4. You were offered a kidney from 23-year-old male DBD (donor after brain stem death) donor who suffered from HSV encephalitis. His baseline S Cr was 60 µmol/L. On admission S Cr was reported to be 71 µmol/L (0.8 mg/dl). His urine output is 130 mls during the last hour and 3.4 L over the last 24 hours. The recipient is 25 years old, 000 mismatch, no DSA. He is on the waiting list for the last 7 years secondary to reflux nephropathy.
- Would you accept this donor?
- If yes, what is the prognosis?
Dear All
There is a typo regarding serum creatinine. It is corrected now. Thank you for highlighting this to me.
Dear All
Many of you accepted this donor, but we must reduce the transmission risk. What are the measures taken to reduce this risk?
Herpes simplex virus (HSV) reactivation in SOT recipients is more frequent, may become more invasive, takes longer to heal, and has greater potential for dissemination to visceral organs than it does in the immunocompetent host(1).
Prophylactic regimens for CMV are also effective chemoprophylaxis against HSV; in the absence of CMV prophylaxis, aciclovir, valaciclovir or famciclovir should be used as HSV prophylaxis in seropositive recipients.
References
1.Slifkin M, Doron S, Snydman DR. Viral prophylaxis in organ transplant patients. Drugs. 2004;64(24):2763-92. doi: 10.2165/00003495-200464240-00004. PMID: 15563248.
Dear Dr Saja,
My suggesting ‘how one would reduced the risk of life-threatening HSV from such a donor’, I might erroneously sound as if I am agreeing with you.
I like your argument and scientific suggestions.
Ajay
Measures to reduce risk of virus transmission in solid organ transplantation
1- The choice of induction (Basilixumab vs ATG and Alemtuzumab) and maintenance immunosupression (CNI, anti metabolite, steroid and mTOR).
2- The identification of recipient serology for the virus if positive or negative if negative we may use immunoglobulins, in positive serology recipient early start of anti viral prophylaxis, in our case prolonged prophylaxis for alost one month is required and me be extended.
Reference:
UpToDate – Prevention of viral infections in transplant recipients
Hi Dr Alshaikh,
My suggesting ‘how one would reduced the risk of life-threatening HSV from such a donor’, I might erroneously sound as if I am agreeing with you.
I like your argument and scientific suggestions.
Ajay
Current HSV prevention techniques are focused on behavioural and antiviral methods.
HSV‐specific prophylaxis should be considered for all HSV‐1 and HSV‐2–seropositive organ recipients who are not receiving antiviral medication for CMV replication.
Herpes simplex virus prophylaxis in SOT recipients is effective with acyclovir administered at doses of 200 mg three or four times a day.
The majority of severe HSV disease occurs within the first month after transplant, so antiviral prophylaxis should continue for at least a month. Resumption of prophylaxis can be considered for patients being treated for rejection (with T cell-depleting agents). For patients receiving CMV antiviral prophylaxis active against HSV, additional prevention is not necessary.
Reference:
Lee DH, Zuckerman RA. Herpes simplex virus infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clinical Transplantation. 2019;33:e13526.
Hi Dr Huda,
My suggesting ‘how one would reduced the risk of life-threatening HSV from such a donor’, I might erroneously sound as if I am agreeing with you.
I like your argument and scientific suggestions.
Ajay
Hi Dr Ben,
I like your argument and scientific suggestions. My suggesting ‘how one would reduced the risk of life-threatening HSV from such a donor’, I might erroneously sound as if I am agreeing with you.
Ajay
United Kingdom Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) guidelines recommend the routine screening of recipients at 1 year posttransplant for presence of pathogens potentially transmitted from the donor.
Nucleic acid testing is preferred to account for the effect of immunosuppression on serological test accuracy, and ideally, samples from the recipient taken pretransplantation would be available to differentiate between preexisting and newly acquired disease.
The SaBTO guidelines make the following recommendations where there is potential transmission
Where recipient infection is detected and indicates potential transmission from the donor, it is then the duty of the recipient’s physician to ensure that recipients of organs and tissues from the same donor are notified as soon as possible and made aware of the infection risk. The National Health Service Blood and Transplant Directorate for Organ Donation and Transplantation (ODT) has a Duty Office that is able to assist in informing the relevant clinicians. All incidents reported to the ODT Directorate are managed by the Clinical Governance Team within ODT.
The Clinical Governance Team forms the Clinical Governance Improvement Group, which is responsible for reviewing and monitoring serious adverse events and reactions, and aims to complete investigations within 90 days or less. Once an incident has undergone a full review, the individual who reported the incident will be sent a summary of the outcome and any key actions or learning that is required. The central remit of the Clinical Governance Improvement Group is to have oversight of all incidents, review in detail individual incidents, and ensure areas of concern are addressed, learning is shared, and practice is changed as appropriate; and identify and review key themes and trends across incidents, and to develop key actions following these reviews.
\
reffernce :
Guidance on the microbiological safety of human organs, tissues and cells used in transplantation. London, United Kingdom: Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO), Department of Health; 2011. [Google Scholar]
Antiviral prophylaxis during the first month after transplantation has been shown to reduce the incidence of symptomatic HSV infections, preventing potentially fatal infections from occurring from the start.
Acyclovir is the preferred agent for prophylaxis of HSV infections , although it is appropriate to use ganciclovir or valganciclovir as a single agent in patients requiring prophylaxis for both CMV and HSV . Valacyclovir and famciclovir have also been used successfully for prophylaxis against HSV recurrences, although valacyclovir appears to be the superior of the two.
Reference
-Ison M G et al. Donor-Derived Infections in Solid Organ Transplantation. American journal of transplantation Volume13, Issues4 ,Special Issue: The American Society of Transplantation Infectious Diseases Guidelines 3rd Edition March 2013 ,Pages 22-30
Thankyou but:
Are we dealing D+toR- serological infection or
A heavy virus load transmitted in the graft to an immuno compromised recipient.This can influence the decision.
although in this case it is contraindicated but if he accepted as donor the prophylactic measure to reduce the risk of transmission are :
identify the recipient if seropositive or negative.
prophylactic acyclovir therapy should be given,
monitoring the recipient postrenal transplant closely for any evidence of transisthmian(LFT, skin examination…..)
refernces
Pass RF, Whitley RJ, Whelchel JD, Diethelm AG, Reynolds DW, Alford CA. Identification of patients with increased risk of infection with herpes simplex virus after renal transplantation. J Infect Dis. 1979;140:487. [PubMed] [Google Scholar]
2. Ho M. Virus infections after transplantation in man. Arch Virol. 1977;55:1. [PubMed] [Google Scholar]
3. Naraqi S, Jackson GG, Jonasson O, Yamashiroya HM. Prospective study of prevalence, incidence, and source of herpes virus infections in patients with renal allografts. J Infect Dis. 1977;136:531. [PubMed] [Google Scholar]
Would you accept this donor?
The donor has excellent kidney function and his match is very good but unfortunately, he has encephalitis due to HSV which carries high risk of transmission
So it’s better to reject this donor
As HSV can cause dissimenated herpes.
Contraindication for kidney donation :
Encephalitis or meningitis of unknown cause
Encephalitis or meningitis due to herpes simplex
Jc viral infection
Cryptococcal infection
Rabies
Reference:
Koneru B, Tzakis AG, DePuydt LE, Demetris AJ, Armstrong JA, Dummer JS, Starzl TE. Transmission of fatal herpes simplex infection through renal transplantation. Transplantation. 1988 Mar;45(3):653-6.
Patient and graft survival in these transplants were similar to other types of deceased donors. Thus, after assessment of risk-benefits in the case of transplantation of this patient, chemoprophylaxis for HSV with aciclovir, valaciclovir or famciclovir should be used.
Patient and graft survival in
these transplants were similar to other types of deceased donors. Thus, after
assessment of risk-benefits in the case of transplantation of this patient,
chemoprophylaxis for HSV with aciclovir, valaciclovir or famciclovir should be
used.
HSV encephalitis is an absolute contraindication for Tx, so i shall discard this donor.
If yes, the process shall involve antiviral and a reduction in immunosuppression.
KTR is 25 years old and on the waiting list for the last 7 years secondary to reflux nephropathy. He needed to be transplanted as early as possible because while remaining in dialysis, he loses survival benefit and his vessels will be calcified and difficult to anastomose the transplant kidne.
But in this scenarios, untreated systemic infection is one of the absolute contraindications to organ donation
We should be balance between the risk of infection transmission and the morbidity and mortality risk of patient on waiting list for 7 years. The decision should be discussed in MDT between transplant team, surgeon and ID physician.
The patient had HSV meningitis which causative agent is not known, so, the risk of disease transmission is greater, and more meticulous about selection should be exercised.
