Iain Stephenson

Cross-Reactivity to Highly Pathogenic Avian Influenza H5N1 Viruses after Vaccination with Nonadjuvanted and MF59-Adjuvanted Influenza A/Duck/Singapore/97 (H5N3) Vaccine: A Potential Priming Strategy

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.

Development of adenoviral-vector-based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice

INTRODUCTIONnAvian H5N1 influenza viruses currently circulating in southeast Asia could potentially cause the next pandemic. However, currently licensed human vaccines are subtype-specific and do not protect against these H5N1 viruses. We aimed to develop an influenza vaccine and assessed its immunogenicity and efficacy to confer protection in BALB/c mice.nnnMETHODSnWe developed an egg-independent strategy to combat the avian influenza virus, because the virus is highly lethal to chickens and the maintenance of a constant supply of embryonated eggs would be difficult in a pandemic. We used a replication-incompetent, human adenoviral-vector-based, haemagglutinin subtype 5 influenza vaccine (HAd-H5HA), which induces both humoral and cell-mediated immune responses against avian H5N1 influenza viruses isolated from people.nnnFINDINGSnImmunisation of mice with HAd-H5HA provided effective protection from H5N1 disease, death, and primary viral replication (p<0.0001) against antigenically distinct strains of H5N1 influenza viruses. Unlike the recombinant H5HA vaccine, which is based on a traditional subunit vaccine approach, HAd-H5HA vaccine induced a three-fold to eight-fold increase in HA-518-epitope-specific interferon-gamma-secreting CD8 T cells (p=0.01).nnnINTERPRETATIONnOur findings highlight the potential of an Ad-vector-based delivery system, which is both egg-independent and adjuvant-independent and offers stockpiling options for the development of a pandemic influenza vaccine.

Confronting the avian influenza threat: vaccine development for a potential pandemic

n Summaryn n 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.n n

Seroprevalence of Anti-H5 Antibody among Thai Health Care Workers after Exposure to Avian Influenza (H5N1) in a Tertiary Care Center

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.

Seasonal influenza vaccination predicts pandemic H1N1 vaccination uptake among healthcare workers in three countries

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 (<5%) chose scientific publications as their primary source of information, but this group was more likely to receive vaccination. The acceptance of pandemic vaccine among healthcare workers was poor (13-41% of respondents). Breaking barriers to accept seasonal influenza vaccination should be part of the influenza pandemic preparedness plan. Mandatory vaccination even during pandemic is likely to arouse substantial discontent.

Differences in the compliance with hospital infection control practices during the 2009 influenza H1N1 pandemic in three countries.

BACKGROUNDnIn 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.nnnAIMnTo study the practice of infection control measures during the 2009 influenza H1N1 pandemic among healthcare workers (HCWs) in three countries.nnnMETHODSnA 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.nnnFINDINGSnA 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.nnnCONCLUSIONSnCompliance with infection control measures for pandemic influenza appears to vary widely depending on the setting.

Hypogonadism in the HIV-Infected Man

Opinion statementLow testosterone levels are frequently observed among men with treated and untreated HIV infection. However, the interpretations of biochemical measurements of testicular function are challenging and need to be considered in the context of the clinical presentation and scenario. The distinction between primary and secondary hypogonadism and determination of the underlying clinical pathophysiology are not always straightforward. Early recognition of clinical hypogonadism and appropriate treatment may improve clinical outcomes and quality of life for affected individuals. A principal aim of testosterone replacement is to maintain serum testosterone concentrations in the normal physiological range and should be considered in clinically symptomatic patients.