Ebola 2014

Blood, Sweat, and Ebola – Information Worth Transmitting

Shiyi Geng, PharmD Intern, Steven Lee, PharmD Intern, & Jennifer Seltzer, PharmD

August 2014

Ebolavirus, a type of filovirus, is one of several possible pathogens that can cause viral hemorrhagic fever with a mortality rate of up to 90%.1,2 Ebola virus disease (EVD) outbreaks are typically endemic to regions of Africa, but are still considered a worldwide public health threat due to possible imported infections or biological terrorism.2 The current outbreak, caused by Zaire ebolavirus, is suspected to have originated from a two-year-old boy from southeastern Guinea in December 2013.3 EVD has since spread to other parts of Guinea, Liberia, Sierra Leone, and Nigeria, with a total of 1,848 suspected and confirmed cases resulting in 1,013 deaths as of August 9, 2014.4

There are currently four strains of EVD that cause disease in humans: Zaire ebolavirus, Sudan ebolavirus, Tai Forest ebolavirus, and Bundibugyo virus. Reston ebolavirus has only caused disease in non-human primates.5 EVD was first identified in two outbreaks in Sudan and Democratic Republic of the Congo (formerly known as Zaire) in 1976. The Sudan ebolavirus strain was responsible for the epidemic in southern Sudan.6 The first cases developed in three cotton factory employees located near the town of Nzara and later exported to several nearby towns. The outbreak resulted in 284 reported cases with a 53% mortality rate.7 A different strain, Zaire ebolavirus, caused a nearly simultaneous outbreak in the village of Yambuku and surrounding areas in Democratic Republic of the Congo, where 318 cases were reported with an 88% mortality rate.6,8 EVD then reemerged in the mid-1990s and again in the 2000s, causing several sporadic outbreaks near the equatorial regions of Africa.9 While the natural host of EVD is currently unknown, several species of bats may serve as potential reservoirs.10 EVD can be transmitted between humans through direct contact with bodily fluids (e.g., blood, sweat) from an infected person or contaminated objects.5,9 Potential modes of entry include mucosal surfaces or breaks and abrasions in the skin.2

EVD generally develops following an incubation period of 2 to 21 days and is only contagious in symptomatic individuals.11 Early symptoms of EVD are nonspecific and commonly include fever, chills, malaise, and myalgia.2  An erythematous maculopapular rash of varying severity and gastrointestinal symptoms, such as diarrhea, vomiting, and abdominal pain, often appear by day 5 to 7.  Hemorrhagic manifestations, such as petechiae, ecchymoses, uncontrolled oozing from venipuncture sites, mucosal hemorrhages, and visceral hemorrhagic effusions, occur during the peak of the disease.2 Fever in patients with non-fatal disease typically resolves by day 6 to 11, while patients with a fatal disease experience more severe initial symptoms.12

Diagnosis of EVD can be difficult due to the initial nonspecific disease symptoms and may often be mistaken for malaria, typhoid fever, meningococcal septicemia, typhus, or yellow fever.2 EVD should be considered in the differential diagnosis for those persons experiencing these symptoms and having risk factors (e.g., travel history to affected areas of Africa three weeks prior to the onset of illness, direct exposure to a suspected or confirmed EVD patient, contact with bats, rodents, or primates from endemic areas).13 Viral antigen and nucleic acid can be identified in blood 3 to 16 days after symptom onset. Reverse transcriptase polymerase chain reaction (RT-PCR) testing as well as attempts at virus isolation may assist clinicians in definitively diagnosing patients with EVD.2,14

There is currently no approved drug therapy targeting EVD.  Management of the disease mainly involves isolation and symptom control, which often includes intravenous fluids, antipyretics, and analgesics.2 Treatment with passive immunization using serum from patients who survived the disease has been attempted, but has not shown definite efficacy.15 A “cocktail” comprised of three monoclonal antibodies developed in Nicotiana plants has shown success in non-human primates when used as either postexposure prophylaxis or treatment upon infection confirmation and fever presentation.16,17 This experimental drug, ZMappTM, is currently produced by Mapp Biopharmaceutical, Inc. in San Diego, California, but safety has not been demonstrated in humans and supply is currently limited.18 Two American missionaries and one Spanish priest have received this experimental treatment during the current outbreak.19 As of August 12, 2014, the two Americans showed signs of improvement after receiving the medication, but the Spanish priest has died.20 The efficacy of ZMappTM is still unclear without supportive randomized control trials. Several other companies, including Tekmira Pharmaceutical Corp. and BioCryst Pharmaceuticals, Inc., are also developing experimental treatments or vaccines for EBV.21

The Centers for Disease Control and Prevention has issued a level 3 travel warning for Liberia, Guinea, and Sierra Leone, which strongly encourages all United States residents to avoid any unnecessary travel to these areas.22 In the event that healthcare workers are exposed to EVD cases, preventive measures should be implemented to avoid direct contact with blood or secretions from infected patients or deceased bodies. These include protective clothing, sterilizing equipment, routinely disinfecting work areas, and isolating EVD patients.23 In the midst of mass media attention, healthcare workers can support their community by staying informed and communicating professional, evidence-based data about Ebola.

