Ebola: responding to the challenge

Ebola - not a retrovirus but an international emergency

Ebola did in months what HIV took years to do. There were over 23,000 cases and more than 9,000 deaths as of last week.  The emergency medical coordinator for Ebola in Liberia, Dr Gilles Van Cutsem, of Medecins Sans Frontieres (MSF), described the response to the challenge.  

Ebola is a RNA virus in the same family as Marberg and Lassa fever. The incubation period is 2-21 days with an early febrile stage, then overwhelming GI symptoms, shock and death or recovery.  

The case fatality rate is 30-90%, severity is related to a high viral load at presentation. Transmission is from human to human, via contact with infected fluids. It is not airborne. The animal host is thought to be bats.  

This epidemic is different from previous Ebola epidemics with more cases than all other epidemics combined; previous epidemics have been confined to rural or remote areas and gradually burned out. Now there are massive outbreaks in cities. 

The index patient was a three-year-old child probably infected by a bat in Guinea in December 2013. All family members died rapidly then it spread to distant family and other villages. The first epidemic spread through 500 km.

In March 2014 the second outbreak occurred with rapid spread through neighbouring countries of Liberia and Sierra Leone.  Then there was a third wave of epidemic involving the cities of Monrovia and Freetown and further spread. The hIghest risk of transmission is thought to be later in disease progression; a small infectious viral load only is needed. Five hundred health care workers in Liberia have died. 

The Lagos outbreak was well handled by the Nigerian Ministry of Health. The interventions were based on community education/mobilisation with distribution of protective kits, case/outbreak investigation and contact tracing (which must be rapid), home disinfection, safe transport of patients (for isolation and treatment) and safe burial (it takes six people many hours to ensure decontamination).  One hundred percent of cases on contact lists were traced in Liberia but this is much less in the surrounding countries; in Guinea, 16% of contacts are traced and there the incidence is not falling. 

Current case fatality has been estimated at 51% but the death rate is declining over time in most centres.  A decreased VL on presentation for care has become more common.  The reason for this is unclear; perhaps decreased viral fitness or perhaps a lower infective inoculum in cases because of behaviour change.  

A pregnant woman about to deliver presented to a MSF care station. She was otherwise  asymptomatic and was accepted into the unit only because delivery was very close. She was checked for Ebola because it was routine and found to have a high viral load.  She remained asymptomatic for 3 days.  

Health system closures mean that people are dying from other disease. MSF isolation capacity has been close to full and people died waiting outside the centres. WHO declared a public health emergency only in August 2014 despite several earlier calls for MSF for a response.  MSF had actually called for civil and military biohazard response - unusual for MSF, and the response is still slow and not coordinated. There is a real difficulty balancing patient care and outbreak control.  WHO called for coordination and community organisation on 18 February 2015.   

There is no functional global response to epidemics in countries with fragile health systems. The decreasing incidence in Liberia is largely due to the quality of the response.  The national case manager from Liberia spoke of the country's response - they trained all their HCW and provide training to those who come to help. If there is any next time, the situation should not repeat. 

There was a standing ovation.  

Prevention and Treatment

Prevention and treatment were discussed by H. Clifford Lane from the National Institute of Health.  The NIH was involved following a direct government to government invitation.  

Ebola represents HIV compressed into a couple of months.  Ebola is different from HIV in that  survival means immunity but there is no clear correlate of protective immunity.  There are two current vaccine candidates: recombinant VSV and recombinant chimpanzee adenovirus.  There are the usual vaccine side effects including transient reactive arthritis.  Antibody induction post vaccination has been demonstrated.  

He proposed a trial of a vaccine candidate with probable 50% efficacy and assuming a 1% incidence in Liberia, initially focussing on people at higher risk such as contacts, HCWs and burial teams.  A clinical endpoint study is feasible because of the relatively high mortality and short clinical course. 

Potential therapeutic approaches are neutralising antibodies, nucleoside or nucleotide analogues and agents related to cellular cytotoxicity. Currently there is a monoclonal antibody focused on glycoprotein, a drug called brincidovir, convalescent plasma and an antisense compound. 

An adaptive trial of an investigational intervention would be added to supportive/standard of care. If the experimental arm is effective, then it becomes SOC.  The fatality rate means only 

small sample numbers. Historical controls may not be effective because of changes in the virus over time (74% morality in mid 2014, now at 25%).  The FDA have agreed to easing their licensing  process in this situation.       

Dr Lane emphasised "doing things the right way" and not just "doing something"; compassionate studies muddy the water and complicate subsequent decision making.  Rigorous research programs by extension enhance the local healthcare systems and may improve coordination of the various countries and organisations working in Ebola affected areas.