Diagnosis Of Herpes Simplex Virus Research Articles

Rapid diagnosis of herpes simplex virus 1 and 2 bloodstream infections utilizing a sample-to-answer platform.

Rapid, accurate, and definitive diagnosis of herpes simplex virus (HSV) infections is crucial in clinical settings for patient management. The absence of FDA-authorized molecular assays for HSV-1/2 detection in blood, coupled with a lack of consensus on the optimal sample type, underscores the need for improved diagnostic methods. Furthermore, rapid diagnosis of HSV bloodstream infections enables timely administration of antiviral treatment, influences patient management decisions for those at high risk, and can contribute to shorter hospital stays, thereby reducing healthcare costs.

Epidemiology and risk stratification of young infants presenting to the emergency department with hypothermia.

Hypothermic infants are presumed to be at high risk for a serious bacterial infection (SBI) or herpes simplex virus (HSV) infection. In contrast to febrile infants, the emergency department (ED) management of hypothermic infants is variable in the absence of consensus guidelines, potentially resulting in low-value care and missed diagnoses. We investigated the diagnostic workup conducted for hypothermic infants in our academic pediatric ED, the incidence of SBI and HSV infection, and risk factors associated with infection. We conducted a single-center retrospective study of infants ≤90 days of age with a rectal temperature ≤36.5°C in the ED between 2013 and 2022. From their medical records, we abstracted the type(s) of testing each infant received in the ED and the diagnosis of SBI and HSV, analyzing characteristics associated with each. Of 1095 hypothermic infants identified, 402 (37%) underwent testing for SBI or HSV. Among these, 34/402 (8.5%) had an SBI or HSV. A minimum temperature below 36°C and hospital admission were characteristics associated with higher rates of infectious testing. Infants aged 29‒90 days, compared to 0‒28 days, were more likely to have a urinary tract infection (odds ratio 3.28, 95% confidence interval 1.47‒7.32). Hypothermic infants have slightly lower rates of SBI or HSV than febrile infants, for whom infectious studies are widely recommended, but still high enough to warrant an infectious workup in most cases. Further research is required to risk stratify hypothermic infants in the ED to standardize care and improve outcomes while optimizing resource utilization.

Two Waves of Specific B Cell Memory Immunoreconstruction Observed in Anti-HHV1-3 IgG Kinetics after Hematopoietic Stem Cell Transplantation.

Humoral memory and specific antibody levels depend on the kind of antigen and individual immunofactors. The presence of IgM antibodies or a fourfold rise in specific IgG levels are generally accepted as diagnostic factors in the serology of acute viral infections. This basic model is not adequate for the herpes virome, especially after hematopoietic stem cell transplantation (HSCT), due to continuous, usually multifocal antigenic stimulation, various donor serostatuses, immunosuppression, and individual immunoreconstitution. A case-control study was conducted to identify active infection cases of human herpesvirus (HHV) (from 300 diagnosed immunocompromised patients) and to evaluate historically associated humoral factors to look at outcomes. We considered only the data of patients with meticulous differential diagnosis to exclude other causes, and thereby to observe pathways and temporal relationships, not the statistical ones usually collected in cohorts. Despite the small number, such data collection and analysis methods avoid a number of biases and indicate cause and effect. In this observational study, a retrospective analysis of data from 300 patients with clinical diagnosis of herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation showed a number of biases. Two well-differentiated cases (confirmed by a Tzanck test) with various diseases and conditioning evolutions of immune parameters showed an interesting pathway. Exponential decreases in specific IgGs after HSCT preceded virus replication were observed, with a cytopathic effect (shingles, VZV encephalitis and HSV-induced mucositis). The minima (lowest IgG levels) before herpesvirus reactivation were 234.23 mIU/mL and 94 RU/mL for VZV and HSV, respectively. This coincided with a low CD4 titer, but without other infectious processes. Other immune response parameters such as Treg, cytotoxic T cells, and complement and total IgG level were the same as they were before the transplant procedure. Interestingly, a second wave of immunoreconstitution with an anamnestic antibody response was not always observed. It coincided with prolonged herpes viral infection. A patient with lymphocyte depletion in conditioning showed an earlier second wave of immunoreconstitution (6th vs. 14th month). As is typical for infancy, the kinetics of the IgG level is unique after HSCT (the decline phase is first). Host microbiome factors (e.g., HHV1-3-serostatus) should be taken into account to predict risk of non-relapse mortality and survival after HSCT. The levels of specific antibodies help in predicting prognoses and improve disease management. A lack of differentiation and the confusing bias of the assessor (i.e., observer selection bias) are the main obstacles in statistical HHV1-3 research. Such time-lapse case studies may be the first to build evidence of a pathway and an association between immune parameters and HHV disease.

