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We present a case of a primigravida in her 30s who had a caesarean delivery of dichorionic diamniotic twins at 33 weeks of gestation. Her postpartum course was complicated by a herpes simplex virus (HSV) infection of her nipple, found after her neonates were diagnosed with HSV encephalitis. She was evaluated at her 3-week postpartum visit and reported that her neonates were concurrently admitted to the neonatal intensive care unit with disseminated neonatal HSV-1. The patient and her partner were in a monogamous relationship with no known history of HSV. Physical examination demonstrated a vertical fissure on the face of her right nipple and a small cluster of vesicles on her left hand. PCR swabs of the lesions were positive for HSV-1 at both locations. The patient was started on oral valacyclovir 1000 mg two times per day, topical acyclovir ointment applied 4-6 times per day and mupirocin ointment applied 3 times per day to her breast with resolution of her breast lesions. She was able to continue expressing her breastmilk with the help of a pump and then resumed breastfeeding once her infection was cleared. Her infants recovered after prolonged parenteral antiviral therapy with age-appropriate development at follow-up., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Neonatal herpes simplex virus (HSV) infection is rare, with an estimated incidence of 3.58 per 100 000 live births in the UK and should be suspected in any newborn with fever and bacterial culture-negative sepsis. We describe a case of a previously well full-term male neonate who presented with persistent fever and elevated ferritin level that was carried out during the era of the COVID-19 pandemic as part of SARS-CoV-2 panel investigations. Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. He made a full recovery after acyclovir therapy. This case highlights the importance of maintaining a high clinical index of suspicion of HSV infection in any febrile neonate even with absence of maternal history and negative serology, particularly if associated with hyperferritinaemia. We also address the challenge of interpreting inflammatory biomarkers' results for SARS-CoV-2 infection in neonates., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Herpes simplex virus (HSV) can affect the central nervous system causing meningitis, encephalitis and, rarely, acute retinal necrosis. We present a case of a 46-year-old man, previously healthy complaining of a 5-day persistent headache and sudden loss of vision of his left eye that progressed to the right. We started ceftriaxone, methylprednisolone and acyclovir for suspected encephalitis with vasculitis. HSV-1 was identified in vitreous and aqueous humour. Therapy with acyclovir was maintained and two intravitreous boluses of foscarnet were administered, without improvement. Usually being a benign infection, HSV can, in rare cases like this, have catastrophic effects in the optic tract., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

We describe the case of a 22-year-old man who presented with right eye visual impairment and oral mucositis. MRI revealed findings compatible with right optic neuritis. Herpes simplex virus 1 was detected in oral swab. He has a previous history of acute myeloid leukaemia (AML) and was in clinical remission. Initial investigations for possible relapse of AML with central nervous system (CNS) involvement were negative. Treatment for HSV-related optic neuritis was initiated but the patient's vision deteriorated. Repeat MRI revealed right optic nerve infarct, new left optic nerve abnormality and new leptomeningeal enhancement in the brain. Repeated cerebrospinal fluid analysis confirmed CNS relapse of AML. Despite prompt initiation of pulse steroid and high dose intrathecal cytarabine followed by cranial irradiation, the patient never regained his vision. We present a case of unexpected optic neuropathy as first and sole presentation of CNS relapse of AML., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

