza virus. InflexalR V and InfluvacR are two virosomal vaccines that have been shown to be efficacious against influenza infection (147, 148) . STP702, another nanotherapeutic agent, is an siRNA under development designed to inhibit conserved regions in H1N1 and H5N1 strains of the influenza virus and prevent viral replication (116) . Nanotraps such as sialylneolacto-N-tetraose c (LSTc)-bearing liposomal decoys bind to hemagglutinins on the influenza virus and prevent viral spread in vitro, demonstrating the potential have shown to be effective against influenza virus (117) . The influenza polymerase inhibitor T-705 (favipiravir) has been demonstrated significant attenuation of influenza virus activity (149) . Interestingly, at higher concentration, it has also shown to be effective against poliovirus, rhinovirus and RSV (149) . Other agents under investigation include CS-8958, a long-acting neuraminidase inhibitor, and DAS181, an attachment inhibitor (150) . Animal studies have also shown promising results with combination therapy (150) . Various immunomodulatory agents have also been posited to temper the dysregulated host inflammatory response in severe influenza (151) , including cyclooxygenase-2 inhibitors (152), doxycycline (153) , glucocorticoids (154) , macrolides (155, 156) , peroxisome proliferator-activated receptor agonists such as gemfibrozil (157), sphingosine-1-phosphate (158) , and the Tie2 receptor activator vasculotide (65) . Further studies are needed to determine the efficacy of these treatments in human influenza infection.