Guidance

Organ donation and seasonal influenza: guidance from SaBTO's virology review subcommittee

Updated 23 October 2019

Every winter, 10 to 20% of the general population may become infected with influenza A or B viruses.

Given this recurrent seasonality of influenza and high incidence of infection in the population, potential organ donors may present with demonstrable infection or have infection suspected at the time of donation. Proof of infection may become available after donation has taken place.

Likewise, organ transplant recipients are also at risk of acquiring respiratory infections in the community, particularly during periods of high transmission activity and if unvaccinated against influenza. Published data from observations of limited numbers of recipients of organs from Influenza A (H1N1)pdm09 virus-infected donors indicate lack of evidence of virus transmission or increased recipient morbidity^{[footnote 1] [footnote 2] [footnote 3] [footnote 4]}. In the absence of a systematic approach to detect infection and collect such data, under-recognition is a possibility.

There are 2 reports ^{[footnote 5] [footnote 6]} of possible transmission of seasonal influenza A and B viruses by transplantation of lungs and kidneys from infected donors, but detailed molecular studies as proof of imputability were lacking. Given the pathogenesis of seasonal influenza viruses, it remains appropriate that lungs from potential donors who died of proven influenza infection or who have clear lower respiratory tract involvement should not be used for transplantation.

The spectrum of presentation of influenza infection is broad and a directed assessment of the donor status may enable identification of more organs that could be made available for transplantation.

The last influenza pandemic in 2009 led to a reactive SaBTO assessment of this infection regarding organ donation, and although the true impact of donor seasonal influenza infection on recipients’ outcomes remains unknown, SaBTO has reviewed its advice in the light of experience and data acquired on the nature of A (H1N1)pdm09, which has become a seasonal influenza strain.

Summary of recommendations

Lungs from donors infected with seasonal influenza

Where demonstrable lung involvement exists, these should not be offered for transplantation.

Where there is no evident lower respiratory tract disease, lungs should be offered for transplantation. These can be considered for transplantation following detailed donor characterisation, according to the needs of suitable recipients.

All other organs (including bowel and pancreas)

In the absence of organ-specific contra-indications, organs should be offered for transplantation.

Organ specific contra-indications

These must be observed (for example, lung consolidation and myocarditis)

1 Influenza virus infection

Seasonal influenza

Influenza activity in the UK extends over a period of approximately 16 weeks during the winter months. In a typical year, 10 to 20% of the population may be affected, hence the number of potential donors infected with influenza is likely to be significant. Likewise, organ recipients will also be frequently exposed to the virus in the community, hence the importance of annual vaccination.

Due to the broad spectrum of disease presentation, only the minority of infected individuals are tested for respiratory viruses with most cases being diagnosed clinically or not being diagnosed at all. Most people will have mild illness and will not need medical care, hence incidental or concomitant finding of influenza infection in potential organ donors is likely to be the commonest scenario encountered during organ procurement.

Clinical conditions leading to higher risk of seasonal influenza complications are well described. These include chronic liver, kidney or lung disease and immunosuppression ^{[footnote 7]}. Extremes of age is another risk factor.

Although fatal seasonal influenza might occur in the absence of predisposing conditions, this is not common. Currently, the circulating seasonal strains are Influenza A (H1N1), A (H3N2) and two Influenza B lineages, B/Yamagata and B/Victoria.

Avian influenza (‘bird flu’)

Zoonotic human infections with influenza A virus strains of avian origin are rare. They do not infect people easily and are not usually spread from human to human, so cases usually have history of direct contact with infected birds.

Limited numbers of human cases have been described in restricted geographical areas, mostly in China, but also in other countries in south-east Asia and in Egypt. No cases have been described in the UK. There are established criteria and diagnostic algorithms for suspected cases and this guidance does not apply to avian influenza. In the event of a patient being investigated for avian influenza, organs should not be considered for donation.

Pandemic influenza

The introduction of a new strain of influenza virus to which there is little or no pre-existing immunity in the human population can trigger a global epidemic, as it was the case in 2009.

As the exact characteristics of viruses that cause pandemics are not predictable, guidance in relation to microbiological safety of cells, tissues and organs in this setting need to be issued based on specific risk-assessments performed at the time of the pandemic. This guidance does not apply to pandemic influenza.

2 Preventative measures

The current recommendations for seasonal influenza vaccine in the influenza chapter of the Green Book: immunisation against infectious disease cover a wide range of chronic diseases and increased risk clinical groups. Inactivated influenza vaccine should be administered to all patients in the transplant waiting list, Solid Organ Transplant (SOT) recipients, household members and other close contacts.

Healthcare professionals and transplant staff involved in direct patient care are advised to have influenza immunisation annually.

Adherence to infection control policies is also important in the prevention of nosocomial spread of respiratory viruses.

3 Testing potential donors

Routine influenza testing of donors is not recommended. In the presence of signs and symptoms suggestive of an influenza-like illness, testing for respiratory viruses should be done as part of standard of care for clinical and infection control purposes. These results can then be used to inform donor and recipient management, as appropriate.

4 Possible clinical scenarios

A few clinical scenarios have been anticipated, and broad advice is given for each. These scenarios relate to seasonal influenza A and B only. In all scenarios, the final decision to accept or decline an organ offer lies with the implanting surgeon (with patient consent), balancing risks from a particular donor versus the benefits to a particular recipient.

