Cost-effectiveness of childhood influenza vaccination in England and Wales: Results from a dynamic transmission model.

This study uses a dynamic influenza transmission model to directly compare the cost-effectiveness of various policies of annual paediatric influenza vaccination in England and Wales, varying the target age range and level of coverage. The model accounts for both the protection of those immunised and the indirect protection of the rest of the population via herd immunity. The impact of augmenting current practice with a policy to vaccinate pre-school age children, on their own or with school age children, was assessed in terms of quality adjusted life years and health service costs. Vaccinating 2-18 year olds was estimated to be the most cost-effective policy in an incremental cost-effectiveness analysis, at an assumed annual vaccine uptake rate of 50%. The mean incremental cost-effectiveness ratios for this policy was estimated at £251/QALY relative to current practice. Paediatric vaccination would appear to be a highly cost-effective intervention that directly protects those targeted for vaccination, with indirect protection extending to both the very young and the elderly.

Estimating the clinical impact of introducing paediatric influenza vaccination in England and Wales.

Influenza causes a significant burden of disease each year in England and Wales, with the young and the elderly suffering the greatest burden. Children are recognised as playing an important role in the dissemination of the influenza virus. This study examines the population impact of implementing a programme of paediatric vaccination. A dynamic transmission model was used to simulate the impact of vaccination programmes with varying levels of coverage across pre-school and school age children. These analyses suggest that vaccinating as few as 50% of 2-18 year olds could result in a substantial reduction in the annual incidence of influenza related morbidity and mortality across the population. Herd immunity may extend this protection to the young and the elderly. It is assumed that such programmes would be implemented in concert with the current strategy of vaccinating the elderly and younger at risk groups with an inactivated vaccine. In England and Wales, paediatric vaccination of two to eighteen year olds reduced the estimated number of general practice consultations, hospitalisations and deaths arising from influenza A and B infections by up to 95%. This translates into an annual average reduction of approximately 52,000, 1500 and 1200 events, respectively. A policy of paediatric vaccination could significantly reduce the clinical burden of influenza in England and Wales, in all age groups, with the added value of herd immunity helping to protect the young and the elderly who are at highest risk of complications.

Assessing the burden of influenza and other respiratory infections in England and Wales.

OBJECTIVES: To estimate the burden of influenza in England and Wales, in terms of general practice consultations, hospital admissions and deaths. METHODS: Multivariable regression was used to estimate the influenza attributable fraction of general practice consultations recorded in the general practice research database, of hospital admissions from hospital episode statistics and of deaths recorded by the Office of National Statistics. RESULTS: An estimated 779,000 (95%CI+/-258,000)-1,164,000 (95%CI+/-425,000) general practice consultations, 19,000 (95%CI+/-5000)-31,200 (95%CI+/-11,000) hospital admissions and 18,500 (95%CI 2500)-24,800 (95%CI+/-2500) deaths annually are attributable to influenza infections. In primary care, the bulk of the burden falls on those under the age of 45, whereas the elderly are more likely to be hospitalised and to die. CONCLUSIONS: Although there are significant uncertainties, and considerable year on year variations, it is clear that the burden of influenza is considerable. Although much of this burden falls on the elderly, significant numbers of general practice consultations, hospitalisations and even some deaths occur annually in children in England and Wales.

Dendritic cells from HIV-1-infected patients naturally express HIV-1 gp120 V3 loop-derived peptide ligands.

Little is known of the peptide ligands expressed in vivo on antigen-presenting cells (APC) or of the APC lineages involved. In this study we have addressed this question using HLA-DRbeta1*0101-restricted CD4 T cell clones (TLC) specific for a synthetic peptide based on the HIV-1 gp120 V3 loop consensus sequence for the Clade B isolates predominantly found in European and North American patients. These TLC were found to respond, in a dose-dependent manner, to freshly isolated HIV-infected patient APC in the absence of exogenously added peptides. Further APC purification showed that the naturally expressed peptide ligands were present in both the APC lineages shown to be infected with the virus and were most strongly detectable on purified blood dendritic cells. Peptides based on consensus sequences of viruses isolated from one of the patients over the period when naturally expressed peptide ligands could be detected were all found to stimulate TLC proliferation. These studies, therefore, show that peptide ligands derived from natural infection are detectable on APC lineages, particularly on dendritic cells which play an important role in the immune response to viruses. Even small differences in sequence between the vaccine isolate and the natural infection, if they occur in the key residues of protective T cell epitopes, could therefore have a profound effect on the efficacy of vaccines against viruses with high rates of mutation.

CD4+ T-cell recognition of diverse clade B HIV-1 isolates.

OBJECTIVES: To evaluate the effect of sequence variation within the gp120 V3 loop on CD4 T-cell recognition. DESIGN: CD4 T-cell clones were generated using synthetic peptides to circumvent the difficulties of using polyclonal T-cell responses. Peptides based on other HIV isolates were then used to determined the influence of single and multiple sequence differences. RESULTS: Three of the panels of T-lymphocyte clones (TLC), which were all specific to diverse HIV-1 clade B gp120 V3-loop peptides differing in a limited number of residues, had heterogeneous patterns of response to peptides differing in length and sequence indicating that they recognized distinct but overlapping epitopes. The panels of TLC also differed in the extent to which they tolerated sequence differences between cell-culture-adapted or primary HIV-1 isolates. One panel responded to peptides based on several clade B and one clade D isolate. In contrast, two panels, generated from two different donors using the same peptide, only responded to a limited number of clade B isolates, whereas another only recognized HIV-1BRU. Two of the panels were also stimulated by peptides based on clinical isolates from one patient with some sequence changes enhancing T-cell recognition. CONCLUSIONS: These data are consistent with highly diverse CD4 T-cell recognition of the HIV-1 gp120 V3 loop, which is influenced by the sequence differences within the T-cell epitopic region and has implications for the pathogenesis and design of vaccines against HIV-1.

No evidence of antibody to human foamy virus in widespread human populations.

The first human foamy virus (HFV) to be described was isolated from nasopharyngeal carcinoma tissue from a Kenyan patient. Early seroepidemiology concluded that there was a significant infection rate, particularly among Africans. Awareness of foamy viruses as potential vectors has stimulated interest in the natural seroprevalence of HFV infection. We, therefore, investigated the prevalence of HFV infection in more than 5000 human sera collected from diverse populations. To maximize the chances of including the major antigenic epitopes, recombinant proteins derived from the HFV gag and env genes divided into three (the 5' amino terminal, the 3' carboxy terminal, and an internal overlapping region) were used as antigens in an ELISA. In contrast to most other seroepidemiological investigations of HFV infection, highly reactive sera identified by ELISA were subjected to further analysis by additional serological assays and, where PBMCs were available, PCR. None of the serum samples were confirmed as positive. It is worth noting that with our ELISA, the highest level of serum reactivity to HFV was found in subjects from Pacific islands (17%), and in Central Africa (34% in Malawi), areas previously cited as having a high level of HFV infection. Taken together with sequence analysis endorsing the phylogenetic closeness of HFV to SFV-6/7, these data strongly suggest that HFV is not naturally found in the human population.