Reducing Risk of Relevant Transfusion-Transmitted Infection

Recommendations for Assessment of
Blood Donor Eligibility, Donor
Deferral and Blood Product
Management in
Response to Ebola Virus
Guidance for Industry

Additional copies of this guidance are available from the Office of Communication, Outreach
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring,
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010, or email [email protected], or
from the Internet at
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida
nces/default.htm.
For questions on the content of this guidance, contact OCOD at the phone numbers or email
address listed above.

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research
January 2017

Contains Nonbinding Recommendations

Table of Contents
I.

INTRODUCTION............................................................................................................. 1

II.

BACKGROUND ............................................................................................................... 2

III.

RECOMMENDATIONS.................................................................................................. 3
A.
B.
C.

Donor Educational Material and Donor History Questionnaire...................... 4
Donor Deferral ...................................................................................................... 5
Product Retrieval, Quarantine, and Notification............................................... 6

IV.

REPORTING A BIOLOGICAL PRODUCT DEVIATION (BPD) ............................. 7

V.

CONVALESCENT PLASMA ......................................................................................... 8

VI.

IMPLEMENTATION ...................................................................................................... 9

VII.

REFERENCES ................................................................................................................ 11

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Contains Nonbinding Recommendations

Recommendations for Assessment of Blood Donor Eligibility, Donor
Deferral and Blood Product Management in Response to
Ebola Virus
Guidance for Industry
This guidance represents the current thinking of the Food and Drug Administration (FDA or
Agency) on this topic. It does not establish any rights for any person and is not binding on FDA
or the public. You can use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff
responsible for this guidance as listed on the title page.

I.

INTRODUCTION

We, FDA, are notifying you, blood establishments that collect blood and blood components for
transfusion or further manufacture, including Source Plasma, that we have determined Ebola
virus to be a transfusion-transmitted infection (TTI) under Title 21 of the Code of Federal
Regulations (CFR) 630.3(l). We are also providing you with recommendations for assessing
blood donor eligibility, donor deferral and blood product management in the event that an
outbreak of Ebola virus disease (EVD) with widespread transmission occurs in at least one
country. This guidance document applies to Ebola virus (species Zaire ebolavirus).1 The
recommendations in section III. of this guidance document apply to the routine collection of
blood and blood components for transfusion or further manufacture, including Source Plasma.
The collection of convalescent plasma from EVD survivors is addressed in section V. of this
guidance document. This guidance finalizes the draft guidance entitled, “Recommendations for
Assessment of Blood Donor Suitability, Donor Deferral and Blood Product Management in
Response to Ebola Virus,” dated December 2015.
FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be
viewed only as recommendations, unless specific regulatory or statutory requirements are cited.
The use of the word should in FDA’s guidances means that something is suggested or
recommended, but not required.

1

FDA will assess whether the recommendations apply to other viruses of the Ebolavirus genus should widespread
transmission of such viruses occur.

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II.

