Specific interventions for gastrointestinal virus infections

A variety of approaches have been used to try and reduce the duration and severity of gastrointestinal virus infections with the aim of changing the natural history of the infection. These interventions include the use of antiviral agents and other forms of antimicrobial chemotherapy, oral administration of immunoglobulins, probiotics and oral administration of growth factors.

Viral oesophagitis due to infection with herpes simplex virus (HSV) or cytomegalovirus (CMV) and CMV colitis are found most commonly in individuals with HIV infection. These infections in the immunocompromised host require treatment with antiviral agents. In severely symptomatic patients with HSV oesophagitis, aciclovir 5mg/kg should be given intravenously every 8 hours for 7—10 days (Genereau et al 1996). In these patients oral maintenance therapy with 400 mg aciclovir orally twice daily should probably also be given. Milder infections may respond to oral aciclovir. When HSV is resistant to aciclovir an alternative therapy is foscarnet 40—60 mg/kg intravenously every 8 hours for 2—3 weeks.

CMV oesophagitis and colitis should be treated with ganciclovir 5mg/kg intravenously twice daily for 3—6 weeks (Dieterich et al 1988, Nelson et al 1991). Maintenance therapy with oral ganciclovir 1000 mg orally three times daily may also be considered. An alternative drug is foscarnet.

Currently no antiviral agent is recommended for the treatment of viral gastroenteritis. However, human interferon a (IFNa) has been evaluated in a pig model of rotavirus infection (Lecce et al 1990). IFNa reduced virus excretion and mortality and improved weight gain compared to controls. The cysteine protease inhibitor E-64-c decreased diarrhoea and resulted in more rapid resolution of small intestinal changes in suckling mice infected with a human rotavirus strain (Ebina & Tsukada 1991). These findings are clearly of interest, but it is unlikely that these agents will find a place in the routine management of this infection.

Attempts have been made to reduce the duration and severity of rotavirus infection by the oral administration of anti-rotavirus immunoglobulin with the aim of reducing intraluminal viral load. Initial experiments were performed in children which showed that orally administered human serum immunoglobulin could survive passage through the gastrointestinal tract (Losonsky et al 1985). Cows were then immunized with rotavirus to produce hyperimmune bovine colostrum. Several clinical trials have shown that colostrum-treated children had reduced stool weight and frequency, required less ORS, cleared rotavirus more rapidly from the stool and had a shorter duration of illness (Hilpert et al 1987, Guarino et al 1994, Mitra et al 1995, Sarker et al 1998). Despite these promising results hyperimmune colostrum has as yet not found a place in the management of this infection.

Probiotics

The concept of feeding innocuous bacteria to treat or prevent intestinal infection is not new and was considered by Louis Pasteur at the end of the last century. Several strains of lactobacilli have been evaluated as adjunctive therapy in children with rotavirus infection and preliminary studies indicate that early administration reduces the duration of diarrhoea compared to controls (Kaila et al 1992, 1995, Isolauri et al 1994, Majamaa et al 1995, Shornikova et al 1997). In addition treatment with lactobacilli may also enhance the specific antibody response to rotavirus infection. Further work is required to confirm these findings before implementation can be widely recommended.

Growth factors

Growth factors such as epidermal growth factor (EGF) and transforming growth factor a (TGFa) are known to promote epithelial cell growth in the small intestine.

Both growth factors have been evaluated in a pig model of rotavirus infection. Orally administered EGF at supraphysiological doses increased villus height and lactase activity in the small intestine but did not speed recovery from diarrhoea (Zijlstra et al 1994). TGFa, again administered orally, promoted mucosal recovery and improved epithelial barrier function but did not affect the functional capacity of the small intestine (Rhoads et al 1995). These are interesting mechanistic studies showing the potential of naturally occurring growth factors to promote tissue recovery, but as yet there is no indication that they have a role in the management of human infection.

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