Effectiveness of seasonal 2010/11 and pandemic influenza A(H1N1)2009 vaccines in preventing influenza infection in the United Kingdom: mid-season analysis 2010/11.

This study provides mid-season estimates of the effectiveness of 2010/11 trivalent influenza vaccine and previous vaccination with monovalent influenza A(H1N1)2009 vaccine in preventing confirmed influenza A(H1N1)2009 infection in the United Kingdom in the 2010/11 season. The adjusted vaccine effectiveness was 34% (95% CI: -10 - 60%) if vaccinated only with monovalent vaccine in the 2009/10 season; 46% (95% CI: 7 - 69%) if vaccinated only with trivalent influenza vaccine in the 2010/11 season and 63% (95% CI: 37 - 78%) if vaccinated in both seasons.

Effectiveness of pandemic and seasonal influenza vaccine in preventing pandemic influenza A(H1N1)2009 infection in England and Scotland 2009-2010.

Following the global spread of pandemic influenza A(H1N1)2009, several pandemic vaccines have been rapidly developed. The United Kingdom and many other countries in the northern hemisphere implemented seasonal and pandemic influenza vaccine programmes in October 2009. We present the results of a case­control study to estimate effectiveness of such vaccines in preventing confirmed pandemic influenza infection. Some 5,982 individuals with influenza-like illness seen in general practices between November 2009 and January 2010 were enrolled. Those testing positive on PCR for pandemic influenza were assigned as cases and those testing negative as controls. Vaccine effectiveness was estimated as the relative reduction in odds of confirmed infection between vaccinated and unvaccinated individuals. Fourteen or more days after immunisation with the pandemic vaccine, adjusted vaccine effectiveness (VE) was 72% (95% confidence interval (CI): 21% to 90%). If protection was assumed to start after seven or more days, the adjusted VE was 71% (95% CI: 37% to 87%). Pandemic influenza vaccine was highly effective in preventing confirmed infection with pandemic influenza A(H1N1)2009 from one week after vaccination. No evidence of effectiveness against pandemic influenza A(H1N1)2009 was found for the 2009/10 trivalent seasonal influenza vaccine (adjusted VE of -30% (95% CI: -89% to 11%)).

Pandemic (H1N1) 2009 influenza in the UK: clinical and epidemiological findings from the first few hundred (FF100) cases.

The UK was one of few European countries to document a substantial wave of pandemic (H1N1) 2009 influenza in summer 2009. The First Few Hundred (FF100) project ran from April-June 2009 gathering information on early laboratory-confirmed cases across the UK. In total, 392 confirmed cases were followed up. Children were predominantly affected (median age 15 years, IQR 10-27). Symptoms were mild and similar to seasonal influenza, with the exception of diarrhoea, which was reported by 27%. Eleven per cent of all cases had an underlying medical condition, similar to the general population. The majority (92%) were treated with antiviral drugs with 12% reporting adverse effects, mainly nausea and other gastrointestinal complaints. Duration of illness was significantly shorter when antivirals were given within 48 h of onset (median 5 vs. 9 days, P=0.01). No patients died, although 14 were hospitalized, of whom three required mechanical ventilation. The FF100 identified key clinical and epidemiological characteristics of infection with this novel virus in near real-time.

An internally controlled, one-step, real-time RT-PCR assay for norovirus detection and genogrouping.

BACKGROUND: Reverse transcription (RT)-PCR for norovirus detection is prone to false-negative results due to inhibitory substances in faeces. An internal control is needed to monitor extraction efficiency and to detect inhibition. OBJECTIVES: To further develop a one-step RT-PCR assay for norovirus detection/genogrouping by addition of MS2 bacteriophage as an internal control. STUDY DESIGN: Our norovirus RT-PCR assay was modified by addition of MS2 phage to the extraction tray and primers/probe for MS2 detection to the reaction mix. The effect of addition of MS2 phage and MS2 primers/probe on the sensitivity/specificity of the PCR assay was examined. RESULTS: The addition of MS2 as an internal control showed no loss of sensitivity or specificity for norovirus detection. CONCLUSIONS: A triplex, one-step, type-specific, real-time RT-PCR with MS2 internal control has been developed for use in routine laboratory diagnosis of norovirus infection.

Neural transplantation in Huntington's disease: the NEST-UK donor tissue microbiological screening program and review of the literature.

