Interim Guidance for Management of Survivors of Ebola Virus Disease in U.S. Healthcare Settings
This interim guidance may be updated based upon new data if indicated.
Background and Rationale
In the wake of the largest outbreak of Ebola virus disease (EVD) in West Africa from 2014 to 2016, and with the improvements seen in supportive care delivery in field settings, there are now many EVD survivors, including those experiencing sequelae of the disease. Of the eleven patients with EVD who were managed in U.S. healthcare facilities during 2014-2015, nine survived. It is possible that some EVD survivors could seek medical care in the U.S. The purpose of this document is to provide:
- Information about sequelae and Ebola virus persistence in EVD survivors.
- Infection prevention and control recommendations for U.S. healthcare providers when evaluating a patient who is an EVD survivor.
Data on the pathogenesis of sequelae in EVD survivors and complications related to viral persistence are very limited; few data are available from animal models. In most cases, persons who have completely recovered from EVD do not experience a relapse of EVD associated with systemic illness. However, in 2015, one nurse who recovered from acute EVD infection experienced a relapse of EVD.1
Survivors can experience complications after surviving acute EVD. The timing of onset, severity, and duration of complications among EVD survivors are variable. Reported complications among EVD survivors include non-specific fatigue, joint pain, muscle aches, headaches, suppurative parotitis, pericarditis, orchitis, sexual dysfunction, hair loss, vision loss (including uveitis and permanent blindness), hearing loss, tinnitus, paresthesia or dysesthesia, memory loss, insomnia, depression, anxiety, and post-traumatic stress disorder2-10).
Ebola virus (EBOV) can persist for several months after acute infection in organs that are considered “immunologically privileged sites” – sites that are shielded from the survivor’s immune system (e.g., testes, eye, central nervous system). EBOV was isolated from a semen specimen collected 82 days after acute EVD onset from a male survivor12. Molecular evidence suggested sexual transmission of EBOV from an asymptomatic male survivor to a female partner 179 days after the survivor’s EVD onset13. The potential for residual infectious risk from EBOV persistence is further highlighted by recovery of infectious EBOV in cerebrospinal fluid collected at 282 days after EVD onset from a survivor who experienced late onset of meningoencephalitis signs and symptoms 14, and isolation of EBOV from an intraocular fluid specimen of an eye affected by panuveitis collected at 14 weeks after EVD onset 15, It is unknown whether EBOV can persist in synovial fluid with or without accompanying arthritis. Table 1 summarizes data available to date on detection of EBOV RNA by reverse transcription-polymerase chain reaction (RT-PCR) or recovery of viable EBOV in viral culture from different clinical specimens.
The risk of infectivity from patients with persistent infection is unknown but appears to be low and is likely to decrease over time. Because patients who recover from acute EVD and later become ill with neurological or ocular symptoms might have persistent EBOV replication, appropriate infection control practices such as those recommended for evaluating persons under investigation for EVD should be adhered to until EBOV testing is negative. This also includes any situations where there is the possibility of contact with spinal fluid, semen, or ocular contents (e.g., lumbar puncture, spinal anesthesia, prostate or testicular surgery, and intraocular procedures).
EVD survivors who have any new or recurrent ocular or neurologic symptoms should seek care for complications associated with potential EBOV persistence. EVD survivors with fever should be assessed for both common community-acquired infections (e.g., malaria, influenza, common cold, typhoid fever, gastroenteritis, etc.), as well as possible complications related to EBOV persistence.
