Rotavirus Vaccine Caused Rotavirus Infection In Two Immune-Suppressed Babies

Two infants receiving the first two of three scheduled doses of the live, attenuated-virus rotavirus vaccine (RotaTeq) developed infections traced to the product, according to Niraj C. Patel, M.D., of Baylor College of Medicine in Houston.

After the babies were hospitalized with diarrhea and other symptoms consistent with rotavirus infection, it was discovered that they had severe combined immunodeficiency syndrome (SCID).

These are the first reported cases of infection caused by the rotavirus vaccine, which was approved in 2006, Dr. Patel said in a late-breaking research session here at the American Academy of Allergy, Asthma, and Immunology meeting.

Dr. Patel said molecular analyses showed that the vaccine caused the infections. All the attenuated virus strains used in the vaccine contain two bovine genes that aren’t found in wild-type human rotavirus. Both were present in the rotavirus isolates obtained from the babies.

Source: Medpage Today, March 18 2009.

Possible Rotavirus From Rotavirus Vaccine

My baby is sick. Possibly sick from the vaccine intended to protect her from illness. And I am sick at heart. You see, I took her in for her 9-month well baby visit three days ago. At that time, she received two vaccinations: DTaP and Rotavirus. Those of you really savvy about vaccinations might see the problem already. I didn’t realize it at the time, but the rotavirus vaccine is not recommended after the baby reaches the age of 32 weeks (about 8 months).

My baby was overdue for her third and final dose of RotaTeq. I had put it off because we were on the waiting list for the Hib vaccine, which is in short supply and must be rationed out by pediatricians. In hindsight I realize I should have proceeded on schedule with my daughter’s other vaccinations, and I should have re-read the information about each vaccine, rather than relying on my previous decision to approve that vaccination. My initial reasoning was that I have had rotavirus before, and I had never been so sick in my life!

Two days after my baby received the vaccine, she started having mild diarrhea. I didn’t think much of it, until 12 hours later when she threw up (and I earned a Mommy Medal by catching it in my hand, thankyouverymuch!) The next day, she spiked a fever of over 102. I am not worried for her. She is generally content and just a bit sleepy. Thank goodness for breastfeeding, which keeps her both hydrated and happy!

I am not “pro-vaccine” or “anti-vaccine.” I am all about the informed decision. I fully recognize that my daughter might not actually have rotavirus, or that she might have rotavirus but have contracted it from a source other than the live vaccine. I do feel though that this diarrhea, vomiting, and fever constitute a potential adverse reaction to the vaccine.


Intussusception Rates After Rotavirus Vaccine ‘Underestimated’

Because a previous rotavirus vaccine was associated with intussusception, new rotavirus vaccines are monitored postlicensure for any such association. Accurate background intussusception rates are needed to determine whether the number of cases observed after vaccination exceeds that expected by chance. Previously, intussusception rates were obtained from inpatient discharge databases. We sought to determine the rate of intussusception among infants managed only with short‐stay or emergency department care.

Methods.Intussusception cases occurring in infants were identified retrospectively at 3 children’s hospitals from January 2001 through March 2006, a period without rotavirus vaccine use, by a search of discharge, billing, and radiology databases for International Classification of Diseases, Ninth Revision, Clinical Modification code 560.0 (intussusception) and procedure codes and by review of medical records.

Results.Of 156 infants with intussusception fulfilling Brighton level 1 criteria, 81 (52%) were billed as inpatients, 68 (44%) as short‐stay patients, and 7 (4%) as emergency department patients only. The use of only inpatients assigned code 560.0 underestimated the total number of level 1 cases at the hospitals by 44%. The mean annual intussusception rate for the hospitals’ catchment counties was 49.3 cases per 100,000 live births (inpatient cases: 27.1 cases per 100,000 live births; short‐stay or emergency department cases: 22.3 cases per 100,000 live births).

