SPATIOTEMPORAL TRENDS OF CASES OF PANDEMIC INFLUENZA A(H1N1)PDM09 IN ARGENTINA, 2009-2012

The aim of this paper was to analyze the spatiotemporal variations of cases of influenza A(H1N1)pdm09 in Argentina. A space-time permutation scan statistic was performed to test the non-randomness in the interaction between space and time in reported influenza A(H1N1)pdm09 cases. In 2009, two clusters were recorded in the east of Buenos Aires Province (May and June) and in the central and northern part of Argentina (July and August). Between 2011 and 2012, clusters near areas bordering other countries were registered. Within the clusters, in 2009, the high notification rates were first observed in the school-age population and then extended to the older population (15-59 years). From 2011 onwards, higher rates of reported cases of influenza A(H1N1)pdm09 occurred in children under five years in center of the country. Two stages of transmission of influenza A(H1N1)pdm09 can be characterized. The first stage had high rates of notification and a possible interaction with individuals from other countries in the major cities of Argentina (pattern of hierarchy), and the second stage had an increased interaction in some border areas without a clear pattern of hierarchy. These results suggest the need for greater coordination in the Southern Cone countries, in order to implement joint prevention and vaccination policies.

Surveillance of influenza A H1N1 2009 among school children during 2009 and 2010 in São Paulo, Brazil

INTRODUCTION: Influenza A H1N1 2009 is associated with a high morbidity rate among children around the world, including Brazil. This survey was conducted on samples of symptomatic children (< 12 years) to investigate the influenza virus as the etiological agent of respiratory infections in a day care school in a health facility during the first and second pandemic wave of H1N1 (2009-2010) in São Paulo, Brazil. METHODS: Influenza infections were determined by real-time PCR in 34% (47/137) of children with a median age of 5 years (8 months - 12 years), from June to October 2009 and in 16% (14/85) of those with median age of 6 years (1-12 years), from March to November 2010. RESULTS: In general, most positive cases (64%) occurred in children aged 5-12 years, this age group was significantly the most affected (39.8%, p = 0.001, OR = 8.3, CI 95% 1.9-36.9). Wheezing was reported by 31% (19/61) and dyspnea by 23% (14/61) of the studied patients. An outbreak of influenza H1N1 with an attack rate of 35.7% among children (median age 6 years) was documented in April 2010, before the vaccination campaign against the pandemic virus was extended for children up to 5 years in Brazil. CONCLUSIONS: Therefore, the study reinforces the recommendation to immunize school children to reduce the incidence of the disease.

The characteristics, clinical manifestations and outcomes of pandemic influenza A (H1N1) 2009 in the elderly

IntroductionThe objetctive of this study was to evaluate the 2009 Pandemic Influenza A (H1N1) in the elderly and identify the clinical characteristics, mortality and prognostic factors of the infection in these patients.MethodsThis was an observational, retrospective study. Data were collected from the National Notifiable Diseases (SINAN), from the Brazilian Ministry of Health. Only patients 60 years old or more that had laboratory confirmed infections were included. The socio-demographic and clinical variables and outcomes were evaluated to compare mortality rates in the presence or absence of these factors.ResultsWe included 93 patients in the study, 16.1% of whom died. The symptoms of cough and dyspnea, the use of the antiviral oseltamivir, influenza vaccine and comorbidities influenced the outcomes of cure or death. Chest radiography can aid in diagnosis.ConclusionsAlthough relatively few elderly people were infected, this population presented high lethality that can be justified by the sum of clinical, physical and immunological factors in this population. Treatment with oseltamivir and vaccination against seasonal influenza have significantly reduced rates of hospitalization and mortality.

Fine structural variations of alphabetaTCRs selected by vaccination with natural versus altered self-antigen in melanoma patients.

