Sweet's syndrome as an initial manifestation of pediatric human immunodeficiency virus infection.

We report a 3-month-old infant in whom Sweet's syndrome was a presenting manifestation of pediatric human immunodeficiency virus infection. Although rare in children, Sweet's syndrome may be associated with certain infections and malignancies. The diagnosis of Sweet's syndrome in a child should always prompt a thorough evaluation to assess for an associated systemic disease.

Immunization with recombinant varicella-zoster virus expressing herpes simplex virus type 2 glycoprotein D reduces the severity of genital herpes in guinea pigs.

Varicella-zoster virus (VZV) is an attractive candidate for a live-virus vector for the delivery of foreign antigens. The Oka vaccine strain of VZV is safe and effective in humans, and recombinant Oka VZV (ROka) can be generated by transfecting cells with a set of overlapping cosmid DNAs. By this method, the herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) gene was inserted into an intergenic site in the unique short region of the Oka VZV genome. Expression of gD2 in cells infected with the recombinant Oka strain VZV (ROka-gD2) was confirmed by antibody staining of fixed cells and by immunoblot analysis. Immune electron microscopy demonstrated the presence of gD2 in the envelope of ROka-gD2 virions. The ability of ROka-gD2 to protect guinea pigs against HSV-2 challenge was assessed by inoculating animals with three doses of uninfected human fibroblasts, fibroblasts infected with ROka VZV, or fibroblasts infected with ROka-gD2. Neutralizing antibodies specific for HSV-2 developed in animals immunized with ROka-gD2. Forty days after the third inoculation, animals were challenged intravaginally with HSV-2. Inoculation of guinea pigs with ROka-gD2 significantly reduced the severity of primary HSV-2 infection (P < 0.001). These experiments demonstrate that the Oka strain of VZV can be used as a live virus vector to protect animals from disease with a heterologous virus.

Herpes simplex virus infections in children.

This paper focuses on the advances that have been made in our understanding of the pathogenesis, diagnosis, treatment, and prevention of herpes simplex virus (HSV) infections. Insights have been gained into the immune defense mechanisms that may be active in protecting the fetus from HSV infection. An animal model that closely mimics human neonatal HSV disease may permit exploration of novel interventional strategies. Brain biopsy for the diagnosis of HSV encephalitis has been supplanted by polymerase chain reaction detection of HSV DNA in the cerebrospinal fluid and, to a lesser extent, by detection of intrathecal HSV-specific antibodies. Prolonged immune activation within the nervous system following HSV encephalitis has been demonstrated and may implicate immune activation in the pathogenesis of HSV-induced neurologic damage. The continuing emergence of antiviral drug resistance further underscores the need for new strategies for treatment and prevention of HSV infections.

Quantity of latency-associated transcript produced by herpes simplex virus is not predictive of the frequency of experimental recurrent genital herpes.

The role of the latency-associated transcript (LAT) in control of recurrent herpes simplex virus type 2 (HSV-2) infection was investigated by examining whether LAT concentration in vitro during productive infection or in ganglia during latency correlated with frequency of recurrent genital herpes. Clinical HSV-2 isolates from frequent or infrequent recurrent genital disease produced comparable amounts of glycoprotein D and infected cell polypeptide 0 RNA, but the isolate from frequent disease produced about seven times more LAT. The guinea pig model of genital herpes was used to determine whether the quantity of LAT produced during acute infection in vitro correlated with recurrence phenotype; the frequency of recurrent disease was similar for the 2 clinical isolates. Likewise, there was no correlation between the recurrence phenotype of individual animals and LAT concentration in their ganglia. Thus, while absence of LAT may impair HSV reactivation and recurrence, once a threshold concentration is exceeded, LAT has no further effect on recurrence frequency.

Herpes simplex viremia: report of eight pediatric cases and review of the literature.

