Medication Summary
Supportive therapy should be the primary focus for clinicians treating patients with suspected or confirmed filovirus infection, including treatment for hypovolemia; electrolyte, metabolic, and hematologic abnormalities; shock; multiorgan failure; and disseminated intravascular coagulation.
Large-volume intravenous (IV) fluids have been used in resuscitation of patients with Ebola virus disease (EVD) evacuated from West Africa. Broad-spectrum antimicrobials have also been used in patients with evidence of septic shock.
Several experimental therapeutics and vaccines are in development for the treatment of EVD. ZMapp, a biopharmaceutical agent comprising three monoclonal antibodies against Ebola virus surface glycoproteins, was developed in a joint Canadian-US effort in 2014, and has shown efficacy in nonhuman primate trials. [32] Although it was used experimentally in 7 patients in 2014 (two of whom died), the utility of ZMapp in these patients was unclear. A multicenter randomized study of ZMapp versus standard therapy did not show clear efficacy, although there was a trend suggesting benefit in patients who received ZMapp. [33]
During the Ebola virus disease outbreak in the Democratic Republic of Congo, Mulangu et al conducted a trial comparing ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, and the triple monoclonal antibody REGN-EB3. On interim analysis, MAb114 and REGN-EB3 showed superiority to ZMapp and remdesivir in reducing mortality. [34]
In 2020, the US Food and Drug Administration (FDA) approved the first therapeutic for Zaire ebolavirus disease in adult and pediatric patients, a mixture of three monoclonal antibodies. [35]
Lassa fever and hemorrhagic fever with renal syndrome (HFRS) due to Hantavirus infection have been treated effectively with IV and oral ribavirin. Because of this, ribavirin has been recommended as a potential treatment for other arenaviruses and bunyaviruses. Treatment is most effective when given early in the clinical course. Ribavirin also is recommended for postexposure prophylaxis. Other potential antiviral therapies against Lassa fever include novel benzimidazole compounds such as ST-193 and other related heterocyclic compounds. [36]
Research into the development of antiarenaviral drugs has focused on broad screening of small molecules with potential antiviral activity. This high-throughput screening (HTS) strategy has previously identified antiviral drugs and may potentially provide novel inhibitors of viral cell entry in the future. [37, 38]
Development of a Lassa virus vaccine is continuing at the US Centers for Disease Control and Prevention (CDC). Yellow fever vaccine is readily available and is both safe and effective. A bivalent vaccine is being developed from the preexisting 17D yellow fever vaccine that would express not only yellow fever glycoproteins but also Lassa glycoproteins, theoretically stimulating a protective immune response against both viruses. [39] A study evaluating the safety and efficacy of a tetravalent dengue vaccine demonstrated full seroconversion against all World Health Organization (WHO) dengue serotypes in flavivirus-naive adults. [40]
Argentine hemorrhagic fever (HF) vaccine (Junin virus vaccine) is also effective and may protect against Bolivian HF as well. Rift Valley fever and Hantaan (HFRS) vaccines are also available.
Although there is no approved vaccine for either Ebola or Marburg virus, significant progress has been made in developing effective experimental Ebola vaccines using multiple viral vector strategies, including vesicular-stomatitis virus (VSV-EBOV) and chimpanzee adenovirus (cAd3-EBO-Z). Human trials in Africa and Europe have yielded safe, immunogenic vaccines against both Ebola and Marburg, based on post-vaccine testing of antibody and T-cell response of trial participants. [41, 42]
Antivirals
Class Summary
The goals in the use of antivirals are to shorten the clinical course, prevent complications, prevent the development of latency and/or subsequent recurrences, decrease transmission, and eliminate established latency.
Ribavirin (Virazole)
Nucleoside analog with antiviral activity; may significantly reduce mortality in Lassa fever and Hantavirus infection if treatment begun within 6 d of onset.
