2017 European guidelines for the management of genital herpes.

Genital herpes is one of the commonest sexually transmitted infections worldwide. Using the best available evidence, this guideline recommends strategies for diagnosis, management, and follow-up of the condition as well as for minimising transmission. Early recognition and initiation of therapy is key and may reduce the duration of illness or avoid hospitalisation with complications, including urinary retention, meningism, or severe systemic illness. The guideline covers a range of common clinical scenarios, such as recurrent genital herpes, infection during pregnancy, and co-infection with human immunodeficiency virus.

Stability of glycoprotein gene sequences of herpes simplex virus type 2 from primary to recurrent human infection, and diversity of the sequences among patients attending an STD clinic.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is sexually transmitted, leading to blisters and ulcers in the genito-anal region. After primary infection the virus is present in a latent state in neurons in sensory ganglia. Reactivation and production of new viral particles can cause asymptomatic viral shedding or new lesions. Establishment of latency, maintenance and reactivation involve silencing of genes, continuous suppression of gene activities and finally gene activation and synthesis of viral DNA. The purpose of the present work was to study the genetic stability of the virus during these events. METHODS: HSV-2 was collected from 5 patients with true primary and recurrent infections, and the genes encoding glycoproteins B,G,E and I were sequenced. RESULTS: No nucleotide substitution was observed in any patient, indicating genetic stability. However, since the total number of nucleotides in these genes is only a small part of the total genome, we cannot rule out variation in other regions. CONCLUSIONS: Although infections of cell cultures and animal models are useful for studies of herpes simplex virus, it is important to know how the virus behaves in the natural host. We observed that several glycoprotein gene sequences are stable from primary to recurrent infection. However, the virus isolates from the different patients were genetically different.

CD11c(+) dendritic cells rather than Langerhans cells are reduced in normal skin of immunosuppressed renal transplant recipients.

The increased risk of squamous cell carcinomas (SCC) in renal transplant recipients (RTR) is related to impaired immunosurveillance as a consequence of immunosuppressive therapy. Since dendritic cells (DC) play an important role in immunosurveillance, we investigated the quantity of DC subsets and macrophages in normal skin of RTR and immunocompetent controls by immunohistochemistry. In this comparative study Langerhans' cells (LC) were present in similar numbers in RTR and controls. The number of CD11c+ DC was significantly reduced in RTR, particularly in patients on triple treatment therapy, compared with controls. Macrophages were significantly increased. Plasmacytoid DC were not detected in normal skin. The reduced quantity of CD11c+ DC and increased number of macrophages in normal skin of immunosuppressed RTR may contribute to the increased incidence of SCC in RTR. This finding underlines the role of DC subsets in immunosurveillance, and may have implications for our understanding of the effect of immunosuppression on DC subsets.

Herpes simplex virus infection and genital ulcer disease among patients with sexually transmitted infections in Dar es Salaam, Tanzania.

The relative importance of Haemophilus ducreyi and Treponema pallidum in genital ulcer disease in Africa has decreased recently, whereas that of herpes simplex virus (HSV) type 2 has increased. We analysed 301 lesional specimens from Tanzanian patients with genital ulcer disease for the presence of H. ducreyi, T. pallidum and HSV-1/HSV-2 by performing a separate PCR for each pathogen. Infectious agents were detected in 211 (70%) of the cases. A single pathogen was found in 191 samples and two or more pathogens in the remaining 20. HSV-2 represented 83% of all identified pathogens, HSV-1 8%, T. pallidum 4% and H. ducreyi 5%. HSV-1 was identified as a single pathogen in four samples, in combination with others in an additional 14 samples. Thus, HSV-1 can also be the cause of genital ulcer disease in Africa. Regular surveillance of genital ulcer disease aetiology is important in programs for management of genital ulcer disease and HIV in Africa.

Prevalence of antibodies against herpes simplex virus types 1 and 2 in children and young people in an urban region in Tanzania.

