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Biomedical subjects

Anna Wald

Publications and source records attributed to Anna Wald.

At least 19 recordsLinked to original sources
PubMed2004

Targeting virological core groups: a new paradigm for controlling herpes simplex virus type 2 epidemics.

BACKGROUND: Classic modeling of sexually transmitted diseases has focused on modeling behavioral heterogeneity and designing epidemic control strategies targeted at behavioral core groups. METHODS: We analyzed a new mathematical model of herpes simplex virus type 2 (HSV-2) epidemics that includes virological core groups (i.e., groups of individuals with high rates of viral reactivation) and suggest a new paradigm for epidemic control. We used our model, in conjunction with virological data, to determine the potential role of virological core groups in contributing to transmission and the effect that daily antiviral therapy (DAT) could have on reducing transmission if virological core groups were targeted. RESULTS: We estimated that a virological core group (11% of infected individuals) can cause a disproportionately large percentage (44%) of new infections and that a median of only 6.4 person-years of DAT would be necessary to prevent 1 HSV-2 infection. We determined that relatively few individuals would need to receive DAT to substantially reduce the incidence of HSV-2 infection. CONCLUSION: Identifying and targeting individuals in the virological core group could be an effective and practical public health strategy for reducing transmission. Treating individuals who are high-frequency viral shedders should be evaluated as a strategy for reducing HSV-2 transmission.

Antiviral Agents↗
PubMed2004

Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract.

BACKGROUND: Valacyclovir exhibits better oral absorption and higher, more prolonged serum concentrations than oral acyclovir. The efficacy of valacyclovir and acyclovir on genital herpes simplex virus (HSV) shedding was assessed in a double-blind, 3-period crossover trial. METHODS: Sixty-nine immunocompetent participants with genital HSV-2 received oral valacyclovir, acyclovir, and matching placebo in random order for 7-week periods. Participants provided daily genital mucosal swabs for HSV detection by viral culture and polymerase chain reaction (PCR). RESULTS: HSV was detected at least once in 62 (90%) participants by culture and in 68 (98%) by PCR. During placebo, the total HSV shedding rate was 15.4% of days by culture (PCR, 40.2%); the subclinical shedding rate was 6.6% by culture (PCR, 27.1%). Both antivirals were associated with lower HSV shedding by culture (relative risk [RR], 0.03 [95% confidence interval [CI], 0.01-0.07] for valacyclovir and RR, 0.05 [95% CI, 0.03-0.10] for acyclovir) and PCR (RR, 0.18 [95% CI, 0.12-0.26] for valacyclovir and RR, 0.20 [95% CI, 0.15-0.28] for acyclovir), compared with placebo. No significant differences in frequency and quantity of HSV were detected by PCR between the valacyclovir and acyclovir arms. CONCLUSIONS: Although the suppression of viral replication is not complete, valacyclovir and acyclovir are highly effective in suppressing the frequency and quantity of genital HSV shedding.

Acyclovir↗
PubMed2004

Frequent reactivation of herpes simplex virus among HIV-1-infected patients treated with highly active antiretroviral therapy.

The effect of highly active antiretroviral therapy (HAART) on control of herpes simplex virus (HSV) in human immunodeficiency virus (HIV) type 1-infected subjects is not known. Among 28 HAART-treated and 49 untreated subjects with HIV-1 and HSV-2 infections, mucosal HSV shedding (median, 18% and 29% of days positive for HSV DNA, respectively; P=.08) and HSV DNA level (median, 56,250 and 50,000 copies/mL, respectively; P=.20) were similar. Treated subjects reported significantly fewer days with HSV lesions, compared with untreated subjects (2.8% vs. 11.3% of days, respectively; P=.001). Thus, mucosal HSV shedding and HSV-2 reactivation were still frequent among treated subjects, even though HAART was associated with fewer days with HSV lesions.

Adult↗
PubMed2004

The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics.