A 60-year-old man with a history of severe herpes simplex virus type 1 (HSV-1) encephalitis 2 years prior presented with acute onset of visual loss in the left eye. Dilated funduscopic examination showed retinitis and occlusive vasculitis with retinal necrosis. PCR of the vitreous fluid was positive for HSV-1, and he was diagnosed with acute retinal necrosis (ARN) due to HSV-1. The patient was treated with intravenous acyclovir and intravitreous foscarnet for 2 weeks, followed by high dose oral valacyclovir for 2 weeks. He was subsequently placed on planned life-long suppressive valacyclovir. His case demonstrates that acute visual loss concomitant with or subsequent to HSV-1 encephalitis warrants suspicion of ARN. Prompt therapy with effective antiviral medication is necessary to reduce the risk of sight-threatening complications. Chronic suppression with oral antiviral therapy after ARN is recommended to prevent involvement of the contralateral eye, though there is no consensus on the duration and dosage of antivirals., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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A 4-month-old female infant presented with a vesicular lesion on her left hand present since 1 day. A few days prior to presentation, she had a similar lesion on the lower lip. Two days after presentation, she returned with new lesions on her thorax and upper eyelid. PCR of the vesicle was positive for herpes simplex virus type 1. The transmission to her chest and face probably resulted from autoinoculation, caused by rubbing of the hand on other parts of the body. Transmission of herpes simplex through skin-to-skin contact is a common route of infection in people engaging in contact sports. Antiviral therapy was started because of the extensiveness and expansion of lesions and risk of developing herpetic keratitis. The patient completely recovered. This case shows that in an otherwise healthy infant, multiple herpetic skin lesions were not due to disseminated infection, but through autoinoculation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We present a case of severe fatal hepatitis in a young patient presumably triggered by two ubiquitous viral diseases which occurred in close succession. This case is unusual because of the exceptional chronological sequence of primary Epstein-Barr virus and herpes simplex virus type 1 infection causing systemic immune dysregulation associated with rapidly developing liver failure and consecutive multiorgan failure. Clinical, laboratory and histopathological findings indicated the development of secondary haemophagocytic lymphohistiocytosis triggered by these closely succeeding viral primary infections., (2017 BMJ Publishing Group Ltd.)

Objectives: Herpes simplex virus (HSV) type-discriminating antibody tests (glycoprotein G (gG) directed) are used to identify naïve persons and differentiate acute infections from recurrences. We studied test characteristics of three commercially available antibody tests in patients with recurrent (established by viral PCR tests) herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) genital herpes episodes., Methods: Serum samples (at minimum 3 months after t=0) were examined for the presence of gG-1-specific or gG-2-specific antibodies using the HerpeSelect 1 and 2 Immunoblot IgG, the HerpeSelect 1 and 2 enzyme linked immunoassays IgG and the LIAISON HSV-1 and HSV-2 IgG indirect chemiluminescence immunoassays., Results: The immunoblot was HSV-1 positive in 70.6% (95% CI 44.0% to 89.7%), the LIAISON in 88.2% (95% CI 63.5% to 98.5%) and the ELISA in 82.4% (95% CI 56.6% to 96.2%) of the 17 patients with a recurrent HSV-1 episode. From 33 patients with a recurrent HSV-2 episode, the immunoblot was HSV-2 positive in 84.8% (95% CI 68.1% to 94.9%), the LIAISON in 69.7% (95% CI 51.3% to 84.4%) and the ELISA in 84.8% (95% CI 68.1% to 94.9%). Among 15/17 (88.2%; 95% CI 63.5% to 98.5%) patients with HSV-1 and 30/33 (90.1%; 95% CI 75.7% to 98.1%) patients with HSV-2, HSV-1 or HSV-2 antibodies, respectively, were detected in at least one of the three antibody tests., Conclusions: Commercial type-specific gG HSV-1 or HSV-2 antibody assays were false negative in 12-30% of patients with recurrent HSV-1 or HSV-2 DNA positive genital lesions. The clinical and epidemiological use of type-specific HSV serology can be hampered by false-negative results, especially if based on a single test., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

We present a case of a preterm infant of 28 weeks' gestation with unique cutaneous lesions characteristic of a congenital herpes simplex virus (HSV) type 1 infection. The infant was prematurely delivered due to intractable labour. The mother had no history or clinical signs of genital infection before or during pregnancy. The infant's skin lesions were described as rough white-yellow plaques; a skin biopsy demonstrated calcified plaques and absent epidermis. HSV type 1 was later determined using PCR on the infant's skin biopsy and cerebral spinal fluid as well as the mother's vaginal swab and the placenta. Calcifications have already been described by Allee et al, alongside a diagnosis of HSV type 2. As is well known, the morbidity and mortality of congenital herpes infections are very high., (2015 BMJ Publishing Group Ltd.)

