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Biomedical subjects

Anna Wald

Publications and source records attributed to Anna Wald.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2004

Synergistic interactions between herpes simplex virus type-2 and human immunodeficiency virus epidemics.

Several factors clearly influence HSV-2 transmission, such as female gender and number of sexual contacts.3,4 Some are less well defined, and may be confounded by other factors, but include time since While the concept linking herpes simplex virus (HSV) shedding to transmission is plausible, few data support shedding as a surrogate marker. If shedding is to be used as a surrogate marker in future clinical studies, it must be clear how far shedding must be reduced, and what the shape of the transmission:viral load curve (or transmission:detection frequency curve) is before transmission is reduced. It remains unclear whether peak virus load, frequency of detection of virus, or the area under curve of the time:virus load plot is the critical parameter in the transmission of HSV. This paper reports on an international meeting of experts and a debate at the International Herpes Management Forum (IHMF) Annual Meeting (2004), convened to examine whether a surrogate marker for HSV transmission is necessary, and whether there is any evidence, either in studies involving HSV or other viral infections, to suggest that viral shedding could be used as such a surrogate.

Disease Outbreaks↗
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↗
PubMed2003

T cell immunity to herpes simplex viruses in seronegative subjects: silent infection or acquired immunity?

During the course of investigating T cell responses to HSV among volunteers entering trials of investigational genital herpes vaccines, 6 of the 24 immunocompetent subjects with no prior history of oral/labial or genital herpes possessed HSV-specific T cell immunity but, by multiple determinants of even the most sensitive serological assays, remained seronegative to HSV-1 and -2. Of these six immune seronegative (IS; HSV-seronegative with HSV-specific T cell responses) subjects, two had transient HSV-specific T cell responses, while four had CD4(+) and CD8(+) T cell responses directed at HSV that persisted for up to 4 years. CD4(+) T cell clones were isolated that recognized and had high binding affinities to epitopes in HSV-2 tegument proteins. All six IS subjects had potential sexual exposure to an HSV-2-infected sexual partner. Oral and genital mucosal secretions were sampled and tested for the presence of infectious HSV and HSV DNA. No evidence of HSV was detected in >1500 samples obtained from these IS subjects. The identification of persistent T cell responses to HSV in seronegative subjects is a novel finding in the herpesvirus field and suggests either undetected infection or acquired immunity in the absence of infection. Understanding the basis of these acquired immune responses may be critical in developing effective vaccines for genital herpes.

Adult↗
PubMed2003

Transferred herpes simplex virus immunity after stem-cell transplantation: clinical implications.

Herpes simplex virus (HSV) commonly reactivates after stem-cell transplantation (SCT), despite acyclovir prophylaxis. Whether HSV-seropositive recipients with HSV-seronegative or type-discordant donors had more frequent and severe HSV infections than those with HSV type-concordant donors was explored. Banked serum samples from HSV-positive SCT recipients and their donors were tested for the presence of HSV antibodies. HSV-1-positive SCT recipients from HSV-1-negative donors had more frequent and longer episodes than HSV-1-positive SCT recipients from HSV-1-positive donors; the proportion of patients receiving antiviral treatment for >10% of follow-up days was 27.4% versus 7.2% (P<.001). Both HSV-1 visceral infection (9.8% vs. 2.2%; P=.001) and acyclovir resistance (5.8% vs. 1.8%; P=.03) were more common in type-discordant than -concordant patients, respectively; these associations were confirmed in multivariable models. Serological testing of donors can identify patients who are at highest risk for HSV-related morbidity, for whom prolonged prophylaxis or donor vaccination (once available) could be considered.

Acyclovir↗
PubMed2003

Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant.