Increasing evidence demonstrates a substantial link between the epidemics of sexually transmitted HIV-1 and herpes simplex virus (HSV)-2 infection. More than 30 epidemiologic studies have demonstrated that prevalent HSV-2 is associated with a 2- to 4-fold increased risk of HIV-1 acquisition. Per-sexual contact transmission rates among couples from Rakai, Uganda indicate that at all levels of plasma HIV-1 RNA in the source partner, HSV-2-seropositive HIV-1-susceptible persons have a 5-fold greater risk of acquiring HIV-1 compared with HSV-2-negative persons. In vitro and in vivo studies suggest that mucosal HIV-1 shedding is more frequent and in greater amounts during mucocutaneous HSV-2 replication, including subclinical mucosal reactivations. Most HIV-1-infected persons are coinfected with HSV-2, and most experience frequent subclinical and clinical reactivations of HSV-2. Subclinical HSV reactivation elevates serum HIV-1 RNA levels, and daily therapy with acyclovir appears to reduce plasma HIV-1 RNA. These data show that greater attention to the diagnosis and treatment of HSV-2 among HIV-1-infected persons is warranted, especially those who continue to be sexually active, those not on antiretroviral therapy, or those whose disease is not well suppressed by antiretrovirals.

Acyclovir↗
PubMed2004

Vitamin A supplementation and genital shedding of herpes simplex virus among HIV-1-infected women: a randomized clinical trial.

Cross-sectional analyses have associated vitamin A deficiency with genital shedding of herpes simplex virus (HSV) among human immunodeficiency virus type 1 (HIV-1)-infected women. A randomized clinical trial of vitamin A supplementation given daily for 6 weeks was conducted among 376 women in Mombasa, Kenya, who were coinfected with HSV-2 and HIV-1. At follow-up, there was no significant difference in the detection of genital HSV DNA between women receiving vitamin A supplementation and women receiving placebo (40% vs. 44%, respectively; P = .5) Among women shedding HSV, there was no significant difference in the mean HSV DNA quantity between the group that received vitamin A supplementation and the group that received placebo (4.51 vs. 4.67 log10 copies/swab; P = .6). HSV shedding was associated with significantly higher vaginal and cervical HIV-1 shedding, even after controlling for the plasma HIV-1 load and the CD4 count. Vitamin A supplementation is unlikely to decrease HSV shedding and infectivity.

Adult↗
PubMed2004

HIV infection and human herpesvirus-8 oral shedding among men who have sex with men.

Human herpesvirus-8 (HHV-8) is frequently detected in oropharyngeal secretions from HIV-infected men who have sex with men (MSM), and contact with saliva may be an important mode of HHV-8 transmission. A total of 196 MSM were followed over 2 years to determine the correlates of HHV-8 oropharyngeal shedding. A total of 134 (68%) of 196 participants were HHV-8 seropositive upon enrollment, and 9 (15%) of 62 participants seroconverted to HHV-8 during follow-up. HHV-8 DNA was detected in 43 (22%) of 196 participants: 39 (27%) of 134 HHV-8 seropositive, 4 (8%) of 53 HHV-8 seronegative, and 5 (56%) of 9 seroconverters to HHV-8. HHV-8 was detected in 101 (15%) of 696 total oral specimens: 84 (17%) of 481 samples from HHV-8-seropositive men, 6 (3%) of 180 samples from HHV-8-seronegative men, and 11 (31%) of 35 samples from seroconverters. Using adjusted marginal structural models, HHV-8 shedding was higher in men not receiving highly active antiretroviral therapy (odds ratio 2.4, 95% CI 1.0-6.0, P = 0.06), with CD4 counts > 200 cells/mm (odds ratio 4.8, 95% CI 1.0-22.8, P = 0.05), or with detectable oral leukocyte esterase (odds ratio 5.0, 95% CI 2.0-12.5, P < 0.01). CD4 count, antiretroviral therapy, and oral inflammation may influence HHV-8 oropharyngeal shedding.

Adult↗
PubMed2004

Once-daily valacyclovir to reduce the risk of transmission of genital herpes.