For now It is not ethical to accept this donor.
Donor-derived HSV infection affected two clusters of recipients because of transplantation of organs from a prior organ recipient. HSV should be considered as a possible cause of illness in febrile SOT recipients in the immediate post-transplant period and may cause disseminated disease and re-infection in HSV-2-seropositive recipients. Testing of HSV serology and prophylaxis may be considered in SOT recipients not receiving cytomegalovirus prophylaxis
Yes I will accept this donor but first we should know the serology of both donor and recipeint , the choice of induction therapy ( ATG or Basiliximab ) and the use of prophylaxis anti viral ( acyclovir or valgancylovir )
overall patient and graft survival in recipients of organs from donors with meningitis or encephalitis were similar to those for all other types of deceased organ donor.
Herpes simplex virus-2 transmission following solid organ transplantation: Donor-derived infection and transplantation from prior organ recipientsNenad Macesic 1 2, Iain J Abbott 3, Matthew Kaye 3, Julian Druce 3, Allan R Glanville 4, Paul J Gow 5 6, Peter D Hughes 7, Tony M Korman 8, William R Mulley 9 10, Phillip J O’Connell 11, Helen Opdam 12, Miranda Paraskeva 13, Matthew C Pitman 14, Stella Setyapranata 7, William D Rawlinson 15, Paul D R Johnson 1 6
Herpesviruses (CMV, human herpes simplex virus (HSV), EBV, human herpesvirus-6 (HHV-6)) can be transmitted via transplantation; generally, post transplantation primary infection, i.e., in previously seronegative patients, is associated with a higher risk of clinical manifestations and severity. However, prevention might be achieved by prophylaxis or preemptive therapy, enabling transplantation between herpesvirus serodiscordant donor-recipient pairs.(1)
Donor organs have not been considered as a potential route of transmission of HSV. There is a recent report presenting evidence that donor kidneys could act as a vehicle for transmission of HSV . HSV normally enters the body through abraded skin or mucosal surfaces. The virus is known to establish latency in ganglionic neurons after primary infection . Following genital HSV infection, it is possible that the virus could reach the ureter and kidney along rich periureteric and perinephric autonomic nerve plexuses and remain latent there. Other possible routes to the kidney would be viremia during a primary HSV infection , or via an ascending route from the external genitalia in a catheterized patient. Although one report discusses the isolation of HSV from 5 of 10 normal kidneys, the author did not actually isolate the virus in tissue culture, and other investigators have not been able to confirm their results. Thus it remains unclear whether HSV can establish latency in the kidney.(2)
Donor kidneys have been shown to be a source of cytomegalovirus infections but evidence has been minimal regarding their role in HSV infections . there is recently documented one instance of transmission of primary HSV-2 infection by renal transplantation but thought this was a rare occurrence, but 21 months after that a tragic experience occured in which two renal recipients died of disseminated herpes infection with fulminant hepatitis after receiving organs from the same donor.(2)
Disseminated infection with herpes simplex virus type 2 was identified in two patients 20 days after they had received kidney transplants from the same organ donor. Neither patient had neutralizing antibody to herpes simplex virus before transplantation, and both had herpes simplex virus isolated from surveillance cultures of urine before the onset of clinical symptoms. A clear focus of primary infection was not found in either patient. Analysis of the patients’ isolates by DNA restriction endonuclease analysis strongly suggested that the strains were identical. These data implicate the allografts as the source of the viral infection.(3)
ref
1-Westphal GA, Garcia VD, Souza RL, Franke CA, Vieira KD, Birckholz VR, Machado MC, Almeida ER, Machado FO, Sardinha LA, Wanzuita R, Silvado CE, Costa G, Braatz V, Caldeira Filho M, Furtado R, Tannous LA, Albuquerque AG,
2- Koneru B, Tzakis AG, DePuydt LE, Demetris AJ, Armstrong JA, Dummer JS, Starzl TE. Transmission of fatal herpes simplex infection through renal transplantation. Transplantation. 1988 Mar;45(3):653-6. doi: 10.1097/00007890-198803000-00031. PMID: 2831642; PMCID: PMC3228318.Abdala E; Associação de Medicina Intensiva Brasileira; Associação Brasileira de Transplante de Órgãos. Guidelines for the assessment and acceptance of potential brain-dead organ donors. Rev Bras Ter Intensiva. 2016 Sep;28(3):220-255. doi: 10.5935/0103-507X.20160049. PMID: 27737418; PMCID: PMC5051181.
3- Dummer JS, Armstrong J, Somers J, Kusne S, Carpenter BJ, Rosenthal JT, Ho M. Transmission of infection with herpes simplex virus by renal transplantation. J Infect Dis. 1987 Feb;155(2):202-6. doi: 10.1093/infdis/155.2.202. PMID: 3027191.
I will accept him
if yes Donor dying with meningitis or encephalitis are valuable source of organs for transplantation.The risk of disease transmission is low, especially if the causative agent is known and prophylaxis is taken
A study showed that overall patient and graft survival in recipients of organs from donors with meningitis or encephalitis were similar to those for all other types of deceased organ donor.
Prophylactic regimens for CMV are also effective against HSV.
Trotter PB, Robb M, Hulme W. et al. Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis. Transpl Infect Dis. 2016 Dec;18(6):862-871.
Slifkin M, Doron S, Snydman DR. Viral prophylaxis in organ transplant patients. Drugs. 2004;64(24):2763-92.
Would you accept this donor?
I would accept this donation offer:
Donor: 23 y male, DBD, post HSV encephalitis, good renal function before death
Recipient: 25 y old, ESRD because of reflux nephropathy, 000 mismatch, no DSA, on transplant waiting list for 7 years.
This is a low immunological offer; the main concern now is the risk of HSV transmission from donor to recipient. Induction immunosuppression will be basiliximab.
Herpesviruses can be transmitted from donors to recipients during solid organ transplantation. The risk of transmission is low (3.5%-10 %) and is affected by many factors especially donor-recipient serological status, Immunosuppressive medications and anti-viral prophylactic medications.
HSV infection in donors is considered a contra-indication for donation.
Pre-transplantation counselling is very important, risks and benefits should be discussed with the recipient.
If the recipient is HSV serology is negative–à increased risk of re-activation.
If the recipient is HSV serology is positive–à low risk of re-activation.
This recipient will need prophylactic anti-viral medication. Either Aciclovir or foscarnet if acyclovir resistant strain.
If yes, what is the prognosis?
the graft outcome is similar between recipients of DCD or DBD with meningitis and encephalitis compared to recipients of deceased donors without meningitis and encephalitis.
· Q1: This donor has an active HSV encephalitis. Therefore, it would be contraindication for donation.
· Q2: According to a UK registry analysis, among 258 deceased donors
with meningoencephalitis (M/E) with known etiology in 72.9%, there was only one
case of disease transmission of unknown cause. Patient and graft survival in
these transplants were similar to other types of deceased donors. Thus, after
assessment of risk-benefits in the case of transplantation of this patient,
chemoprophylaxis for HSV with aciclovir, valaciclovir or famciclovir should be
used.
Trotter PB, Robb M, Hulme W, Summers DM, Watson CJ, Bradley JA, Neuberger J. Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis. Transpl Infect Dis. 2016 Dec;18(6):862-871.
· Q1: This donor has an active HSV encephalitis. Therefore, it would be contraindication for donation.
Q2: According to a UK registry analysis, among 258 deceased donors
with meningoencephalitis (M/E) with known etiology in 72.9%, there was only one
case of disease transmission of unknown cause. Patient and graft survival in
these transplants were similar to other types of deceased donors. Thus, after
assessment of risk-benefits in the case of transplantation of this patient,
chemoprophylaxis for HSV with aciclovir, valaciclovir or famciclovir should be
used.
I will not accept this donor as he has viral encephalitis and carries a high risk of transmission to the recipient.
The prognosis will be poor as immunosuppression may lead to activation and dissemination resulting in poor patient outcome.
Basavaraju SV, Kuehnert MJ, Zaki SR, Sejvar JJ. Encephalitis caused by pathogens transmitted through organ transplants, United States, 2002-2013. Emerg Infect Dis. 2014 Sep;20(9):1443-51. doi: 10.3201/eid2009.131332. PMID: 25148201; PMCID: PMC4178385.
This donor can’t be accepted for donation in my point of view, the burden of such a disease in young patient 23 year old, with progressing to encephalitis (who is not immunosuppressed like renal transplant recipient) which causes him further death is expected to become even worse in our renal transplant candidate up to severe viraemia and ending his life especially on immunosuppressive therapy.
Sometimes the use of suboptimal organs, can be hazardous carrying the risk of disease transmission and reactivation.
