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West Nile virus (WNV) is a mosquitoborne flavivirus that causes a spectrum of human illnesses, ranging from asymptomatic infection to an undifferentiated febrile syndrome (West Nile fever) and potentially lethal [...]

The article discusses the causes, symptoms, diagnosis and treatment methodologies for Herpes Zoster or Shingles. The case study of a 70-year-old woman with Shingles is highlighted to better understand the epidemiologic features of the ailment as well as management of the disease.

A case study of 64-year-old man in generally good health, who visited his internist for an annual examination eight months after being treated for pneumonia with a course of oral antibiotics, is presented. A discussion on whether the patient should receive the varicella-zoster vaccine for the prevention of herpes zoster is presented.

The diagnosis and treatment of herpes zoster are reviewed. Herpes zoster is caused by the same virus that causes chickenpox. After children get over chickenpox, the virus remains dormant in the body. If it reactivates during adulthood, it is called herpes zoster, or shingles.

Due to lack of effective therapy, primary brain tumors are the focus of intense investigation of novel experimental approaches that use vectors and recombinant viruses. Therapeutic approaches have been both indirect, whereby vectors are used, or direct to allow for direct cell killing by the introduced virus. Genetically engineered herpes simplex viruses are currently being evaluated as an experimental approach to eradicate malignant human gliomas. Initial studies with [[Gamma].sub.1]34.5 mutants, R3616 (from which both copies of the [[Gamma].sub.1]34.5 gene have been deleted) and R4009 (a construct with two stop codons inserted into the [[Gamma].sub.1]34.5 gene), have been assessed. In a syngeneic scid mouse intracranial tumor model, recombinant herpes simplex virus can be experimentally used for the treatment of brain tumors. These viruses and additional engineered viruses were subsequently tested in human glioma cells both in vitro and in vivo. Using a xenogeneic scid mouse intracranial glioma model, R4009 therapy of established tumors significantly prolonged survival. Most importantly, long-term survival was achieved, with histologic evidence that R4009 eradicated intracranial tumors in this model. Furthermore, the opportunity to evaluate [[Gamma].sub.1]34.5 mutants that have enhanced oncolytic activity, e.g., R8309 where the carboxyl terminus of the [[Gamma].sub.1]34.5 gene has been replaced by the murine homologue, MyD116, are considered.

Biomedical studies of a malignant glioma model in mice indicate the efficiency of a gamma1 34.5 gene-disrupted recombinant virus R4009 over another recombinant virus R3616 to function as an oncolytic agent. The survival rate depends on the dosage of these viruses, which have therapeutic use in treatment of brain tumors.

Individuals of child-bearing age, who contract the herpes simplex virus infection, vertically transmit the virus to their offspring, leading to neonatal herpes simplex virus infection in the child. Drugs such as vidarabine and acyclovir are used in neonatal herpes treatment and development of vaccines are underway.

The pyridinone non-nucleoside reverse transcriptase inhibitor L-967,661 shows significant dose-related activity against HIV-1 and is also well tolerated by patients, but the rapid emergence of resistant strains of the virus may limit the effectiveness of this and other non-nucleoside reverse transcriptase inhibitors. The non-nucleoside reverse transcriptase inhibitors are atypical antiretroviral agents with selective activity in vitro against human immunodeficiency virus type 1 (HIV-1). They perform through direct inhibition of reverse transcriptase and are not incorporated into DNA. However, in vitro studies have indicated additive or synergistic activity between nucleoside and non-nucleoside antiretroviral agents. These agents may continue to be useful in combination regimens. When the genetic complexity of the virus is extensive and subpopulations of resistant virus are more probable, the use of non-nucleoside agents for very early infection or post-exposure prophylaxis may be especially beneficial.

Acyclovir has been used for approximately 10 years to treat patients with infections caused by herpes virus. It interferes with the replication of herpes simplex virus (HSV) and varicella-zoster virus, the virus that causes chickenpox. Several different forms of acyclovir are available. It has been effective for the treatment of patients with genital herpes, but not for those with oral herpes. Immunocompromised children with chickenpox are treated with acyclovir to prevent complications. It is also used to prevent cytomegalovirus disease in transplant recipients and to treat infections caused by Epstein-Barr virus. HSV and varicella-zoster virus can become resistant to acyclovir over time, especially in AIDS patients. Very few side effects have been reported for acyclovir, but it rarely may cause reversible kidney impairment and disturbances of the central nervous system.

