Herpes Simplex Virus Serology Research Articles

Herpes Simplex Virus Seroprevalence among Pregnant Finnish Women and Their Spouses-A Six-Year Follow-Up Cohort Study.

The aim was to evaluate the herpes simplex virus (HSV) seroprevalence and seroconversion among 285 pregnant women and their 120 male spouses in Finland during a six-year follow-up (FU) between 1998–2008. We also studied the effect of sexual habits, pregnancy, and other demographic factors on the acquisition of HSV infection. Combined HSV-1 and HSV-2-IgG antibodies were assessed in the first baseline serum samples with an indirect enzyme immunoassay method. The individuals with seronegative or borderline HSV serology at baseline were additionally tested using their latest FU serum sample available. The overall HSV seroprevalence during the FU was 58.9% (168/285) among the women and 53.3% (64/120) among their spouses. The seroconversion rate was 11.4% (15/132) and 12.5% (8/64) among women and their spouses, respectively. Both spouses were HSV seropositive in 39.2% (47/120). To determine the HSV-2 seroprevalence, we also tested all HSV-seropositive participants using HSV-2-specific antigen. HSV-2 seropositivity was detected in 10.9% (44/405) of the participants. The age (p = 0.006) and history of genital warts (p = 0.006) of the women were associated with combined HSV-1 and/or HSV-2 seropositivity, while a younger age was related to HSV seroconversion (p = 0.023). Among the male spouses, HSV seropositivity was associated with the practice of oral sex (p = 0.033). To conclude, women of childbearing age acquire primary HSV infections and the presence of HSV in oral epithelium is common among HSV-seropositive individuals.

Vulval dermatoses (venereal and nonvenereal) among female patients presenting to a tertiary care hospital in North India.

The skin and mucosa of the vulva are different from the rest of the human body, as it is derived from all three embryological layers. It is more prone to dermatological diseases, both infectious and noninfectious. Our study was a prospective descriptive study on female patients attending the skin outpatient department with complaints of vulval dermatoses. Our aim was to determine the prevalence of venereal and nonvenereal dermatoses (infectious and non-infectious) along with age-wise distribution of these in our area. All female patients presenting with visible skin lesions on the vulva from January 2019 to December 2019 were included in this study. Various diagnostic tests such as Gram staining, Tzanck smear, KOH mount, herpes simplex virus serology, and skin biopsy were performed wherever necessary. The study included 520 patients in whom 525 lesions were identified. These were grouped under venereal and non-venereal dermatoses. Nonvenereal dermatoses were further grouped under infectious and non-infectious conditions. Maximum patients were in the age group of 21-40 years (50.19%). The most common dermatoses were non-venereal infections, seen in 220 (42.30%) patients followed by non-venereal, non-infectious dermatoses seen in 177 (34.04%) patients whereas venereal dermatoses were seen in 128 (24.61%) patients. Most of the patients were in the reproductive age group, and the prevalence of infectious dermatoses both venereal and non-venereal was much more than that of non-infectious conditions affecting the vulval skin as per our study.

Herpes Simplex Virus Serotyping in Pregnant Women With a History of Genital Herpes and an Outbreak in the Third Trimester of Pregnancy: A Cost-Effectiveness Analysis.

To estimate whether serotyping women with a history of genital herpes simplex virus (HSV) and an outbreak during the third trimester of pregnancy is cost effective compared with no serotyping. We designed a decision-analytic model using TreeAge Pro software to assess an approach of routine HSV serotyping in a theoretical cohort of 63,582 women (an estimate of the number of women in the United States with a history of genital HSV and an outbreak during the third trimester of pregnancy). Outcomes included mild, moderate, and severe neonatal HSV, neonatal death, costs, and quality-adjusted life-years (QALYs) for both the woman and neonate. Probabilities, utilities, and costs were derived from the literature, and we used a willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were performed to assess the robustness of the results. In our theoretical cohort, HSV serology screening resulted in 519, 8, and 15 cases of mild, moderate, and severe neonatal HSV, whereas no serology screening resulted in 745, 65, and 85 cases, respectively. Thus, HSV serology screening led to 226, 57, and 70 fewer cases of mild, moderate, and severe neonatal HSV, respectively, as well as 91 fewer neonatal deaths. Additionally, serology screening saved $61 million and gained 7,900 QALYs, making it a dominant strategy. Univariate sensitivity analysis demonstrated that serology screening was cost effective until the chance of progression from neonatal HSV infection to disease despite empiric antiviral treatment was greater than 23%. Serology screening in pregnant women with an outbreak in the third trimester of pregnancy and a history of genital HSV resulted in improved outcomes and decreased costs.

