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• In elderly COVID-19 inpatients, admission NEWS2 scores did not predict mortality. • Of components of NEW2 score, only systolic blood pressure predicted mortality. • A high variability in NEW2 score predicted mortality. • NEWS2 score does not consider the degree of supplemental oxygen patients require. • A more sensitive early warning score for COVID-19 is needed.

BackgroundMigration is a major global driver of population change. Certain migrants may be at increased risk of infectious diseases, including tuberculosis (TB), HIV, hepatitis B and hepatitis C, and have poorer outcomes. Early diagnosis and management of these infections can reduce morbidity, mortality and onward transmission and is supported by national guidelines. To date, screening initiatives have been sporadic and focused on individual diseases; systematic routine testing of migrant groups for multiple infections is rarely undertaken and its impact is unknown. We describe the protocol for the evaluation of acceptability, effectiveness and cost-effectiveness of an integrated approach to screening migrants for a range of infectious diseases in primary care.Methods and analysisWe will conduct a mixed-methods study which includes an observational cohort with interrupted time-series analysis before and after the introduction of routine screening of migrants for infectious diseases (latent TB, HIV, hepatitis B and hepatitis C) when first registering with primary care within Leicester, UK. We will assess trends in the monthly number and rate of testing and diagnosis for latent TB, HIV, hepatitis B and hepatitis C to determine the effect of the policy change using segmented regression analyses at monthly time-points. Concurrently, we will undertake an integrated qualitative sub-study to understand the views of migrants and healthcare professionals to the new testing policy in primary care. Finally, we will evaluate the cost-effectiveness of combined infection testing for migrants in primary care.Ethics and disseminationThe study has received HRA and NHS approvals for both the interrupted time-series analysis (16/SC/0127) and the qualitative sub-study (16/EM/0159). For the interrupted time-series analysis we will only use fully anonymised data. For the qualitative sub-study, we will gain written, informed, consent. Dissemination of the results will be through local and national meetings/conferences as well as publications in peer-reviewed journals.

Summary Clinical challenges exist in the management of hospitalized patients returning to the UK with potential Middle East respiratory syndrome coronavirus (MERS-CoV) infection, particularly with its clinical overlap with influenza, as demonstrated in this case-series and cost-analysis review of returning Hajj pilgrims. These patients were hospitalized with acute febrile respiratory illness, initially managed as potential MERS-CoV infections, but were eventually diagnosed with influenza. Additional costs were small, yet enhanced infection prevention measures created significant burdens on isolation rooms and staff time. Planning for predictable events such as Hajj is important for resource management. Here, in-house MERS-CoV diagnostic testing would have facilitated earlier diagnosis and discharge.

Current influenza vaccines are limited by the need for annual immunisation, frequent antigenic updating to match the evolution of circulating influenza virus strains, and reduced efficacy in elderly persons. On 9-10 November 2009, the Initiative for Vaccine Research of the World Health Organization convened jointly with the Wellcome Trust in London, United Kingdom, the fourth meeting on 'Influenza vaccines that induce broad spectrum and long-lasting immune responses'. Presentations were made by representatives from industry, academia, governmental and non-governmental organisations. The objectives of the meeting were to update the progress of research in the field of influenza vaccine strategies able to generate cross protection against divergent influenza virus strains. Improvements in existing strategies including live attenuated influenza vaccines and adjuvantation of inactivated vaccines were summarised. Developments in novel antigen production methods, new routes of vaccine delivery and administration, and vaccine approaches based on conserved virus antigens were explored. In addition, correlates of immune protection and regulatory issues for the evaluation and approval of future novel vaccine strategies were discussed.

