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Ebola and Thoracic Organ Transplantation: Too Near Yet Too Far


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Hannah Nicole Kozlowski
Student





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Shahid Husain, MD, MS
University of Toronto
Toronto, ON, CANADA
Shahid.husain@uhn.ca



Introduction
Ebola virus causes an acute and serious illness, which is usually fatal. The virus belongs to family Filoviridae. The virus causing the 2014 West African outbreak belongs to the Zaire ebolavirus species. In mid-2014, Ebola Virus Disease (EVD) became a concern for nations across the globe. The epidemic, primarily in West Africa, has killed over 9000 people, and has resulted in several satellite cases in the United States, United Kingdom, Spain, France, Norway and Germany [1]. The epidemic of EVD in West Africa has increased the potential risk of Ebola virus transmission in all geographical locations, including Europe and North America due to population movements.

Symptoms typically occur between 2-21 days after infection and may include fever, diarrhea, vomiting, muscle pain, stomach pain and unexplained bleeding. Currently there have been no studies examining the risk of EVD transmission through solid organ transplant but the likelihood of EVD exposure for potential organ transplant donors is very low.

Transmission
The natural hosts for Ebola virus are the fruit bats of the Pteropodidae family. EVD is spread through bat-to-human or human-to-human transmission, which requires direct contact with the blood, secretions, organs or other bodily fluids of infected individuals/animals or with surfaces and materials contaminated with these fluids. It is important to note that Ebola virus cannot be transmitted by air, water or food, but the virus can be maintained within animal reservoirs. In the health care setting, health-care workers have been infected while treating patients with suspected or confirmed EVD. This can occur through close contact with patients when infection control precautions are not strictly practiced. However, the risk of EVD transmission is minimized by safe handling of contaminated materials and the implementation of strict infection control measures.

The incubation period for EVD can be up to 21 days but EVD may spread before symptom onset [2]. It is important to note that the presence and quantity of virus in organs, tissues, blood and other bodily fluids changes over the course of the infection. The viral concentration peaks when the patient is most sick. In EBV infected individuals, virus can be detected and isolated from breast milk and semen weeks after recovery. However the data on when patients become viremic and infectious during the incubation period is limited. During the symptomatic phase of EVD, the virus is present in high concentrations in all bodily fluids, tissues and organs.

Diagnostic Tests
Several tests have been developed to diagnose the disease while still in the symptomatic phase. Ebola is currently being tested in laboratories, largely through the detection of the virus's nucleic acid (genetic material), using commercial or in-house tests. Nucleic acid tests (NATs) are more accurate, but are complex to use and require well-established laboratories and fully trained personnel. In addition, turn-around time can vary between 12 and 24 hours. Recently WHO has approved the ReEBOV Antigen Rapid Test Kit (Corgenix, USA). The test provides results in 15 minutes and is based on the detection of Ebola protein, rather than nucleic acid. When compared to standardized NAT testing, ReEBOV Antigen Rapid Test is able to correctly identify about 92% of Ebola infected patients and 85% of those not infected with the virus. It is recommended to confirm the results from ReEBOV antigen Rapid Test Kit by testing a new blood sample using an approved Ebola NAT [3].

Implications for Transplantation
In the transplantation setting, the picture may be clearer when the potential recipient or donor is manifesting the symptoms of EVD. In these scenarios, the option of transplantation or consideration of donation should be withdrawn. However, the situation becomes more complicated if the potential recipient or the donor may have travelled to endemic area (West Africa) within the last six weeks but may not show any symptoms of EVD. Alternatively, a potential recipient or donor could have been in close contact with a health care worker who was treating EVD patients. In these cases, there may be a risk of EVD transmission from the organ donor.

In the absence of available rapid diagnostic tests for EVD various transplantation societies have recommended epidemiological screening. The screening questionnaire should be updated to facilitate accurate risk assessment with regard to the current epidemic. The most important factors to consider are epidemiological in nature: including recent travel to outbreak areas with or without known exposure to infected individuals or animals [2]. Any travel history to the outbreak area, monitoring after EVD exposure or treatment for EVD should result in organ donor decline. Furthermore, prior studies have shown that EVD DNA can persist for three days after antigen clearance and virions can persist in the semen for 101 days, vaginal fluid for 33 days, urine for 23 days, breast milk for 15 days and skin for 6 days after symptom onset [4,5]. Therefore the duration of risk for EVD transmission through organ transplantation cannot yet be determined.

The European Union, including the UK, has taken a conservative approach: excluding individuals from donation of blood or any ''substance of human origin'' for 60 days after returning from an area of EVD activity or other known exposure, with an exception of 1 month in the case of ''urgent need for organ transplantation'' if negative Ebola virus nucleic-acid amplification testing is performed. In the United States, the Organ Procurement and Transplantation Network/United Network for Organ Sharing Ad Hoc Disease Transmission Advisory Committee recommends excluding from donation for 21 days after an area of EVD activity or known exposure. No provision for urgent need of organ transplantation is provided. In donors who have recovered from Ebola infection, the European Union recommend deferral of living donation for 12 months from onset of illness or from detection of EBV infection. In addition, such living or deceased donors should test negative for EBV by NAT. In exceptional cases, potential deceased organ donors can be considered if more than two months has passed since recovery AND if negative for EBV by NAT [2,6,7].

No specific guidance has been provided for the potential organ recipients. However, it seems prudent to apply the same criteria as of donors in asymptomatic potential recipients.

Organ transplantation requires that each donor is highly scrutinized to maximize the probability of survival and success. EVD provides a great risk to transplant recipients, visitors and health care workers. Therefore each case should be examined individually. Current research is looking for a treatment for EVD, and the results of these studies will again change the donor screening process to continue to protect transplant patients. ■

Disclosure Statement: The authors have no conflicts of interest to disclose.


References:

  1. http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html: Last accessed 2/21/15.
  2. Transplant Pro: Guidance Regarding Ebola Virus Disease (EVD). 2014. Available at:
    http://transplantpro.org/guidance-regarding-ebola-virus-disease-evd/: last accessed on 2/21/15
  3. http://www.who.int/medicines/ebola-treatment/1st_antigen_RT_Ebola/en/: Last accessed on 2/21/15.
  4. Towner JS, Rollin PE, Bausch DG, et al. Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome. J Virol. 2004 Apr;78(8):4330-41
  5. Rodriguez LL, 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. J Infect Dis. 1999 Feb;179 Suppl 1:S170-6.
  6. https://www.hta.gov.uk/sites/default/files/SaBTO_Guidance_on_Ebola_Virus_and_SoHO_15_October_2014.pdf: last accessed at 2/21/2015.
  7. Kaul DR, Mehta AK, Wolfe CR, et al. Ebola virus disease:implications for solid organ transplantation. Am J Transplant. 2015 Jan;15(1):5-6.Epub 2014 Dec 15.



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