Herpes simplex virus serology in genital ulcer disease in a tertiary care hospital

Herpes simplex virus serology in genital ulcer disease in a tertiary care hospital

Utility of HSV Serology for Chronic Corneal Pathology.

The purpose of this study is to determine the utility of obtaining herpes simplex virus (HSV) serology for patients presenting with chronic corneal pathology of unknown etiology for which HSV is a diagnostic consideration. A retrospective analysis was performed of all patients presenting to one cornea specialist (J.M.G.) between August 2011 and April 2018 with a chronic (>6 weeks) corneal condition for which HSV was suspected and serology was performed. Patient demographics, clinical presentation, treatment, final diagnosis, and follow-up duration were recorded. Fifty-four patients with a median age of 52 (range: 5-85) years were included in the study. Patients were classified by presenting clinical features as corneal ulcer (46.2%), stromal keratitis (24.1%), superficial keratitis (18.5%), or keratouveitis (11.1%). The seroprevalence of HSV-1 and HSV-2 antibodies were 42.6% and 18.5%, including 5 patients (9.3%) positive for both HSV-1 and HSV-2. Serology impacted management for all patients with negative titers (48.1%), defined as discontinuing antiviral medication, electing not to start antiviral medication, or continuing antiviral medication for a non-HSV etiology (e.g., varicella zoster keratitis). No patients with HSV serology were ultimately diagnosed with HSV keratitis. Median follow-up duration was 1.5 years (range 0.8-6.6 years). Although only useful when negative, our study confirms that serology may be useful for excluding HSV as a diagnostic consideration for patients presenting with chronic corneal pathology. The seroprevalence of HSV antibodies for our patient cohort was comparable with previous population-based studies.

P.008 Triphasic waves in powassan encephalitis: a case report

Background: Powassan virus is a tick borne virus which can lead to encephalitis. Methods: 63 year old woman with history of migraine presented with 2 days of fever, headache, language difficulty and right sided facial droop. Her examination revealed right upper motor neuron type facial weakness and expressive aphasia. She rapidly deteriorated within 24 hours becoming non verbal and ultimately comatose. Results: MRI brain revealed T2 hyperintensities in bilateral caudate and putamen. Subsequent MRI brain showed progression of the caudate and basal ganglia changes and new T2 hyperintensities in bilateral thalami and midbrain with no abnormal enhancement. CSF revealed lymphocytic pleocytosis with normal protein and glucose. Viral Encephalitis was suspected and she was continued on Acyclovir until Varicella zoster and Herpes simplex virus serology in CSF returned negative. Prolonged video EEG showed near continuous generalized triphasic pattern without any evolution or seizure pattern. There was no improvement in clinical status or EEG with antiepileptic treatment. Paraneoplastic panel , serum HIV, Lyme and 14-3-3 protein were negative. Extensive viral serologies were sent and ultimately Powassan serology came back positive. Conclusions: This case highlights powassan virus as a cause of encephalitis and occurrence of triphasic waves in non metabolic causes of encephalopathy such as infectious encephalitis.

Performance of Commercial Enzyme-Linked Immunoassays for Diagnosis of Herpes Simplex Virus-1 and Herpes Simplex Virus-2 Infection in a Clinical Setting.