UK guidelines from the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) (2011) highlighted that ‘Material from cases of meningoencephalitis for which no infection is identified should not be used for donation ’.The guidelines also recommend that ‘if there is any possibility of acquisition of a neurotropic infection from abroad the donation is contraindicated owing to the risk of rabies, West Nile virus or other exotic neurotropic infections’.
Although he is on waiting list for 7 years, but he is still young to risk his life, proper counselling to elaborate the adverse effects of DBD donation of this case must be expressed clearly to the patient. The prognosis would be poor in case of viral dissemination and reactivation for this young patient.
If accepted, after detailed counselling for the identifiable predicted risk, the following should be evaluated; the patient serum viral serostatus either positive and immunized requiring prophylaxis for average three months , or seronegative states requiring vaccination and both prophylaxis preferably by acyclovir or ganciclovir also for three months at least .
Monitoring the patient viral load (PCR is the best accurate tool) ,ought to be frequent especially in the first 3 to 6 months .keeping drug level to least optimum dose is recommended in such cases. Along with the recommended chemoprophylaxis three months acyclovir adjusted to renal functions.
References:
Transplantation of Organs from Deceased Donors with Meningitis and Encephalitis: a UK Registry Analysis
Herpes zoster in kidney transplant recipients: protective effect of anti-cytomegalovirus prophylaxis and natural killer cell count. A single-center cohort study Mario Fernandez-Ruiz , Julia Origuen , David Lora , Francisco Lopez-Medrano , Esther Gonzalez , Natalia Polanco , Rafael San Juan , Tamara Ruiz-Merlo , Patricia Parra , Amado Andres & Jose Mara Aguado
The Transplantation Society of Australia and New Zealand
Clinical Guidelines for Organ Transplantation from Deceased Donors Version 1.5 – April 2021T
The given Brain dead donor is a 23 year old male who had HSV encephalitis…The donor had normal baseline creatinine with good urine output…
This donor is a potential donor and I will accept this offer to a recipient of similar age group who has been waiting on the cadaver list for the last 7 years…There is no DSA and full match which makes it the best choice for the recipient…
Donor transmission of HSV encephalitis is a very small insignificant concern and it is not an absolute contraindication…Other viruses like HIV, Prion diseases, HTLV are contraindicated for organ donation… There have been reports of transmission of unknown virus from the donor to the recipient in one patient in the UK registry analyzed from 2003 to 2015 which proved to be fatal, but the other recipients who received kidney from DBD due to virus encephalitis were doing fine
In this patient I would warn them about a very small risk of transmission and keep the recipient on prophylaxis with Acyclovir to prevent the disease
Herpesviruses (CMV, human herpes simplex virus (HSV), EBV, human herpesvirus-6 (HHV-6)) are DNA viruses that can be transmitted via SOT transplantation.
As per the weak evidence from the UK registry study, the chance of transmission is low and it’s affected by multiple factors like the serological status of the recipient, and type of immunosuppression especially if the patient received induction and using of antiviral either treatment or prophylactic dose. Usually, the risk of transmission is around 10% and decreases with antiviral prophylactic to 3.5%
The cause of encephalitis can be bacteria, viruses, fungi, and protozoa. Based on a retrospective study between 2003 and 2015, 258 deceased donors with M/E were identified and the causative agent was known in 72.9% of cases (not known in 27.1%). The only recorded case of disease transmission was from a donor with encephalitis of unknown cause at the time of transplantation who transmitted a fatal nematode infection to 2 kidney transplant recipients and overall, patient and graft survival in recipients of organs from donors with M/E was similar to those for all other types of a deceased organ donor.
So, in our case
1. the pathogen of encephalitis is well-known (viral infection)
2. the immunological risk is low.
3. this recipient has been on a waiting list for> 7 years waiting and his serological status is unknown.
After consideration of risks and benefits and after clear counseling of the recipient I will accept the potential donor
There are 3 main regimes for antiviral drugs
There is no clear data regarding the rate of successful treatment of CNS viral infection as Herpes simplex encephalitis is still possible exclusion criteria
For this patient pre-emptive therapy: acyclovir doses of up to 10 mg/kg every 8 hours intravenously should be initiated. Acyclovir-resistant HSV is less common in SOT patients and can use foscarnet as an alternative treatment.
References:
1. Westphal GA, Garcia VD, Souza RL, et al; Guidelines for the assessment and acceptance of potential brain-dead organ donors. Rev Bras Ter Intensiva. 2016 Sep;28(3):220-255. doi: 10.5935/0103-507X.20160049. PMID: 27737418; PMCID: PMC5051181.
2. White, Sarah L, et al; Infectious Disease Transmission in Solid Organ Transplantation: Donor Evaluation, Recipient Risk, and Outcomes of Transmission. Transplantation Direct: January 2019 – Volume 5 – Issue 1 – p e416.
3. Ison MG, Nalesnik MA. An update on donor-derived disease transmission in organ transplantation. Am J Transplant. 2011;11:1123–1130
4. Stewart DE, Tlusty SM, Taylor KH, et al. Trends and patterns in reporting of patient safety situations in transplantation. Am J Transplant. 2015;15:3123–3133.
5. BTS/RA Living Donor Kidney Transplantation Guidelines 2018 126.
Transplant Ifect.disease.. 2016 Dec;18(6):862-871. doi: 10.1111/tid.12621. Epub 2016 Dec 3
6. Pass RF, Whitley RJ, Whelchel JD, Diethelm AG, Reynolds DW, Alford CA. Identification of patients with increased risk of infection with herpes simplex virus after renal transplantation. J Infect Dis. 1979;140:487.
7. Ho M. Virus infections after transplantation in man. Arch Virol. 1977;55:1.
A recipient will be immunocompromised so the donation with HSV encephalitis would cause dissemination and make prognosis worse, despite good antiviral prophylaxis.so I will not accept donation.
1)Would you accept this donor?
Nope. The kidney transplant recipient has risk of disseminated HSV infection.
2)If yes, what is the prognosis?
Guarded prognosis.
Reference :
1) Dockrell DH, Paya CV: Human herpesvirus-6 and -7 in transplantation. Rev Med Virol 11 : 23 –36, 2001
2)Mitchell BM, Bloom DC, Cohrs RJ, Gilden DH, Kennedy PG: Herpes simplex virus-1 and varicella-zoster virus latency in ganglia. J Neurovirol 9 : 194 –204, 2003
Herpes simplex virus infection is a well-known opportunistic pathogen among immunocompromised patients including kidney transplant recipients. This infection is usually caused by reactivation of latent virus among these patients; however, it has also been recognized as a potential donor-to-host transmission infection after transplantation. In the absence of prophylaxis, HSV may be seen early, even during the first post transplant month).
Although it usually presents oral or genital lesions, it can also be a life threatening disease with high morbidity and mortality among infected patients
routinely tested for IgM and IgG anti–HSV antibodies before transplantation while recipients should be monitored for reactivation of latent virus following immunosuppressive treatments. PLUS prophylaxis for HSV
The donor in this scenario is a standard criteria donor (age less than 50 years) with brainstem death. But this prospective donor has HSV encephalitis, which is a contraindication for donation (1). Hence I will not accept this donor.
Registry data from UK has shown that the graft outcome in organ recipients of deceased donors with meningitis and encephalitis is similar to those of non-meningitis/encephalitis donors, except in those with unknown etiology (2).
If accepted, antiviral prophylaxis with reduced immunosuppression (avoiding induction therapy as it is a 000 mismatch and no DSA, with lower trough levels of tacrolimus) will be required.
References:
1) Westphal GA, Garcia VD, Souza RL, Franke CA, Vieira KD, Birckholz VR, Machado MC, Almeida ER, Machado FO, Sardinha LA, Wanzuita R, Silvado CE, Costa G, Braatz V, Caldeira Filho M, Furtado R, Tannous LA, Albuquerque AG, Abdala E; Associação de Medicina Intensiva Brasileira; Associação Brasileira de Transplante de Órgãos. Guidelines for the assessment and acceptance of potential brain-dead organ donors. Rev Bras Ter Intensiva. 2016 Sep;28(3):220-255. doi: 10.5935/0103-507X.20160049. PMID: 27737418; PMCID: PMC5051181.
2) Trotter PB, Robb M, Hulme W, Summers DM, Watson CJ, Bradley JA, Neuberger J. Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis. Transpl Infect Dis. 2016 Dec;18(6):862-871. doi: 10.1111/tid.12621. Epub 2016 Dec 3. PMID: 27699935.
The available donor is 23 years old male with DBD history of HSV encephalitis basal creatinine is 60 ummol and on admission 71 ummol UOP 3.4 L /24H with 000 mismatches and no DSA
I will not accept this donor, high risk of transmission of infection which is life threatening in such immuno-compromised patients.