BACKGROUND

Ebola virus is a member of the family Filoviridae that can cause severe hemorrhagic fever in
humans and non-human primates (NHPs) with historically high morbidity and mortality rates of
up to 90% (Refs. 1 and 2). However, in the 2014 outbreak in West Africa, the mortality rate was
lower, with 28,652 suspected, probable, and confirmed cases, including 15,261 laboratoryconfirmed cases, and 11,325 deaths reported as of April 2016.2 Ebola virus is a lipid-enveloped
zoonotic pathogen that, when studied in the laboratory, requires the highest level of biosafety
containment (BSL-4). The Centers for Disease Control and Prevention (CDC) has classified it as
a “Category A” bioterrorism agent/disease.3 Ebola virus is reported to be inactivated by heating
at 60oC for 60 minutes, and also following incubation at pH 2.5 (Ref. 3). Solvent-detergent
treatment and pathogen inactivation technologies are also known to inactivate lipid-enveloped
viruses (Refs. 4 through 8).
In humans, EVD is typically characterized at onset by fever, severe headache, muscle pain and
weakness, followed by diarrhea, vomiting, abdominal pain and sometimes diffuse hemorrhage
(bleeding or bruising). In previous outbreaks of EVD, symptoms generally appeared within 21
days and most often within 4-10 days following infection (Refs. 9 and 10). Based on
mathematical models, symptom onset later than 21 days is estimated as possible in 0.1 to 12% of
cases (Refs. 10 and 11). In a retrospective study in which 500 patients diagnosed with EVD in
2014 recalled their likely source of infection, 5% reported symptom onset > 21 days (up to a
maximum of 43 days) post-exposure (Ref. 10).
Viremia and virus shedding escalate rapidly after onset of symptoms and infectivity appears to
correlate with severity and stage of disease. Although viremia in survivors typically resolves
within 21 days of disease onset, infectious virus and viral RNA has been detected in other body
components or fluids (e.g., aqueous humor, semen and vaginal fluids) for longer periods. For
instance, viable Ebola virus was detected in aqueous humor obtained from the eye 14 weeks after
the onset of the initial symptoms of EVD and 9 weeks after the clearance of viremia (Ref. 12).
Infectious virus and viral RNA have been detected in semen up to 82 and 272 days post EVD
onset, respectively (Refs. 13 through 17).4 Further, a case of sexual transmission of Ebola virus
was reported in which the patient was exposed to Ebola virus through sexual contact with a
survivor 179 days after likely disease onset (Refs. 18 and 19). These findings raise the
theoretical possibility, which has not been documented in humans or animal models, of an
intermittent low level viremia after recovery from illness. In addition, there have been isolated
reports of apparently asymptomatic Ebola virus infection in individuals who had contact with
Ebola patients (Ref. 18), and of antibody to Ebola virus in rural African populations reportedly
unassociated with acute illness (Ref. 19). These reports raise the possibility that there may be an
asymptomatic infection or mild disease in some individuals; if this condition exists, the
infectivity of these individuals is uncertain but likely to be less than that of severely ill persons.

2

See CDC website: http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html.
See CDC website: http://emergency.cdc.gov/bioterrorism/overview.asp#categories.
4
See also the CDC Review of Human-to-Human Transmission of Ebola Virus,
http://www.cdc.gov/vhf/ebola/transmission/human-transmission.html.
3

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Ebola virus is transmitted from human to human by direct contact with body fluids (such as
blood, urine, stool, saliva, semen, vaginal fluids or vomit) of symptomatic infected individuals.
Therefore, blood and blood products from symptomatic individuals, if they were to donate,
would have the potential of transmitting Ebola virus to recipients. The theoretical possibility of
pre-symptomatic viremia has not been extensively investigated. If this condition exists the
infectivity is uncertain, but likely to be less than of symptomatic persons. Healthcare providers
caring for symptomatic Ebola patients, and family and friends in close contact with symptomatic
Ebola patients, are at the highest risk of becoming infected because they may come in direct
contact with infected blood or other body fluids of sick patients. Because of the severity of the
disease and the risk of transmission by blood and blood products, we have determined that Ebola
virus meets the definition of TTI in 21 CFR 630.3(l).5
III.

