Arvid Nilsen

Changing trends in genital herpes simplex virus infection in Bergen, Norway

Aim of study. To document the proportion of each herpes simplex virus (HSV) type in genital HSV infection and changes over time during a 10 year period.

A longitudinal study of phagocyte function in HIV-infected patients

ObjectiveTo study the influence of HIV infection on phagocyte function. To date, the results of phagocyte function studies in HIV-infected patients have been contradictory. This is the first longitudinal study of these functions in HIV infection. DesignWe followed 50 individuals with HIV infection for 2–51 months (mean, 28 months) and examined polymorphonuclear leukocyte (PMNL) and monocyte functions at intervals of 0.5–1 years. MethodsPMNL random migration and chemotaxis were assessed using an under-agarose method, and PMNL and monocyte oxidative metabolism by chemiluminescence production during phagocytosis of opsonized zymosan. ResultsPMNL random migration and chemotaxis were impaired at entry into the study by 15 and 19%, respectively. After 3 years the reduction was 35 and 32%, respectively. The mean chemiluminescence production by PMNL was reduced by 6% at entry into the study. After 4 years a decrease of 18% was observed. The decrease in PMNL function was most marked in patients with lymphadenopathy syndrome or AIDS. No significant change in monocyte chemiluminescence production was detected at any time during the study. ConclusionsA distinct and progressive decrease of PMNL function occurs during HIV infection. This may contribute to increased susceptibility to opportunistic infections in HIV-infected patients. For monocytes, chemiluminescence production is not influenced by HIV infection.

Prevalence of Antibodies against Herpes Simplex Virus Types 1 and 2 in Children and Young People in an Urban Region in Tanzania

ABSTRACT 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.

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, and risk factors for, HSV-2 antibodies in sexually transmitted disease patients, healthy pregnant females, blood donors and medical students in Tanzania and Norway

The prevalence of specific HSV-2 antibodies was studied in Tanzanian and Norwegian sexually transmitted disease (STD) patients (1095) and non-STD patients (488). Correlates to demographic and behavioural factors were evaluated. Seropositivity was determined by the non-commercial peptide-55 enzyme-linked immunoassay. The prevalence of HSV-2 antibodies was 70% in Tanzanian and 17% in Norwegian STD patients, 35% in Tanzanian blood donors and pregnant women, and 4, 7 and 14% in Norwegian medical students, blood donors and pregnant women respectively. A higher HSV-2 prevalence was associated with female sex, increasing age, previous STDs, history of genital HSV infection, coitarchal age (age at first intercourse) <15 years and HIV seropositivity. Compared to previous data, the prevalence of HSV-2 antibodies in Tanzanian STD patients has increased remarkably. In Norwegian STD patients our results are consistent with, or lower than, the prevalence previously reported in Western Europe. Demographic rather than behavioural factors were associated with higher prevalence of HSV-2 antibodies in STD patients.

Serum antibodies to viral pathogens and Toxoplasma gondii in HIV-infected individuals

Sera from 38 HIV‐infected individuals were examined longitudinally for antibodies to viruses that may increase morbidity in HIV infection, as well as commensal viruses and Toxoplasma gondii. HTLV infection was seen in Norway for the first time as four patients had antibodies to HTLV‐II and one had antibodies to HTLV‐I. Antibodies to hepatitis B virus (HBV) were found in 47.2%, while 21.6% of the patients had antibodies to hepatitis C virus (HCV). There was no evidence of acquisition of HBV or HVC during the mean observation period of 2 years. A titre increase in CMV antibody with time was observed for 7 out of 21 patients and a decrease for 2 patients. For Epstein‐Barr virus, herpes simplex, varicella‐zoster, rubella and measles viruses, human polyomavirus BK as well as for Toxoplasma gondii, antibody prevalences and titres were within the range seen in normal populations. Also, no longitudinal changes were observed in titres of these antibodies, indicating that humoral immunity remained intact during the study period. The high prevalences of HTLV‐I/II, HBV and HCV antibodies in HIV‐infecled patients reflect common modes of virus transmission, and the fluctuations in CMV antibody titre are indicative of reactivations. Such coinfections may influence disease progression.

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 manufacturers 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.

Diagnosis of infection with human T-lymphotropic virus type II (HTLV-II) in Norwegian HIV-infected individuals

Sera from 298 HIV-infected individuals from Southern Norway were examined for antibodies against HTLV. 30 sera (10.1%) were HTLV-II positive and 1(0.3%) HTLV-I positive. 25 of the HTLV-II infected subjects were intravenous drug abusers (IVDAs), giving a prevalence of HTLV-II infection of 24.5% in this group. Examination of blood samples by polymerase chain reaction followed by restriction enzyme analysis or sequencing confirmed the serological diagnosis. To evaluate current screening and verification HTLV tests, 44 sera were examined using a gelatin particle agglutination test, 5 different enzyme-linked immunoassays (ELISA) and 4 Western blots (WB). While earlier ELISAs and WBs were inadequate, a recent ELISA and WB including recombinant envelope glycoproteins from both viruses permitted serological diagnosis and distinction between HTLV-I and HTLV-II. Thus, HTLV-II now spreads among IVDAs in a North-European country. Health authorities in other countries should estimate the magnitude of the problem to decide upon measures to avoid transmission through blood transfusion.

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.

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

BackgroundHerpes 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.MethodsHSV-2 was collected from 5 patients with true primary and recurrent infections, and the genes encoding glycoproteins B,G,E and I were sequenced.ResultsNo 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.ConclusionsAlthough 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.