Executive Summary
The Advisory Committee for Blood and Tissue Safety (ACBTSA) met on December 1 to determine whether children ages 10 and under should be exempt from pre-transplant testing for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV). Presentations outlined current and previous Public Health System (PHS) pre-transplant requirements, responses from various organizations to this pre-transplantation testing requirement, and CDC data on the overall risk of HIV, HBV, and HCV in young children. After a discussion, ACBTSA members voted unanimously to revise the existing testing requirement, exempting children 10 and younger from pre-transplant testing if they were already tested during or after registration for a transplant waitlist.
Action Items
Claudia Cohn will write the specific pediatric recommendation revision and disseminate it to the committee for comments and edits in January 2022.
Meeting Summary
Welcome and Opening Remarks
Claudia Cohn provided a few brief welcoming remarks, and Jim Berger conducted roll call to confirm quorum. Admiral Rachel Levine, the Assistant Secretary of Health, provided initial comments regarding the purpose of the meeting.
Opening Remarks
Admiral Rachel Levine, Assistant Secretary of Health, Health and Human Services (HHS)
Admiral Rachel Levine began with the recognition and commemoration of World AIDS Day on December 1. Forty years ago, the first five acquired immunodeficiency syndrome (AIDS) cases were officially reported. Admiral Levine saw the beginning of the HIV/AIDS epidemic at Mount Sinai Hospital and the resulting effects on the blood community and infectious disease testing. Now, over 700,000 individuals in the U.S. have died from AIDS-related illnesses.
Admiral Levine commended ACBTSA for its recent recommendations to improve the resiliency of the supply chain and data infrastructure in the blood and plasma industries in the wake of the COVID-19 pandemic. She also welcomed Claudia Cohn as the new chair for the ACBTSA.
Health and Human Services (HHS) has tasked the ACBTSA with determining if current data support the potential revision to exempt solid organ transplant recipients ages ten or younger from HIV, HBV, and HCV testing at admission for transplant if they have already received postnatal testing for these diseases. The goal is to improve transplant outcomes and reduce the burdens on patients and their families.
The 2020 PHS Guideline and Proposed Revision to Pediatric Pre-transplant HIV, HBV, HCV Testing
Sridhar V. Basavaraju, MD, Centers for Disease Control (CDC)
A Brief History of Solid Organ Transplant Guidelines
Sridhar Basavaraju provided an overview of the history of PHS’s guidelines to prevent the transmission of HIV, HBV, and HCV through solid organ transplantation. PHS’s organ transplant guidelines are updated based on data analyzed from published literature, outbreak investigations, and infectious disease surveillance. Formulation of new and revised guidelines is an open process that includes the ACBTSA, the Federal Register, and meetings with the public. The process of generating new guidance is meant to ensure every usable organ is transplanted safely.
In 1985, PHS released initial guidance for HIV testing of organ, tissue, and semen donors. In 1994, these HIV testing guidelines were amended to include risk stratification criteria for individuals with risk factors for HIV. The PHS updated this guidance in 2013 to reflect advances in HIV lab screening of organ donors and increased understanding of HIV risk factors. Testing was also expanded to include HBV and HCV. A 2020 update included universal donor testing, recipient pre- and post-transplant testing, and changes to donor risk designation criteria.
Implications of 2020 PHS Guidance for Children
Sridhar Basavaraju outlined the relevant guidance changes from 2020 relevant to the purpose of the 55th Annual ACBTSA Meeting. All solid organ transplant recipients should receive HIV, HBV, and HCV serology and nucleic acid tests at hospital admittance for transplantation and post-transplantation. Previous public comments pointed out that in pediatric patients with low body weight and/or chronic co-morbid conditions, pre-transplant testing requirements may cause undue burden and worsen transplant outcomes. Additionally, the utility of these test results is likely marginal because patients have already been tested for HIV, HBV, and HCV prior to placement on an organ donation waitlist. For young children, the time between being waitlisted and receiving a transplant can be relatively short. Among young children, risk behaviors for these infectious diseases are unlikely between waitlisting and transplantation. Because of these concerns, CDC is collaborating with the Organ Procurement and Transplantation Network (OPTN) to evaluate changes to pre-transplant testing requirements.
Members of the ACBTSA were asked to consider the following question:
“Does the available data support exempting solid organ transplant candidates who are ≤10 years of age at the time of transplant (and who have received postnatal infectious disease testing) from the recommendation for HIV, Hepatitis B virus, and Hepatitis C virus testing during the hospital admission for transplant but prior to anastomosis of the first organ?”