Avian influenza H9N2 viruses are considered as a pandemic threat. We assessed the safety and immunogenicity of fourteen H9N2 vaccine formulations. A randomized, phase I trial was done in 353 adults, aged 18-82 years. Subjects received two doses of A/Hong Kong/1073/99 (H9N2) whole-virus, alum-adjuvanted whole-virus, virosomal, or intradermal whole-virus vaccine at four doses (1.7, 5, 15 or 45 microg haemagglutinin). Sera were obtained before and three weeks after each vaccination (days 0, 21, and 42) for haemagglutination-inhibition (HAI) and neutralization assays. All formulations were well tolerated. Pre-vaccination sera from subjects aged below or above 40 years had baseline antibody to H9N2 in 1% and 16% of samples. Compared to intramuscular whole-virus vaccine, alum-adjuvanted vaccine was more immunogenic, intradermal vaccine was comparable, and virosomal vaccine less immunogenic. Among subjects under 40 years, two doses (45, 15, and 5 microg) of alum-adjuvanted vaccine achieved seroprotective HAI titres in 50%, 41%, and 39% respectively, and neutralization seroconversions in 83%, 82%, and 78% of recipients. Among subjects over 40 years, one dose (45, 15, and 5 microg) of alum-adjuvanted vaccine achieved seroprotective HAI titres in 50%, 25% and 0% respectively, and neutralization seroconversions in 88%, 63% and 63% of recipients. Among immunologically naive subjects under 40 years, two doses of vaccine are required and alum-adjuvanted vaccines were most immunogenic. Among immunologically primed subjects over 40 years, one dose of whole-virus or alum-adjuvanted vaccine induced immune responses; the second dose provided less additional benefit. However, no vaccine formulation satisfied all European regulatory criteria for pandemic vaccines.

Older adults (> or =65 years of age) are particularly vulnerable to influenza illness. This is due to a waning immune system that reduces their ability to respond to infection, which leads to more severe cases of disease. The majority ( approximately 90%) of influenza-related deaths occur in older adults and, in addition, catastrophic disability resulting from influenza-related hospitalization represents a significant burden in this vulnerable population. Current influenza vaccines provide benefits for older adults against influenza; however, vaccine effectiveness is lower than in younger adults. In addition, antigenic drift is also a concern, as it can impact on vaccine effectiveness due to a mismatch between the vaccine virus strain and the circulating virus strain. As such, vaccines that offer higher and broader protection against both homologous and heterologous virus strains are desirable. Approaches currently available in some countries to meet this medical need in older adults may include the use of adjuvanted vaccines. Future strategies under evaluation include the use of high-dose vaccines; novel or enhanced adjuvantation of current vaccines; use of live attenuated vaccines in combination with current vaccines; DNA vaccines; recombinant vaccines; as well as the use of different modes of delivery and alternative antigens. However, to truly evaluate the benefits that these solutions offer, further efficacy and effectiveness studies, and better correlates of protection, including a precise measurement of the T cell responses that are markers for protection, are needed. While it is clear that vaccines with greater immunogenicity are required for older adults, and that adjuvanted vaccines may offer a short-term solution, further research is required to exploit the many other new technologies.

Results for clade 1 viruses were more consistent among laboratories when a standard antibody was used., Hemagglutination-inhibition (HI) and neutralization are used to evaluate vaccines against influenza virus A (H5N1); however, poor standardization leads to interlaboratory variation of results. A candidate antibody standard (07/150) was prepared from pooled plasma of persons given clade 1 A/Vietnam/1194/2004 vaccine. To test human and sheep antiserum, 15 laboratories used HI and neutralization and reassortant A/Vietnam/1194/2004, A/turkey/Turkey/1/2005 (clade 2.2), and A/Anhui/1/2005 (clade 2.3.4) viruses. Interlaboratory variation was observed for both assays, but when titers were expressed relative to 07/150, overall percentage geometric coefficient of variation for A/Vietnam/1194/2004 was reduced from 125% to 61% for HI and from 183% to 81% for neutralization. Lack of reduced variability to clade 2 antigens suggested the need for clade-specific standards. Sheep antiserum as a standard did not reliably reduce variability. The World Health Organization has established 07/150 as an international standard for antibody to clade 1 subtype H5 and has an assigned potency of 1,000 IU/ampoule.

