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Preventing Vaccine-Acquired Rotavirus in Immunocompromised Patients

CHORI clinical scientist Ann Petru, MD, has contributed to an article just published in the New England Journal of Medicine (NEJM) that documents significant safety concerns for children with undiagnosed severe combined immunodeficiency (SCID) who are vaccinated against rotavirus infection. A world-wide endemic, rotavirus is a virus that causes diarrhea in many children and has caused 5 million deaths in the last 10 years alone, representing a significant global health burden.

"Rotavirus diarrhea can be very severe, especially in young children. It affects such a huge proportion of the population in many countries, about 40 percent of kids in Malawi, for example. The rotavirus vaccine, made from live but attenuated viruses, is really critical worldwide. It can save the lives of about 2 million kids."

For the very small number of children with undiagnosed SCID, however, receiving the live rotavirus vaccine can be life-threatening. A collection of congenital deficiencies that results in a tremendous susceptibility to infection, SCID is 100 percent fatal if not treated, and treatment requires enzyme replacement or bone marrow or stem cell transplantation.

“Kids with SCID syndromes don’t have properly functioning T cells, which are  needed for a normal response to viruses,” explains Dr. Petru. “Without T cells, the viruses multiply without control, which is why children with SCID should not get live vaccines until their immune systems have been replaced through transplantation.”

SCID does not usually manifest until children are 4-6 months old, so it is seldom diagnosed before the age of 3-4 months.  However, rotavirus disease most significantly affects very young infants, and in the United States, the current recommendation is to give a 3-dose series of rotavirus vaccines starting at 6 weeks of age---thus, long before most children with SCID are diagnosed.

Dr. Petru’s concern about the rotavirus vaccine as a risk for a child with SCID arose with the diagnoses of severe and prolonged rotavirus diarrhea in one of her own patients, who became one of the three cases described in the latest NEJM publication.

As Dr. Petru explains: "This was not a planned, prospective study. I was very concerned about a little baby who had very severe and prolonged rotavirus diarrhea, but he was also failing to thrive and had very severe respiratory disease at the same time, suggesting SCID."
"I suspected that my patient's rotavirus was caused by the vaccine. I wanted to find a laboratory that could help me determine whether his rotavirus was wild type, which would have come from another person, or the type that results only from vaccination."
The search for such a laboratory led to a collaboration with scientist physicians at Baylor College of Medicine, and eventually to discovery that the rotavirus was the vaccine strain, not wild type, and that there were two other patients also diagnosed with both SCID and vaccine-associated rotavirus.

"Nothing had been published about this before, so we felt we ought to make people aware of the risk. This publication serves as notification to pediatricians that children with SCID might develop severe disease if given the rotavirus vaccine," says Dr. Petru, whose own patient remained hospitalized with the infection for over 12 months, and has finally cleared the infection, about 15 months after he was immunized and only after having undergone unrelated-donor bone marrow transplantation.

"More importantly," Dr. Petru adds, "this publication coincided with a nationwide decision to require SCID screening at birth."
Dr. Petru refers to the decision at the end of January by the Secretary's Advisory Committee for Heritable Disorders in Newborns and Children (ACHDNC) to add SCID screening to the mandatory panel of newborn screenings required by state public health programs. Early identification would mean that children could be identified as having SCID well before symptoms appeared and early enough to avoid giving live virus vaccines, such as the rotavirus vaccine that infected Dr. Petru's patient.

"Of course, any added screening test adds a cost, but that added cost prevents a tremendous health burden later for those kids who might contract a life-threatening disease from the vaccine," says Dr. Petru. "An earlier diagnosis will make a huge difference to this very small but very vulnerable population of patients."


Tuesday, May 17, 2011 8:19 AM

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