Guidance on Increased Measles Activity and Solid Organ Transplantation

February 18, 2015
AST ID COP executive committee
Camille Kotton, chair
Shirish Huprikar, co-chair

Note: This guidance document was developed and approved by the ID COP Executive Committee but it has not been through an independent peer review process.

Introduction

As of February 13, 2015, 141 people from 17 states and Washington DC were reported to have measles in 2015 alone, most of whom are part of a large, ongoing outbreak related to an amusement park in California.1 There were a record number of cases in the United States in 2014 with 644 cases from 27 states reported to CDC's National Center for Immunization and Respiratory Diseases (NCIRD). Many of the cases have been imported into the United States and potentiated by unvaccinated populations.

Similarly, Canada reported 127 cases in 2014 and has also seen an increase in measles activity for some regions in the early part of 2015.2 Internationally, outbreaks continue to occur in several parts of the world and travelers should be aware of the increased risk in some countries.

Prevention: Knowledge of Serostatus and Role of Vaccination

Measles vaccine (MMR or MMRV) is a live-attenuated vaccine and should be avoided after transplant in adults and most children since there are only limited safety data in pediatric cases on low dose immunosuppression.3 A single antigen measles vaccine is not currently available in the United States. The only measles virus vaccines currently available in the United States are MMR, a combination vaccine with live-attenuated strains of measles, mumps and rubella, and MMRV (ProQuad), which also includes varicella.

When serologic status (measles IgG) is obtained before transplant, seronegative recipients can be immunized (if not on active exogenous immunosuppression, and if transplant can be deferred for at least 4 weeks after immunization). Those born before 1957 are likely to have been exposed to wild type virus, although it may be prudent to confirm serologic status. Alternatively, transplant patients can verify that they have previously received two doses of vaccine. Otherwise, it may be prudent to check the serologic status of patients after transplant, especially for those at increased risk due to travel, occupation, or community exposures to see whether they may be non-immune and thus potentially need post-exposure prophylaxis. Children who underwent organ transplant as infants are unlikely to have received vaccination prior to transplant, and those who underwent organ transplant before 5 years of age would be unlikely to have received booster doses.

Non-immune household members should be vaccinated to prevent disease transmission into the home. Healthcare workers should also be aware of their vaccination and/or serologic status and should receive vaccination if in doubt.

Post-exposure Prophylaxis

After exposure, intramuscular gammaglobulin may be helpful for seronegative organ transplant recipients if given within 6 days of exposure, per CDC guidelines.4 Transplant recipients who have positive serum measles IgG levels have evidence of protective antibodies and do not need gammaglobulin if exposed to measles. The recommended dose of gammaglobulin for immunocompromised persons is 0.5mL/kg of body weight (maximum 15 mL) intramuscularly. (The standard dose is 0.25 mL/kg body weight, with a same maximum of 15 mL intramuscularly.) Gammaglobulin is not needed if they have had intravenous immunoglobulin (IVIG) treatment recently (depending on dose, likely with the past 1-3 months). No measles-specific antiviral therapy is known to be effective.

Symptoms and Treatment

Measles may have an atypical presentation in a transplant patient, and may mimic other viral infections. Usual symptoms include:
• fever
• irritability, somnolence
• cough, coryza, and conjunctivitis (the three “C”s)
• photosensitivity
• small white spots on the inside of the mouth and throat (Koplik’s spots)
• maculopapular rash that starts on the face three to seven days after the start of the symptoms and progresses down the body.

The CDC definition is an acute illness characterized by
• generalized, maculopapular rash lasting ≥3 days; and
• temperature ≥101°F or 38.3°C; and
• cough, coryza, or conjunctivitis.

Whether measles is more likely to be severe or even fatal in transplant patents remains unknown given the relatively small number of reported cases thus far.5, 6 Symptoms of subacute measles encephalitis, which may arise 2-4 weeks after a usual case of measles, include altered mental status, intractable seizures, and lack of fever, and has been fatal in 4 of 6 transplant patients.5

There is no specific antiviral treatment for measles. Symptomatic treatment with antipyretics and fluids is indicated. In organ transplant recipients, strong consideration should be given for reduction in immunosuppression. Ribavirin therapy has been used in some cases but its effectiveness is unknown. As for many viral infections where there is no specific antiviral therapy, IVIG may be used. The decision for specific treatments should be made on a case-by-case basis, in part based on disease severity and overall net state of immunosuppression.

Donors with Measles

Organs from donors (living or deceased) with proven, recent, or suspected measles or donors that are suspected contacts of a measles case should not be transplanted. This is due to the concern of potential transmission, potential severity of illness and lack of measles-specific antiviral therapy.

Infection Control

Infection control is critical for appropriate outpatient and inpatient management. Transplant recipients with suspected measles should not come to clinic, nor should they be admitted to an inpatient transplant unit unless significant precautions are made in advance. Measles is among the most contagious of all infectious diseases; approximately 90% of nonimmune subjects with close exposure to a measles patient will develop measles. Measles is transmitted by droplets and/or by airborne spread and can remain infectious in the air for up to two hours after an infected person leaves an area, and also on surfaces. The incubation period from exposure to clinical prodrome averages 10–12 days, and from exposure to rash onset averages 14 days (range, 7–18 days).4

Per CDC, “Infected people should be isolated for four days after they develop a rash. Healthcare providers should follow respiratory etiquette and airborne precautions in healthcare settings. Regardless of presumptive immunity status, all healthcare staff entering the room should use respiratory protection consistent with airborne infection control precautions (use of an N95 respirator or a respirator with similar effectiveness in preventing airborne transmission). Because of the possibility, albeit low, of MMR vaccine failure in healthcare providers exposed to infected patients, they should all observe airborne precautions in caring for patients with measles. The preferred placement for patients who require airborne precautions is in a single-patient airborne infection isolation room (AIIR). People without evidence of immunity who have been exempted from measles vaccination for medical, religious, or other reasons and who do not receive appropriate PEP within the appropriate timeframe should be excluded from affected institutions in the outbreak area until 21 days after the onset of rash in the last case of measles.”7

For more information:
Measles Cases and Outbreaks, Centers for Disease Control
http://www.cdc.gov/measles/cases-outbreaks.html

Measles (Rubeola), for health care professionals, CDC
http://www.cdc.gov/measles/hcp/index.html

Measles, The Pink Book
http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/meas.pdf

References

1. in Measles Cases and Outbreaks (http://www.cdc.gov/measles/cases-outbreaks.html) (Centers for Disease Control and Prevention, Atlanta, GA, 2015).
2. in Measles and Rubella Weekly Monitoring Report, Week 53, 2014: December 28, 2014 to January 3, 2015 http://www.phac-aspc.gc.ca/mrwr-rhrr/2014/w53/index-eng.php (Public Health Agency of Canada, 2015).
3. Kawano, Y. et al. Effectiveness and safety of immunization with live-attenuated and inactivated vaccines for pediatric liver transplantation recipients. Vaccine (2015).
4. in Measles, The Pink Book, Centers for Disease Control and Prevention, http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/meas.pdf (Atlanta, GA, 2015).
5. Waggoner, J.J., Soda, E.A. & Deresinski, S. Rare and emerging viral infections in transplant recipients. Clin Infect Dis 57, 1182-8 (2013).
6. Turner, A. et al. Measles-associated encephalopathy in children with renal transplants. Am J Transplant 6, 1459-65 (2006).
7. in Measles (Rubeola), for health care professionals, Centers for Disease Control and Prevention, http://www.cdc.gov/measles/hcp/index.html (Atlanta, GA, 2015).