CONTEXT: Neonatal herpes most commonly results from fetal exposure to infected maternal genital secretions at the time of delivery. The risk of transmission from mother to infant as it relates to maternal herpes simplex virus (HSV) serologic status and exposure to HSV in the maternal genital tract at the time of labor has not been quantified. Furthermore, no data exist on whether cesarean delivery, the standard of care for women with genital herpes lesions at the time of delivery, reduces HSV transmission. OBJECTIVE: To determine the effects of viral shedding, maternal HSV serologic status, and delivery route on the risk of transmission of HSV from mother to infant. DESIGN: Prospective cohort of pregnant women enrolled between January 1982 and December 1999. SETTINGS: A university medical center, a US Army medical center, and 5 community hospitals in Washington State. PATIENTS: A total of 58 362 pregnant women, of whom 40 023 had HSV cultures obtained from the cervix and external genitalia and 31 663 had serum samples tested for HSV. MAIN OUTCOME MEASURE: Rates of neonatal HSV infection. RESULTS: Among the 202 women from whom HSV was isolated at the time of labor, 10 (5%) had neonates with HSV infection (odds ratio [OR], 346; 95% confidence interval [CI], 125-956 for neonatal herpes when HSV was isolated vs not isolated). Cesarean delivery significantly reduced the HSV transmission rate among women from whom HSV was isolated (1 [1.2%] of 85 cesarean vs 9 [7.7%] of 117 vaginal; OR, 0.14; 95% CI, 0.02-1.08; P =.047). Other risk factors for neonatal HSV included first-episode infection (OR, 33.1; 95% CI, 6.5-168), HSV isolation from the cervix (OR, 32.6; 95% CI, 4.1-260), HSV-1 vs HSV-2 isolation at the time of labor (OR, 16.5; 95% CI, 4.1-65), invasive monitoring (OR, 6.8; 95% CI, 1.4-32), delivery before 38 weeks (OR, 4.4; 95% CI, 1.2-16), and maternal age less than 21 years (OR, 4.1; 95% CI, 1.1-15). Neonatal HSV infection rates per 100 000 live births were 54 (95% CI, 19.8-118) among HSV-seronegative women, 26 (95% CI, 9.3-56) among women who were HSV-1-seropositive only, and 22 (95% CI, 4.4-64) among all HSV-2-seropositive women. CONCLUSION: Neonatal HSV infection rates can be reduced by preventing maternal acquisition of genital HSV-1 and HSV-2 infection near term. It can also be reduced by cesarean delivery and limiting the use of invasive monitors among women shedding HSV at the time of labor.

Antibodies, Viral↗
PubMed2003

Natural history of genital herpes simplex virus type 1 infection.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) has been increasingly reported as a cause of genital herpes, yet there have been few studies on the long-term natural history of this infection. GOAL The goal was to examine the clinical course of genital HSV-1 infection. STUDY DESIGN: This was a cohort study of patients presenting with culture-proven primary genital HSV-1 infection. RESULTS: The median follow-up of the 77 patients was 736 days. The overall rate of recurrences was 1.3/year in the first year of infection, decreasing to 0.7/year in the second year. In the first year of infection, 43% of study patients did not have a recurrence. In the second year of infection, 67% of study patients did not have a recurrence. CONCLUSION: Genital HSV-1 recurs infrequently in most patients, and the rate decreases further in the subsequent years of infection. Because the prognoses of genital HSV-1 and HSV-2 infections differ, determination of the viral type is important for patient counseling.

Adolescent↗
PubMed2003

Time course of seroconversion by HerpeSelect ELISA after acquisition of genital herpes simplex virus type 1 (HSV-1) or HSV-2.

BACKGROUND: HerpeSelect HSV-1 and HSV-2 ELISAs are glycoprotein G-based, type-specific antibody detection tests that are approved by the US Food and Drug Administration for diagnosis of genital herpes. GOAL: The goal was to determine seroconversion times by means of HerpeSelect ELISAs. STUDY DESIGN: Four-hundred thirteen sera from 113 patients with recently acquired genital herpes were tested by HerpeSelect ELISAs and Western blot (WB). Thirty-one patients had primary genital HSV-1 (group 1), 56 had primary HSV-2 (group 2), and 26 had prior HSV-1 antibodies and newly acquired HSV-2 (group 3). RESULTS: Median interval from onset of symptoms to seroconversion was 25 days, as determined by HerpeSelect HSV-1, versus 33 days by WB for group 1; 21 days by HerpeSelect HSV-2 versus 40 days by WB (group 2; P = 0.0005); and 23 days by HerpeSelect HSV-2 ELISA versus 47 days by WB (group 3; P = 0.02). In long-term follow-up, transient reversion to HerpeSelect negativity occurred in 3 of 31 HSV-1-infected subjects (10%) and in 2 of 82 HSV-2-infected subjects (2%). CONCLUSION: Seroconversion to HSV-2 was determined faster by HerpeSelect than by WB.