RECOMMENDATIONS

Under 21 CFR 630.10(a), a donor must be in good health and free from TTIs. A donor must also
have a normal temperature at the time of donation (21 CFR 630.10(f)(1)). Additionally, under
21 CFR 630.10(a) a donor is not eligible if you identify any factor(s) that may cause the donation
to adversely affect the safety, purity, or potency of the blood or blood component. Such factors
include symptoms of a recent or current illness, as well as travel to, or residence in, an area
endemic for a TTI (21 CFR 630.10(e)(2)(i) and (iii)).
Standard procedures that are already in place to assure that the donor is healthy at the time of
donation serve as an effective safeguard against collecting blood or blood components from a
donor who seeks to donate after the onset of clinical symptoms of EVD. The following
recommendations are intended to reduce the risks of collecting blood and blood components
from potentially Ebola virus-infected persons during the asymptomatic incubation period before
the onset of clinical symptoms, as well as from individuals with a history of Ebola virus infection
or disease.
This guidance contains a recommendation for updating your donor educational materials in
section III.A.1. The recommendations in section III.A.2. and III.B. should be implemented when
the CDC has classified one or more countries as having widespread transmission of Ebola virus.
We recommend that you continue to follow the recommendations for 4 weeks after the date CDC
classifies the last affected country as a country with former widespread transmission. After this
period, when there are no countries classified by CDC as having widespread transmission of
Ebola virus, it is appropriate to discontinue asking donors questions related to risk of Ebola virus
infection or disease. (See http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/distributionmap.html for CDC’s classification of countries with reported Ebola cases and for the specific
dates when a country is classified as a country with former widespread transmission of Ebola
virus.)

5

We have determined that Ebola virus does not meet the definition of a relevant transfusion-transmitted infection
because it may not have sufficient incidence and/or prevalence to affect the potential donor population (see
21 CFR 630.3(h)(2)(ii)(A)).

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A.

Donor Educational Material and Donor History Questionnaire
1. Donor Educational Material
We expect very few individuals with a history of Ebola virus infection or disease
to present as blood donors. When there are no countries classified by CDC as
having widespread transmission of Ebola virus, self-deferral of donors with a
history of Ebola virus infection or disease should provide sufficient protection.
We recommend that you update your donor educational materials to instruct
donors with a history of Ebola virus infection or disease to not donate blood or
blood components.
2. Donor History Questionnaire
In the event that one or more countries is classified by CDC as having widespread
transmission of Ebola virus, your donor history questionnaire (DHQ), including
your full-length and abbreviated DHQ, and accompanying materials, must
incorporate elements to assess prospective donors for symptoms of recent or
current illness with Ebola virus infection or disease, and travel to, or residence in,
an area endemic for Ebola virus in accordance with 21 CFR 630.10(e)(2). We
recommend that your DHQ assess donors for:
a. A history of Ebola virus infection or disease.
b. A history of residence in or travel in the past 8 weeks to a country with
widespread transmission of EVD or cases in urban areas with uncertain
control measures. (See http://www.cdc.gov/vhf/ebola/outbreaks/2014west-africa/distribution-map.html).
In addition, we also recommend that the updated DHQ include the following
elements to further assess prospective donors for risk of Ebola virus infection or
disease:
a. A history of close contact in the past 8 weeks with a person confirmed to
have Ebola virus infection or disease or a person under investigation (PUI)
for Ebola virus infection or disease in whom diagnosis is pending. For the
purposes of this guidance, close contact is defined as contact that could
have resulted in direct exposure to body fluids. Individuals falling into
this close contact category include healthcare workers and other persons
who care for, have lived with, or have otherwise been in contact with a
PUI or a person confirmed to have Ebola virus infection or disease.6

6

For additional information on epidemiologic risk factors to consider when evaluating a person for exposure to
Ebola virus see: http://www.cdc.gov/vhf/ebola/exposure/risk-factors-when-evaluating-person-for-exposure.html.
We expect individuals in the “high risk,” “some risk,” and “low risk” categories would fall into this close contact
category.

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•

Additionally, this close contact category includes individuals with
a history of sexual contact in the past 8 weeks with a person known
to have recovered from EVD prior to that instance of sexual
contact, regardless of the time since the person’s recovery.

b. A history of notification by a public health authority that he or she may
have been exposed in the past 8 weeks to a person with EVD.
We note that educational material may assist donors in assessing their risk factors
for Ebola virus infection or disease as described above. Relevant information on
risk factors can be found on CDC’s website at http://www.cdc.gov/vhf/ebola.
B.

