Is the MMR vaccination programme failing to protect women against rubella infection?

In recent years the number of pregnant women susceptible to rubella has increased markedly. In the West Midlands the proportion has risen from 1·4% in 2004 to 6·9% in 2011. Locally, the proportion of non-immune women ranges from 1·6% in those born prior to 1976 to 17·8% in those born since 1986. The latter group comprises those given MMR in their second year with no further booster doses. The number of non-immune women will continue to rise as a consequence of low MMR uptake in the late 1990s. Repeat testing of samples with values <10 IU/ml and the need to vaccinate women postnatally have increased the workload of laboratory and maternity units. Screening for rubella in pregnancy has no advantages for the current pregnancy and it may be time to review the universal MMR vaccination programme which in turn would remove the need for continuing this practice.

Assessing Human Embryonic Stem Cell-Derived Dopaminergic Neuron Progenitor Transplants Using Non-invasive Imaging Techniques.

PURPOSE: Human pluripotent stem cell (hPSC)-derived dopaminergic neuron progenitor cells (DAPCs) are a potential therapy for Parkinson's disease (PD). However, their intracranial administration raises safety concerns including uncontrolled proliferation, migration and inflammation. Here, we apply a bimodal imaging approach to investigate the fate of DAPC transplants in the rat striatum. PROCEDURES: DAPCs co-expressing luciferase and ZsGreen or labelled with micron-sized particles of iron oxide (MPIOs) were transplanted in the striatum of RNU rats (n = 6 per group). DAPCs were tracked in vivo using bioluminescence and magnetic resonance (MR) imaging modalities. RESULTS: Transgene silencing in differentiating DAPCs accompanied with signal attenuation due to animal growth rendered the bioluminescence undetectable by week 2 post intrastriatal transplantation. However, MR imaging of MPIO-labelled DAPCs showed that transplanted cells remained at the site of injection for over 120 days. Post-mortem histological analysis of DAPC transplants demonstrated that labelling with either luciferase/ZsGreen or MPIOs did not affect the ability of cells to differentiate into mature dopaminergic neurons. Importantly, labelled cells did not elicit increased glial reactivity compared to non-labelled cells. CONCLUSIONS: In summary, our findings support the transplantation of hPSC-derived DAPCs as a safe treatment for PD.

The essential role of ERK in 4-oxo-2-nonenal-mediated cytotoxicity in SH-SY5Y human neuroblastoma cells.

Lipid peroxidation byproducts, such as 4-hydroxynonenal (HNE) and 4-oxo-2-nonenal (ONE), induce cell death in a wide variety of cell types, partly by modulating intracellular signaling pathways. However, the specific mechanisms involved, particularly for ONE, are unclear while c-Jun N-terminal kinase (JNK) has been shown to be essential in HNE-mediated cytotoxicity. In this study, we examined the role of mitogen-activated protein kinases signaling pathways in ONE-induced cytotoxicity in SH-SY5Y human neuroblastoma cells and found that ONE strongly induces the phosphorylation of extracellular signal-regulated kinase (ERK) and JNK, but not p38 MAPK. Interestingly, a transient exposure of the cells to ONE resulted in cell death, which contrasts with HNE-mediated toxicity. Importantly, blocking the ERK pathway, but not the JNK pathway, protected cells against ONE-induced cytotoxicity indicating a striking difference between the ONE- and HNE-mediated cytotoxicity mechanisms. Furthermore, inhibition of ERK reduced ONE-induced phosphorylation of p53, a key modulator of the cellular stress response, and the proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), a hallmark of apoptosis. Overall, these data strongly suggest that ERK plays an essential role in ONE-mediated cytotoxicity and that ERK is an upstream component of p53-mediated apoptosis.

A case study of delayed HIV-1 seroconversion highlights the need for Combo assays.

This report describes a case in which a patient took at least four months to seroconvert to anti-HIV positivity. A concomitant CMV infection probably contributed to the profound immune suppression observed. It is essential that fourth generation HIV antigen/antibody combo assays be used to ensure that such cases are not missed.

Prevalence and distribution of plasmid-mediated quinolone resistance genes in clinical isolates of Escherichia coli lacking extended-spectrum beta-lactamases.

