Asymptomatic Viral Shedding Research Articles

Herpès

Herpes Simplex Viruses (HSV1 and HSV2) refer to members of the herpes-viridae family that infect strictly human beings and cause a range of benign and recurrent diseases from mild muco-cutaneous infections to more severe forms such as meningo-encephalitis and visceral complications in newborns and immuno-depressed patients. HSV1 oro-facial infection is acquired in infancy, whereas HSV2 usually causes genital herpes (60-80 %), the most frequent ulcerous sexually transmitted infection worldwide which facilitates VIH infection. After primary contact (primary infection) both viruses establish latent infection in sensitive ganglionnic neurons, and reactivation causes herpetic muco-cutaneous recurrences. Asymptomatic viral shedding in genital areas (cervix, vulva, anal, urethral) represents a major source of HSV2 transmission. Aciclovir and precursor drugs (valaciclovir, famciclovir) are highly effective in treating HSV infections, preventing recurrences and improving patient's quality of life. Potential seriousness of neonatal herpes justifies its prophylactic management.

Effect of Prophylactic Valacyclovir on the Presence of Human Herpesvirus DNA in Saliva of Healthy Individuals after Dental Treatment

Human herpesviruses (HHVs) are ubiquitous pathogens that intermittently reactivate from latency. Transmission is believed to be facilitated by their frequent appearance in saliva. This study sought to understand the factors that influence the appearance of these viruses in saliva by examining the prevalence, pattern, and quantity of all eight HHVs in saliva of immunocompetent adults with a history of recurrent oral herpes simplex virus (HSV) infections following dental treatment and antiviral therapy. Valacyclovir or matched placebo was given (2 g twice on the day of treatment and 1 g twice the following day) to 125 patients in a randomized, double-blind controlled trial. Saliva, collected on the day of dental treatment and 3 and 7 days later, was analyzed using real-time quantitative PCR. At all visits, HHVs coinfected saliva. Over the course of the week, the DNAs of HHV-6 and HHV-7 were detected significantly more often (97% to 99% of patients) than Epstein-Barr virus (EBV; 64.8%), HSV-1 (13.0%), HHV-8 (3.2%), cytomegalovirus (2.4%), HSV-2 (0%), and varicella-zoster virus (0%), irrespective of drug treatment (P < 0.002). Mean genome copy numbers were highest for HSV-1 and HHV-6. Dental treatment did not influence asymptomatic viral shedding patterns. However, valacyclovir treatment resulted in significantly fewer patients shedding EBV at both postoperative visits compared with placebo (P < 0.008). These results suggest that HHVs are simultaneously present in the saliva of healthy adults at levels that could facilitate transmission, and valacyclovir therapy decreases the prevalence of EBV in saliva but has little effect on HHV-6 and HHV-7.

Frequent Detection of Respiratory Viruses in Adult Recipients of Stem Cell Transplants with the Use of Real-Time Polymerase Chain Reaction, Compared with Viral Culture

Background. Respiratory virus infections have been recognized as important causes of severe pneumonia in patients who have undergone stem cell transplantation (SCT). Reported incidences of respiratory virus infection in adult SCT recipients vary in the literature from 3.5% to 36% when determined by viral culture. However, a more sensitive method to assess the presence of respiratory viruses in the lower airways may be important for delineation of the true incidence of respiratory virus—associated pneumonia and may be essential for guidance on implementation of antiviral therapy and prevention or limitation of nosocomial spread of infection with respiratory viruses. Methods. To determine the incidence and severity of respiratory tract illness (RTI) and to assess the diagnostic value of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) versus viral culture, 72 SCT recipients were monitored during a 6-month period. Results. A respiratory virus was detected in 21% of episodes of RTI by viral culture and in 63% of RTI episodes by real-time RT-PCR (P < .0001). In lower respiratory tract illness, real-time RT-PCR was much more sensitive than viral culture for detection of respiratory virus (73% vs. 9%; P = .008). The mortality rate for patients with respiratory virus—associated lower respiratory tract illness (25%) was similar to rates reported elsewhere. Respiratory viruses (predominantly rhinovirus) were detected by real-time RT-PCR in 9% of samples obtained from symptom-free SCT recipients at predetermined times by real-time RT-PCR and by viral culture in 1% (P < .0001), indicating that asymptomatic shedding of respiratory viruses also occurs. Conclusion. We conclude that, although asymptomatic shedding of respiratory virus occurs, respiratory viruses are frequent causes of RTI in SCT recipients.