As the spectrum of infection and disease presentation is broad, when assessing cases of proven or possible seasonal influenza infection in potential donors and risks to recipients, considerations should include:

• clinical presentation and course of infection
• diagnosis (clinical or virological) and virological monitoring (PCR results)
• use of anti-virals and response to treatment
• time elapsed since diagnosis

In addition to absolute contra-indications for organ donation as per SaBTO guidance, NHS Blood and Transplant (NHSBT) advisory groups have developed a list of organ specific contra-indications, which may overlap with syndromic manifestations of severe influenza infection:

• lungs:
  • chest X-ray evidence of major pulmonary consolidation
  • donation after circulatory death (DCD) donor age 65 years or more unless non-smoker for 10 years or more
  • donation after brainstem death (DBD) donor age 70 years or more unless non-smoker for 10 years or more
• heart:
  • urgent recipient listing age of 65 years or more
  • non-urgent recipient listing:
    • myocarditis
    • left ventricular ejection fraction (LVEF) of 30% or less on more than one occasion
    • massive inotropic or pressor support, only if adequate circulating volume has been confirmed by monitoring
• liver: acute hepatitis of viral, drug or other known aetiology

4.1 Potential donor dying of proven seasonal influenza as the primary cause of death

Seasonal influenza mortality is highest in the immunocompromised and individuals with underlying chronic diseases, particularly liver, renal and neurological conditions. Individuals in these clinical groups are more likely to be unsuitable organ donors regardless of their influenza status.

Severe seasonal influenza infection is most often associated with lower respiratory tract infection and respiratory failure. There are reports of viral genome detected in organs other than the lungs, and of plasma viraemia. Evidence is lacking on whether detection of virus genomic material in blood represents a risk of transmission from blood.

Recommendation: Lungs should not be used from donors with proven seasonal influenza as the primary cause of death. Other organs may be offered.

4.2 Potential donor with confirmed concomitant diagnosis of seasonal influenza infection

Donors may be diagnosed in the community or after admission to hospital, and influenza infection confirmed by testing, but come to donation because of another condition in the absence of overt signs of influenza infection.

Recommendation: A thorough assessment may indicate suitability of lungs for transplantation – recipient prophylaxis advised (see section 4.4). Other organs can be offered.

4.3 Potential donor with suspected concomitant seasonal influenza infection

Donors may be diagnosed syndromically in the community to have ‘flu’ and come to donation because of another condition. This may happen commonly in an epidemic when a clinical diagnosis will suffice for public health purposes.

Recommendation: Virological confirmation should be attempted by taking a nose/throat swab and endotracheal aspirate for influenza (and other respiratory viruses) PCR.

A positive result (if time permits) puts the donor in category 4.2 above.

If time does not permit, suitability of lungs for transplantation can be assessed – other organs may be offered.

4.4 Use of post-exposure anti-viral prophylaxis for recipients

Clinical management of recipients is outside the scope of this document – brief notes and references are provided and current recommendations must be consulted. Decision to use an anti-viral in recipients of organs from donors with confirmed or highly suspected influenza infection will depend on donor factors that may influence risk of transmission through the graft, as well as recipient factors.

Where post-exposure prophylaxis is used:

• full treatment doses, and not prophylactic regimens should be used ^{[footnote 8] [footnote 9]}. Consider surveillance testing of recipient’s respiratory samples by PCR between post-transplant day 2 to 10

• choice of neuraminidase inhibitors, dose and duration should follow up-to-date recommendations – virological or infectious diseases advice should be sought. As antiviral resistance patterns may change, it is important to consult Public Health England (PHE) guidance on use of antiviral agents for the treatment and prophylaxis of seasonal influenza for up-to-date guidance

References

1. Smith CJ, McCulloch MA, Shirley D-A, L’Ecuyer TJ. ‘Pediatric heart transplantation from an influenza B–positive donor’. Pediatric transplantation, 0:e13353. ↩

2. Halliday N, Wilmore S, Griffiths PD, Neuberger J, Thorburn D. ‘Risk of transmission of H1N1 influenza by solid organ transplantation in the United Kingdom’. Transplantation 2012, 93:551-4. ↩

3. Cockbain AJ, Jacob M, Ecuyer C, Hostert L, Ahmad N. ‘Transplantation of solid organs procured from influenza A H1N1 infected donors’. Transplant international: Official Journal of the European Society for Organ Transplantation 2011, 24:e107-10. ↩

4. Kuppuswamy M, Popov AF, Carby M, et al. ‘Bilateral lobar lung transplantation using H1N1-positive lungs in the presence of anti-HLA antibodies’. American Journal of Respiratory and Critical Care Medicine 2012, 186:108-9. ↩

5. Meylan PRA, Aubert JD, Kaiser L. ‘Influenza transmission to recipient through lung transplantation’. Transplant Infectious Disease 2007, 9:55-7. ↩

6. Le Page AK, Kainer G, Glanville AR, Tu E, Bhonagiri D, Rawlinson WD. ‘Influenza B Virus transmission in recipients of kidney and lung transplants from an infected donor’. Transplantation 2010, 90:99-102. ↩

7. PHE. The Green Book: immunisation against infectious disease, chapter 19, influenza: 27. ↩

8. Cockbain AJ, Jacob M, Ecuyer C, Hostert L, Ahmad N. ‘Transplantation of solid organs procured from influenza A H1N1 infected donors’. Transplant international: Official Journal of the European Society for Organ Transplantation 2011, 24:e107-10. ↩

9. Manuel O, Estabrook M. ‘RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice’. Clin Transplant 2019: e13511. ↩