Activation of Double-Stranded RNA-Activated Protein Kinase in the Dorsal Root Ganglia and Spinal Dorsal Horn Regulates Neuropathic Pain Following Peripheral Nerve Injury in Rats.

Double-stranded RNA (dsRNA)-activated kinase (PKR) is an important component in inflammation and immune dysfunction. However, the role of PKR in neuropathic pain remains unclear. Here, we showed that lumbar 5 spinal nerve ligation (SNL) led to a significant increase in the level of phosphorylated PKR (p-PKR) in both the dorsal root ganglia (DRG) and spinal dorsal horn. Images of double immunofluorescence staining revealed that p-PKR was expressed in myelinated A-fibers, unmyelinated C-fibers, and satellite glial cells in the DRG. In the dorsal horn, p-PKR was located in neuronal cells, astrocytes, and microglia. Data from behavioral tests showed that intrathecal (i.t.) injection of 2-aminopurine (2-AP), a specific inhibitor of PKR activation, and PKR siRNA prevented the reductions in PWT and PWL following SNL. Established neuropathic pain was also attenuated by i.t. injection of 2-AP and PKR siRNA, which started on day 7 after SNL. Prior repeated i.t. injections of PKR siRNA prevented the SNL-induced degradation of IκBα and IκBß in the cytosol and the nuclear translocation of nuclear factor κB (NF-κB) p65 in both the DRG and dorsal horn. Moreover, the SNL-induced increase in interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) production was diminished by this treatment. Collectively, these results suggest that peripheral nerve injury-induced PKR activation via NF-κB signaling-regulated expression of proinflammatory cytokines in the DRG and dorsal horn contributes to the pathogenesis of neuropathic pain. Our findings suggest that pharmacologically targeting PKR might be an effective therapeutic strategy for the treatment of neuropathic pain.

Randomized clinical trial of famciclovir or acyclovir for the treatment of herpes zoster in adults.

BACKGROUND: This study investigated the safety and efficacy of famciclovir compared to acyclovir in patients with herpes zoster, to determine whether the two regimens are equally effective for the treatment of patients with uncomplicated herpes zoster over a period of 7days. METHODS: Patients were randomly assigned to receive either famciclovir 500mg (one tablet) three times daily or acyclovir 800mg (two capsules) five times daily for 7 days. The primary endpoint was defined as the time to full crusting of herpes zoster lesions. Secondary endpoints were the proportion of patients who achieved complete cure and the change in score of signs/symptoms (pain, vesicular lesions, loss of sensitivity, burning pain, and pruritus) according to the patient diary. This study has been registered at ClinicalTrials.gov (NCT01327144). RESULTS: One hundred and seventy-four patients were enrolled and randomized; 151 of these patients completed treatment (n=75 famciclovir, n=76 acyclovir). A similar proportion of patients who received acyclovir (94.74%) and famciclovir (94.67%) achieved complete cure. The mean time to full crusting of herpes zoster lesions was 15.033days in the acyclovir group and 14.840days in the famciclovir group (log-rank p-value=0.820). The most common adverse events in the pooled groups were headache, diarrhea, nausea, back pain, cold, and drowsiness, but none of these was deemed to be clinically important. CONCLUSIONS: Both interventions obtained high rates of cure and had a similar time to full crusting of lesions. Analysis of the primary efficacy endpoint proved that famciclovir is non-inferior to acyclovir, as the confidence interval for the difference in efficacy did not violate the non-inferior margin. Therefore, the results are not different enough to be clinically relevant.

Migraine Headache Treated with Famciclovir and Celecoxib: A Case Report.

INTRODUCTION: Herpes simplex virus (HSV) has been speculated to play a role in migraine headache pathophysiology. We present the first successful migraine headache treatment with therapy specifically targeting HSV infection. CASE PRESENTATION: A previously healthy 21-year-old white woman presented with a severe headache and was diagnosed with severe migraine headache disorder. She initially was treated with standard migraine headache medications without symptomatic improvement. She was then given famciclovir and celecoxib. The patient fully recovered within days and continues to enjoy significant reduction in severity and frequency of symptoms. DISCUSSION: Famciclovir and celecoxib may work synergistically against HSV. The virus may play a role in the pathophysiology of migraine headaches, and this is the first case report of successful migraine headache treatment with these medications. Further studies are needed to elucidate the efficacy of these medications in treating migraine disorder.