Background Oseltamivir, a specific influenza neuraminidase inhibitor, is an effective treatment for seasonal influenza. Emergence of drug-resistant influenza viruses after treatment has been reported, particularly in children in Japan, where the dosing schedule is different from that used throughout the rest of the world. We investigated the emergence of drug-resistant infection in children treated with a tiered weight-based dosing regimen. Methods We analyzed sequential clinical nasopharyngeal samples, obtained before and after tiered weight-based oseltamivir therapy, from children with acute influenza during 2005-2007. We isolated viruses, tested for drug resistance with use of a fluorescence-based neuraminidase inhibition assay, performed neuraminidase gene sequencing, and determined quantitative viral loads. Results Sixty-four children (34 with influenza A subtype H3N2, 11 with influenza A subtype H1N1, and 19 with influenza B virus) aged 1-12 years (median age, 3 years, 1 month) were enrolled. By days 4-7 after initiation of treatment, of 64 samples tested, 47 (73.4%) and 26 (40.6%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. By days 8-12 after initiation of treatment, of 53 samples tested, 18 (33.9%) and 1 (1.8%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. We found no statistically significant differences in the reduction of viral shedding or time to clearance of virus between viral subtypes. Antiviral-resistant viruses were recovered from 3 (27.3%) of 11 children with influenza A subtype H1N1, 1 (2.9%) of 34 children with influenza A subtype H3N2, and 0 (0%) of 19 children with influenza B virus, all of whom were treated with oseltamivir (P = .004). There was no evidence of prolonged illness in children infected with drug-resistant virus. Conclusions Drug resistance emerges at a higher rate in influenza A subtype H1N1 virus than in influenza A subtype H3N2 or influenza B virus after tiered weight-based oseltamivir therapy. Virological surveillance for patterns of drug resistance is essential for determination of antiviral treatment strategies and for composition of pandemic preparedness stockpiles.

Healthcare workers may be at risk during the next influenza pandemic. Priming with stockpiled vaccine may protect staff and reduce nosocomial transmission. Despite campaigns to increase seasonal influenza vaccine coverage, uptake among healthcare workers is generally low; creating uncertainty whether they would participate in pre-pandemic vaccine programmes. We conducted a cross-sectional questionnaire survey of healthcare workers in a UK hospital during, and 6 months after, a period of media reporting of an H5N1 outbreak at a commercial UK poultry farm. A total of 520 questionnaires were returned, representing 20% of frontline workforce. More respondents indicated willingness to accept stockpiled H5N1 vaccine during the period of media attention than after (166/262, 63.4% vs. 134/258, 51.9%; p = 0.009). Following multivariate analysis, factors associated with willingness to accept H5N1 vaccine included: previous seasonal vaccine (OR 6.2, 95% CI 3.0–12.8, p < 0.0001), awareness of occupational seasonal vaccine campaigns (OR 2.2, 95% CI 1.4–3.5, p = 0.001), belief that seasonal vaccine benefits themselves (OR 2.5, 95% CI 1.6–4.0, p < 0.0001) or the hospital (OR 3.6, 95% CI 2.3–5.8, p < 0.0001), belief that pandemic risk is high/moderate (OR 14.1, 95% CI 7.6–26.1, p < 0.0001) and would threaten healthcare workers (OR 2.9, 95% CI 1.8–4.5, p < 0.0001). Those who would not accept vaccine (220 respondents, 42.7%) if offered before the pandemic do not perceive pandemic influenza as a serious threat, and have concerns regarding vaccine safety. A majority of healthcare workers are amenable to accept stockpiled H5N1 vaccine if offered in advance of pandemic activity.

A study was performed to investigate the reproducibility of haemagglutinin-inhibition (HI) and virus neutralising (VN) assays for detection of anti-influenza antibody. Participants in 11 laboratories from eight countries measured antibody to egg-grown A/Japan/434/2003, cell-grown A/Japan/434/2003 and A/Panama/2007/99 (H3N2) viruses in 18 human and two post-infection ferret sera. There was significant intra-laboratory assay variability for VN compared to HI. For replicate assays within laboratories, 14/410 (3%) and 130/631 (21%) titres differed by2-fold (p0.0001), and 0/410 (0%) and 35/631 (6%) titres differed by5-fold (p0.0001) by HI and VN, respectively. Although both assays showed inter-laboratory variation, VN assays were significantly more variable than HI. Median geometric coefficients of variation (GCV) for VN assays with each virus were 256%, 323% and 359% compared to 138%, 155% and 261% with HI. A serum standard improved inter-laboratory agreement and reduced median GCVs. This study raises concern about comparability of serology results from H5N1 vaccine trials and it is proposed that an International Standard for influenza H5N1 antibody is developed.

