[Molecular epidemiology of herpes simplex virus and geographic localization of a variant of herpes simplex virus type 1].
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Chronic cutaneous herpes simplex virus infection is described in a 68-year-old man who was immunocompromised because of chronic lymphocytic leukemia. The herpes infection was not amenable to therapy with acyclovir. Clinical isolates of herpes simplex virus were assessed for viral thymidine kinase activity, which was markedly decreased in two isolates. By the method of viral plaque autoradiography, these isolates were determined to be composed primarily of mutant thymidine kinase-negative herpes simplex virus mixed with occasional standard thymidine kinase-positive herpes simplex virus. Viral plaque autoradiography permitted the quantitation of proportions of thymidine kinase-negative and thymidine kinase-positive herpes simplex virus in the mixed virus populations. The chronic cutaneous infection persisted, unlike other reported infections by thymidine kinase-negative herpes simplex virus.
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OBJECTIVE: To determine the efficacy of daily suppressive therapy with a 1-g dose of valacyclovir in reducing total (clinical and subclinical) herpes simplex virus 2 (HSV-2) shedding compared with placebo in Immunocompetent patients diagnosed as having recurrent HSV-2 genital herpes. PATIENTS AND METHODS: From June 18, 2004, to December 17, 2004, patients from 27 US sites with a history of 6 or more genital herpes recurrences per year were randomized in a 3:1 ratio to receive 1 g/d of valacyclovir or placebo. During the double-blind suppressive therapy, patients were provided with the study drug (500-mg valacyclovir caplets or matching placebo) and Instructed to take 2 caplets once daily without regard to meals for 60 days. Daily genital and anal or rectal swabs were self-collected during the 60-day study period for evaluation of HSV-2 viral shedding as determined by quantitative type-specific polymerase chain reaction assay. RESULTS: One hundred fifty-two patients were randomized into this study, 43 to placebo and 109 to 1 g/d of valacyclovir. A total of 134 completed the study (40 placebo [93%], 94 valacyclovir [86%]), and 18 prematurely withdrew (3 placebo [7%], 15 valacyclovir [14%]). Valacyclovir significantly reduced the percentage of days with total (clinical and subclinical) HSV-2 shedding throughout 60 days compared with placebo. In the intent-to-treat population, a 71% reduction in total shedding (P < .001), a 58% reduction in subclinical shedding (P < .001), and a 64% reduction in clinical shedding (P = .01) were observed. Valacyclovir was not associated with any significant toxic effects compared with placebo. CONCLUSION: This study demonstrated that 1 g/d of valacyclovir administered for 60 days was generally well tolerated and was an effective suppressive therapy that significantly reduced total (clinical and subclinical) HSV-2 shedding compared with placebo in immunocompetent patients diagnosed as having recurrent HSV-2 genital herpes.
Large papillomatous lesions clinically resembling verrucous carcinoma may be caused by viruses other than human papillomavirus. We report a case of recurrent vegetations covering the entire vulva in a pregnant patient with common variable immunodeficiency. Herpes simplex virus was recovered from these lesions. The patient did not respond to intravenous acyclovir, but her lesions dramatically healed with two courses of intravenous foscarnet. Repeated biopsies may prove necessary in cases such as this to ensure proper diagnoses.
Diagnosis of herpes simplex encephalitis in the acute stage is based on clinical symptoms (nonspecific prodromi, neuropsychological deficits, epileptic seizures) in combination with typical CSF abnormalities (lymphomonozytic pleocytosis) and MR imaging abnormalities assumed to be typical for herpes simplex encephalitis (increased fluid-attenuated inversion recovery and T2 hyperintensities in the mesiotemporal lobe region). Definite diagnosis of herpes simplex encephalitis is based on positive polymerase chain reaction in the CSF, usually available some days after hospital admission. Suspected herpes simplex encephalitis requires immediate treatment with acyclovir. Bacterial encephalitis caused by spirochetes may present with similar features but requires different treatment. This should therefore be considered in the differential diagnosis of herpes simplex encephalitis. We report a young patient with neurosyphilis whose correct diagnosis could be made only several days after beginning specific treatment.