EPIDEMIOLOGIC EVALUATION OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 3B INFECTION IN AN AFRICAN ELEPHANT (LOXODONTA AFRICANA).

This epidemiologic study follows a 5-yr-old male African elephant ( Loxodonta africana ) during an episode of hemorrhagic disease (HD) due to elephant endotheliotropic herpesvirus 3B (EEHV3B) utilizing data from complete blood counts, electrophoresis and acute phase protein analysis, and polymerase chain reaction (PCR) of multiple body fluids during and after the clinical episode. The elephant presented with sudden onset of marked lethargy and inappetence followed by hypersalivation, hyperemia of the conjunctivae and focally on the tongue, and swellings on the head and ventrum. A moderate leukocytopenia with band neutrophilia, lymphopenia, monocytopenia, and thrombocytophilia was followed by a rise in all three cell types by day 10. Moderate increases in serum amyloid A and C-reactive protein were noted in the first weeks of illness. Conventional PCR of whole blood yielded a strong positive result for EEHV3B. Quantitative PCR revealed moderate viremia, which slowly returned to undetectable levels by day 35 of treatment. EEHV3B was shed in trunk wash samples starting at day 22 for 10 days at moderate levels, and then at low levels for up to 8.5 mo. All three female herd mates shed low levels of EEHV3B in trunk washes intermittently starting from day 28 of the calf's illness until over 7 mo afterward. The majority of saliva samples from the calf over the 8.5-mo period were also positive for EEHV3B. A subfraction of saliva samples from a female herdmate was positive from days 127-190 following disease onset in the calf. Four elephant gammaherpesviruses were detected sporadically from the calf and female herdmates during this same time period. Treatment was started at the onset of clinical signs and consisted of rectal and oral fluids and oral famciclovir. This is the first case of EEHV3B HD in an elephant species and the first thorough epidemiologic evaluation of EEHV HD in an African elephant.

Acute urinary retention and constipation precipitated by herpes zoster infection.

A 76-year-old man presented to the emergency department complaining of acute urinary retention (AUR) and severe constipation. His recent medical history included 4 days of treatment in the community for gluteal herpes zoster with famciclovir. A transurethral catheter was passed and the patient completed a full course of famciclovir with resolution of constipation. The patient's catheter was successfully removed 3 weeks after his presentation. We report on the clinical presentation and management of an unusual case of AUR and constipation caused by a zoster viral infection of the S2-S4 dermatome.

Comparison of Acyclovir and Famciclovir for Ramsay Hunt Syndrome.

OBJECTIVE: Although antiviral agents are widely used to treat Ramsay hunt syndrome (RHS), their relative effectiveness has not been assessed. This study retrospectively compared clinical outcomes in patients with RHS treated with the antiviral agents acyclovir and famciclovir. PATIENTS AND METHODS: This study involved 227 patients diagnosed with RHS from 2003 to 2015. Patients were treated with prednisolone plus acyclovir (n = 102) or famciclovir (n = 125). Patient outcomes were measured using the House-Brackmann scale according to age, initial severity of disease, electroneurography, and underlying disease. RESULTS: Based on complications (p = 0.019) and disease severity (p = 0.013), the overall complete recovery rate was significantly higher with famciclovir than with acyclovir, whereas rates of recovery in patients with severe (p = 0.111) and initially moderate (grades III-IV; p = 0.070) facial palsy were similar. Electroneurography also showed no difference in remission rate between the two groups (p = 0.692). Complete recovery rates in patients with hypertension and/or diabetes mellitus were similar in the two groups. However, the complete recovery rate of patients without hypertension and diabetes was significantly higher in patients treated with famciclovir than acyclovir (p = 0.018). CONCLUSION: Recovery rates in patients with RHS were higher following treatment with steroid plus famciclovir than with steroid plus acyclovir, especially in patients without hypertension and diabetes mellitus.

Effects of Physician-directed Pharmaceutical Promotion on Prescription Behaviors: Longitudinal Evidence.

