Infección por virus pandémico (H1N1) 2009 en Andalucía

In April 2009, in response to the WHO's alert due to the existence of human infection cases with a new AH1N1 influenza virus, known as swine flu, Andalusian Health Authorities trigger an specific action plan. The surveillance actions developped provided us with appropriate clinical, epidemiological and virological characteristics of the disease. During the first few days, contingency plans were set up based on epidemiological surveillance and outbreak control measures were adopted through early alert and rapid response systems. After phase 6 was declared, influenza sentinel and severe cases surveillance were used in order to plan healthcare services, to reduce transmission and to identify and protect the most vulnerable population groups. Behaviour of pandemic influenza in Andalusia was similar to that observed in the rest of the world. Atack rate was similar to a seasonal flu and the peak was reached at the 46th/2009 week. Most of them were mild cases and affected particularly to young people. The average age of hospitalised patients was 32. Prior pulmonary disease, smoking and morbid obesity (BMI>40) were the most common pathologies and risk factors in severe cases. An impact scenario of pandemic wave in Andalusia, with an expected attack rate from 2 to 5%, was prepared considering watt observed in the southern hemisphere. Characteristics of the epidemic concerning its extent, severity and mortality rate were adjusted to this scenario.

Pandemic influenza control in Europe and the constraints resulting from incoherent public health laws.

Background With the emergence of influenza H1N1v the world is facing its first 21st century global pandemic. Severe Acute Respiratory Syndrome (SARS) and avian influenza H5N1 prompted development of pandemic preparedness plans. National systems of public health law are essential for public health stewardship and for the implementation of public health policy[1]. International coherence will contribute to effective regional and global responses. However little research has been undertaken on how law works as a tool for disease control in Europe. With co-funding from the European Union, we investigated the extent to which laws across Europe support or constrain pandemic preparedness planning, and whether national differences are likely to constrain control efforts. Methods We undertook a survey of national public health laws across 32 European states using a questionnaire designed around a disease scenario based on pandemic influenza. Questionnaire results were reviewed in workshops, analysing how differences between national laws might support or hinder regional responses to pandemic influenza. Respondents examined the impact of national laws on the movements of information, goods, services and people across borders in a time of pandemic, the capacity for surveillance, case detection, case management and community control, the deployment of strategies of prevention, containment, mitigation and recovery and the identification of commonalities and disconnects across states. Results Results of this study show differences across Europe in the extent to which national pandemic policy and pandemic plans have been integrated with public health laws. We found significant differences in legislation and in the legitimacy of strategic plans. States differ in the range and the nature of intervention measures authorized by law, the extent to which borders could be closed to movement of persons and goods during a pandemic, and access to healthcare of non-resident persons. Some states propose use of emergency powers that might potentially override human rights protections while other states propose to limit interventions to those authorized by public health laws. Conclusion These differences could create problems for European strategies if an evolving influenza pandemic results in more serious public health challenges or, indeed, if a novel disease other than influenza emerges with pandemic potential. There is insufficient understanding across Europe of the role and importance of law in pandemic planning. States need to build capacity in public health law to support disease prevention and control policies. Our research suggests that states would welcome further guidance from the EU on management of a pandemic, and guidance to assist in greater commonality of legal approaches across states.

Development and Preliminary Evaluation of a Rapid Oligochromatographic Assay for Specific Detection of New Human Influenza A H1N1 Virus

A new oligochromatographic assay, Speed-Oligo Novel Influenza A H1N1, was designed and optimized for the specific detection of the 2009 influenza A H1N1 virus. The assay is based on a PCR method coupled to detection of PCR products by means of a dipstick device. The target sequence is a 103-bp fragment within the hemagglutinin gene. The analytical sensitivity of the new assay was measured with serial dilutions of a plasmid that contained the target sequence, and we determined that down to one copy per reaction of the plasmid was reliably detected. Diagnostic performance was assessed with 103 RNAs from suspected cases (40 positive and 63 negative results) previously analyzed with a reference real-time PCR technique. All positive cases were confirmed, and no false-positive results were detected with the new assay. No cross-reactions were observed when other viral strains or clinical samples with other respiratory viruses were tested. According to these results, this new assay has 100% sensitivity and specificity. The turnaround time for the whole procedure was 140 min. The assay may be especially useful for the specific detection of 2009 H1N1 virus in laboratories not equipped with real-time PCR instruments

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza.

