Herpes Simplex Virus Reactivation Research Articles

Reactivation of Herpes Simplex Virus Type 1 and Varicella‐Zoster Virus and Therapeutic Effects of Combination Therapy With Prednisolone and Valacyclovir in Patients With Bell's Palsy

To determine whether reactivation of herpes simplex virus (HSV) type 1 or varicella-zoster virus (VZV) is the main cause of Bell's palsy and whether antiviral drugs bring about recovery from Bell's palsy. Randomized, multicenter, controlled study. One hundred fifty patients with Bell's palsy were enrolled in this study. The patients were randomly assigned to a prednisolone group or a prednisolone-valacyclovir group, in whom virologic examinations for HSV-1 and VZV were performed by simple randomization scheme in sealed envelopes. The recovery rates among various groups were analyzed using the Kaplan-Meier method and the Cox proportional hazards model. Reactivation of HSV-1, VZV, and both viruses was detected in 15.3%, 14.7%, and 4.0% of patients, respectively. There was no significant difference in recovery rates between the prednisolone group and the prednisolone-valacyclovir group, although recovery in the patients with HSV-1 reactivation tended to be higher in the prednisolone-valacyclovir group than in the prednisolone group. There was a significant difference in recovery among age groups and between individuals with complete and incomplete paralysis. Reactivation of HSV-1 or VZV was observed in 34% of the patients with Bell's palsy. The effect of combination therapy with prednisolone and valacyclovir on recovery was not significantly higher than that with prednisolone alone.

Clinical and Therapeutic Issues for Herpes Simplex Virus-2 and HIV Co-Infection

A synergy between HIV type-1 (HIV-1) and herpes simplex virus-2 (HSV-2) has been demonstrated in many epidemiological and clinical studies over the last decade. HIV-1 infection exacerbates the clinical impact and frequency of HSV-2 reactivation events; furthermore, HSV-2 infection exacerbates the risk of HIV acquisition and transmission and may accentuate HIV disease progression. In order to maximise the impact of existing and future therapeutic and preventive interventions, this article reviews the epidemiological, clinical and therapeutic considerations associated with episodic treatment and suppression of HSV-2 infection in HIV-infected individuals.Specifically, this article describes the current expanding epidemics of both HIV and HSV-2, and how high rates of asymptomatic herpes virus shedding contribute to the under-diagnosis and continued spread of both HSV-2 and HIV. Furthermore, multiple clinical trials have studied the efficacy and clinical utility of aciclovir and other nucleoside analogues for treating and suppressing HSV-2. We review these studies and summarise the guidelines for these regimens, particularly noting the accumulated experience documenting the utility of herpes treatment and suppression in altering the natural history of symptoms and documenting the low rate of HSV-2 drug resistance to nucleoside analogues observed after more that a decade of use. Finally, there are now also growing data describing the benefits of herpes suppression in the context of individuals co-infected with HIV/HSV-2, with additional clinical trials poised to further elucidate these issues in the near future.

Active Cytomegalovirus Infection in Patients with Septic Shock

Cytomegalovirus (CMV) is a pathogen of emerging importance for patients with septic shock. In this prospective study, 25 immunocompetent CMV-seropositive patients with septic shock and an intensive care unit stay of > or =7 days were monitored by using quantitative pp65-antigenemia assay, shell vial culture, and virus isolation. Within 2 weeks, active CMV infection with low-level pp65-antigenemia (median 3 positive/5x10(5) leukocytes) developed in 8 (32%) patients. Infection was controlled within a few weeks (median 26 days) without use of antiviral therapy. Duration of intensive care and mechanical ventilation were significantly prolonged in patients with active CMV infection. CMV reactivation was associated with concomitant herpes simplex virus reactivation (p = 0.004). The association between active CMV infection and increased illness could open new therapeutic options for patients with septic shock. Future interventional studies are required.

Efficient Reactivation of Latent Herpes Simplex Virus from Mouse Central Nervous System Tissues

For decades, numerous ex vivo studies have documented that latent herpes simplex virus (HSV) reactivates efficiently from ganglia, but rarely from the central nervous systems (CNS), of mice when assayed by mincing tissues before explant culture, despite the presence of viral genomes in both sites. Here we show that 88% of mouse brain stems reactivated latent virus when they were dissociated into cell suspensions before ex vivo explant culture. The efficient reactivation of HSV from the mouse CNS was demonstrated with more than one viral strain, viral serotype, and mouse strain, further indicating that the CNS can be an authentic latency site for HSV with the potential to cause recurrent disease.

