Combination Antiviral Therapy in Influenza Epidemics

Currently, only four drugs in two classes (adamantanes [AMs] and neuraminidase inhibitors [NAIs]) are approved for the treatment and prophylaxis of influenza infection; resistance to AMs (A/H3N2) > A/H1N1 and A/H5N1) and oseltamivir (A/H1N1) have become major public health problems. Because combination therapy might reduce or delay the development of drug resistance, we consider the use of combination therapy for the mitigation of an influenza epidemic. We follow our previous approach (Stilianakis et al. 1998) by developing a mathematical susceptible-infected-recovered (SIR) model that describes the effects of drug treatment and resistance on the transmission dynamics of an influenza outbreak in a closed population. We expand our model to explore whether treatment with one AM in combination with one NAI, alone or together with prophylaxis with one AM or one NAI, would be an effective intervention strategy during an influenza epidemic, compared to monotherapy. We investigate three intervention scenarios: treatment of symptomatic persons, prophylaxis of susceptibles, and both prophylaxis and treatment combined. We find that continuous chemoprophylaxis throughout an epidemic can reduce the number of illness by approximately 80%. We show that, depending on the duration of prophylaxis, combination therapy can dramatically reduce the number of illnesses compared to monotherapy, and hence delay the development of drug resistance significantly. With monotherapy, drug resistance develops quickly, reducing treatment efficacy; combination therapy would offer a significant improvement over monotherapy in these respects as well.

STILIANAKIS Nikolaos;  MURILLO Lisa;  MURILLO Michael;  HAYDEN Frederick;  PERELSON Alan; 

2009-05-19

Los Alamos Center for Bio-Security Science

JRC51700

https://publications.jrc.ec.europa.eu/repository/handle/JRC51700,