Patient had poor prognosis , significant risk of transmission of infection , high risk of sepsis , made patient need treatment with antiviral therapy with decrease dose of immmosuppressive medication which make risk of rejection high in such condition.
Sorry for the previous post, please ignore.
Yes, I would accept this one. Although transmission of HSV causes significant morbidity and occasional mortality, it´s rare.
· If yes, what is the prognosis?
Positive prognosis because we have prophylaxis, even if they prioritize the reactivation of latent disease. And the possibility of preemptive disease treatment can be considered, although there is no guidance for this.
Bibliography:
1 – Transmission of fatal herpes simplex infection through renal transplantation. Transplantation. 1988 March ; 45(3): 653–656.
2 – Herpes simplex virus -2 transmission following solid organ transplantation: Donor -derived infection and transplantation from prior organ recipientes. Transpl Infect Dis. 2017 Oct;19(5). doi: 10.1111/tid.12739. Epub 2017 Jul 31.
As there is no absolute contraindication and the recipient has been in the queue for many years and without sensitization, I would accept this donor.
The prognosis is positive as long as antibiotic treatment is carried out in the post-transplantation phase.
Bibliography:
– Transmission of Syphilis by Solid Organ Transplantation. American Journal of Transplantation 2006; 6: 2497–2499. doi: 10.1111/j.1600-6143.2006.01461.x
This potential donor has an active infection which contra indication for donation.
So, it should have been treated first before offering the organs. Because risk of transmission is high, and this is CNS infection and the recipient is going to be immunosuppressed.
Yes, the recipient is on the waiting list for 7years, however doing no harm is priority.
The risk of transmission of the infection to recipient is significant. We will need to treat actively with anti-viral, acyclovir up to 10mg/kg 8hourly with reduction of immunosuppression in case of active infection which will put him on high rejection risk in the first days post transplant.
Reference:
Clin Transplant 2019 Sep;33(9):e13526.
Donor-derived viral transmissions like CMV and HBV are expected. Although HSV is not in the routine screening, HSV types 1/2 and to are not transmitted much through blood because of neurotropism (affinity to nervous tissue). some centres use acyclovir, while the majority use valacyclovir (most widely) for the first 90 days post-transplantation. as both are effective against HSV, I may accept this donor. The viral prophylaxis will help prevent reactivation.
Another secondary issue is reflux history. Need to be evaluated in the follow-up
With the preemptive prophylaxis and effective treatment, we expect a good prognosis.
………….
Jenkins, F. J., Rowe, D. T., & Rinaldo Jr, C. R. (2003). Herpesvirus infections in organ transplant recipients. Clinical and Vaccine Immunology, 10(1), 1-7.
A Report from the British Society for Antimicrobial Chemotherapy Working Party* on Antiviral Therapy, Management of herpes virus infections following transplantation, Journal of Antimicrobial Chemotherapy, Volume 45, Issue 6, June 2000, Pages 729–748, https://doi.org/10.1093/jac/45.6.729
I will not accept this donor because high risk of spreading infection but this patient is young and on waiting list for long time and has good matching with donor but unfortunately this donor infected/ so he may become on long time on antiviral prophylactic agent like acyclovir but still risk very high of transmission of infection to recipient
HSV is the most common form of encephalitis in transplant recipients. HSV PCR and cultures from cerebrospinal fluid can assist diagnosis.
Diagnosis may be made with the aid of direct fluorescence antibody for HSV from vesicular lesions or PCR from cerebrospinal fluid or visceral tissue samples. Due to high seroprevalence in the adult population, serologies are rarely helpful in the setting of active infection
Since its identification in 1994, Kaposi sarcoma herpes vi- rus (KSHV) has been demonstrated to be associated with all forms of Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease
Pre‐transplant screening of potential organ donors and recipients is essential to optimal outcome of solid organ transplantation.
The goals of pre‐transplant infectious disease screening are to identify conditions which may disqualify either donor or recipient, to identify and treat active infection pre‐transplant, to recognize and (if possible) define the risk of infection, and, lastly, to develop and implement strategies that prevent and mitigate post‐transplant infections.
Candidates should be evaluated for risk of infection by obtaining a thorough medical history, including details of prior infections, places of travel and residence, occupation and/or lifestyle, and exposures to animal and environmental pathogens. In addition to standard testing ,a detailed history can determine the need for additional testing to assess risk for reactivation of latent infection post‐transplant.
I will not accept this donor due to presence of encephalitis and active viremia put the recipient at high risk for transmission of fatal viral infection
1-ScreeningScreening of donor and candidate prior to solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice
Maricar Malinis1 | Helen W. Boucher2 | on behalf of the AST Infectious Diseases Community of Practice of donor and candidate prior to solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice
Maricar Malinis1 | Helen W. Boucher2 | on behalf of the AST Infectious Diseases Community of Practice
Received: 5 March 2019 DOI: 10.1111/ctr.13548
| Accepted: 15 March 2019
S P E C I AL I S S U E : T R AN S P L ANT INF E C T I OU S DI S E A S E S
2-Viral Infection in Renal Transplant Recipients
Jovana Cukuranovic, Sladjana Ugrenovic, Ivan Jovanovic, Milan Visnjic, and Vladisav Stefanovic
Faculty of Medicine, University of Nis, 18000 Nis, Serbia
Correspondence should be addressed to Vladisav Stefanovic, stefan@ni.ac.rs Received 2 December 2011; Accepted 10 January 2012
Academic Editors: S. Basmaciogullari, B. Harrach, and K. Mansfield.
The Scientific World Journal
Volume 2012, Article ID 820621, 18 pages doi:10.1100/2012/820621
Would you accept this donor?
No, I would not accept this donor because donors who have died as a result of meningitis or encephalitis have a high risk of transmitting life-threatening meningitis or encephalitis to the immunocompromised recipient
If yes, what is the prognosis?
Poor prognosis because it may lead to transmission of fatal infection
Reference:
-P. B.Trotter1 et al. Transplantation of Organs from Deceased Donors with Meningitis and Encephalitis: a UK Registry Analysis.
Would you accept this donor?
This 23 year old DBD has excellent renal parameters and excellent match. The donor has suffered from HSV encephalitis. So the donation in this case will be associated with higher risk of HSV transmission. HSV infection following renal transplant increases morbidity and mortality.
There can be risk of disseminated herpes with fulminant hepatitis.
Other viral infections in which there is clear contraindication of renal transplantation are Encephalitis or meningitis, CJ disease , JC virus infection, west Nile virus and also cryptococcal infections.
So I will not accept this donor.
If yes, what is the prognosis?
There will be higher risk of transmission and also risk of systemic sepsis with poor graft ooutcomes
Reference
1-Koneru B, Tzakis AG, DePuydt LE, Demetris AJ, Armstrong JA, Dummer JS, Starzl TE. Transmission of fatal herpes simplex infection through renal transplantation. Transplantation. 1988 Mar;45(3):653-6.
2-Uptodate 2022
I will not accept the donor
as The transplantation of organs from donors infected with the following infections is contraindicated: viral meningoencephalitis or of unknown origin
Herpesviruses (CMV, human herpes simplex virus (HSV), EBV, human herpesvirus-6 (HHV-6)) Can be transmitted via transplantation especially on seronegative patients however prophylaxis or pre-emptive therapy can be given enabling renal transplantation.
Also HIV infection, positive serology for HTLV-I and II, acute viral hepatitis, active tuberculosis, malaria, acute viral infections (e.g., rubella, rabies, West Nile virus, adenoviruses, enteroviruses, parvoviruses, cryptococcal meningitis, and prion diseases are contraindicated.
Sepsis that is not controlled is considered to be contraindicated until if he is hemodynamically stable or with gradual tapering of vasopressor.
If Yes
high risk of transmission may occur with high morbidity and mortality if the patient is seronegative however seropositivity of the same virus and prophylaxis taken may decrease the risk of transmission
Ref :
Dockrell DH, Mendez JC, Jones M, Harmsen WS, Ilstrup DM, Smith TF, et al. Human herpesvirus 6 seronegativity before transplantation predicts the occurrence of fungal infection in liver transplant recipients. Transplantation. 1999;67(3):399–403.
Ison MG, Grossi P, AST Infectious Diseases Community of Practice Donor-derived infections in solid organ transplantation. Am J Transplant. 2013;13(Suppl 4):22–30.
1- Iwill not accept this donor as has active infection ,herps encephalitis .
2-if ,yeas the prognosis is unfavorable as risk of transimmsion is high .
