Lawrence T. Ch'ien

Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study.

We evaluated adenine arabinoside (vidarabine) for treatment of herpes simplex encephalitis in a placebo-controlled study. In 28 cases proved by isolation of Type 1 virus from brain biopsy, treatment reduced mortality from 70 to 28 per cent (P = 0.03), and over 50 per cent of treated survivors had no or only moderately debilitating neurologic sequelae. This improvement was achieved without evidence of acute drug toxicity. Thus, adenine arabinoside has a good therapeutic index (efficacy/toxicity) for the treatment of Type 1 herpes simplex encephalitis. However, the drug must be given early in the course of infection before the advent of coma to have a beneficial effect. Moreover, it should be coupled with brain biopsy for specific diagnosis to avoid unnecessary treatment of nonresponsive encephalitides that can mimic herpes simplex.Abstract We evaluated adenine arabinoside (vidarabine) for treatment of herpes simplex encephalitis in a placebo-controlled study. In 28 cases proved by isolation of Type 1 virus from brain biopsy, treatment reduced mortality from 70 to 28 per cent (P = 0.03), and over 50 per cent of treated survivors had no or only moderately debilitating neurologic sequelae. This improvement was achieved without evidence of acute drug toxicity. Thus, adenine arabinoside has a good therapeutic index (efficacy/toxicity) for the treatment of Type 1 herpes simplex encephalitis. However, the drug must be given early in the course of infection before the advent of coma to have a beneficial effect. Moreover, it should be coupled with brain biopsy for specific diagnosis to avoid unnecessary treatment of nonresponsive encephalitides that can mimic herpes simplex. (N Engl J Med 297:289–294, 1977)

Adenine Arabinoside Therapy of Biopsy-Proved Herpes Simplex Encephalitis

We evaluated adenine arabinoside (vidarabine) for treatment of herpes simplex encephalitis in a placebo-controlled study. In 28 cases proved by isolation of Type 1 virus from brain biopsy, treatment reduced mortality from 70 to 28 per cent (P = 0.03), and over 50 per cent of treated survivors had no or only moderately debilitating neurologic sequelae. This improvement was achieved without evidence of acute drug toxicity. Thus, adenine arabinoside has a good therapeutic index (efficacy/toxicity) for the treatment of Type 1 herpes simplex encephalitis. However, the drug must be given early in the course of infection before the advent of coma to have a beneficial effect. Moreover, it should be coupled with brain biopsy for specific diagnosis to avoid unnecessary treatment of nonresponsive encephalitides that can mimic herpes simplex.Abstract We evaluated adenine arabinoside (vidarabine) for treatment of herpes simplex encephalitis in a placebo-controlled study. In 28 cases proved by isolation of Type 1 virus from brain biopsy, treatment reduced mortality from 70 to 28 per cent (P = 0.03), and over 50 per cent of treated survivors had no or only moderately debilitating neurologic sequelae. This improvement was achieved without evidence of acute drug toxicity. Thus, adenine arabinoside has a good therapeutic index (efficacy/toxicity) for the treatment of Type 1 herpes simplex encephalitis. However, the drug must be given early in the course of infection before the advent of coma to have a beneficial effect. Moreover, it should be coupled with brain biopsy for specific diagnosis to avoid unnecessary treatment of nonresponsive encephalitides that can mimic herpes simplex. (N Engl J Med 297:289–294, 1977)

Adenine arabinoside therapy of herpes zoster in the immunosuppressed. NIAID collaborative antiviral study.

We evaluated adenine arabinoside treatment of herpes zoster in immunodeficient patients in a randomized, controlled crossover study. The two study groups had similar characteristics. In spite of rapid natural healing, those receiving adenine arabinoside over the first five days had accelerated clearance of virus from vesicles (P = 0.01), and cessation of new vesicle formation (P = 0.004), and a shorter time to total pustulation (P = 0.001). Factors modifying the response to therapy included age, underlying disease, and the duration of zoster prior to therapy. Clinical toxicity was minimal. Laboratory assessment of bone-marrow, liver and renal function showed insignificant alterations as a result of therapy. These studies show that adenine arabinoside is a drug with promise for therapy of systemic herpes zoster in immunocompromised patients. It is most efficacious when administered during the first six days of disease (P = 0.001) to those who have reticuloendothelial neoplasia (P = 0.001) and are less than 38 years of age (P = 0.001).

