Stacee Lerret PhD, RN, CPNP-AC/PC, FAAN

Associate Professor, Medical College of Wisconsin

Nurse Practitioner, Children’s Hospital of Wisconsin

NATCO President

Vanderbilt Transplant Symposium

October 7, 2019

Live Vaccines for Pediatric Liver Transplant Recipients:

A Quality Improvement Project

Vaccines and Solid Organ Transplant Patients

WHAT DO WE KNOW? WHAT DOES THIS MEAN FOR OUR PATIENTS?

HOW CAN WE MAKE A DIFFERENCE?

Recommendations

Inactivated and Live Vaccines

Tetanus

• Tetanus toxoid is a potent antigen conferring immunity for over 10 years

• Widespread immunization has resulted in very few cases each year in the US

• Protective antibodies are formed in 100% of children with End Stage Liver Disease (ESLD) in one small study

• No cases ever reported in solid organ transplant patients

Balloni A, et al. Vaccine; 1999

Diphtheria

• Widespread vaccination has made diphtheria rare in the US

• Protected by herd-immunity

• Protective antibodies are formed in 88% of children with ESLD in one small study

• Antibody titers seem to wane post-transplant

• After approximately 12 months

• None ever reported in transplant patients

Balloni A, et al. Vaccine; 1999

Pertussis

• Number new cases has increased √ Low in 1980 of 0.76/100,000

√ 6.1/100,000 in 2011

• No immunogenicity data in children with end stage liver disease

National Center for Health Statistics, 2014Deen JL, et al. Clin Infect Dis. 1995

Polio

• Excellent immunogenicity • Both healthy children and children with

liver disease

• Seroconversion similar in both groups• After 2 doses 95%

• After 3 doses 99-100%

Balloni A, et al. Vaccine; 1999

Hepatitis A• Important to protect patients with liver

disease from other infectious hepatotrophic viruses when possible

• Hepatitis A vaccine has good immunogenicity in children with chronic liver disease with detectable Ab

• HBV pts - 87% at 1 mos, 88% at 6 mos

• HCV pts – 92% at 1 mos, 75% at 6 mos

Majda-Stanislawska E, et al. Pediatr Infect Dis. 2004

Hepatitis B• Hepatitis B in liver transplant patients is

more severe and damages the liver more rapidly than healthy patients

• Like HAV, important to protect liver patients from this virus pre- and post-transplant

Hepatitis B

• 31 patients from Taiwan

• Stable >1 year post liver transplant

• All patients completed primary HBV series before transplant

• 65% (n = 20) had immunity post-transplant

• Booster shots to remaining 35% (n = 11)o 2/3 seroconverted after 1 booster dose

o Remaining seroconverted after 2nd booster dose

Ni Y, et al. Transplantation, 2008

Live Vaccines• Varicella

• Varicella outbreaks have drastically declined in the last 20 years

• Early 1990s an average of 4 million people had varicella

• Survey of six states reported only 33 in 2012

• Measles• Officially declared eliminated in the

United States in 2000• It’s back

Current Events: Measles

January to August 2019

• Greatest number of cases reported in the U.S. since 1992

• And…since measles was declared eliminated in 2000

• As of August 8, 2019

• 1,182 individual cases of measles have been confirmed in 30 states

• 124 of the people were hospitalized

• 64 reported complications

• Pneumonia and encephalitis

• The majority of cases are among people who were not vaccinated against measles.

• Measles is more likely to spread and cause outbreaks in U.S. communities where groups of people are unvaccinated

Where Are You?