BACKGROUND: Nucleoside analogues against herpes simplex virus (HSV) have been shown to suppress shedding of HSV type 2 (HSV-2) on genital mucosal surfaces and may prevent sexual transmission of HSV. METHODS: We followed 1484 immunocompetent, heterosexual, monogamous couples: one with clinically symptomatic genital HSV-2 and one susceptible to HSV-2. The partners with HSV-2 infection were randomly assigned to receive either 500 mg of valacyclovir once daily or placebo for eight months. The susceptible partner was evaluated monthly for clinical signs and symptoms of genital herpes. Source partners were followed for recurrences of genital herpes; 89 were enrolled in a substudy of HSV-2 mucosal shedding. Both partners were counseled on safer sex and were offered condoms at each visit. The predefined primary end point was the reduction in transmission of symptomatic genital herpes. RESULTS: Clinically symptomatic HSV-2 infection developed in 4 of 743 susceptible partners who were given valacyclovir, as compared with 16 of 741 who were given placebo (hazard ratio, 0.25; 95 percent confidence interval, 0.08 to 0.75; P=0.008). Overall, acquisition of HSV-2 was observed in 14 of the susceptible partners who received valacyclovir (1.9 percent), as compared with 27 (3.6 percent) who received placebo (hazard ratio, 0.52; 95 percent confidence interval, 0.27 to 0.99; P=0.04). HSV DNA was detected in samples of genital secretions on 2.9 percent of the days among the HSV-2-infected (source) partners who received valacyclovir, as compared with 10.8 percent of the days among those who received placebo (P<0.001). The mean rates of recurrence were 0.11 per month and 0.40 per month, respectively (P<0.001). CONCLUSIONS: Once-daily suppressive therapy with valacyclovir significantly reduces the risk of transmission of genital herpes among heterosexual, HSV-2-discordant couples.

Acyclovir↗
PubMed2004

Invasive aspergillosis before allogeneic hematopoietic stem cell transplantation: 10-year experience at a single transplant center.

Hematopoietic stem cell transplantation (HCT) in patients with prior or active invasive aspergillosis (IA) is a frequent consideration. We reviewed outcomes of 2319 patients who underwent transplantation between 1992 and 2001 in our institution, among whom 45 patients (1.9%) had a known history of IA before HCT. Posttransplantation IA occurred in 13 of these 45 patients with a pretransplantation history (29%). Nine infections were considered recurrent by anatomic site and timing. Compared with all other patients who received allogeneic HCT during the same period, patients with histories of IA had lower overall survival (56% versus 77%; P =.0001) and higher transplant-related mortality (TRM; 38% versus 21%; P =.0001) 100 days after HCT, associated mainly with IA and other pulmonary complications. Among patients with prior IA, posttransplantation IA occurred more frequently in patients who received <1 month of antifungal therapy before HCT (4/6 versus 6/39; P =.001). The probability of posttransplantation IA and overall survival among patients who received >1 month of antifungal therapy and had resolution of radiographic abnormalities were not different from those of patients without prior IA. Patients with prior IA who received conditioning with total body irradiation (TBI) had higher TRM compared with those who received nonmyeloablative and non-total body irradiation-based regimens (16/31 versus 2/14; P =.024). Thus, the duration of antifungal therapy before transplantation, the resolution of radiographic abnormalities, and conditioning regimens are important variables to consider for minimizing the risk for IA recurrence and TRM after allogeneic HCT.

Academic Medical Centers↗
PubMed2004

Development and use of a type-specific antibody avidity test based on herpes simplex virus type 2 glycoprotein G.

OBJECTIVES: It is difficult to discriminate between lesions resulting from recently acquired versus established genital herpes simplex virus type 2 (HSV-2) infection. Methods not based on history or serum IgM status are needed. GOAL: Our goal was to use type-specific gG-2 antibody avidity determinations based on HerpeSelect HSV-2 enzyme-linked immunosorbent assay (ELISA) to identify new infections. STUDY: Sera (N = 168) from 71 patients with first-episode genital herpes and 45 sera from 21 patients with recurrent episodes were tested. RESULTS: Median avidity increased from 30.2 in sera drawn </=6 weeks to 54.9 >6 weeks after infection (P <0.001). Patients with recurrent episodes and established HSV-2 infections (median, 6.1 years' duration) had higher avidity antibodies (median, 92.7; range, 55.1-100) than patients after first episodes (median, 33.7; range, 6.4-73.9; P <0.001). CONCLUSION: Avidity testing based on HerpeSelect ELISA could be a cost-effective method to identify patients with new HSV-2 infections.