Native Kidney BK Nephropathy Post Cardiac Transplantation

BK virus reactivation post renal transplantation has become increasingly diagnosed over the last decade, probably as a result of the widespread usage of more potent immunosuppressive agents. Manifestations of viral reactivation post renal transplantation include asymptomatic viruria, hemorrhagic cystitis, ureteric stricture, and interstitial nephritis, the latter often associated with progressive renal impairment and graft loss. For reasons that remain poorly understood, BK virus induced interstitial nephritis (BKIN) and associated renal failure occurs very infrequently in the nonrenal transplant setting even in patients with similar or even greater levels of immune suppression. This is despite the fact that asymptomatic viral reactivation and shedding may be quite common in these patients (1). Only a handful of case reports appear in the literature describing BKIN in native kidneys; in association with HIV infection (2), congenital immunodeficiency (3), post bone marrow transplantation (4), and post pancreatic transplantation (5). We report a unique case of BKIN in native kidneys associated with severe renal failure occurring 2-years post cardiac transplantation. The patient is a 59-year-old female who presented in October 2001 with increasing symptomatic cardiac failure. Past medical history included focal breast carcinoma resected in 1990 and thyroidectomy in 1999. A severe dilated cardiomyopathy was confirmed on echocardiogram and cardiac biopsy revealed giant cell myocarditis. Despite treatment with pulse methylprednisolone and cyclosporine, the patient deteriorated requiring admission to intensive care for inotropic support and insertion of a left ventricular assist device. She remained in intensive care for 3 months until undergoing a heart transplant in January of 2002. This was complicated by three episodes of severe rejection treated with pulse methylprednisolone and antithymocyte globulin as well as by the development of steroid induced diabetes requiring insulin therapy. In view of the recurrent rejection a decision was made for increased maintenance immunosuppression including prednisolone, tacrolimus, mycophenolate mofetil, and sirolimus. Of note, serum creatinine was 0.04 mmol/L on admission and 0.16 mmol/L on discharge. Over the subsequent 12 months, cardiac function remained stable but there was a gradual decline in renal function with serum creatinine climbing to 0.28 mmol/L despite early withdrawal of tacrolimus. In June of 2003 the patient underwent a renal biopsy, which confirmed BKIN (Fig. 1). Urine decoy cells were not detected but urine polyomavirus PCR was found to be strongly positive.FIGURE 1.: Electron microscopy of renal biopsy demonstrates viable and degenerate virions with morphology in keeping with polyoma virus infection.Immunosuppression was considerably reduced to prednisolone 5 mg and sirolimus 4 mg daily with serial cardiac biopsies reintroduced to monitor for cardiac rejection. Although cardiac function remained stable over the subsequent months, serum creatinine continued to rise to 0.40 mmol/L with ongoing strongly positive urine PCR for polyomavirus. The patient was then treated with intermittent low doses of the antiviral agent cidofovir for a period of 3 months. Despite this, there was no improvement in renal function and urine PCR remained strongly positive for polyomavirus. Currently the patient has a serum creatinine of 0.44 mmol/L and preparations are being made for her to commence dialysis. It is unclear why BKIN occurs relatively frequently post renal transplantation and so rarely in any other setting. Some authors have suggested that renal tubular injury specific to the process of renal transplantation or allograft rejection is a necessary co-factor in the pathogenesis of invasive BK virus infection (6). Solomon A. Menahem Katherine M. McDougall Napier M. Thomson Department Renal Medicine Alfred Hospital Melbourne, Australia John P. Dowling Department Anatomical Pathology Alfred Hospital Melbourne, Australia

Reducing Genital Herpes Transmission Using Antiviral Therapy.