Effects of Latency-associated Transcripts During Herpes Simplex Virus Latency and Reactivation

潜伏相关转录体是单纯疱疹病毒潜伏期间大量存在和被转录的RNA,也是目前研究单纯疱疹病毒潜伏-复发机制的热点.通过近30年的研究,对潜伏相关转录体在单纯疱疹病毒潜伏-复发中所起的作用有了更进一步的认识,但对其作用机制了解甚少.在这一未知领域,不断有新的假说提出,但其科学性有待进一步考证.为此,总结近年来对单纯疱疹病毒潜伏相关转录体作用机制的研究成果,为开展相关研究提供理论基础。

Oral shedding of herpes simplex virus type 1 in immunocompetent persons

Reactivation of herpes simplex virus-1 (HSV-1) can result in recurrent herpes labialis lesions (RHL) and in oral shedding of virus. This study utilized polymerase chain reaction (PCR) to document the frequency and quantity of such shedding. Thirty adults with greater than three RHL episodes per year were followed through one recurrence. They collected swabs for PCR every 12 h starting at prodrome and for 10 days thereafter. Shedding was analyzed with regard to frequency, timing and quantity. HSV-1 was detectable in 87% of participants for a mean of 4 days. Shedding occurred most frequently during the vesicle/ulcer stage (91% of subjects), but was common in both clinical and subclinical stages (50% vs. 23%, average log DNA copy number/ml(2) 2.6 vs. 1.4). The majority of RHL patients shed viral DNA. Shedding occurred before and after the appearance of clinical lesions. Such findings may be useful in designing methods to reduce viral shedding and prevent transmission.

Prophylactic Perioperative Antiviral Therapy for LASIK in Patients With Inactive Herpetic Keratitis

To report the outcome of LASIK in patients with inactive herpetic keratitis in which perioperative antiviral prophylaxis was used to prevent the recurrence of ocular herpes. We report an uncontrolled series of five patients with inactive herpetic keratitis for at least 1 year before surgery in whom LASIK was successfully performed. All patients showed normal topography, pachymetry, and corneal sensitivity with no central corneal scarring. Perioperative prophylaxis was used in each case with oral valacyclovir and topical acyclovir ointment. None of the eyes developed reactivation of herpetic keratitis during follow-up. This study suggests that perioperative antiviral prophylaxis may protect the cornea from herpes simplex virus reactivation after LASIK.

Narrowband ultraviolet B (UVB) phototherapy in children

While narrowband ultraviolet B (UVB) phototherapy is a well-established treatment for a range of skin conditions in adults, there is little in the literature about its use in children and data regarding its long-term carcinogenic potential are lacking. We undertook a retrospective review of the use of narrowband UVB phototherapy in a paediatric population attending two Glasgow Hospitals. Phototherapy case notes for all children aged 16 years and under at time of treatment were reviewed at two hospital sites between 1996 and 2002. In total, 77 children had been treated (median age 12 years, range 4-16). The conditions treated most frequently were psoriasis (45%) and atopic eczema (32%). Other dermatoses treated included alopecia areata, acne, hydroa vacciniforme and polymorphic light eruption. Treatment courses for atopic conditions were longer than those required for psoriatic conditions: median number of treatments 24 for atopic eczema (range 3-46), and 17.5 for psoriasis (range 9-35). By the end of treatment, 68% of the atopic patients and 63% of the patients with psoriasis had cleared. The adverse event profile was similar to that in adults, with erythema, herpes simplex reactivation and PLE all recorded. Anxiety was a problem for five patients. We conclude that narrowband UVB phototherapy is a useful and well-tolerated treatment for children with severe or intractable inflammatory skin disease, but concerns remain regarding long-term side-effects.