OBJECTIVES: The aac(6')-Ib-cr gene has been described in plasmids from CTX-M-15-producing Escherichia coli in the worldwide ST131 lineage, but has not been systematically sought in other quinolone-resistant strains in the UK. A rise in quinolone resistance in bacteraemia isolates in the UK preceded the increased prevalence of CTX-M-producing strains. This study aimed to describe the presence of plasmid-encoded quinolone resistance genes in historical and current strains of E. coli not producing extended-spectrum beta-lactamases (ESBLs). METHODS: Ciprofloxacin-resistant, non-ESBL-producing E. coli isolates included nationally distributed isolates from the BSAC UK bacteraemia surveillance programme between 2001 and 2005, urinary isolates from a regional project in 2000 and local strains in 2006. The aac(6')-Ib-cr gene was detected using PCR followed by restriction fragment length polymorphism analysis. Multiplex PCR was used to detect qnr genes. Isolates with aac(6')-Ib-cr were assessed for aminoglycoside susceptibilities and were serotyped. RESULTS: The prevalence of the aac(6')-Ib-cr gene was 3% and 9% in current local urinary and historic national bacteraemia quinolone-resistant non-ESBL-producing E. coli, respectively. Of 521 regional urinary E. coli isolates from 2000, 14 were norfloxacin-resistant, none of which carried the aac(6')-Ib-cr gene. National positive bacteraemia isolates from 2001/2 were type O102-ST405 and, in 2004/5, types O1-ST645 and O25-ST131. Positive local urinary isolates from 2006 included serotypes O1 and O25. CONCLUSIONS: In the UK, aac(6')-Ib-cr occurs in E. coli in the absence of CTX-M-15, but with a restricted serotype distribution. Its presence in widespread bacteraemia isolates of a single type from 2001 to 2002, prior to the spread of CTX-M-15 in Britain, might suggest a lineage from which plasmid recombination occurred in man or other species.

Increasing the uptake of hepatitis C virus testing among injecting drug users in specialist drug treatment and prison settings by using dried blood spots for diagnostic testing: a cluster randomized controlled trial.

The objective of this study was to assess whether introducing dried blood spot testing can increase hepatitis C virus (HCV) diagnostic testing. A cluster randomized controlled trial was conducted. Sites were matched into pairs, with one site in each pair randomly allocated to receive the intervention (training and use of dried blood spot). Data were collected from all sites for 6 months before and 6 months after the start of the intervention. The participants were 22 specialist drug clinics and six prisons in England and Wales. The main outcome measure of this study was percentage point difference in individuals tested for HCV (the difference between the percentage of patients tested 6 months after and 6 months before the introduction of dried blood spot tests). Before the trial, 8% of patients at control and intervention sites had been tested for HCV, with 16 sites testing less than 5% of their caseload. The average percentage point difference between intervention and control sites was 14.5% (95% CI 1.3-28%, paired t-test, P = 0.03); with 13 of the 14 pairs contributing to the positive effect of the intervention (Wilcoxon matched-pairs signed-rank-test, P = 0.002). The size of the difference between intervention and control sites varied considerably. The study provides preliminary supporting evidence that dried blood spot testing may increase the uptake of HCV diagnostic testing, by increasing the opportunity for patients to be offered testing. Additional trials with a larger number of sites are justified, ideally in the context of drug and treatment policies that gave clearer priority (and targets) to infection control and testing.

Validation of COBAS Taqman CT for the detection of Chlamydia trachomatis in vulvo-vaginal swabs.

BACKGROUND: Vulvo-vaginal swabs (VVSs) are not validated for use by the manufacturers of two widely used nucleic acid amplification tests (NAAT) for the detection of Chlamydia trachomatis. However, there is evidence that this type of swab is suitable for diagnosis. OBJECTIVE: To validate the Cobas Taqman CT assay for the detection of C trachomatis in VVS. METHOD: Women aged 18-24 years attending a genitourinary medicine clinic were invited to take part in the study. Participants provided a self-taken VVS and the results obtained with these samples were compared with those obtained with an endocervical swab collected by a healthcare worker. A total of 267 women took part. RESULTS: 255/267 (96%; 95% CI 92 to 98%) sets of samples gave concordant results. 12/267 (4.5%) VVSs were invalid/inhibitory and so no result was available for these samples. This compared with 2/267 (0.7%) for endocervical swabs. CONCLUSION: VVS are suitable samples for detecting C trachomatis.