Aims: To determine the efficacy of a new helicase-primase inhibitor, ASP2151, for treating herpetic keratitis., Methods: Murine corneas were infected with herpes simplex virus type 1 (HSV-1). ASP2151 was administered orally or topically, and the severity of epithelial dendritic keratitis was determined. The effectiveness of ASP2151 was compared with that of acyclovir and valacyclovir. The reduction of the amount of HSV in tears, enucleated eyes and trigeminal ganglia was determined by real-time PCR or plaque assay., Results: Orally administered ASP2151 reduced the epithelial keratitis score significantly more than that of the vehicle-treated group (p<0.01). It also lowered the HSV-DNA levels in the tears significantly more than that by valacyclovir (p<0.01). ASP2151 ointment resulted in the same reduction of the keratitis score as acyclovir ointment, and lowered the HSV DNA in tears more than acyclovir ointment. Topical instillation of ASP2151 improved the herpetic dendritic keratitis score significantly and reduced the titre of HSV DNA in the tears in a dose-responsive way., Conclusions: ASP2151 had significantly better anti-HSV activity against herpes simplex keratitis than valacyclovir and acyclovir after systemic or topical use. These findings indicate that ASP2151 should be considered as an alternative treatment for herpes simplex keratitis.

Background: Herpes Simplex Virus (HSV) keratitis is a leading cause of corneal blindness. Definitive laboratory diagnosis is essential for timely management. Collection of corneal scrapings in patients with advanced epithelial keratitis and corneal thinning poses perforation risks; tear fluid is a feasible and convenient alternative but has not been widely evaluated for HSV detection., Methods: Tear fluid alone (229) or along with corneal scrapings (153) from patients of suspected herpetic keratitis was tested for HSV-1 antigen by indirect immunofluorescence assay, virus isolation in Hep 2 cells and PCR to amplify the 111bp region of the thymidine kinase (tk) coding gene and the 144bp region from the DNA polymerase coding gene of HSV., Results: HSV 1 antigen was detected in 31/229 (13.53%) tear specimen and 35/153 (22.87%) corneal scrapings in immunofluorescence assay; virus was isolated from 12/229 (5.2%) tear and 17/153 (11.11%) corneal scrapings, and PCR was positive for both the genes in 32/229 (13.97%) tear specimen and 56/153 (36.66%) corneal scrapings., Conclusion: Corneal scrapings yielded a significantly better HSV positivity than tears in both the PCR assay (p<0.0005) and immunofluorescence assay. PCR was much more sensitive than immunofluorescence and virus isolation. However, tears should be tested for definitive laboratory diagnosis of HSV infection whenever corneal scraping collection is not possible.

Objectives: To develop, evaluate and implement a new multiplex real-time PCR test for the detection of herpes simplex virus (HSV)1, HSV2 and syphilis in a single sample using a single test., Methods: A multiplex real-time PCR test detecting HSV1, HSV2 and Treponema pallidum was designed, validated and evaluated for a period of 6 months on patients attending the Sandyford Initiative (a series of genitourinary medicine clinics in and around Glasgow). A total of 692 samples were tested, and T pallidum PCR positives were confirmed by a second PCR at the Scottish Reference Laboratory (SBSTIRL). All PCR results were aligned with dark ground microscopy findings and serological results where available and compared., Results: The laboratory validation of the multiplex assay showed the test to be sensitive, specific and robust. Of the 692 samples, 139 were positive for HSV1, 136 for HSV2, 15 for syphilis, one for both syphilis and HSV1, and 401 were negative; the reference laboratory confirmed all T pallidum PCR-positive samples. The PCR test was more sensitive than both dark ground microscopy and serological testing for the diagnosis of primary syphilis., Conclusions: The introduction of this new test has led to a better turnaround time for the diagnosis of genital ulcer disease, better detection of primary syphilis infection, and the detection of unexpected cases of syphilis where the aetiological agent suspected was HSV.