Since the last influenza pandemic in 1968, neuraminidase (NA) inhibitors have been licensed for the treatment and prophylaxis of seasonal influenza. Continuing outbreaks of highly pathogenic avian influenza H5N1 since 2004 have focused attention on the timing of the next pandemic and preparedness plans. Although immunization is the principal means of influenza prophylaxis, a well-matched efficacious vaccine is unlikely to be widely available for several months following the emergence of the pandemic strain. NA inhibitors could be used to contain and eliminate an emerging pandemic virus at source. If unsuccessful, they could still play a crucial role in reducing the medical impact of pandemic influenza as it spreads through countries. Accordingly, many authorities are creating stockpiles of NA inhibitors. However, the use of stockpiled drugs for treatment or prophylaxis, the rapid delivery to newly diagnosed cases and unknown characteristics of an emergent pandemic strain pose significant challenges to determining optimal use of stockpiles.

Antigenically well-matched vaccines against highly pathogenic avian influenza H5N1 viruses are urgently required. Human serum samples after immunization with MF59 or nonadjuvanted A/duck/Singapore/97 (H5N3) vaccine were tested for antibody to 1997-2004 human H5N1 viruses. Antibody responses to 3 doses of nonadjuvanted vaccine were poor and were higher after MF59-adjuvanted vaccine, with seroconversion rates to A/HongKong/156/97, A/HongKong/213/03, A/Thailand/16/04, and A/Vietnam/1203/04 of 100% (P < .0001), 100% (P < .0001), 71% (P = .0004), and 43% (P = .0128) in 14 subjects, respectively, compared with 27%, 27%, 0%, and 0% in 11 who received nonadjuvanted vaccine. These findings have implications for the rational design of pandemic vaccines against influenza H5.

Summary Sporadic human infection with avian influenza viruses has raised concern that reassortment between human and avian subtypes could generate viruses of pandemic potential. Vaccination is the principal means to combat the impact of influenza. During an influenza pandemic the immune status of the population would differ from that which exists during interpandemic periods. An emerging pandemic virus will create a surge in worldwide vaccine demand and new approaches in immunisation strategies may be needed to ensure optimum protection of unprimed individuals when vaccine antigen may be limited. The manufacture of vaccines from pathogenic avian influenza viruses by traditional methods is not feasible for safety reasons as well as technical issues. Strategies adopted to overcome these issues include the use of reverse genetic systems to generate reassortant strains, the use of baculovirusexpressed haemagglutinin or related non-pathogenic avian influenza strains, and the use of adjuvants to enhance immunogenicity. In clinical trials, conventional surfaceantigen influenza virus vaccines produced from avian viruses have proved poorly immunogenic in immunologically naive populations. Adjuvanted or whole-virus preparations may improve immunogenicity and allow sparing of antigen.

Background . Dengue occurs in many tourist destinations, and is increasingly imported by returning travellers. We review the epidemiology and clinical features of confirmed dengue in returning travellers presenting to a UK regional infectious diseases unit. Methods . A retrospective, case-record review of febrile returning travellers, admitted to Leicester Royal Infirmary during 2000–2002. The presenting clinical features of patients with positive dengue serology were compared to those who had negative serological tests. Results . Dengue, including two cases of dengue haemorrhagic fever (DHF) and 1 shock syndrome, was diagnosed in 16 of approximately 250 (6.4%) hospitalised returning travellers. 10/16 (62.5%) patients returned from Asia. There was no difference in symptoms between those with or without serological evidence of dengue. Dengue was associated with thrombocytopenia ( p =0.001), leucopenia ( p =0.03) and elevated alanine transminase ( p =0.01). Following multivariate analysis, dengue was associated with first time travel to an endemic area (odds ratio 10.9, 95% CI 1.21–99.9), early onset of symptoms after return (OR 1.91, 95% CI 1.07–3.43), duration of time overseas (OR 1.08, 95% CI 1.01–1.15) and thrombocytopenia (OR 29.4, 95% CI 1.8–494). Conclusions . Dengue is an important cause of illness in hospitalised febrile returning travellers. It should be considered in first-time travellers, with thrombocytopenia and negative malaria films who present with symptoms soon after return.