Epidemiological, social, diagnostic and economic evaluation of population screening for genital chlamydial infection.

OBJECTIVES: To investigate epidemiological, social, diagnostic and economic aspects of chlamydia screening in non-genitourinary medicine settings. METHODS: Linked studies around a cross-sectional population-based survey of adult men and women invited to collect urine and (for women) vulvovaginal swab specimens at home and mail these to a laboratory for testing for Chlamydia trachomatis. Specimens were used in laboratory evaluations of an amplified enzyme immunoassay (PCE EIA) and two nucleic acid amplification tests [Cobas polymerase chain reaction (PCR), Becton Dickinson strand displacement amplification (SDA)]. Chlamydia-positive cases and two negative controls completed a risk factor questionnaire. Chlamydia-positive cases were invited into a randomised controlled trial of partner notification strategies. Samples of individuals testing negative completed psychological questionnaires before and after screening. In-depth interviews were conducted at all stages of screening. Chlamydia transmission and cost-effectiveness of screening were investigated in a transmission dynamic model. SETTING AND PARTICIPANTS: General population in the Bristol and Birmingham areas of England. In total, 19,773 women and men aged 16-39 years were randomly selected from 27 general practice lists. RESULTS: Screening invitations reached 73% (14,382/19,773). Uptake (4731 participants), weighted for sampling, was 39.5% (95% CI 37.7, 40.8%) in women and 29.5% (95% CI 28.0, 31.0%) in men aged 16-39 years. Chlamydia prevalence (219 positive results) in 16-24 year olds was 6.2% (95% CI 4.9, 7.8%) in women and 5.3% (95% CI 4.4, 6.3%) in men. The case-control study did not identify any additional factors that would help target screening. Screening did not adversely affect anxiety, depression or self-esteem. Participants welcomed the convenience and privacy of home-sampling. The relative sensitivity of PCR on male urine specimens was 100% (95% CI 89.1, 100%). The combined relative sensitivities of PCR and SDA using female urine and vulvovaginal swabs were 91.8% (86.1, 95.7, 134/146) and 97.3% (93.1, 99.2%, 142/146). A total of 140 people (74% of eligible) participated in the randomised trial. Compared with referral to a genitourinary medicine clinic, partner notification by practice nurses resulted in 12.4% (95% CI -3.7, 28.6%) more patients with at least one partner treated and 22.0% (95% CI 6.1, 37.8%) more patients with all partners treated. The health service and patients costs (2005 prices) of home-based postal chlamydia screening were 21.47 pounds (95% CI 19.91 pounds, 25.99) per screening invitation and 28.56 pounds (95% CI 22.10 pounds, 30.43) per accepted offer. Preliminary modelling found an incremental cost-effectiveness ratio (2003 prices) comparing screening men and women annually to no screening in the base case of 27,000 pounds/major outcome averted at 8 years. If estimated screening uptake and pelvic inflammatory disease incidence were increased, the cost-effectiveness ratio fell to 3700 pounds/major outcome averted. CONCLUSIONS: Proactive screening for chlamydia in women and men using home-collected specimens was feasible and acceptable. Chlamydia prevalence rates in men and women in the general population are similar. Nucleic acid amplification tests can be used on first-catch urine specimens and vulvovaginal swabs. The administrative costs of proactive screening were similar to those for opportunistic screening. Using empirical estimates of screening uptake and incidence of complications, screening was not cost-effective.

Incidence and severity of viral hepatitis in pregnancy.

A prospective field study was carried out during an epidemic of non-A non-B hepatitis for determining the incidence and severity of hepatitis in pregnant women, nonpregnant women of child bearing age and men (15 to 45 years old). In 36 (17.3 percent) of 208 pregnant women viral hepatitis developed, as compared to 71 (2.1 percent) of 3,350 nonpregnant women and 107 (2.8 percent) of 3,822 men. The incidence of disease in pregnant women was higher than in the two control groups. The incidence of viral hepatitis in the first, second and third trimesters was 8.8 percent, 19.4 percent, and 18.6 percent, respectively. The incidence in all three trimesters was higher, when compared to that in nonpregnant women. In eight pregnant women (22.2 percent) with viral hepatitis, fulminant hepatic failure developed, as compared to its occurrence in three men (2.8 percent) and in no nonpregnant women. This significantly increased incidence of fulminant hepatitis in pregnancy was indicative of a greater severity of hepatitis during pregnancy. Increased susceptibility to fulminant hepatitis was observed exclusively in the last trimester. Nonfulminant viral hepatitis did not influence the course of pregnancy or fetal well-being. Fetal loss in fatal fulminant hepatitis was a consequence of maternal death and could not be ascribed to direct effect on the fetus or pregnancy.