Laboratory Diagnosis of Herpes Simplex Virus in Mucocutaneous Lesions by Light Microscopy, ELISA and PCR: A Cross-sectional Study from a Tertiary Care Hospital

Laboratory Diagnosis of Herpes Simplex Virus in Mucocutaneous Lesions by Light Microscopy, ELISA and PCR: A Cross-sectional Study from a Tertiary Care Hospital

P-459 Sexually transmitted infections in women and fecundability – A prospective cohort study

Abstract Study question Does a previous infection with Chlamydia trachomatis (CT) or genital herpes simplex virus (HSV) affect fecundability, and does recency of infection play a role? Summary answer Previous infection with CT or HSV in women was not appreciably associated with fecundability. However, a recent CT infection was associated with slightly lower fecundability. What is known already Worldwide, 1 million people contract sexually transmitted infections (STIs) every day. CT and genital HSV infections are among the most common STIs. Untreated CT in women can cause pelvic inflammatory disease (PID), which can lead to scarring and narrowing of the fallopian tubes and the lower uterus, thus complicating the ability to conceive. Also, an association between genital HSV in women and PID has been suggested. However, it is uncertain to what extent CT and HSV infections in women are associated with fecundability, defined as the per-cycle probability of conception, and whether recency of the infection plays a role. Study design, size, duration We conducted a prospective cohort study of female participants included in two Danish preconception cohorts: SnartGravid.dk (‘Soon Pregnant’, 2007-2011) and SnartForældre.dk (‘Soon Parents’, 2011-ongoing). At enrollment, participants had to be non-pregnant, aged 18-45 years, in a relationship with a male partner, not using contraception or fertility treatment, and trying to conceive. Participants completed a baseline questionnaire and bimonthly follow-up questionnaires until conception or up to 12 months after study entry. Participants/materials, setting, methods We analyzed data from 10475 women. At study entry, participants reported if they had ever been diagnosed (including year of first diagnosis) with CT or HSV. Fecundability ratios (FRs) were calculated using proportional probability regression models and 95% confidence intervals (CIs). The analyses were adjusted for age, income, educational attainment, other STIs, and smoking, reported at study entry. The reference groups were either women with no CT or no HSV diagnosis. Main results and the role of chance At study entry, 2603 (24.9%) of participants reported a history of infection with CT, and 766 (7.3%) with HSV. Using life table methods, 84.7% of participants conceived within 12 cycles of follow-up. Compared with the reference group, the adjusted FR for women ever diagnosed with CT was 0.98 (CI: 0.93-1.04) and 0.96 (CI: 0.88-1.06) for women ever diagnosed with HSV. Compared with the reference group, a recent CT infection was associated with slightly lower fecundability: adjusted FRs for women diagnosed 0-2 years, 2-5 years, and more than 5 years before study entry were 0.84 (CI: 0.71-0.99), 1.01 (CI: 0.90-1.12), and 1.00 (CI: 0.93-1.07), respectively. The association between recency of a HSV infection compared to the reference group was less evident: adjusted FRs for 0-2 years, 2-5 years, and more than 5 years since study entry were 0.93 (CI: 0.72-1.21), 0.97 (CI: 0.77-1.22), and 0.91 (0.75-1.09), respectively. Limitations, reasons for caution Misclassification of exposure is possible, as CT and HSV infections are often asymptomatic and hence undiagnosed. In addition, self-report may have resulted in misclassification of infection type and year. Further, we lacked information on severity or frequency of infections. Wider implications of the findings Women diagnosed with STIs often experience psychological distress concerning their future ability to conceive. Our finding of no overall association between previous diagnoses of CT or HSV may reassure women wanting to conceive. Still, testing for STIs remains important because untreated infections can damage the female reproductive system. Trial registration number Not applicable

Clinical progress note: Evaluation and management of neonatal herpes simplex virus disease.

