Given the phase trial results we sought

Given the phase 1 trial results, we sought to address a complementary question whether VIS410 could be successfully deployed in the event of an epidemic outbreak to improve public health outcomes. We predicted that given VIS410\'s half-life, its distribution to the primary site of influenza A infection (nasopharynx) and its potency, that limited, directed use of the agent would reduce the total burden of disease. We note that universal prophylaxis is unlikely to be practical or feasible. To test the fbpase of the ability of VIS410 to reduce influenza disease burden, we developed a micro-simulation of seasonal influenza that is in good general agreement with observed attack rates. In multiple scenarios, administration of a broadly neutralizing antibody like VIS410 at an estimated dose of 8–16mg/kg to the at-risk elderly, for example in nursing homes and within the hospital, prior to the peak of an influenza outbreak reduces the frequency of serious influenza. We find that this effect can be achieved even with administration of VIS410 at a relatively low coverage (between 2% and 6%), having a measurable impact on mitigating hospitalization events in an influenza A outbreak. Sensitivity analysis of the models indicates that timing of administration may be a crucial component of the decision-making process for the deployment of VIS410 as a prophylaxis. Our analysis suggests that between four to eight weeks prior to an epidemic peak is the optimal timing for deployment, and this is also dependent on the dose given which determines the length of an individual\'s protective period. As recently developed climate-based models have made influenza peak forecasting possible with a four to six week lead time (Shaman et al., 2013; Shaman and Karspeck, 2012), it may in fact be possible to have accurate enough influenza prediction to begin the early roll-out of a prophylaxis. One of the key challenges may be determining whether an influenza season will be short or long, and the forecasting exercises would need to be re-run with this exact scenario in mind: timed deployment of a population-level prophylactic whose aim is to stem transmission and reduce hospitalizations in the elderly. Desirable outcomes for influenza public health interventions include reductions in attack rates and hospitalizations across all age groups. For hospitalization reductions in particular, chorionic villi sampling (CVS) is usually not possible to prioritize one age group over another, and for this reason there is a long unresolved question in influenza about the age-targeting of public health interventions — should high-contact or high-vulnerability individuals be targeted for intervention? Targeting high-contact individuals may have a larger impact on mitigating the epidemic as a whole, including larger attack-rate reductions in high-vulnerability individuals (Fig. 3a). On the other hand, targeting high-vulnerability individuals has a more direct and measurable impact on the individuals that receive prophylaxis (Fig. 3c), and it may make it easier to argue for higher coverage levels if it can be clearly seen that protection is highly efficacious on an individual level.
Acknowledgments
Introduction Otitis media (OM) is the second most important cause of hearing loss, which ranked fifth on the global burden of disease and affected 1.23 billion people in 2013 (Global Burden of Disease Study 2013 Collaborators, 2015). It is one of the most common childhood illnesses and constitutes a major chronic disease in low and middle-income countries (Global Burden of Disease Study 2013 Collaborators, 2015; World Health Organization, 2004). The incidence of OM in sub-Saharan Africa (SSA), South Asia and Oceania is two- to eight-fold higher than in developed world regions with India and SSA accounting for the majority of OM related deaths (Monasta et al., 2012; Acuin, 2004). Common types of OM include acute otitis media (AOM), otitis media with effusion (OME), and chronic suppurative otitis media (CSOM) (Paparella et al., 1985). OM is often misdiagnosed, or not diagnosed at all, and consequently treated incorrectly which may lead to serious, or even life-threatening complications (Asher et al., 2005; Buchanan and Pothier, 2008; Legros et al., 2008).