Biomedical subjects

L R Stanberry

Publications and source records attributed to L R Stanberry.

At least 55 records · Page 3Linked to original sources

PubMed1996

Effect of age and route of inoculation on outcome of neonatal herpes simplex virus infection in guinea pigs.

The morbidity and mortality of neonatal herpes simplex virus infection remains unacceptably high despite antiviral therapy. A better understanding of factors that might contribute to this poor outcome is needed but has been hindered by a lack of a good animal model. The recently described guinea pig model of neonatal HSV-2 infection was used to explore the effect of age and route of inoculation on the outcome of infection. After intranasal inoculation the onset, extent, and severity of the primary disease, as well as the number of recurrent lesion days, varied inversely with age. The route of inoculation also affected the outcome. Newborn animals were inoculated either intradermally on the scalp or by the intranasal, oral or corneal route. Animals inoculated on the scalp had the best outcome with no deaths or evidence of neurologic disease while the intranasal route produced the most severe disease, 88% mortality. Neurologic disease was common after oral (41%) and corneal (56%) inoculation but resolved spontaneously whereas following intranasal (39%) inoculation all animals with neurologic disease died. Recurrent disease manifest by cutaneous lesions was observed in all survivors of each group but also differed by the route of inoculation. The guinea pig model of neonatal HSV-2 disease appears to mimic human disease. The studies presented here show that the outcome of infection is influenced by the age and route of inoculation.

Age Factors↗

PubMed1996

DNA immunization confers protective immunity on mice challenged intravaginally with herpes simplex virus type 2.

The immunogenicity and protective efficacy of a nucleic acid vaccine encoding the herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) gene under the control of the CMV immediate early gene promoter was examined. Mice immunized three times by intramuscular injection with the vaccine developed an HSV specific IgG but not IgA antibody response detectable in both serum and vaginal secretions. In addition, antigen-specific cellular immune responses were detected in splenic lymphocytes isolated from DNA immunized animals. Immunization reduced virus replication in the genital tract following a lethal intravaginal HSV-2 challenge. Furthermore, symptomatic genital HSV disease was reduced in immunized mice and the animals were completely protected from death. We conclude that a nucleic acid vaccine expressing HSV-1 gD induced both humoral and cell mediated immune responses in mice which proved highly protective against disease following virus challenge.

Animals↗

PubMed1996

Effect of antibody alone and combined with acyclovir on neonatal herpes simplex virus infection in guinea pigs.

Neonatal herpes simplex virus (HSV) infection produces severe disease with unacceptable morbidity and mortality with current antiviral therapies. The effect of therapy with passive anti-HSV antibody and acyclovir was evaluated using a guinea pig model of neonatal HSV. Newborn animals were inoculated intranasally and treated with acyclovir (60 mg/kg/day) or antibody (or both), beginning on days 0, 2, or 3 after HSV-2 inoculation. Acyclovir alone was effective only when begun on day 0, and antibody alone was effective when begun on or before day 2. Only combination therapy was effective on day 3, reducing mortality from 82% (14/17) in controls to 44% (7/16; P < .05). Combined therapy also significantly reduced the duration of skin, eye, and mouth disease and respiratory symptoms but not recurrent disease. These data suggest that addition of antibody therapy to acyclovir may improve the outcome of neonatal HSV disease.

Acyclovir↗

PubMed1996

DNA immunization against experimental genital herpes simplex virus infection.

A nucleic acid vaccine, expressing the gene encoding herpes simplex virus (HSV) type 2 glycoprotein D (gD2) under control of the cytomegalovirus immediate-early gene promoter, was used to immunize guinea pigs against genital HSV-2 infection. The vaccine elicited humoral immune responses comparable to those seen after HSV-2 infection. Immunized animals exhibited protection from primary genital HSV-2 disease with little or no development of vesicular skin lesions and significantly reduced HSV-2 replication in the genital tract. After recovery from primary infection, immunized guinea pigs experienced significantly fewer recurrences and had significantly less HSV-2 genomic DNA detected in the sacral dorsal root ganglia compared with control animals. Thus, immunization reduced the burden of latent infection resulting from intravaginal HSV-2 challenge, and a nucleic acid vaccine expressing the HSV-2 gD2 antigen protected guinea pigs against genital herpes, limiting primary infection and reducing the magnitude of latent infection and the frequency of recurrent disease.

Animals↗

PubMed1996

Downstream regulatory elements increase acute and latent herpes simplex virus type 2 latency-associated transcript expression but do not influence recurrence phenotype or establishment of latency.

