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.

Hepatitis B virus transmission in pre-adolescent schoolchildren in four multi-ethnic areas of England.

The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7-11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0.26%, 95% confidence interval (CI) 0.14-0.44]. The estimated average annual incidence of hepatitis B was estimated to be 29.26/100 000 children (95% CI 16.00-49.08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5.00 and 12.49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.

Respiratory viral infections during the 2009-2010 winter season in Central England, UK: incidence and patterns of multiple virus co-infections.

Acute viral respiratory infections are the most common infections in humans. Co-infection with different respiratory viruses is well documented but not necessarily well understood. The aim of this study was to utilise laboratory data from the winter season following the 2009 influenza A(H1N1) outbreak to investigate rates of respiratory virus co-infections, virus prevalence in different age groups and temporal variations in virus detection. The Health Protection Agency Public Health Laboratory (HPA PHL) Birmingham, UK, routinely uses polymerase chain reaction (PCR) to detect common respiratory viruses. The results from specimens received for respiratory virus investigations from late September 2009 to April 2010 were analysed. A total of 4,821 specimen results were analysed. Of these, 323 (13.2 %) had co-detections of two viruses, 22 (0.9 %) had three viruses and four (0.2 %) had four viruses. Reciprocal patterns of positive or negative associations between different virus pairs were found. Statistical analysis confirmed the significance of negative associations between influenza A and human metapneumovirus (HMPV), and influenza A and rhinovirus. Positive associations between parainfluenza with rhinovirus, rhinovirus with respiratory syncytial virus (RSV) and adenovirus with rhinovirus, parainfluenza and RSV were also significant. Age and temporal distributions of the different viruses were typical. This study found that the co-detection of different respiratory viruses is not random and most associations are reciprocal, either positively or negatively. The pandemic strain of influenza A(H1N1) was notable in that it was the least likely to be co-detected with another respiratory virus.

Microbial contamination of non-invasive ventilation devices used by adults with cystic fibrosis.

BACKGROUND: There is currently little evidence regarding potential risks of bacterial contamination of non-invasive ventilation (NIV) devices used by cystic fibrosis (CF) patients. AIM: The aim of this study was to determine the extent of bacterial contamination of NIV devices in our regional adult CF centre. METHODS: Seven NIV devices recently used by CF patients chronically infected with Pseudomonas aeruginosa or Burkholderia cepacia complex (BCC) were swabbed in seven areas, both external and internal. Two devices had undergone ethylene oxide (EtO) sterilization between patient use and swabbing, and five devices had not undergone EtO sterilization. FINDINGS: Swabs from five devices had insignificant growth of environmental organisms and two devices had significant growth of environmental organisms. No CF pathogens were isolated from any machine. CONCLUSIONS: No evidence was found of pathogenic microbial contamination of NIV devices used by CF patients in this small study. We suggest that further studies examine for evidence of bacterial contamination of NIV devices and that this issue should be included in future CF infection control guidelines.

Viral respiratory infections during the 2009 influenza A(H1N1) outbreak in the West Midlands Region, UK.

In spring 2009 a new strain of influenza A(H1N1) emerged and caused a worldwide pandemic. This study utilized a large collection of respiratory specimens from suspected cases of influenza A(H1N1) in the UK West Midlands during the pandemic in order to investigate which other respiratory viruses were circulating and whether they played any role in the increased hospitalization rates seen during that period. Study specimens were selected from community and hospitalized patients positive and negative for influenza A(H1N1) and tested by PCR for other respiratory viruses. A number of infections diagnosed as influenza during the summer influenza outbreak were found to be due to other virus infections (most commonly rhinovirus). No statistically significant difference was found between the rates of respiratory virus co-infection with H1N1 in patients from community or hospital locations suggesting underlying factors were likely to be more significant than viral co-infections in determining severity of influenza A(H1N1) disease.

Follow-up of pregnant women exposed to chicken pox: an audit of relationship between level of antibody and development of chicken pox.