Gastrointestinal hemorrhage secondary to cytomegalovirus after renal transplantation: A case report and review of the problem

Generalized cytomegalovirus infection was associated with massive and ultimately fatal upper gastrointestinal bleeding in a renal allograft recepient and persisted even after subtotal gastric resection. The surgical specimen and the remaining stomach at autopsy revealed multiple superficial ulcerations with cytomegalic inclusion bodies within the gastric mucosa. Renal failure in the terminal stages of the patients illness required hemodialysis but did not seem to be the sole result of allograft rejection, suggesting that the renal dysfunction may be caused by the systemic viral infection.

Studies on Adenine Arabinoside—A Model for Antiviral Chemotherapeutics

Publisher Summary This chapter presents studies on adenine arabinoside (ara-A). It presents a model for antiviral chemotherapeutics. The initial laboratory and metabolic studies paved the way for limited field trials of ara-A. The clinical and virologic studies have been performed primarily at the University of Alabama in Birmingham. The patients selected for treatment came exclusively from a population in which viral infections were recognized as leading to potentially serious complications. Thus, these patients included organ transplant recipients, newborns, and those with underlying diseases, such as leukemia, lymphoma, or generalized malignancy, particularly, those receiving immunosuppressive therapy with steroids, antimetabolites, or radiation. The truly significant advantage of ara-A over its counterpart pyrimidine analogs is its virtual lack of acute toxicity. All patients treated with ara-A, to date, have been monitored serially for changes in biochemical and hematologic status.

Neonatal Herpes Simplex Virus Infection

Many viruses are capable of infecting the central nervous system of neonates; however, herpes simplex virus (HSV) is among the most severe and has significant mortality and morbidity associated with it. Fortunately, HSV is treatable utilizing the commercially available antiviral drug acyclovir. Neonatal HSV infection is usually acquired in the peripartum period, which enhances the likelihood that antiviral therapy can be beneficial since viral damage is of a relatively short duration compared with injury to the developing fetal brain from viruses such as rubella, cytomegalovirus, and Zika virus that primarily are acquired in utero. Studies conducted over several decades have advanced our knowledge of the impact of antiviral therapy on neonatal HSV disease outcomes. Consequently, many neonates now are effectively treated and experience no or lesser long-term sequelae of this potentially devastating infection.Purpose of review In spite of the availability of antiviral therapy for the treatment of neonatal herpes simplex virus infections, the outcome remains poor, particularly for babies with disseminated multi-organ infection or central nervous system disease. This review considers recent advances that impact on disease management. Recent findings Two areas of investigation have impacted on our understanding of neonatal herpes simplex virus infection. First, the transmission of infection from mother to baby has been clarified by extensive epidemiological investigations of genital herpes in pregnant women at term. Risk factors for neonatal herpes simplex virus disease include first-episode maternal infection in the third trimester, invasive monitoring, delivery before 38 weeks, and maternal age of less than 21 years. Regarding the management of neonatal herpes simplex virus disease, the utilization of high-dose acyclovir (20 mg/kg every 8 h) for 21 days significantly reduces mortality for babies with either encephalitis or disseminated disease. Summary Recent findings from epidemiological studies have identified women at risk of delivering a child who develops neonatal herpes simplex virus infection, and suggest methods to decrease maternal-fetal transmission. If infection is identified in the pregnant woman, cesarean delivery decreases the frequency of neonatal disease. With neonatal disease, acyclovir should be administered promptly at higher dosages and for longer periods than previously reported.

HERPES SIMPLEX VIRUS (HSV) INFECTION IN NEONATES, TREATED WITH ADENINE ARABINOSIDE (ARA-A)

Among 13 neonates with HSV (8 type 2, 4 typel) infection, 8 had disseminated disease and in 4 the infection was localized to the skin and eyes. Ara-A, 10-20 mg/kg/day, was given by a continuous 12 hour intravenous drip for 10-15 days. In all, ara-A was started from 4-6 days after the first appearance of skin vesicles (s.v.) which represented the hallmark of diagnosis. Eight infants (4 disseminated and 4 localized) with s.v. as the earliest sign of infection received ara-A early within 3 days of the onset of neurologic signs (n.s.). All survived with no neurologic deficit at 6 months to 1 year of age. The other 5 infants in group I having nonspecific n.s. with delayed appearance of absence of s.v. were treated late with ara-A, (avg. 14 days after the onset of n.s.). Four died and 1 was left with severe neurologic deficits. They were initially misdiagnosed as neonatal sepsis and treated with antibiotics for 10.5 days while 4 others in the same group with good outcome received antibiotics for only 1.5 days prior to diagnosis. There was no apparent toxicity of ara-A to the bone marrow, liver or kidney. These data suggest that ara-A may be efficacious in treatment of neonatal HSV infection if given early and that early recognition of the infection even in the absence of s.v. appears essential.