|Anatomic compartment||Body fluid(s) or tissue(s)||Longest time from illness onset that Ebola virus RNA or infectious virus was detected in clinical specimens after illness onset, days [reference]|
|Ebola virus RNA detected by RT-PCR or viral antigens detected by other assays||Infectious Ebola virus recovered|
|101 days by RT-PCR15
28 days by RT-PCR16
28 days by RT-PCR16
|98 days by virus isolation15|
|Central nervous system||Cerebrospinal fluid||283 days by RT-PCR14||Approximately 10 months by virus isolation14|
|Testes||Seminal fluid||965 days by RT-PCR14||82 days by virus isolation12|
|Breast||Breast milk||16 months by RT-PCR18,19||15 days by virus isolation11|
|Urinary tract||Urine||64 days by RT-PCR20||26 days by virus isolation21|
|Genito-urinary tract||Vagina||33 days by RT-PCR12||No published data|
|Joints||Synovial fluid||No animal model data, very limited EVD patient data, unknown|
|Gastrointestinal tract||Rectal swab
|29 days by RT-PCR11
8 days by RT-PCR10
12 days by RT-PCR15
8 days by virus culture10
|Lower respiratory tract||Ebola viral antigens detected in alveolar macrophages; viral inclusions observed in intra-alveolar macrophages, with free virus particles within alveolar spaces in fatal cases23||No published data|
|40 days by RT-PCR
6 days by RT-PCR11
>38 days by RT-PCR22
>38 days by RT-PCR22
>38 days by RT-PCR22
No published data
Guidance for Clinical Assessment of EVD Survivors
All patient care delivery (i.e., in patients both known and not known to be EVD survivors) should be performed using Standard Precautions. These constitute the minimum set of infection control practices used to ensure that healthcare personnel do not contract infections from patients, whether or not they are known to be infectious, and that personnel do not spread infectious material to other patients during routine medical care†
For patients who fully recovered from EVD and subsequently seek medical care (EVD survivors who have recovered and been discharged after their acute EVD clinical course):
- Standard Precautions† and correct waste management should remain in effect while appropriate clinical evaluation and care is performed. Based on observations during the 2014 West African EVD outbreak and previous outbreaks, there is no current evidence that the routine clinical care of EVD survivors poses any special risk to healthcare personnel when this care involves contact with intact skin, sweat, tears, conjunctivae, saliva, or cerumen.
- Women who become pregnant after recovery should receive routine prenatal care. Standard Precautions* and correct waste management should be used during labor and delivery with attention paid to splash prevention. In the absence of neurologic symptoms, regional anesthesia should not pose a risk to hospital staff. (For those pregnant survivors with neurologic symptoms who require spinal anesthesia during delivery, see below). Available evidence indicates that persons who have fully recovered from EVD and are not febrile, do not manifest EBOV viremia and do not pose a risk of EBOV exposure through phlebotomy.
- Specific procedures that create the opportunity for contact with body fluids from immunologically protected sites merit special consideration. Although data are limited, there is recognized potential for virus persistence in certain body fluids and tissues as summarized in Table 1. Examples include: obtaining and handling CSF from an EVD survivor with CNS symptoms; performing an invasive ophthalmologic procedure on an affected eye in a patient with ocular disease such as uveitis or cataract; and procedures involving exposure to semen, such as infertility evaluations, or performing invasive procedures on the testes, prostate gland, or seminal vesicles. It is unknown whether EBOV may persist in synovial fluid of survivors. For these and any other care activities that might involve contact with such body fluids (including lumbar puncture, spinal anesthesia), healthcare facilities and clinicians should:
- Arrange expert consultation in advance or on an urgent basis as needed (i.e., through the state health department and/or CDC)
- Assess capabilities of the facility and ability to correctly implement and maintain infection control, including contact precautions, environmental hygiene, and infectious waste management as needed (including in consultation with CDC in advance or on an urgent basis)
- Assess the readiness, training and competence of all staff potentially involved in care, and their willingness to remain part of the care team knowing the possible risk of virus persistence (this should include any diagnostic laboratory and imaging personnel, environmental services staff, as well as direct care providers)
- Determine appropriate personal protective equipment (PPE) based on a risk assessment of potential exposure during the procedure(s) and related care and ensure training on its use. Based on these assessments, and in consultation with public health authorities, safe care delivery can be arranged either at the original facility or, at the discretion of local and State public health authorities and in consultation with CDC, at an appropriate referral facility.
The continued need for these additional recommendations will presumably diminish over time; this guidance will be updated accordingly as more information becomes available.
†Standard Precautions include the minimum practices that apply to all patient care, regardless of suspected or confirmed infection status of the patient, in any setting where healthcare is delivered. These practices are designed to both protect HCP and prevent HCP from spreading infections among patients. Standard Precautions include: 1) hand hygiene, 2) use of personal protective equipment (e.g., gloves, gowns, masks) when there is any potential for contact with blood, body fluids or broken skin*, 3) safe injection practices, 4) safe handling of potentially contaminated equipment or surfaces in the patient environment, and 5) respiratory hygiene/cough etiquette.
*Healthcare personnel should use precautions when there is potential contact with blood, body fluids or broken skin, and any potential for splashing or exposure to a soiled surface during care, for which non-sterile gloves, disposable gowns, and face protection to prevent mucosal exposure should be used based on the expected risk.