In 1997, influenza A/Hong Kong/97 (H5N1) emerged as a potential human threat. In 1999, a randomised study comparing two doses of MF59-adjuvanted and non-adjuvanted influenza A/Duck/Singapore/97 (H5N3) surface-antigen vaccine found non-adjuvanted vaccine was poorly immunogenic. Addition of MF59 significantly boosted antibody to H5N1 to levels associated with protection. At 16 months, we undertook a follow-up study to assess the effect of H5N3 revaccination. Geometric mean titres (GMTs) of antibody by haemagglutination-inhibition (HI), microneutralisation (MN) and single radial haemolysis (SRH) indicated that protective antibody titres did not exist at 16 months after two-dose priming. Twenty-one days after revaccination, there was significant boosting of antibody compared to GMTs achieved 21 days after two-dose priming in the original study (P

Introduction Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009–10 pandemic. Methods In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres. Results Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1∶40) was detected in 58 (75.3%, 95% CI 64.2–84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3–38.1) from unvaccinated women (P

Background In December 2009, the World Health Organization (WHO) issued updated guidelines on the prevention of H1N1 influenza virus in healthcare settings. In 2010, the WHO pandemic influenza alert level was still at phase 6. Aim To study the practice of infection control measures during the 2009 influenza H1N1 pandemic among healthcare workers (HCWs) in three countries. Methods A standardized, self-administered anonymous questionnaire survey was conducted in 2010 among doctors, nurses and allied HCWs in 120 hospital-based clinical departments in Hong Kong, Singapore and the UK. Questions were asked on demographics; previous experience and perceived severity of influenza; infection control practices; uptake of seasonal influenza vaccination and H1N1 vaccination. Multiple logistic regression was used to test the independent association with different factors. Findings A total of 2100 HCWs in the three countries participated. They reported high compliance (>80%) with infection control procedures regarded as standard for droplet-transmitted infections including wearing and changing gloves, and washing hands before and after patient contact. However, the reported use of masks with indirect or direct patient contact (surgical or N95 as required by their hospital) varied considerably (96.4% and 70.4% for Hong Kong; 82.3% and 87.7% for Singapore; 25.3% and 62.0% for the UK). Reported compliance was associated with job title, number of patient contacts and perceived severity of pandemics. There was no association between the uptake for seasonal or 2009 H1N1 vaccines and compliance. Conclusions Compliance with infection control measures for pandemic influenza appears to vary widely depending on the setting.

Haemagglutination-inhibition (HI) and virus neutralisation (VN) assays are used to evaluate immunogenicity of pandemic H1N1 vaccines; however these bioassays are poorly standardised leading to inter-laboratory variation. A candidate International Standard (IS) for antibody to H1N1 pdm virus (09/194) was prepared from pooled sera of subjects who had either recovered from H1N1 pdm infection or who had been immunised with an adjuvanted subunit vaccine prepared from reassortant virus NYMC X-179A (derived from A/California/7/2009 virus). Ten laboratories from seven countries tested the candidate IS, 09/194 and a panel of human sera by HI and VN using the A/California/7/2009 virus (six laboratories) and/or the reassortant virus NYMC X-179A (ten laboratories). As expected, the inter-laboratory variability for HI and VN assay results was high. For results of antibody tests to NYMC X-179A, the % geometric coefficient of variation (%GCV) for 09/194 between laboratories was 83% for HI and 192% for VN. For tests of all sera, the median %GCV ranged from 95 to 345% for HI (80-fold variation) and 204 to 383% for VN (109-fold variation), but for the titres relative to 09/194 the median %GCV was much reduced (HI 34-231%; VN 44-214%). For tests of antibody to the A/California/7/2009 wild type virus there were similar reductions in %GCV when 09/194 was used. These results suggest that 09/194 will be of use to standardise assays of antibody to A/California/7/2009 vaccine and 09/194 has now been established by WHO as an IS for antibody to A/California/7/2009 with an assigned potency of 1300 IU per ml.