Objective: To develop a real-time PCR assay that reliably and accurately detects the predominant sexually transmitted aetiological agents of genital ulcer disease (GUD) (Haemophilus ducreyi, Treponema pallidum and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)) and to assess the use of real-time PCR diagnostic testing in a rural African field site., Methods: Two multiplex real-time PCR reactions were used to detect H ducreyi/and HSV-1/HSV-2 in ulcer swabs from 100 people with symptomatic genital ulcers in rural Rakai, Uganda. Results were compared with syphilis, HSV-1 and HSV-2 serology., Results: Of 100 GUD samples analysed from 43 HIV positive and 57 HIV negative individuals, 71% were positive for one or more sexually transmitted infection (STI) pathogens by real-time PCR (61% for HSV-2, 5% for T pallidum, 3% for HSV-1, 1% for H ducreyi and 1% for dual H ducreyi/HSV-2). The frequency of HSV in genital ulcers was 56% (32/57) in HIV negative individuals and 77% (33/43) in HIV positive individuals (p = 0.037). Assay reproducibility was evaluated by repeat PCR testing in the USA with 96% agreement (kappa = 0.85)., Conclusions: STI pathogens were detected in the majority of GUD swab samples from symptomatic patients in Rakai, Uganda, by real-time PCR. HSV-2 was the predominant cause of genital ulcers. Real-time PCR technology can provide sensitive, rapid and reproducible evaluation of GUD aetiology in a resource-limited setting.

Aim: To document the histological features of multinucleated epithelial giant cells (MEGs) in colorectal hyperplastic polyps and determine a possible aetiological agent., Methods: Hyperplastic polyps were assessed for MEGs during the routine reporting at a private laboratory and public hospital laboratory. The histological features and clinical data were assessed, and immunohistochemical stains were performed to assess for viral infection (cytomegalovirus (CMV) and herpes simplex virus (HSV) 1 and 2) and to assist in the assessment of dysplasia (Ki-67, beta-catenin and p53). Ultrastructural examination was performed in one case., Results: MEGs were identified in 27 polyps (24 patients). There was active inflammation in the polyps in nearly all cases (n = 24) and most showed changes in adjacent non-hyperplastic bowel mucosa such as focal basal cryptitis and apoptosis of crypt epithelium (16 patients). Immunohistochemistry for CMV, HSV and p53 was negative in all cases. The MEGs showed nuclear positivity for the proliferative marker Ki-67 and membranous positivity for beta-catenin. Ultrastructural studies failed to reveal viral particles., Conclusions: All the polyps containing MEGs showed active inflammation and apoptosis, and in most there was also focal inflammation and apoptosis in the adjacent mucosa. Inflammation in conjunction with the increased epithelial proliferation characteristics of hyperplastic polyps could be the mechanism for the MEG formation. In this series, all the polyps were associated with sodium phosphate bowel preparation (NaP) and the pro-inflammatory properties of NaP may be a stimulus for the induction of giant cells.

Aims: To evaluate three tests used routinely for the diagnosis of herpes simplex virus (HSV) keratitis., Methods: Corneal scrapings from 28 patients with clinically typical dendritic corneal ulcer suggestive of HSV keratitis, and 30 patients with clinically non-viral corneal ulcers, were tested by (i) Giemsa stain for multinucleated giant cells, (ii) immunofluorescence assay (IFA) for HSV-1 antigen, and (iii) polymerase chain reaction (PCR) for HSV-1 DNA, by investigators masked to clinical diagnosis. The control subjects were also investigated by smears and cultures for bacteria, fungus, and Acanthamoeba., Results: The specificity and positive predictive values of all three tests for the diagnosis of HSV keratitis were between 95-100%. The sensitivity of IFA and PCR was 78.6% and 81.2%, respectively, and the difference was not significant; however, their sensitivity and negative predictive value were significantly higher than Giemsa stain., Conclusions: While a combination of IFA and PCR constitute the choice of tests in clinically suspected cases of HSV keratitis, multinucleated giant cells in Giemsa stain can pre-empt testing by IFA and PCR in otherwise atypical cases of HSV keratitis.