Neural transplantation of human fetal tissue for Huntington's disease (HD) is now entering the clinical arena. The safety of the procedure has now been demonstrated in a number of studies, although the efficacy of such an approach is still being investigated. Stringent but practicable screening of the donor tissue for potential pathogens is an essential prerequisite for successful implementation of any novel transplant program that uses human fetal tissue. In this article we summarize the UK-NEST protocol for the screening of human fetal tissue being grafted to patients with mild to moderate HD. We describe the results of microbiological screening of 87 potential tissue donors in a pilot study, and of the first four donor-recipient patients included in the UK-NEST series. The rationale for the adoption and interpretation of the various tests is described and our methodology is compared with those previously used by other centers. This article therefore presents a comprehensive, logical yet pragmatic screening program that could be employed in any clinical studies that use human fetal tissue for neurotransplantation.

Extended ganciclovir prophylaxis in lung transplantation.

BACKGROUND: Positive cytomegaloviral status of the donor or of the recipient adversely affects survival and enhances the development of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. The role of ganciclovir prophylaxis in cytomegalovirus infection in respect to obliterative bronchiolitis or to BOS development is not known. METHODS: From the Papworth transplant database, we identified 146 patients who received organs from cytomegalovirus-positive donors. We classified patients into 3 groups as follows: Group 1 consisted of 42 patients who underwent transplantation between 1990 and 1992 when no prophylaxis was given; Group 2 consisted of 49 patients who underwent transplantation between 1992 and 1995 when 4 weeks of IV ganciclovir was given as prophylaxis; and Group 3 consisted of 55 patients who underwent transplantation between 1995 and 1998 when cytomegalovirus prophylaxis consisted of IV (1 week) followed by oral ganciclovir for a total of 3 months. Donor management, recipient management during and after surgery, and pharmacotherapy were uniform during the study period. We used survival and regression methods to compare these groups, adjusting for the transplantation type (single lung, double lung, or heart-lung) and for HLA typing. RESULTS: We found a significant difference among all 3 groups in numbers of cytomegaloviral disease episodes in the 1st year after transplantation. The number of rejection episodes in the 3 groups during the 1st post-transplant year gradually decreased from Group 1 to Group 3. We identified no statistically significant benefit in the time to BOS occurrence or in actuarial survival. CONCLUSION: Extended prophylaxis with IV and oral ganciclovir practically abolishes cytomegaloviral disease and is related to a decreased incidence of rejection episodes. However, ganciclovir prophylaxis is not related to a decreased incidence or progression of BOS or survival.

Cytomegalovirus infection in immunocompetent patients.

Symptoms associated with cytomegalovirus (CMV) infection in immunocompetent patients are not well documented. From December 1998 through June 2001, serum samples obtained from 7630 patients in Cambridge and Chelmsford, United Kingdom, were tested for CMV immunoglobulin M. CMV immunoglobulin G avidity was used to confirm CMV infection. A total of 124 patients (106 patients treated by general practitioners [GPs] and 18 hospitalized patients) with CMV infection were identified. The most frequent symptoms were malaise (67%), fever (46%), and sweats (46%), and the most frequent finding was abnormal liver function test results (69%). Twelve percent of patients had a relapsing illness, and many had symptoms that lasted for up to 32 weeks (mean duration of symptoms, 7.8 weeks). GPs reported that there was a significant benefit in making the diagnosis of CMV infection; it provided reassurance and avoided the need for further investigations. We have identified symptoms associated with CMV infection in immunocompetent patients who present to GPs or who are admitted to the hospital.

Prevalence of measles susceptibility among health care workers in a UK hospital. Does the UK need to introduce a measles policy for its health care workers?

OBJECTIVES: First, to determine the prevalence of measles non-immunity in a group of health care workers (HCW), and secondly, to investigate what pre-employment screening for measles is carried out by NHS occupational health departments. METHODS: Two hundred and eighteen HCWs with patient contact on the medical wards at Addenbrooke's hospital provided an oral fluid sample and answered a questionnaire. A postal survey of Association of National Health Occupational Physicians Society (ANHOPS) members was conducted to assess whether UK NHS Trusts identify measles non-immune individuals. RESULTS: Of the HCWs tested, 3.3% of were found to be non-immune to measles (both oral fluid and confirmatory serum sample were measles IgG negative). Less than one third of a sample of 80 NHS occupational health departments enquired about measles immunity. CONCLUSION: The prevalence of measles non-immune health care workers is low, but with a fall in uptake of MMR immunization and increased likelihood of measles outbreaks, it is important to identify these at-risk individuals. Serum testing is the most reliable method to use. Oral fluid testing and history of measles disease or vaccination are unreliable methods of identifying non-immune individuals. To achieve complete immunity, it is cost-effective to screen and then offer immunization. NHS trusts vary greatly in their measles policies for health care workers.