Monoclonal Antibodies
Atoltivimab/maftivimab/odesivimab (Inmazeb, Ebola monoclonal antibodies, REGN-EB3)
Inmazeb is a combination of 3 monoclonal recombinant human IgG1-kappa monoclonal antibodies: atoltivimab, maftivimab, and odesivimab-ebgn. These antibodies simultaneously bind to the glycoprotein on the Ebola virus surface and block attachment and entry of the virus on host cell membranes.
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Ebola virus. Electron micrograph courtesy of the Centers for Disease Control and Prevention.
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Marburg virus. Negative stain image courtesy of the Centers for Disease Control and Prevention.
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Mastomys rodent, natural host of Lassa virus. Image courtesy of the Centers for Disease Control and Prevention.
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Bunyavirus infection. Ecchymoses encompassing left upper extremity one week after onset of CCHF. Ecchymoses often are accompanied by hemorrhage in other locations: epistaxis, puncture sites, hematemesis, melena, and hematuria. Image provided by Robert Swaneopoel, PhD, DTVM, MRCVS, National Institute of Virology, Sandringham, South Africa.
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Apodemus agrarius, the vector of Korean hemorrhagic fever caused by a hantavirus. Photo courtesy of David McClain, MD.
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Bunyavirus infection - Hantaan virus. Patient with Korean hemorrhagic fever caused by Hantaan virus demonstrating typical 'sunburn flush' of cheeks, chin, and base of neck. Photo courtesy of John Huggins, PhD.
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Bunyavirus infection. A patient with Korean hemorrhagic fever demonstrating conjunctival hemorrhages, facial petechiae, and "sunburn flush" of the cheeks. Photo courtesy of John Huggins, PhD.
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Filovirus disease - Ebola fever. Patient with Ebola hemorrhagic fever during 1976 outbreak in Zaire demonstrating palatal petechiae and hemorrhage. Photo courtesy of Joel Breman.
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Patient with morbilliform exanthem of dengue fever. Note islands of sparing, which is characteristic for dengue. Photo courtesy Duane Gubler, PhD.
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Patient with dengue hemorrhagic fever complicated by ecchymoses. Photo courtesy of Duane Gubler, PhD.
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Dengue Virus Notice posted outside Maracanã Stadium, Rio de Janeiro, Brazil, 2012. Translation: This site is a strategic point for controlling Dengue.
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Mastomys natalensis, natural host of Lassa virus. Photo courtesy of BioMed Central, originally published in Kelly JD, Barrie MB, Ross RA, Temple BA, Moses LM, Bausch DG. Housing equityfor health equity: a rights-based approach to the control of Lassa fever inpost-war Sierra Leone. BMC Int Health Hum Rights. 2013 Jan 2;13:2.
Tables
Virus Family |
Disease (Virus) |
Natural Distribution |
Usual Source of Human Infection |
Incubation (Days) |
Arenaviridae |
|
|
|
|
Arenavirus |
Lassa fever |
Africa |
Rodent |
5-16 |
|
Argentine HF (Junin) |
South America |
Rodent |
7-14 |
|
Bolivian HF (Machupo) |
South America |
Rodent |
9-15 |
|
Brazilian HF (Sabia) |
South America |
Rodent |
7-14 |
|
Venezuelan HF (Guanarito) |
South America |
Rodent |
7-14 |
Bunyaviridae |
|
|
|
|
Phlebovirus |
Rift Valley fever |
Africa |
Mosquito |
2-5 |
Nairovirus |
Crimean-Congo HF |
Europe, Asia, Africa |
Tick |
3-12 |
Hantavirus |
Hemorrhagic fever with renal syndrome, Hantavirus pulmonary syndrome |
Asia, Europe, worldwide |
Rodent |
9-35 |
Filoviridae |
|
|
|
|
Filovirus |
Marburg and Ebola |
Africa |
Fruit bat |
2-216 |
Flaviviridae |
|
|
|
|
Flavivirus |
Yellow fever |
Tropical Africa, South America |
Mosquito |
3-6 |
|
Dengue HF |
Asia, Americas, Africa |
Mosquito |
Unknown for dengue HF, 5-7 for dengue |