Introduction: Herpes simplex virus (HSV) type 1 or 2 can cause chronic genital viral infections, most of which are asymptomatic [1,2]. HSV-2 is the more likely of the two types to cause genital herpes (GHSV) and is more commonly associated with recurrent clinical infection than is HSV-1. HSV-2 is now the leading cause of genital ulcer disease worldwide [3]. For example, in the United States there are approximately 1.6 million new cases each year against a background prevalence of 22% in adults [4]. When coupled with the association of genital ulcer disease with the acquisition and transmission of HIV infection, these high incidence and prevalence rates [5,6] represent a public health imperative to identify effective mechanisms to prevent transmission. Although it is known that acyclovir, its prodrug valacyclovir, and other antivirals can reduce clinical recurrence of GHSV [7] and asymptomatic viral shedding [8], it is unknown if this observed reduction translates into reduced risk for sexual transmission of the virus.

The potential epidemiological impact of a genital herpes vaccine for women

Background: In two phase III vaccine trials immunisation of women previously uninfected by herpes simplex virus provided protection against genital herpes disease. In deciding policy, an evaluation of the epidemiological...

Polymerase chain reaction for laboratory diagnosis of orf virus infections.

The orf virus of sheep and goats is one of several zoonotic parapoxviruses. In the ovine/caprine host it causes contagious ecthyma (contagious pustular dermatitis, scabby mouth), but in humans it normally causes solitary or clustered orf lesions, typically on hands, arms or face. In addition to disease in the animals, the virus can be quite a nuisance as an occupational hazard in farmers and butchers. Clinical diagnosis is often possible, but laboratory diagnosis is sometimes necessary. For virus isolation, primary ovine or bovine cells, not routinely present, are needed. Serological methods exist, but electron microscopy is the most commonly used method. To develop a reliable method for the laboratory diagnosis of orf zoonoses, without virus culture and without access to an electron microscope. A suitable primer pair was designed for orf polymerase chain reaction (PCR), using the Oligo software and sequence information from GenBank. Orf positive controls and specimens were kindly provided by several public health centers. Molluscum contagiosum specimens were provided by a dermatologist. HSV-1, HSV-2 and VZV positive swab specimens came from our routine diagnostic service. Asymptomatic skin specimens were obtained from sheep heads from the abattoir, and swab specimens from the heads of asymptomatic sheep. Selected amplified orf PCR positive specimens were sequenced to ensure the authenticity of the PCR products. Orf positive specimens were sent to another laboratory for electron microscopy. A robust PCR was developed, with very small inter-run variation. All specificity demands were met, and the sensitivity seems to be good or excellent. All negative specificity controls from cell cultures and non-orf viruses were negative. Twenty-two (95.7%) of 23 scab or swab specimens with suspected orf etiology were orf PCR positive. Five of eight skin specimens from sheep heads from the abattoir were positive, and all 11 swab specimens from asymptomatic sheep were negative. Electron microscopy demonstrated orf-like particles in orf-PCR positive specimens. This PCR seems to be suitable as a diagnostic test for orf in humans, but asymptomatic virus shedding in sheep or goats may complicate veterinary applications of the assay.

The importance of diagnosing genital herpes.

Genital herpes is the result of infection by herpes simplex virus type 2 (HSV-2) and, to a lesser extent, HSV-1. Recent years have seen a rise in the prevalence of genital HSV infection in both industrialized and developing countries. The main factors attributed to the spread of HSV infection include asymptomatic virus shedding, and under-recognition and under-diagnosis of the disease. At the level of the individual patient, genital herpes is associated with significant psychosocial morbidity and complications such as neonatal herpes, the result of transmission of HSV from mother to baby. HSV-2 infection is also implicated in the transmission and acquisition of human immunodeficiency virus (HIV). As genital HSV infection has substantial public health implications, increased awareness of the disease and its prevalence, together with better use of diagnostic tests, may be one step towards more effective management and infection control.

