Age: 2.0
Sex: M
Vaccine: RV5
Symptoms: Bacteria stool no organisms observed, Body temperature increased, Diarrhoea, Gastroenteritis, Gastroenteritis rotavirus
Clinical narrative: Information has been received from a health professional, concerning a 3 year old child patient (male) who was never vaccinated, developed chronic diarrhea (lasting more than one month) and tests demonstrated the presence of rotavirus. Upon further molecular analyses, tests revealed that the virus in the stool samples was the bovine WC3 virus based on nucleotide sequence identity analyses for at least gene segments 5 (NSP1), 6 (VP6), and 10 (NSP4). These data may indicate that the child is chronically ill and infected with a vaccine virus. Tests for other viral (norovirus, astrovirus, coronavirus, adenovirus) and bacterial (clostridium, E. Coli, salmonella, among others) agents were all negative. The child became sick a week after his sibling was vaccinated with ROTATEQ. This is one of the reports received from the same source. Follow up information was obtained in a published article, title as stated above that a male child aged 30 months was identified with acute gastroenteritis (AGE) that required emergency department care in January 2009, approximately 48 to 60 hours after the onset of vomiting and subsequent diarrhea. The child had been referred to the ED for evaluation and rehydration by his primary care provider. The child was alert at ED admission and had a blood pressure of 133/88, pulse rate of 120 beats per minute, respiratory rate of 24 respirations per minute, 95% oxygen saturation, and a maximum temperature of 100.7 degrees F. Abdominal examination revealed a non-tender and non-distended abdomen. The patient received ZOFRAN for the prevention of nausea and vomiting and was discharged from the ED. Following New Vaccine Surveillance Network protocols, epidemiologic data and a whole stool specimen were collected in the ED. Past medical history revealed that the child had achieved full gestational age, had a birth weight of 6 lbs 5 oz, was breastfed for 1 to 3 months, was growing and developing well, and was not taking medications. The patient had never received rotavirus vaccine but was up-to-date on all other vaccinations. His only hospitalization since birth occurred at 4 months of age, when abdominal distention was noted and he was diagnosed with ileocolic intussusception that required manual reduction during surgery. The stool sample obtained at the ED visit was positive according to a Rotaclone enzyme immunoassay, with an optical density of 1.811 (Rotaclone-positive 00 > 0.15). The specimen was sent to the CDC for routine surveillance confirmation by reverse transcription-polymerase chain reaction and nucleotide sequencing to determine the G and P genotypes (defined by the VP7 and VP4 genes, respectively). The VP7 gene open-reading frame and a 650-base pair fragment of the VP4 gene were 100% identical to cognate gene fragments from the corresponding viruses in ROTATEQ and closely related to wild-type human P (8) G1 strains (95.7% - 98.3% similarity for VP4 and 92.2% similarity for VP7). Subsequent analysis reveled that partial sequences of other genes (NSP1, 313 bp; NSP2, 177 bp; NSP3; 421bp, NSP4, 131 bp; NSP5, 229 bp; VP1; 879 bp; VP3, 500 bp; VP6, 368 bp) were 100% identical to the WC3 cognate genes of ROTATEQ. In addition, a partial gene sequence of VP2 (541 bp) exhibited 99.7% identity with the WC3 sequence of ROTATEQ. The P (8) and G1 components of the vaccine are found in 2 separate strains. Analyses by RT-PCR detected no additional rotavirus serotypes. These results suggest that the unvaccinated 30 month old child was shedding a P (8) G1 vaccine-virus ROTATEQ, a reassortment also detected among 2 subjects during a clinical trial of a prototype quadrivalent formulation of the vaccine. Electron microscopy performed on the sample revealed sporadic rotavirus-like particles that represented empty or broken capsids. Results of tests for other viral agents by real-time RT-PCR (norovirus genogroups I, II, and IV, sapovirus, astrovirus) or real-time PCR (adenovirus group F) and for bacterial agents (Salmonella, Shigella, Campylobacter, Escherichia coli0157, other enteric E. coli, and Vibrio spp.) by cultivation techniques were all negative. An investigation into possible sources of ROTATEQ exposure for the child revealed that he did not attend day care, but he did have a 2 month old male sibling who had received his first dose of ROTATEQ approximately 10 days before the older child's onset of AGE symptoms and was the likely source other vaccine virus. The younger sibling was asymptomatic. Medical chart review and consultation with the primary care provider 11 months after the ED visit indicated no diagnosed immunologic dysfunction or further hospitalization for either child. If the reassortment event did take place in the vaccinated infant, the presence of AGE symptoms only in the 30 month old sibling may reflect greater susceptibility to infection from this reassortant in the absence of protective maternal antibodies. Although neither child described in this report was known to have any underlying medical conditions. Upon internal review, vaccine derived acute gastroenteritis and chronic diarrhea were considered to be an other important medical events.