- Jacobs M, Rodger A, Bell DJ, Bhagani S, Cropley I, Filipe A, Gifford RJ, Hopkins S, Hughes J, Jabeen F, Johannessen I, Karageorgopoulos D, Lackenby A, Lester R, Liu RSN, MacConnachie A, Mahungu T, Martin D, Marshall N, Mephan S, Orton R, Palmarini M, Patel M, Perry C, Peters SE, Porter D, Ritchie D, Ritchie ND, Seaton RA, Sreenu VB, Templeton K, Warren S, Wilikie GS, Zambon M, Gopal R, Thomson EC. Late Ebola virus relapse causing meningoencephalitis: a case report. The Lancet. 10043 (2016): 498-503.
- Qureshi AI, Chughtai M, Loua TO, Pe Kolie J, Camara HF, Ishfaq MF, N’Dour CT, Beavogui K. Study of Ebola Virus Disease Survivors in Guinea. Clin Infect Dis. 2015 Oct 1;61(7):1035-42.
- Nanyonga M, Saidu J, Ramsay A, Shindo N, Bausch DG. Sequelae of Ebola Virus Disease, Kenema District, Sierra Leone. Clin Infect Dis. 2016 Jan 1;62(1):125-6.
- Epstein L, Wong KK, Kallen AJ, Uyeki TM. Post EVD signs and symptoms in U.S. survivors. N Engl J Med. 2015;373:2484-6.
- Mohammed A, Sheikh TL, Gidado S, Poggensee G, Nguku P, Olayinka A, Ohuabunwo C, Waziri N, Shuaib F, Adeyemi J, Uzoma O, Ahmed A, Doherty F, Nyanti SB, Nzuki CK, Nasidi A, Oyemakinde A, Oguntimehin O, Abdus-Salam IA, Obiako RO. An evaluation of psychological distress and social support of survivors and contacts of Ebola virus disease infection and their relatives in Lagos, Nigeria: a cross sectional study–2014. BMC Public Health. 2015 Aug 27;15:824.
- Clark DV, Kibuuka H, Millard M, Wakabi S, Lukwago L, Taylor A, Eller MA, Eller LA, Michael NL, Honko AN, Olinger GG Jr, Schoepp RJ, Hepburn MJ, Hensley LE, Robb ML. Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study. Lancet Infect Dis. 2015 Aug;15(8):905-12.
- Kibadi K, Mupapa K, Kuvula K, Massamba M, Ndaberey D, Muyembe-Tamfum JJ, Bwaka MA, De Roo A, Colebunders R. Late ophthalmologic manifestations in survivors of the 1995 Ebola virus epidemic in Kikwit, Democratic Republic of the Congo. J Infect Dis. 1999 Feb;179 Suppl 1:S13-4.
- Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y, Katwiki KR, Kibadi K, Kipasa MA, Kuvula KJ, Mapanda BB, Massamba M, Mupapa KD, Muyembe-Tamfum JJ, Ndaberey E, Peters CJ, Rollin PE, Van den Enden E, Van den Enden E. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis. 1999 Feb;179 Suppl 1:S1-7.
- Chancellor JR, Padmanabhan SP, Greenough TC, Sacra R, Ellison RT, Madoff LC, Droms RJ, Hinkle DM, Asdourian GK, Finberg RW, Stroher U, Uyeki TM, Cerón OM. Uveitis and systemic inflammatory markers in convalescent phase of Ebola virus disease. Emerg Infect Dis. 2016 Feb [date cited]. http://dx.doi.org/10.3201/eid2202.151416external icon
- Mattia JG, Vandy MJ, Chang JC, Platt DE, Dierberg K, Bausch DG, Brooks T, Conteh S, Crozier I, Fowler RA, Kamara AP, Kang C, Mahadevan S, Mansaray Y, Marcell L, McKay G, O’Dempsey T, Parris V, Pinto R, Rangel A, Salam AP, Shantha J, Wolfman V, Yeh S, Chan AK, Mishra S. Early clinical sequelae of Ebola virus disease in Sierra Leone: a cross-sectional study. Lancet Infect Dis. 2015 Dec 22. pii: S1473-3099(15)00489-2. doi: 10.1016/S1473-3099(15)00489-2. [Epub ahead of print]
- Bausch DG, Towner JS, Dowell SF, Kaducu F, Lukwiya M, Sanchez A, Nichol ST, Ksiazek TG, Rollin PE. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis. 2007 Nov 15;196 Suppl 2:S142-7.