US Food and Drug Administration-approved enzyme-linked immunoassays (EIA) for determining type-specific herpes simplex virus (HSV) serostatus are widely used in clinical practice. We compared the performance of such assays with the University of Washington Western blot (UW WB) in patients who sought confirmation of their HSV serology result. We reviewed charts of all persons evaluated at the Westover Heights Clinic in Portland, Oregon, from July 2010 through September 2015, who had a HSV EIA, followed by UW WB. Of 864 persons, 47% were women. The median age was 36 years (range, 18-73 years). Using UW WB to define infection status, 286 (33%) persons were HSV-1 seropositive only, 104 (12%) were HSV-2 seropositive only, 134 (16%) were both HSV-1 and HSV-2 seropositive, 235 (27%) were HSV seronegative, and 105 (12%) had indeterminate results. Compared with the UW WB as the criterion standard, EIA was 70.2% sensitive and 91.6% specific for HSV-1, and 91.9% sensitive and 57.4% specific for HSV-2.Among 278 persons who were HSV-1 seropositive by EIA, 255 were confirmed by the UW WB (positive predictive value [PPV], 91.7%). Of the 360 persons that were HSV-1 seronegative by the EIA, 252 were seronegative by UW WB (negative predictive value [NPV], 70.0%). Among 381 persons with HSV-2 EIA seropositivity, 193 tested HSV-2 seropositive by the UW WB (PPV, 50.7%). Of the 270 persons HSV-2 seronegative by EIA, 17 were seropositive with the UW WB (NPV, 93.7%). Among 261 persons with an EIA HSV-2 index value = 1.1-2.9, 39.8% of results were confirmed by UW WB, compared with 78.6% of the 70 persons with an EIA index value of 3 or greater (P < 0.001). The risk of false-positive HSV-2 EIA results was higher in those with HSV-1 antibody (47.1% vs 37.1%, P = 0.036). US Food and Drug Administration-approved EIAs have poor PPV for HSV-2 and poor NPV for HSV-1 in clinical practice. More accurate rapid type-specific HSV antibody tests are needed.

Herpes simplex virus seroprevalence and seroconversion among active duty US air force members with HIV infection

Herpes simplex virus (HSV) infection is associated with an increased risk of both HIV transmission and acquisition. We evaluated longitudinal HSV serology and sexually transmitted infections (STIs) among active duty US Air Force (USAF) members with HIV infection. USAF members diagnosed with HIV between 1996 and 2012 were included and divided into 2 groups: 1996-2004 (n=131) and 2005-2012 (n=266). HSV-1 and -2 serology was evaluated at HIV diagnosis. Longitudinal HSV-1 and -2 serology and ICD-9 codes for HSV and non-HSV STIs were also examined for those with ≥ 1 year of follow-up. Patients were most commonly Caucasian (44.2%) or African American (43.4%) men with a median age of 28 years at HIV diagnosis. HSV-2 seroprevalence at HIV diagnosis decreased from the period of 1996-2004 (48.8%) to 2005-2012 (30.1%; P<0.01). Odds of HSV-2 seropositivity was significantly greater for non-Caucasians (OR 2.19, 95% CI 1.33-3.60) and for HIV diagnosis between 1996 and 2004 (OR 2.06, 95% CI 1.29-3.27), with a trend observed for those age >30 years at HIV diagnosis (OR 1.73, 95% CI 0.94-3.18). A total of 81 (20.4%) patients developed STIs by ICD-9 codes, including 24 (6.1%) new genital herpes diagnoses, during a median follow-up of 4.6 years. HSV-2 seroconversion occurred in 33 of 253 (13.0%) with an incidence rate of 5.07 per 100 person-years (95% CI 4.76-5.37). Although HSV-2 seroprevalence at HIV diagnosis decreased over time, high-risk sexual behaviors were ongoing as evidenced by the high proportion of new STI diagnoses and HSV-2 seroconversions. Continued education to reduce risk behaviors is warranted to prevent acquisition and transmission of STIs in HIV-infected persons.