The role of putative promoter or activator sequences downstream of the herpes simplex virus type 2 latency-associated transcript (LAT) promoter and upstream of the LAT intron was investigated in vivo by constructing and evaluating mutant viruses with deletions in this region. The deletion of LAT promoter sequences upstream of the primary LAT transcript reduced levels of LAT expression during productive infections, compared with the LAT expression level of wild-type virus, and abolished LAT expression during latency. The deletion of the putative downstream regulatory elements reduced but did not eliminate LAT expression during productive and latent infections. The deletion of both regions almost completely eliminated acute LAT transcription, although additional acute LAT-region transcription directed by sequences upstream of either region was detected by reverse transcriptase PCR. The deletion of the downstream elements did not influence the ability of the virus to reactivate from latently infected guinea pigs relative to the ability of the wild-type virus to reactivate; thus, decreased LAT expression did not affect the frequency of recurrence. The deletion of both regions did not affect the ability of the virus to establish latency. We conclude that downstream regulatory elements are necessary for maximal acute LAT expression but do not constitute an independent promoter during latency and do not play an obvious role in the establishment of our reactivation from latency.

Animals↗

PubMed1995

Expression of the herpes simplex virus type 2 latency-associated transcript enhances spontaneous reactivation of genital herpes in latently infected guinea pigs.

The latency-associated transcript (LAT) is the only herpes simplex virus (HSV) gene product detectable in latently infected humans and animals. In this report, we show that a 624-bp deletion in the promoter of the HSV-2 LAT had no discernable effect on viral growth in tissue culture or in acute genital infection of guinea pigs, but impaired LAT accumulation and led to a marked decrease in spontaneous genital recurrences when compared with the behavior of wild-type and rescuant strains. Differences in the ability of the mutant to replicate, or in how readily it established or maintained latency did not account for this finding. Thus, HSV LAT expression facilitates the spontaneous reactivation of latent virus.

Acute Disease↗

PubMed1995

Parents, peers, and the acquisition of an STD. Developmental changes in girls.

PURPOSE: The purpose of this study was to examine the relationship between age and number of sexually transmitted diseases (STD) episodes in sexually active girls with their perceptions of the interpersonal implications of STD acquisition. METHODS: The sample consisted of 248 girls (mean age = 16.9 years); 74% had an STD history. Adolescents responded to statements using a five-point Likert scale regarding their interpersonal expectations, and rated the perceived prevalence of STD among their friends and among all adolescents. RESULTS: The results of logistic regression analyses indicated that older girls were less likely to tell their parents but did not perceive parental support differently than younger girls. Older girls were more likely to tell their partners and to be more embarrassed by the acquisition. Those with a greater number of STD episodes perceived the acquisition as a less negative event. Girls with a greater number of STD episodes perceived the prevalence of STD to be significantly greater among their friends and among all adolescents than those girls with fewer episodes. Overall, the perceived prevalence among friends (40%) was significantly lower than the perceived prevalence among teens in general (74%). CONCLUSIONS: Future research and practice in aiding adolescent girls to manage STD acquisition must incorporate developmental theory, and, when appropriate, methods to involve families while preserving privacy.

Adolescent↗

PubMed1995

Sexual histories of adolescent girls: comparison between interview and chart.

PURPOSE: The purpose of this study is to determine the reliability of sexual histories obtained from adolescents and the adequacy of chart documentation by providers of adolescent health care. METHODS: Responses to an interview by a female research assistant about sexual activity were compared to chart-documented sexual histories taken by physicians and nurse practitioners. The setting was an urban, hospital-based adolescent clinic. The subjects were 106 females, 15-18 years old; 82% were African-American and 18% Caucasian. RESULTS: Significant correlations between interview and chart were seen for information about menarche, age at first intercourse, number of sexually transmitted diseases (STDs), and number of sexual partners. Accuracy of reporting sexually transmitted infections varied according to the organism; HPV infection was underreported more than other infections. Chart documentation of sexual histories was inadequate. CONCLUSIONS: Adolescents generally provide reliable sexual histories, but health care providers may not be documenting these histories adequately.

Adolescent↗

PubMed1995

Herpes simplex virus vaccines as immunotherapeutic agents.

As persistent viruses can escape immune surveillance, chronic or recurrent disease can be a major problem. Only after nearly 60 years of work have recent reproducible data, using herpes simplex virus infection as a model for persistent viral disease, established that vaccine immunotherapy is effective in the treatment of such viral infections.

Animals↗

PubMed1995

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.

Acyclovir↗

PubMed1995

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.

Animals↗

PubMed1995

Strategies for coping with sexually transmitted diseases by adolescent females.