Spending on prescription drugs (Rx) represents one of the fastest growing components of US healthcare spending and has coincided with an expansion of pharmaceutical promotional spending. Most (83%) of Rx promotion is directed at physicians in the form of visits by pharmaceutical representatives (known as detailing) and drug samples provided to physicians' offices. Such promotion has come under increased public scrutiny, with critics contending that physician-directed promotion may play a role in raising healthcare costs and may unduly affect physicians' prescribing habits towards more expensive, and possibly less cost-effective, drugs. In this study, we bring longitudinal evidence to bear upon the question of how detailing impacts physicians' prescribing behaviors. Specifically, we examine prescriptions and promotion for a particular drug class based on a nationally representative sample of 150,000 physicians spanning 24 months. The use of longitudinal physician-level data allows us to tackle some of the empirical concerns in the extant literature, virtually all of which have relied on aggregate national data. We estimate fixed-effects specifications that bypass stable unobserved physician-specific heterogeneity and address potential targeting bias. In addition, we also assess differential effects at both the extensive and intensive margins of prescribing behaviors and differential effects across physician-level and market-level characteristics, questions that have not been explored in prior work. The estimates suggest that detailing has a significant and positive effect on the number of new scripts written for the detailed drug, with an elasticity magnitude of 0.06. This effect is substantially smaller than those in the literature based on aggregate information, suggesting that most of the observed relationship between physician-directed promotion and drug sales is driven by selection bias. We find that detailing impacts selective brand-specific demand but does not have any substantial effects on class-level demand. The increase in brand-specific demand appears to crowd out demand for the substitute branded drug although not for the generic alternative. Results also indicate that most of the detailing response may operate at the extensive margin; detailing affects the probability of prescribing the drug more than it affects the number of prescriptions conditional on any prescribing. We draw some implications from these estimates with respect to effects on healthcare costs and public health. Copyright © 2016 John Wiley & Sons, Ltd.

Prevalence of Ocular Manifestations and Visual Outcomes in Patients With Herpes Zoster Ophthalmicus.

PURPOSE: To investigate the prevalence of ocular manifestations and visual outcomes in patients with herpes zoster ophthalmicus (HZO). METHODS: Consecutive cases diagnosed with HZO who attended 2 hospitals between July 1, 2011, and June 30, 2015, were retrospectively reviewed. Patient demographics, clinical presentations, and management were reviewed. The logistic regression model was used to estimate the odds ratio of visual loss with ocular manifestations. RESULTS: A total of 259 patients were included. Of these, 110 (42.5%) patients were <60 years old and 149 patients (57.5%) were ≥60 years old. None of the patients had received zoster vaccination before presentation. Ocular manifestations were present in 170 (65.6%) patients with no difference between both age groups (P = 0.101). Conjunctivitis was the most common ocular manifestation, followed by anterior uveitis and keratitis. After resolution of HZO, 58.7% of patients had a visual acuity of 6/12 or worse. Epithelial keratitis and stromal keratitis were independent risk factors for visual loss after resolution of HZO (P = 0.003 and P = 0.004, respectively). The corresponding odds ratio was 6.59 [95% confidence interval (CI): 1.87-23.19] and 7.55 (95% CI: 1.88-30.30), respectively. The number of ocular manifestations was also associated with an increased risk of visual loss with an odds ratio of 1.49 (95% CI: 1.01-2.20; P = 0.043). CONCLUSIONS: A substantial proportion of patients with HZO were <60 years old in this study. The absence of zoster vaccination across the study cohort was noteworthy. Keratitis was the main reason for poor visual outcome in these patients.

European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment.

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus-based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction in the incidence of postherpetic neuralgia (PHN) and other complications. The guideline development followed a structured and pre-defined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence-Based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this second part of the guideline, therapeutic interventions have been evaluated. The expert panel formally consented recommendations for the treatment of patients with HZ (antiviral medication, pain management, local therapy), considering various clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

Clinical study in genital herpes: natural Gene-Eden-VIR/Novirin versus acyclovir, valacyclovir, and famciclovir.