Outbreak of hepatitis A infection among intravenous drug users in Suffolk and suspected risk factors.

A prolonged outbreak of hepatitis A infection amongst drug users in Suffolk prompted a study of the natural immunity against hepatitis A in this population, and a retrospective analysis of the relationship between specific drug-taking behaviours and the risk of hepatitis A infection. Prior to the outbreak, age-specific seroprevalence of hepatitis A IgG in drug users was similar to that amongst blood donors in the region. Of those without effective immunity, intravenous drug users, multiple drug users and those injecting frequently were more likely to have developed hepatitis. The reported frequency of equipment sharing and the number of injecting partners were not related to the risk of infection. The potential for blood-to-blood, and a suggested faecal-blood transmission were considered to be important in propagating the outbreak in this population. We suggest that a single dose of hepatitis A vaccine administered opportunistically should be used in outbreaks involving drug users.

Risk factors, clinical features and genotype distribution of diagnosed hepatitis C virus infections: a pilot for a sentinel laboratory-based surveillance.

Hepatitis C is a global public health problem. A cross-sectional survey was undertaken to determine the frequency of reported risk factors and possible transmission routes in individuals in whom HCV antibody (anti-HCV) was newly detected. Seven public health laboratories in England and Wales reported persons with positive anti-HCV tests over a three-month period (1st November 1996-31st January 1997). A questionnaire was then sent to the clinician or general practitioner (GP) who requested the test. A total of 320 laboratory reports were received from participating laboratories and 221 (69%) questionnaires were received from clinicians and GPs. Of those patients from whom a questionnaire was received (median age 36 years; males 72.9%, females 23.1%), 86% had one or more risk factors for infection reported by the clinician/GP. Injecting drug use (68%) was the main risk factor reported. Reasons for testing included being in a known risk group (65%), liver disease (19%) and blood donation (1.4%). Of the total responders, 67% were asymptomatic, and of those that had had liver function tests 50% were abnormal. The most prevalent HCV genotypes were 3a and 1a. Risk factors for HCV infection can be identified using a simple postal questionnaire to clinicians/GPs who request patient screening.

Causes of morbilliform rash in a highly immunised English population.

AIMS: To determine the causes of morbilliform rash and fever in a population with high vaccination coverage for measles and rubella. METHODS: Comprehensive laboratory investigation additional to routine oral fluid testing of children presenting to primary care physicians in East Anglia, England. RESULTS: Laboratory confirmation of infection was obtained in 93 (48%) of 195 children: parvovirus B19 in 34 (17%); group A streptococcus in 30 (15%); human herpesvirus type 6 in 11 (6%); enterovirus in nine (5%); adenovirus in seven (4%); and group C streptococcus in six (3%) (four individuals tested positive for two agents). None had measles or rubella. CONCLUSIONS: Oral fluid testing to cover infections additional to measles and rubella aids clinical management and is likely to maintain uptake of testing, which is essential for measles and rubella surveillance in highly immunised low incidence populations.

Guidelines for laboratory monitoring of treatment of persistent virus infections.

A growing number of antiviral agents are available for treatment of persistent viral infections. This has increased the requirement for virology laboratories to undertake sophisticated assays for monitoring the efficacy of treatment and identifying drug failure at an early stage. The consensus guidelines within this article address the laboratory requirements for monitoring treatment of the herpes viruses, HIV-1, Hepatitis B and Hepatitis C.

Processing of cardiac valve allografts: 2. Effects of antimicrobial treatment on sterility, structure and mechanical properties.

This is the second in a series of papers that report experiments to investigate the properties required for effective tissue valve implants. This paper is concerned with investigations into alternative antimicrobial treatments and the effect these treatments produce on the structural and biomechanical properties of ovine aortic valves. Six treatments were studied: heat, peracetic acid (at two concentrations), chlorine dioxide, a surfactant cleaning agent and a solvent/detergent treatment. Samples of myocardial tissue were exposed to a mixed bacterial culture or one of three virus cultures and then decontaminated. Two of the six treatments (0.35% peracetic acid and heat) were effective in removing both bacterial and viral contamination, reducing levels of contamination by 2.5 to 3 logs, whilst a third (chlorine dioxide) was effective against viruses ( approximately 3 log reduction). Valves subjected to these treatments were examined by microscopy and measurements of mechanical properties were made. All three treatments seriously damaged endothelial cells and leaflet fibroblasts. Heat treatment also damaged connective tissue components (collagen and elastin) but these changes were not seen after chemical treatment. Mechanical testing confirmed severe damage following heat treatment but chemical treatment showed only minor effects on the elasticity of the leaflets and none on extensibility. These minor effects could be mitigated by exposure to a lower dose of peracetic acid and this treatment could be safely combined with cryopreservation or storage in 85% glycerol. Peracetic acid was the preferred disinfection method for use in the subsequent in vivo studies in sheep.