Donor Deferral

You must defer a donor found to be ineligible because of symptoms of a recent or current
illness, as well as travel to, or residence in an area endemic for a TTI, including Ebola
virus (21 CFR 630.10(e)(2) and (h)). We recommend the following deferral periods for
such donors:
1. Indefinite7 deferral of a donor with a history of Ebola virus infection or
disease.
Note: This recommendation excludes the collection of convalescent plasma
for treatment of EVD as described in section V. of this guidance.
2. Eight week8 deferral from the date of his or her departure a donor who has
been a resident of or has travelled to a country with widespread transmission
of EVD or with cases in urban areas with uncertain control measures. (See
http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/distributionmap.html.)
Note: Longer deferral periods may apply based on recommendations for
deferral due to risk of malaria exposure. See FDA document entitled,
“Guidance for Industry: Recommendations for Donor Questioning, Deferral,
Reentry and Product Management to Reduce the Risk of TransfusionTransmitted Malaria,” dated August 2014.
http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinf
ormation/guidances/blood/ucm365191.htm.

7

Until more data regarding the persistence of Ebola virus in survivors becomes available, we recommend you defer
such donors indefinitely.
8
Although symptoms generally appear within 21 days of infection, we recommend an extended deferral period of 8
weeks to prevent blood and blood component collection from an individual who could be infected and have an
extended incubation period. In addition, 8 weeks is consistent with the inter-donation interval for Whole Blood
donations.

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In addition, we recommend the following additional deferral periods:
1. Eight week8 deferral after the last contact a donor who has had close contact
with a person confirmed to have Ebola virus infection or disease or a PUI in
whom the diagnosis is pending. Individuals falling into this category include
healthcare workers and other persons who care for, or have lived with, or
person confirmed to have Ebola virus infection or disease or a PUI.5
•

In addition, we recommend that you defer for 8 weeks8after the last
sexual contact a donor who has had sexual contact with a person
known to have recovered from EVD regardless of the time since the
person’s recovery.9

2. Eight week deferral after exposure8 a donor who has been notified by a
federal, state, or local public health authority that he or she may have been
exposed to a person with EVD.
C.

Product Retrieval, Quarantine, and Notification
1. Blood and Blood Components Collected from Donors at Risk for Ebola Virus
Infection or Disease Because of Risk Factors Related to Residency, Travel or
Close Contact
If you collected blood or blood components intended for transfusion or further
manufacture into injectable and non-injectable products from a donor who should
have been deferred for risk factors for EVD related to residency, travel, or close
contact, according to the recommendations in section III.B. of this document, we
recommend that you quarantine and destroy all undistributed in-date blood and
blood components from that donor.
a. If you distributed blood or blood components intended for transfusion or
for further manufacture into injectable and non-injectable products from a
donor who should have been deferred for risk factors for EVD related to
residency, travel or close contact according to the recommendations in
section III.B. of this document, we recommend that you notify consignees
to retrieve, quarantine and destroy the in-date blood and blood
components collected from that donor.
b. We do not recommend retrieval or quarantine of plasma pooled for further
manufacturing into products that are manufactured under processes that
include multiple validated viral inactivation and clearance steps, which

9

Until additional data regarding the length of time semen could be infectious post EVD becomes available, we
recommend that you defer for 8 weeks after the last sexual contact a donor who has had sexual contact with a person
known to have recovered from EVD.

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have been shown to be robust in the inactivation and clearance of lipidenveloped viruses.
2. Blood and Blood Components Collected from Donors Later Determined to
Have Ebola Virus Infection or Disease
We recommend you contact FDA10 as soon as possible upon learning that you
collected blood or blood components from a donor later determined to have
Ebola virus infection or disease. This recommendation applies to the
collection of blood components in the 8 weeks prior to disease onset or any
time after disease onset. In addition, blood establishments should consider the
need to notify state and local public health authorities.
a. If you collected blood or blood components within a recommended
deferral period as specified in section III.B. of this document from a donor
later determined to have Ebola virus infection or disease, you should
promptly retrieve and quarantine the blood and blood components
collected in the 8 weeks prior to disease onset and any time after disease
onset.
•

