May 14, 2012, 12:35 PM
Last week, the World Health Organization endorsed the use of experimental drugs in the fight against the Ebola epidemic in West Africa. That is the right decision. There is no proven vaccine or treatment for Ebola, and in light of the severity of the current outbreak, experimental treatments that have not been tested on humans should be an option.
The problem is that these drugs are in exceedingly short supply. Recently, two American aid workers infected with the Ebola virus were treated with the experimental drug ZMapp, and they survived. Unfortunately, only a handful of doses of ZMapp have been produced. For the foreseeable future, even limited deployment of this and other experimental drugs will be impossible.
Is there anything else that could be used to treat Ebola patients? Surprising as it may seem, we believe that several widely available drugs that were initially developed to treat patients with cardiovascular diseases and diabetes may be effective.
More than a decade ago, clinicians noted striking similarities between patients with Ebola and those with bacterial sepsis. Both diseases involve severe dysfunction of the endothelial cells that line blood vessels throughout the body. This dysfunction in turn precipitates major abnormalities in blood coagulation. Both can eventually lead to the failure of internal organs, primarily the liver and kidneys, and organ failure often leads to death. Something similar is seen in many patients with other forms of acute critical illness, including pneumonia and influenza.
Researchers have since discovered that abnormalities of endothelial function and coagulation can be modified or reversed by treatment with drugs such as statins, angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), which were developed to treat patients with cardiovascular diseases and diabetes. Known as immunomodulatory drugs, they also have the ability to modify the body’s response to infection. While they don’t prevent infection itself, they can prevent complications like organ failure.
A clinical trial published in the journal Critical Care in 2012 demonstrated, for example, that early treatment of sepsis patients with a statin reduced the occurrence of organ failure (a complication that often kills Ebola patients) by 83 percent.
Unlike experimental Ebola treatments, these immunomodulatory drugs have been approved and are produced as inexpensive generics. They are available to anyone who lives in a country with a basic health care system, and this includes the countries in West Africa that are struggling to cope with Ebola.
Representatives from the World Health Organization have expressed reservations about what we are proposing. They have suggested, for instance, that the use of such drugs could increase viral replication and worsen the disease. But several studies have shown that statins actually reduce viral replication in human diseases like hepatitis C and improve clinical outcomes.
Our proposal would not be without risk. But the best evidence we have suggests that Ebola patients and their doctors should be given a chance to consider the benefits as well as the risks that these drugs may offer. Nothing should stop physicians from using them as long as they document the impact of treatment on disease outcome.
We want to stress that we support the public health measures that are being used to combat the outbreak. That said, the urgent needs of individual Ebola patients demand that something more be offered.
The challenge presented by Ebola in West Africa could be viewed as one aspect of a larger problem. Perhaps one day these immunomodulatory drugs might be used in the treatment of patients with many forms of acute critical illness, including pneumonia and influenza, much as oral rehydration solution is used to treat patients with severe diarrhea, regardless of the cause.
Viewed in this way, the challenge of treating Ebola patients also represents an opportunity to transform the way acute critical illness is managed throughout the world. We should not pass it by.
Opinion piece by David S. Fedson and Steven M. Opal. David S. Fedson is a retired professor of medicine at the University of Virginia. Steven M. Opal is a professor of medicine at Brown University.
“We want to stress that we support the public health measures that are being used to combat the outbreak. That said, the urgent needs of individual Ebola patients demand that something more be offered”.
David S. Fedson and Steven M. Opal