The frequency of herpes simplex virus changes in anal Pap smear and its association with squamous intraepithelial lesions in high‐risk male patients

While there are studies postulating a model of synergism between human papillomavirus (HPV) and herpes simplex virus (HSV) in cervical carcinogenesis, the frequency of anal herpes as well as its association with anal squamous intraepithelial lesions (ASILs) has been understudied in men. This study evaluates the frequency of HSV changes in anal Pap smears and its association with ASILs in a high-risk population. A computerized search for specimens associated with anal cytology that had positive findings of HSV was performed. The electronic medical records were examined for past diagnosis of herpes, HSV serology prior to or after cytology, and if the patient received treatment after cytologic diagnosis of HSV. Of the 470 anal Pap smears (Thin-prep) examined, seven had cellular changes consistent with HSV infection. All patients were asymptomatic human immunodeficiency virus (HIV) positive males with no prior HSV serology tests. Two patients had prior diagnoses of HSV infection. Cytologic abnormalities were identified in 86% ranging from atypical squamous cells of undetermined significance to high grade squamous intraepithelial lesion. Three patients were treated after the HSV cytologic diagnosis. The frequency of HSV changes in anal Pap smear is low (1.48%), but the presence of concomitant cytologic abnormalities is high (86%). While our findings suggest the possible role of HSV as a HPV co-factor in ASILs, larger studies are needed to support this. Identification of HSV infection on anal Pap smear is important for institution of patient treatment and subsequent reduction of transmission.

Viral Load Before and After Exchange Transfusion in a Neonate with Hyperbilirubinemia and Congenital Cytomegalovirus Infection

Introduction: Cytomegalovirus is the most common cause of intrauterine infection in developed countries. Between 10% and 15% of infants infected with congenital cytomegalovirus exhibits the clinically apparent or symptomatic form of the disease. Exchange transfusion is an established therapy for hyperbilirubinemia and severe anemia. However, to the best of our knowledge, the viral load of cytomegalovirus before and after exchange transfusion has not been previously reported. Case report: A Japanese female was delivered at 36 weeks of gestation to a 29-year-old gravida 3 para 3 by emergency Cesarean section because of non-reassuring fetal status. Hepatomegaly, splenomegaly, generalized petechiae, leptocephaly, and jaundice were noted at birth. On admission, her total bilirubin was 14.2 mg/dL, cytomegalovirus immunoglobulin M was positive (4.63 mg/dL), and her head ultrasound and computed tomography showed left intraventricular calcification and bilateral ventriculomegaly. Toxoplasma, rubella, and herpes simplex virus serologies were negative. The exchange transfusion was performed for the treatment of early onset hyperbilirubinemia, not for the treatment of congenital cytomegalovirus infection. The cytomegalovirus viral load before and after exchange transfusion was investigated by real-time polymerase chain reaction, and the plasma viral load of cytomegalovirus was not significantly decreased from before (8.7×105/mL) to after (4.3×105/mL) exchange transfusion. Conclusion: Exchange transfusion did not reduce the viral load of cytomegalovirus in severe congenital cytomegalovirus infection.

P5.068 Role of Type Specific Herpes Simplex Virus Serology in Diagnosis of Primary and Recurrent Genital Herpes- a Study in the Indian Population

