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Biomedical subjects

Anna Wald

Publications and source records attributed to Anna Wald.

At least 19 recordsLinked to original sources
PubMed2006

Frequent and asymptomatic oropharyngeal shedding of human herpesvirus 8 among immunocompetent men.

BACKGROUND: Little is known about the clinical and virologic manifestations of human herpesvirus (HHV)-8 infection in immunocompetent persons in the absence of malignancy. METHODS: A total of 46 human immunodeficiency virus-negative, HHV-8-seropositive men collected saliva daily, and 25 recorded 15 common symptoms daily (gastrointestinal, constitutional, and oropharyngeal) and absences from work or school. Quantitative polymerase chain reaction measured HHV-8 DNA in saliva. RESULTS: Some 44 (96%) of 46 men reported having sex with men (MSM). Of the 44 MSM, 27 (61%) had HHV-8 detected in saliva on > or = 1 day; heterosexual men also shed HHV-8. In analyses restricted to MSM, HHV-8 DNA was detected on 636 (22%) of 2897 days. Among MSM with HHV-8 detected in saliva, the median rate was 20% (range, 1%-100%), with 30% shedding on > 50% of days, and the median quantity was 4.5 log10 copies/mL (range, 2.0-7.3 log10 copies/mL). The quantity of HHV-8 shed was lower in nonwhites (P<.001) and younger participants (P=.03). The frequency of HHV-8 detection and quantity were correlated (r=0.62; P<.001). Symptoms were reported on 10 (9%) of 114 days when HHV-8 was present, compared with 78 (9%) of 830 days without (odds ratio, 0.93 [95% confidence interval, 0.30-2.88]; P=.9). CONCLUSIONS: HHV-8 is detected frequently and intermittently in the saliva of chronically infected immunocompetent MSM, but this infection is asymptomatic.

Adult↗
PubMed2006

Oral herpes simplex virus type 2 reactivation in HIV-positive and -negative men.

BACKGROUND: Previous studies using viral cultures rarely reported herpes simplex virus type 2 (HSV-2) isolation from the mouth. We sought to characterize oral HSV-2 shedding as detected by HSV DNA polymerase chain reaction among HSV-2-seropositive men. METHODS: Participants collected daily swabs from oral and anogenital areas for HSV detection with a quantitative polymerase chain reaction assay. RESULTS: A total of 109 HSV-2-seropositive men (59 of whom were human immunodeficiency virus [HIV] negative, and 50 of whom were HIV positive) were sampled for a median of 64 consecutive days. Forty-four (40.4%) had HSV-2 detected from oral swabs on at least 1 day. Oral HSV-2 was detected on 148 (2.3%) of 6,422 days, genital HSV-2 was detected on 1,110 (17%) of 6,505 days, oral HSV-1 was detected on 220 (5.5%) of 4,018 days, and genital HSV-1 was detected on 88 (2.2%) of 4,073 days. Oral HSV-2 shedding was never associated with an oral lesion, but it was often concurrent with genital HSV-2 shedding. Both oral and genital HSV-2 were detected on 90 (61%) of 148 days with oral HSV-2 shedding. Oral HSV-2 shedding occurred on 90 (8.2%) of 1,110 days with genital HSV-2 shedding, versus 58 (1.1%) of 5,316 days without genital HSV-2 shedding (P<.001). The HIV-positive men shed HSV-2 orally more frequently than did the HIV-negative men (odds ratio, 2.7 [95% confidence interval, 1.1-7.1]). CONCLUSIONS: Oral HSV-2 reactivation was common (especially among HIV-positive men), was always asymptomatic, and often occurred on days of genital HSV-2 reactivation.

Adult↗
PubMed2006

Management of herpes simplex virus type 2 infection in HIV type 1-infected persons.