Objective: To compare the relative proportions of varicella zoster virus (VZV) and herpes simplex viruses in specimens obtained from the genital lesions of adults presenting with presumed genital herpes infection., Methods: Swabs of genital lesions from 6210 patients attending general practices, infectious diseases clinics within hospitals, or sexual health centres for treatment of their genital lesions were tested using polymerase chain reaction (PCR) technology. The multiplexed PCR was capable of detecting herpes simplex virus types 1 and 2 (HSV-1, HSV-2), VZV, and cytomegalovirus in a single sample., Results: A total of 2225 patients had viruses detected by PCR. HSV-1 was detected in 36%, HSV-2 in 61%, and VZV in 2.9% of PCR positive samples. Of the 65 patients with VZV genital infection, many were thought to have HSV infection before laboratory testing., Conclusions: The finding of VZV in nearly 3% of virus positive genital specimens demonstrates that this virus needs to be considered as a differential diagnosis for genital herpetic lesions. Advice provided to patients with VZV genital infection regarding the source of infection, likelihood of recurrence, and potential for transmission of the virus will be different from that given to patients with HSV infection.

There have been several important advances in the range of available diagnostic tests for genital herpes simplex virus (HSV) infection in recent years; polymerase chain reaction (PCR) is emerging in routine clinical use and the potential role of type specific serological tests is currently under debate. Several large trials of prophylactic vaccines, subsequently proved to be ineffective, have expanded knowledge of the transmission and epidemiology of HSV infection. This article discusses optimal application of recent research evidence to clinical care, structured around the key issues for patients and their partners. These include acquisition and transmission of genital HSV-1 and HSV-2 infection, the natural history of genital herpes, and the role of partner notification.

Objective: To establish risk factors for the presence of HSV-2 and HSV-1 infections in pregnant women. DESIGN, POPULATION, AND SETTING: A prospective study of 3306 women attending the antenatal department Westmead Hospital, Sydney, between June 1995 and April 1998., Methods: Women completed a self administered questionnaire to establish risk factors for the presence of HSV-2 and HSV-1. Sera were tested for antibodies to HSV-2 and HSV-1. Data were analysed using SPSS and SAS., Main Outcome Measures: Seroprevalence of and risk factors for HSV-2 and HSV-1., Results: 375 (11.3% (95% CI 10.3-12.5)) women were HSV-2 antibody positive. Increasing age, Asian country of birth, lower education level, public hospital status, confirmed genital herpes, a partner with genital herpes, early age of first sex, more than one lifetime sexual partner, and previous chlamydia infection were independently associated with HSV-2 seropositivity. Of 408 women tested for HSV-1 antibodies, 323 (79.2% (95% CI 74.9-83.0)) were positive. Oral herpes, oral blisters or sores, and being HSV-2 seropositive were independently associated with HSV-1 seropositive status. When the logistic regression model was rerun without HSV-2 status, parity of two or more and one or more sexual partners in the past 3 months were significant predictors of HSV-1 seropositivity., Conclusions: The presence of antibodies to HSV-2 and HSV-1 is related to a number of sexual and demographic risk factors. Public health campaigns directed at encouraging young people to delay the onset of sexual activity and reduce the number of sexual partners need to be evaluated. However, the possible availability of an HSV-2 vaccine that is able to protect over 70% of women offers the best hope for control of genital herpes.