Salvage non-myeloablative allogeneic transplantation after failure of an autologous transplantation in multiple myeloma

male (22), female (11), median age 56 years (range 39–70), Stage II (9), Stage III (24), IgG (22), IgA (9), free light chain (2). Median paraprotein at initiation of consolidation was 0 (range 0–3.6) (n 33), day 1 cycle 4 was 0.1 (range 0–2.1) (n 23), and at end of study was 0.35 (range 0–3.4) (n 20). With a median follow up of 14 months, disease progression has occurred in 5 patients with 1 death. Fourteen patients (42%) experienced reactivation of VZV, 2 patients had human herpes virus 6 reactivation, and 1 patient had oral herpes simplex virus reactivation, all requiring therapy. The median absolute lymphocyte count at the onset of viral reactivation was 1336/mcl (range 600–4800/mcl). A significant difference was seen in the mean CD8 count just prior to transplantation between those patients with viral reactivation (243, range 77–685) and the rest of the study population (392, range 87–1339) (P .03). The median time from enrollment to VZV reactivation was 189 days (range 25–375). Ten patients had grade 1/2 and none had grade 3/4 neuropathy at study enrollment. At initiation of post transplant bortezomib 21 (64%) had grade 1/2 neuropathy and 1 (3%) had grade 3/4 neuropathy. Treatment emergent neuropathy on once weekly bortezomib was seen in only 3 patients (9%), necessitating dose reduction (1 patient) or discontinuation of therapy (2 patients). No grade 3/4 thrombocytopenia or neutropenia was observed with consolidation bortezomib. We conclude that bortezomib when administered preand post HDCT in MM patients results in a very high rate of viral reactivation. This finding may be explained by a decrease in circulating CD8 T cells and has implications for future clinical trials of bortezomib in this setting.

Oral Herpes Simplex Reactivation After Intrathecal Morphine: A Prospective Randomized Trial in an Obstetric Population

Oral Herpes Simplex Reactivation After Intrathecal Morphine: A Prospective Randomized Trial in an Obstetric Population

Genital Herpes Simplex Virus Infection and Perinatal Transmission of Human Immunodeficiency Virus

To assess the risk of perinatal human immunodeficiency virus (HIV) transmission in HIV-infected women clinically diagnosed with genital herpes simplex virus (HSV) infection during pregnancy. This retrospective analysis included 402 HIV-infected pregnant women who enrolled from 1994-1999 in a multicenter prospective cohort study in New York City, who delivered a liveborn singleton infant with known HIV infection status, and who had information on diagnosis of genital HSV infection during pregnancy. Study participants were determined to have genital HSV infection during pregnancy by documentation of clinical diagnosis. Forty-six (11.4%) of the study participants delivered HIV-infected infants. Twenty-one (5.2%) had clinical diagnosis of genital HSV infection in pregnancy. Six (28.6%) of the 21 HIV-infected women with a clinical diagnosis of genital HSV infection delivered an HIV-infected infant. In univariate analyses, HIV-infected pregnant women with clinical diagnosis of genital HSV infection during pregnancy had a significantly increased risk of perinatal HIV transmission (odds ratio 3.4, 95% confidence interval 1.3-9.3; P = .02). When other factors associated with perinatal HIV transmission were included in a logistic regression model (lack of zidovudine therapy during pregnancy or delivery, prolonged rupture of membranes, and preterm delivery), clinical diagnosis of genital HSV infection during pregnancy remained a significant independent predictor of perinatal HIV transmission (adjusted odds ratio 4.8, 95% confidence interval 1.3-17.0; P = .02). Clinical diagnosis of genital HSV infection during pregnancy in HIV-infected women may be a risk factor for perinatal HIV transmission. If future studies confirm this association, therapy to suppress genital HSV reactivation during pregnancy may be a strategy to reduce perinatal HIV transmission.

Oral Herpes Simplex Reactivation after Intrathecal Morphine: A Prospective Randomized Trial in an Obstetric Population

Oral Herpes Simplex Reactivation after Intrathecal Morphine: A Prospective Randomized Trial in an Obstetric Population

Herpes encephalitis after meningioma resection

Herpes simplex encephalitis (HSE) is the most common and gravest sporadic form of acute encephalitis.1,2 Between 30 and 70% of cases are fatal, and the majority of patients who survive have serious neurologic complications. In adults, HSE mostly results from reactivation of latent herpes simplex virus (HSV) infection of trigeminal nerve ganglia or brain parenchyma. We present a case of HSE in an immunocompetent patient after uneventful meningioma resection, which shows that HSE is a rare3,4 but severe complication after neurosurgery. We also show that decompressive craniotomy can be a lifesaving option for HSE treatment. A 47-year-old woman presented with headache and a slowly progressive right-sided disturbance of vision. Otherwise, the medical history of the patient was unremarkable. On examination, apart from a decreased visual acuity of the right eye, no neurologic deficit was detected. A CT scan revealed a meningioma …

Bortezomib (Velcade) When Given Pretransplant and Once Weekly as Consolidation Therapy Following High Dose Chemotherapy (HDCT) Leads to High Rates of Reactivation of Varicella Zoster Virus (VZV).