Human immunodeficiency virus type 1 (HIV-1)-infected persons have high rates of herpes simplex virus type 2 (HSV-2) infection, ranging from 50% to 90% in studies of HIV-infected populations from different parts of the world. Genital herpes in persons with HIV type 1 (HIV-1) infection is associated with more-severe and chronic lesions, as well as increased rates of asymptomatic genital shedding of HSV-2. Nucleoside analogues (acyclovir, valacyclovir, and famciclovir) decrease the frequency and severity of HSV-2 recurrences and asymptomatic HSV-2 reactivation and are effective, safe, well-tolerated drugs in patients with HIV-1 infection. These anti-HSV drugs may result in additional clinical and public health benefits for persons with HIV-1 and HSV-2 coinfection by decreasing HIV-1 levels in the blood and genital tract. Given these benefits, HIV-1-infected persons should be routinely tested for HSV-2 infection using type-specific serologic tests. Persons with HSV-2 infection should be offered HSV-2 education and treatment options. Studies to quantify the potential clinical and public health benefits of treating individuals who have HIV-1 and HSV-2 coinfection with anti-HSV therapy are underway.

Antiviral Agents↗
PubMed2006

Knowledge of partners' genital herpes protects against herpes simplex virus type 2 acquisition.

BACKGROUND: Prospective studies of herpes simplex virus type 2 (HSV-2) infection in discordant couples have shown a low rate of transmission. However, unlike partners with genital herpes in prospectively monitored couples, most persons who transmit genital herpes are not aware of having the infection. METHODS: Because HSV has a short incubation period and most persons who acquire genital herpes can identify the transmitting partner, a time-to-event design was used to assess risks of HSV acquisition among patients with newly acquired genital herpes. RESULTS: Among 199 persons with laboratory-documented newly acquired genital herpes, the median duration of the sexual relationship with the transmitting partner was 3.5 months, and the median number of sex acts before transmission was 40. The median time to HSV-2 acquisition was greater among participants whose partners disclosed that they had genital herpes, compared with participants whose partners did not disclose their status (270 vs. 60 days; P = .03). In multivariate models, having a partner who disclosed that he or she had genital herpes remained a strong protective factor against genital HSV-2 acquisition (hazard ratio, 0.48 [95% confidence interval, 0.25-0.91]). CONCLUSION: These findings suggest that testing persons with HSV type-specific serologic assays and encouraging disclosure may result in a decreased risk of HSV-2 transmission to sex partners.

Adolescent↗
PubMed2006

Clinical correlates of index values in the focus HerpeSelect ELISA for antibodies to herpes simplex virus type 2 (HSV-2).

BACKGROUND: Clinical correlates of HerpeSelect ELISA index values are poorly understood. OBJECTIVES: This study was designed to determine the effects of time of infection, test variability, and antibody avidity on index values. STUDY DESIGN: Sera (N=313) from 81 patients with new HSV-2 infections and 236 sera from 32 patients with long-standing (median 11.3 years) HSV-2 were tested by HerpeSelect HSV-2 ELISA. High positive, low positive and negative controls were run on 42 test plates to establish test variability. RESULTS: Index values tended to rise after infection, peaking a median of 9-10 weeks post-infection (range 8-323 days). Of 32 patients with established HSV-2 infections, 7 (22%) had at least one low index value (>1.1 to < or =3.5), and one had a transient seroreversion event. Test variability of index values was substantially lower than inter- or intra-patient variability. Median antibody avidity was higher in sera with high versus low index values in established infections, but unrelated to index value in patients with early infections. CONCLUSIONS: Index values or index value changes are not absolute indicators of early versus established HSV-2 infection or solely a function of test variability. Low antibody avidity may contribute to low index values once infection is established.

Antibodies, Viral↗
PubMed2006

Repeat-region polymorphisms in the gene for the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related molecule: effects on HIV-1 susceptibility.

