APPENDIX 2 Marburg Virus • Classified among the highest priority for bioterrorism agents by the CDC (Category A) Disease Agent: Common Human Exposure Routes: • Marburg virus (MARV) • Original cases resulted from extremely close contact Disease Agent Characteristics: with monkey blood or cell cultures. • Body fluids, including those from skin or mucous • Family: Filoviridae; Genus: Marburgvirus, Species: membranes, are infectious. Risk exists from Lake Victoria Marburgvirus parenteral inoculation with contaminated needles • Virion morphology and size: Enveloped, helical, and syringes. cross-striated nucleocapsid symmetry, with filamen- • Sexual transmission is theoretically possible but tous or pleomorphic virions that are flexible with unconfirmed. Nucleic acid has been detected in extensive branching, 80 nm in diameter and 790- semen for many weeks after clinical recovery. 860 nm in length • MARV is present in infected human alveoli and in • Nucleic acid: Linear, negative-sense, single-stranded aerosol particles. This could lead to human transmis- RNA, ~19.1 kb in length sion by the aerosol route but is considered to be • Physicochemical properties: Stable at room tempera- inefficient. ture and can resist desiccation; inactivated at 60°C for • Infectivity seems to be higher during the patient’s 30 minutes; infectivity greatly reduced or destroyed hemorrhagic phase. by UV light and gamma irradiation, lipid solvents, b-propiolactone, formaldehyde, sodium hypochlo- Likelihood of Secondary Transmission: rite, and phenolic disinfectants • In the original outbreak, 6 of 31 infections observed Disease Names: among health-care workers represented secondary transmission. They were associated with blood and • Marburg hemorrhagic fever (MHF) body fluid (possibly vomit, urine, and stools) expo- • Marburg virus disease sures. In one study, the secondary attack rate was esti- • Durba syndrome mated as 23% for family members sleeping in the Priority Level: same room with the patient versus 81% for those pro- viding direct care. • Scientific/Epidemiologic evidence regarding blood • MARV remains viable for 4-5 days in dried blood. safety: Theoretical; viremia is a feature of symptom- atic infection with this agent. Asymptomatic viremia At-Risk Populations: has been neither well studied nor sought aggressively, so there are few or no data to make a critical assess- • Humans in contact with Marburg infected sick ment of risk. persons, dead primates, infected tissues, or cell • Public perception and/or regulatory concern regard- cultures. ing blood safety: Very low/Absent • A threat as a bioterrorist weapon for populations not • Public concern regarding disease agent: Low previously considered being at risk Background: Vector and Reservoir Involved: • 1967: Initially described in Marburg (Germany) and • Suspected to be a zoonosis with incidental transmis- Belgrade (former Yugoslavia), when African green sion to humans. Given the high and rapid death rate monkeys (Cercopithecus aethiops) were brought from that occurs in primates following infection, consider- Uganda for use in vaccine production and biomedical ation of this population as a viable reservoir for the research resulting in transmission from monkeys to disease seems implausible. 31 humans with seven deaths • Reservoir is still unknown; bats are considered a • 1975-1982: six cases in Zimbabwe, South Africa, and leading contender. Kenya in travelers and health-care workers Blood Phase: • 1998: Large outbreak in Africa (Democratic Republic of Congo, in the Watsa/Durba region), linked to gold • Virus has been demonstrated by antigen detection, mining activity, with 154 cases and 128 deaths culture and NAT in blood from patients in the 2004- (83%) 2005 Angolan outbreak. • October 2004-November 2005 (last outbreak): Angola • MARV was cultured from the anterior chamber of the (Northern province of Uige) with more than 370 cases eye aspirated 80 days after onset of illness and up to 3 and 320 deaths (86%) months from the semen of recovered patients. Volume 49, August 2009 Supplement TRANSFUSION 127S APPENDIX 2 Survival/Persistence in Blood Products: Treatment Available/Efficacious: • Unknown • No specific therapy is available and treatment should be supportive (intravenous fluid replacement, anal- Transmission by Blood Transfusion: gesics, and standard nursing care). • Never documented Agent-Specific Screening Question(s): • Transmission has apparently occurred following contact with the blood and body fluids of clinical • No specific question is in use; however, current geo- cases. graphic deferrals for malaria and group O HIV would Cases/Frequency in Population: exclude at-risk populations from endemic sub- Saharan Africa if an asymptomatic viremic interval • All age groups are susceptible, although