- Rodriguez LL, De Roo A, Guimard Y, Trappier SG, Sanchez A, Bressler D, Williams AJ, Rowe AK, Bertolli J, Khan AS, Ksiazek TG, Peters CJ, Nichol ST. Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis. 1999 Feb;179 Suppl 1:S170-6.
- Mate SE, Kugelman JR, Nyenswah TG, Ladner JT, Wiley MR, Cordier-Lassalle T, Christie A, Schroth GP, Gross SM, Davies-Wayne GJ, Shinde SA, Murugan R, Sieh SB, Badio M, Fakoli L, Taweh F, de Wit E, van Doremalen N, Munster VJ, Pettitt J, Prieto K, Humrighouse BW, Ströher U, DiClaro JW, Hensley LE, Schoepp RJ, Safronetz D, Fair J, Kuhn JH, Blackley DJ, Laney AS, Williams DE, Lo T, Gasasira A, Nichol ST, Formenty P, Kateh FN, De Cock KM, Bolay F, Sanchez-Lockhart M, Palacios G. Molecular Evidence of Sexual Transmission of Ebola Virus. N Engl J Med. 2015 Dec 17;373(25):2448-54.
- Jacobs M, Rodger A, Bell DJ, et al. Late Ebola virus relapse causing meningoencephalitis: a case report. Lancet. 2016 May 18. pii: S0140-6736(16)30386-5. doi: 10.1016/S0140-6736(16)30386-5. [Epub ahead of print].
- Varkey JB, Shantha JG, Crozier I, Kraft CS, Lyon GM, Mehta AK, Kumar G, Smith JR, Kainulainen MH, Whitmer S, Ströher U, Uyeki TM, Ribner BS, Yeh S. Persistence of Ebola Virus in Ocular Fluid during Convalescence. N Engl J Med. 2015 Jun 18;372(25):2423-7.
- Mora-Rillo M, Arsuaga M, Ramírez-Olivencia G, de la Calle F, Borobia AM, Sánchez-Seco P, Lago M, Figueira JC, Fernández-Puntero B, Viejo A, Negredo A, Nuñez C, Flores E, Carcas AJ, Jiménez-Yuste V, Lasala F, García-de-Lorenzo A, Arnalich F, Arribas JR; La Paz-Carlos III University Hospital Isolation Unit. Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid, Spain. Lancet Respir Med. 2015 Jul;3(7):554-62.
- Fischer WA, Brown J, Wohl DA, Lofts AJ, Tozay S, Reeves E, Pewu K, Gorvego G, Quellie S, Cunningham CK, Merenbloom C, Napravnik S, Dube K, Adjasoo D, Jones E, Bonarwolo K, Hoover D. Ebola Virus Ribonucleic Acid Detection in Semen More Than Two Years After Resolution of Acute Ebola Virus Infection. Open Forum Infectious Diseases. 4, No. 3. Oxford University Press, 2017.
- World Health Organization (WHO). Clinical care for survivors of Ebola virus diseasesexternal icon. Geneva: WHO, 2018. Accessed 25 May 2018.
- Nordenstedt H, Bah EI, de la Vega MA, Barry M, N’Faly M, Barry M, et al. Ebola Virus in breast milk in an Ebola virus–positive mother, with twin babies, Guinea, 2015 [letter]. Emerg Infect Dis. 2016 Mar [date cited]. http://dx.doi.org/10.3201/eid2204.151880
- Howlett P, Brown C, Helderman T, Brooks T, Lisk D, Deen G, Solbrig M, Lado M. Ebola Virus Disease Complicated by Late-Onset Encephalitis and Polyarthritis, Sierra Leone. Emerg Infect Dis. 2016 Jan;22(1):150-152.
- Kreuels B, Wichmann D, Emmerich P, Schmidt-Chanasit J, de Heer G, Kluge S, Sow A, Renné T, Günther S, Lohse AW, Addo MM. A case of severe Ebola virus infection complicated by gram-negative septicemia. New england journal of medicine. 2014 Dec 18;371(25):2394-401.
- Caluwaerts S, Fautsch T, Lagrou D, Moreau M, Modet Camara A, Günther S, Di Caro A, Borremans B, Raymond Koundouno F, Akoi Bore J, Logue CH. Dilemmas in managing pregnant women with Ebola: 2 case reports. Clinical Infectious Diseases. 2015 Dec 17;62(7):903-5.
- Martines RB, Ng DL, Greer PW, Rollin PE, Zaki SR. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses. J Pathol. 2015 Jan;235(2):153-74.