In 1716 individuals--801 human immunodeficiency virus (HIV)-1-seropositive individuals, 217 high-risk HIV-1-seronegative individuals, and 698 general HIV-1-seronegative individuals--from a Seattle cohort and a Multicenter AIDS Cohort Study cohort, the association between HIV-1 susceptibility and repeat-region polymorphisms in the gene for the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related molecule (DC-SIGNR) was investigated; 16 genotypes were found in the DC-SIGNR repeat region. The DC-SIGNR homozygous 7/7 repeat was found to be associated with an increased risk of HIV-1 infection (17.5% in high-risk HIV-1-seronegative individuals vs. 28.5% in HIV-1-seropositive individuals; P=.0015), whereas the DC-SIGNR heterozygous 7/5 repeat tended to be correlated with resistance to HIV-1 infection (35.5% in high-risk HIV-1-seronegative individuals vs. 27.6% in HIV-1-seropositive individuals; P=.0291). These findings suggest that DC-SIGNR polymorphisms may influence susceptibility to HIV-1.

Cell Adhesion Molecules↗
PubMed2006

Human herpesvirus 8 infection among adolescents in the REACH cohort.

OBJECTIVE: Human herpesvirus 8 (HHV-8) infection is common among children in areas where Kaposi sarcoma is endemic. Human herpesvirus 8 is uncommon in children but prevalent in adults at risk for human immunodeficiency virus (HIV) infection in the United States, including men who have sex with men (MSM) and women who engage in high-risk sexual behavior. We examined the prevalence and predictors of HHV-8 infection among adolescents with or at high risk for acquiring HIV infection. DESIGN: Cross-sectional analysis. SETTING: National study of HIV infection among adolescents in primary care. PARTICIPANTS: A total of 537 young adults practicing high-risk sexual behavior, of which 403 were women and 134 were men; among the 134 men, 75% were MSM. INTERVENTIONS: Detailed questionnaires and testing for serum antibodies to HHV-8. OUTCOME MEASURE: Detection of serum antibodies to HHV-8. RESULTS: Sixty (11.2%) of 537 young adults were HHV-8 seropositive, including 20 MSM (19.6%), 2 male heterosexuals (6.5%), and 27 female heterosexuals (8.2%). The prevalence of HHV-8 in HIV-positive MSM (17/74 [23.0%]) was twice as high as that in HIV-negative MSM (3/28 [10.7%]) (P = .18), but no characteristic predicted HHV-8 infection among MSM. In multivariate analysis, history of gonorrhea (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.4-5.7; P<.01), history of having sex with women (OR, 2.4; 95% CI, 1.1-5.3; P = .03), and African American race (OR, 3.4; 95% CI, 1.1-10.0; P = .03) were associated with HHV-8 infection among women. CONCLUSIONS: Human herpesvirus 8 is common among US adolescents practicing high-risk sexual behaviors. Sexual identity, race, and sexual behavior may influence the risk of infection with HHV-8 in women.

Adolescent↗
PubMed2006

Diagnostics for herpes simplex virus: is PCR the new gold standard?

Herpes simplex virus (HSV) is one of the most common, yet frequently overlooked, sexually transmitted infections. Since the type of HSV infection affects prognosis and subsequent counseling, type-specific testing to distinguish HSV-1 from HSV-2 is recommended. Although PCR has been the diagnostic standard for HSV infections of the central nervous system, until now viral culture has been the test of choice for HSV genital infection. However, HSV PCR, with its consistently and substantially higher rate of HSV detection, will likely replace viral culture as the gold standard for the diagnosis of genital herpes in people with active mucocutaneous lesions, regardless of anatomic location or viral type. Alternatively, type-specific serologic tests based on glycoprotein G should be the test of choice to establish the diagnosis of HSV infection when no active lesion is present. Given the difficulty in making the clinical diagnosis of HSV, the growing worldwide prevalence of genital herpes and the availability of effective antiviral therapy, there is an increased demand for rapid, accurate laboratory diagnosis of patients with HSV.

DNA, Viral↗
PubMed2006

Targeted prenatal herpes simplex virus testing: can we identify women at risk of transmission to the neonate?