Recipient HLA-DR3, tumour necrosis factor-alpha promoter allele-2 (tumour necrosis factor-2) and cytomegalovirus infection are interrelated risk factors for chronic rejection of liver grafts.

BACKGROUND/AIMS: The tumour necrosis factor (TNF)-2 promoter allele, which elicits elevated expression of TNF-alpha, is in linkage disequilibrium with the extended haplotype HLA-A1-B8-DR3-DQ2. TNF-2 and HLA-DR3 have been implicated in renal and cardiac graft rejection and loss. Cytomegalovirus (CMV) infection has been associated with chronic allograft rejection. We examined the relationship between HLA-DR3, promoter allele TNF-2 and cytomegalovirus in relation to chronic rejection following liver transplantation. METHODS: (i) Retrospective analysis of HLA-DR3 was performed in 307 liver transplant recipients and 283 donors. (ii) Prospective analysis of TNF-alpha promoter allele status, HLA-DR3 status and cytomegalovirus infection was assessed in 123 recipients. RESULTS: (i) Retrospective analysis. Recipient HLA-DR3 (relative risk 1.9; 95% C.I. 1.01-3.58) was a risk factor for chronic rejection. (ii) Prospective analysis. Recipient HLA-DR3 was a risk factor for chronic rejection (relative risk 3.41; 95% C.I. 1.66-7.03) which was elevated further by superimposed CMV infection (relative risk 5.01; 95% C.I. 2-12.55). Recipient TNF-2 was associated with chronic rejection (relative risk 2.29; 95% C.I. 0.9-5.83) through linkage to HLA-DR3. CONCLUSIONS: Recipient HLA-DR3, TNF-2 status and CMV infection were inter-related risk factors for chronic rejection of liver grafts.

Laboratory policies on testing for rotavirus affect surveillance data. PHLS East Epidemiology and Virology Subcommittees.

The effect of different laboratory testing policies on the surveillance of rotavirus was assessed in eight laboratories between 1995 and 1998. In 1995, five laboratories tested all faecal specimens from children aged 5 years and under all year, two tested all specimens from children aged 4 years and under all year, and one tested all specimens from children aged 3 years and under between November and May only. Five laboratories changed their testing policy between 1995 and 1998. By 1998, three tested all specimens from children aged 5 years and under all year and two from the same age group during the 'season' only. Three laboratories had unique policies: one tested all specimens from children aged 2 years and under between January and June, one tested all specimens from children aged 4 years and under all year, and one tested specimens only on clinical request. The onset date of the rotavirus infection 'season' as determined by retrospective scrutiny of reported cases varied by up to 15 weeks between laboratories, starting as early as week 45 (November) and as late as week 13 (March). Laboratories with more restrictive testing policies yielded fewer reports of rotavirus and changes in policy within a particular laboratory affected the number of reports. Temporal and geographic trends were visible, even within the relatively small area covered by this study, and showed how laboratory testing policies affect surveillance data.

An association between cytomegalovirus infection and chronic rejection after liver transplantation.

BACKGROUND: Previous studies suggest a link between cytomegalovirus (CMV) infection and chronic rejection. Since these studies, more sophisticated diagnostic methods with high sensitivity and specificity for CMV have been developed and effective therapy/prophylaxis for CMV is now available. We sought CMV prospectively by polymerase chain reaction of serum and urine and by conventional methods in a group of 33 patients undergoing 57 transplants during 1993 or 1994, selected from a larger series. There were 13 grafts lost to chronic rejection. The remaining 44 grafts that did not develop chronic rejection served as controls and comprised 15 successful primary grafts, 15 second transplants, 8 third transplants, and 6 primary grafts that were lost for reasons other than chronic rejection. RESULTS: The combination donor CMV antibody negative with recipient antibody positive and the duration of CMV infection >30 days were associated with an increased relative risk of chronic rejection. In contrast, the presence of CMV infection alone, symptomatic CMV infection, the detection of CMV by PCR of serum or urine, and the peak/cumulative viral load were not predictive. CMV infection occurred earlier in those undergoing a second transplant for chronic rejection than for those undergoing a second transplant for other reasons. In addition, a human leukocyte antigen B mismatch was associated with prolonged CMV infection. CONCLUSION: These data are consistent with the hypothesis that prolonged subclinical cytomegalovirus infection is associated with an increased risk of chronic rejection.