Coping strategies of adolescent girls in response to the acquisition of a sexually transmitted disease (STD) were evaluated. Perceptions of control over acquisition of an STD and emotional impact were assessed. The sample consisted of 177 adolescent girls recruited from their source of primary care (mean age = 16.8). There were no differences in the use of coping strategies by age group or STD history. Subjects used a wide variety of coping strategies; those who viewed the future acquisition of an STD more negatively used more strategies. Wishful thinking was used by most of the subjects, but was not felt to be helpful; despite this, adolescents with a previous STD were no less likely to use wishful thinking. It was concluded that adolescent health care providers must understand girls' responses to STD and help them develop effective coping skills to reduce the incidence of STD.

Adaptation, Psychological↗

PubMed1994

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.

Antiviral Agents↗

PubMed1994

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.

Adult↗

PubMed1994

Neonatal herpes simplex virus infection: pathogenesis and treatment in the guinea pig.

Intranasal inoculation of newborn guinea pigs with herpes simplex virus (HSV) resulted in local skin-eye-mouth (SEM), central nervous system (CNS), and disseminated infections with high but not universal mortality. Cutaneous HSV inoculation produced self-limited SEM infection without evidence of CNS or disseminated disease. HSV infection of the upper respiratory tract of the newborn guinea pig resulted in early spread to the CNS and frequent viral dissemination. The outcome of infection was favorably affected by treatment with acyclovir. Spontaneous cutaneous recurrences occurred in most survivors. The newborn guinea pig should provide a useful model to explore both the pathophysiology and control of neonatal HSV infection.

Acyclovir↗

PubMed1994

Knowledge of gonorrhea in adolescent females with a history of STD.

The purpose of this study is to examine how a previous infection with gonorrhea or another sexually transmitted disease (STD) will impact on patients' knowledge of gonorrhea. Adolescent girls were recruited from a primary-care adolescent clinic. Those with a history of an STD were overrecruited. Participants were given a standardized questionnaire regarding several symptoms and sequelae of STD. The results of this study revealed that girls (N = 248, mean age = 16.9 years) with a personal history of gonorrhea had more correct responses than those with no history of an STD, but they were not statistically different from those with a nongonococcal STD. No group had a mean correct score greater than 6.66 out of 13. Nearly two out of three participants reported that an individual had to always have one of four symptoms (discharge, pain on urination, rash, or sores) when there is a gonococcal infection. Overall, adolescents have an inaccurate foundation of knowledge regarding symptoms and sequelae of gonorrhea. Although those with a previous history of gonorrhea had higher mean scores than those with no history of an STD, they still identified the correct responses only half the time. Additionally, adolescents with a history of gonorrhea or another STD were no more likely to have identified the possibility of asymptomatic infection, despite several having only a history of asymptomatic infection.

Adolescent↗

PubMed1994

Reasons for condom utilization among high-risk adolescent girls.

Two hundred forty-eight adolescent girls responded to a list of 30 statements describing reasons for using and not using condoms. For 24 of the statements, most adolescents (> 70%) gave the same response regarding why they did or did not use condoms. Therefore, only the six remaining statements were used in further analyses. The relationship between the six statements and psychosexual history, condom use, and sexually transmitted disease (STD) history was examined. Those adolescent girls who had been sexually active longer were more likely to report lack of enjoyment as a reason that they did not use condoms (P < .03), and those adolescents who had been sexually active less time were more likely to report personal (P < .005) and partner (P < .0006) enjoyment of sex with condoms as a reason for using condoms. Longer relationships before intercourse were associated with having condoms available (P < .01) and partner insistence on their use (P < .02). Partner insistence on condom use was related to fewer episodes of sexually transmitted diseases (P = .03). These findings indicate the importance of relationship and partner variables in adolescent girls' perceptions of condom use.

Adolescent↗

PubMed1994

The concept of immune-based therapies in chronic viral infections.

Treatment of recurrent herpes simplex virus (HSV) infection with a vaccine was attempted as early as 1938. The concept of immune therapy is based on the premise that vaccine administration may augment host immunity, resulting in better control of the infection. The guinea pig model is useful in the study of recurrent HSV infection for several reasons. This animal model mimics human infection, with self-limited primary vulvovaginitis developing after inoculation with HSV. Despite a full range of host immune responses, the virus persists in a latent state within sensory ganglia. Periodically, the latent virus reactivates to produce recurrent genital infections. Use of the guinea pig model has made it possible to demonstrate that the administration of HSV glycoprotein vaccines to infected animals results in a significant reduction in the frequency and severity of recurrences. Studies demonstrate that a variety of factors influence the effectiveness of immunotherapy. These factors include not only immunogen and dose but also the route of administration, timing of treatment relative to primary infection, and adjuvant formulation. Investigations of HSV immunotherapy in the guinea pig model provide the first controlled experimental data indicating that vaccine administration to an infected host can favorably alter the natural history of a persistent infection.

Adjuvants, Immunologic↗