OBJECTIVE: Potential strategies to prevent neonatal herpes include herpes simplex virus (HSV) serologic testing and counseling of pregnant women and rapid HSV polymerase chain reaction (PCR) testing of maternal genital secretions at delivery. The cost-effectiveness of these interventions would be improved if high-risk pregnancies could be easily identified for targeted testing. STUDY DESIGN: Washington State birth certificate data for all singleton live births from 1987 through 2002 were linked with infant death and hospital discharge data for birth and subsequent hospitalizations in a population-based case-control study of risk factors for neonatal herpes. A case was defined as an infant with a discharge diagnosis of HSV infection (International Classification of Diseases 9th edition [ICD-9] code 054.X) from birth admission or readmission within 30 days of life. Five controls per case were frequency matched to cases by year of birth. RESULTS: Ninety-one neonatal HSV cases were identified (8.4/100,000 live births). Risk factors for infection included maternal age younger than 25 years (adjusted odds ratio [aOR] = 1.9, 95% CI 1.1-3.3) and paternal age younger than 20 years or unknown (aOR = 1.7, 95% CI 0.7-3.7). Testing couples with either risk factor would require testing 36% of couples and could potentially prevent up to 60% of cases. Maternal history of genital herpes, fever during labor, and premature rupture of membranes were also associated with neonatal disease; using all risk factors identifiable at delivery would require screening 60% of pregnancies and identifying 84% of cases. CONCLUSION: Targeted HSV testing would miss a substantial proportion of neonatal herpes.

Case-Control Studies↗
PubMed2006

Maternal herpes simplex virus antibody avidity and risk of neonatal herpes.

OBJECTIVE: The objective of the study was to assess whether herpes simplex virus antibody avidity is associated with risk of transmission of herpes simplex virus to the neonate. STUDY DESIGN: We developed a novel herpes simplex virus type 1 avidity test based on the commercially available Focus HerpeSelect-1 enzyme-linked immunosorbent assay kit using sera from nonpregnant subjects with genital herpes simplex virus-1 infection. We used this test, and the previously developed herpes simplex virus type 2 avidity test, to compare maternal herpes simplex virus-1 and herpes simplex virus-2 antibody avidity in women who transmitted herpes simplex virus to the neonate and women who had herpes simplex virus isolated from genital secretions at delivery but who did not transmit herpes simplex virus to their infants. RESULTS: Among nonpregnant subjects with genital herpes simplex virus-1 infection whose sera were used to develop the herpes simplex virus-1 avidity test, a significant relationship between herpes simplex virus-1 antibody avidity and time since herpes simplex virus-1 acquisition was observed (P < .001, mixed-effects model), with median avidity values increasing over time after primary infection. Among pregnant, herpes simplex virus-1, or herpes simplex virus-2 seropositive women, 4 of 8 women (50%) with avidity 40 or greater transmitted herpes simplex virus to the neonate, compared with only 12 of 97 (12%) of women with avidity greater than 40 (P = .02). CONCLUSIONS: Herpes simplex virus-1 antibody avidity increased over time after genital herpes simplex virus-1 acquisition, as has been previously observed for herpes simplex virus-2. Among women with herpes simplex virus antibody at delivery, low antibody avidity was associated with herpes simplex virus transmission to the neonate and may be a useful marker for recent seroconversion.

Adult↗
PubMed2006

Isolation of herpes simplex virus from the genital tract during symptomatic recurrence on the buttocks.

OBJECTIVE: To estimate the frequency of isolation of herpes simplex virus (HSV) from the genital tract when recurrent herpes lesions were present on the buttocks. METHODS: Data were extracted from a prospectively observed cohort attending a research clinic for genital herpes infections between 1975 and 2001. All patients with a documented herpes lesion on the buttocks, upper thigh or gluteal cleft ("buttock recurrence") and concomitant viral cultures from genital sites including the perianal region were eligible. RESULTS: We reviewed records of 237 subjects, 151 women and 86 men, with a total of 572 buttock recurrences. Of the 1,592 days with genital culture information during a buttock recurrence, participants had concurrent genital lesions on 311 (20%, 95% confidence interval [CI] 14-27%) of these days. Overall, HSV was isolated from the genital region on 12% (95% CI 8-17%) of days during a buttock recurrence. In the absence of genital lesions, HSV was isolated from the genital area on 7% (95% CI 4%-11%) of days during a buttock recurrence and, among women, from the vulvar or cervical sites on 1% of days. CONCLUSION: Viral shedding of herpes simplex virus from the genital area is a relatively common occurrence during a buttock recurrence of genital herpes, even without concurrent genital lesions, reflecting perhaps reactivation from concomitant regions of the sacral neural ganglia. Patients with buttock herpes recurrences should be instructed about the risk of genital shedding during such recurrences. LEVEL OF EVIDENCE: II-2.