BACKGROUND: This paper reports the results of a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on the number of genital herpes outbreaks. The results in this study were compared to those published in clinical studies of acyclovir, valacyclovir, and famciclovir. METHODS: The framework was a retrospective chart review. The population included 139 participants. The treatment was one to four capsules of Gene-Eden-VIR/Novirin per day. The duration of treatment was 2-48 months. The study included three controls recommended by the US Food and Drug Administration (FDA): baseline, no treatment, and dose response. RESULTS: The treatment decreased the number of outbreaks per year in 90.8% of the participants. The treatment also decreased the mean number of outbreaks per year from 7.27 and 5.5 in the control groups to 2.39 (P<0.0001 and P<0.001, respectively). The treated participants reported no adverse experiences. Out of the 15 tests that compared Gene-Eden-VIR/Novirin to the three drugs, Gene-Eden-VIR/Novirin had superior efficacy in eight tests, inferior efficacy in three tests, and comparable efficacy in four tests. Gene-Eden-VIR/Novirin also had superior safety. CONCLUSION: The clinical study showed that the natural Gene-Eden-VIR/Novirin decreases the number of genital herpes outbreaks without any side effects. The study also showed that the clinical effects reported in this study are mostly better than those reported in the reviewed studies of acyclovir, valacyclovir, and famciclovir.

Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006-2013).

OBJECTIVE To evaluate outcomes for cats treated with orally administered famciclovir 3 times/d for clinical signs attributed to naturally occurring feline herpesvirus type 1 (FHV-1) infection and to assess variables related to owner satisfaction with the treatment. DESIGN Retrospective case series. ANIMALS 59 client-owned cats. PROCEDURES Medical records were reviewed to identify cats treated for presumed FHV-1 infection from 2006 through 2013 with ≥ 1 follow-up visit. Signalment, duration of clinical signs, prior treatment, examination findings, diagnostic test results, concurrent treatments, and outcome data were recorded. Owners were asked to complete a survey regarding patient- and treatment-related variables. Data were compared between cats that received low (approx 40 mg/kg [18 mg/lb]) and high (approx 90 mg/kg [41 mg/lb]) doses of famciclovir, PO, 3 times/d. RESULTS Patient age ranged from 0.03 to 16 years. Conjunctivitis (51/59 [86%]), keratitis (51 [86%]), blepharitis (19 [32%]), nasal discharge or sneezing (10 [17%]), and dermatitis (4 [7%]) were common findings. Clinical improvement was subjectively graded as marked in 30 (51%) cats, mild in 20 (34%), and nonapparent in 9 (15%). Median time to improvement was significantly shorter, and degree of improvement was significantly greater in the highdose group than in the low-dose group. Adverse effects potentially attributable to famciclovir administration were reported for 10 cats. On the basis of survey responses, most (29/32 [91%]) owners were satisfied with their cat's treatment. CONCLUSIONS AND CLINICAL RELEVANCE Famciclovir at the prescribed dosages was associated with improved clinical signs in cats with presumed FHV-1 infection, and few adverse effects were attributed to the treatment. Further studies are needed to assess whether a famciclovir dosage of 90 versus 40 mg/kg, PO, 3 times/d would result in increased efficacy and shorter treatment time.

Early application of low-level laser may reduce the incidence of postherpetic neuralgia (PHN).

BACKGROUND: Postherpetic neuralgia (PHN) is difficult to treat, and currently there are no available treatments that effectively reduce its incidence. Low-level laser therapy (LLLT) has been proposed for indirect virus deactivation in treating recurrent herpes simplex infections. OBJECTIVE: This study seeks to investigate whether LLLT could reduce the incidence of PHN. METHODS: We retrospectively reviewed the incidence of PHN at the first, third, and sixth months after rash outbreak in 3 groups: the acute group of patients who received LLLT during the first 5 days; the subacute group of patients who received LLLT during days 6 to 14 of the eruption; and the control group of patients who did not receive LLLT. RESULTS: There were 48, 48, and 154 patients in the acute, subacute, and control groups, respectively. After adjusting for confounding factors, including age, sex, and use of famciclovir, the incidence of PHN was significantly lower in the acute group versus the control group after 1 month (odds ratio [OR] 0.21, P = .006, 95% confidence interval [CI] 0.068-0.632), 3 months (OR 0.112, P = .038, 95% CI 0.014-0.886), and 6 months (OR 0.123, P = .021, 95% CI 0-0.606). The subacute group only had a lower incidence (OR 0.187, P = .032, 95% CI 0.041-0.865) after 3 months when compared with the control group. LIMITATIONS: This is a retrospective study lacking double-blind randomization, and the placebo effect may be a major concern. Lack of standardized and prospective evaluation measures is also a limitation of this study. CONCLUSION: Applying LLLT within the first 5 days of herpes zoster eruption significantly reduced the incidence of PHN. LLLT may have the potential to prevent PHN, but further well-designed randomized controlled trials are required.