The aim of this study was to identify the common barriers and facilitators for acceptance of pandemic influenza vaccination across different countries. This study utilized a standardized, anonymous, self-completed questionnaire-based survey recording the demographics and professional practice, previous experience and perceived risk and severity of influenza, infection control practices, information of H1N1 vaccination, acceptance of the H1N1 vaccination and reasons of their choices and opinions on mandatory vaccination. Hospital-based doctors, nurses and allied healthcare workers in Hong Kong (HK), Singapore (SG) and Leicester, United Kingdom (UK) were recruited. A total of 6318 (HK: 5743, SG: 300, UK: 275) questionnaires were distributed, with response rates of 27.1% (HK), 94.7% (SG) and 94.5% (UK). The uptake rates for monovalent 2009 pandemic H1N1 vaccine were 13.5% (HK), 36.2% (SG) and 41.3% (UK). The single common factor associated with vaccine acceptance across all sites was having seasonal influenza vaccination in 2009. In UK and HK, overestimation of side effect reduced vaccination acceptance; and fear of side effect was a significant barrier in all sites. In HK, healthcare workers with more patient contact were more reluctant to accept vaccination. Drivers for vaccination in UK and HK were concern about catching the infection and following advice from health authority. Only a small proportion of respondents agreed with mandatory pandemic influenza vaccination (HK: 25% and UK: 42%), except in Singapore where 75.3% were in agreement. Few respondents (

Summary Introduction Enteric fever is an increasingly common diagnosis in returning travellers in the UK. Methods We performed a retrospective descriptive study of culture-confirmed cases of enteric fever admitted to University Hospitals Leicester, UK between January 1999 and April 2009. Results 100 cases of enteric fever were identified in adults ( n = 76) and children ( n = 24). The median age of adult subjects was 38 (range 18–71) and 55% were male. Of the 61 adult cases with notes available, 60 (98.3%) were of Asian ethnicity and 56 (92%) had a recent travel history, principally to the Indian Subcontinent. Symptoms included fever (100%), headache (62%), diarrhoea (59%) and abdominal pain (44%). Common examination findings included pyrexia and mild generalized abdominal tenderness. Mild hyponatraemia, transaminitis and a normal white cell count were commonly identified. Reduced ciprofloxacin sensitivity was common and increased over the study period. Median fever clearance time was 6 days, and treatment failure occurred in 20% of cases. Relapse occurred in 2 patients. Complications were unusual, and one patient died. Discussion Patients with enteric fever presented with a non-specific febrile illness within one month after returning from travel, and most had an uncomplicated clinical course. Increasing ciprofloxacin insensitivity was the likely explanation for a high treatment failure rate and this agent can no longer recommended as empirical treatment.

Background Specific anti-influenza drugs are available for the management of seasonal influenza. Objectives To evaluate European recommendations and guidelines for the use of antiviral drugs in treatment and prevention of seasonal influenza. Design Guidelines issued between January 2003 and September 2007 were scored using the AGREE appraisal instrument and evaluated. Results Guidelines were obtained from France, Germany, Italy, Netherlands, Poland, Portugal, Sweden and the UK. Most guidelines recommend neuraminidase inhibitors over M2 inhibitors, but three countries were unclear or suggested M2 inhibitor use in some circumstances. Clinical diagnosis of patients eligible for treatment during periods of influenza activity is acceptable except in Poland where virological confirmation is required. Guidelines recommend antiviral use in patients at high risk of complications, except in Germany where there is a strong recommendation to treat all patients. Post-exposure prophylaxis for household contacts is recommended in Sweden and Germany, but not other countries. Only UK guidelines are regularly updated. All scored fairly poorly by the AGREE instrument. French, Polish, Swedish and UK guidelines were recommended. Conclusion Major variations exist in recommendations for treatment and prevention of seasonal influenza. Development of Pan-European guidance should be considered. Updating is important to reflect emerging patterns of antiviral resistance.

Because of the time required to identify and produce an antigenically well-matched pandemic vaccine, vaccines that offer broader cross-reactive immunity and protection are desirable. We have compared a live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) based on a related H5 hemagglutinin (HA) from a nonpathogenic avian influenza virus, A/Duck/Pottsdam/1042-6/86 (H5N2), for the ability to induce cross-reactive immunity and/or cross-protective efficacy against a contemporary highly pathogenic H5N1 viruses. Both LAIV and IIV provided cross-protection from systemic infection, severe disease, and death following lethal challenges with antigenically distinct A/Vietnam/1203/2004 (VN/1203) virus. Substantial levels of serum anti-VN/1203 HA IgG were detected in mice that received either IIV or LAIV, while nasal wash anti-VN/1203 HA IgA was detected in mice that received LAIV. Formulation of IIV with alum adjuvant augmented neutralizing antibody responses and protective efficacy. These results demonstrated that vaccination of mice with H5 IIV or LAIV induced a high degree of cross-protection from illness and death following lethal challenges with a heterologous H5N1 virus.