Adolescent↗
PubMed2006

Comparative efficacy of famciclovir and valacyclovir for suppression of recurrent genital herpes and viral shedding.

BACKGROUND: Daily antiviral therapy with famciclovir and valacyclovir has been shown to be effective in reducing both symptomatic and asymptomatic reactivation of herpes simplex virus type 2 (HSV-2) when compared to placebo. However, few comparative studies between the 2 antivirals have been performed. OBJECTIVES: To compare the clinical and virologic effects of famciclovir and valacyclovir administered as daily suppressive therapy for persons with genital herpes. STUDY DESIGN: Two randomized, double-blind, placebo-controlled studies comparing daily famciclovir 250 mg bid with valacyclovir 500 mg qd were performed. Study 1 randomized 320 participants and compared the clinical effect of the drugs given for 16 weeks, and study 2 enrolled 70 HSV-2 seropositive subjects and compared the virologic effect of the drugs given for 10 weeks. RESULTS: In study 1, the time to first recurrence was similar in famciclovir and valacyclovir recipients, hazard ratio (HR) 1.17 (95% CI, 0.78-1.76), but time to first virologically confirmed recurrence was shorter among famciclovir recipients, HR = 2.15 (95% CI, 1.00-4.60). In study 2, HSV was detected on 3.2% of days among famciclovir recipients and 1.3% of days among valacyclovir recipients, relative risk 2.33 (95% CI, 1.18-4.89). CONCLUSION: Valacyclovir appear to be somewhat better than famciclovir for suppression of genital herpes and associated shedding. Further comparative trials of antiviral drugs for various indications should be performed as acyclovir and penciclovir appear to have different ability to abrogate HSV reactivation.

2-Aminopurine↗
PubMed2006

Sequence-based methods for identifying epidemiologically linked herpes simplex virus type 2 strains.

Traditional methods for confirming the identity of herpes simplex virus (HSV) isolates use restriction fragment length polymorphism (RFLP). However, RFLP is less amenable to high-throughput analyses of many samples, and the extent to which small differences in RFLP patterns distinguish between different viral strains remains unclear. Viral HSV type 2 (HSV-2) DNA isolates from 14 persons experiencing a primary HSV-2 infection and from their sexual partners were analyzed by RFLP and heteroduplex mobility assays. We also compared the HSV-2 sequences from seven regions, including noncoding regions between UL19 and UL20, UL24 and UL25, UL37 and UL38, and UL41 and UL42 and coding segments of the gC, gB, and gG genes. Although the resulting RFLP patterns of the couples were almost identical, minor banding differences existed between the source and susceptible partners in five couples. Heteroduplex mobility assays were unable to distinguish between unrelated strains. Overall, 22 sites of sequence variation were found in 1,482 bp of analyzed sequence. The DNA sequences differentiated between all unrelated infections, and epidemiologically related isolates had identical sequences in all but two pairs. Our results suggest that a multilocus assay based on several DNA sequences has the potential to be an informative tool for identifying epidemiologically related HSV-2 strains.

DNA, Viral↗
PubMed2006

Fulminant, acyclovir-resistant, herpes simplex virus type 2 hepatitis in an immunocompetent woman.

We report an immunocompetent woman with multisystem organ failure following herpes simplex virus type 2 (HSV-2) hepatitis. After she initially responded to intravenous acyclovir, she was switched to oral valacyclovir. She developed respiratory failure and opportunistic infections and died. Autopsy confirmed disseminated HSV infection, and lung tissue grew acyclovir-resistant HSV-2.