Background Type specific serologic tests for herpes simplex virus (HSV)-1&2 are used for sero-epidemiological studies. Its early application has also been shown to be of benefit in testing for primary & recurrent infections in diagnosis and patient management. The present study was conducted to evaluate the role of type specific HSV-1&2 antibody detection as a diagnostic modality in patients with clinically suspected genital herpes. Methods Sera obtained from 44 patients with clinically suspected genital herpes attending the STD clinic of our institution over last 7 months were tested for type specific HSV-1&2 IgG antibody by glycoprotein G based ELISA (HerpeSelect 1&2, Focus Diagnostics, USA). Direct Fluorescent Antibody testing (DFA) (BIO-RAD laboratories, USA) was used for identification and typing of HSV-1& 2 in genital ulcer specimens in all cases. Results There were 21 cases of primary & 23 cases of recurrent genital ulceration. DFA was positive in 68% samples (43% only HSV-2, 9% only HSV-1, 16% both HSV-1&2). On comparison with DFA, the sensitivity, specificity, positive and negative predictive value of HSV-2 IgG ELISA in primary herpetic ulcer was 8%, 75%, 33%, 33%, while it was 79%, 89%, 92%, 73% in recurrent genital ulceration. The sensitivity, specificity, positive predictive and negative predictive values of HSV-1 IgG ELISA in primary herpetic ulcer was 50%, 67%, 37.5%, 77%, while it was 80%, 39%, 27%, and 87.5% in recurrent genital ulceration. Conclusion Our results highlight the importance of HSV-2 IgG detection in strengthening the diagnosis of recurrent HSV-2 disease, while absence of HSV-2 IgG antibody helps in excluding genital herpes as a likely cause of recurrent genital ulceration. The identification of HSV-1 IgG antibody may not be useful for diagnosis in patients of genital ulcer disease highlighting the need for typing HSV-1 strains from the genital lesion.

Paraneoplastic Pemphigus and Castleman’s Disease in the Setting of Herpes Simplex Virus Infection

A 14-year-old girl presented with a 3-week history of mucosal erosions, injected conjunctiva, dehydration, and respiratory distress. She had been treated with intravenous acyclovir for herpes simplex infection with positive herpes simplex virus immunoglobulin M and immunoglobulin G. Physical examination and imaging revealed a large abdominal mass. Incisional biopsy was obtained, and pathology demonstrated angiofollicular hyperplasia with hyalinized germinal centers and Castleman's syndrome-like features. Based on the mucosal erosions, herpes simplex virus serology and positive herpes simplex virus-1 direct fluorescent antibody, Castleman's disease secondary to overwhelming herpes simplex virus infection was the initial impression. The poor response to antivirals and subsequent development of a bullous eruption on the hands resulted in dermatology consultation. Skin biopsy was obtained from a bullae and revealed suprabasilar acantholysis with necrosis as well as upper dermal, perivascular, and interface infiltrate of lymphocytes and eosinophils. No viropathic changes were present. Direct immunofluorescence was significant for immunoglobulin G deposition intercellularly and along the dermoepidermal junction and focal trace C3 deposition along the dermoepidermal junction consistent with paraneoplastic pemphigus, later confirmed by indirect immunofluorescence. We report this case of paraneoplastic pemphigus secondary to Castleman's syndrome confounded by herpes simplex virus-1 positive mucosal erosions.

Evaluation of a Novel Serology Algorithm to Detect Herpes Simplex Virus 1 or 2 Antibodies

Herpes simplex virus (HSV)-type specific serology (TSS) testing has been commercially available for nearly a decade. Guidelines on appropriate use of such testing exist, including Canadian-based recommendations. Despite this, most Canadian laboratories do not offer HSV-type specific serology and many provide only nontype-specific HSV serology tests. At the Alberta Provincial Laboratory, HSV TSS is performed using the following algorithm (termed the Alberta algorithm). Eligible specimens are first tested with a nontype-specific kit (Behring Enzygnost IgG). If positive, sera are then tested using the Focus HerpeSelect-2 assay to establish HSV-2 infection. If the HerpeSelect-2 result is negative, the result is reported as anti-HSV-1 positive. In this study we sought a validation of the Alberta algorithm by testing 344 serum samples with the Behring Enzygnost IgG assay, the type specific Focus HerpeSelect 1 and 2 assays, and by Western blot (WB). Taking the WB as a gold standard, the Behring Enzygnost IgG assay showed a sensitivity of 94% and a specificity of 100%, whereas the Alberta algorithm had a sensitivity of 92% and a specificity of 97% for the detection of HSV-2 antibodies, and a sensitivity of 94% and a specificity of 100% for the detection of HSV-1 antibodies in HSV-2 negative sera. Focus HerpeSelect 1 and HerpeSelect 2 sensitivities against WB were 88% and 91%, whereas specificities were 95% and 97% for HSV-1 and HSV-2, respectively. The Alberta algorithm was at least equivalent to HerpeSelect 1 and 2 in detecting anti-HSV antibodies. Although sensitivity and specificity were higher, the differences were not statistically significant.