Clinical progress note: Evaluation and management of neonatal herpes simplex virus disease.

ORAL MANIFESTATION OF HERPES SIMPLEX CONCOMITANT TO GRAFT-VERSUS-HOST DISEASE POST HEMATOPOIETIC STEM CELL TRANSPLANTATION

A 29-year-old female patient, 90 days after hematopoietic stem cell transplantation (HSCT) due to severe aplastic anemia, presented with small ulcers spread over the hard palate and a painful ulcer of 1 cm in diameter in the region of the left lingual alveolar mucosa. The patient had cytomegalovirus viremia and had red blood cells and platelets transfused weekly. Cytology confirmed the diagnosis of herpes simplex virus (HSV) in the ulcer of alveolar mucosa and nonspecific inflammatory process in the palate, compatible with graft-versus-host disease (GVHD). Treatment with systemic acyclovir was initiated, with HSV ulcer remission in 7 days. After 3 days, new lesions appeared, and the treatment was extended. The treatment of viral manifestations concomitant with oral manifestation of GVHD is a challenge in patients post-HSCT. The correct diagnosis and the therapeutic choice are extremely important for a better evolution in these highly complex cases.

Healthcare resource utilisation pattern and costs associated with herpes simplex virus diagnosis and management: a systematic review

ObjectivesLittle is known about the economic burden of herpes simplex virus (HSV) across countries. This article aims to summarise existing evidence on estimates of costs and healthcare resource utilisation associated...

Neonatal Herpes Simplex Virus Infection: Epidemiology and Outcomes in the Modern Era.

Over the past several decades, there have been advances in diagnosis and treatment of neonatal herpes simplex virus (HSV) disease. There has been no recent comprehensive evaluation of the impact of these advances on the management and outcomes for neonates with HSV. Clinical data for initial presentation, treatment, and outcomes were abstracted from medical records of neonates with HSV treated at Seattle Children's Hospital between 1980 and 2016. One hundred thirty infants with a diagnosis of neonatal HSV were identified. Between 1980 and 2016, high-dose acyclovir treatment for neonatal HSV infection increased from 0% to close to 95%, with subsequent decrease in overall HSV-related mortality from 20.9% to 5.6%. However, even among infants treated with high-dose acyclovir, mortality was 40.9% for infants with disseminated (DIS) disease, and only 55% of infants with central nervous system (CNS) disease were without obvious neurologic abnormalities at 24 months. Over the study period, the time between initial symptoms and diagnosis decreased. Skin recurrences were more common with HSV-2 than HSV-1 (80% vs 55%; P = .02) and in infants with lesions at initial diagnosis (76% vs 47%; P = .02). Changes in the standard of care for management of neonatal HSV disease have led to improvements in timeliness of diagnosis and outcome but mortality in infants with DIS disease and neurologic morbidity in infants with CNS disease remain high. Future research should focus on prevention of perinatal infection and subsequent recurrences.

Herpes simplex diagnosis and treatment are not associated with incident dementia

AbstractBackgroundAlthough an association between dementia and certain infectious diseases, such as HIV, has been well‐established, recent publications have also concerningly hinted at the possibility of its association with a much more common infectious disease, as well: herpes simplex virus (HSV). We sought to better investigate potential associations between HSV diagnosis and treatment with incident dementia in a large, retrospective cohort.MethodWe conducted our analysis among members of Kaiser Permanente Northwest aged 50 and older between 2000‐2019. We matched individuals with an HSV diagnosis during this time frame to three individuals, each, without HSV, based on age at index date (HSV diagnosis date for cases and a reference date for controls), sex, and membership length prior to index date. Follow‐up time started at the index date and ended on the date of dementia diagnosis, membership end date, death, or end of follow‐up, whichever came first. We defined HSV and dementia diagnoses by ICD‐9/‐10 codes recorded in the electronic health record. We defined herpes simplex antiviral treatment, based on in‐network pharmacy fills. We used survival analysis to examine the associations between dementia with HSV diagnosis (yes/no, overall, by sex, age, and HSV type) and HSV medication fills (yes/no; and by tertiles of medication dispensed). We adjusted models by demographic and clinical factors.Result87,432 persons (21,661 with HSV) were included. The mean age was 60.9 years and 69% were female. Over a mean follow‐up of 6.1 years, 4,507 developed dementia. HSV diagnoses – overall and Type 2 – was significantly associated with lower risk of dementia (Figure). Anti‐viral medication (any versus none) was not associated with dementia, and we did not see a dose response when examining dose by tertile (Figure).ConclusionIn contrast to the recent reports, we found a slight, but statistically‐significant association between HSV diagnosis with dementia. We did not observe a lower risk of dementia associated with anti‐herpetic treatment, also as had been previously reported. The relationship between HSV and dementia may be complex and deserves further study. However, that we did not see a positive association between HSV and dementia in our study is very encouraging.