Abdominal Pain↗
PubMed2006

Genital herpes: antiviral therapy for symptom relief and prevention of transmission.

The episodic and daily suppressive treatment of genital herpes is safe and effective with the currently available antiviral agents: acyclovir, valacyclovir and famciclovir. Clinical strategies for the comprehensive management of genital herpes simplex virus infections are recommended. Data from recent clinical trials demonstrating the efficacy of shorter duration of therapy for recurrences and the use of antivirals for the prevention of transmission are reviewed in this article. The factors influencing the choice of therapy, such as cost, ease of dosing and acyclovir resistance are also discussed.

2-Aminopurine↗
PubMed2005

The relationship between condom use and herpes simplex virus acquisition.

BACKGROUND: Few studies have evaluated the relationship between condom use and herpes simplex virus type 2 (HSV-2) and HSV type 1 (HSV-1) acquisition. OBJECTIVE: To assess the relationship between condom use and acquisition of HSV-2 and HSV-1 among men and women. DESIGN: Analysis of data collected as part of a clinical trial of an ineffective candidate vaccine for HSV-2. SETTING: Sexually transmitted disease clinics. PARTICIPANTS: Men and women at risk for HSV-2 acquisition, defined as having 4 or more sexual partners or having a sexually transmitted disease in the past year. MEASUREMENT: Acquisition of HSV-2 and HSV-1 as measured by viral culture or change to positive HSV serostatus. RESULTS: Of 1843 participants, 118 (6.4%) became infected with HSV-2. In multivariate analyses, participants reporting more frequent use of condoms were at lower risk for acquiring HSV-2 than participants who used condoms less frequently (hazard ratio, 0.74 [95% CI, 0.59 to 0.95]); categories of increasing condom use were 0% to 25%, 25% to 75%, and greater than 75% of sexual acts. Nineteen (2.9%) of 659 participants at risk for infection with HSV-1 became infected. No statistically significant association between condom use and infection with HSV-1 was found (hazard ratio, 0.79 [CI, 0.48 to 1.31]). LIMITATIONS: Use of condoms was measured by self-report, and persons who used condoms may have differed from those who did not. CONCLUSIONS: Consistent use of condoms is associated with lower rates of infection with HSV-2 and should be routinely recommended.

Adult↗
PubMed2005

A randomized controlled trial of a replication defective (gH deletion) herpes simplex virus vaccine for the treatment of recurrent genital herpes among immunocompetent subjects.

BACKGROUND: A replication incompetent herpes virus lacking the glycoprotein H gene has been developed as a potential therapeutic vaccine for genital herpes. GOAL: To determine vaccine efficacy on reducing HSV reactivation and clinical disease among immunocompetent persons with recurrent genital HSV-2 infection. STUDY DESIGN: Randomized multicenter placebo-controlled trial. Healthy volunteers who had six or more recurrences of genital herpes per year were randomized to receive injections of vaccine at 0 and 8 or 0, 4, and 8 or 0, 2, 4, and 8 weeks or placebo and were followed for subsequent recurrences for 1 year. RESULTS: The median times to first recurrence of genital herpes (40 days versus 30 days versus 37 days versus 42 days, respectively), mean number of recurrences (3 versus 3 versus 2.4 versus 1.9, respectively), and time to lesion healing of the first recurrence (8 days versus 7.8 days versus 7.4 days versus 7.5 days, respectively), were similar for all treatment groups. Asymptomatic viral shedding was detected by PCR in 61/74 (82%) persons performing daily sample collection following completion of the vaccination series. No differences were noted in the proportion of days with shedding between treatment groups (11.9% versus 17.2% versus 13.1% versus 16.4%, respectively). CONCLUSION: This replication incompetent HSV-2 vaccine lacking the glycoprotein H gene was safe but had no clinical or virologic benefit in the amelioration of genital HSV-2 disease among immunocompetent men and women.

Adolescent↗