Sporothrix schenckii is a widespread dimorphic fungus which can cause cutaneous infection following local implantation. Disseminated sporotrichosis may occur in immunodeficient individuals but meningitis remains a rare complication. Diagnosis is usually difficult, requiring isolation of the organism from the CSF or skin so appropriate treatment can be promptly initiated. We present the first case of S. schenckii meningitis reported in the UK in a patient with AIDS. He presented with insidious features of meningoencephalitis, hydrocephalus and multiple cutaneous lesions and failed to respond to therapy.

Human metapneumovirus (HMPV) is a recently identified Paramyxovirus first isolated from hospitalized children with acute respiratory tract infections (ARTI). We sought evidence of HMPV infection in patients who had visited general practitioners, had influenzalike illnesses (ILI), and had negative tests for influenza and Human respiratory syncytial virus (HRSV). As part of national virologic surveillance, sentinel general practices in England and Wales collected samples from patients of all ages with ILI during winter 2000–01. Reverse transcriptase-polymerase chain reaction (PCR) for HMPV, influenza A (H1 and H3), influenza B, and HRSV (A and B) was used to screen combined nose and throat swabs. PCR products from the HMPVpositive samples were sequenced to confirm identity and construct phylogenetic trees. Of 711 swabs submitted, 408 (57.3%) were negative for influenza and HRSV; HMPV was identified in 9 (2.2%) patients. HMPV appears to be associated with community-acquired ARTI. The extent of illness and possible complications related to this new human virus need to be clarified. espite control of many infectious diseases in the industrialized world, acute viral respiratory tract infections (ARTI) remain a leading cause of illness. Although usually self-limiting in healthy adults, these infections are responsible for a substantial loss of productive time and are important factors in the illness and death of the elderly population. Various genetically diverse viruses, often with multiple types, may cause respiratory illness; of these, influenza receives the greatest attention (1). Human respiratory syncytial virus (HRSV) is also increasingly implicated as an important pathogen (2). The association between the incidence of ARTI and excess winter deaths in the United Kingdom is well recognized (1). Regression modeling associates excess winter deaths with influenza and HRSV but also suggests that other pathogens may be involved (3). Studies of the impact of respiratory virus infections are limited by difficulty in distinguishing respiratory pathogens clinically and in the laboratory (4,5). Despite improved sensitivity with diagnostic techniques such as reverse transcriptasepolymerase chain reaction (RT-PCR), approximately 40% of specimens from patients with community-acquired respiratory illnesses during peak winter months contain no identified viral pathogen (2,5,6). A new pneumovirus, Human Metapneumovirus (HMPV), has recently been isolated in the Netherlands (7). The Pneumovirinae subfamily is classified into Pneumovirus, containing HRSV, and Metapneumovirus genera. In 2001, Van den Hoogen et al. (7) reported the detection of HMPV in nasopharyngeal aspirates taken in a 10-year period from 28 hospitalized children and infants with respiratory tract infections who had signs and symptoms similar to those of HRSV infection. Establishing sensitive methods for virus detection helps to clarify the relative contribution of different pathogens to the extent of illness in the community. This information is important for future development of specific antiviral therapies and vaccines. We examined specimens submitted from patients seen in general practice with influenzalike illnesses (ILI) during winter 2000–01 to detect HMPV as a possible cause of influenza- and HRSV-negative ILI.

After the initial atypical presentation of a patient with avian influenza (H5N1) infection, paired acute-phase and convalescent-phase serum samples obtained from 25 health care workers (HCWs) who were exposed to the patient were compared with paired serum samples obtained from 24 HCWs who worked at different units in the same hospital and were not exposed to the patient. There was no serologic evidence of anti-H5 antibody reactivity or subclinical infection in either of the groups.