Seroprevalence and factors associated with herpes simplex virus type 2 among HIV-negative high-risk men who have sex with men from Rio de Janeiro, Brazil: a cross-sectional study

Submitted by Frederico Azevedo ([email protected]) on 2010-11-04T17:19:23Z No. of bitstreams: 1 seroprevalence_and_factors.pdf: 273577 bytes, checksum: 742e51b14ff9ef765bf31b52f3fc8f1a (MD5)Made available in DSpace on 2010-11-04T17:19:23Z (GMT). No. of bitstreams: 1 seroprevalence_and_factors.pdf: 273577 bytes, checksum: 742e51b14ff9ef765bf31b52f3fc8f1a (MD5) Previous issue date: 2009Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Comunicação e Informação Científica e Tecnológica em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Background: Herpes simplex virus type 2 (HSV-2) is the leading cause of genital ulcer disease in developing countries, including Brazil, and is especially prevalent among men who have sex with men (MSM). HSV-2 infection represents a risk factor for the acquisition and transmission of other sexually transmitted diseases. The goal of the present cross-sectional study was to estimate HSV- 2 seroprevalence and to determine the factors associated with HSV-2 seropositivity in HIVnegative high-risk MSM from Rio de Janeiro, Brazil. Methods: Stored sera were tested to estimate HSV-2 seroprevalence, while socio-demographic and sexual behavior data were used to measure associations between risk factors and HSV-2 seropositivity. Using the Poisson regression model with robust variance, prevalence ratios (PR) were used to estimate de degree of association between risk factors and HSV-2 seropositivity in bivariate and multivariate analyses. Results: Seroprevalence of HSV-2 was of 45.7% (184 out of 403). Factors independently associated with HSV-2 seroprevalence in the multivariate model were: older age (≥ 26 years, PR: 1.41 95% Confidence Interval: 1.11–1.78), non-white race (PR: 1.32 95%CI: 1.06–1.64), positive serology for syphilis (PR: 1.65 95%CI: 1.33–2.05), positive serology for hepatitis B (PR: 1.25 95%CI: 0.99–1.57), stable male partner in the past 6 months (PR: 1.42 95%CI: 1.12–1.79), and unprotected anal sex with a stable female partner (PR: 1.46 95%CI: 1.05–2.04) in the 6 months preceding the crosssectional assessment. Conclusion: The present study made evident a high prevalence of HSV-2 infection in a sample of HIV-negative high-risk MSM from Rio de Janeiro. This finding indicates the need and urgency for implementing integrated programs for the prevention of HSV-2 and other sexually transmitted diseases, and, in particular, programs targeting high-risk MSM

Valganciclovir for suppression of human herpesvirus-8 replication: a randomized, double-blind, placebo-controlled, crossover trial.

BACKGROUND: Human herpesvirus-8 (HHV-8) replication is critical in the induction and maintenance of Kaposi sarcoma, primary effusion lymphoma, and some cases of Castleman disease. In vitro and observational studies suggest that ganciclovir inhibits HHV-8 replication, but no randomized clinical trials have been conducted. METHODS: A total of 26 men infected with HHV-8 were randomized to receive 8 weeks of valganciclovir administered orally (900 mg once per day) or 8 weeks of placebo administered orally. After a 2-week washout period, participants in each group received the study drug they had not yet taken (either valganciclovir or placebo), for 8 additional weeks. Oral swab samples were collected daily during the study, and HHV-8 and CMV DNA were quantified by real-time PCR. RESULTS: A total of 16 human immunodeficiency virus (HIV)-positive men and 10 HIV-negative men enrolled in and completed the study. Of the 3,439 swab samples that participants had been expected to provide, 3029 (88%) were available for analysis. HHV-8 was detected on 44% of swabs collected from participants who were receiving placebo, compared with 23% of swabs collected from participants who were receiving valganciclovir (relative risk [RR], 0.54 [95% confidence interval {CI}, 0.33-0.90]; P = .02). Valganciclovir reduced oropharyngeal shedding of cytomegalovirus by 80% (RR, 0.20 [95% CI, 0.08-0.48]; P < .001). Shedding of HHV-8 and shedding of cytomegalovirus were independent. Hematologic, renal, or hepatic toxicities were no more common among participants who received the active drug, compared with those who received placebo, though participants who received valganciclovir reported more days of diarrhea. CONCLUSIONS: Valganciclovir administered orally once per day is well tolerated and significantly reduces the frequency and quantity of HHV-8 replication