INTRODUCTION Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.

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.

Pandemic 2009 A(H1N1) infection requiring hospitalization of elderly Spanish adults.

To describe the clinical presentation and prognosis of elderly adults hospitalized with pandemic 2009 A(H1N1) influenza infection and to compare these data with those of younger patients. DESIGN: Prospective, observational, multicenter study. SETTING: Thirteen hospitals in Spain. PARTICIPANTS: Adults admitted to the hospital with confirmed pandemic 2009 A(H1N1) influenza infection. MEASUREMENTS: Demographic, clinical, laboratory, radiological, and outcome variables. RESULTS: Between June 12 and November 10, 2009, 585 adults with confirmed 2009 A(H1N1) influenza were hospitalized, of whom 50 (8.5%) were aged 65 and older (median age 72, range 65-87). Older adults (≥ 65) were more likely to have associated comorbidities (88.0% vs 51.2%; P < .001), primarily chronic pulmonary diseases (46.0% vs 27.3%; P < .001). Lower respiratory tract symptoms and signs such as dyspnea (60.0% vs 45.6%) and wheezing (46.0% vs 27.8%; P = .007) were also more common in these elderly adults, although pulmonary infiltrates were present in just 14 (28.0%) of the older adults, compared with 221 (41.3%) of the younger adults (P = .06). Multilobar involvement was less frequent in elderly adults with pulmonary infiltrates than younger adults with pulmonary infiltrates (21.4% vs 60.0%; P = .05). Rhinorrhea (4.0% vs 21.9%; P = .003), myalgias (42.0% vs 59.1%; P = .01), and sore throat (14.0% vs 29.2%; P = .02) were more frequent in younger adults. Early antiviral therapy (<48 hours) was similar in the two groups (34.0% vs 37.9%; P = .58). Two older adults (4.0%) died during hospitalization, compared with 11 (2.1%) younger adults (P = .30). CONCLUSION: Elderly adults with 2009 A(H1N1) influenza had fewer viral-like upper respiratory symptoms than did younger adults. Pneumonia was more frequent in younger adults. No significant differences were observed in hospital mortality.

Long-term outcomes of pandemic 2009 influenza A(H1N1)-associated severe ARDS.

BACKGROUND: No data on long-term outcomes of survivors of 2009 influenza A(H1N1) (A[H1N1])-associated ARDS are available. The objective of this study was to compare the 1-year outcomes of survivors of A(H1N1)-associated ARDS, according to use or no use of extracorporeal lung assist (ECLA), using its need as an ARDS severity surrogate. METHODS: Survivors of ARDS (12 with ECLA use vs 25 without, corresponding to 75% and 54% of the eligible patients for each group, respectively) selected from the Réseau Européen de Ventilation Artificielle (REVA) registry had previously been healthy, with only pregnancy and/or moderate obesity (BMI ≤ 35 kg/m²) as known risk factors for A(H1N1) infection. Lung function and morphology, health-related quality of life (HRQoL), and psychologic impairment were evaluated. RESULTS: At 1 year post-ICU discharge for the ECLA and no-ECLA groups, respectively, 50% and 40% reported significant exertion dyspnea, 83% and 64% had returned to work, and 75% and 64% had decreased diffusion capacity across the blood-gas barrier, despite their near-normal and similar lung function test results. For both groups, exercise test results showed diminished but comparable exercise capacities, with similar alveolar-arterial oxygen gradients at peak exercise, and CT scans showed minor abnormal findings. HRQoL assessed by the 36-Item Short-Form Health Survey was poorer for both groups than for a sex- and age-matched general population group, but without between-group differences. ECLA and no-ECLA group patients, respectively, had symptoms of anxiety (50% and 56%) and depression (28% and 28%) and were at risk for posttraumatic stress disorder (41% and 44%). CONCLUSIONS: One year post-ICU discharge, a majority of survivors of A(H1N1)-associated ARDS had minor lung disabilities with diminished diffusion capacities across the blood-gas barrier, and most had psychologic impairment and poorer HRQoL than a sex- and age-matched general population group. ECLA and no-ECLA group patients had comparable outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01271842; URL: www.clinicaltrials.gov