Infectious considerations in the evaluation of potential organ donors and recipients (possible exclusion criteria*)
Central nervous system (CNS) infection
1-Encephalitis and/or meningitis of unknown etiologyUntreated or incompletely treated 2.encephalitis and/or meningitisHerpes simplex
3.encephalitisHistory of JC virus infectionWest Nile virus infection or other active arbovirus infection
4.Cryptococcal infection of any site (or other disseminated fungal infection
5.)RabiesCreutzfeld-Jacob diseaseViral infection (also refer to CNS infections above)
6.Acute viremia (eg, herpes simplex virus, cytomegalovirus, adenovirus, lymphocytic choriomeningitis virus, hepatitis A, West Nile virus)Active shingles (varicella-zoster infection) or herpes virus pneumonitisAcute Epstein-Barr virus
2Bacterial infectionActive tuberculosisUntreated pneumoniaUntreated bacterial or fungal sepsis
referenc
from uptodate
Despite this young DBD donor is a perfect donor with a 000 match and no DSA and has excellent renal function for this recipient who is waiting for a long time on the waiting list. I will still reject this offer since acute untreated herpes infection that resulted in encephalitis with viremia is a contraindication to donation.
-Encephalitis and/or meningitis of unknown etiology
-Untreated or incompletely treated encephalitis and/or meningitis
-Herpes simplex encephalitis
-History of JC virus infection
-History of JC virus infection
-Cryptococcal infection of any site (or other disseminated fungal infection)
-West Nile virus infection or other active arbovirus infection
-Rabies
-Creutzfeld-Jacob disease
European guidelines state that organs can be accepted from donors with latent herpes family viral infections, except in the case of acute herpes viremia in the donor without effective antiviral treatment.
International guidelines do not require donor screening for HSV-1 or HSV-2, and no contraindication exists to organ donation with latent herpes family viral infections due to high rates of donor and recipient exposure and routine effective antiviral prophylaxis (acyclovir, valaciclovir, ganciclovir, valganciclovir).
A Careful explanation should be provided to the recipient about the potential high risks and the poor prognostic outcome if he receives this offer.
The majority of severe HSV disease occurs within the first month after transplant and may become more invasive with a greater potential for dissemination to visceral organs compared to the immune-competent host. Therefore to reduce the risk ,antiviral prophylaxis for HSV should be used during the first month and may be extended in positive serology recipients but those receiving CMV prophylactic regimens is considered effective chemoprophylaxis against HSV. This should be coupled with tailoring both induction and maintenance immunosuppression.
References:
1) Jovana Cukuranovic, Sladjana Ugrenovic, Ivan Jovanovic, Milan Visnjic, and Vladisav Stefanovic. Viral Infection in Renal Transplant Recipients. Review Article. The Scientific World Journal Volume 2012, Article ID 820621, 18 pages
2) UpToDate – Prevention of viral infections in transplant recipients
Infections can be transmitted by both blood transfusion and organ donation
Human Herpes Virus 8 (HHV8) may be transmitted by organ transplantation and is associated with an increased risk of Kaposi sarcoma
Screening for other infections should be screened well
prophylactic acyclovir therapy should strongly be considered for at least 3 months
whenever a kidney is transplanted from a seropositive donor to a seronegative recipient
my decision
============
I will not accept him as a donor although he has perfect matching with good kidney function
My rationale is based on:
——————————-
This DBD has an active infection and it may be part of other opportunistic infections secondary to a condition of immunosuppression like HIV and no sufficient time to screen for other serious infection
Based on the risk-benefit ratio, there is a high risk of transmitting the infection to the recipient with catastrophic sequela
Review article
Prevention and therapy of viral infections in patients with solid organ
transplantation; Enferm Infecc Microbiol Clin. (2021);39(2):87–97
Koneru, B., Tzakis, A. G., DePuydt, L. E., Demetris, A. J., Armstrong, J. A., Dummer, J. S., & Starzl, T. E. (1988). TRANSMISSION OF FATAL HERPES SIMPLEX INFECTION THROUGH RENAL TRANSPLANTATION. Transplantation, 45(3), 653. https://doi.org/10.1097/00007890-198803000-00031
Well done
– Yes I would accept this donor because this transplant harbours 000 mismatch with no DSA, also the donor’s age ,creatinine and urinary output are satisfactory from one side and from the other side the recipient is young with long dialysis period.
– Recipient and graft survival receiving organs from donors with meningitis or encephalitis were similar to those for all other types of deceased organ donor , as those donors represent a valuable source of organs for transplantation and the risk of disease transmission is low.
Italian National Center for Transplantation/European risk classification system published2002 defines donors in multiple criteria involving a calculated risk includes all cases even in the presence of transmissible diseases, transplantation is allowed for recipients with the same disease or with a protective serological status; this risk applies also to donors with documented bacteremia and/or bacterial meningitis provided that the donor was on targeted antimicrobial treatment for a minimum duration of 24–48 h.
Reference
-Trotter PB, Robb M, Hulme W, Summers DM, Watson CJ, Bradley JA, Neuberger J. Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis. Transpl Infect Dis. 2016 Dec;18(6):862-871.
-Ison M G et al. Donor-Derived Infections in Solid Organ Transplantation. American journal of transplantation Volume13, Issues4 ,Special Issue: The American Society of Transplantation Infectious Diseases Guidelines 3rd Edition March 2013 ,Pages 22-30
Looking back at the index case ,he has HS encephalitis heavy enough to cause brain death with an expected viremia state.
did he and how long antivirus treatment he received?!
Potenial recipient is immuno compromised even with moderate induction plan.
!
Deceased organ donors, where the cause of death is meningitis or encephalitis, are a potential concern because of the risks of transmission of a potentially fatal infection to recipients.
Donors dying with M/E represent a valuable source of organs for transplantation. The risk of disease transmission is low but, where the causative agent is unknown, caution is required.
In this case the causative agent is known (HSV),we should know the serostatus of the recipient and we must use prophylactic antiviral (acyclovir)
I will accept this donor giving that the recipient is waiting for a long time. With Consideration to be taken for the induction and maintenance immunosuppression protocols to avoid the risk of infection.
Herpes simplex virus (HSV) reactivation is more frequent, may become more invasive, takes longer to heal, with a potential for dissemination to visceral organs
If the causative agent is known the risk of transmission is low given that we will used prophylactic agent.
Reference:
Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis
Patrick B Trotter et al. Transpl Infect Dis. 2016 Dec.
Hi Dr Asmaa,
I like your argument and scientific suggestions. My suggesting ‘how one would reduced the risk of life-threatening HSV from such a donor’, I might erroneously sound as if I am agreeing with you.
Ajay
In the current scenario of excellent immunological profile of potential donor/recipient with obstacle of potential deceased donor with viral encephalitis (HSV encephalitis).
First of all, Infections are the second cause of death in solid organ transplant patients in the first three years. The incidence ranges from 3-50 per 100 patients, depending on the antiviral prophylaxis.
Herpes simplex virus (HSV) type 1 infection is mostly due to viral reactivation (the virus replicates in the oral and genital mucosa and is transported to regional ganglia where it establishes latency) and is rarely due to transmission from the donor to the recipient. One of the causes of HSV type 1 reactivation in transplant patients is treatment with mycophenolate mofetil, muromonab-CD3 (OKT3), alemtuzumab or medications with significant T-cell depletion.
Antiviral prophylaxis in transplantation has reduced the incidence of HSV type 1 encephalitis by up to 70%, using ganciclovir and valganciclovir. In a meta-analysis which included nine studies with 1,483 transplant patients, the reduction in the incidence of HSV or herpes zoster virus (HZV) infections was significant using valganciclovir or ganciclovir prophylaxis versus placebo.
As per UK Registry Analysis patient and graft survival in recipients of organs from donors with meningitis and encephalitis (with known etiology) were similar to those for all other types of deceased organ donor. Donors dying with meningitis and encephalitis represent a valuable source of organs for transplantation. The risk of disease transmission is low.
US guidance (2013) states that donors dying of encephalitis without a proven cause should likely be avoided. The UK and US guidance is mirrored by that from the Council of Europe (2015), which states that ‘if the aetiology of an active infection cannot be established the donor is not a suitable candidate for donation.
So based on the previous reviews, I will accept the offer with precautions and under cover of Antiviral prophylaxis with acyclovir, valacyclovir, and famciclovir
References
Gilden DH, Mahalingam R, Cohrs RJ, Tyler KL. Herpesvirus infections of the nervous system.Nat Clin Pract Neurol[Internet]. 2007 Feb [cited 2019 Apr 29];3(2):82-94.
Hodson EM, Ladhani M, Webster AC, Strippoli GF, Craig JC. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.Cochrane Database Syst Rev[Internet]. 2013 Feb 28 [cited 2019 May 7];(2):CD003774.