Trace anomalies in chiral theories revisited

Motivated by the search for possible CP violating terms in the trace of the energy-momentum tensor in theories coupled to gravity we revisit the problem of trace anomalies in chiral theories. We recalculate the latter and ascertain that in the trace of the energy-momentum tensor of theories with chiral fermions at one-loop the Pontryagin density appears with an imaginary coefficient. We argue that this may break unitarity, in which case the trace anomaly has to be used as a selective criterion for theories, analogous to the chiral anomalies in gauge theories. We analyze some remarkable consequences of this fact, that seem to have been overlooked in the literature

Testing A (Stringy) Model of Quantum Gravity

I discuss a specific model of space-time foam, inspired by the modern non-perturbative approach to string theory (D-branes). The model views our world as a three brane, intersecting with D-particles that represent stringy quantum gravity effects, which can be real or virtual. In this picture, matter is represented generically by (closed or open) strings on the D3 brane propagating in such a background. Scattering of the (matter) strings off the D-particles causes recoil of the latter, which in turn results in a distortion of the surrounding space-time fluid and the formation of (microscopic, i.e. Planckian size) horizons around the defects. As a mean-field result, the dispersion relation of the various particle excitations is modified, leading to non-trivial optical properties of the space time, for instance a non-trivial refractive index for the case of photons or other massless probes. Such models make falsifiable predictions, that may be tested experimentally in the foreseeable future. I describe a few such tests, ranging from observations of light from distant gamma-ray-bursters and ultra high energy cosmic rays, to tests using gravity-wave interferometric devices and terrestrial particle physics experients involving, for instance, neutral kaons.Comment: 25 pages LATEX, four figures incorporated, uses special proceedings style. Invited talk at the third international conference on Dark Matter in Astro and Particle Physics, DARK2000, Heidelberg, Germany, July 10-15 200

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

Genital Herpes Has Played a More Important Role than Any Other Sexually Transmitted Infection in Driving HIV Prevalence in Africa

Extensive evidence from observational studies suggests a role for genital herpes in the HIV epidemic. A number of herpes vaccines are under development and several trials of the efficacy of HSV-2 treatment with acyclovir in reducing HIV acquisition, transmission, and disease progression have just reported their results or will report their results in the next year. The potential impact of these interventions requires a quantitative assessment of the magnitude of the synergy between HIV and HSV-2 at the population level.A deterministic compartmental model of HIV and HSV-2 dynamics and interactions was constructed. The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs). The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub-Saharan Africa than other STIs. We estimate that in settings of high HSV-2 prevalence, such as Kisumu, Kenya, more than a quarter of incident HIV infections may have been attributed directly to HSV-2. HSV-2 has also contributed considerably to the onward transmission of HIV by increasing the pool of HIV positive persons in the population and may explain one-third of the differential HIV prevalence among the cities of the Four City study. Conversely, we estimate that HIV had only a small net impact on HSV-2 prevalence.HSV-2 role as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV particularly by facilitating HIV spread among the low-risk population with stable long-term sexual partnerships. This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships

