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Brief Reports Indian Pediatrics 2000;37: 1239-1241. |
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Oral
Acyclovir in Varicella Zoster Virus Infections in Children with
Acute |
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Rakesh Lodha Sanjay Tomar L.S. Arya S.K. Kabra
Immunocompromised children with varicella zoster virus infection are at a greater risks for dissemination and development of complications than immunocompetent individuals(1-3). Without any therapy the mortality may range from 7 to 10 per cent(2,4). Standard management of these children involves hospitalization and administration of intravenous acyclovir for 7 to 10 days(5,6). However, this approach is expensive and inconvenient. An alternative to the standard case management is oral acyclovir therapy. There are limited reports on the use of oral acyclovir alone in the management of varicella/herpes zoster in immunocompromised children(7,8). We report here our experience in treating children with acute lymphoblastic leukemia (ALL) who developed varicella/herpes zoster.
The records of children with acute lymphoblastic leukemia undergoing treatment in the Division of Pediatric Oncology, Department of Pediatrics, AIIMS, who developed varicella/zoster during the course of their therapy (between 1991 and 1999) and received oral acyclovir therapy were reviewed in this retrospective study. The diagnosis of varicella/herpes zoster was made clinically. The children’s examination finding and the hematological parameters were recorded. All children were offered intravenous acyclovir therapy. However, because of high cost of intravenous therapy [at present prices: Rs 3600 ($85/m2/day or Rs 85 ($2)/kg/day] and need for isolation in hospital, the same could not be administered. Also, there was poor availability of intravenous preparation in the early part of the study period. Therefore, these children were treated with oral acyclovir in a dose of 20 mg/kg/dose 4 times a day for 5 days (cost at present prices : Rs 3 (8 cents/kg/day). An informed verbal consent was obtained from the parents of these children after providing full information on the cost and benefits of intravenous and oral acyclovir therapy. Anticancer chemotherapy was discontinued. These children were evaluated every third day in the outpatient clinic till all the lesions healed. If any child showed worsening or evidence of dissemination, intravenous therapy was planned.
Twenty six children (20 boys, 6 girls) undergoing chemotherapy for acute lymphoblastic leukemia developed varicella (n = 6) or herpes zoster (n = 20) between 1991 and 1999. The median (range) age of the children was 7 (2-13) years. Six children were in the induction phase, 1 in consolidation phase, and 19 in the maintenance phase of chemotherapy, administered according to MCP-841 Protocol of the Indo-US Group for the study and treatment of lymphoid neoplasia. All these children presented within 2 days of the onset of the lesions. None of these children had evidence of disseminated disease. All children with zoster had only a single dermatome involvement. The median total leukocyte count was 2150 (500-7800) per ml. Eight children had neutropenia (absolute neutrophil count<500 per ml). The lesions healed in all the children by day 6. None of the twenty-six children worsened or developed features of dissemina-tion. Oral acyclovir was well tolerated. Anticancer chemotherapy was restarted in all the children two weeks after all the lesions had crusted.
Our experience shows that immuno-compromised children with uncomplicated varicella zoster infections can be treated effectively and safely with oral acyclovir. Acyclovir, a prodrug, is phosphorylated by herpes virus specific thymidine kinase to a monophosphate form and subsequently to a triphosphate metabolite; this metabolite inhibits the virus replication. Intravenous acyclovir is effective in preventing dis-semination of varicella in immuno-compromised individuals and shortens the time to healing(2,9,10). Because of the high cost of therapy and the need for hospitalization, it is worthwhile to look for alternative forms of therapy, which are effective yet, inexpensive. Oral acyclovir therapy is a potential alternative. In healthy children, oral acyclovir reduces the duration and severity of varicella when the therapy is initiated during the first 24 hours of the rash(11,12). A few studies have investigated the use of oral acyclovir in immunocompromised children(7,8). Novelli et al. treated 4 children with acute lymphoblastic leukemia and varicella with oral acyclovir; all the children recovered without any evidence of dissemination(7). In another study, 25 immunocompromised children with varicella were treated with oral acyclovir in a dose of 800 mg five times a day for 7 days(8). Of these, only 2 patients had to be shifted over to intravenous acyclovir therapy – one developed varicella pneumonitis and the other continued to have formation of new lesions on day 4 of therapy. In a recent study, a combination of intravenous followed by oral acyclovir was evaluated in a cohort of 26 immuno-compromised children with chickenpox(13). Twenty five of these children could be successfully switched from intravenous to oral therapy after 48 hours of initiation of therapy, all of whom had resolution of their infection. Available data suggests lower bio-availability of oral acyclovir in children than in adults(13,14). Still, oral acyclovir appears to be effective in immunocompromised children with varicella/herpes zoster. The possible reasons may be underestimation of the bioavailability, use of a higher dose by the oral route, and poor correlation between serum concentrations and clinical response. Oral form of therapy will be inexpensive and convenient to the patients. Also, this will be useful especially in developing countries where isolation facility may not be readily available in a busy general ward. This was a case series without any control group. Our preliminary experience suggests that short course of oral acyclovir may be safe and effective in immunocompromised children with varicella/herpes zoster. A randomized controlled trial comparing the oral and intravenous acyclovir therapy is desirable before routine administration of oral acyclovir can be recommended for varicella zoster virus infections in immunocompromised patients. Contributors: YJ, LSA coordinated the clinical management. YJ, LSA, ST collected the data. YJ, RL analysed the data. YJ, RL, SKK prepared the manuscript. SKK will act the guarantor for the paper. Funding: None.
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