Conclusions.Intussusception rates based solely on inpatient discharge databases could underestimate the true incidence of level 1 intussusception by >40%. Background rates used for assessment of risk after vaccination should account for cases managed only with short‐stay or emergency department care.
Source: The Journal of Infectious Diseases 2009;200:S264–S270

Rotavirus Spread From Vaccinated Child to Unvaccinated Sibling

Although rotavirus vaccines are known to be shed in stools, transmission of vaccine-derived virus to unvaccinated contacts resulting in symptomatic rotavirus gastroenteritis has not been reported to our knowledge. We document here the occurrence of vaccine-derived rotavirus (RotaTeq [Merck and Co, Whitehouse Station, NJ]) transmission from a vaccinated infant to an older, unvaccinated sibling, resulting in symptomatic rotavirus gastroenteritis that required emergency department care. Results of our investigation suggest that reassortment between vaccine component strains of genotypes P7[5]G1 and P1A[8]G6 occurred during replication either in the vaccinated infant or in the older sibling, raising the possibility that this reassortment may have increased the virulence of the vaccine-derived virus.

Source: PEDIATRICS (doi:10.1542/peds.2009-1901)

Increased risk of intussusception associated with Rotavirus Vaccine

The relation between the risk of intussusception and age at the time of receipt of the first dose of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) has been studied extensively on the basis of Centers for Disease Control and Prevention (CDC) matched case-control study data, using various statistical methods, including conditional logistic regression and quadratic smoothing splines. However, different conclusions have been reported in published analyses regarding the dependence of the risk of intussusception on age at first dose. The authors reanalyzed the CDC matched case-control data set using unrestricted and restricted quadratic smoothing spline methods for various exposure windows (i.e., intervals postvaccination). These analyses indicated that the use of different models may lead to different conclusions. The restricted quadratic smoothing spline with appropriately chosen knot locations showed a statistically significant increased risk of intussusception associated with RRV-TV for the exposure window 3–14 days after the first dose at an age as young as 49 days, the youngest age in the data set at which vaccine was administered; this implies an increased risk of intussusception associated with RRV-TV at all ages studied.


American Journal of Epidemiology Advance Access published online on April 16, 2010
American Journal of Epidemiology, doi:10.1093/aje/kwq048

Rotavirus Infection from Rotavirus Vaccine in Immune-Compromised Infants

Addition of Severe Combined Immunodeficiency as a Contraindication for Administration of Rotavirus Vaccine
June 11, 2010 / 59(22);687-688

In response to reported cases of vaccine-acquired rotavirus infection in infants with severe combined immunodeficiency (SCID) following rotavirus vaccine administration, both Merck & Co. and GlaxoSmithKline Biologicals have revised the prescribing information and patient labeling for their respective rotavirus vaccine products, pentavalent rotavirus vaccine (RV5) and monovalent rotavirus vaccine (RV1), with approval from the Food and Drug Administration (1,2). Merck revised the prescribing information and patient labeling for RV5 in December 2009, and GlaxoSmithKline Biologicals did so for RV1 in February 2010. After the revision to the RV5 prescribing information, CDC sought consultation from members of the former Rotavirus Vaccine Work Group of the Advisory Committee on Immunization Practices (ACIP). On the basis of that consultation and available data, CDC is updating the list of contraindications for rotavirus vaccine. Rotavirus vaccine (both RV5 and RV1) is contraindicated in infants diagnosed with SCID.

SCID includes a group of rare, life-threatening disorders caused by at least 15 different single gene defects that result in profound deficiencies in T- and B- lymphocyte function (3). The estimated annual incidence of SCID is one case per 40,000–100,000 live births, or a total of approximately 40–100 new cases among infants in the United States each year (3). SCID usually is diagnosed after an infant has acquired a severe, potentially life-threatening infection caused by one or more pathogens. Infants with SCID commonly experience chronic diarrhea, failure to thrive, and early onset of infections. Chronic, wild-type rotavirus infection has been reported in infants with SCID, with resulting prolonged diarrhea or shedding of rotavirus (4). Diagnosis and hematopoietic stem cell transplantation before onset of severe infections offer the best chance for long-term survival of SCID patients (3,5).