Etiology of Genital Ulcer Disease. A Prospective Study of 278 Cases Seen in an STD Clinic in Paris

The goal of this study was to identify the causes and factors associated with genital ulcer disease (GUD) among patients attending a sexually transmitted disease (STD) clinic in Paris. This study was a prospective investigation of GUD cases. Data were collected from 1995 to 2005. In each case, a Dark Field Examination (DFE), Gram stain, inoculation onto Thayer Martin agar, Columbia agar and chocolate agar with 1% isovitalex and 20% fetal calf serum, PCR Chlamydia trachomatis (Amplicor Roche), culture for herpes simplex virus (HSV) on MRC 5 cells and PCR HSV (Argene Biosoft) were obtained from the ulceration. First Catch Urine (FCU) PCR for Chlamydia trachomatis and syphilis, HIV, HSV, and HBV serologies were also performed. A total 278 cases of GUD were investigated, 244 (88%) in men and 34 (12%) in women. Primary syphilis accounted for 98 cases (35%), genital herpes for 74 (27%), chancroid for 8 (3%), other infections for 12 (5%). In 91 (32%) patients, no identifiable microorganism was documented. Primary syphilis was more prevalent in MSMs (P < 0.0001), while genital herpes and chancroid were significantly associated with heterosexuality (both P < 0.0001). A high level of HIV infection (27%) was found, particularly in patients with primary syphilis (33%). In the univariate analysis, no statistical difference was found between syphilis and herpes according to clinical presentation, pain being the only item slightly more frequent in herpes (P = 0.06). In the multivariable model syphilis was associated with being MSM (OR: 51.3 [95% CI: 14.7-178.7], P < 0.001) and with an ulceration diameter >10 mm (OR: 9.2 [95% CI: 2.9-30.7], P < 0.001). Genital herpes was associated with HIV infection in the subgroup of MSWs (OR: 24.4 [2.4-247.7], P = 0.007). We did not find significant differences in the clinical presentation of the ulcers according to HIV status. The profound changes of the epidemiology of GUD during the decade, due to disappearance of chancroid and reemergence of infectious syphilis have led to a new distribution of pathogens, genital herpes, primary syphilis and GUD from unknown origin, accounting each for one third of cases. No clinical characteristic is predictive of the etiology, underlining the importance of performing a thorough microbiologic evaluation. Close association with HIV is still a major public health problem.

Acute retinal necrosis and cystic encephalomalacia in a premature neonate.

To report a case of an infant born at 30 weeks gestational age (GA) who, at 37 weeks GA, presented with bilateral acute retinal necrosis (ARN) syndrome and herpes simplex virus (HSV) encephalomalacia. Observational case report. A premature infant was found to have ARN based on dilated funduscopic examination and positive HSV serologies. Herpes simplex virus encephalomalacia was diagnosed base on magnetic resonance imaging (MRI). To our knowledge, this is the youngest reported patient with ARN. This case demonstrates that neonatal ARN may present with posterior chorioretinal lesions and highlights the importance of considering HSV infection of the central nervous system with MRI findings of cystic encephalomalacia.