Chickenpox is one of the more common childhood diseases. It is caused by the varicella-zoster virus. About 3.5 million cases of chickenpox are thought to occur in the US each year; about 4,500 patients require hospitalization. Complications are not common, but chickenpox may lead to secondary bacterial infection of the skin, inflammation of the lungs, cerebellar ataxia (an abnormality of gait resulting from effects on the cerebellum), and encephalitis. The death rate for otherwise healthy children with chickenpox is about 1 in 50,000. The antiviral drug acyclovir has been used successfully to treat varicella infections in normal adults and immunocompromized patients. A study has now been conducted to evaluate the effectiveness of acyclovir in treating normal children with chickenpox. A total of 815 children with chickenpox were randomly assigned to receive treatment with acyclovir or placebo within the first 24 hours of the appearance of the symptomatic "pocks". The children treated with acyclovir had fewer lesions than the children treated with placebo, with an average of 294 versus 347 lesions, respectively. Furthermore, over 95 percent of the children treated with acyclovir stopped developing new skin lesions by the fourth day of infection. In contrast, one-fifth of the placebo-treated children continued to develop new lesions after day five. Four children in the acyclovir group and six in the placebo group developed bacterial infections as a complication of chicken pox. One case of cerebellar ataxia was noted in the placebo group. The incidence of complications was too small, however, to draw any conclusions. Although the results clearly show that acyclovir reduces the severity and the duration of chickenpox, it remains uncertain if the rate of complications is also decreased by acyclovir treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

The gene disignated [γ.sub.1]34.5 maps in the inverted repeats flanking the long unique sequence of herpes simplex virus-1 (HSV-1) DNA, and therefore it is present in two copies per genome. [...]

In a review of viral encephalitis, author Richard J. Whitley discusses the many aspects of this disease. More precisely, he discusses the aspects of these diseases, since a wide variety of different viruses may infect the brain. Some, like rabies, essentially affect only the brain; most encephalitis is the result of a common virus, like herpes simplex or measles, which infects the brain only occasionally. Different viruses take different routes into the brain, but most are carried by the blood, and are often transmitted by a mosquito. It is not always clear how viruses cross the blood-brain barrier, which protects the brain from unwanted elements in the blood. Recently the AIDS virus has joined the ranks of viruses infecting the brain. While the pathological picture is different from classic encephalitis viruses like herpes simplex, AIDS encephalitis manages to produce dementia in virtually all patients by the time of death. (Consumer Summary produced by Reliance Medical Information, Inc.)

Objective. During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made. Design/Methods. Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported. Results. Comparisons between patients treated in the periods between 1981-1988 and 1989-1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of ([is greater than or equal to])10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy. Conclusion. Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981-1988 vs 1989-1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within. Pediatrics 2001;108:223--229; newborn, herpes simplex virus, acyclovir., ABBREVIATIONS. HSV, herpes simplex virus; CNS, central nervous system; SEM, skin, eyes, or mouth; NIAID, National Institute of Allergy and Infectious Diseases; CASG, Collaborative Antiviral Study Group; CSF, cerebrospinal fluid; [...]

Objective. The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. Participants. Infants who were [is less than or equal to] 28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses. Methods. The study was an open-label evaluation of intravenous acyclovir at dosages higher than the 30 mg/ kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) acyclovir (45 mg/kg/d), and the next 72 patients received HD acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) acyclovir for 10 days and in which identical methods (with the exception of acyclovir dosage and duration of therapy) were used. Results. Six (21%) of 29 HD acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count [is less than] 500/[mm.sup.3], and 5 patients had an absolute neutrophil count (ANC) between 500/[mm.sup.3] and 1000/[mm.sup.3]. In all 6 cases, the ANC recovered during continuation of acyclovir at the same dosage or after completion of acyclovir therapy, and there were no apparent adverse sequelae of the transient neutropenia. No other drug-related adverse events were reported among ID or HD recipients, and no other laboratory aberrations could be correlated specifically with antiviral therapy. The survival rate for the patients with disseminated HSV disease treated with HD acyclovir was significantly higher than for those in the previous study treated with SD acyclovir, with an odds ratio (OR) of 3.3 (95% confidence interval [CI]: 1.4-7.9). For patients with CNS disease, however, survival rates were similar for the HD and SD groups. To assess the effect of HD acyclovir on survival for the entire population with neonatal HSV disease, the Cox proportional hazards regression analysis was performed with stratification for disease category (CNS versus disseminated). In performing this analysis, differences in mortality for each disease category were weighted to allow statistical comparison of the treatment dosage groups (HD, ID, and SD). This analysis indicated that the survival rate for patients treated with HD acyclovir was statistically significantly higher than for patients treated with SD acyclovir (OR: 3.3; 95% CI: 1.5-7.3). Recipients of HD acyclovir had a borderline significant decrease in morbidity compared with SD recipients, after stratification for the extent of disease (SEM vs CNS vs disseminated) and controlling for the potential confounding factors of HSV type (HSV-1 vs. HSV-2), prematurity, and disease severity (seizures). Patients treated with HD acyclovir were 6.6 times (adjusted OR; 95% CI: 0.8-113.6) as likely to be developmentally normal at 12 months of age as patients treated with SD therapy. Conclusion. These data support the use of a 21-day course of HD (60 mg/kg/d) intravenous acyclovir to treat neonatal CNS and disseminated HSV disease. Throughout the course of HD acyclovir therapy, serial ANC determination should be made at least twice weekly. Decreasing the acyclovir dosage or administering granulocyte colony-stimulating factor should be considered if the ANC remains below 500/[mm.sup.3] for a prolonged period. Pediatrics 2001;108:230-238; newborn, herpes simplex virus, acyclovir., ABBREVIATIONS. HSV, herpes simplex virus; ID, intermediate-dose; HD, high-dose; SD, standard-dose; CNS, central nervous system; SEM, skin, eyes, or mouth; CASG, Collaborative Antiviral Study Group; CSF, cerebrospinal fluid; OR, odds [...]