Immunotherapy of cancer is often performed with altered "analog" peptide Ags optimized for HLA class I binding, resulting in enhanced immunogenicity, but the induced T cell responses require further evaluation. Recently, we demonstrated fine specificity differences and enhanced recognition of naturally presented Ag by T cells after vaccination with natural Melan-A/MART-1 peptide, as compared with analog peptide. In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A(26-35)-specific CD8 T cells derived from both cohorts of patients. Although a strong preference for TRAV12-2 segment usage was present in nearly all patients, usage of particular TRAJ gene segments and CDR3alpha composition differed slightly after vaccination with natural vs analog peptide. Moreover, TCR beta-chain repertoires were broader after natural than analog peptide vaccination. In all patients, we observed a marked conservation of the CDR3beta amino acid composition with recurrent sequences centered on a glycyl-leucyl/valyl/alanyl-glycyl motif. In contrast to viral-specific TCR repertoires, such "public" motifs were primarily expressed by nondominant T cell clonotypes, which contrasted with "private" CDR3beta signatures frequently found in T cell clonotypes that dominated repertoires of individual patients. Interestingly, no differences in functional avidity were observed between public and private T cell clonotypes. Collectively, our data indicate that T cell repertoires generated against natural or analog Melan-A peptide exhibited slightly distinct but otherwise overlapping and structurally conserved TCR features, suggesting that the differences in binding affinity/avidity of TCRs toward pMHC observed in the two cohorts of patients are caused by subtle structural TCR variations.

Disease-driven T cell activation predicts immune responses to vaccination against melanoma.

Tumor vaccines may induce activation and expansion of specific CD8 T cells which can subsequently destroy tumor cells in cancer patients. This phenomenon can be observed in approximately 5-20% of vaccinated melanoma patients. We searched for factors associated with T cell responsiveness to peptide vaccines. Peptide antigen-specific T cells were quantified and characterized ex vivo before and after vaccination. T cell responses occurred primarily in patients with T cells that were already pre-activated before vaccination. Thus, peptide vaccines can efficiently boost CD8 T cells that are pre-activated by endogenous tumor antigen. Our results identify a new state of T cell responsiveness and help to explain and predict tumor vaccine efficacy.

Surveillance of influenza in Northern Ireland

The influenza season started later than normal, clinical indices began to increase marginally in mid-February, much later than previous seasons, and activity remained very low throughout, with community syndromic indicators not reaching the baseline warning threshold during the season. The peak GP influenza-like illness consultation rates in 2011/12 were the lowest since surveillance began in Northern Ireland in 2000. No one age-group appeared predominantly affected, with low levels of activity in all age groups, however, GP consultation rates increased in both children and adults.Influenza A (H3) was the predominant strain of the virus circulating, with small numbers of the influenza B strain circulating later in the season. Unlike the 2010/11 season when Influenza A (H1N1)2009 strain dominated in Northern Ireland, there were no detections of this subtype in 2011/12; virological activity generally corresponded to clinical activity.There were however, patients with confirmed influenza admitted to Intensive care units, across Northern Ireland during the season. Numbers were low, the average age of these patients increased compared with the previous season and one fatality was reported in this group.The proportion of over 65 year olds who received the 2011/12 seasonal influenza vaccine was 77.0%, and in those in a clinical risk group aged under 65 years was 81.7%, both of these vaccination uptake figures were a slight increase on the previous year. Influenza vaccine uptake in frontline healthcare workers also increased marginally this season to 20.8%, as did the proportion of pregnant women vaccinated during the season.

From the Cover: Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination.

The ability of vaccines to induce memory cytotoxic T-cell responses in the lung is crucial in stemming and treating pulmonary diseases caused by viruses and bacteria. However, most approaches to subunit vaccines produce primarily humoral and only to a lesser extent cellular immune responses. We developed a nanoparticle (NP)-based carrier that, upon delivery to the lung, specifically targets pulmonary dendritic cells, thus enhancing antigen uptake and transport to the draining lymph node; antigen coupling via a disulfide link promotes highly efficient cross-presentation after uptake, inducing potent protective mucosal and systemic CD8(+) T-cell immunity. Pulmonary immunization with NP-conjugated ovalbumin (NP-ova) with CpG induced a threefold enhancement of splenic antigen-specific CD8(+) T cells displaying increased CD107a expression and IFN-γ production compared with immunization with soluble (i.e., unconjugated) ova with CpG. This enhanced response was accompanied by a potent Th17 cytokine profile in CD4(+) T cells. After 50 d, NP-ova and CpG also led to substantial enhancements in memory CD8(+) T-cell effector functions. Importantly, pulmonary vaccination with NP-ova and CpG induced as much as 10-fold increased frequencies of antigen-specific effector CD8(+) T cells to the lung and completely protected mice from morbidity following influenza-ova infection. Here, we highlight recruitment to the lung of a long-lasting pool of protective effector memory cytotoxic T-cells by our disulfide-linked antigen-conjugated NP formulation. These results suggest the reduction-reversible NP system is a highly promising platform for vaccines specifically targeting intracellular pathogens infecting the lung.