Mycoplasma pneumoniae Encephalitis and Reactivation of Herpes Simplex Virus: In Reply

We thank Dr Eisenhut for his interest in our prospective 12-year study of herpes simplex encephalitis in children.1 Because of the standardized comprehensive prospective microbiologic investigations performed on all children who were admitted to our institution with acute encephalitis, evidence of infection with >1 potential pathogen is often observed. This approach is very different from retrospective reviews of cases in which the final diagnosis is the point of entry into the study. In a recent review of our data, approximately one fourth of the cases showed evidence of infection (of variable strength) with ≥2 pathogens.2 In situations such as this, it is often not possible to determine with certainty which pathogen is the causative agent. Furthermore, in some cases, >1 of the potential pathogens may be playing a role.In regard to the specific cases mentioned by Dr Eisenhut, we disagree with his conclusion that Mycoplasma pneumoniae is the more likely pathogen. We believe that most experts would consider the detection of herpes simplex virus (HSV) in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) as strong evidence of causality irrespective of HSV serologic results or microbiologic evidence of infection with other potential pathogens. The failure to detect a rise in complement fixation titer to HSV (cases 7 and 8) between acute and convalescent sera could be a result of the well-known limited sensitivity of this assay.3,4 In regard to case 9, it is possible that the convalescent sample was obtained too early (51 days) for HSV seroconversion to have occurred. In 1 prospective study of HSV seroconversion, the median time between onset of genital tract symptoms and seroconversion was 56 days (interquartile range: 16–121 days).5 In addition, there is a paucity of data on the sensitivity of HSV serology in the setting of HSV encephalitis. We acknowledge that when both HSV and M pneumoniae are detected by PCR in the CSF (cases 7 and 9), it is difficult to assign causality solely to 1 pathogen. To avoid subjective assignment of causality, we set rigid inclusion criteria for herpes simplex encephalitis; these criteria are detailed in the methods section of our article.1Dr Eisenhut refers to “local reactivation” of HSV as a possible explanation for the delayed detection of HSV in the CSF of case patient 9. We do recognize that local reactivation (not causally related to the encephalitis) may be an explanation for some patients with positive HSV CSF PCR results but believe this to be unlikely in this case because of the aforementioned stringent criteria used to define HSV encephalitis. We did exclude several cases in which HSV was detected in the CSF by PCR because of a clear alternative diagnosis or absence of typical CSF, electroencephalographic, or neuroimaging findings, again in accordance with preselected exclusion criteria. As discussed in our article, we support a full course of therapy for possible HSV encephalitis for children in whom HSV is detected in the CSF by PCR irrespective of the suspected cause of the encephalitic process. In addition, it has been shown that the detection of HSV in the CSF by PCR of patients with HSV encephalitis can be delayed.6 Hence, HSV should not be excluded as a possible cause of encephalitis solely on the basis of a single negative CSF PCR assay, particularly if the lumbar puncture was performed during the first 48 to 72 hours of illness.We agree that M pneumoniae is an important cause of acute encephalitis in children and that additional research into the role of this pathogen in neurologic disease is needed. In a previous publication pertaining to M pneumoniae and acute childhood encephalitis, we stratified cases into probable, possible, and indeterminate categories in accordance with the strength of microbiologic evidence implicating M pneumoniae as the cause.7 Accordingly, M pneumoniae was considered to be the probable cause of 6.9% of the acute childhood encephalitis cases. As indicated in that article, cases in which the only evidence of M pneumoniae infection was serologic were often associated with more compelling evidence of infection with other potential pathogens. This observation suggests that many of the positive immunoglobulin M assays for M pneumoniae were probably falsely positive, perhaps as a result of cross-reactivity of M pneumoniae antigens and human brain antigens8–10 or other inherent limitations in the specificity of serologic tests for M pneumoniae.11Determining the etiology and pathogenesis of acute childhood encephalitis remains a major hurdle to the appropriate management of this condition. Ultimately, new innovative diagnostic and treatment strategies will be needed to improve the outcome of this often devastating entity.

Herpes Simplex Virus Type‐Specific Serology: Where Does it Fit in the Diagnostic Armamentarium?

Herpes Simplex Virus Type‐Specific Serology: Where Does it Fit in the Diagnostic Armamentarium?