If such blood components were transfused, we recommend that
consignees notify the transfusion recipient’s physician of record
regarding the need for notification and monitoring of the recipient
for possible Ebola virus infection or disease.

b. Manufacturers should contact the appropriate FDA review division to
discuss their conduct of an adequate risk analysis if plasma collected from
a donor later determined to have Ebola virus infection or disease has been
pooled for further manufacturing or manufactured into a finished product.
Finished products manufactured from such plasma pools should not be
released prior to completion of an adequate risk analysis demonstrating
that the product will not place patients at risk of EVD. Finished products
manufactured from such plasma pools that have already been released
should also undergo a risk analysis.
IV.

REPORTING A BIOLOGICAL PRODUCT DEVIATION (BPD)

If you have distributed blood or blood components for transfusion or further manufacture
collected from a donor at risk for or known to have Ebola virus infection or disease according to
section III.B. of this document, you should report a BPD as soon as possible but you must report
at a date not to exceed 45 calendar days from the date you acquire the information reasonably
suggesting that a reportable event has occurred (21 CFR 606.171).
10

Contact CBER’s Office of Communication, Outreach and Development (OCOD) by calling 1-800-835-4709 or
240-402-8010. After regular business hours and on weekends, call the FDA emergency number: 1-866-300-4374
or 301-796-8240.

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If you have distributed finished products manufactured from blood or blood components
collected from a donor later determined to have Ebola virus infection or disease according to
section III.B. of this guidance, you should report a BPD as soon as possible but you must report
at a date not to exceed 45 calendar days from the date you acquire the information reasonably
suggesting that a reportable event has occurred (21 CFR 600.14).

V.

CONVALESCENT PLASMA

As of the date of issuance of this guidance, there are no FDA-approved therapeutics or licensed
vaccines for EVD. Standard treatment for EVD is limited to supportive care, which includes
intravenous fluids and electrolytes, treatment of secondary infections, and pain control.
Serum and plasma therapies have been used to treat many infectious diseases, including Junin
Virus, a virus that also causes hemorrhagic fever (Ref. 22). There is similar interest in whether
convalescent serum or plasma collected from EVD survivors may be an effective therapy in
Ebola virus outbreaks. Neutralizing antibodies are generated during filovirus infection in
humans (Ref. 23). Ebola virus-infected individuals develop humoral immune responses (Ref.
24) that include neutralizing antibodies in some survivors. In previous studies conducted using
non-human primates, passive transfer of certain neutralizing monoclonal antibodies (Refs. 25
and 26) and convalescent immunoglobulin concentrate prepared from non-human primates that
were vaccinated and virus challenged (Ref. 27) have resulted in protection against lethal
challenge with Ebola virus. However, whole blood from Ebola virus vaccinated and challenged
monkeys did not protect against Ebola virus challenge in non-human primates (Ref. 28).
Treatment of EVD patients with convalescent human sera has been used in uncontrolled studies
(Refs. 29 through 31). Based on the available scientific evidence, the World Health
Organization (WHO) has developed interim guidance for national health authorities and blood
transfusion services, entitled, “Use of Convalescent Whole Blood or Plasma Collected from
Patients Recovered from Ebola Virus Disease for Transfusion, as an Empirical Treatment during
Outbreaks,” dated September 2014,
http://www.who.int/csr/resources/publications/ebola/convalescent-treatment/en/.
As noted above, this investigational treatment has not yet been proven to be effective and results
of a clinical trial in Guinea were negative (Ref. 32). However, the effectiveness of convalescent
plasma or immune globulin concentrates made from convalescent plasma remains biologically
plausible and further studies may still be considered. Convalescent plasma or serum collected
from donors who have recovered from EVD is an investigational product, and controlled studies
with an adequate number of patients are needed to assess safety and effectiveness. Blood
establishments wishing to collect or distribute convalescent plasma intended for transfusion in
the United States must submit an investigational new drug application in accordance with

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21 CFR Part 312, and sponsors seeking to develop devices containing convalescent plasma are
subject to the investigational device regulations in 21 CFR Part 812 (see 21 CFR 601.21). Such
sponsors should contact FDA to discuss the submission.11

VI.

