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.

Table 1. Ebola virus persistence data in different clinical specimens to date (March 4, 2016).
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
Eye Aqueous humor 14 weeks after illness onset by RT-PCR16 14 weeks after illness onset by virus isolation16
Conjunctival swab 22 days after illness onset by RT-PCR13

 

No published data
Central nervous system Cerebrospinal fluid 10 months after illness onset by RT-PCR1 No published data
Testes Seminal fluid 40 months after illness onset by RT-PCR15 157 days after illness onset by virus isolation26
Breast Breast milk 16 months (500 days) after discharge from ETU by RT-PCR25 15 days after illness onset by virus isolation11
Urinary tract Urine 64 days after illness onset by RT-PCR21 26 days by virus isolation22
Genito-urinary tract Vagina 36 days after illness onset 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 after illness onset by RT-PCR13 No published data
Saliva 8 days after illness onset by RT-PCR11 4-8 days after illness onset by virus culture11
Vomit No published data No published data
Feces 12 days after illness onset by RT-PCR11 No published data
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 cases24 No published data
Other Sweat (underarm) 44 days after illness onset by RT-PCR21  No published data
Skin (on the hand) 6 days after illness onset by RT-PCR11 No published data
Amniotic fluid >=32 days after disappearance of virus from maternal blood by RT-PCR23 No published data
Placenta >32 days after disappearance of virus from maternal blood by RT-PCR23 No published data
Cord blood >32 days after disappearance of virus from maternal blood by RT-PCR23 No published data

 

Nasal blood 10 days after illness onset by RT-PCR11 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.

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