Mini outbreak of Kaposi′s varicelliform eruption in skin ward: A study of five cases

Kaposis varicelliform eruption (KVE) represents widespread cutaneous herpes simplex virus (HSV) infection in patients with preexisting dermatoses. Occasionally, this infection can present as a nosocomial infection in skin wards, if adequate bed-spacing and barrier nursing methods are not followed. We are reporting five cases of KVE; four cases acquired the infection in a makeshift ward after admission of the first case in May 2005, due to the renovation work of the regular skin ward. The purpose of this study is to create clinical awareness about this uncommon dermatologic entity and to stress upon the importance of bed-spacing and barrier nursing in skin wards. Five cases of KVE, three females and two males with different primary dermatoses (pemphigus foliaceus--one, pemphigus vulgaris--two, paraneoplastic pemphigus--one and toxic epidemal necrolysis--one) were included in this study. Diagnosis was made clinically and supported with Tzanck smear and HSV serology. All the cases were treated with oral acyclovir. Four out of five cases of KVE recovered with treatment, one case of extensive pemphigus vulgaris with KVE succumbed to death. Mini outbreaks of KVE can occur in skin wards with inadequate bed-spacing and overcrowding of patients. Therefore adequate bed-spacing, barrier nursing and isolation of suspected cases are mandatory to prevent such life-threatening infections.

Paraneoplastic pemphigus resembling linear IgA bullous dermatosis

A 69-year-old Chinese man presented in 2001 with a blistering eruption over the upper and lower limbs associated with oral ulceration for 1 month. He had stage IIIA follicular small cell cleaved non-Hodgkin's lymphoma diagnosed 5 years previously, and had received several lines of palliative chemotherapy, including two courses of chlorambucil, six cycles of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP), and two four-cycle courses of rituximab, with disease stabilization at the time of presentation. Examination revealed erythematous, annular plaques with raised, urticarial borders studded with tense bullae and vesicles over the thighs. Some lesions were arciform and annular, with vesicles arranged in a ring at the border (Fig. 1). There was involvement of the feet with desquamation at the tips of the toes (Fig. 2). Severe erosions with hemorrhagic crusts on the lips, tongue, and buccal mucosa were seen. Herpes simplex virus serology was negative. A biopsy specimen from a vesicle on the left thigh showed suprabasal acantholysis (Fig. 3), some apoptotic keratinocytes (Fig. 4), satellite cell necrosis in the epidermis, and a superficial perivascular infiltrate of lymphocytes and eosinophils. Direct immunofluorescence showed intercellular immunoglobulin G (IgG) and C3 within the epidermis and along the basement membrane zone. Indirect immunofluorescence on monkey esophagus was positive for anti-intercellular antibody at a titre of 1/160 and positive on rat bladder at a titre of 1/80. A presumptive diagnosis of paraneoplastic pemphigus was made. This was later confirmed by the presence of antibodies against envoplakin (210 kDa), periplakin (190 kDa), and desmoglein 1 on immunoprecipitation studies. He was started on prednisolone 60 mg/day (1 mg/kg/day), with complete resolution of skin lesions within 1 week, but persistence of oral ulcers. Cyclophosphamide was added at a low dose of 1 mg/kg/day as he had baseline leukopenia. Cyclosporine was later added to a maximum of 4 mg/kg/day with only mild improvement of the oral lesions. He declined rituximab therapy. He died 2 months later from fulminant pneumonia.

The Laboratory Diagnosis of Herpes Simplex Virus Infections

Herpes simplex virus (HSV) types 1 and 2 cause genital herpes infections and are the most common cause of genital ulcer disease in industrialized nations. Although these infections are very common, the majority of them remain underdiagnosed because they are asymptomatic or unrecognized. A clinical diagnosis of genital herpes should always be confirmed by laboratory testing; this can be accomplished through the use of direct tests for viral isolation, the detection of antigen or, more recently, the detection of HSV DNA using molecular diagnostic techniques. Testing for serotypes is recommended because of the different prognostic and counselling implications. Type-specific HSV serology is becoming more readily available and will enhance the ability to make the diagnosis and guide clinical management in select patients.