CDC will draft revised recommendations in January 2022 for HHS clearance and posting to the Federal Register for comment. The final revised recommendations are expected between April and June 2022.
OPTN Data on Organ Transplantation in the <10 Population
David Klassen, MD, United Network for Organ Sharing (UNOS)
David Klassen presented OPTN’s 2015-2020 pediatric organ transplant data.
Pediatric Transplant Programs
Only some transplant programs have performed at least one transplant in a patient aged 10 or younger. From 2015-2020, there were 108 kidney, 64 liver, 60 heart, and 10 lung pediatric transplant programs. The sizes of these programs widely vary, ranging from 1-150+ liver transplants and 1-90 heart transplants per program.
Pediatric Waiting List and Transplant Recipients
The OPTN dataset contains information about the number of new pediatric (≤10 years old) waitlist registrations and transplants. Typically, 1 in 40 transplants are to patients 10 or younger. The data table below displays annual information about the approximate number of waitlist registrants, median age of registrants, proportion of registrants that receive a transplant, median age at transplant, and the most frequent diagnoses for transplantation.
| Organ Type | Liver | Heart | Kidney | Lung |
|---|---|---|---|---|
| New Waitlist Registrants Per Year | 400-600 | 400-500 | 400 | 50 |
| Median Age of Waitlist Registrants | 1 | <1 | 5 | 3 |
| Waitlist Registrants Receiving Transplant (%) | 80% | 70% | 90% | 45-75% |
| Median Age at Transplant | 1 | 1 | 5 | 3 |
| Frequent Primary Diagnoses | Primary biliary atresia | Congenital heart disease or cardiomyopathy. | Wide array, but mostly congenital or metabolic diseases. | Pulmonary hypertension or cystic fibrosis. |
Infectious Disease Testing in Organ Transplant Recipients
OPTN collected select information related to infectious disease testing in organ transplant recipients. For HCV, 0.2% of tested patients were seropositive with no nucleic acid test (NAT) positivity, and these may be false positives. There were no positive NAT results for HBV, although 10.8% of patients tested positive for the HBV surface antibody and 0.4% tested positive for the surface antigen. Similarly, no patients tested positive for HIV using NAT, and only three seropositive cases were reported. However, these seropositive cases were likely false positives, as the false positives for adult recipients are common. Important caveats for this data include unknown testing timing and a large portion of recipients were either not tested or their status was reported as unknown
Discussion
Importantly, the pediatric transplant population is unique from the adult population. Typically, pediatric transplant patients are already very sick and hospitalized, so the results of these tests will not determine whether a patient is sent home or not. Additionally, pediatric patients typically require smaller organs, except for a split liver donation from an adult.
Because OPTN’s infectious disease testing in organ transplant recipients is very limited, current data do not provide insight on whether HIV, HBV, or HCV test results change from original postnatal testing to pre-transplantation testing.
CDC recommendations regarding HIV testing in organ recipients do not require simultaneous serology and NAT. Normally, the patient would only undergo NAT if serology for HIV antibody and antigen was positive.
Pediatric Candidate Pre-Transplant HIV, HBV, and HCV Testing Requirement
Lara Danziger-Isakov, MD, MPH, Cincinnati Children’s Hospital Medical Center
After the 2020 update to PHS guidelines, OPTN changed their testing requirements for all organ transplant candidates in April 2021 to require testing upon hospital admission for transplant. Dr. Lara Danziger-Isakov summarized public comments related to the pre-transplant testing requirement.
Public Comment Feedback
Various organizations provided feedback to this added requirement. The OPTN Pediatric Transplantation Committee expressed concern about the burden of testing immediately prior to transplant in very ill pediatric patients. The Society of Pediatric Liver Transplantation pointed out the challenge of obtaining more blood than was already taken from pediatric patients pre-transplantation and suggested the requirement for repeat testing in this patient population should be evaluated. Families of pediatric transplant patients expressed similar sentiments. The American Society of Transplantation specifically cited a potential for increased transplant complication rates due to anemia and graft failures. They suggested children under 20 kg should not have repeat testing if HIV, HBV, and HCV tests were already performed within the past year. At OPTN regional meetings, attendees expressed concern for this repeat testing in patients under 12 kg.
A pediatric transplant program wrote to the OPTN Disease Transmission Advisory Committee (DTAC) and Pediatric Committees about the dangers of drawing blood from small transplantation candidates. They cited health risks even for healthy children when greater than 1-5% of their blood is drawn. Other blood tests required pre-transplant are conducted over a span of weeks in small children to mitigate these risks. Pediatric patients are at a much lower risk of contracting HIV, HBV, and HCV between testing for registration on the transplant waitlist and the time of transplant.