Cervical shedding of herpes simplex virus and cytomegalovirus throughout the menstrual cycle in women infected with human immunodeficiency virus type 1

Objective: Our purpose was to evaluate the frequency and patterns of the shedding of herpes simplex virus and cytomegalovirus in the female genital tract throughout the menstrual cycle. Study Design: Seventeen women, all seropositive for herpes simplex virus types 1 and 2, cytomegalovirus, and human immunodeficiency virus type 1, underwent daily evaluation of cervical viral shedding for the duration of 1 menstrual cycle (21-31 visits per woman). Serum estradiol and progesterone levels were monitored 3 times weekly. Results: Overall, herpes simplex virus deoxyribonucleic acid was detected in 43 (10%) of 450 cervical swabs, and cytomegalovirus deoxyribonucleic acid was detected in 232 (52%) of 450 cervical swabs. For individual women there was considerable variability in the percentage of days on which virus was detected, ranging from 0% to 33% for herpes simplex virus and from 20% to 97% for cytomegalovirus. Shedding of herpes simplex virus did not vary significantly with menstrual cycle; however, shedding of cytomegalovirus was significantly more frequent in the luteal phase (odds ratio, 1.9; 95% confidence interval, 1.1-3.4). A CD4 + lymphocyte count <200/μL was associated with increased frequency of the detection of herpes simplex virus (odds ratio, 5.7; 95% confidence interval, 1.1-29.4). Conclusions: Asymptomatic cervical shedding of both herpes simplex virus and cytomegalovirus occurs very frequently in women infected with human immunodeficiency virus type 1. The risk of transmitting these viruses to sexual partners and neonates may be higher than previously recognized. (Am J Obstet Gynecol 2000;183:948-55.)

Update on antiviral therapy for genital herpes infection.

For the primary infection of genital herpes, antiviral therapy with acyclovir is the gold standard. For recurrences, there are two options: antiviral treatment of each outbreak as it arises, or suppression of outbreaks with daily oral therapy. Patients tend to prefer the latter because it can decrease the number and severity of outbreaks, but it increases asymptomatic viral shedding and, therefore, the risk of unwittingly transmitting herpes simplex virus to uninfected sexual partners.

Asymptomatic shedding of herpes simplex virus into the oral cavity of patients with atopic dermatitis.

Asymptomatic shedding of herpes simplex virus (HSV) into the oral cavity is one of the important sources of the infection. We anticipated that the oral cavity is one of the possible sites of initial recurrence in patients with recurrent-type eczema herpeticum. Oral swabs were collected from 24 patients with atopic dermatitis aged from 13 to 29 years, and as a control population, from seven patients with skin diseases other than atopic dermatitis aged from 16 to 29 years. We tried to detect HSV DNA by the polymerase chain reaction method. HSV DNA was detected in eight out of 31 specimens from 15 patients with facial lesions of atopic dermatitis, and in one of 15 specimens from nine patients without facial atopic dermatitis, and in two of ten specimens from seven patients with other skin diseases. However, these differences are not statistically significant. Moreover, no patients developed eczema herpeticum during the period of this study. These results suggest that facial atopic dermatitis may not lead to oral HSV shedding, and there may be little opportunity for the virus in the oral cavity to contaminate other skin sites in adolescents and adults.

Herpes simplex virus infection in a paediatric burn patient: case report and review

Herpes simplex virus (HSV) infection in the burn patient is thought to occur relatively frequently. Most commonly, children with significant burns, particularly involving the head and neck, are affected. Burn related immunosuppression is thought to allow reactivation of latent HSV in most cases, although primary HSV infection has been recognized. Clinical manifestations vary from asymptomatic viral shedding, to prolonged fever with eruption of vesicles, to rare cases of systemic visceral dissemination. Healing partial thickness wounds and donor sites are most prone to infection. Laboratory confirmation of HSV infection relies on direct demonstration of the virus and/or observation of a rise in antibody titer. Treatment of an established HSV infection includes use of IV Acyclovir, meticulous wound care, and efforts to prevent nosocomial spread. The vast majority of cases resolve without sequelae unless complicated by systemic, multiorgan HSV infection.