A radioimmunoassay for hepatitis A antigen and antibody.

The HAVAB radioimmunoassay for the detection of antibody to hepatitis A is assessed. Its modification to detect virus in faecal samples is described and in this it was found to be more sensitive and specific than electron microscopy.

Chronic hepatitis C in long term survivors of haematological malignancy treated in a single centre.

AIMS: To investigate the impact of hepatitis C virus (HCV) infection in long term survivors of haematological malignancy treated before the introduction of blood donor screening in September 1991. METHOD: Patients were tested for evidence of HCV infection by third generation enzyme linked immunosorbent assays, a recombinant immunoblot assay and reverse transcriptase polymerase chain reaction. Serum aspartate aminotransferase activities were measured. The number and type of blood component units received by each patient were recorded. RESULTS: Forty two patients were studied who had received a total of 7143 blood component units. Two patients (4.8%) were found to have HCV infection, both had histological evidence of chronic active hepatitis, and one is now receiving treatment with alpha-interferon. Both of these patients had been missed by the ongoing look-back programme which aims to detect recipients of all known HCV infected blood components. CONCLUSION: Although HCV infection affects a minority of long term survivors of haematological malignancy, infected patients may benefit from alpha-interferon treatment. The screening of all patients treated for haematological malignancy before September 1991 is advocated.

Report of a joint DMRQC/Organon field trial to detect hepatitis A IgM by ELISA.

The results of a field trial of a joint DMRQC/Organon ELISA kit for the detection of hepatitis A IgM antibody are reported. The participating laboratories were asked to use the kit to test a panel of 360 specimens consisting of duplicate coded samples of 180 sera. The panel was also tested by MACRIA in the Virus Reference Laboratory, Colindale. The ELISA was shown to be specific and sensitive giving good discrimination between acute and late convalescent hepatitis A sera. It was proposed that the same cut-off control as is used in the RIA (equivalent to 10 RIA units) should be adopted for the ELISA also.

Viral hepatitis in Nigeria--sickle-cell disease and commercial blood donors.

Hepatitis virus infection is a major cause of morbidity and mortality in sub-Saharan Africa. The high prevalence of hepatitis B virus (HBV) infection in this region is thought to be due to horizontal transmission during childhood. Hepatitis C virus (HCV) infection is also quite prevalent in Africa, but the epidemiology of this infection has yet to be defined. We examined the prevalence of HBV and HCV serological markers in 220 patients attending sickle-cell anaemia clinics in Benin City, Nigeria, in 228 healthy locals, and in 104 local commercial blood donors, to test the hypothesis that patients requiring blood transfusion from unscreened commercial blood donors (in this area of high prevalence for viral hepatitis) are at great risk for the acquisition of post-transfusion hepatitis. Overall, the frequency of hepatitis viraemia in blood donors was high (14% of donors were either HbsAg or anti-HCV positive). Evidence of previous exposure to HBV was common in all three study groups. Risk of HBV infection for sickle-cell patients was not clearly increased by blood transfusion. HCV exposure, however, appears related to transfusion requirement, and all Western-blot-confirmed anti-HCV-positive sicklers had a history of blood transfusion. Screening of blood products in sub-Saharan Africa is unlikely to reduce prevalence of HBV, but may minimize the risks of HCV transmission.

Small virus particles in faeces of patients with infectious hepatitis (hepatitis A).

Forty-one faecal samples from infectious-hepatitis patients and their contacts were investigated for the presence of hepatitis-A-associated viral particles. Of these, 16 gave a positive result by immune electronmicroscopy or caesium-chloride density-gradient centrifugation. The latter method proved invaluable in detecting small numbers of virus particles. The particles found had buoyant density of 1-34-1-35 and a size range of 21-28 nm. Epidemiological evidence suggested that they might be the causative agent of hepatitis A.