Herpes simplex virus infections among rural residents in eastern China

<p>Abstract</p> <p>Background</p> <p>Herpes simplex virus (HSV) has two types: HSV-1 and HSV-2. Both infect epithelial cells and establish latent infections in neurons causing an infection that persists for life. Information on age- and gender-specific seroprevalence of HSV-1 and HSV-2 is valuable for understanding HSV transmission dynamics and designing population-based prevention and intervention programs for HSV. However, such information is not available for China.</p> <p>Methods</p> <p>Cryopreserved serum samples of all subjects aged 5 to 60 years from two randomly selected rural villages in Zhejiang province in Eastern China who had participated in the China national seroepidemiological survey of hepatitis B virus (HBV) infection conducted in 2006 were tested. Seroprevalence of HSV-1 and HSV-2 infections were determined by type-specific IgG antibody tests using an ELISA technique. Their 95% confidence intervals adjusted for the sampling fraction were calculated according to the Clopper-Pearson method.</p> <p>Results</p> <p>A total of 2,141 residents participated in the survey, with a response rate of 82.3%. HSV-1 seroprevalence was 92.0% overall, 89.1% for males and 94.2% for females. HSV-1 seroprevalence was 61.6% among children aged 5-9 years, 90.3% among 25-29 years, and nearly 100% among those aged > = 40 years. HSV-2 seroprevalence was 13.2% overall, 10.5% for males and 15.3% for females. No children aged 5-14 years were HSV-2 positive, and HSV-2 seroprevalence was 7.1% among 15-19 years and peaked at 24.3% among those aged 45-49 years. Neither HSV-1 nor HSV-2 infections were significantly different by gender. About 11.8% of study subjects were co-infected with both types of HSV. Among 549 participating couples, 8.6% were HSV-1 serodiscordant and 11.8% were HSV-2 serodiscordant. No one tested positive for HIV. The overall prevalence of HBsAg was 16.2%, 16.9% for males and 15.4% for females.</p> <p>Conclusions</p> <p>HSV-1 was highly prevalent among all rural residents aged between 5-60 years in Eastern China, whereas HSV-2 was prevalent among sexually active people. HSV-1 and HSV-2 have different transmission modes and dynamics. Future HSV prevention and control programs in China should be type specific.</p

Three little pieces for computer and relativity

Numerical relativity has made big strides over the last decade. A number of problems that have plagued the field for years have now been mostly solved. This progress has transformed numerical relativity into a powerful tool to explore fundamental problems in physics and astrophysics, and I present here three representative examples. These "three little pieces" reflect a personal choice and describe work that I am particularly familiar with. However, many more examples could be made.Comment: 42 pages, 11 figures. Plenary talk at "Relativity and Gravitation: 100 Years after Einstein in Prague", June 25 - 29, 2012, Prague, Czech Republic. To appear in the Proceedings (Edition Open Access). Collects results appeared in journal articles [72,73, 122-124

Effects of Combined Aspirin and Clopidogrel Therapy on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

BACKGROUND: Aspirin and clopidogrel monotherapies are effective treatments for preventing vascular disease. However, new evidence has emerged regarding the use of combined aspirin and clopidogrel therapy to prevent cardiovascular events. We therefore performed a comprehensive systematic review and meta-analysis to evaluate the benefits and harms of combined aspirin and clopidogrel therapy on major cardiovascular outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings to identify studies to fit our analysis. Eligible studies were randomized controlled trials assessing the effect of combined aspirin and clopidogrel therapy compared with aspirin or clopidogrel monotherapy. We identified 7 trials providing data with a total of 48248 patients. These studies reported 5134 major cardiovascular events, 1626 myocardial infarctions, 1927 strokes, and 1147 major bleeding events. Overall, the addition of aspirin to clopidogrel therapy as compared to single drug therapy resulted in a 9% RR reduction (95%CI, 2 to 17) in major cardiovascular events, 14% RR reduction (95%CI, 3 to 24) in myocardial infarction, 16% RR reduction (95%CI, 1 to 28) in stroke, and 62% RR increase (95%CI, 26 to 108) in major bleeding events. We also present the data as ARR to explore net value as the reduction in cardiovascular events. Overall, we observed that combined therapy yielded 1.06% decrease (95%CI, 0.23% to 1.99%) in major cardiovascular events and 1.23% increase (95%CI, 0.52% to 2.14%) in major bleeding events. CONCLUSION/SIGNIFICANCE: Although the addition of aspirin to clopidogrel resulted in small relative reductions in major cardiovascular events, myocardial infarction, and stroke, it also resulted in a relative increase in major bleeding events. In absolute terms the benefits of combined therapy, a 1.06% reduction in major cardiovascular events, does not outweigh the harms, a 1.23% increase in major bleeding events

Infant Safety during and after Maternal Valacyclovir Therapy in Conjunction with Antiretroviral HIV-1 Prophylaxis in a Randomized Clinical Trial

<div><h3>Background</h3><p>Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described.</p> <h3>Methods</h3><p>Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm³ were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher’s Exact and Wilcoxon rank-sum tests were used for analysis.</p> <h3>Results</h3><p>One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6–4.19).</p> <h3>Conclusions</h3><p>Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events.</p> <h3>Trial Registration</h3><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00530777">NCT00530777</a></p> </div