Antibodies, Viral↗
PubMed2003

Correlates of human herpesvirus-8 seropositivity among U.S. military members recently infected with human immunodeficiency virus.

BACKGROUND: Human herpesvirus 8 (HHV-8), the cause of Kaposi's sarcoma, is common among HIV-infected persons. The exact route of transmission of HHV-8 in various populations is still debated. GOAL: The goal was to define the correlates of HHV-8 infection among men recently infected with human immunodeficiency virus. STUDY DESIGN: Three hundred forty-two HIV-infected U.S. military men were evaluated using a questionnaire regarding potential risk factors and laboratory data, including HHV-8, herpes simplex virus 2 (HSV-2), syphilis, hepatitis B, and hepatitis C serologies. RESULTS: The seroprevalence of HHV-8 was 32%. HHV-8 was significantly associated with hepatitis B seropositivity (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.5-4.1), and black ethnicity was negatively associated with HHV-8 (OR, 0.6; 95% CI, 0.3-0.9) in the multivariate analysis. HHV-8 was not associated with drug use or hepatitis C seropositivity. Among men who have sex with men (MSM), HHV-8 infection correlated with hepatitis B seropositivity (OR, 2.2; 95% CI, 1.1-4.3) and HSV-2 (OR, 2.6; 95% CI, 1.4-4.9). Among heterosexuals, the correlates of HHV-8 were different; blacks as compared with whites (OR, 0.3; 95% CI, 0.1-0.8) and married versus single status (OR, 0.4; 95% CI, 0.2-0.9) were associated with a lower rate of HHV-8 infection. Among heterosexuals, hepatitis B, HSV-2, and sexual behaviors were not associated with HHV-8. CONCLUSION: This study suggests that the seroprevalence of HHV-8 is increased in both MSM and heterosexual men with HIV infection, and that the route(s) of HHV-8 acquisition might be different between MSM and heterosexuals.

Adolescent↗
PubMed2003

Prevalence and risk factors for infection with herpes simplex virus type-1 and -2 among lesbians.

BACKGROUND AND OBJECTIVES: Sexual transmission of bacterial and viral sexually transmitted disease has been reported between women. No data are available on seroprevalence of herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) among lesbians. GOAL: The goal was to define prevalence of infection with HSV-1 and HSV-2 among lesbians, and associated risk factors. STUDY DESIGN: Women who reported sex with another woman in the preceding year were eligible. Medical and sexual histories were obtained. Serum was tested for HSV-1 and HSV-2 antibodies using Western Blot assay. RESULTS: Among 392 subjects, antibodies to HSV-1 were detected in 46% and to HSV-2 in 8%. Increasing age predicted higher seroprevalence to both HSV types, and HSV-2 seropositivity was associated with a history of male partner with genital herpes. Of 78 women reporting no prior sex with men, 3% were HSV-2-seropositive. Most HSV-2-seropositive subjects (71%) reported no history of genital herpes. HSV-1 seroprevalence increased significantly with an increasing number of female sex partners. CONCLUSIONS: HSV-2 infection occurs in nearly 1 in 10 lesbians and is not predicted by report of sex with men or sexual identity. Most lesbians infected with HSV-2 are not aware of their infection. Sexual transmission of HSV-1 may occur more frequently among lesbians than among heterosexual women.

Adolescent↗
PubMed2002

Serological testing for herpes simplex virus (HSV)-1 and HSV-2 infection.

Serological tests for herpes simplex virus (HSV) that can accurately distinguish between HSV-1 and HSV-2 are now commercially available. These tests detect antibodies to HSV glycoproteins G-1 and G-2, which evoke a type-specific antibody response. Focus Technologies produces the HerpeSelect-1 and HerpeSelect-2 enzyme-linked immunosorbent assay tests and the HSV-1 and HSV-2 HerpeSelect1/2 Immunoblot. Diagnology has marketed POCkit-HSV-2, a point-of-care test for HSV-2 that allows blood from a finger stick to be tested in a clinic. These tests can be used to confirm a genital herpes diagnosis, establish diagnosis of HSV infection in patients with atypical complaints, identify asymptomatic carriers, and identify persons at risk for acquiring HSV. Potential settings for use of these tests include sexually transmitted disease clinics, prenatal clinics, and clinics that care for patients with human immunodeficiency virus. Patient interest in HSV serological tests appears high.

HIV Infections↗