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Give an account of the treatment of infections caused by members of the herpes virus family

 

Many types of infections caused by members of the herpesvirus family are now amenable to treatment with specific anti-viral chemotherpy. For a long time, herpesviruses are the only virus family for which antiviral chemotherapy is relatively developed.

Herpes Simplex Viruses

The indications for specific antiviral treatment of herpes simplex are controversial. It is probably only necessary in a minority of situations, such as;

  1. Unusually severe primary infection

  2. Eye involvement

  3. Disseminated disease

  4. In immunocompromized or ezematous patients

  5. Neontal dissminated disease

  6. Herpes simplex encephalitis

There is no role for chemotherapy in recurrent disease, unless the episode is unusually severe or if the eye is involved. Prophylactic antiviral chemotherapy may be considered in two clinical settings;-

  1. Frequently recurrent severe oral or genital herpes

  2. Patients undergoing bone marrow transplantation

Acyclovir is a drug of choice for the treatment of systemic infections and prophylaxis. It is only taken up by cells infected by HSV and has few side effects. It can be given intravenously or orally. It is also available in the form of an ointment for the treatment of local oral, genital or eye infections. Should acyclovir resistance be encountered then forscarnet or ara-A may be considered for the treatment of systemic infections.

Valacylovir and famciclovir can be given orally for the treatment of primary or recurrent genital herpes. They can also be given to suppress recurrent genital herpes. Ara-A, idoxuridine, F3T and EDU are also available in the form of an ointment or lotion for the treatment of local infections. Idoxuridine, F3T and EDU are not suitable for systemic use as they are highly toxic.

Varicella-Zoster Virus

There are no indications for antiviral chemotherapy for a healthy individual with varicella unless complications such as pneumonia and encephalitis are present. Antiviral chemotherpay is also indicated for immunocompromised individuals with varicella where the disease can be serious and even fatal.  More severe, in particular disseminated forms of zoster may be seen in immunocompromised individuals and antiviral chemotherpay should be considered. Acyclovir is the drug of choice for treating VZV infections even though VZV is less susceptible than HSV to acyclovir. Other drugs which may be considered include Ara-A. Newer drugs such as valacyclovir are being developed whose action is much more specific on VZV than acyclovir. Prophylactic acyclovir in patients undergoing bone marrow transplant reduces the incidence of varicella and zoster in the post-transplant period.

In addition to acyclovir, valacyclovir and famciclovir may be used for the treatment of shingles. Time to healing is reduced as is the duration of post-herpetic neuralgia.
The International Herpes Management Forum now recommends that antiviral therapy should be offered routinely to all patients over 50 years of age presenting with herpes zoster. The advent of newer agents such as valaciclovir and famciclovir will expand the range of antiviral therapies available to the practitioner. In an intent-to-treat analysis of all patients treated within 72 hours of rash onset, famciclovir, the oral pro-drug of penciclovir offered no advantage over acyclovir. However, valaciclovir was reported to resolve zoster-associated pain about one-third faster than acyclovir. There had been no published comparative studies of valaciclovir and famciclovir.

CMV

Primary or recurrent CMV infection is usually subclinical in healthy individuals although in a few cases, primary infection may result in an infectious mononucleosis syndrome. In immunocompromised individuals, primary or recurrent CMV infection can be very serious, being life or sight-threatening. The following serious complications may be seen in immunocompromised individuals;

AIDS patients - CMV retinitis, gastrointestinal problems such as colitis, and encephalopathy

Bone marrow transplant recipients - pneumonitis, encephalopathy, GI problems

Renal and other organ transplant recipients - pneumonitis, encephalopathy, GI problems, retinitis.

Where complications are present, antiviral chemotherapy is indicated. Ganciclovir is the drug of choice for the treatment of CMV infections. However, it is toxic to the bone marrow and can only be given intravenously. Where there is suspicion of ganciclovir resistance, forscarnet can be considered instead. Ganciclovir is becoming the drug of choice for the treatment of CMV retinitis in patients with AIDS. However, like ganciclovir, it is associated with significant toxicity, especially on renal function.

The use of antiviral chemotherapy in organ graft recipients who excrete CMV but are otherwise healthy is controversial. In general, if CMV is detected from the urine or saliva of the patient only, then no antiviral chemotherapy is required. However, if it is detected in the blood or bronchioalveolar lavage, then treatment is indicated. Although acyclovir does not have any beneficial effect on the treatment of established CMV infection, it is thought to be useful if given prophylactically to patients undergoing bone marrow transplant.

A number of options are available for the treatment of CMV retinitis in AIDS patients. Besides systemic therapy with ganciclovir and forscarnet. Local therapy in the form of ganciclovir or fomvirisen implants may be used. Another systemic agent, cidofovir is also effective in the treatment of CMV retinitis.

EBV

Specific antiviral therapy is not indicated in uncomplicated cases of infectious mononucleosis, nor is it of use in EBV-associated tumours such as Burkitt's lymphoma and nasopharyngeal carcinoma. However, unusual life-threatening EBV infections, such as the lymphoproliferative syndromes which occur after organ transplant, may be amenable to treatment with acyclovir.

HHV-6 and HHV-7

There are no indications for the use of antiviral therapy in the treatment of infections caused by HHV-6 and HHV-7.

To conclude, effective antiviral chemotherapy is now available for many infections caused by members of the herpesvirus family. More effective antiviral agents are expected to be available in the nearby future.

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