Factors associated with vaccination against Influenza A (H1N1) in the elderly

This study aimed to investigate the sociodemographic, clinical and behavioral factors and receiving information about the vaccine against pandemic influenza A (H1N1) associated with vaccination of elderly people. Study of quantitative and transversal nature, in which 286 elderly residents in Fortaleza, CE, Brazil participated. The association between variables was analyzed by the Pearson chi-square test, considering a 95% confidence interval and significance level (p≤0.05). The results revealed that, unlike the sociodemographic characteristics, many clinical, behavioral and informational aspects correlated significantly with adherence to Influenza A (H1N1) vaccination. It is believed that the findings can be used in strategies to control and prevent infection by viral subtypes within the elderly population, extensible even to other vaccine-preventable diseases, especially in light of possible future pandemics.

Factores asociados a la predisposición a vacunarse contra la gripe pandémica A/H1N1 en población adulta del Departamento de Salud de Elche (España): influencia de las fuentes de información

Fundamento. Evaluar en población general las fuentes de información, actitudes y predisposición hacia la vacunación contra la gripe pandémica A/H1N1 de 2009. Métodos. Estudio descriptivo de carácter transversal realizado entre el 25 de noviembre y 30 de diciembre de 2009 mediante entrevista personal cara a cara a una muestra aleatoria (826) de adultos residentes en el Departamento de Salud de Elche (España). Resultados. Los encuestados manifestaron que la televisión (57%) y el médico de familia (47,9%) eran su fuente principal de información sobre vacunas. El 82,2% tenía una buena opinión sobre las vacunas, un 30,5% percibía la gripe A/H1N1 como más grave que la estacional, siendo esta percepción creciente entre los de mayor edad y con menos estudios. Un 25,4% de encuestados sentía preocupación por padecerla, sobre todo los de menor nivel educativo. Un 42,1% manifiesta su buena predisposición para vacunarse contra la gripe estacional, disminuyendo hasta un 18,4% la intención hacia la gripe A/H1N1. La predisposición hacia la vacunación crece con la edad y en el caso de la gripe A/H1N1 decrece a mayor nivel educativo. El médico de familia es la fuente de información más determinante para inmunizarse frente a gripe estacional (OR 1,43) y gripe A/H1N1 (OR 2,47). Conclusiones. Existe baja aceptabilidad de la vacuna pandémica y baja percepción de gravedad sobre la gripe A/H1N1. La experiencia previa de vacunación ante gripe estacional predispone hacia la inmunización contra gripe A/H1N1. Aunque los medios de comunicación encabezan la fuente de información más usual durante este episodio, la influencia del médico de familia en la decisión de vacunarse resulta significativa.

Identificación de subpoblaciones de macrófagos y linfocitos T en pulmones de pacientes fallecidos por influenza A H1N1

