Sex: U
Vaccine: VARCEL
Symptoms: Varicella virus test positive
Clinical narrative: Information has been received from a published article. Abstract: Case reports have linked varicella-zoster virus (VZV) to gastrointestinal disorders, including severe abdominal pain preceding fatal varicella and acute colonic pseudo-obstruction (Ogilvie's syndrome). Because the authors had previously detected DNA and transcripts encoding latency associated VZV gene products in the human gut, authors sought to determine whether latent VZV is present in the human enteric nervous system (ENS) and, if so, to identify the cells in which it is located and its route to the bowel. Neither DNA, nor transcripts encoding VZV gene products, could be detected in resected gut from any of seven control children (<1 year old) who had not received the varicella vaccine or experienced varicella; however, VZV DNA and transcripts were each found to be present in resected bowel from 6/6 of children with a past history of varicella and in that 6/7 of children who received the varicella vaccine. Both wild-type (WT) and vaccine-type (vOka) VZV thus establish latent infection in human gut. To determine routes by which VZV might gain access to the bowel, authors injected guinea pigs with human or guinea pig lymphocytes expressing green fluorescent protein (GFP) under the control of the VZV ORF66 gene (VZVOKA66.GFP). GFP expressing enteric neurons were found throughout the bowel within 2 days and continued to be present for greater than 6 weeks. DNA encoding VZV gene products also appeared in enteric and dorsal root ganglion (DRG) neurons following intradermal administration of WT-VZV and in enteric neurons after intradermal injection of VZVOKA66.GFP; moreover, a small number of guinea pig DRG neurons were found to project both to the skin and the intraperitoneal viscera. Viremia, in which lymphocytes carry VZV, or axonal transport from DRG neurons infected through their epidermal projections are thus each potential routes that enable VZV to gain access to the ENS. Specimens of human gut: Surgical specimens of gut were obtained at a hospital from 20 children; surgery was carried out for medically indicated reasons. Following removal of segments of bowel, specimens that normally would have been discarded were coded and sent for analysis, accompanied only with information about each child's age, varicella vaccination status, and history of varicella. Ages of children in the control group (N=7) were: newborn (1), 2 months (2), 4 months (3), and 1 year (1), and 12 years (1). Ages of children with a history of varicella (N=6) were 6 years (1), 15 years (1), 16 years (2), and 17 years (1). An Institutional Review Board (IRB) approved this study. Specimens were transmitted immediately to the laboratory for processing. Each specimen was divided in two; one half was placed in RNA later for analysis of nucleic acids, while the other half was fixed for immunocytochemistry with 4% formaldehyde (from paraformaldehyde) at pH 7.4, for histological examination. Results: VZV is present in the gut of children exposed to VZV. Three groups of children were studied. Controls consisted of infants, each of whom were less than 1 year of age, were not vaccinated, and had no history of varicella. The second group consisted of children (6-17 years of age) who had not received the varicella vaccine but in whom a history of natural varicella was documented. The third group consisted of children (1.3-12 years of age) who were vaccinated against varicella but lacked a history of natural varicella. RNA isolated from each specimen was converted to cDNA, and nested PCR was employed to determine whether transcripts encoding members of a panel of latency-associated (ORFs 4, 29, 62, 63, 66) and/or lytic infection-associated (ORFs 31, 61, 68) VZV gene products could be detected. Latency-associated gene products were considered to be those reported to be expressed during latency in human ganglia and in isolated guinea pig enteric neurons. Lytic infection-associated gene products were considered to be those reported to be expressed during lytic infection and but not during latency. At least one latency-associated gene product was detected in each of the six specimens from children in whom there was a history of natural varicella. The most commonly detected transcript was ORF63 followed by ORFs4 and 66. No lytic infection-associated transcripts were found in any of the six specimens. At least one latency associated gene product was also found in most of the specimens from vaccinated children although one of seven lacked any transcripts encoding a VZV gene product. The most commonly detected transcript again was ORF63, followed by ORFs 62 and 66. As after natural infection, no lytic infection-associated transcripts were found in any of the seven specimens from vaccinated children. These observations are consistent with the ideas that VZV is commonly latent in the human bowel and that its presence depends on prior exposure to VZV, either in the form of natural varicella or receipt of the varicella vaccine. This report concerns 6/7 of children (third group) who received the varicella vaccine (manufacturer unknown) without a history of natural varicella. VZV DNA and transcripts were each found to be present in resected bowel from the 6 children. Ages of the children who had received varicella vaccine (N=7) were 1.3 years (1), 1.6 years (1), 3.5 years (2), 4.1 years (1), 5.7 years (1), and 12 years (1). Information was not provided to distinguish the identifiers of the six children (VZV DNA presented in resected bowel) from the other one. The authors considered that administration of varicella vaccine was the reason that VZV DNA and transcripts present in the children's resected bowel: "These observations are consistent with the ideas that VZV is commonly latent in the human bowel and that its presence depends on prior exposure to VZV, either in the form of natural varicella or receipt of the varicella vaccine." "Because the infection of the gut was relatively restricted to the caudal bowel following intradermal administration of VZV between the forelegs and hind legs of the guinea pigs, but generalized from stomach to colon after experimental viremia, it is likely that both a sensory neuronal conduit of virus from skin to gut and viremia are able to establish latency in the bowel and the two routes of infection are not mutually exclusive. Both might function either after varicella or after administration of varicella vaccine." Additional information has been requested.