Bloodstream infection due to herpes simplex virus (HSV) is rare in the immunocompetent host but may be important in the pathogenesis of disseminated HSV infection in the immunocompromised patient. Using a simple blood-culture method, we detected herpes simplex viremia in eight immunologically compromised or immature children: two neonates, two oncology patients, and four transplant recipients. Only two patients initially exhibited evidence of mucocutaneous HSV infection. Blood was cultured for HSV because of perinatal exposure, for routine surveillance, or for the evaluation of fever, esophagitis, or oral lesions in immunocompromised patients. In five cases HSV was recovered only from the blood; in two other instances blood cultures for HSV were the first positive cultures. The time required for the detection of HSV by blood culture ranged from 1 day to 12 days. In one case viremia was transient and cleared without specific therapy. The other seven cases were treated with intravenous acyclovir; in four of these cases, therapy was initiated because of the positive blood culture. The detection of HSV in blood may promote early initiation of antiviral therapy and thereby improve prognosis.

Detection of varicella-zoster virus DNA in nasopharyngeal secretions of immune household contacts of varicella.

Persons immune to varicella-zoster virus (VZV) are not at risk for developing clinical infection after exposure to varicella. However, the extent to which they might serve as vectors for the transmission of VZV to others is not known. Information in this regard would be important in establishing hospital infection control policies, especially in relation to the care of immunocompromised hosts. A polymerase chain reaction-based detection system was used to detect the presence of VZV DNA in the nasopharyngeal secretions of household contacts of children with varicella. VZV DNA was identified in 4 of 5 immune adults and 1 susceptible sibling when sampled within 3 days of recognition of a household case of varicella. Further investigations are needed to determine whether this represents a limited window of VZV replication in the nasopharynx of immune persons during which they may serve as vectors of VZV.

Animal models of varicella.

Varicella-zoster virus (VZV) is highly species-specific and has been demonstrated to naturally infect only humans and great apes. Simian varicella, a group of antigenically related agents distinct from VZV, infects cercopithecoids producing severe varicella-like disease but does not infect humanoids. Seroconversion following inoculation of VZV in small laboratory animals has been demonstrated in the rat, rabbit, and guinea pig; however, animal-to-animal spread, viremia, and exanthem have been demonstrated only in guinea pigs. Both humoral and cellular immune responses to VZV infection have also been examined in the guinea pig model. Ocular infection with VZV has been explored in both the guinea pig and rabbit. Animal models of VZV persistence have been elusive although persistence may be established in the rat.

Varicella in hairless guinea pigs.

A high proportion of depilated newborn or euthymic congenitally hairless adult guinea pigs develop an erythematous papular exanthem during infection with varicella-zoster virus (VZV) previously cultivated in guinea pig cell culture. Virus has been demonstrated in tissues during varicella using polymerase chain reaction amplification and nucleic acid hybridization methods. The frequency of exanthem expression can be reduced by the prophylactic administration of VZV convalescent-phase guinea pig serum. This model should prove useful for further study of VZV pathogenesis as well as for testing putative antiviral compounds.

Epizootic guinea pig herpes-like virus infection in a breeding colony.

A breeding colony of strain-2 guinea pigs which had been relatively free of indigenous caviid herpesviruses experienced an explosive outbreak of guinea pig herpes-like virus apparently as a consequence of intermixing groups and contamination of the water supply. A new breeding colony has been established and has been maintained apparently free of recognized caviid herpesviruses.

Detection of Pseudomonas mesophilica as a source of nosocomial infections in a bone marrow transplant unit.

Pseudomonas mesophilica was isolated from fungal blood cultures of two bone marrow transplant recipients who consecutively occupied the same room. The isolation of P. mesophilica was temporally associated with febrile illness in these two granulocytopenic patients at 1 and 3 weeks posttransplant. A third patient, housed separately on the same bone marrow transplant unit, had nasopharyngeal colonization by this organism. Epidemiologic risk factors in common included staff, medications, and oral and perineal irrigations with tap water. Surveillance cultures detected P. mesophilica in none of 24 pharmaceutical preparations and in 10 of 40 tap water samples (100 to 600 CFU/ml) from implicated and control rooms on the same floor. Antimicrobial susceptibility testing of 14 patients and environmental isolates by agar dilution revealed similar profiles; some environmental isolates exhibited higher MICs. Because of restrictive nutritional and temperature requirements, P. mesophilica is undetected by many clinical laboratory protocols and may represent a previously undetected source of febrile illness in neutropenic patients.