September 7, 2014

Ebola Virus Disease Response: Public Health Insfrastructure and Experimental Drugs

Ebola virus disease (EVD) has appeared in several West African nations over the last several months, and is now spreading with increasing speed. The international public health response has involved World Health Organization (WHO), Centers for Disease Control (CDC), Doctors Without Borders (MSF), and local public health authorities, among others. WHO has now formulated an Ebola response roadmap for the crisis.The history of Ebola virus outbreaks shows the first recognition of the pathogen in 1976, followed by several decades of periodic outbreaks with various virus subtypes. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease (NIAID), placed the current EVD outbreak in historical context
In most instances, the virus emerged in geographically restricted, rural regions, and outbreaks were contained through routine public health measures such as case identification, contact tracing, patient isolation, and quarantine to break the chain of virus transmission. In early 2014, EVD emerged in a remote region of Guinea near its borders with Sierra Leone and Liberia. Since then, the epidemic has grown dramatically, fueled by several factors. First, Guinea, Sierra Leone, and Liberia are resource-poor countries already coping with major health challenges, such as malaria and other endemic diseases, some of which may be confused with EVD. Next, their borders are porous, and movement between countries is constant. Health care infrastructure is inadequate, and health workers and essential supplies including personal protective equipment are scarce. Traditional practices, such as bathing of corpses before burial, have facilitated transmission. The epidemic has spread to cities, which complicates tracing of contacts. Finally, decades of conflict have left the populations distrustful of governing officials and authority figures such as health professionals. Add to these problems a rapidly spreading virus with a high mortality rate, and the scope of the challenge becomes clear. 
To date, at least 3,000 cases and over 1800 deaths have been reported in the West Africa nations of Sierra Leone, Guinea, and Liberia, with numbers rising. Isolated cases are also observed in Nigeria and Senegal. To date, the case fatality rate is estimated at around 60%. No vaccine or effective antiviral is currently available against the virus. An unapproved cocktail of monoclonal antibodies produced by Mapp Biopharmaceutical of San Diego, called ZMapp, was administered to several health workers from the U.S.; their recovery may be partially explained by the use of this drug (although their access raises ethical questions regarding how to allocate scarce countermeasures). That drug essentially transfers an immune response to the patient (passive immunity). The other modalities for EVD treatment and prevention are the more commonly known avenues of vaccines that elicit the patient’s own immune response and/or antiviral drugs which interfere with virus replication. The availability of vaccines and antivirals for “emerging or reemerging diseases” illustrates the deficiencies in matching market realities to public health demands. The research that led to ZMapp was partially funded by the U.S. government as part of its program to establish medical countermeasures against a bioterrorist attack (resources that greatly expanded after 9/11). The supply of ZMapp is limited; HHS is now funding expanded production and formal clinical trials of the drug. In addition, several Ebola vaccines will enter clinical trials soon. But the availability of countermeasures, while necessary, is not the only determinant of how soon the outbreak (not yet called a pandemic) will be contained. The international public health infrastructure, ideally coordinated by WHO, is dependent on funding from national governments, and mandated funding has declined over the years, undercutting WHO's capabilities. WHO did not declare a public health emergency until August,  despite the fact that cases began to spread in March. While more vaccines and antivirals can make a difference in any viral disease outbreak, the spread of EBV could have been managed with a more robust public health emergency response earlier this year. MSF has called for countries with biological disaster response teams (e.g., U.S.) to send these personnel to the regions to augment field hospitals, diagnostic laboratories, and other facilities needed to manage the crisis.