Herpes zoster in chronic lymphocytic leukemia: Effect of vaccination and treatment.

7527 Background: Patients with Chronic Lymphocytic Leukemia (CLL) are susceptible to infections due to impaired humoral immunity as a complication of the disease, treatments received and age at diagnosis. Herpes zoster (HZ) is a painful, vesicular rash from reactivation of varicella-zoster virus that is common in immunocompromised patients. While HZ vaccines can reduce both varicella-zoster reactivation and post-herpetic neuralgia, vaccination rates are low. The aim of this study is to determine the effect of vaccination on rates of HZ infection in patients with CLL. Methods: We identified patients diagnosed with CLL between September 1999 and October 2015 using Veterans Administration Central Cancer Registry (VACCR). Pharmacy records were used to identify patients who received treatment for CLL and HZ. HZ events were defined as patients with International Classification of Diseases 9th Revision (ICD-9) codes for HZ infection (053) or prescriptions of acyclovir or valacyclovir at a dose of 1500 mg/day or higher or famciclovir at a dose of 1000 mg/day or higher without a diagnosis of Herpes simplex or Bell’s palsy, or an ICD-9 code and prescription above. Cox proportional hazards regression model was used to assess the association between vaccination as a time-varying exposure and developing HZ while controlling age at CLL diagnosis, co-morbidity score, and receipt of first and second line chemotherapy. The study was approved by the St. Louis VA Medical Center institutional review board. Results: A cohort of 7155 patients with CLL was identified using VACCR. 2640 patients (36.9%) and 1161 patients (16.2%) received first and second line chemotherapy respectively. Mean age at first chemotherapy was 69.5 years. We detected 1115 cases of HZ (15.6%) using ICD-9 codes, prescriptions or both. 615 patients (8.6%) received HZ vaccinations. Patients with HZ were younger (mean 68.0 vs. 69.8 years, p < 0.001), had similar co-morbidities, and were more likely to get treatment for CLL (58.1% vs. 33.0%, p < 0.001). Using a time-varying analysis, there was a trend for HZ vaccine to decrease the risk of developing HZ (HR 0.71, 95% CI 0.49-1.04, p = 0.082). When adjusting for age and co-morbidity, patients with CLL treated with first line chemotherapy had a higher risk of HZ (HR 2.34, 95% CI 2.02-2.71, p < 0.001) compared to those never receiving therapy. Second line chemotherapy increased risk of HZ (HR 1.32, 95% CI 1.13-1.55, p < 0.001) beyond first line treatment. Conclusions: HZ is prevalent in patients with CLL and affects younger patients who require chemotherapy. The risk of developing HZ increases in recipients of first and second line chemotherapy. In the time-varying analysis, there was a trend towards decreased infection in patients who received HZ vaccination. Further studies in a more modern cohort that assess infection risk using a larger vaccinated group with the newer and more effective HZ vaccine are warranted.