pediatric exists. cases are uncommon under the age of 5. • Not indicated because transfusion transmission has • Several IFA seroprevalence studies in individuals (not not been demonstrated blood donors) from drier areas of tropical Africa, par- • No sensitive or specific question is feasible. ticularly Uganda, Zimbabwe, Democratic Republic of • Under circumstances of a bioterrorism threat, the Congo, and Angola, revealed prevalence rates ranging need for and potential effectiveness of specific donor- from 0 to 3.2%. screening questions would need to be addressed. Incubation Period: Laboratory Test(s) Available: • 3-9 days (range: 2-19 days); transmission by nonper- • No FDA-licensed blood donor screening tests exist. cutaneous routes does not appear to occur during the • In the US, assays are available only at CDC or the incubation period. US Army Research Institute of Infectious Diseases Likelihood of Clinical Disease: (USAMRIID). Confirmatory tests need to be performed. • High • EIA (IgG using recombinant nucleoprotein antigens), • In one study, no serologic evidence for asymptomatic IFA, western blot, real-time RT-PCR, and Vero cell or mild infection was found. cultures; molecular methods, though available in several labs, still require interlaboratory validation. Primary Disease Symptoms: • In outbreaks, the diagnosis is often made with immu- • Nonspecific, with abrupt fever, myalgia, headache, noperoxidase staining of formalin-fixed biopsies nausea, vomiting, abdominal pain, diarrhea, chest from sick or deceased persons. Coinfection with pain, cough, pharyngitis, conjunctival injection, malaria is common, so this should be ruled out by jaundice, lymphadenopathy, and pancreatitis proper laboratory tests. • CNS involvement occurs in a subsequent phase Currently Recommended Donor Deferral Period: (somnolence, delirium, coma) followed by wasting and bleeding manifestations (petechiae, mucous • No FDA Guidance or AABB Standard exists for membrane hemorrhages, ecchymoses, particularly patients previously diagnosed with MHF or persons around punctures) in 50% of cases. who have had contact with the blood of infected pri- • After 14 days, the patient either markedly improves or mates or patients. dies because of multiorgan dysfunction and dissemi- • There are insufficient data to make recommendations nated intravascular coagulation. regarding an indefinite or other deferral period. Severity of Clinical Disease: • The deferral interval due to geographic risk for malaria and group O HIV is expected to be longer • High than what might be recommended for donors from Marburg endemic areas who have clinically recovered Mortality: from their disease. • Mortality is ~25% (Marburg outbreak, 1967) to higher Impact on Blood Availability: than 80% (Democratic Republic of Congo and Angola outbreaks in 1998 and 2004-2005, respectively). • Agent-specific screening question(s): Not applicable; Chronic Carriage: in response to a bioterrorism threat, impact of a local deferral would be significant. •No • Laboratory test(s) available: Not applicable 128S TRANSFUSION Volume 49, August 2009 Supplement APPENDIX 2 Impact on Blood Safety: Stuyft P. Serosurvey on household contacts of Marburg hemorrhagic fever patients. Emerg Infect • Agent-specific screening question(s): Not applicable; Dis 2006;12:433-9. unknown impact in response to a bioterrorism threat 3. Centers for Disease Control and Prevention. Filovirus • Laboratory test(s) available: Not applicable fact sheet. [cited 2009 May]. Available from: http:// Leukoreduction Efficacy: www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ Fact_Sheets/Filovirus_Fact_Sheet.pdf • Leukoreduction might reduce virus levels because 4. Martini GA, Knauff HG, Schmidt HA, Mayer G, Baltzer monocytes appear to support replication. However, it G. A hitherto unknown infectious disease contracted also is likely that the virus is circulating free in plasma, from monkeys. “Marburg-virus” disease. Ger Med and leukoreduction could not be relied upon. Mon 1968;13:457-70. • Animal studies suggest that lymphocytes are nonper- 5. Monath TP. Ecology of Marburg and Ebola viruses: missive to infection, unlike monocytes. speculations and directions for future research. J Infect Dis 1999;179 Suppl 1:S127-38. Pathogen Reduction Efficacy for Plasma Derivatives: 6. Peters CJ. Marburg and Ebola Virus Hemorrhagic • Multiple pathogen reduction steps used in the frac- Fevers. In: Mandell GL, Bennett JE, Dolin R, editors. tionation process have been shown to be robust in Mandell, Douglas and Bennett’s principles and prac- removal of enveloped viruses. tice of infectious diseases, 5th ed. Philadelphia (PA): Churchill-Livingstone; 2000. p. 1821-3. Other Prevention Measures: 7. Peterson AT, Bauer JT, Mills JN. Ecologic and geo- graphic