Aims: Viral uveitis and retinitis, usually caused by herpesviruses, are common in immunosuppressed patients. The diagnosis of viral anterior uveitis and retinitis is usually clinical. The polymerase chain reaction (PCR) has been used for the diagnosis of some viral infections, especially those caused by herpesviruses. This paper reports the use of PCR in the diagnosis of viral retinitis in vitreous samples from Brazilian patients., Methods: PCR was used for the diagnosis of necrotising retinitis in vitreous samples from patients from the Hospital São Geraldo, Universidade Federal de Minas Gerais, Brazil. The vitreous samples were collected by paracentesis and stored until analysis. Samples were analysed by PCR using specific primers designed to amplify herpes simplex virus 1 (HSV-1), varicella zoster virus (VZV), or human cytomegalovirus (HCMV). In a case of anterior uveitis, PCR was performed with a sample from the anterior chamber., Results: Herpesvirus DNA was amplified in 11 of 17 samples. HCVM DNA was detected in nine samples but DNA from HSV-1 and VZV were detected only once each., Conclusion: These results strongly suggest that PCR could be used for a rapid complementary diagnosis of viral uveitis and retinitis. A prospective study to evaluate the PCR results, clinical evolution, and treatment is imperative to corroborate the real value of PCR in diagnosis and how it could help the clinicians' approach.

Aim: To study the value of polymerase chain reaction (PCR) analysis, to detect viral DNA in recipient corneal buttons taken at the time of penetrating keratoplasty (PKP) in patients with an initial diagnosis of herpetic stromal keratitis (HSK). Since HSK has a tendency to recur, an accurate diagnosis of previous HSK could be the reason to start antiviral treatment immediately, thereby possibly decreasing the number of graft failures due to recurrent herpetic keratitis., Methods: Recipient corneal buttons and aqueous humour (AH) samples were obtained at the time of PKP from HSK patients (n=31) and from other patients (n=78). Eye bank corneas were also used (n=23). Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), and varicella zoster virus (VZV) infection were assessed by PCR and antibody detection., Results: The clinical diagnosis HSK could be confirmed by PCR for HSV-1 in 10/31 (32%). In these corneal buttons HSV-2 DNA was detected in 1/31 (3%) and VZV DNA in 6/31 (19%). Intraocular anti-HSV antibody production was detected in 9/28 AH samples tested (32%). In the other patient derived corneas HSV-1 DNA was detected in 13/78 (17%), including eight failed corneal grafts without clinically obvious herpetic keratitis in the medical history. In clear eye bank corneas HSV-1 was detected in 1/23 (4%)., Conclusions: PCR of HSV-1 on corneal buttons can be a useful diagnostic tool in addition to detection of intraocular anti-HSV antibody production. Furthermore, the results were suggestive for the involvement of corneal HSV infection during allograft failure of corneas without previous clinical characteristic signs of herpetic keratitis.

Background/aims: It is reported by the national surveillance of ocular infectious diseases in Japan that 4.3% of cases of epidemic keratoconjunctivitis (EKC) diagnosed clinically were caused by herpes simplex virus (HSV). Clinical and virological studies of patients with HSV conjunctivitis were carried out., Methods: The study population consisted of 478 patients with acute follicular conjunctivitis. Virological analysis was carried out for adenovirus (Ad) and HSV by the cell culture method and fluorescein antibody (FA) method. Polymerase chain reaction for Chlamydia trachomatis was also carried out., Results: From 23 patients, HSV type 1 was isolated but Ad or C trachomatis was not isolated. 87% of cases were unilateral. Most cases showed clinical resolution within 9 days. Early corneal lesions and preauricular lymphadenopathy were less frequent in HSV conjunctivitis than in adenoviral conjunctivitis, especially that due to subgenus D. No case showed a positive result for HSV by the FA method using conjunctival swabs; however, the FA test was positive in all strains isolated by cell culture., Conclusions: These results indicate that it is difficult clinically to differentiate HSV conjunctivitis from adenoviral conjunctivitis in the acute stage, since the clinical features of adenoviral conjunctivitis are similar to those of HSV conjunctivitis. A biological difference may exist between HSV strains causing keratitis and conjunctivitis.

