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372

M. Hussein and D.K Coats

 

 

appropriate dose, agent, and long-term effects of treatment are not clear. Ganciclovir has been used [145– 147]. Like in adults, granulocytopenia and thrombocytopenia are the main complications. Because of the possible carcinogenic and toxic effect of this drug, treatment of infants and children should be limited to those where the potential benefit is expected to outweigh the risks until more information is available. The prognosis for infants with congenital CMV infection depends on the severity of the disease in the perinatal period. Before the advent of anti-CMV treatment, the prognosis of these infants was very poor with death rate of around 30% with survivors having a high rate of severe CNS disorders [148].

AIDS Patients: Before the advent of HAART, patients with CMV retinitis required treatment with anti-CMV drugs for life. It is now possible to discontinue CMV treatment in selected patients who develop immune reconstitution after initiation of HAART therapy [149, 150]. Drugs commonly used in the treatment of CMV Retinitis in AIDS patients include Ganciclovir, foscarnet, cidofovir, and fomivirsen. Cidofovir and Fomivirsen are new drugs, and their effectiveness in therapy of HIV-infected children is not well studied. Ganciclovir and Foscarnet, however, have been used successfully in treating HIV-infected children [146, 147].

Ganciclovir is a viral DNA polymerase inhibitor, which can be administered intravenously or intravitreally, either by repeated injections or by local implant. Intravenously, therapy is carried out with an initial induction course of therapy (5 mg/kg/12 h) for 2 weeks followed by a maintenance dose of 5 mg/kg daily [151, 152]. Intervitreally, administration of ganciclovir is used mainly as a salvage therapy for patients intolerant to systemic therapy [153, 154], which can cause severe bone marrow toxicity. A dose of 0.2–0.4 mg/injection results in relapses at a rate of 33–53% ,that is comparable to that of IV ganciclovir and foscarnet [153, 155, 156]. Higher doses of intravitreal ganciclovir appear to be safe and well tolerated by the patients with encouraging results [156, 157].

Ganciclovir intraocular implants provide a sustained release drug delivery system specifically designed for treatment of CMV retinitis. The implants have shown good ability to achieve control of CMV retinitis when implanted into the eye of patients with newly diagnosed retinitis [159] and may have a role in treatment of recurrent CMV retinitis [159]. A combination of

systemic ganciclovir orally with local implants has been suggested for control of both local and systemic manifestations of the disease [160].

Foscarnet is a viral DNA polymerase inhibitor that can be used systemically and locally in the treatment of CMV retinitis. Intravenously, administration involves induction therapy with 60 mg/kg every 8 h for 14 days, followed by a maintenance therapy of 90/120 mg/kg/day [161, 162]. Foscarnet can be given intravitreally in a dose of 1,200 microgram of drug/ injection. The injection is given every 2–3 days for induction therapy, followed by weekly injection of maintenance therapy [163, 164]. Foscarnet is associated with greater incidence of side effects than ganciclovir, the most serious of which is renal toxicity.

Non-HIV immunosuppressed patients: Patients having CMV retinitis secondary to use of immunosuppressive drugs can usually be effectively treated by stopping the immunosuppressive agent. If this is not possible, concurrent treatment with anti-CMV drugs is needed. The treatment response is more favorable than treatment in patients with AIDS [165, 166].

16.3.2  Varicella Zoster Virus

Like other herpes viruses, Varicella zoster possesses double stranded linear DNA surrounded by a capsid. Only enveloped virions are infectious, and this accounts for the marked lability of the virus, with infectivity readily destroyed by both physical and chemical agents.

Varicella zoster virus is responsible for two distinct clinical entities, Varicella (chickenpox) and herpes zoster (shingles). Varicella is a mostly benign illness occurring primarily in children and characterized by an exanthematous vesicular rash. Zoster results with reactivation of latent virus in adulthood, often in response to stress.

Approximately, 3 million cases of varicella occur in the United States every year with the peak incidence in spring [167]. Generally, disease in children is benign, but aggressive disease with a high morbidity and occasionally mortality occurs in adults, immunosuppressed children, and fetuses born to nonimmune mothers. In the USA, more than 90% of adults have positive serology for previous infection with varicella-zoster virus, and almost all carry varicella-zoster virus in a latent state [168]. Up to 20% of individuals may have activation of