Response to Public Comment from the Pediatric Transplant Program
OPTN DTAC and the Pediatric Committees formed a working group with the CDC and Health Resources and Services Administration (HRSA) members to evaluate concerns from the public. This working group included pediatric infectious disease physicians, pediatric liver and kidney transplant physicians, a transplant coordinator, representatives from the CDC Office of Blood, Organ, and Other Tissue Safety, and HRSA representatives. This working group highlighted important considerations for a potential change to pediatric pre-transplant testing: the age at which risk of infectious disease transmission is very low and the weight at which it would be harmful to draw blood for these tests. Working group members reviewed OPTN data on previous donor-derived transmissions to children under the age of 18. According to this data, since 2006, only one potentially donor-derived transmission of HBV was recorded in a pediatric patient, and this was due to pending HBV results at the time of transplant.
CDC Data on Proposed Question
Rebecca Free, MD, MPH, CDC
Rebecca Free presented CDC data on incidence, prevalence, exposure risk, and testing of HIV, HBV, and HCV in children under the age of 13.
Pediatric HIV
The incidence of HIV in the U.S. in people under the age of 13 has been declining due to efforts to eliminate perinatal transmission. In this age group, less than 100 children are diagnosed annually, and less than 2,000 are currently HIV positive. From 2015-2019, 524 children were diagnosed with HIV, and 35% of those diagnoses were made within the first six months of life. Perinatal testing and pediatric follow-up for HIV-exposed children catches most, if not all, HIV cases in children under 13.
Children under the age of 13 are one of the lowest HIV risk groups in the U.S. Most of these infections are perinatally acquired. Very rarely, a child under 13 can acquire HIV through receipt of an infected blood product or through pre-chewing of food by an infected person.
Pediatric HBV
Because more than 90% of 2-year-olds are vaccinated for HBV in the U.S., less than 1 in 100,000 children under age 20 are diagnosed with acute HBV infection. In 2019, only 17 cases of HBV in U.S. children were reported in 2019.
Pediatric HCV
The incidence of HCV in people under the age of 20 in the U.S. was 1 per 1,000,000 in 2019. Perinatal exposure is the most common route of transmission for HCV in children.
Other Considerations for Pre-Transplant Pediatric Recipient Testing
Because pediatric HBV and HCV cases are exceedingly rare, pre-transplant testing is likely unnecessary for very young children with low body weight. Seroconversions between testing prior to registration on a transplant waitlist and time of transplant are not tracked. Once perinatal transmission is excluded, the overall incidence of HIV, HBV, and HCV is extremely low in pre-pubescent children not engaging in risk behaviors. Overall, this suggests that the pre-transplant testing requirement is unnecessary for young children.
Description of Comments received to DTAC
Lara Danziger-Isakov, MD, MPH, Cincinnati Children’s Hospital Medical Center
Summary of DTAC Discussion Regarding CDC Data
DTAC agreed that data show a very low risk for acquiring HIV, HBV, and HCV between initial evaluation and transplant for pediatric patients. CChildren aged 10 and under have the lowest behavioral risk factors for these diseases. DTAC argued exempting a smaller age range from pre-transplant testing may result in unnecessary testing in some candidates in harmfully low weight categories.
OPTN Workgroup’s Proposed Revision
The OPTN Working Group proposed maintaining testing requirements for all transplant candidates at the time of initial evaluation. However, children 10 and younger would be exempt from testing during hospital admission for transplant if they were tested at or after waitlist registration.
Next Steps for Revision Implementation
The timeline for this policy change will involve an initial period for public comment from January-March 2022. The OPTN Board of Directors will consider the proposed change and public comments in June 2022. If approved, members will be notified, and the policy will be implemented. Importantly, any policy change must be consistent with recommendations from the CDC for testing to prevent the spread of infectious disease.
Committee Discussion on Pediatric Recommendation
Attendees engaged in a final discussion of the proposed pediatric revision.
Historic Reasoning for Pre-Transplant Testing in Organ Recipients
Disease surveillance is a crucial part of reducing the transmission of infectious diseases. Pre- and post-transplantation testing of organ recipients is meant to help physicians understand the etiology of transmission in this patient population. If a patient received no pre-transplant testing and tested positive for HIV, HBV, or HCV after transplantation, it would be extremely difficult to determine if the disease was transmitted via the organ transplant procedure. However, because of the extremely low risk of children acquiring HIV, HBV, or HCV between initial evaluation and transplantation, this data is not informative or very useful. Additionally, testing for a disease in any very low prevalence population will not provide much value, as any positive test is likely a false positive.