The purpose of this study was to validate through natural exposure a cut-off level of varicella zoster IgG as protective against infection with varicella zoster virus (VZV). Laboratory testing to determine VZV immune status of pregnant women exposed to varicella is recommended. Quantitative assays are now available which are sensitive and specific. More than 200 consecutive requests for screening in pregnant patients with recent varicella contacts were followed-up by questionnaire. DiaSorin LIAISON and VZV time resolved fluorescence immuno assay (VZV TRFIA) were used to measure VZV antibody level. One hundred fifty out of 209 (72%) questionnaires were returned; 14 patients developed varicella, 129 did not and seven were not known. Patients who had been given VZIG and developed varicella on follow-up had a mean antibody level before VZIG of 28 mIU/ml and 62 mIU/ml, by LIAISON and TRFIA, respectively. The mean IgG level of those that did not develop varicella was 885 and 866 mIU/ml by LIAISON and TRFIA, respectively. Those with levels <100 mIU/ml were more likely to develop chicken pox than those with levels >100 mIU/ml (relative risk of 10.4 for LIAISON and 8.8 for TRFIA). On the basis of the relatively small numbers in this study, quantitative assays, using a 100mIU/ml cut-off, can differentiate between those who are susceptible and those who are protected against exposure, however follow-up studies should include sampling for VZV DNA and IgM.

The problem with using computer programmes to assign ethnicity: immigration decreases sensitivity.

OBJECTIVES: It is recognized that ethnic group is important in describing differences in infection and disease, but is often not routinely available to surveillance systems. Computerized programmes, such as NamPehchan, can assign ethnicity according to name; however, sensitivity and positive predictive value (PPV) can vary. The aim of this study was to assess whether the sensitivity and PPV of NamPehchan had changed, after an observation that surnames previously associated with South Asians were increasingly reported as Black. STUDY DESIGN: Cross-sectional. METHODS: NamPehchan was used to classify women as South Asian using name, and compared with the gold standard (midwife-reported ethnicity). Sensitivity and PPV were calculated overall and by year. Frequency of infection by ethnic group was estimated. RESULTS: A total of 627 women positive for hepatitis B surface antigen were identified. The majority were from minority ethnic groups, particularly Asian. The overall sensitivity of NamPehchan was 74.5% and PPV was 68.5%. Almost 50% of Black African women were classified as South Asian by NamPehchan. CONCLUSIONS: Immigration from African countries has reduced the sensitivity of NamPehchan in this group. Care is needed when using NamPehchan for groups which include Africans from Muslim areas, as misclassification is likely to occur.

Comparison of the performance of the LIAISON VZV-IgG and VIDAS automated enzyme linked fluorescent immunoassays with reference to a VZV-IgG time-resolved fluorescence immunoassay and implications of choice of cut-off for LIAISON assay.

BACKGROUND: Determination of Varicella Zoster virus (VZV) immune status in pregnant women without history of chickenpox is important in identifying those who genuinely need VZV immune globulin prophylaxis following significant exposure to chickenpox or shingles. Immune status testing requires highly sensitive and specific immunoassays for timely and accurate results. OBJECTIVES: To compare the performance of DiaSorin LIAISON and Biomerieux VIDAS VZV-IgG assays with reference to a VZV-IgG time-resolved fluorescence immunoassay (TRFIA). STUDY DESIGN: A panel of sera collected from 65 pregnant contacts of VZV and 62 individuals tested for VZV immunity was tested in all three assays. Dose-response curves were generated using International Standards W1044 and 90/690. RESULTS: Sensitivity and specificity of VIDAS compared to VZV-TRFIA was 54.5% and 97.9% respectively and for LIAISON compared to VZV-TRFIA was 67% and 100% respectively. Both assays correlated well with TRFIA with R2 correlation coefficients of 0.79 and 0.76 respectively. Dose-response curves showed both Standards behaved in a similar manner in each assay. For VIDAS, the test cut-off value of 0.9 correlated with 275-280mIU/ml and for LIAISON a cut-off value of 150mIU/ml correlated with 208-219mIU/ml. CONCLUSIONS: By dose-response data and in comparison with TRFIA, LIAISON is more sensitive and specific than VIDAS.

An educational and audit tool to reduce prescribing error in intensive care.

AIM: To reduce prescribing errors in an intensive care unit by providing prescriber education in tutorials, ward-based teaching and feedback in 3-monthly cycles with each new group of trainee medical staff. METHODS: Prescribing audits were conducted three times in each 3-month cycle, once pretraining, once post-training and a final audit after 6 weeks. The audit information was fed back to prescribers with their correct prescribing rates, rates for individual error types and total error rates together with anonymised information about other prescribers' error rates. RESULTS: The percentage of prescriptions with errors decreased over each 3-month cycle (pretraining 25%, 19%, (one missing data point), post-training 23%, 6%, 11%, final audit 7%, 3%, 5% (p<0.0005)). The total number of prescriptions and error rates varied widely between trainees (data collection one; cycle two: range of prescriptions written: 1-61, median 18; error rate: 0-100%; median: 15%). CONCLUSION: Prescriber education and feedback reduce manual prescribing errors in intensive care.

