Treatment/Control
The unknown source(s) harboring the virus, the poorly understood host/pathogen correlates of immunity, the lack of a good animal model system, and the need to have special laboratory facilities when dealing with infected materials are among the challenges that have plagued and hindered the progress in developing effective therapeutic and prophylactic treatments to combat the lethal infection caused by Ebola virus. Due to the fact that there is a rapid onset of infection and a high rate of pathogenicity once the virus starts replicating, there is little time for the generation of an adequate antiviral immune response by the host. Due to the many roadblocks, there are no known treatments to prevent or treat the infection to date. Conventional treatment methods are limited to providing supportive palliative care to the afflicted patients. These supportive measures include hydrating the patient by administering fluids and electrolytes, supplementing oxygen as needed, monitoring blood pressure and cardiac rhythms, and treating the patient for any complicating infection (antiretroviral therapy as needed). To prevent nosocomial infection among healthcare and research workers as well as third parties individuals, such as friends and family members, the Centers for Disease Control has published general guidelines and has recommended the use of Universal Precautions when caring for a patient suspected to have contracted the virus as well as for handling infected materials. These guidelines include the isolation of the patient to a private room, that may or may not require to be equipped with a negative pressure system; this will depend on how advanced the patient's symptoms are. Access to the room should only be permitted to essential personnel, such as the doctor and an auxiliary nurse. All the materials that have come in contact with the patient or the patient s fluids should be either disposed in appropriate, marked containers or, when applicable, should be sterilized. If the patient dies, it is generally recommended that the patient be wrapped in a sealed, leakproof material and be either cremated or buried in a sealed casket within few hours after death. (click image for bigger version) |
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In spite of the difficulties and due to the severe pathogenesis and the potential for the virus to be used a biological weapon, research is continuously being done to find adequate treatments. For instance, some studies have suggested that neutralizing antibodies may play a protective role against the viral attack at the onset of infection. Thus, it has been speculated that administration of neutralizing antibodies to patients in the early phase of infection, may at the very least ameliorate the symptoms of the disease and may even, in some cases, retard disease progression. Some studies have shown therapeutic benefits by administration of neutralizing antibody against the viral transmembrane glycoprotein (GP) in rodent models. Furthermore, research done by Russian investigators has used hyper-immune horse serum that appears to have conferred protection to both baboons and guinea pigs; however, it failed to protect Cynomolgus monkeys. A tangible problem with the use of horse hyper-immune sera is that it would not be an acceptable treatment in humans due to the possible severe immunoreactive response to IgG gamma present in the horse serum. Other treatment approaches have included the use of monoclonal and polyclonal antibodies administered alone or in combination with immunomodulators such as IFN-a; these approaches, in particular the combination of antibodies with IFN-a have yielded some encouraging results in mice, but not in macaques. The use of antibodies as therapeutic agents to treat infection has been criticized by some researchers who believe that the presence of antibodies may actually be an ally to the virus by enhancing its ability to infect cells.
Some investigators have also explored sera transfusion from convalescent patients to infected patients as a means of therapy. During the 1995 EBOV-Z outbreak in Zaire there some claims that whole blood infusion offered complete protection to 7 out of 8 patients; however, because the pathogen seemed to have been less virulent during that particular outbreak, it is still unclear whether the transfusion alone was the only factor contributing to the recovery of the patients.
Other treatments that have been explored include the use of chemical compounds, such as S-adenosylhomocysteine hydrolase inhibitors, to block certain biochemical pathways important for virus replication or survival. For instance, S-adenosylhomocysteine hydrolase inhibitors have been shown to prevent in vitro translation of the viral mRNAs and have conferred therapeutic protection to BALB/c mice treated 1 or 2 days post-infection. These compounds have been shown to prevent in vitro translation of the viral mRNAs and have conferred therapeutic protection to BALB/c mice treated 1 or 2 days post-infection. However, these therapeutic benefits were not seen in studies performed on macaques where the only apparent benefit was a delay in death rate by a few days. Other approaches that have been explored include the use of recombinant nematode anticoagulant protein c2 (rNAPc2), which efficiently inhibits factor VIIa/tissue factor. This procoagulant factor has been shown to be overexpressed in primate monocytes and macrophages. A 2003 study done by Thomas Geisbert et al in rhesus monkeys showed that administration of rNAPc2 was able to delay the death rates, and in some cases, enhanced survival rate, among the treated animal subjects compared to the control groups. The benefits of this therapy in human primates have not been determined.
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This page last updated: 14 April 2004.
