Vol. 17, No. 15 THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER Monday, April 13 1998 A. Provided by Marguerite Hawkins, Epidemiology and Disease Control Program, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene
From April 2, 1998 through April 8, 1998, no outbreaks have been reported to the Maryland Department of Health and Mental Hygiene. One case of food-related gastroenteritis reported on March 31, 1998.
B. The Johns Hopkins Hospital: Information provided by Dr. Frank Holmes, Dept. of Pathology
Case History
A two year-old male presented with one week of green-colored, bloody diarrhea. One year ago, he had undergone bone marrow transplant for aplastic anemia and was doing well, having just been tapered off cyclosporine two weeks earlier. The child was afebrile and not complaining of abdominal pain. He was active and eating normally. His only medications included Synthroid and prophylactic Bactrim. Because of the concern for possible graft-versus-host disease, a rectal biopsy was performed which showed a focally active inflammatory lesion without signs of chronicity and with no inclusions or apoptotic bodies. The patient's stool was negative for enteric bacterial pathogens, fungi, and C. difficile toxin, but was, however, positive for adenovirus by culture and indirect immunofluorescence.
Adenoviruses
Adenoviruses are nonenveloped, double-stranded DNA viruses with an icosahedral nucleocapsid having 20 triangular faces and 12 vertices. Protruding from each vertex is a fiber, and dispersed on the triangular faces and edges are the hexon antigens. There are 49 different serotypes based on type-specific utralization results from antibodies against hexon and fiber antigens.
Clinical Disease
Adenoviruses were originally recognized when spontaneous degeneration occurred in adenoidal tissue cultures, as these viruses are able to establish latent infection in adenoidal and tonsillar tissues. Adenoviruses cause a variety of diseases, most of which occur in infants and young children. These include upper and lower respiratory tract infections, gastroenteritis, keratoconjunctivitis, hemorrhagic cystitis, and severe, fatal, disseminated disease in immunocompromised patients. In particular, adenovirus is a serious risk for bone marrow transplant (BMT) patients. Adenovirus has been reported to cause invasive disease in up to 1% of BMT recipients, and the incidence of adenovirus infection is higher in pediatric BMT patients than in adults. This latter fact seems consistent with the epidemiology of adenovirus infection with most primary infections being acquired during childhood. Additionally, moderate to severe acute graft-versus-host disease (aGVHD) is a significant, independent risk factor for the development of adenovirus disease, presumably due to treatment of aGVHD with steroids and other immunosuppressive agents. AIDS patients have also been noted to have a higher incidence of adenovirus in urine cultures, the clinical significance of which is currently unknown.
Certain serotypes are associated with specific diseases. Respiratory tract infections are associated primarily with types 1 through 7. Hemorrhagic cystitis is usually caused by type 11. Adenovirus types 40 and 41 are intestinal pathogens. These enteric adenoviruses are the second most common cause of viral gastroenteritis in infants (after rotavirus), and most patients are younger than two years of age. They generally produce sporadic infection, although epidemics have been described. Most of these adenovirus infections resolve spontaneously.
Adenoviruses can be transmitted by aerosol droplets, by the fecal-oral route, or by direct inoculation, which in ocular infections can occur from contaminated eye instruments, ophthalmic wash solutions, or the hands of medical personnel. Outbreaks can also occur among military recruits, apparently as a result of close living conditions that facilitate transmission. One important epidemiological feature in adenovirus infections is that the virus can be excreted in the stool for months after resolution of symptoms.
Diagnosis
The diagnosis of adenovirus is best accomplished by isolation of the virus in tissue culture. In the microbiology laboratory, the A549, HNK (human neonatal kidney), and fibroblast cell lines are used, and each culture is held for three weeks. If the virus is present, the infected cells will show evidence of cytopathic effect typical of adenovirus, including enlargement, rounding, and aggregation into irregular clusters. The tissue culture is confirmed by indirect immunofluorescence, which uses a mouse antibody against an adenovirus group-specific hexon antigen. Serotyping of isolates is not necessary for clinical purposes in most situations. If desired, serotyping is performed at the Maryland State Health Department, which also performs serologic tests on acute- and convalescent-phase sera. However, an ELISA test for types 40 and 41 is available in the microbiology laboratory here at The Johns Hopkins Hospital in order to help confirm significant adenovirus gastrointestinal disease.
A new PCR assay is also available in the microbiology laboratory. It can detect the presence of adenovirus in urine by using a set of primers to amplify a well-conserved region of the hexon gene, among the different serotypes.
Important for one to realize with all of these laboratory tests is that the virus can be present in body sites, such as the pharynx, or in stool, without necessarily causing disease. Approximately half of all adenovirus infections are asymptomatic, and virus can be shed in the stool for months after resolution of disease. Therefore, proper clinical correlation with the laboratory results is obviously needed.
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