Herpes simplex virus type 1 (HSV-1) is transmitted by close contact, both sexual and nonsexual, and infections are acquired during childhood and adolescence. Herpes simplex virus type 2 (HSV-2), however, is thought to be transmitted mainly by sexual contact. Most HSV-2 infections are consequently expected to occur after the onset of sexual activity. Recent reports indicate an increasing prevalence of HSV-2 on the African continent, but most studies have been performed on adult cohorts. In the present study, we collected sera from Tanzanian children and young persons from 1 to 20 years old, with at least 100 individuals in each age group. Antibodies against HSV-1 and HSV-2 were detected by an in-house Western blot method which was shown to perform well in comparison with a commercial Western blot assay. Type-specific antibodies were also analyzed by two noncommercial enzyme-linked immunosorbent assay methods based upon the antigenicities of branched synthetic oligopeptides corresponding to epitopes in glycoprotein G of HSV-1 or HSV-2. The prevalence of HSV-1 antibodies increased gradually from 73% for the age group of 1 to 4 years to 92% for the age group of 17 to 20 years. The prevalence of HSV-2 antibodies was unexpectedly high, as 15% of the children were infected by the age of 8 years, with the incidence increasing gradually to 40% in the age group of 17 to 20 years. The reason for this unexpectedly high frequency is not clear but could suggest that nonsexual transmission of HSV-2 is more common than previously thought. There was no statistically significant association between seropositivities for HSV-2 and human immunodeficiency virus.

Demographic and behavioural factors in Tanzanian and Norwegian patients with sexually transmitted infections.

To evaluate whether differences in demographic or behavioural factors might explain differences in reported or diagnosed sexually transmitted infections (STI), we have compared data from 1097 Tanzanian and Norwegian STI patients. Most demographic data were similar, whereas some behavioural data differed. Norwegian patients reported significantly higher numbers of sexual partners than Tanzanian. Thirty-three percent of Tanzanian patients tested positive for HIV antibodies, females more often (43%) than males (26%). Approximately one-third and two-thirds of the female HIV-positive Tanzanian STI patients had already seroconverted at the age of 25 and 30 years, respectively. The national differences encountered probably reflect cultural differences, different panoramas of STI and a lower accessibility to optimal health services in Tanzania. Lack of expected statistical associations between some of the data in the Tanzanian STI group might question the validity of the retrospectively collected data in this group, or indicate that questions not included in the questionnaire might be of importance.

A branched, synthetic oligopeptide corresponding to a region of glycoprotein G of HSV-1 reacts sensitively and specifically with HSV-1 antibodies in an ELISA.

Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2), which are common worldwide, are so similar that antibodies directed against one serotype may crossreact with antigens from the other one. Methods for specific detection of antibodies against HSV-1 or HSV-2 are based upon the antigenicities of glycoproteins G. However, due to the cost, the available commercial methods may not readily be used in developing countries. A different enzyme-linked immunosorbent assay (ELISA) method, based upon a synthetic oligopeptide corresponding to an immunogenic region in glycoprotein G of HSV-2, has been used recently and successfully for detection of HSV-2 antibodies. In the present study, the sequences of a newly identified immunogenic and type-specific region in glycoprotein G of HSV-1 was used to synthesize three different, branched oligopeptides. The performances of these peptides in an ELISA were investigated by testing Scandinavian and African sera which were characterized by commercial ELISA and Western blotting methods and divided into four groups either lacking HSV antibodies, containing antibodies against one or the other virus, or against both types. The peptide which corresponded in sequence to the immunodominant region was as specific and sensitive by an ELISA as were the commercial methods. The method is inexpensive and reliable.

Performance characteristics of a glycoprotein G based oligopeptide (peptide 55) and two different methods using the complete glycoprotein as assays for detection of anti-HSV-2 antibodies in human sera.

Assays for serological diagnosis of HSV-2 infection in clinical settings have been generally available only recently. We wanted to investigate and compare the diagnostic utility of three different ELISAs for detection of anti-HSV-2 IgG antibodies, using intact glycoprotein G or an oligopeptide from a portion of the protein as antigens. HSV-1 negative/HSV-2 negative sera (n = 32), HSV-1 positive/HSV-2 negative sera (n = 30) and sera from HSV-2 culture positive individuals (n = 36), collected at least 6 months after culture verified HSV-2 genital infection were examined. Cut-off values were determined according to the manufacturer's instructions, and also by establishing new cut-off values at the level of highest diagnostic efficiency. Sensitivities and specificities were compared for each assay. In addition, test accuracies were compared using receiver-operating characteristics (ROC) methodology. Establishment of new cut-off values increased the performance characteristics for all three tests. At similarly set cut-off values, the peptide 55 assay showed the highest diagnostic sensitivity (100%) and specificity (98%). All three assays displayed high efficiency and also high agreement between the tests (kappa > 0.85 for all comparisons). The performance of all three assays were satisfactory although the highest efficiency and accuracy was obtained with the peptide 55 assay.