Interferon assay as a viral diagnostic test.

The early production of interferons (IFNs) following viral infection has led to their detection being investigated as a method of diagnosis of such infections. The assay described here for alpha-IFN can be completed in one day and therefore has advantages over previously used bioassays. However, because production of IFN is transient, collection of samples must be soon after the onset of illness. For this reason the assay is more useful in cases where patients are seen early after the onset of symptoms. We have been looking at several such groups; the one reported here is children admitted to a paediatric infectious disease unit. 24/34 sera where a virus was found were positive for IFN and 14/52 where no virus was isolated. Control sera and those from patients with a bacterial infection were negative for IFN. We feel that the test is useful for certain groups of patients and are continuing to assess the assay for inclusion as a routine diagnostic test.

Tropical aspects of viral hepatitis. Hepatitis E.

Hepatitis E (HEV) is a faeco-orally transmitted hepatitis virus. It has many features similar to hepatitis A but some differences, notably the high mortality caused by HEV in pregnant women. A vaccine is being developed but at the moment only a clean water supply will reduce the number of cases in areas where the virus is endemic.

Acute bronchitis in the community: clinical features, infective factors, changes in pulmonary function and bronchial reactivity to histamine.

A descriptive study of acute bronchitis in patients without pre-existing pulmonary disease was undertaken in the community during the winter months of 1986-87. Forty-two episodes were investigated in 40 individuals. The cardinal symptom was the acute onset of cough (100%), usually productive (90%). Wheezing was noted by 62% of patients, but heard on auscultation in only 31%. A potential pathogen was isolated in 29% of cases with a virus (eight cases) being identified more frequently than either Mycoplasma pneumoniae (three cases) or a bacterium (three cases). The acute illness was associated with significant reductions in forced expired volume in 1 second (P less than 0.02) and peak expiratory flow (P less than 0.001) but not forced vital capacity compared to 6 weeks later. Ten of the 27 (37%) patients who had a histamine challenge test performed at 6 weeks had a PD20 of less than 7.8 mumol histamine. Thirty-nine episodes (93%) were treated with antibiotics by the general practitioner, the clinical course being unremarkable apart from one patient who developed a lingular pneumonia despite antibiotic therapy. Further studies are required to assess whether acute bronchitis causes an acute increase in bronchial hyperresponsiveness and whether either antibiotics or inhaled bronchodilators or anti-inflammatory therapy has a useful role in the management of this predominantly viral illness.

Anonymized sero-survey of HIV in a genitourinary medicine clinic population.

An anonymized sero-survey of the prevalence of HIV antibody was performed at an inner city Genitourinary medicine clinic in Birmingham. In 1991 8686 patients undergoing routine serological syphilis tests were anonymously tested for HIV antibodies once during the year. Demographic information was recorded for each sample but they were otherwise unlinked. There were 31 samples which tested positive for anti-HIV 1 from this group compared with 13 diagnosed by concomitant voluntary named testing. Sero-prevalence rates of 0.17% for women and heterosexual men and 4.37% for homosexual/bisexual men were found. No drug users tested positive. The survey provided evidence of occult disease outside the recognized risk behaviour patterns of homosexual men and injecting drug users outside London.

Positive nucleic acid amplification tests for Neisseria gonorrhoeae in young people tested as part of the National Chlamydia Screening Programme.

Little information is available on the prevalence of Neisseria gonorrhoeae (GC) infections outside genitourinary (GU) medicine clinics. A number of National Chlamydia Screening Programme areas now carry out simultaneous testing for Chlamydia trachomatis (CT) and GC in a single sample using nucleic acid amplification tests (NAATs). The aim of this study was to gather together data on dual testing from community settings. Information was collected from five programme areas. A total of 219,412 results were recorded with 18,370 CT positives, 1226 GC positives and among these 554 were with dual CT/GC infection. These figures highlight the fact that substantial numbers of positive GC NAAT results are found outside GU settings. An assessment of both the prevalence of GC and the proportion of extra cases that can be detected in all settings is needed, together with the implementation of robust plans to confirm, treat and manage these patients.