ORAL HERPES SIMPLEX VIRUS INFECTION IN 100 PATIENTS WITH CANCER: AN EXPERIENCE OF A SINGLE CANCER CENTER

Introduction: Oral herpes simplex virus (HSV) infection is a common complication in patients with cancer undergoing oncologic treatment. HSV in these patients often has an atypical presentation and can remain unrecognized or misdiagnosed. Objective: The aim of this study was to evaluate the clinical outcomes of oral HSV in patients with cancer, as well as to determine the specificity of cytology technique for its diagnosis. Medical records of 100 patients with cancer who presented with oral lesions or a clinical diagnosis of oral HSV and had a cytology exam between January 2010 to December 2014 were reviewed. Results: Seventy-two patients had solid tumors and 28 had diseases of hematologic origin. In relation to cancer treatment, 74 patients received chemotherapy, 17 had surgery, 7 underwent radiotherapy, and 2 were taking immunosuppressive drugs. The tongue was the most affected site (31.3%), followed by the palate (20.6%), and the lip (19.3%). Regarding the cytology exam, 36 out of 100 (36.0%) patients had confirmed HSV infection. All patients were treated with systemic acyclovir with complete remission of the oral lesions in a mean time of 5 days. Oral HSV mostly affects patients undergoing chemotherapy, and the tongue was the most common site for viral reactivation in the oral cavity. Cytology was not considered very effective.

Challenges of aciclovir-resistant HSV infection in allogeneic bone marrow transplant recipients

The emergence of herpes simplex virus (HSV) resistance to aciclovir (ACV) has increasingly been reported among hematopoietic stem cell transplant (HSCT) recipients and often associated with extended ACV prophylaxis. Between June 2011 and June 2019, medical records of 532 HSCT recipients with suspected HSV infection were retrospectively analyzed. HSV-1 and HSV-2 positive samples were identified in 47 and 16 patients respectively. Analysis of HSV resistance to antivirals was performed at the Public Health England reference laboratory in London using phenotypic and/or genotypic resistance assays. The prevalence of ACV-resistant HSV accounted for 17% (8/48) of infected HSV-1 cases. All 8 patients received T-cell depleted allogeneic HSCT for hematological malignancies. Half of these patients were male with a median age was 57.5 years (range; 26-63). Chronic Graft versus Host disease (cGVHD) affected 7 patients before HSV-1 diagnosis. HSV-1 infection developed while receiving either intravenous ACV (n = 2) or oral ACV (n = 6 patients) prophylaxis at a median of 373 [range,18-2183] days post-HSCT. ACV resistance was clinically suspected at a median of 25 [range,16-109] days after initial HSV diagnosis and subsequently laboratory confirmed at a median of 25 (range,10-59) days. All patients presented with hemorrhagic oral mucositis refractory to treatment dose ACV. Foscarnet (FOS) treatment was initiated in all 8 patients (pending laboratory confirmation of ACV resistance) with some effect but associated with significant toxicity burden. Four patients presented again with recurrent HSV infection or no resolution. Three with recurrent HSV died from other causes while suffering from persistent oral HSV lesions. A prolonged immunosuppressed state following T-deplete HSCTs alongside extended use of ACV, early onset systemic HSV infection, presence of cGVHD, and treatment toxicities pose a significant challenge to the management of ACV resistant HSV infections and alternative effective antiviral options remains an unmet need in this clinical setting.

CONDITION OF HUMORAL IMMUNITY IN PATIENTS WITH SYSTEMIC DISEASES OF CONNECTIVE TISSUE WITH ACTIVATED CHRONIC SIMPLE HERPETIC INFECTION

The aim - to study and to analyze the indicators of the humoral link of the immune system in patients with systemic connective tissue diseases with chronic activated HSV 1/2 infection and to assess the effect of the revealed disorders on the development of autoimmune pathology.
 Materials and methods. We examined 380 patients with systemic diseases of the connective tissue (systemic lupus erythematosus, systemic vasculitis, rheumatoid arthritis, psoriasis) with chronic HSV 1/2 infection at the age of 21-67 years. In 45 of them, using the modern molecular genetic diagnosis of herpes simplex, the active phase of chronic HSV 1/2 infection was verified based on the results of the polymerase chain reaction, and in the other 335, the latent phase was verified. The control group consisted of 20 healthy individuals of the appropriate age and gender. In patients with systemic connective tissue diseases with chronic HSV 1/2 infection, the humoral immunity indices were studied: levels of complement component C3 and IFN-a in saliva and blood and acquired: concentration of common major immunoglobulinins: IgG, IgM IgA, IgE; specific IgM and IgG to HSV 1/2; levels of cryoglobulins, cryofibrinogen, CІC in serum. Statistical processing of the results of the study was carried out using generally accepted methods of variation statistics.
 Results. In patients with systemic diseases of connective tissue with chronic HSV 1/2 infection, activation of the humoral immunity was detected, it was especially evident in the active phase of the infection and was characterized by an increase in the antibody production of specific IgM HSV 1/2 and IgG HSV 1/2, аn increase in the levels of CIC, IgM, IgA and IgE, cryoprecipitation proteins, IFN-a in the blood. In the latent phase of HSV 1/2 infection the levels of IgG production of HSV 1/2, IgE, CEC, cryofibrinogen and cryoglobulins in the blood serum of these patients increased.
 Conclusions. The presence of chronic activated HSV 1/2 infection in patients with systemic diseases of the connective tissue causes activation of the humoral immunity, creates the conditions for the development of autoimmune processes.