Objectives: To determine the proportion of herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2) in first episodes of genital herpes. To evaluate the use of HSV specific serology for classifying first episodes of genital herpes and for defining HSV serostatus in the patients' sexual partners., Methods: 108 consecutive patients with first episodes of genital herpes seen at three STD clinics in Sweden from 1995 to 1999 were included in the study. HSV culture and typing were performed and serum was tested for antibodies against a type common HSV antigen and a type specific HSV-2 antigen, glycoprotein G2 (gG2). A structured interview including questions about sexual behaviour and sexual partners was taken. "Steady" partners were offered a blood test for HSV serology and counselling., Results: Of 108 patients, 11 had a negative HSV culture. Of the 97 who were HSV culture positive, 44% (43/97) were typed as HSV-1 and 56% (54/97) as HSV-2. For 86 of these 97 patients, HSV serology from the initial visit was available. Of 52 primary infections, thus initially seronegative, 64% were HSV-1 infections and of 19 female primary infections 16 (84%) were HSV-1. In 17% the first episode of genital herpes corresponded to the first clinical recurrence of an infection acquired earlier in life. There was a significant correlation between having orogenital sex and being infected with HSV-1 and also a history of labial herpes in the partner. Only 20% of partners of patients with an HSV-2 infection had a history of genital herpes., Conclusions: Almost half of first episodes of genital herpes are caused by HSV-1. In young women with a primary genital infection, HSV-1 is much more frequent than HSV-2. Besides HSV typing, we found specific HSV serology of value for classifying first episodes and for diagnosing a subclinical HSV-2 infection in partners. Anamnestic data supported the suggestion that the orogenital route of transmission was common in genital HSV-1 infections.

Aims: To determine the sensitivity and specificity of culture, immunohistochemistry (IHC), the polymerase chain reaction (PCR), and in situ hybridisation (ISH) for detecting herpes simplex virus (HSV-1) in the cornea of patients undergoing penetrating keratoplasty. To compare the incidence of HSV-1 in the cornea with that of varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV)., Methods: The corneas of 110 patients, 52 with a documented history of herpes keratitis (HSK) and 58 with non-herpetic corneal disease, were investigated using IHC, PCR, ISH, and culture., Results: HSV-1 DNA and antigen were detected in 82% and 74% respectively, of corneas of patients with HSK and in 22% and 15% of corneas of patients with no history of HSK. The sensitivity of PCR and IHC was 82% and 74% with a specificity of 78% and 85%, respectively. HSV-1 DNA and antigen were found more frequently and in increased amounts in corneas of patients with a short interval between their last attack of HSK and surgery. There was a good correlation between PCR and IHC in 71%. HSV-1 was isolated by culture in 2%. Latency associated transcripts were not detected using ISH. Evidence of VZV DNA or antigen was found significantly more frequently in the corneas of patients with a history of HSK (p<0.001). No evidence of EBV or CMV was found in any cornea., Conclusions: PCR and IHC are both sensitive for the detection of HSV-1 in the cornea. A combination of PCR and IHC increases the specificity for the diagnosis of HSK to 97%. HSV-1 appears to be slowly removed from the cornea. VZV and HSV-1 may co-infect the cornea.

Objective: To measure the burden of infection with herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2) in the general population of England and Wales and to assess temporal changes in the incidence of HSV-1 infection in childhood., Methods: 4930 residual blood samples taken from people aged 0-69 years and submitted to 15 public health laboratories in England and Wales between January 1994 and June 1995, and 500 samples taken from people aged 10-14 years between November 1986 and December 1987, were screened for IgG antibody to HSV-1 and HSV-2 using type specific ELISA assays., Results: The prevalence of antibody to HSV-1 in 10-14 year olds declined from 34% in samples collected in 1986-7 to 24% in samples collected in 1994-5 (p < 0.001). HSV-1 antibody prevalence in adults increased with age and was higher in females than males, reaching 54% in females aged 25-30 years in 1994-5. In samples collected in 1994-5 from people aged 16-69 years HSV-2 antibody was detected in sera from 3.3% of men and 5.1% of women., Conclusions: The incidence of HSV-1 infection in childhood is falling in England and Wales. The prevalence of HSV-2 infection in the general population is low, with the rate of infection significantly lower than that described for the general population in the United States and developing countries. The falling rate of HSV-1 infection in childhood may be one factor contributing to the increasing incidence of genital HSV-1 infection.