Adolescent↗
PubMed2004

Type-specific testing for herpes simplex virus.

The prevalence of genital herpes is increasing worldwide. Type-specific antibody tests for herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are widely available, however, only those based on glycoprotein G have acceptable accuracy. When diagnosing genital herpes, it is important to use type-specific tests in order to distinguish HSV-1 from HSV-2 since the type of HSV infection affects prognosis and subsequent counseling. Populations appropriate for type-specific serologic testing for HSV include people with an uncertain clinical diagnosis, high-risk patients, partners of an HSV-infected individual, HIV-infected individuals and pregnant women.

Adult↗
PubMed2004

Herpes simplex virus type 2 transmission: risk factors and virus shedding.

The prevalence of herpes simplex virus type 2 (HSV-2) infection is not uniform, with some populations bearing a greater burden of disease than others. Potential risk factors that influence HSV-2 transmission rates have been identified, largely from observational prospective and retrospective studies. Risk factors can be categorized as biological or behavioural. These risk factors can be markers of population subgroups that are likely to have acquired, or are at high risk of acquiring, HSV-2. Major factors associated with HSV-2 seropositivity include female gender, race (black), history of sexually transmitted infections, increasing numbers of sexual partners, sexual contact with commercial sex workers and low socio-economic status or level of education. Age-related risk factors are important, likely reflecting the cumulative number of sex partners, age of initiation of sexual activity, and duration of sexual activity as well as chronic nature of HSV-2 infection. Understanding and identifying these factors may help to direct interventions to reduce HSV-2 transmission and acquisition. An important contributing factor to the spread of genital herpes is unrecognized virus shedding, often allowing transmission from individuals who are not aware that they are infected or who are not having a recurrence. Antiviral therapy reduces both the frequency and amount of HSV reactivation, whereas behavioural risk factors can be addressed in part with educational initiatives. Clinical history is a poor predictor of HSV-2 infection and type-specific serological testing is recommended to detect HSV-2 seropositivity.

CD4 Lymphocyte Count↗
PubMed2004

Genital herpes and human immunodeficiency virus: double trouble.

The synergistic relationship between herpes simplex virus type 2 (HSV-2) and transmission of human immunodeficiency virus (HIV) can be substantial in developing countries that have high prevalences of both viral infections. Genital herpes, most frequently caused by HSV-2, has become the leading cause of genital ulcer disease worldwide. This review of recent research on genital herpes and enhanced susceptibility to, and transmission of, HIV is part of the "Advances in HIV/AIDS research series" which endeavours to form a bridge between the research into HIV and acquired immunodeficiency syndrome (AIDS) and the practice of HIV/AIDS prevention, care and support in developing countries. Research findings have shown that being seropositive for HSV-2 can increase the risk of HIV acquisition among high-risk HIV-negative people exposed to HIV and, likewise, the infectiousness of individuals co-infected with HIV-1 and HSV-2 can increase during periods of HSV-2 reactivation. These observations have led to the initiation of several intervention trials and could ultimately lead to the setting of new priorities in public health and clinical practice. WHO has recently issued new guidelines for the syndromic management of genital ulcer disease that include antiviral treatment for lesions consistent with genital herpes. The United States Centers for Disease Control and Prevention issued updated Sexually Transmitted Diseases Treatment Guidelines in 2002 that recommended the use of type-specific serological tests for diagnosing HSV-2. Recently launched proof-of-concept, HSV-2 intervention trials in several countries will help to determine the proportion of new HIV infections that could be prevented by suppression of HSV-2, and the findings from these studies will inform those involved in setting prevention and treatment priorities and strategies in developing countries.

Africa↗
PubMed2003

Remission of HHV-8 and HIV-associated multicentric Castleman disease with ganciclovir treatment.

Multicentric Castleman disease (MCD) is a lymphoproliferative disorder associated with human herpesvirus 8 (HHV-8) infection among persons with human immunodeficiency virus (HIV) infection. Treatment often includes chemotherapy, and progression to non-Hodgkin lymphoma frequently occurs. MCD is characterized in part by active HHV-8 replication, and many of the symptoms of MCD may be attributable to viral gene products. We describe the effect of ganciclovir on the clinical and virologic course of MCD in a series of 3 case reports. Two patients experienced a reduction in the frequency of episodic flares of MCD and detectable HHV-8 DNA with intravenous or oral ganciclovir, whereas the third patient recovered from an acute episode of renal and respiratory failure with intravenous ganciclovir therapy. These data provide in vivo evidence for the utility of antiviral agents against HHV-8 in the management of MCD.