Diagnosis of acute hepatitis C virus infection and estimated incidence in low- and high-risk English populations.

The diagnosis of acute hepatitis C virus (HCV) infection is not straightforward; few people exhibit clinical symptoms and genome/antigen detection techniques do not indicate when infection had occurred. Here, a strategy to detect HCV RNA in the absence of antibody ('window-period') for diagnosis of acute infection is assessed. The sentinel surveillance of hepatitis testing study was used to retrospectively identify anti-HCV negative samples from high-risk individuals (2002-2003), for testing singly for HCV RNA. Additional samples were identified prospectively (2005) and tested in pools for HCV RNA. Positive samples were genotyped. Incidence and costs of adopting the pooling strategy were estimated. In the retrospective study, 8/390 (2.1%) samples were confirmed HCV RNA positive, anti-HCV negative. Prospectively, 3237 samples were tested in 325 pools. Five positive pools identified four confirmed HCV RNA positive patients (one false positive). Estimated incidence was 12.9 per 100 person-years in injecting drug users (IDUs) (retrospective study) and 3.7 per 100 person-years among drug/alcohol services and prison attendees (prospective study). Estimated costs were pound 850 per positive sample, in areas of higher risk. The yield from a window-period strategy depends upon the population tested. Pooled HCV RNA testing of anti-HCV negative samples from the current IDUs is realistic and relatively inexpensive to identify recently infected individuals.

Ante-natal screening and post-natal follow-up of hepatitis B in the West Midlands of England.

BACKGROUND: We established at Queen Elizabeth Hospital in Birmingham a post-natal follow-up care service for hepatitis B virus (HBV) positive women diagnosed through ante-natal screening. AIM: Virological and clinical follow-up of HBsAg positive mothers detected through ante-natal screening in Birmingham. DESIGN: Retrospective observational study. METHOD: We evaluated 117 post-natal mothers with chronic HBV infection between April 2003 and December 2006. Patients were first seen at least 3 months post-delivery and followed up. RESULTS: Most of the women were of Asian or African origin (107 of 117 patients). Five out of 117 (4%) patients had undergone serum HBsAg clearance by the time of post-natal review, and 112 patients had persisting HBsAg-positivity (seven HBeAg positive and 105 HBeAg negative). HBeAg positive women were younger than HBeAg negative patients (median 21 vs 30-years old). Fifty percent of HBeAg negative women had detectable serum HBV DNA at the time of initial review. HBeAg positive women had higher serum HBV DNA titres than those negative for HBeAg (median 40 million copies/ml vs 4323 copies/ml). The majority of patients had normal serum transaminases. A single case of clinically significant liver disease was identified in a woman with HBV and delta virus infection. CONCLUSION: Very few women who were diagnosed with chronic HBV infection at ante-natal screening have clinical evidence of liver disease. However, many have high levels of virus replication and remain at risk for the future development of liver disease.

Sentinel laboratory surveillance of hepatitis C antibody testing in England: understanding the epidemiology of HCV infection.

This paper describes sentinel laboratory surveillance of hepatitis C antibody testing in England. Demographic and test result data were supplemented by follow-up questionnaires sent to the requesting clinician. Between October 2002 and September 2003 almost 75000 anti-HCV tests were performed in eight sentinel centres. More males were tested than females and over half of those tested were aged 25-44 years. Overall 5.7% (3333/58144, range 2.8-7.7%) individuals tested positive. Follow-up questionnaire data showed that 82% (1043/1277) of the positives had injecting drug use reported as the main risk exposure. The majority of negative individuals were undergoing routine screening as recommended for specific patient groups. Most individuals were asymptomatic. Antibody prevalence was estimated to be 34% in current injecting drug users and 42% in former injectors. Comparing positives to routine national surveillance suggests that only 53% (1782/3333) of diagnosed cases were reported. Sentinel laboratory data can provide valuable supplementary data to national surveillance.

Transfusion-transmitted hepatitis E in a 'nonhyperendemic' country.

Indigenous hepatitis E is increasingly recognized in developed countries, where it may be a zoonosis. We describe the first case of transfusion-transmitted hepatitis E in the UK from a blood donor who had no history of recent travel abroad. Follow-up of the donor and recipients of the blood products was carried out using serological and molecular techniques. Acute hepatitis E was transmitted to one of two recipients. The infected patient would have received a larger volume of the donor's plasma. HEV subgenomic sequences carried by the donor and recipient were identical. This is the first case of post-transfusion hepatitis E in the UK. Secondary transmission of hepatitis E indigenous to a nonhyperendemic country may occur by blood transfusion. It is important that blood donors inform the transfusion service of all post-donation illnesses so that appropriate interventions can take place.

Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers.

BACKGROUND: Hepatitis B vaccine and hepatitis B immunoglobulin are considered for newborn infants of HBsAg-positive mothers to prevent hepatitis B infection. OBJECTIVES: To assess the beneficial and harmful effects of hepatitis B vaccines and hepatitis B immunoglobulin in newborn infants of HBsAg-positive mothers. SEARCH STRATEGY: Trials were identified through The Cochrane Neonatal Group Controlled Trials Register, The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, and EMBASE (until February 2004), authors of trials, and pharmaceutical companies. SELECTION CRITERIA: Randomised clinical trials comparing: plasma-derived vaccine (PDV) or recombinant vaccine (RV) versus no intervention, placebo, or other active vaccines; hepatitis B immunoglobulin versus no intervention, placebo, or other control immunoglobulin; as well as PDV or RV plus hepatitis B immunoglobulin versus no intervention, placebo, or other control vaccines or immunoglobulin. DATA COLLECTION AND ANALYSIS: Outcomes are assessed at maximal follow-up. The primary outcome measure was hepatitis B occurrence, based on a blood specimen positive for HBsAg, HBeAg, or antibody to hepatitis B core antigen (anti-HBc). Binary outcomes are reported as relative risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed with regard to methodological quality of the trial, mother's HBe-Ag status, and time of immunisation after birth. MAIN RESULTS: We identified 29 randomised clinical trials, five of which were considered high quality. Only three trials reported inclusion of hepatitis B e-antigen negative mothers. Compared with placebo/no intervention, vaccine reduced hepatitis B occurrence (RR 0.28, 95% confidence interval (CI) 0.20 to 0.40, 4 trials). No significant differences of hepatitis B occurrence were found comparing recombinant vaccine (RV) versus plasma-derived vaccine (PDV) (RR 1.00, 95% CI 0.71 to 1.42, 4 trials) and high-dose versus low-dose vaccine (PDV: RR 0.97, 95% CI 0.55 to 1.68, 3 trials; RV: RR 0.78, 95% CI 0.31 to 1.94, 1 trial). Compared with placebo/no intervention, hepatitis B immunoglobulin or the combination of vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (hepatitis B immunoglobulin: RR 0.50, 95% CI 0.41 to 0.60, 1 trial; PDV plus hepatitis B immunoglobulin: RR 0.08, 95% CI 0.03 to 0.17, 3 trials). Compared with vaccine, vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (RR 0.54, 95% CI 0.41 to 0.73, 10 trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe, but few trials reported on adverse events. AUTHORS' CONCLUSIONS: Vaccine, hepatitis B immunoglobulin, and vaccine plus hepatitis B immunoglobulin prevent hepatitis B occurrence in newborn infants of HBsAg positive mothers.

Natural history of hepatitis B in perinatally infected carriers.

OBJECTIVES: To establish natural seroconversion rates and incidence of hepatic pathology in perinatally infected hepatitis B carriers. METHODS: Seventy three perinatally infected hepatitis B carriers identified through maternal screening were evaluated. Fifty three were born to parents from the Indian subcontinent, nine were Oriental, six were Afro-Caribbean, and five were white. Median follow up was 10.24 (range 2.02-20.16) years. RESULTS: Only three of the children followed up had cleared hepatitis B surface antigen during this period, and 30% of the children had seroconverted to anti-HBe. Seroconversions to anti-HBe were observed in Asian (18/50) and white (4/5) children, but not in Oriental or Afro-Caribbean children. More girls (40%) than boys (23%) had seroconverted, but the difference was not significant. All children were asymptomatic with normal physical examination, growth, and development. Almost half (48%) of the hepatitis B e antigen (HBeAg) positive children had normal hepatic transaminases and liver function. Thirty five liver biopsies were performed in children with active virus replication (HBeAg or hepatitis B virus DNA positive) who were being considered for antiviral treatment as part of a clinical trial and were scored using the Ishak method. Two thirds (62%) of the children had mild hepatitis, 60% had mild fibrosis, and 18% had moderate to severe fibrosis. There was a weak correlation between histological evidence of hepatitis and hepatic transaminase activity, implying that biochemical monitoring of hepatic disease activity may be ineffective. CONCLUSIONS: These asymptomatic hepatitis B virus carrier children remain infectious in the medium to long term with notable liver pathology. They should receive antiviral treatment to reduce infectivity and to prevent further progression of liver disease. Hepatic transaminases alone are not a reliable marker of liver pathology, and liver histology is essential before consideration for antiviral treatment.