Ison MG, Hager J, Blumberg E, Burdick J, Carney K, Cutler J, et al. Donor‐ Derived Disease Transmission Events in the United States: Data Reviewed by the OPTN/UNOS Disease Transmission Advisory Committee. Am J Transplant 2009; 1:9(8):1929–35.
Hi Dr Foud,
I like your argument and scientific suggestions. My suggesting ‘how one would reduced the risk of life-threatening HSV from such a donor’, I might erroneously sound as if I am agreeing with you.
Ajay
This is acase of young DBD low immune risk with viral infection HSV encephalitis
And good renal function
As donor had viral encephalitis so it would be a state of viremia so there are a high risk for transmission
On the other hand my patient had a very long waiting list so I will counseling the recipiant with the risks and benifits and I will reduce the risk of transmission by proghylacting Drugs especially IV acyclovir
I think that IVIG can give some protection
Hi Dr Huda,
I like your argument and scientific suggestions. My suggesting ‘how one would reduced the risk of life-threatening HSV from such a donor’, I might erroneously sound as if I am agreeing with you.
Ajay
A 23-year-old male, DBD, history of herpes viral encephalitis, good renal function, compatible with the recipient, the recipient is 7 years on the waiting list.
we need to know the HSV serostatus of the recipient.
Antiviral prophylaxis is required to reduce the risk of viral transmission; the most widely used agent is acyclovir.
Most guidelines recommend not accepting offers with unknown causes of encephalitis.
For this donor, the cause is known and the transmission rate is low, so we can accept this donor giving that the recipient is waiting for a long time. Consideration should be done for the induction and maintenance immunosuppression protocols to avoid the risk of infection.
the risk of transmission is low, antiviral prophylaxis needs to be considered, MMF dose needs to be adjusted.
References:
HI Dr Huda,
I would not agree that ‘risk of transmission of HSV is low’.
Ajay
I will not accept that donation due to viral infection as it could be considered severe as the donor is of young age; high transmission incidence due to positive CSF viremia .
But if accepted due to other considerations favouring not staying on dialysis, antiviral prophylaxis is required together with suitable modification of immunosuppressive therapy.
Encephalitis caused by pathogens transmitted through organ transplants, United States, 2002-2013.
AU
Basavaraju SV, Kuehnert MJ, Zaki SR, Sejvar JJ
SO
Emerg Infect Dis. 2014;20(9):1443.
I like your argument, dear Dr Omran.
1.This potential 23 years old DBD donor had HSV encephalitis , which having excellent matching with the recipient 000 mis-match ,with no DSA which gives an excellent graft survival and low risk for rejection, so i would rather accept this potential donor taking into consideration: 1. long term waiting period of that recipient. 2. Good matching between potential donor and recipient so, considering low immunological risk so no need for induction therapy. 3. Management of HSV. 4. DBD Donors with encephalitis represent a valuable source of organs for transplantation because of low risk of disease transmission. 4. Recipient should also be informed about the risks of transmission. 5. Close monitoring of recipient viral load.
2.Because of incidence rate of virus transmission So, routine prophylaxis of HSV should be taken ( Anti-CMV could be effective in both prophylaxis and eradication of HSV and CMV viruses ) plus, some manipulation in classic triple immunosuppression , there is evidence of usage of m-TORs inhibitors medications in decreasing incidence of HSV infection. Prophylactic dose acyclovir for 3 months post- transplant should be given.
References:
1.Wilck MB, Zuckerman RA and the AST Infectious Disease Community of Practice : Herpes simplex virus in solid organ transplantation. Am J Transplant, 2013; 13:121-127
2.Trotter PB, Robb M,etal.: Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis. Transpl Infect Dis. 2016 Dec;18(6):862-871.
Hi Dr Omar,
I like your argument and scientific suggestions. My suggesting ‘how one would reduced the risk of life-threatening HSV from such a donor’, I might erroneously sound as if I am agreeing with you.
Ajay
Patients with viral or parasitic encephalitis should not be considered for organ donation. Donor-to-recipient transmission has been reported for West Nile virus, rabies virus lymphocytic choriomeningitis virus and Balamuthia mandrillaris with very poor recipient outcomes.(up to date)
In view of above I think we should reject this donation as he had HSV encephalitis with viremia.
Thank you, Zahid
You have not answered the rest of the questions
Our potential donor is ;
-23 years old
-DBD
-HSV encephalitis
-perfect match
-No ABO data
-normal renal functions
This scenario highlights the herpes simplex infection potential transmission to the
Recipient .
literature and Prognosis:
*life-threatening de novo infections have occurred in naïve recipients of organs from latently-infected donors and due to reactivation in latently-infected recipients.
*Recipient HSV IgG serostatus should be determined prior to transplant .
*HSV seropositive recipients are at risk of clinical reactivation posttransplant in the absence of antiviral prophylaxis even if they had not had prior clinical HSV disease. The incidence of clinically apparent HSV disease in HSV-seropositive adult transplant patients who are not receiving antiviral prophylaxis ranges from 35% to 68% .
*Given high rates of donor and recipient exposure, routine prophylaxis seems a more efficient approach than donor and recipient HSV-1 and HSV-2 IgG testing.
*Routine HSV prophylaxis is supported by a number of guidelines(1,2). Where it is administered, CMV antiviral prophylaxis will also be effective against HSV.
*In the event that CMV prophylaxis is not given, acyclovir, famciclovir or valaciclovir would be the anti-HSV agents commonly utilised, usually recommended for at least one month post-transplantation.
*Active infection in donors should also be considered where there are clinical features suggestive of HSV ( here in the case we know for sure).
*Organs can be accepted from donors with latent herpes family viral infections, and HSV screening is not required where antiviral prophylaxis is routinely administered.
*Organs from donors with acute herpes viraemia should only be considered with the administration of HSV-active antiviral treatment to the recipient.
*Historically, use of anti-CD3 antibody muromonab (OKT3) and mycophenolate mofetil have been associated with an increased risk of HSV reactivation after transplantation .
*There have been no evaluations to date comparing different induction regimens (T cell depleting agents such as rabbit-antithymocyte globulin or alemtuzumab vs. nondepleting agents such as basiliximab or daclizumab) or maintenance immunosuppressive regimens with regards to HSV reactivation rates.
*However, there are some data to suggest use of the mTOR inhibitors (e.g. rapamycin) with reduced calcineurin inhibitor exposure leads to reduced herpes virus infections .
*The medical urgency of transplantation for some patients may mean that
transplantation with an organ from a donor with increased risk of disease transmission is considered.
“Particularly where transplantation is life saving, an increased risk of disease transmission may be regarded as acceptable to the recipient. Conversely, where transplantation is not immediately life saving but instead aims to improve the
quality of the recipient’s life, a greater margin of safety is appropriate”
So if the transplant procedure here is not the absolute only way for our recipient’s life ( eg: No access for HDx ) then i won’t accept this donor suffering from CNS encephalitis.
References :
1-Wilck MB, Zuckerman RA and the AST Infectious Disease Community of Practice. Herpes simplex virus in solid organtransplantation. Am J Transplant, 2013; 13:121-127
2- Abad CL, Razonable RR. Alpha herpes virus infections amoung renal transplant recipients. Sem Nephrol, 2016; 36(5): 344-350
3- Minhas V and Wood C. Epidemiology and transmission of Kaposi’s sarcoma-associated herpesvirus. Viruses, 2014; 6(11), p.4178-94.
4- Luppi M, Barozzi P, Santagostino G, et al. Molecular evidence of organ-related transmission of Kaposi sarcoma-associatedherpesvirus or human herpesvirus-8 in transplant patients. Blood, 2000; 96(9):3279-81
5- Barozzi P, Luppi M, Facchetti F, et al. Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors.Nat Med, 2003; 9(5):554-61
6- Lebbe C, Porcher R, Marcelin A, et al. Human herpesvirus 8 (HHV8) transmission and related morbidity in organ recipients. Am JTransplant, 2012; 13(1):207-13
7- Regamey N, Tamm M, Wernli M et al. Transmission of human herpesvirus 8 infection from renal-transplant donors to recipients.New Engl J Med, 1998; 339(19):1358-63.
8- Vijgen S, Wyss C, Meylan P, et al. Fatal outcome of multiple clinical presentations of human herpesvirus 8-related disease aftersolid organ transplantation. Transplantation, 2015; 100(1): 134-40.
Thank you.
23-year-old male DBD who suffered from HSV encephalitis.His baseline S Cr was 60 µmol/L. On admission S Cr was reported to be 71 µmol/L (0.8 mg/dl). His urine output is 130 mls during the last hour and 3.4 L over the last 24 hours. The recipient is 25 years old, 000 mismatch, no DSA. He is on the waiting list for the last 7 years secondary to reflux nephropathy.