Aim: To determine the relative impact of CD4+ T cells and CD8+ T cells in protecting mice against ocular HSV-1 challenge., Methods: CD4+ T cell knockout mice (CD4-/- mice), CD8+ T cell knockout mice (CD8-/- mice), and mice depleted for CD4+ or CD8+ T cells by antibody (CD4+ depleted and CD8+ depleted mice), were examined for their ability to withstand HSV-1 ocular challenge. The parental mice for both knockout mice were C57BL/6J., Results: These results suggest that: (1) both CD4+ deficient mice (CD4-/- and CD4+ depleted mice) and CD8+ deficient mice (CD8-/-, and CD8+ depleted mice) developed significantly more corneal scarring than their C57BL/6J parental strain; (2) the duration of virus clearance from the eyes of the CD4+ deficient mice was 4 days longer than that of the CD8+ deficient mice; and (3) the severity of corneal scarring in the CD4+ deficient mice was approximately twice that of the CD8+ deficient mice., Conclusions: It was reported here that: (1) CD4+ and CD8+ T cells were both involved in protection against lethal ocular HSV-1 infection; and (2) CD4+ and CD8+ T cells were both involved in protection against HSV-1 induced corneal scarring.

Objectives: To investigate the current use of diagnostic methods for genital herpes simplex virus (HSV) infection, to determine how information from these tests influences clinical practice, and to identify areas for future guideline development within genitourinary medicine (GUM) clinics in the United Kingdom., Methods: National survey of 173 consultants in UK GUM clinics., Results: Completed questionnaires were returned by 146 (84%) consultants. Cell culture was the first line diagnostic method for 133 (91%) respondents, the remaining 13 (9%) used antigen detection tests. Typing of isolates (HSV-1 or HSV-2) was available in their local laboratory to 109 (75%) clinicians; however, less than two thirds routinely pass this information on to their patients. Although 74 (51%) respondents had access to serological diagnosis, the majority of methods described were non-specific; only three (2%) had access to type specific tests. Only 81 (56%) respondents frequently (> 90% of the time) recommend notification of recent sexual partners of genital herpes patients., Conclusions: While access to culture based diagnosis is widespread, type specific serology has limited availability. Information on typing of isolates as HSV-1 or 2, although available in three quarters of centres, is underutilized in counselling patients. As HSV type influences both clinical and subclinical reactivation rates and may also affect probability of transmission, this is an important omission. Future guidelines need to address the optimal use of viral typing and new diagnostic tests to optimise health gain; there is also a need for evidence based recommendations about partner notification in genital herpes.

Objective: To develop a new, rapid, and convenient technique for the diagnosis and typing of herpes simplex virus (HSV) in genital herpes (GH)., Methods: Using samples from skin vesicle fluid and urogenital mucosal swabs of subjects with GH, conventional polymerase chain reaction (PCR) (directed to polymerase gene: PCRpG) were compared with a newly developed PCR (directed to HSV glycoprotein gene: PCRgG). Both PCR methods were compared with virus isolation culture (VI) with indirect immunofluorescent staining (IIF)., Results: 80 samples from 40 GH patients (25 males) were tested. Positive results were seen in 52.5% (42/80) using PCRgG compared with 40% (32/80) by VI. Most of PCRgG positive samples (95.1%) were caused by HSV-2 infection. In samples from healing lesions, HSV was detected more often by PCRgG, than by VI. The results of typing by PCRgG and IIF were highly consistent., Conclusion: PCRgG is more sensitive than VI and PCRgG in detecting HSV in urogenital samples from subjects with GH. PCRgG is a convenient technique for the rapid detection and typing of GH.