HBV DNA levels and transmission of hepatitis B by health care workers.

BACKGROUND: Laboratory-based study funded by the Research and Development Division of the Department of Health to inform the decision making on guidelines for the conduct of exposure prone procedures (EPPs) by health care workers who are hepatitis B carriers. OBJECTIVES: Define the quantity and nature of hepatitis B virus (HBV) DNA in hepatitis carriers whose serum does not contain hepatitis B e antigen (HBeAg) and in surgeons previously cleared to conduct EPPs who have transmitted HBV to their patients. STUDY DESIGN: Cross-sectional survey using HBV DNA quantification, genotyping and sequencing comparing transmitting surgeons and asymptomatic carriers. RESULTS: HBV DNA could be detected and quantified in 64.5% (136 of 211) of carriers whose serum did not contain HBeAg with a median level 3.6 log(10) copies/ml (range of 5.7 log(10) copies). Pre-core mutation appeared not to affect the HBV DNA level, however, all surgeons carried codon 28 variants and transmitted these variants to their patients. The lowest HBV DNA level in a transmitting surgeon was 4 x 10(4) copies/ml. CONCLUSIONS: Pre-core mutations are common in carriers whose serum does not contain HBeAg and do not specifically identify carriers whose HBV DNA levels are high. It was possible to define a level of virus above which transmission of hepatitis B during conduct of EPPs could not be excluded.

Comparison of commercial assays for the quantification of HBV DNA load in health care workers: calibration differences.

Until recently, carriers of hepatitis B virus (HBV) were allowed to undertake exposure prone procedures providing their serum did not contain HBeAg. However, the recent description of hepatitis B transmission events occurring from HBV-infected health care workers who conduct exposure prone procedures demonstrated that the then current Department of Health guidelines needed to be revised. As part of a series of studies carried out to determine if viral load measurements are a more secure means of assessing the conduct of exposure prone procedures, the suitability of commercially available assays for HBV DNA detection and quantification were investigated. This study describes a comparative analysis on the performances of three assays each based on a different methodology. The assays included the QUANTIPLEX HBV DNA Assay (bDNA), (Chiron Diagnostics Ltd.), the AMPLICOR HBV Monitor Test, (Roche Diagnostics Systems) and the Digene Hybrid Capture System HBV DNA Assay (Digene Corporation). Calibration curves from experiments using the Eurohep ad and ay HBV DNA standard controls indicated a close correlation between the three assays over the dynamic ranges claimed by the manufacturers, although the Quantiplex assay did appear to be over-reporting. This became more apparent when testing patients undergoing anti-viral therapy where the Quantiplex assay consistently over-reported by 0.5 log(10) when compared with the Amplicor assay. The results of this study indicate that based on its dynamic range, the Amplicor HBV Monitor test is the most appropriate assay for the routine investigation of anti-HBe carriers, which will have lower levels of HBV DNA. The investigation also highlights the need for using accepted standard HBV DNA control sera. This will be essential when using an assay to establish whether health care workers who are hepatitis B carriers can be allowed to perform exposure prone procedures under the new guidelines of the UK Department of Health.

The diagnostic significance of an assay for 'total' hepatitis C core antigen.

A measurable serological response to hepatitis C infection is delayed on average until 70 days after infection. In addition, it may not occur in some immunocompromised people. Detection of free hepatitis C (HCV) core antigen in blood has enabled diagnosis in the pre-seroconversion period. The ability to detect 'total' HCV core antigen, both free and antibody bound, would widen its use for confirming anti-HCV antibody positive patients and monitoring a therapeutic response. This study has evaluated a prototype 'total' HCV core antigen immunoassay. Sera from 145 HCV negative blood donors gave a mean value of 54.9 (+/-46.2) pg/ml based on recombinant antigen standards. Using these figures, the HCV core antigen cut-off was set as 200 pg/ml. Two hundred blood donors sera with indeterminant (a single-band on recombinant immunoblot assay) HCV antibody statuses gave fully concordant HCV core antigen results compared to their polymerase chain reactions (PCRs)--three positive, and 197 negative. HCV core antigen and PCR results were compared for 59 sera from 19 HCV positive liver disease patients. The HCV core antigen results were in complete agreement with their PCRs for the nine patients always PCR positive and the three continuously negative. For six patients on antiviral therapy whose qualitative PCRs changed from positive to negative, the HCV core antigen results paralleled the PCR results. The only discrepant results were from one patient whose PCR results went from negative to positive. 'Total' HCV core antigen testing will greatly improve the scope of diagnostic tests for hepatitis C.