Administration, Oral↗
PubMed2003

Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture.

This study compared the rate of isolation of herpes simplex virus (HSV) from >36000 samples of mucosal secretions obtained from 296 HSV-infected persons versus the rate of detection of HSV DNA, by means of a real-time quantitative polymerase chain reaction (PCR) assay. Overall, HSV was isolated in 3.0% of samples, and HSV DNA was detected in 12.1% of samples. The mean number of HSV DNA copies was 10(4.9) in samples obtained on days when HSV lesions were present and 10(4.4) in samples from days when HSV lesions were absent. There was a linear relationship between the ability to isolate virus in culture and the log number of copies of HSV DNA in the sample; this relationship persisted in samples from men or women, in samples from human immunodeficiency virus-negative or -positive participants, and in samples obtained on days when lesions were present or absent. In home-collected specimens, the ratio of PCR positivity to viral-culture positivity rose from 3.8:1 in the winter to 8.8:1 in the summer months, reflecting the lability of viral-culture specimens transported during warm weather.

Adult↗
PubMed2003

Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor.

The study of immunodominance within microbe-specific CD8 T cell responses has been challenging. We used a previously undescribed approach to create unbiased panels of CD8 cytotoxic T lymphocyte clones specific for herpes simplex virus type 2, a pathogen with a complex genome encoding at least 85 polypeptides. Circulating herpes simplex virus type 2-specific cells were enriched and cloned after sorting for expression of the skin homing-associated receptor, cutaneous lymphocyte-associated antigen, bypassing restimulation with antigen. The specificity of the resultant cytotoxic clones was determined. Clonal frequencies were compared with each other and with the total number of cytotoxic clones. For each subject within the homing receptor-positive compartment, the CD8 cytotoxic response was dominated by T cells specific for only a few peptides. Previously undescribed antigens and epitopes in viral tegument, capsid, or scaffold proteins were immunodominant in some subjects. Clone enumeration analyses were confirmed in some subjects with dominance studies by using herpes simplex mutants, vaccinia recombinants, and/or enzyme-linked immune spots. We conclude that among circulating cells expressing a homing-associated receptor, during chronic herpes type 2 infection, the CD8 T cell response becomes quite focused despite the presence of many potential antigenic peptides.

Antigens, CD↗
PubMed2003

Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects.

To determine the efficacy and safety of valacyclovir (500 mg twice daily) for the suppression of recurrent genital herpes simplex virus infections in human immunodeficiency virus (HIV)-infected subjects, a randomized, double-blind, placebo-controlled, multicenter international trial was conducted. A total of 293 HIV-seropositive subjects receiving antiretroviral therapy were enrolled. The proportion of subjects who did not have a recurrence of genital herpes at 6 months was 65% among valacyclovir recipients versus 26% among placebo recipients (relative risk, 2.5; 95% confidence interval, 1.8-3.5). The time to first genital herpes recurrence was significantly shorter in the placebo group (median, 59 days) than in the valacyclovir group (median, >180 days). Valacyclovir was well tolerated; the incidence of adverse events for the 2 treatment groups was similar when the duration of treatment was considered. There were no episodes of thrombotic microangiopathy. Valacyclovir was safe and effective for the suppression of recurrent genital herpes infection in HIV-infected individuals.

Acyclovir↗
PubMed2003

Disseminated sporotrichosis associated with treatment with immunosuppressants and tumor necrosis factor-alpha antagonists.

We report a case of disseminated sporotrichosis in a 49-year-old man who was treated with multiple immunosuppressants, including tumor necrosis factor (TNF)-alpha antagonists (etanercept and infliximab), for presumed inflammation arthritis. This case illustrates the potential for infectious complications related to the use of cytotoxic immunosuppressants and anticytokine agents, such as TNF-alpha antagonists.

Antibodies, Monoclonal↗