Bortezomib is a selective inhibitor of the 26S proteasome with proven efficacy in relapsed multiple myeloma (MM). Current trials are evaluating bortezomib both as single agent and combination therapy in a variety of clinical settings. No data exists on the tolerability of bortezomib in the immediate post transplant setting. We conducted a prospective pilot study of bortezomib administered to MM patients both prior to, and as consolidation therapy following HDCT. Patients received 2 cycles of bortezomib 1.3mg/m2 on days 1, 4, 8 and 11 of every 21 days, beginning 42 days prior to stem cell collection. HDCT comprised melphalan 100mg/m2/day x 2 days followed by reinfusion of peripheral blood stem cells 48 hours later. All patients received six cycles of consolidation bortezomib 1.3mg/m2 given once weekly (for ease of administration) for 4 of every 5 weeks, 90–120 days following transplantation. To date, 40 patients have been enrolled. 3 patients did not receive HDCT (medical complications unrelated to therapy 1, failure to mobilize sufficient stem cells 1, disease progression 1). 4 patients did not proceed to consolidation therapy after HDCT (disease progression 1, grade 3/4 neuropathy 3). 33 patients have received at least one post transplantation cycle of consolidation bortezomib. Patient and disease characteristics at diagnosis were as follows (no. of patients): male (22), female (11), median age 56 years (range 39–70), Stage II (9), Stage III (24), IgG (22), IgA (9), free light chain (2). Median paraprotein at initiation of consolidation was 0 (range 0–3.6)(n=33), Day 1 cycle 4 was 0.1 (range 0–2.1)(n=23) and at end of study was 0.35 (range 0–3.4)(n=20). With a median follow up of 14 months 5 patients have had disease progression and 1 has died from progressive disease. 13 of 33 patients (39%) experienced reactivation of varicella zoster virus (VZV), 2 patients had human herpes virus 6 reactivation and 1 patient had oral herpes simplex virus reactivation, all requiring therapy. The median absolute lymphocyte count (ALC) at the onset of viral reactivation was 1336/mcl (range=600–4800/mcl). No significant difference was seen in the median ALC at initiation of consolidation therapy between the study population (1400/mcl, range 700–3500/mcl) and those patients with viral reactivation (1300/mcl, range 800–3700/mcl). The median time from enrollment to VZV reactivation was 189 days (range 25–375). 10 of 33 patients had grade 1/2 and none had grade 3/4 neuropathy at study enrollment. At initiation of post transplant bortezomib 21 of 33 (64%) had grade 1/2 neuropathy and 1 of 33 (3%) had grade 3/4 neuropathy. Treatment emergent neuropathy on once weekly bortezomib was seen in only 3 of 33 (9%) patients, necessitating dose reduction in 1 and discontinuation of therapy in the other 2 individuals. No grade 3/4 thrombocytopenia or neutropenia was observed with once weekly bortezomib. In conclusion, we observed a very high rate of VZV reactivation in this prospective study. Elsewhere we report that bortezomib therapy results in a decrease in circulating CD8 T cell and CD56 natural killer cell counts. Alterations in proportions of T cell subsets may therefore explain this finding which has major implications for future clinical trials of bortezomib in the peritransplant setting.

Reactivation of Herpes Simplex Virus after Liver Transplantation

Reactivation of herpes simplex virus (HSV) after liver transplantation occurs but the incidence and clinical significance are unknown. We recruited 12 consecutive male patients listed for liver transplantation and positive for HSV antibody. HSV polymerase chain reaction was performed on mouth and penile swabs before and at days 5 and 10 after transplant. Data were recorded regarding clinical evidence of HSV infection, degree of immune suppression, length of intensive care stay, and use of antiviral agents. Five out of twelve patients (42%) had evidence of oral reactivation after transplant although only one had clinical manifestations. Genital reactivation was not seen. Reactivation did not correlate with immune suppression but duration of intensive care stay was a possible risk factor. Ganciclovir prescribed for cytomegalovirus prophylaxis in one patient was ineffective. Oral reactivation of HSV after liver transplantation is common; although clinical significance appears low in this small series, routine testing could be implemented readily.