References:

  1. Bausch DG. Viral hemorrhagic fevers. In: Goldman L, Schafer AI, eds. Goldman’s Cecil medicine. 24th  ed. Philadelphia, PA: Elsevier Inc.; 2012:2147-56.
  2. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011;377(9768):849-62.
  3. Baize S, Pannetier D, Oestereich L, et al. Emergence of Zaire Ebola virus disease in Guinea – preliminary report. New Engl J Med. Apr 16 2014. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1404505.
  4. The Centers for Disease Control and Prevention. 2014 Ebola outbreak in West Africa. Available at: http://www.cdc.gov/vhf/ebola/outbreaks/guinea/index.html.  Accessed August 11, 2014.
  5. The Centers for Disease Control and Prevention. About Ebola hemorrhagic fever.  Available at:  http://www.cdc.gov/vhf/ebola/about.html.  Accessed August 10, 2014.
  6. Pourrut X, Kumulungui B, Wittmann T, et al. The natural history of Ebola virus in Africa. Microbes Infect. 2005;7(7-8):1005-14.
  7. Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team. Bull World Health Organ. 1978;56(2):247-70.
  8. Ebola haemorrhagic fever in Zaire, 1976. Bull World Health Organ. 1978;56(2):271-93.
  9. World Health Organization. Ebola virus disease fact sheet. Available at: http://www.who.int/mediacentre/factsheets/fs103/en/.   Accessed August 10, 2014.
  10. Groseth A, Feldmann H, Strong JE. The ecology of Ebola virus. Trends Microbiol. 2007;15(9):408-416.
  11. The Centers for Disease Control and Prevention. Questions and Answers on Ebola. Available at: http://www.cdc.gov/vhf/ebola/outbreaks/guinea/qa.html.  Accessed August 11, 2014.
  12. The Centers for Disease Control and Prevention. Ebola virus disease information for clinicians in U.S. healthcare settings. Available at: http://www.cdc.gov/vhf/ebola/hcp/clinician-information-us-healthcare-settings.html.  Accessed August 11, 2014.
  13. The Centers for Disease Control and Prevention. Case definition for Ebola virus disease (EVD). Available at: http://www.cdc.gov/vhf/ebola/hcp/case-definition.html.  Accessed August 12, 2014.
  14. Rowe AK, Bertolli J, Khan AS, et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidemies a Kikwit. J Infect Dis. 1999;179 Suppl 1:S28-35.
  15. Mupapa K, Massamba M, Kibadi K, et al. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. J Infect Dis. 1999;179 Suppl 1:S18-23.
  16. Pettitt J, Zeitlin L, Kim do H, et al. Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail. Sci Transl Med. 2013;5(199):199ra113.
  17. Olinger GG, Jr., Pettitt J, Kim D, et al. Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques. Proc Natl Acad Sci U S A. 2012;109(44):18030-35.
  18. Mapp Biopharmaceutical, Inc. ZMappTM information sheet. Available at: http://www.mappbio.com/zmapinfo.pdf.  Accessed August 11, 2014.
  19. Richardson V. Ebola drug ZMapp tested in Europe, on Spanish priest infected in Liberia. The Washington Times. Available at: http://www.washingtontimes.com/news/2014/aug/10/ebola-drug-zmapp-tested-in-europe-on-spanish-pries/?utm_source=RSS_Feed&utm_medium=RSS.  Accessed August 13, 2014.
  20. Cheng M, Giles C. UN: OK to use untested Ebola drugs in outbreak. Associated Press. Available at: http://hosted.ap.org/dynamic/stories/E/EBOLA?SITE=AP&SECTION=HOME&TEMPLATE=DEFAULT.  Accessed August 12, 2014.
  21. The Centers for Disease Control and Prevention. Questions and answers on experimental treatments and vaccines for Ebola. Available at: http://www.cdc.gov/vhf/ebola/outbreaks/guinea/qa-experimental-treatments.html.  Accessed August 11, 2014.
  22. The Centers for Disease Control and Prevention. Travel health notices. Available at: http://wwwnc.cdc.gov/travel/notices.  Accessed August 12, 2014.
  23. The Centers for Disease Control and Prevention. Ebola hemorrhagic fever:  prevention. Available at: http://www.cdc.gov/vhf/ebola/prevention/index.html.  Accessed August 13, 2014.