Narcolepsie avec cataplexie après vaccination anti-H1N1

IntroductionIt has been suggested that the H1N1 vaccine may be a trigger for the onset of narcolepsy-cataplexy, a rare disease whose autoimmune origin is suspected.ObservationsWe report two patients (a 9-year-old boy and an 18-year-old man) with severe narcolepsy-cataplexy, in whom the illness appeared within 3-4 weeks after H1N1 vaccination. In both cases, symptoms developed unusually abruptly and they presented with severe daytime sleepiness and multiple daily cataplexy attacks. Other similar cases have been recently reported associated with H1N1 vaccine.ConclusionAlthough no formal link can be established, the unusual characteristics of the reported cases and the striking temporal relationship suggests that narcolepsy may be the result of an autoimmune reaction triggered by H1N1 vaccination in susceptible individuals.

VaxcineTM: an oil-based adjuvant for influenza vaccines

Vaccination is the method of choice for the prevention of influenza infection. However, the quantity of the antigen available, especially in the case of pandemics, often fails to meet the global demand. However, improved adjuvants can overcome this problem. Preliminary results obtained in this study revealed that one year after a single subcutaneous immunisation with influenza A H3N2 virus in an oil-based carrier, VaxcineTM, outbreed mice produced a high immunoglobulin G response that lasted for up to one year and exhibited less variation in titre compared with the response of the control group treated with alum. The haemagglutination-inhibition titres induced by VaxcineTM were also higher than those generated by alum. These data indicate that VaxcineTM is a good adjuvant candidate for seasonal influenza vaccines.

Comparison of adverse events following immunization with pandemic influenza A (H1N1)pdm09 vaccine with or without adjuvant among health professionals in Rio de Janeiro, Brazil

A vaccination campaign against pandemic influenza A (H1N1)pdm09 was held in Brazil in March 2010, using two types of monovalent split virus vaccines: an AS03-adjuvanted vaccine and a non-adjuvanted vaccine. We compared the reactogenicity of the vaccines in health professionals from a Clinical Research Institute in Rio de Janeiro, Brazil and there were no serious adverse events following immunization (AEFI) among the 494 subjects evaluated. The prevalence of any AEFI was higher in the AS03-adjuvanted vaccine at 2 h and 24 h post-vaccination [preva-lence ratio (PR): 2.05, confidence interval (CI) 95%: 1.55-2.71, PR: 3.42, CI 95%: 2.62-4.48, respectively]; however, there was no difference between the vaccines in the assessments conducted at seven and 21 days post-vaccination. The group receiving the AS03 post-adjuvanted vaccine had a higher frequency of local reactions at 2 h (PR: 3.01, CI 95%: 2.12-4.29), 24 h (PR: 4.57, CI 95%: 3.29-6.37) and seven days (PR: 6.05, CI 95%: 2.98-12.28) post-vaccination. We concluded that the two types of vaccines caused no serious AEFI in the studied population and the adjuvanted vaccine was more reactogenic, particularly in the 24 h following vaccination. This behaviour must be confirmed and better characterised by longitudinal studies in the general population.

Influenza A virus infection of healthy piglets in an abattoir in Brazil: animal-human interface and risk for interspecies transmission

Asymptomatic influenza virus infections in pigs are frequent and the lack of measures for controlling viral spread facilitates the circulation of different virus strains between pigs. The goal of this study was to demonstrate the circulation of influenza A virus strains among asymptomatic piglets in an abattoir in Brazil and discuss the potential public health impacts. Tracheal samples (n = 330) were collected from asymptomatic animals by a veterinarian that also performed visual lung tissue examinations. No slaughtered animals presented with any noticeable macroscopic signs of influenza infection following examination of lung tissues. Samples were then analysed by reverse transcription-polymerase chain reaction that resulted in the identification of 30 (9%) influenza A positive samples. The presence of asymptomatic pig infections suggested that these animals could facilitate virus dissemination and act as a source of infection for the herd, thereby enabling the emergence of influenza outbreaks associated with significant economic losses. Furthermore, the continuous exposure of the farm and abattoir workers to the virus increases the risk for interspecies transmission. Monitoring measures of swine influenza virus infections and vaccination and monitoring of employees for influenza infection should also be considered. In addition regulatory agencies should consider the public health ramifications regarding the potential zoonotic viral transmission between humans and pigs.

