Jennifer M. Best

Serologic Evidence of Human Herpesvirus 8 Transmission by Homosexual but Not Heterosexual Sex

Epidemiologic studies link Kaposis sarcoma with a sexually transmitted agent. Human herpesvirus 8 (HHV-8) is likely to be that agent, but routes of transmission are poorly described. A seroepidemiologic study was conducted to determine whether HHV-8 is transmitted sexually between heterosexuals. Sera from 2718 patients attending a sexually transmitted disease (STD) clinic were tested for antibodies to HHV-8 and herpes simplex virus type 2 (HSV-2). Information on sex partners in the previous 12 months and past STDs were obtained by questionnaire. Relationships between possible risk factors and HHV-8 infection were assessed by logistic regression. Overall, seroprevalence of HHV-8 was 7.3%. Independent risk factors for HHV-8 in the whole group were homo/bisexuality and birth in Africa and, among homo/bisexual men, a history of syphilis and HSV-2 and human immunodeficiency virus seropositivity. Among heterosexuals there was no evidence for sexual transmission; the only independent risk factor for HHV-8 seropositivity was birth in Africa.

Mumps and the UK epidemic 2005

The United Kingdom is in the grip of a nationwide mumps epidemic with almost 5000 notifications in the first month of 2005 alone.1 Most patients are aged between 19 and 23, and there is now the threat of outbreaks among under-immunised children. As a result of the measles, mumps, and rubella (MMR) vaccine, which was introduced in 1988, the current generation of practising doctors have little experience of mumps infection. Mumps may have permanent sequelae, and not all cases can be diagnosed clinically. Here we explain the basis of the current epidemic and review the epidemiology, clinical presentation, complications, laboratory confirmation, and treatment of mumps. We searched Medline for evidence based information on the internet, using a range of search terms. Other internet based resources included the websites of the Health Protection Agency (HPA), the World Health Organization (WHO), and the US Centers for Disease Control (CDC). We also used various formal texts. Mumps is an enveloped, single stranded RNA virus belonging to the family paramyxoviridae, which causes an acute infectious disease mainly in children and young adults.2 Transmission is by droplet spread, and humans are the only known host. Mumps is highly infectious and spreads rapidly in susceptible people living in close proximity. The number of secondary cases of infection expected to result from an index case of mumps in a fully susceptible population (R or basic reproduction number) is 10-12. By comparison, measles—a notoriously infectious virus—has an R of 15-17.3 The incubation period from infection to appearance of the characteristic swelling of the parotid glands is 15-24 days.4 The infectious period starts several days before the onset of parotitis and continues for several days afterwards.4 w1Infection control guidance for schools and nurseries advises that children stay away from school for …

Failure of acyclovir cream in treatment of recurrent herpes labialis.

A double blind, randomised, crossover placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 45 patients with recurrent herpes labialis. These patients had a total of 72 episodes, 34 of which were treated with the 5% acyclovir cream and 38 with placebo cream. Treatment was begun by the patients as soon as possible after the onset of prodromal symptoms. There was no significant clinical benefit from treatment with acyclovir cream compared with placebo cream. The median healing times were nine days with acyclovir cream, 10 days with placebo cream, and 13 days when no treatment was given. The possibility that the 40% propylene glycol cream base alone has a therapeutic effect must therefore be considered.

Human herpesvirus 8: Seroepidemiology among women and detection in the genital tract of seropositive women

An indirect IFA to detect antibodies against latent nuclear antigens of human herpesvirus 8 (HHV-8) was used to determine the prevalence of HHV-8 antibodies in 169 women attending a sexually transmitted diseases clinic and a human immunodeficiency virus (HIV) clinic at a London hospital. Nested polymerase chain reaction was used to detect HHV-8 DNA in 93 blood samples and 89 cervical brush scrapes (CBS). Another 96 CBS from women attending a colposcopy clinic were also analyzed. The overall seroprevalence of HHV-8 was 18.3%. The seroprevalence was higher among women born in Africa (24.7%) than among women born elsewhere (11.5%; P=.06) and was independent of HIV serostatus. HHV-8 DNA was detected in 3 CBS and 6 peripheral blood samples from 11 HHV-8-seropositive women but not in CBS from 78 seronegative women, 96 women from the colposcopy clinic, or in blood samples from 82 seronegative women.

RUBELLA VIRAEMIA AND ANTIBODY RESPONSES AFTER RUBELLA VACCINATION AND REIMMUNISATION

Eleven 4-13 year old schoolgirls, who were seronegative by haemagglutination inhibition (HI) and radioimmunoassay (RIA) tests despite having been given HPV77-DE5 vaccine 3-9 years previously, were revaccinated with RA27/3. They showed evidence of residual immunity since they had accelerated immune responses, little or no rubella-specific IgM, no viraemia, and no vaccine-induced reactions. In contrast, all but one of the five adult women who were primary vaccinees showed a more delayed immune response. Three of four women tested had viraemia and two had vaccine-induced reactions. Enhanced HI and enhanced RIA showed that many of the schoolgirls had antibody before challenge, as did a fifth adult, who also showed an accelerated immune response, yet became viraemic.