Surviving and fatal Elephant Endotheliotropic Herpesvirus-1A infections in juvenile Asian elephants - lessons learned and recommendations on anti-herpesviral therapy.

BACKGROUND: Elephant Endotheliotropic Herpesviruses (EEHVs) can cause acute haemorrhagic disease in young Asian elephants (Elephas maximus) and clinical EEHV infections account for the majority of their fatalities. The anti-herpesviral drug famciclovir (FCV) has been used routinely to treat viraemic at-risk elephants, but thus far without proven efficacy. This paper presents clinical and virological investigations of two EEHV-1A infected elephants treated with FCV, and discusses anti-herpesvirus therapies of viraemic elephants. CASES PRESENTATIONS: Two 1.5 year old male Asian elephants at a zoological collection in the UK developed clinical EEHV-1A infections. Case 1 showed signs of myalgia for the duration of 24 hours before returning back to normal. EEHV-1A DNAemia was confirmed on the day of clinical signs and continued to be present for 18 days in total. Trunk shedding of the virus commenced 10 days after detection of initial DNAemia. Case 2 tested positive for EEHV-1A DNAemia in a routine blood screening sample in the absence of clinical signs. The blood viral load increased exponentially leading up to fatal clinical disease seven days after initial detection of DNAemia. Both calves were treated with 15 mg/kg FCV per rectum on detection of DNAemia and penciclovir, the FCV metabolite, could be detected in the blood at assumed therapeutic levels. The early indicators for clinical disease were a marked absolute and relative drop in white blood cells, particularly monocytes prior to the detection of viraemia. The most prognostic haematological parameter at later stages of the disease was the platelet count showing a continuous sharp decline throughout, followed by a dramatic drop at the time of death. CONCLUSIONS: The EEHV-1A viraemic animals investigated here further highlight the ongoing threat posed by these viruses to juvenile Asian elephants. The findings call into question the efficacy of rectal FCV in clinical cases and direct towards the use of alternative anti-herpesvirus drugs and complementary treatments such as plasma infusions if no improvement in either viral load or the above-mentioned blood parameters are observed in the initial days of viraemia despite anti-herpesvirus therapy.

Gastric Enterovirus Infection: A Possible Causative Etiology of Gastroparesis.

BACKGROUND: Gastroparesis (GP) is a disabling chronic gastroenterologic disorder with high morbidity that severely impacts patients' quality of life. GP can present acutely after a viral-like gastrointestinal illness resulting in speculation that in some patients, neurologic damage caused by the infection might underlie the pathogenesis of idiopathic gastroparesis (IGP). AIMS: The aim of this study is to document case reports of Enterovirus (EV) infection as a possible cause of IGP. METHODS: Eleven patients referred with a diagnosis of GP underwent workup to exclude known causes of GP. Those with a history of flu-like symptoms or gastroenteritis prior to onset of GP symptoms had gastric biopsies taken during upper endoscopy to assess for the presence of gastric mucosal EV infection. Data on presenting symptoms, extra-intestinal symptoms and conditions, prior nutritional support requirements, upper endoscopy findings, and response to therapy were cataloged. RESULTS: Eleven patients were diagnosed as IGP. Nine had active EV infection on gastric biopsies and were included (7/9 female, mean age 43 years). Eight out of nine received EV treatment with antivirals and/or immune therapies, with a wide degree of variability in treatment regimens. Four out of eight who received EV treatment had symptomatic improvement. One patient had stable symptoms. Three patients are currently undergoing therapy. CONCLUSIONS: Gastric EV infection was frequently detected (82 %) in patients undergoing investigation for IGP. Antiviral and/or immune therapies against EV seem to be favorable, as most of our patients had resolution of their GP symptoms after treatment. This is the first study to identify EV as a possible infectious etiology of IGP.

RANAVIRUS EPIZOOTIC IN CAPTIVE EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) WITH CONCURRENT HERPESVIRUS AND MYCOPLASMA INFECTION: MANAGEMENT AND MONITORING.