The median age at diagnosis of SCID is 4–7 months, which overlaps with the ages for rotavirus vaccination recommended by ACIP (ages 2, 4, and 6 months for RV5; ages 2 and 4 months for RV1). Prenatal diagnosis is possible for the minority of infants with a known family history of SCID. Newborn screening for SCID through evaluation of dried blood spots is available in two states, Massachusetts and Wisconsin. On January 21, 2010, the Federal Advisory Committee on Heritable Disorders in Newborns and Children recommended that a screening test for SCID be included in the core panel of the recommended uniform screening panel for all newborn infants. On May 21, the U.S. Department of Health and Human Services approved the addition of SCID to the uniform screening panel.

Since introduction of rotavirus vaccine in the United States in 2006, five cases (four in the United States and one in Australia) of vaccine-acquired rotavirus infection in RV5-vaccinated infants with SCID have been reported in the literature (6–8). Two additional U.S. cases of vaccine-acquired infection in RV5-vaccinated infants with SCID and one case of vaccine-acquired infection in an RV1-vaccinated infant with SCID from outside the United States have been reported to the Vaccine Adverse Event Reporting System (VAERS). The eight infants (four males and four females) were diagnosed with SCID between ages 3 months and 9 months and had received 1–3 doses of rotavirus vaccine before the diagnosis. All the infants had diarrhea, and most had additional infections (e.g., Pneumocystis jirovecii, rhinovirus, adenovirus, Salmonella, Escherichia coli, and Giardia) at the time of SCID diagnosis. Rotavirus infection was diagnosed by enzyme immunoassay in seven of the eight patients for whom this information was available. In all eight cases, vaccine-acquired rotavirus infection was confirmed by reverse transcription–polymerase chain reaction (RT-PCR) and nucleotide sequencing. Prolonged shedding of vaccine virus was documented in at least six of these cases, with duration of up to 11 months.

Rotavirus vaccine (both RV5 and RV1) is contraindicated in infants diagnosed with SCID. Consultation with an immunologist or infectious disease specialist is advised for infants with known or suspected altered immunocompetence before rotavirus vaccine is administered (9). General guidelines on immunodeficiency and use of live virus vaccines are available in the 2009 Red Book, Table 1.14 (10).

1. Food and Drug Administration. Product approval-prescribing information [package insert]. RotaTeq [rotavirus vaccine, live, oral pentavalent], Merck & Co, Inc: Food and Drug Administration; 2009. Available at Web Site Icon. Accessed June 4, 2010.
2. Food and Drug Administration. Product approval-prescribing information [package insert]. Rotarix [rotavirus vaccine, live, oral], GlaxoSmithKline Biologicals: Food and Drug Administration; 2010. Available at Web Site Icon. Accessed June 4, 2010.
3. Puck JM. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol 2007;120:760–8.
4. Saulsbury FT, Winkelstein JA, Yolken RH. Chronic rotavirus infection in immunodeficiency. J Pediatr 1980;97:61–5.
5. Buckley RH, Schiff SE, Schiff RI, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 1999;340:508–16.
6. Patel NC, Hertel PM, Estes MK, et al. Vaccine-acquired rotavirus in infants with severe combined immunodeficiency. N Engl J Med 2010;362:314–9.
7. Uygungil B, Bleesing JJ, Risma KA, McNeal MM, Rothenberg ME. Persistent rotavirus vaccine shedding in a new case of severe combined immunodeficiency: a reason to screen. J Allergy Clin Immunol 2010;125:270–1.
8. Werther RL, Crawford NW, Boniface K, Kirkwood CD, Smart JM. Rotavirus vaccine induced diarrhea in a child with severe combined immune deficiency. J Allergy Clin Immunol 2009;124:600.
9. CDC. Cortese MM, Parashar UD. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2009;58(No. RR-2).
10. American Academy of Pediatrics. Immunocompromised children. Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red book: 2009 report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:24–5.

VAN UK’s Comment: As it isn’t diagnosed until between 4 and 7 months, babies will have had several vaccines by then that could put their lives at risk.


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