Interpretation of rubella serology in pregnancy—pitfalls and problems

Clinical and laboratory expertise is essenrial for evaluating rubella specific IgM test results in pregnancy

The involvement of survival signaling pathways in rubella-virus induced apoptosis

Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the development of such defects. Often the outcome of apoptotic stimuli is dependent on apoptotic, proliferative and survival signaling mechanisms in the cell. Therefore we investigated the role of phosphoinositide 3-kinase (PI3K)-Akt survival signaling and Ras-Raf-MEK-ERK proliferative signaling during RV-induced apoptosis in RK13 cells. Increasing levels of phosphorylated ERK, Akt and GSK3β were detected from 24–96 hours post-infection, concomitant with RV-induced apoptotic signals. Inhibition of PI3K-Akt signaling reduced cell viability, and increased the speed and magnitude of RV-induced apoptosis, suggesting that this pathway contributes to cell survival during RV infection. In contrast, inhibition of the Ras-Raf-MEK-ERK pathway impaired RV replication and growth and reduced RV-induced apoptosis, suggesting that the normal cellular growth is required for efficient virus production.

High prevalence of human papillomavirus type 16 infection among children

Infection with high‐risk human papillomaviruses (HPV), is the most significant risk factor for cervical cancer and it may be possible to prevent this malignancy by immunisation. Before immunisation programmes can be designed, however, it is necessary to know the age of acquisition and all routes of infection for these viruses. Sexual transmission is well documented and vertical transmission has also been demonstrated, although the frequency of transmission remains controversial. We previously showed that vertical transmission frequently results in persistent infection, and now present data on the prevalence of HPV‐16 DNA (the most prevalent high‐risk HPV type) in healthy children. Buccal samples from 267 healthy children aged 3–11 years were tested for HPV DNA by generic PCR (MY09/MY11), and a HPV‐16 specific nested PCR. Reverse transcriptase (RT)‐PCR was used to determine the prevalence of transcriptionally active HPV‐16 infection in a subset of children. HPV‐16 DNA was detected by nested PCR in 138 of 267 (51.7%) samples, whereas HPV DNA was detected in only 45 (16.8%) specimens by generic PCR, that has a lower analytical sensitivity. There were no significant differences in prevalence according to age or sex. Early region mRNA was detected by RT‐PCR in six (11.3%) of 53 HPV‐16 E5 DNA positive samples. HPV‐16 E5 DNA sequences from 10 children confirmed the identity of the sequences detected and identified 13 HPV‐16 variants. J. Med. Virol. 61:70–75, 2000.

Detection of E5 oncoprotein in human papillomavirus type 16-positive cervical scrapes using antibodies raised to synthetic peptides

Polyclonal antibodies were raised to partial and full-length synthetic peptides of human papillomavirus type 16 (HPV-16) E5. Antisera specificity for HPV-16 E5 was demonstrated by their ability to recognize not only their peptide immunogens but also full-length peptide and a glutathione S-transferase-E5 fusion protein. The most reactive antiserum, PE-6, raised to a full-length peptide, was used in Western blot analysis to identify HPV-16 E5 protein from exfoliated cervical cells. A strong, single band at approximately 20K was detected in two of six HPV-16-positive samples from women with a history of low-grade cervical intraepithelial neoplasia. The apparent M(r) by SDS-PAGE suggests that HPV-16 E5 forms homodimers in vivo, but not through cysteine linkage.

Molecular Analysis of Rubella Virus Epidemiology across Three Continents, North America, Europe, and Asia, 1961–1997

E1 gene nucleotide sequences of 63 rubella virus isolates from North America, Europe, and Asia isolated between 1961 and 1997 were compared phylogenetically. Two genotypes were evident: Genotype I contained 60 viruses from North America, Europe, and Japan, and genotype II contained 3 viruses from China and India. The genotype I isolates prior to 1970 grouped into a single diffuse clade, indicating intercontinental circulation, while most post-1975 viruses segregated into geographic clades from each continent, indicating evolution in response to vaccination programs. The E1 amino acid sequences differed by no more than 3%; thus, no major antigenic variation was apparent. Among 4 viruses from congenital rubella syndrome that occurred following reinfection, only one amino acid substitution occurred in several important epitopes, indicating that antigenic drift is not important in this phenomenon. However, 2 viruses isolated from chronic arthritis exhibited changes in these epitopes. Isolates of the RA 27/3 vaccine strain were readily identifiable by nucleotide sequence.