IMPLEMENTATION

We recommend that you revise your donor education materials consistent with recommendations
in section III.A.1 no later than 12 weeks after the guidance issue date. The revisions to the donor
history questionnaire and accompanying materials described in section III.A.2 should be
implemented within 4 weeks of the date that CDC classifies one or more countries as having
widespread transmission of Ebola virus.
Licensed manufacturers must report the implementation of the recommendations in this guidance
to FDA under 21 CFR 601.12 as follows:
1. Revision of your donor educational materials must be reported in an Annual Report under
21 CFR 601.12(d), noting the date the process was implemented. See
21 CFR 601.12(a)(3).
2. Revision of your own DHQ and accompanying materials must be reported in an Annual
Report under 21 CFR 601.12(d), noting the date the process was implemented. See
21 CFR 601.12(a)(3).
3. Revision of an FDA accepted DHQ and accompanying materials according to the
directions in the User Brochure or Directions for Use must be reported in an Annual
Report under 21 CFR 601.12(d), noting the date the process was implemented. See
21 CFR 601.12(a)(3).
4. Revision of an FDA accepted DHQ and accompanying materials other than as described
in section VI.2 of this guidance is considered a major change. If you wish to implement
the acceptable DHQ documents modified in a manner other than as described in section
VI.3 of this guidance, you must report such changes as a Prior Approval Supplement
(PAS) under 21 CFR 601.12(b).
We recommend that you include the following in the PAS submission:
a. Form FDA 356h “Application to Market a New or Abbreviated New Drug, or
Biologic for Human Use” which may be obtained at
http://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm;
b. A cover letter describing the request and the contents of the submission;
11

Please contact the appropriate review division in CBER in accordance with CBER SOPP 8101.1: Scheduling and
Conduct of Regulatory Review Meetings with Sponsors and Applicants. See
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ProceduresSOPPs/ucm07
9448.htm.

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c. A written standard operating procedure (SOP) describing the donor questions and
questionnaire process; and
d. The donor history questionnaires and accompanying document(s). Please
highlight the modifications.

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VII.

REFERENCES

1.

Feldmann, H., Jones, S., Klenk, H.D., et al., “Ebola Virus: from Discovery to Vaccine.
Nature Review,” Immunology, 2003; 3:677-685.

2.

Towner, J.S., Sealy, T.K., Khristova, M.L., et al., “Newly Discovered Ebola Virus
Associated With Hemorrhagic Fever Outbreak in Uganda,” PLoS pathogens, 2008;
4:e1000212.

3.

Mitchell, S.W., McCormick, J.B., “Physicochemical inactivation of Lassa, Ebola, and
Marburg Viruses and Effect on Clinical Laboratory Analyses,” J Clin Microbiol, 1984;
20:486-489.

4.

Horowitz, B., Bonomo, R., Prince, A.M., et al., “Solvent/Detergent-Treated Plasma: a
Virus-Inactivated Substitute for Fresh Frozen Plasma,” Blood, 1992; 79:826-831.

5.

Dichtelmuller, H., et al., “Robustness of Solvent/Detergent Treatment of Plasma
Derivatives: A Data Collection from Plasma Protein Therapeutics Association Member
Companies,” Transfusion, 2009; 49:1931-1943.

6.

El-Ekiaby, M., et al., “Solvent-Detergent Filtered (S/D-F) Fresh Frozen Plasma and
Cryoprecipitate Minipools Prepared in a Newly Designed Integral Disposable Processing
Bag System,” Transfusion Medicine, 2010; 20:48-61.

7.

Singh, Y., et al., “Photochemical Treatment of Plasma with Amotosalen and Long
Wavelength Ultraviolet Light Inactivates Pathogens While Retaining Coagulation
Function,” Transfusion, 2006; 46:1168-1177.

8.