Cytopathological Diagnosis of Herpes Simplex Viral Mastitis: Three Rare Cases and a Review of the Literature.

Context:Virus infection has a unique morphological change in cell pathology. It is also of great significance in the diagnosis of herpes simplex mastitis.Aims:To evaluate the practicability and feasibility of cytological diagnosis of herpes simplex virus mastitis.Materials and Methods:Three cases of HSV mastitis diagnosed by cytology smears were collected. The papules were stained with Wright-Giemsa to observe the morphological characteristics of the cells.Statistical Analysis:The cytological characteristics of 3 cases were summarized and compared with the literature.Results:In the background of inflammatory cells in the smear, the cells with characteristic changes can be seen in the mass and scattered distribution. The nuclear size increased significantly, and mononuclear, binuclear, trinuclear and multinuclear nuclei appeared. The nuclei of multinuclear were crowded and mosaic. The chromatin of nucleus changed like frosted glass, and the chromatin became thicker at the edge of nucleus. Inclusion bodies were found in the nucleus, eosinophilic, with different sizes and irregular shapes. These characteristics are helpful to distinguish from other lesions.Conclusion:Scraper cytology is a diagnostic tool with simple operation, small trauma and pain, and it has important application value in the differential diagnosis of HSV infection, which deserves the attention of clinicians.

36-YEAR-OLD MAN WITH ACUTE INFLUENZA AND SECONDARY BACTERIAL PNEUMONIA COMPLICATED BY HERPES VIRUS INFECTION

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Herpes Simplex Virus (HSV) pneumonia is rare in immunocompetent individuals. It has been described in young to middle aged patients with flu-like symptoms [1]. It should be suspected in patients with clinical deterioration despite antimicrobial therapy [2]. Diagnosis is made by PCR, culture, cytopathology and response to acyclovir therapy. Active infection is controversial since HSV-1 is commonly identified in the respiratory tract mucosa of critically ill patients [1-3]. CASE PRESENTATION: Patient is a 36 year-old male with history of bronchial asthma presented to an outside hospital with acute onset dyspnea, productive cough and worsening of hemoptysis for one week prior to admission. Exposures include sand blasting and cotton processing. He presented with fever, bilateral pulmonary infiltrates, and respiratory failure that required intubation with mechanical ventilation. Multifocal consolidative changes with air bronchograms and ground glass opacities were seen on CT Chest. Influenza A/H1 was diagnosed by PCR and treated with oseltamivir as well as antibacterial antibiotics for superimposed bacterial infection. Initial bronchoscopy with BAL did not show fungal or bacterial growth. Autoimmune panel and HIV were negative. Despite appropriate antibiotic coverage, he failed he failed to improve. On hospital day 7, he developed fever and a rash. His antibiotics were changed to vancomycin and meropenem. Repeat bronchoscopy was performed. Erythematous bronchial mucosa with mucopurulent exudate were seen. BAL cultures were negative for bacteria, fungi or PJP. DFA was positive for HSV1 with a positive viral culture. Antibiotics were discontinued, and he was started on acyclovir. Patient’s ventilator requirements decreased and chest imaging improved. He was successfully extubated on day 16th DISCUSSION: Pathogenic mechanisms for HSV pneumonia include stress induced by mechanical ventilation, systemic inflammation and respiratory distress which contribute to viral reactivation in the lower respiratory tract [1-3]. Chronic lung disease can also be an important factor as illustrated in our case. There are no established diagnostic criteria for HSV pneumonia and guidelines on its treatment with acyclovir are sparse. HSV diagnosis is a challenge, and it should be considered after excluding other infection sources, inflammatory and autoimmune causes. CONCLUSIONS: HSV pneumonia can be suspected in patients with prolonged mechanical ventilation. It requires a high index of suspicion. HSV pneumonia is associated with worse outcomes and longer hospital stays. Reference #1: Ishihara T, Yanagi H, Ozawa H, et al. Case report: Severe herpes simplex virus pneumonia in an elderly, immunocompetent patient. BMJ Case Rep (2018) 18 July 2018: 1- 4. Reference #2: Linssen CF, Jacobs JA, Stelma FF, et al. Herpes simplex virus load in bronchoalveolar lavage fluid is related to poor outcome in critically ill patients. Intensive Care Med 2008;34:2202–9. Reference #3: Simoons-Smit AM, Kraan EM, Beishuizen A, et al. Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen or innocent bystander? Clin Microbiol Infect 2006;12:1050–9. DISCLOSURES: No relevant relationships by Mohamed Elmassry, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Barbara Mantilla, source=Web Response No relevant relationships by Arunee Motes, source=Web Response No relevant relationships by Victor Test, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response No relevant relationships by Wasawat Vutthikraivit, source=Web Response