Utility of Pre-Transplant HIV, HBV, and HCV Testing
A positive pre-transplant test for HIV, HBV, or HCV would affect the post-transplant treatment management plan. Clinicians would adjust immunosuppression post-transplantation, and the combination of organ transplant with one of these infections can affect overall survival. However, because seroconversion between initial evaluation and pre-transplant testing is highly unlikely, initial evaluation test results can still provide this vital information for clinicians.
Risk of Missing a Positive Pre-Transplant HIV, HBV, or HCV Test
The medical community has a responsibility to closely track organ transplant-related disease transmission. Because treatments for HIV, HBV, and HCV have drastically improved, PHS guidelines for organ donors related to risk behaviors were relaxed to reduce the potential loss of healthy organs. Compared to PHS’s original guidelines, less risk behavior information is collected from organ donors, and there are no additional risk consent forms for organ recipients detailing that the donor engaged in behaviors that increased risk for HIV, HBV, and HCV undetected by mandatory testing.
The time window between initial evaluation tests for HIV, HBV, and HCV and transplantation in children 10 and younger is often very short. This, paired with low participation in risk behaviors, makes it highly unlikely that a positive HIV, HBV, or HCV test will be missed prior to transplant. There are few reports of false negative tests for these infectious diseases, so a duplicate test at the time of transplant will not improve overall testing accuracy. In contrast, false positives are far more likely and can significantly reduce organ transplant access.
Relative Risk of Complications Due to Blood Loss and Risk of Missing a Positive Test
The risk of complications due to blood loss depends on the age and body weight of the patient and the amount of blood drawn. While the actual blood volume required for HIV, HBV, and HCV tests is very low, the amount of blood requested by clinical labs can be much larger. While there are no documented cases where pre-transplant blood draws adversely affected patients, the committee agreed the perceived relative risk of complications was much higher than the risk of missing a positive test at the time of hospital admission for transplant.
Committee Vote on Pediatric Recommendation
After their discussion, members voted on the essence, but not the specific wording, of the recommendation revision. The revision would remove the requirement for HIV, HBV, and HCV testing during hospital admission for transplant candidates aged ten and under if they were previously tested during or after registration for a transplant waitlist. Voting members unanimously recommended the revision, with 14 votes.
Next Steps
Claudia Cohn will write the specific pediatric recommendation revision and disseminate it to the committee for comments and edits in January 2022. The final version of this revision will be entered into public record.
List of Participants
Voting Members
Claudia Cohn, Chair ACBTSA, University of Minnesota
Sally Caglioti, Creative Testing Solutions
Susan Galel, Roche Molecular Diagnostics
Ray Goodrich, Colorado State University
Elisa Gordon, Northwestern University
Jed Gorlin, Innovative Blood Resources & University of Minnesota
Mary Gustafson, Plasma Protein Therapeutics Association
Michelle Kameka, Florida International University
Daryl Kor, Mayo Clinic
Jim MacPherson, MacPherson Strategies
Gary Marklin, Mid-America Transplant
David Perez, Terumo BCT (retired)
Glenn Ramsey, Northwestern Medicine
Eric Santiago-Justiniano, Fresenius Kabi
Lynne Uhl, Beth Israel Deaconess Medical Center and Harvard University
Ron Waeckerlin, Vitalant (retired)
Ex-officio Members
Sridhar Basavaraju, Centers for Disease Control (CDC)
Scott Brubaker, Food and Drug Administration (FDA)
Marilyn Levi, Health Resources and Services Administration (HRSA)
Nicole Verdun, Food and Drug Administration (FDA)
OASH Staff
ADM Rachel Levine, Assistant Secretary for Health
James Berger, Designated Federal Officer (DFO) ACBTSA, OASH
Debbie Seem, Public Health Analyst, Alternate DFO ACBTSA, OASH
Lauren Overman, Public Health Analyst, OASH
Allison Petkoff, Public Health Analyst, OASH
Additional Attendees
Lara Danziger-Isakov, Cincinnati Children’s Hospital Medical Center
Rebecca Free, Centers for Disease Control (CDC)
David Klassen, United Network for Organ Sharing (UNOS)
Mike Kavounis (Meeting Host), Rose Li and Associates, Inc. (RLA)
Meghan Walsh (Project Manager), RLA
Gina Castelvecchi (Science Writer), RLA