Live Vaccine Studies• Only a few small studies reported

Khan S, et al. Pediatric Transplant, 2006

Varicella in

Pediatric Liver

Transplant

• 3 cohorts (1, 2 or 3 doses)

• Years after transplant were 1-13.4 (3.1)

36 patients

• Age >12 months

• Time from liver transplant >12 months

Demographics

• No rejection 21 months

• Lymphocyte count ≥750

• No recent exposure to WT Varicella

• Afebrile x 72 hours

• No other live vaccines <4 weeks

Clinical History

• Prednisone <2 mg/kg/day

• Tacrolimus trough <8 ng/ml >1 mo, max dose 0.3 mg/kg/day

• No IVIG in 5 months

• No antivirals in 4 weeks

• No ASA

Medication

Adverse Reactions

Posfay-Barbe KM, et al. Am J Transplant, 2012

Varicella and

MMR

• 18 patients

√ 27-133 (43) months after transplant

• Criteria

√ Negative or borderline Ab titers to MMR or varicella

√ Time from liver transplant >2 years

√ No rejection >6 months

√ Immunosuppression

› Prednisone <0.2 mg/kg/day for last 6 months

› Tacrolimus trough <5 ng/ml, cyclosporine trough <100 ng/ml

√ Lymphocyte count ≥1500

√ No recent exposure to WT Varicella

√ IgG >500

Shinjoh M, et al. Vaccine, 2008

Varicella

and MMR

• Good seroconversion rates for all live viruses except 1 mumps strain

• No clinical disease developed

Shinjoh M, et al. Vaccine, 2008

What is Current Practice?• Inactivated vaccines safe to use

starting at approximately 3 months after transplant o Baseline immunosuppression

• Live vaccines avoided o 4 week before transplant

o After transplant

• Avoid live vaccines until further studies are available

Pediatric Immunization

Recommendations

Starting the Conversation…• Avoiding live vaccines following liver transplant is

standard practice for most centers due to concern for active infections

• Children post-liver transplant have low antibody titers despite receiving appropriate vaccinations before transplant

• But…this can increase morbidity and mortality in adulthood from infections like measles and varicella

• Several single center studies have shown administering live vaccines post-transplant is safe and effective in select patients

• Booster immunization in these patients demonstrate a good response

Immunizations

in Pediatric

Liver

Transplant

Candidates

The single most common etiology for pediatric liver transplant is biliary atresia

The average age of transplant in pts with biliary atresia varies somewhat but is common in the first 1-2 years of life

Many of these pts do not complete primary vaccination series due to illness and/or age

Response to vaccination in end-stage liver disease is often suboptimal

Purpose

Increase pediatric liver transplant patients who are fully vaccinated including live vaccines to 95% of eligible patients.

1

Ensure all pediatric liver transplant patients have titers checked.

• Varicella, measles, mumps, Haemophilus influenzae B, hepatitis A and hepatitis B

2

Ensure that 95% of vaccine-eligible pediatric liver patients with low titers are given booster shots.

3

Process: Year 1

Communication

• Education with primary care team and families

Evaluate

• Measure antibody titers at the annual visit

Recommendations

• Recommend vaccinations for patients without immunity based on specific criteria

Criteria

• Recommend vaccinations for patients without immunity based on specific criteria

• All vaccines

• No rituximab within 6 months

• Live vaccines

• Minimum of 1 year post-transplant

• Low titers for varicella, measles or mumps

• Monotherapy with drug level ≤ 8

• No rejection or serious infection within 6 months

• No steroids within 3 months

Titer and

Immunization

Data

N Percentage

Patients with titers obtained at annual visit 69/72 96%

N Percentage

Recommended inactive vaccines 60/69 87%

Received inactive vaccines 25/60 42%

Rechecked titer to inactive vaccines 9/25 36%

Achieved immunity to inactive vaccines 6/9 67%

N Percentage

Recommended live vaccines 30/69 43%

Received live vaccines 12/30 40%

Reactions following vaccine administration 0/12 0%

Rechecked titer to live vaccines 8/12 67%

Achieved immunity to live viruses 7/8 87.5%

Summary

25 patients received inactivated vaccine

12 patients received at least 1 live vaccine

No patients had adverse reactions

Families overall receptive

No PCP has refused to vaccinate based on recommendations and a letter explaining the new process

Conclusions

Maximize immunizations pre-transplantMaximize

Monitor immunization serology pre- and post-transplantContinue

Administer live vaccines post-transplant as primary vaccination or booster in identified low-risk populationContinue

Identify reasons parents did not vaccinate

Tracking of vaccination administration Barriers

Continue to monitor with annual labs

Offer vaccines in transplant clinicFuture

Questions and

Discussion