Can endoscopists differentiate cytomegalovirus esophagitis from herpes simplex virus esophagitis based on gross endoscopic findings?

Differential diagnosis between herpes simplex virus (HSV) esophagitis and cytomegalovirus (CMV) esophagitis is challenging because there are many similarities and overlaps between their endoscopic features. The aims of this study were to investigate the implications of the endoscopic findings for the diagnosis of HSV and CMV esophagitis, and to develop a predictive model for differentiating CMV esophagitis from HSV esophagitis.Patients who underwent endoscopic examination and had pathologically-confirmed HSV or CMV esophagitis were eligible. Clinical characteristics and endoscopic features were retrospectively reviewed and categorized. A predictive model was developed based on parameters identified by logistic regression analysis.During the 8-year study period, HSV and CMV esophagitis were diagnosed in 85 and 63 patients, respectively. The endoscopic features of esophagitis were categorized and scored as follows: category 1 (-3 points): discrete ulcers or ulcers with vesicles, bullae, or pseudomembranes, category 2 (-2 points): coalescent or geographic ulcers, category 3 (1 points): ulcers with an uneven base, friability, or with a circumferential distribution, category 4 (2 points): punched-out, serpiginous, or healing ulcers with yellowish exudates. And previous history of transplantation (2 point) was included in the model as a discriminating clinical feature. The optimal cutoff point of the prediction model was 0 (area under receiver operating characteristic curve: 0.967), with positive scores favoring CMV esophagitis. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 96.8%, 89.4%, 92.6%, 87.3%, and 97.5%, respectively.The predictive model based on endoscopic and clinical findings appears to be accurate and useful in differentiating CMV esophagitis from HSV esophagitis.

Tools for the Diagnosis of Herpes Simplex Virus 1/2: Systematic Review of Studies Published Between 2012 and 2018.