Herpes simplex viruses of the so-called intermediate types were typed by analysis of virus-specific proteins of the infected cells. The results obtained correlate well with the results of typing of these strains by DNA analysis using restriction endonucleases. Strain differences of virus-specific proteins of herpes simplex virus of both types were established.
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Viral factors responsible for HSV neurovirulence in humans are still unknown. The aim of this work was to investigate the hypothesis that viral variants might contribute to the specific neurovirulence of some HSV strains. HSV-1 DNA was recovered from cerebrospinal fluid (CSF) in ten patients with HSV encephalitis (HSE) and the regions of HSV-1 gD gene corresponding to known antigenic sites were analyzed by direct sequencing of PCR products. Twenty-two mutations were found among a total of 6580 bp analyzed over a portion of 1000 bp of gD gene, of which 20 were silent whereas two conferred amino acid substitution. One missense mutation (E117D) was found in two CSF samples as well as in two control laboratory strains. The other one (A269T) was found in a single CSF sample, and lies within a region corresponding to a functionally essential antigenic site. These are the first mutations of the gene encoding gD of HSV identified in vivo in human encephalitis samples. Overall, the results argue against the role of gD in neurovirulence in humans.
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Herpes simplex viruses type 1 (buccal) and type 2 (genital) present a serious threat to neonates. Infection may occur in utero, by transplacental or ascending infection, by exposure to genital lesions during delivery, or postnatally from relatives or attendants. Antiviral drugs, vidarabine and acyclovir are of equal efficacy and toxicity when used in infants with herpes simplex infections. Transplacental infection during early pregnancy is a very rare cause of congenital abnormality but there have been no recommendations for intervention. Most neonatal infections are acquired from the mother during delivery. Antepartum screening for virus excretion is of no value in predicting exposure at delivery and should not be performed. Caesarean section should be reserved for women who have active lesions at delivery. Even if active lesions are present, in women with a history of recurrent herpes, the risks to the infant are low. Prophylactic acyclovir during pregnancy cannot be recommended until evidence of safety and efficacy has been obtained from controlled trials. Staff should be alert to the dangers of postnatal infection and measures should be taken to exclude, or reduce virus excretion from, staff members or visitors who have orolabial or cutaneous herpes lesions.
Genital herpes simplex infection remains an infectious disease having widespread consequences for both adult and neonatal populations. Physicians must understand that the psychologic impact of genital HSV infections frequently is more disabling than the physical manifestations. Sensitivity, compassion, and support are necessary from members of the medical community, and psychologic counseling may help patients cope with HSV and all its implications. Similarly, physicians must downplay the hysteria that has been associated with herpesvirus infections, emerging as a result of intense media coverage in the 1970s and 1980s. Minimizing the number of cases of neonatal herpes through identification of infected women during parturition continues to be important. Recent guidelines suggest a rationale for the management of women at risk for genital HSV. Nevertheless, until newer immunologic and serologic techniques become clinically reliable and allow a correct and rapid diagnosis of herpes simplex infection, identification of the infected woman in labor must be made using detailed clinical history, physical examination, and viral culture.
Herpes simplex virus type 1 and type 2 cause a wide range of illnesses ranging from minor cold sores to severe necrotising encephalitis or disseminated systemic infections seen in immunocompromised patients including neonates. Following primary infection, the virus is not eradicated from the body but is latent in sensory nerve ganglia where it can reactivate and cause recurrent disease. Aciclovir is the most studied and used antiviral agent with activity against herpes simplex virus infections. In most situations the use of aciclovir shortens the duration of clinical illness and viral shedding and reduces morbidity and mortality. All life- or sight-threatening infections should be managed in an inpatient hospital setting with intravenous therapy. The use of oral aciclovir is recommended in patients with non-life-threatening illness who may still have significant symptoms.