A non-randomized comparative study using different doses of acyclovir to prevent herpes simplex reactivation in patients submitted to autologous stem cell transplantation

The reactivation of Herpes Simplex virus (HSV) occurs in 70% to 80% of patients submitted to autologous stem cell transplantation (ASCT); it increases the severity of chemotherapy-induced mucositis. Therefore, the use of acyclovir in ASCT patients is considered standard practice. However, the minimum dose needed to prevent reactivation is a matter of debate. We compared two doses of acyclovir in a non-randomized fashion in 59 patients submitted to ASCT: 32 patients received a dose of 125 mg/m(2) IV every six hours and the subsequent 27 patients received a dose of 60 mg/m(2) IV every six hours. Viral excretion was evaluated through weekly viral culture of oral swabs. Grade 4 mucositis was more frequent in Group 1 (p= 0.03). The reactivation rates in Groups 1 and 2 were 9% and 4%, respectively (p= 0.62, 95% confidence interval -7 - 18). Prophylaxis with reduced doses of intravenous acyclovir seems to be as effective as a higher dose in inhibiting HSV reactivation, with a significant reduction in cost. Prospective randomized studies are needed to confirm our conclusions.

Viral Prophylaxis in Organ Transplant Patients

AbstractFor Abstract see ChemInform Abstract in Full Text.

Delayed cranial neuropathy after neurosurgery caused by herpes simplex virus reactivation: report of three cases

Background Delayed cranial neuropathy is an uncommon complication of neurosurgical interventions of which the exact etiology is uncertain. Several authors have hypothesized that reactivation of herpesviruses may play a role. Case Descriptions The first patient underwent microvascular decompression of the left facial nerve because of hemifacial spasm. Nine days postoperatively, he developed severe facial weakness on the ipsilateral side. The polymerase chain reaction for herpes simplex virus (HSV) was positive in the cerebrospinal fluid (CSF). Treatment with intravenous acyclovir was initiated, after which a rapid and marked improvement was observed. The second patient developed left-sided facial numbness 20 days after microvascular decompression of the left facial nerve. The polymerase chain reaction for HSV was positive in the CSF. Treatment with intravenous acyclovir resulted in full recovery. The third patient underwent a suboccipital craniectomy with excision of a meningioma located at the left petrosal apex. Three months postoperatively, she developed multiple cranial neuropathies (involving cranial nerves V, VI, VIII, and XII). This was accompanied by serologic evidence of HSV reactivation and a positive polymerase chain reaction for HSV in the CSF. The patient was successfully treated with intravenous acyclovir. Conclusions The 3 reported cases provide evidence that delayed postoperative cranial neuropathy can be caused by HSV reactivation and can involve multiple cranial nerves. An increased awareness of this treatable postoperative complication is warranted.

Oral Herpes Simplex Reactivation After Intrathecal Morphine: A Prospective Randomized Trial in an Obstetric Population

There is now evidence for an association between the use of epidural morphine and reactivation of herpes simplex labialis (HSL). There are no studies that definitively demonstrate the relationship between HSL reactivation and spinal intrathecal morphine. To investigate this relationship, we randomized and prospectively studied 100 obstetric patients with a history of HSL undergoing cesarean delivery under spinal anesthesia. One group received intrathecal morphine plus IV morphine via patient-controlled analgesia (ITM+PCA group) for postoperative analgesia, and a second group received only IV morphine via patient-controlled analgesia for postoperative analgesia (PCA-only group). Patients were followed for a 30-day period. In the ITM+PCA group 19 (38%) patients had HSL reactivation whereas eight (16.6%) had HSL reactivation in the morphine PCA-only group (P = 0.028). The incidence of pruritus in the ITM+PCA group was also more frequent in the early postoperative period. Our data show HSL reactivation in both the ITM+PCA group and PCA-only morphine group, with a more frequent incidence in the ITM+PCA group.

Recurrent herpes simplex virus type 2 infection of the hand complicated by persistent lymphoedema

A 33-year-old, immunocompetent woman had recurrent herpes simplex virus reactivation of the right hand presenting with a cellulitis-like picture. She continued to have monthly debilitating recrudescences for more than 3 years until an adequate dosage of prophylactic antiviral therapy was achieved. After 2 years of repeated episodes she had chronic dull pain and developed persistent acquired lymphoedema of the left hand and forearm, which is an extremely rare complication. This case highlights the need for herpes simplex infection of the hand to be included in the differential diagnosis of bacterial cellulitis in order for appropriate and prompt therapy to be achieved.