BackgroundHerpes simplex virus (HSV)-1 and HSV-2 are common infections affecting the global population, with HSV-1 estimated to affect 67% of the global population. HSV can have rare but severe manifestations, such as encephalitis and neonatal herpes, necessitating the use of reliable and accurate diagnostic tools for the detection of the viruses. Currently used HSV diagnostic tools require highly specialized skills and availability of a laboratory setting but may lack sensitivity. The numerous recently developed HSV diagnostic tools need to be identified and compared in a systematic way to make the best decision about which diagnostic tool to use. The diagnosis of HSV is essential for prompt treatment with antivirals. To select the best test for a patient, knowledge of the performance and limitations of each test is critical.ObjectiveThis systematic review has summarized recent studies evaluating HSV-1 and HSV-2 diagnostic tools.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, selection criteria, data extraction, and data analysis were determined before the commencement of the study. Studies assessing the specificity/sensitivity of HSV-1 or HSV-2 diagnostic tools published between 2012 and 2018 were included. Quality assessment of included studies was performed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool.ResultsSearches of the PubMed database yielded 264 studies; 11 studies included 11 molecular assays, and 8 studies included 19 different serological assays for the detection of HSV-1, HSV-2, or both. A greater proportion of molecular assay–based tools are being developed by commercial entities. Studies that tested molecular assays mostly focused on cutaneous and mucosal HSV infections (n=13); 2 studies focused on ocular disease, whereas only 1 study focused on the central nervous system manifestations. The Simplexa HSV 1 & 2 Direct is currently the only Food and Drug Administration–approved device for use on cerebrospinal fluid. No tools focused on prenatal screening. We also present performance metrics of tests for benchmarking of future technology. Most of the included studies had a high risk of bias rating in half of the QUADAS-2 tool risk of bias domains.ConclusionsThe use of serologic tests to diagnose genital lesions is inappropriate because positive results may be due to chronic infection, whereas negative results may overlook recent infection. The incidence of acute infections is rising. As these infections present the greatest risk to fetuses, work needs to be done to prevent vertical transfer. Prenatal screening for primary infection and subsequent medical intervention will assist in lowering the rate of neonatal herpes. In conclusion, HSV diagnosis is moving away from culture-based methods to serology-based or polymerase chain reaction–based methods. Sensitive, rapid, and efficient HSV diagnostic tools should be adopted for the prevention of acute infections and neonatal herpes.

64-Year-Old Man With Subacute Altered Mental Status and Headache

64-Year-Old Man With Subacute Altered Mental Status and Headache

HSV Esophagitis Masquerading as Candidiasis: Is Age to Blame?

Esophageal candidiasis is a common infectious cause for patients presenting with dysphagia, especially if they are immunocompromised. Classic findings on EGD include scattered white plaques lining the esophageal mucosa. However, rarely these white plaques may also be seen in herpes simplex virus (HSV) esophagitis. This is a case of an 88-year-old female with dementia, HTN, and GERD presenting with symptoms of dysphagia. She received a recent EGD with endoscopic dilation two months prior without resolution. The patient had decreased oral intake associated with weight loss. She did not have any causes of immunodeficiency such as steroids, inhalers, history of HIV, or abnormal WBC. She underwent repeat EGD with findings of diffuse, linear, white, plaque-like lesions in the lower third of the esophagus suspicious for candidiasis. Brushings of the esophagus were obtained revealing cellular changes consistent with HSV. The patient was started on acyclovir with complete resolution of her dysphagia. Esophageal candidiasis is primarily seen in patients with impaired cell mediated immunity. The findings of white esophageal plaques was unexpected in this patient given she had no prior underlying immunodeficiency. The patient's age contributing to being biologically immunocompromised was a possible explanation; however, the cytology findings of HSV esophagitis were unanticipated. HSV esophagitis is common in immunocompromised, but very rare in immunocompetent patients with only small case series reported. HSV esophagitis typically presents with acute onset of dysphagia, associated with odynophagia, chest pain, and/or fevers. HSV may affect any part of the GI tract, but the esophagus is the most commonly affected. The most common finding on EGD is friable mucosa with discrete shallow ulcers. It is selflimiting in immunocompetent patients with conservative treatment approaches. However, given the severity of the patient's symptoms and suspicion of being biologically immunosuppressed due to her age, treatment was initiated. This case presents demonstrates that HSV esophagitis may present with atypical endoscopic findings, and that classic endoscopic findings for candidiasis should still prompt further analysis to establish a definite diagnosis. Additionally, it highlights that age must be considered as a potential cause for an immunosuppressed state, reinforcing that a broad differential diagnosis should be maintained in a patient presenting with dysphagia.1719_A Figure 1. Findings of diffuse linear, white, mucosal, plaquelike lesions in the lower third of the esophagus1719_B Figure 2. Findings of diffuse linear, white, mucosal, plaquelike lesions in the lower third of the esophagus1719_C Figure 3. Esophageal histology with margination of the nuclear chromatin, multinucleation and nuclear inclusions confirming diagnosis of herpes simplex virus