Transmissible spongiform encephalopathies (TSEs) are a family of rare, slowly progressive, and universally fatal neurodegenerative syndromes affecting animals and humans. Until recently, TSEs were of little interest to pediatricians. However, since the outbreak in adolescents and the association of TSEs with new-variant Creutzfeldt-Jakob disease (nvCJD), interest among pediatricians and the general public has increased. Even before bovine spongiform encephalopathy and nvCJD were linked, the recognition that iatrogenic Creutzfeldt-Jakob disease (CJD) had been acquired from administration of cadaveric human growth and gonadotropic hormones and from corneal and dura mater transplants prompted medical vigilance. Furthermore, recent concern about the potential for transmission of CJD by blood and blood products has raised awareness among public health and regulatory agencies, pediatricians, and the public, although no epidemiologic data support this concern. Because of worldwide concern (although no cases have been reported in North America), this review focuses on the potential impact of TSEs, particularly CJD and nvCJD, on the pediatric population., ABBREVIATIONS. TSEs, transmissible spongiform encephalopathies; PrP, prion protein; TME, transmissible mink encephalopathy; BSE, bovine spongiform encephalopathy; nvCJD, new-variant Creutzfeldt-Jakob disease; CJD, Creutzfeldt-Jakob disease; CSF, cerebrospinal fluid; EEG, electroencephalogram; FDA, US [...]

Genetically engineered, neuroattenuated herpes simplex viruses (HSVs) expressing various cytokines can improve survival when used in the treatment of experimental brain tumors. These attenuated viruses have both copies of [sub.[Gamma]1]34.5 deleted. Recently, we demonstrated increased survival of C57BL/6 mice bearing syngeneic GL-261 gliomas when treated with an engineered HSV expressing IL-4, as compared with treatment with the parent construct ([sub.Gamma]1][34.5.sup.-]) alone or with a virus expressing IL-10. Herein, we report construction of a conditionally replication-competent mutant expressing both subunits of mIL-12 (M002) and its evaluation in a syngeneic neuroblastoma murine model. IL-12 induces a helper T cell subset type 1 response, which may induce more durable antitumor effects. In vitro studies showed that, when infected with M002, both Vero cells and murine Neuro-2a neuroblastoma cells produced physiologically relevant levels of IL-12 heterodimers, as determined by ELISA. M002 was cytotoxic for Neuro-2a cells and human glioma cell lines U251MG and D54MG. Neurotoxicity studies, as defined by plaque-forming units/[LD.sub.50], performed in HSV-1-sensitive A/J strain mice found that M002 was not toxic even at high doses. When evaluated in an intracranial syngeneic neuroblastoma murine model, median survival of M002-treated animals was significantly longer than the median survival of animals treated with R3659, the parent [sub.[Gamma]1][34.5.sup.-] mutant lacking any cytokine gene insert. Immunohistochemical analysis of M002-treated tumors identified a pronounced influx of [CD4.sup.+] T cells and macrophages as well as [CD8.sup.+] cells when compared with an analysis of R3659-treated tumors. We conclude that M002 produced a survival benefit via oncolytic effects combined with immunologic effects meditated by helper T cells of subset type 1.

The diagnosis of diseaes which mimic herpes simplex encephalitis is studied. A total of 432 patients had tissue samples taken from the brain to test for herpes simplex encephalitis. Three groups of patients were identified. The first group (195 patients) had a diagnosis of herpes simplex encephalitis proven by their brain tissue sample. The second group (95 patients) had diseases that were identified as other than herpes simplex encephalitis; 38 of these patients had treatable diseases, 40 had non-treatable but diagnosed viral infection, and 17 had identified diseases that were neither treatable nor caused by viruses. The third group of 142 people could not be diagnosed even after the brain tissue sample. When these patients came to medical attention their symptoms and appearances were similar. The patients most likely to have full recoveries were those in the subgroup with nontreatable but diagnosed viral infections., ABSTRACT: A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.

Intraocular ganciclovir implants in combination with oral ganciclovir may benefit some AIDS patients with cytomegalovirus retinitis. Cytomegalovirus retinitis is a viral infection of the retina. A 1999 study found that oral ganciclovir in addition to intraocular ganciclovir not only prevented the disease from spreading to the other eye but also to other organs. Unfortunately, oral ganciclovir can suppress the immune system, whereas intraocular ganciclovir does not. The study also found that patients who were taking protease inhibitors for their HIV infection were also less likely to experience a progression of their retinitis.