Would you accept this donor?
Yes, I would accept this donor, however we have an excellent matching with the recipient (MM 000), which gives an excellent graft and patient survival and low risk for rejection, this may allow us to do induction by Basiluximab, with low risk for HSV transmission, especially the recipient has been for long tome on waiting list put him on high risk for death and complications[4].
If yes, what is the prognosis?
Viral pathogens have a deleterious effect on solid organ transplant recipients. Antiviral prophylaxis (Acyclovir, Valaciclovir or Famciclovir) used to abort transmission, avoid reactivation, and prevent progression of disease [2].
Donors dying with meningitis/encephalitis represent a valuable source of organs for transplantation. The risk of disease transmission is low [3].
Herpes simplex virus (HSV) reactivation is more frequent, may become more invasive, takes longer to heal, with a potential for dissemination to visceral organs [2].
HSV should be considered as a possible cause of illness in febrile solid organ transplant in the immediate post-transplant period ( days to weeks), may cause disseminated disease and re-infection in HSV-2-seropositive recipients[1]
Testing of HSV serology and prophylaxis may be considered in SOT recipients not receiving cytomegalovirus prophylaxis [1].
References:
[1] Macesic N, Abbott IJ, Kaye M, Druce J, Glanville AR, Gow PJ, Hughes PD, Korman TM, Mulley WR, O’Connell PJ, Opdam H, Paraskeva M, Pitman MC, Setyapranata S, Rawlinson WD, Johnson PDR. Herpes simplex virus-2 transmission following solid organ transplantation: Donor-derived infection and transplantation from prior organ recipients. Transpl Infect Dis. 2017 Oct;19(5). doi: 10.1111/tid.12739. Epub 2017 Jul 31. PMID: 28618165.
[2] Slifkin M, Doron S, Snydman DR. Viral prophylaxis in organ transplant patients. Drugs. 2004;64(24):2763-92. doi: 10.2165/00003495-200464240-00004. PMID: 15563248.
[3] Trotter PB, Robb M, Hulme W, Summers DM, Watson CJ, Bradley JA, Neuberger J. Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis. Transpl Infect Dis. 2016 Dec;18(6):862-871. doi: 10.1111/tid.12621. Epub 2016 Dec 3. PMID: 27699935.
[4] Andrews PA, Burnapp L. British Transplantation Society / Renal Association UK Guidelines for Living Donor Kidney Transplantation 2018: Summary of Updated Guidance. Transplantation. 2018 Jul;102(7):e307. doi: 10.1097/TP.0000000000002253. PMID: 29688993; PMCID: PMC7228639.
Thank you, Mohamed
Your point is taken
A 23- year male DBD with history of HSV encephalitis and normal creatinine and urine output of 3.4 liter over the last 24 hours is not a candidate for donation to 25 year male with 000 mismatch, and no DSA because of the high risk of transmission of virus in the recipient despite of the waiting time of recipient for seven years.
The European Council 2015 recommendation is that patient cannot donate in the presence of active infection and also BTS guidelines recommendation is that patients with encephalitis and/or meningitis of unknown etiology, herpes simplex , JC virus infection, West Nile virus infection ,Rabies, or parasitic infections should not donate .
Exact risk of transmission of HSV is not clear and its better to avoid donation of donors with history of HSV. But if considered then recipient should be counseled in detail about the risks and immediately be started on antiviral prophylaxis with close monitoring of viral load .
REFERENCES:
1-White SL, Rawlinson W, Boan P, et al.Infectious Disease Transmission in Solid Organ Transplantation: Donor Evaluation, Recipient Risk, and Outcomes of Transmission. Transplant Direct. 2018 Dec 20;5(1):e416.
2-BTS/RA Living Donor Kidney Transplantation Guidelines 2018 .
Thank you, Batool.
Would you accept this donor?
No, I wouldn’t accept this donor:
a) Barring overwhelming sepsis, bacteremia or fungemia in the donor are not absolute contraindications to donations.
b) Infections with human immunodeficiency-virus, herpetic meningo-encephalitis and T-cell leukemia-lymphoma virus preclude organ donation1.
If yes, what is the prognosis?
a) The prognosis is poor, and the risk of transmission is high, although there were reported cases2of successful utilization of both kidneys from a deceased donor with confirmed active, nondisseminated HZ infection at the time of donation. The recipients were both VZV immune prior to trans- plant and received Basiliximab induction therapy with standard triple immunosuppression. They were treated prophylactically with high-dose acyclovir for a one-week period followed by prophylactic dose acyclovir for 3 months post- transplant. Both recipients did well with no evidence of VZV reactivation or infectious complications.
b) Disseminated VZV infection in kidney transplant recipients has been associated with a 30% mortality rate2.
c) Pretransplant vaccination in seronegative patients and antiviral prophylaxis posttransplant with acyclovir or valganciclovir have dramatically reduced the incidence of VZV reactivation; however, the risk persists for many years post- transplant, and there is limited evidence on long-term prophylactic therapy.
Reference
1. “Brain death and care of the organ donor” Lakshmi Kumar .
2. “Successful Use of Kidneys from a Deceased Donor with Active Herpes Zoster Infection” Amanda J. Vinson Hindawi Case Reports in Transplantation Volume 2021, Article ID 7719041, 4 pages https://doi.org/10.1155/2021/7719041
Thank you.
I will accept the donor with recipient consent and prophylaxes therapy.
Herpesviruses (CMV, human herpes simplex virus (HSV), EBV, human herpesvirus-6
(HHV-6)) can also be transmitted via transplantation; generally, posttransplantation
primary infection, i.e., in previously seronegative patients, is associated with a higher
risk of clinical manifestations and severity ,though rarely.
However, prevention might be achieved by prophylaxis or preemptive therapy, enabling
transplantation between herpesvirus(1)
is associated with a higher risk of clinical manifestations and severity.
References:
1-Glauco Adrieno Westphal et al ,Guidelines for the assessment and acceptance of
potential brain-dead organ donors. Joinville (SC), Brazil.: February 2016.
Thank you, Mohamed
What prophylaxis do you suggest in this case?
Would you accept this donor?
This 23-year-old DBD donor has suffered from encephalitis. So there is the potential concern of transmitting this potentially fatal infection to the presumed recipient. However, in spite of this, donors dying with encephalitis/meningitis represent a good source of organs for TX.
The risk of disease transmission is, however, low. Caution is required if the causative agent is unknown.
In the UK (Transplant Registry), between 2003 & 2015, 258 deceased donors with meningitis/ encephalitis were identified & the causative agent was known in 188 (72.9%). They provided 899 solid organs for TX (455 kidneys & 444 others). The only recorded case of disease transmission was from a donor with encephalitis of unknown cause at time of TX who transmitted a fatal nematode infection to 2 KTX recipients; 3 patients (2 liver & 1 heart recipient) died within 30 days of TX from a neurological cause (CVA) with no suggestion of disease transmission. This study showed that both patient & graft survival in recipients of organs from donors with meningitis/ encephalitis were similar to those for all other types of deceased organ donors.
So, in the view of the above encouraging results from the UK, I will accept this donor given that further steps will be taken to delineate the causative agents together with appropriate surveillance & prophylactic measures to reduce risk of infection transmission.
======================
· If yes, what is the prognosis?
Since the risk of disease transmission is low, the prognosis depends on other factors, including immunological workup & the quality of the kidney; both are good in this case(HLA 0 0 0 with no DSA, serum creatinine 71 micromol)
References
1. Patrick B Trotter, Matthew Robb, William Hulme , Dominic M Summers, Christopher J E Watson, J Andrew Bradley, James Neuberger.
Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis. Transpl Infect Dis. Dec 2016; 18(6):862-871. doi: 10.1111/tid.12621.
Thank you, Mohamed
I appreciate the difference in opinion; however, viral encephalitis has a high risk of transmission. What would you do to reduce this risk of transmission?
Would you accept this donor?
Although we need to expand the kidney donor pool but we also want to be a safe option
Such DBD young male donor with HSV encephalitis could not be a safe donor even if renal functions are normal .
I would not accept this donor .
As deceased organ donors where the cause of death is meningitis or encephalitis are a potential concern because of the risks of transmission of a potentially fatal infection to the immunocompromised recipients.
In donors where the causative agent of meningitis is known to be bacterial, the risk of disease transmission is very low, although it is important to ensure that recipients of organs from such donors receive appropriate prophylactic anti-microbial therapy.
For organs where the causative agent is not known / viral the risk of disease transmission is greater, and more caution should be exercised in the use of such organs, as highlighted in various clinical guidelines.