Lin, L., et al., “Inactivation of Viruses in Platelet Concentrates by Photochemical
Treatment with Amotosalen and Long-Wavelength Ultraviolet Light,” Transfusion, 2005;
45:580-590.

9.

Eichner, M., Dowell, S.F., Firese, N., “Incubation Period of Ebola Hemorrhagic Virus
Subtype Zaire,” Osong Public Health Res Perspect, 2011; 2:3-7.

10.

World Health Organization Ebola Response Team. “Ebola Virus Disease in West Africa-the First 9 Months of the Epidemic and Forward Projections,” N Engl J Med, 2014;
371:1481-1495.

11.

Haas, C.N., “On the Quarantine Period for Ebola Virus,” PLOS Currents Outbreaks.
2014 Oct 14, 1st ed.

12.

Varkey, J.B., et al., “Persistence of Ebola Virus in Ocular Fluid during Convalescence,”
N Engl J Med, 2015; 372:2423-2437.

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13.

Bausch, D.G., Towner, J.S., Dowell, S.F., et al., “Assessment of the Risk of Ebola Virus
Transmission from Bodily Fluids and Fomites,” The Journal of Infectious Diseases, Nov
15, 2007; 196 Suppl 2:S142-147.

14.

Rodriguez, L.L., De Roo, A., Guimard, Y, et al., “Persistence and Genetic Stability of
Ebola Virus During the Outbreak in Kikwit, Democratic Republic of the Congo, 1995,”
The Journal of Infectious Diseases, Feb 1999; 179 Suppl 1:S170-176.4.

15.

Rowe, A.K., Bertolli, J., Khan, A.S., 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,” The Journal of Infectious Diseases, Feb 1999; 179 Suppl 1:S28-35.

16.

Richards, G.A., Murphy, S., Jobson, R., et al., “Unexpected Ebola virus in a Tertiary
Setting: Clinical and Epidemiologic Aspects,” Critical Care Medicine, Jan 2000;
28(1):240-244.

17.

Deen, G.F. et al. “Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors –
Preliminary Report,” N Engl J Med, October 2015; DIO: 10.1056/NEJMoas1511410.

18.

Centers for Disease Control and Prevention, “Possible Sexual Transmission of Ebola
Virus – Liberia, 2015,” Morbidity and Mortality Weekly, May 2015; 64(17):479-481.

19.

Mate, S.E. et al. “Molecular Evidence of Sexual Transmission of Ebola Virus,” N Engl J
Med, October 2015; DIO:10.1056/NEJMoa1509773.

20.

Leroy, E.M. et al., “Human Asymptomatic Ebola Infection and Strong Inflammatory
Response,” The Lancet, 2000; 255: 2210-2215.

21.

Nkoghe, D., Padilla, C., Becquart, P., et al., “Risk Factors for Zaire Ebolavirus--Specific
IgG in Rural Gabonese Populations,” J Infect Dis, 2011; 204 Suppl 3:S768-775.

22.

Maiztegui, J.I., Fernandez, N.J., de Damilano, A.J., “Efficacy of Immune Plasma in
Treatment of Argentine Haemorrhagic Fever and Association between Treatment and A
Late Neurological Syndrome,” The Lancet, 1979; 2:1216-1217.

23.

Maruyama, T., Rodriguez, L.L., Jahrling, P.B., et al., “Ebola Virus Can Be Effectively
Neutralized by Antibody Produced in Natural Human Infection,” J Virol, 1999; 73:60246030.

24.

Bradfute, S.B., Bavari, S., “Correlates of Immunity to Filovirus Infection,” Viruses, 2011;
3:982-1000.

25.

Qiu, X., Audet, J., Wong, G., et al., “Successful Treatment of Ebola Virus-Infected
Cynomolgus Macaques with Monoclonal Antibodies,” Sci Transl Med, 2012; 4:138ra81.

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26.

Olinger, G.G., Pettitt, Jr., 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 USA, 2012; 18030-18035.

27.

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