Best Tests To Predict and Monitor CMV Infection

Cytomegalovirus (CMV) infection in renal transplant patients may contribute to graft rejection. How best to distinguish such infection from asymptomatic viral shedding is contingent upon the efficacy of available detection methods. These French investigators compared 6 CMV assays in 30 renal transplant patients to ascertain which were the most useful in determining the …

Shedding of herpes simplex virus type 1 into tears and saliva in healthy Japanese adults.

It is well known that asymptomatic viral shedding is one of the forms of reactivation of herpes simplex virus type-1 (HSV-1). Although there have been some long-term investigations of viral shedding into tears and saliva in healthy subjects in the U.S.A, there have previously been no investigation study in Japan. Racial differences in the incidence of reactivation of HSV-1 have been pointed out, and it has been considered that reactivation is found less often among Japanese people than among Westerners. In the present study, we selected 10 healthy adults (7 males and 3 females) to isolate HSV-1 from tears and saliva 3 times a week over 6 months, and the results were compared with the results of other studies conducted in the U.S.A. It was found that the virus was isolated in 5 (3 males and 2 females) of 10 subjects and of the 5 subjects, the virus was isolated from saliva in 4 and from tears in 1. The number of specimens was 1,742 for tears and 871 for saliva with isolation of 1 and 4, respectively. The duration of shedding was only 1 day in all of the 5 subjects in whom the virus was isolated. The isolation frequency was significantly lower among Japanese people than among American people when our results were compared with the results of studies conducted in the U.S.A. It was clear that the reactivation rate was lower for Japanese people in terms of asymptomatic shedding.

New developments in the epidemiology, natural history and management of genital herpes

The prevalence of genital herpes is increasing in several populations worldwide. Factors that may be contributing to this increase include greater numbers of sexual partners, the high frequency of asymptomatic infections, poor use of safe sexual practices, and possibly the decreased incidence of childhood oral herpes simplex virus infection. Transmission occurs via skin-to-skin or mucous membrane contact during periods of viral shedding when lesions are present but may also occur when the patient is unaware of the lesions or when lesions are not clinically apparent. This has important implications for strategies to prevent transmission of the disease. The introduction of the antiherpes agent, acyclovir, and more recently famciclovir and valacyclovir, facilitates the management of genital herpes. Treatment of first-episode genital herpes reduces the severity and duration of symptoms, time to lesion healing, and cessation of viral shedding. Episodic treatment of recurrences as they occur may be of benefit to some patients. Daily suppressive therapy significantly reduces the frequency of recurrences and asymptomatic viral shedding. Accordingly, patients who experience frequent or severe recurrences, those particularly troubled by their disease, and those who wish to reduce the frequency of asymptomatic infection generally prefer suppressive therapy. The possibility that suppressive therapy may have an impact on transmission of the disease is currently under investigation. Antiviral treatments have important implications for public health and may help reduce the psychological and psychosocial impact of genital herpes on individual patients.

A Randomised Placebo Controlled Trial of Suppressive Acyclovir in Late Pregnancy in Women with Recurrent Genital Herpes Infection