Frog virus 3 (FV3) and FV3-like viruses are members of the genus Ranavirus (family Iridoviridae) and are becoming recognized as significant pathogens of eastern box turtles (Terrapene carolina carolina) in North America. In July 2011, 5 turtles from a group of 27 in Maryland, USA, presented dead or lethargic with what was later diagnosed as fibrinonecrotic stomatitis and cloacitis. The presence of FV3-like virus and herpesvirus was detected by polymerase chain reaction (PCR) in the tested index cases. The remaining 22 animals were isolated, segregated by severity of clinical signs, and treated with nutritional support, fluid therapy, ambient temperature management, antibiotics, and antiviral therapy. Oral swabs were tested serially for FV3-like virus by quantitative real-time PCR (qPCR) and tested at day 0 for herpesvirus and Mycoplasma sp. by conventional PCR. With oral swabs, 77% of the 22 turtles were FV3-like virus positive; however, qPCR on tissues taken during necropsy revealed the true prevalence was 86%. FV3-like virus prevalence and the median number of viral copies being shed significantly declined during the outbreak. The prevalence of herpesvirus and Mycoplasma sp. by PCR of oral swabs at day 0 was 55% and 68%, respectively. The 58% survival rate was higher than previously reported in captive eastern box turtles for a ranavirus epizootic. All surviving turtles brumated normally and emerged the following year with no clinical signs during subsequent monitoring. The immediate initiation of treatment and intensive supportive care were considered the most important contributing factors to the successful outcome in this outbreak.

CLINICAL INFECTION OF CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS) WITH ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 4.

Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease in juvenile Asian elephants. A number of EEHV types and subtypes exist, where most deaths have been caused by EEHV1A and EEHV1B. EEHV4 has been attributed to two deaths, but as both diagnoses were made postmortem, EEHV4 disease has not yet been observed and recorded clinically. In this brief communication, two cases of EEHV4 infection in juvenile elephants at the Houston Zoo are described, where both cases were resolved following intensive treatment and administration of famciclovir. A quantitative real-time polymerase chain reaction detected EEHV4 viremia that correlated with clinical signs. High levels of EEHV4 shedding from trunk wash secretions of the first viremic elephant correlated with subsequent infection of the second elephant with EEHV4. It is hoped that the observations made in these cases--and the successful treatment regimen used--will help other institutions identify and treat EEHV4 infection in the future.

CLINICAL INFECTION OF TWO CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS) WITH ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 1B.

The ability of prior infection from one elephant endotheliotropic herpesvirus (EEHV) type to protect against clinical or lethal infection from others remains an important question. This report describes viremia and subsequent shedding of EEHV1B in two juvenile 4-yr-old Asian elephants within 3 wk or 2 mo following significant infections caused by the rarely seen EEHV4. High levels of EEHV1B shedding were detected in the first elephant prior to emergence of infection and viremia in the second animal. The EEHV1B virus associated with both infections was identical to the strain causing infection in two herd mates previously. High EEHV viremia correlated with leukopenia and thrombocytopenia, which was followed by leukocytosis and thrombocytosis when clinical signs started to resolve. The observations from these cases should be beneficial for helping other institutions monitor and treat elephants infected with EEHV1, the most common virus associated with lethal hemorrhagic disease.

Comparison of acyclovir and famciclovir for the treatment of Bell's palsy.

The relative effectiveness of acyclovir and famciclovir in the treatment of Bell's palsy is unclear. This study therefore compared recovery outcomes in patients with Bell's palsy treated with acyclovir and famciclovir. The study cohort consisted of patients with facial palsy who visited the outpatient clinic between January 2006 and January 2014. Patients were treated with prednisolone plus either acyclovir (n = 457) or famciclovir (n = 245). Patient outcomes were measured using the House-Brackmann scale according to initial severity of disease and underlying disease. The overall recovery rate tended to be higher in the famciclovir than in the acyclovir group. The rate of recovery in patients with initially severe facial palsy (grades V and VI) was significantly higher in the famciclovir than in the acyclovir group (p = 0.01), whereas the rates of recovery in patients with initially moderate palsy (grade III-IV) were similar in the two groups. The overall recovery rates in patients without hypertension or diabetes mellitus were higher in the famciclovir than in the acyclovir group, but the difference was not statistically significant. Treatment with steroid plus famciclovir was more effective than treatment with steroid plus acyclovir in patients with severe facial palsy. Famciclovir may be the antiviral agent of choice in the treatment of patients with severe facial palsy.