INTRODUCTION: Herpes simplex encephalitis (HSE) is the most common cause of infectious encephalitis at all ages. The usual presentation includes a high temperature, headache and confusion associated with convulsions and signs of a focal neurological deficiency. The typical findings shown by magnetic resonance imaging (MRI) consist of hyperintense lesions, in T2 and FLAIR sequences, especially in the medial and inferior temporal lobe. AIMS. The aim of this paper is to report a case of HSE that associated a cerebral haematoma (CH) in its clinical course. CASE REPORT: A 69 year old female patient who was admitted to hospital because of a syndrome of high temperature, confusion and urinary infection. Studies of the cerebrospinal fluid showed only a slight pleocytosis, and a polymerase chain reaction (PCR) for the herpes simplex virus (HSV) was required. Initial MRI scanning showed an image that was compatible with cerebritis in the left parieto occipital lobe. A later RMI scan revealed a cerebral haematoma in the left parieto occipital lobe, together with new haemorrhagic foci in the bifrontal and in the right temporal lobes. The haematoma was drained surgically and empirical therapy was begun with acyclovir, and later a positive HSV PCR was received. The patient responded favourably to the therapy and was discharged from hospital. DISCUSSION: A variety of atypical presentations in HSE have been reported. Our case presented scant pleocytosis, infrequent lesion topography and coursed with CH. Only a few cases of this last occurrence have been reported in the literature. CONCLUSION: The presence of infrequent features, such as CH, within the framework of the clinical features of encephalopathy cannot exclude the possible existence of HSE.
In herpes simplex encephalitis (HSE), simultaneous electro-encephalogram (EEG) and evoked potential studies have not been reported, although EEG changes have been described. In this communication, EEG, somatosensory and motor evoked potentials have been reported in 9 patients with HSE. The patients' age ranged between 2 and 70 years and 3 were females. Seven patients had seizures, CT scan was abnormal in 6 and MRI in remaining 3 patients. Seven patients received acyclovir therapy; one patient died and 6 had poor outcome. The initial EEG was carried out within 5 days of ictus and was abnormal in all the patients. The EEG abnormalities included frontotemporal delta slowing in 5, periodic lateralised epileptiform discharge in 3, runs of spike and periodic activity in one patient each. At 3 months, EEG was normal in 6 patients but it did not correlate with clinical recovery. Central motor conduction time (CMCT) to upper limb and median somatosensory evoked potential (SEP) were normal in all. CMCT to lower limbs and tibial SEPs were unrecordable in one patient who had wide spread herpes simplex virus (HSV-1) infection associated with AIDS, and died on 18th day of illness. From this study, we conclude that EEG although is frequently abnormal and may provide useful diagnostic information in a setting of encephalitis but evoked potential changes are infrequent; and if present an association of HIV infection should be considered.
Neonatal herpes simplex encephalitis (HSE) can represent a difficult diagnostic problem when it occurs without concomitant mucocutaneus lesions and usually requires brain biopsy for diagnosis. Asymptomatic for the initial 2 to 4 weeks of life, the three infants we describe with localized HSE came to medical attention only because they developed persistent seizures and other nonspecific symptoms. Lumbar spinal fluid obtained from these children at clinical presentation showed an encephalitic pattern. Radionuclide brain scans revealed focal uptake of isotope in a variety of cortical areas, and electroencephalograms (EEGs) demonstrated repetitive, high amplitude, polyphasic sharp waves arising from analogous regions. Computed tomography (CT) showed nonspecific ill-defined areas of low density or contrast enhancement that did not correlate well with radionuclide, EEG, or clinical findings in two neonates. No infant had predominant temporal lobe involvement. Because these data suggested a multifocal, encephalitic process, all three infants underwent brain biopsy. A widespread infiltration of leukocytes and macrophages was observed in each specimen, and abundant intranuclear inclusions were present. Electron microscopy revealed abundant herpesvirus particles, and herpes simplex virus (HSV) was subsequently isolated from each sample. From our observations and our review of the literature, we propose the following criteria as indications for brain biopsy: Brain biopsy is warranted to rule out HSE when a neonate presents with seizures, cerebrospinal fluid mononuclear pleocytosis with a negative gram stain, and focal, cortical disease on EEG and radionuclide scan.(ABSTRACT TRUNCATED AT 250 WORDS)