Recommandations de vaccination pour les patients atteints de maladie chronique [Immunization guidelines regarding patients with a chronic disease].

Some chronic diseases--like renal failure, liver insufficiency, chronic lung disease, cardiac involvement, diabetes mellitus, asplenia--present limited defects of the immune system and/or a higher risk of infection; therefore, patients with such pathologies should get selective vaccinations. The efficacy of immunization decreases with disease progression; for this reason, these patients should be immunized as soon as possible. At the beginning of their disease, these patients do not need a specialized treatment and are followed by the general practitioner alone who is in charge of immunizing them as well as contact people of any immunocompromised patient. OFSP's regular vaccinations programme is recommended, as well as selective vaccinations against influenza, pneumococci and viral hepatitis, depending on the underlying chronic disease.

Humoral Response to the Influenza A H1N1/09 Monovalent AS03-Adjuvanted Vaccine in Immunocompromised Patients.

Background. Few data are available regarding the immunogenicity and safety of the pandemic influenza vaccine in immunocompromised patients. We evaluated the humoral response to the influenza A H1N1/09 vaccine in solid-organ transplant (SOT) recipients, in patients with human immunodeficiency virus (HIV) infection, and in healthy individuals. Methods. Patients scheduled to receive the pandemic influenza vaccine were invited to participate. All participants received the influenza A H1N1/09 AS03-adjuvanted vaccine containing 3.75 μg of hemagglutinin. SOT recipients and HIV-infected patients received 2 doses at 3-week intervals, whereas control subjects received 1 dose. Blood samples were taken at day 0, day 21, and day 49 after vaccination. Antibody responses were measured with the hemagglutination inhibition assay (HIA) and a microneutralization assay. Results. Twenty-nine SOT recipients, 30 HIV-infected patients, and 30 healthy individuals were included in the study. Seroconversion measured by HIA was observed in 15 (52%) of 29 SOT recipients both at day 21 and day 49; in 23 (77%) of 30 at day 21 and 26 (87%) of 30 at day 49 in HIV-infected patients, and in 20 (67%) of 30 at day 21 and in 23 (77%) of 30 at day 49 in control subjects (P = .12 at day 21 and P = .009 at day 49, between groups). Geometric means of antibody titers were not significantly different between groups at day 21 or at day 49. Conclusions. Influenza A H1N1/09 vaccine elicited a similar antibody response in HIV-infected individuals and in control subjects, whereas SOT recipients had an overall lower response. A second dose of the vaccine only moderately improved vaccine immunogenicity in HIV-infected patients.

Iowa Influenza Surveillance Network Final Report 2007-2008

The Iowa Influenza Surveillance Network (IISN) was formally established in 2004, though surveillance has been conducted at the Iowa Department of Public Health (IDPH) for more than ten years. The IISN is comprised of four primary surveillance systems- sentinel health care providers, hospital-based, laboratory-based, and school-based. Sentinel health care providers are part of the U.S. Influenza Sentinel Provider Surveillance System. All systems, except certain sentinel sites, report October-March. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Prevalence rate and reasons for refusals of influenza vaccine in elderly.

More knowledge on the reasons for refusal of the influenza vaccine in elderly patients is essential to target groups for additional information, and hence improve coverage rate. The objective of the present study was to describe precisely the true motives for refusal. All patients aged over 64 who attended the Medical Outpatient Clinic, University of Lausanne, or their private practitioner's office during the 1999 and 2000 vaccination periods were included. Each patient was informed on influenza and its complications, as well as on the need for vaccination, its efficacy and adverse events. The vaccination was then proposed. In case of refusal, the reasons were investigated with an open question. Out of 1398 patients, 148 (12%) refused the vaccination. The main reasons for refusal were the perception of being in good health (16%), of not being susceptible to influenza (15%), of not having had the influenza vaccine in the past (15%), of having had a bad experience either personally or a relative (15%), and the uselessness of the vaccine (10%). Seventeen percent gave miscellaneous reasons and 12% no reason at all for refusal. Little epidemiological knowledge and resistance to change appear to be the major obstacles for wide acceptance of the vaccine by the elderly.