>>>> The risk of potentially fatal disease transmission should, however, be balanced against the clinical benefit of an organ transplant .
Reference
Herpes simplex virus-2 transmission following solid organ transplantation: Donor-derived infection and transplantation from prior organ recipients
Nenad Macesic 1 2 , Iain J Abbott 3 , Matthew Kaye 3 , Julian Druce 3 , Allan R Glanville 4 , Paul J Gow 5 6 , Peter D Hughes 7 , Tony M Korman 8 , William R Mulley 9 10 , Phillip J O’Connell 11 , Helen Opdam 12 , Miranda Paraskeva 13 , Matthew C Pitman 14 , Stella Setyapranata 7 , William D Rawlinson 15 , Paul D R Johnson 1 6
Transplantation of Organs from Deceased Donors with Meningitis and Encephalitis: a UK Registry Analysis
P. B.Trotter1,2*, M. Robb2, W. Hulme2, D. Summers1,2, C. J. E. Watson 1, J. A. Bradley1, J. Neuberger2
1National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre and the NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT).
Thank you.
A young DBD donor due to HSV encephalitis is an active infection that is a contraindication for donation due to the high risk of transmission of the infection to the recipient, its prognosis is bad due to the active systemic infection of the donor.
Dear Dr Akram,
I like your decision because a patient who has died of herpetic encephalitis would have had positive CSF that mean would have viremia.
You should have supported your argument by uploading evidence
Summary:
The kidney was offered from a 23-year-old male DBD with HSV encephalitis. Baseline creatinine was normal with good urine output of 3.4 liters in 24 hours.
HSV infections have an incidence of about 3% in transplant patients on prophylaxis while the amount is triple that is 9.8% without prophylaxis during the first year of kidney transplantation. To identify the activity of the disease a PCR from the CSF must be tested.
In a study conducted the journal of Transplantation (2020) a male patient found out that he was positive for HSV treatment and was given neurologically was normal but unfortunately the patient lost the graft. So it is advised that treatment for HSV must be given to prevent infections in recipients and avoid graft loss.
With this in mind, if the donor is on treatment for the HSV and there is no sign of infection that PCR is negative then the patient can be a donor. If, however, the donor is not on treatment and the PCR is positive I think the recipient is at high risk of having HSV infection and graft rejection.
So close monitoring must be made treatment.
Pinto-Ramirez, J., Patino-Jaramillo, N., Garcia-Lopez, A., Giron-Luque, F., Transplantation (2020). Herpes simplex virus type 1 encephalitis in Kidney Transplant patient: September 2020 – Volume 104 – Issue S3 – p S329
Hi Dr Badal,
I would not bother about doing PCR in such a proposed donor.
A kidney from a donor would be unsafe to transplant who has died of herpetic encephalitis would have had positive CSF that mean would have viremia. Would you reconsider this decision if I quote the following recommendations from Up-to-date:
2022 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Infectious considerations in the evaluation of potential organ donors and recipients (possible exclusion criteria*)
Central nervous system (CNS) infection
Encephalitis and/or meningitis of unknown etiology
Untreated or incompletely treated encephalitis and/or meningitis
Herpes simplex encephalitis
Thank you Prof. Ajay
I think, this article given in the reference used by the UpToDate are West Nile virus, rabies virus, lymphocytic choriomeningitis virus, and Balamuthia mandrillaris amebae. should not be applied to other infectious disease with good chance to control by anti viral therapy available.
Yes ,accepted young deceased donor .zero miss match with encephalities due to HSV infection .
Deceased organ donors, where the cause of death is meningitis or encephalitis, are a potential concern because of the risks of transmission of a potentially fatal infection to recipients.
Methods:
Using the UK Transplant Registry, a retrospective cohort analysis of deceased organ donors in the UK was undertaken to better understand the extent to which organs from deceased donors with meningitis and/or encephalitis (M/E) (of both known and unknown cause) have been used for transplantation, and to determine the associated recipient outcomes.
Results:
Between 2003 and 2015, 258 deceased donors with M/E were identified and the causative agent was known in 188 (72.9%). These donors provided 899 solid organs for transplantation (455 kidneys and 444 other organs). The only recorded case of disease transmission was from a donor with encephalitis of unknown cause at time of transplantation who transmitted a fatal nematode infection to 2 kidney transplant recipients. A further 3 patients (2 liver and 1 heart recipient) died within 30 days of transplantation from a neurological cause (cerebrovascular accident) with no suggestion of disease transmission. Overall, patient and graft survival in recipients of organs from donors with M/E were similar to those for all other types of deceased organ donor. Conclusion:
Donors dying with M/E represent a valuable source of organs for transplantation. The risk of disease transmission is low but, where the causative agent is unknown, caution is required.
Reference:
Transplant Infectious Disease; Dec2016, Vol. 18 Issue 6, p862-871, 10p
Hi Dr Nahla Alarm,
A kidney from a donor would be unsafe to transplant who has died of herpetic encephalitis would have had positive CSF that mean would have viremia. Would you reconsider this decision if I quote the following recommendations from Up-to-date:
2022 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Infectious considerations in the evaluation of potential organ donors and recipients (possible exclusion criteria*)
Central nervous system (CNS) infection
Encephalitis and/or meningitis of unknown etiology
Untreated or incompletely treated encephalitis and/or meningitis
Herpes simplex encephalitis
You were offered a kidney from a 23-year-old male DBD (donor after brain stem death) donor who suffered from HSV encephalitis. His baseline S Cr was 60 µmol/L. On admission, S Cr was reported to be 71 µmol/L (0.8 mg/dl). His urine output is 130 mls during the last hour and 3.4 L over the last 24 hours. The recipient is 25 years old, 000 mismatch, no DSA. He is on the waiting list for the last 7 years secondary to reflux nephropathy.
Would you accept this donor?
Most of the transplant candidates are seropositive for HSV-1 or2 (1) and those not on CMV prophylaxis preferred to use acyclovir prophylaxis
Deceased donor kidneys with localized non-genitourinary infections, including pneumonia and meningitis, still can be considered for donation. However, DD with active fungal infections, especially bloodstream and genitourinary infections, unspecified viral infections, suspicion of Encephalitis, or unclear causes of infectious death must be avoided (1).
in severe, disseminated, visceral, or CNS involvement like in this case, acyclovir doses of up to 10 mg/kg every 8 hours intravenously should be initiated. Acyclovir-resistant HSV is less common in SOT patients and can use foscarnet as an alternative treatment, based on reports from UK registry analysis of deceased donors with meningitis and encephalitis we still can accept donations from those DD with the known pathogen of meningitis or encephalitis as it’s associated with low risk of transmission and overall favor patient and graft survival the only precaution is those with the unknown pathogen for encephalitis or meningitis
so based on the review of the available evidence again we should discuss the case individually as the donor had HSV encephalitis which is known and already treated on this line may consider him for donation after repeat CSF PCR and intrathecal sample for HSV PCR IF negative can go ahead with donation after explanation and full discussion with the recipient, especially in the context of the good immunological match and his induction will be as a standard immunological risk with 1L2 monoclonal AB with acyclovir prophylaxis for the recipient
If yes, what is the prognosis?
As per the evidence from the UK registry study, the chance of transmission is low for the known pathogen of encephalitis like this case and the overall prognosis for the both patient and graft are good, this recipient has been on a waiting list for> 7 years waiting the risk and benefit I think in his case we still can accept this offer with caution and after full discussion and get informed consent from the recipient
References
1. Lee DH, Zuckerman RA; AST Infectious Diseases Community of Practice. Herpes simplex virus infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13526.
2. handbook kidney transplantation 6th edition.
3. Trotter PB, Robb M, Hulme W, Summers DM, Watson CJ, Bradley JA, Neuberger J. Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis. Transpl Infect Dis. 2016 Dec;18(6):862-871.
Dear Dr saja,
You would not have enough time to treat viremia of this proposed cadaveric donor. A patient who has died of herpetic encephalitis would have had positive CSF that mean would have viremia.
in that case, active viremia is an absolute contraindication and we should decline this offer
thank you prof Ajay
_ I will not accept the current potential donor, it is clear contraindication for transplantation from active herpetic encephalitis.
_ death from herpetic encephalitis means active viremic state so no doubt about the high risk of viral transmission and death in the recipient especially after commencing immunosupressive therapy.
_ even with the current low immunological risk regarding mismatch and DSA, but inevitable need to immunosupressives make the risk of infection and possibilty of viremia and death also inevitable
Hi Dr Shawky,
I like your decision because a patient who has died of herpetic encephalitis would have had positive CSF that mean would have viremia.
You should have supported your argument by uploading evidence