Objective To evaluate the efficacy and safety of a suppressive course of acyclovir in late pregnancy in women with recurrent genital herpes infection on the incidence of viral shedding, herpes lesion development and caesarean section for recurrent genital herpes. Design Double-blind, randomised placebo controlled clinical trial. Setting Adepartment of genitourinary medicine in Sheffield and an antenatal clinic in London. Population Pregnant women with recurrent genital herpes infection at < 36 weeks of gestation. Methods Participating women were given acyclovir 200 mg four times a day (or matching placebo) from 36 weeks of gestation until the time of delivery. Women were seen weekly and viral cultures were obtained from the cervix and vulva. Decisions regarding mode of delivery were left to the discretion of the attending obstetrician. Main outcome measures Delivery by caesarean section for recurrent genital herpes infection. Number of episodes of recurrent genital herpes infection and number of episodes of asymptomatic viral shedding during the treatment period. In addition blood was taken at two weekly intervals to determine acyclovir levels. Results The total number of women recruited was 63 (3 1 received acyclovir and 32 received placebo). The number of women undergoing delivery by caesarean section for recurrent herpes at the time of delivery was 12 (19%). The odds ratio for delivery by caesarean section in women taking acyclovir, compared with those talung placebo, was 0.44 (95% CI 0.09–1.59). The odds ratio for clinical recurrences during treatment was 0.10 (95% confidence interval 0.00–0.86) and the odds ratio for clinical recurrence or asymptomatic shedding during treatment was 0.32 (95% CI 0.05–1.56). Conclusion This trial was unable to demonstrate that acyclovir can significantly decrease the number of caesarean section deliveries; however, the number of clinical recurrences was significantly reduced. Two episodes of asymptomatic virus shedding both occurred in women taking acyclovir. At the present time there is little evidence to suggest that acyclovir should be used outside randomised controlled trials for the suppression of recurrent genital herpes infection during pregnancy.

HERPES: Atypical Clinical Manifestations

Herpes simplex viruses (HSV) 1 and 2 are responsible for genital herpes which is usually recognized as vesicles that ulcerate and eventually heal but recur periodically. Atypical genital herpes is often described in immunocompromised patients and can present as large, chronic, hyperkeratotic ulcers. Acyclovir-resistant HSV is occasionally isolated from such ulcers. Most cases of HSV infection reproduce subtle signs and symptoms, or more commonly, asymptomatic viral shedding. Such subclinical presentations may be responsible for most of the 30% increase in the prevalence of genital herpes in the United States during the past two decades.

HERPES: Transmission and Viral Shedding

Herpes simplex virus infections are transmitted through contact with infected oral or genital secretions. The virus can be present on mucosa during a symptomatic recurrence or asymptomatically. Most transmissions to neonates and sexual partners occur during asymptomatic viral shedding. The frequency of viral isolation in the absence of lesions ranges from 2% to 6% of days; however, studies using more sensitive tests, such as polymerase chain reaction, show that viral shedding can occur on the average 28% of days.

Herpes simplex viruses.

Herpes simplex virus (HSV) infections of humans have been documented since the advent of writing. The spectrum of disease was expanded to include primary and recurrent infections of mucous membranes (gingivostomatitis, herpes labialis, and genital HSV infections), keratoconjunctivitis, neonatal HSV infection, visceral HSV infections of the immunocompromised host, HSV encephalitis, Kaposi's varicella-like eruption, and an association with erythema multiforme. Cumulative experience suggests that factors associated with pregnancy may place both the mother and fetus at increased risk for severe infection, possibly because of altered cell-mediated immunity. The major risk to the fetus is with primary or initial genital HSV infection of the mother. PCR evaluation of cerebrospinal fluid can be utilized to monitor therapeutic outcome in patients with herpes simplex encephalitis. The use of HSV for gene therapy heralds a new era of herpes biology, the conversion of a hazardous foe into a user-friendly surgical tool. Asymptomatic shedding of virus can continue despite clinically effective suppression with acyclovir, so the possibility of person-to-person transmission persists. Newborns with HSV infections can be classified as having disease that is localized to the skin, eyes, and mouth; affects the central nervous system (CNS); or is disseminated. Drug resistance was considered rare and resistant isolates were thought to be less pathogenic until a series of acyclovir-resistant HSV isolates from patients with AIDS were characterized. The risk of nephrotoxicity can be minimized by administering acyclovir by slow infusion and ensuring adequate hydration.

Famciclovir reduces asymptomatic viral shedding in HSV infection

Famciclovir reduces asymptomatic viral shedding in HSV infection