La infección por el virus de la influenza es un problema de salud pública por su rápida diseminación y alta morbilidad. Los casos graves de infección por éste virus presentan hipercitocinemia, la cual se ha asociado a una respuesta inmune adquirida desfavorable y un mal pronóstico para el paciente. Se han realizado hasta ahora experimentos en suero de pacientes o en tejido pulmonar en modelos de animales, sin embargo, no se tienen reportes del microambiente en el pulmón de pacientes fallecidos por el virus de la influenza. Objetivo: Determinar las subpoblaciones de macrófagos y linfocitos T y su correlación con el daño tisular en pulmón de pacientes fallecidos por influenza A H1N1 y otras enfermedades respiratorias. Material y Métodos: Se identificó y cuantificó el virus de influenza A H1N1 (pdm)09 e influenza A estacional por qRT-PCR, así como se determinó los niveles de citocinas y marcadores de macrófagos por qRT-PCR (IL-2, IL-4,IL-6, IL- 10, IL-12, IL-17, IL-23, IFN-, TGFβ, TNFα, Arg1, Retnlb e iNOS). Se realizaron tinciones de HyE para la determinación del daño tisular. Por otra parte, se realizaron tinciones de inmunohistoquímica para analizar las poblaciones celulares CD14+, CD206+, CD4+, CD8+, FOXP3+ y citocinas (IL-4, IL-10, IL-17 e IFN-) in situ. Resultados: Se determinó la presencia del virus de la influenza A en 10 muestras, de las cuales 4 fueron H1N1 (pdm)09. Además, se obtuvieron 5 muestras de neumonía por Coccidioides spp., y 6 de neumonías de origen bacteriano. No existe diferencia en el daño causado por el virus de la influenza A H1N1 (pdm)09 e influenza A estacional a nivel histopatológico. Las células CD14+ y CD4+ se encontraron aumentadas para todos los grupos de neumonías sin importar el agente etiológico, excepto CD4 para las neumonías bacterianas. Las células que expresaron Foxp3 solo se encontraron aumentadas en el grupo de coccidioidomicosis y neumonías bacterianas. No se encontró diferencia significativa entre los grupos de estudio para las células CD8+, excepto para las neumonías bacterianas. La expresión génica relativa de IL-6 se encontró aumentada 3000 veces la expresión génica en el grupo de influenza pandémica A H1N1 (pdm)09, mientras en influenza estacional se encontró una disminución de 0.08 veces de su expresión. INOS se encontró con expresión disminuida 0.5 veces para los grupos de influenza pandémica, influenza estacional y coccidioidomicosis. La expresión génica de IL-10 se encontró solamente para el grupo de influenza A H1N1 (pdm)09 (P=0.01). Resistin Like Beta se encontró con expresión disminuida solo para el grupo de influenza A H1N1 (pdm)09. Existe un aumento de células positivas para IL4 en todos los grupos, excepto neumonías bacterianas. No se encontró diferencia significativa de células positivas para IL-10 en los grupos de estudio. Existe un aumento de células positivas para IL-17 en influenza A H1N1p/2009, influenza A y neumonías bacterianas. IFN se encontró aumentado en los grupos de neumonía comparados con el control. Conclusiones: Ambos grupos de neumonías por influenza A se caracterizan por daño tisular y un exacerbado ambiente inflamatorio; solamente CD206 es capaz de diferenciar entre influenza A H1N1(pdm)09 e influenza estacional

Pneumonia Grave por Influenza B em Recém-Nascido

A infecção por vírus influenza B é rara no período neonatal com uma incidência desconhecida. Relata-se o caso de uma recém-nascida de termo, reinternada ao nono dia de vida por quadro de má perfusão periférica, gemido, dificuldade alimentar e dificuldade respiratória com necessidade de ventila ção mecânica, óxido nítrico inalado e surfactante. A radiografia de tórax no primeiro dia apresentava infiltrado intersticial ligeiro, difuso. Esteve sob ventilação invasiva durante 11 dias e oxigenoterapia 15 dias, tendo tido alta ao 20º dia, clinicamente bem. É fundamental pensar em infecção por vírus influenza B quando existe história de possível contágio, e em mães sem imunização anti-influenza. Não há terapêutica aprovada neste grupo etário, devendo ser tomadas medidas de suporte, de contenção e prevenção da disseminação da infecção.

La gripe A desde la teoría de la elección racional: propuestas para la toma de decisiones de políticas preventivas

This article is a reflection on the social uncertainty caused by Influenza A and on the consequences that it can have on decision making in health promotion policies. We use concepts and metaphors of the Rational Choice Theory, among them, the “ingratitude effect” or the “distrust effect”, as we analyse how these can become obstacles for the efficiency of prevention policies. Then, we focus on the information asymmetry of the principal-agent relationship, and we propose measures to diminish the “moral risk” that they cause. We finish by advancing some proposals for designing lines and strategies of action in health promotion policies.

Low-dose intradermal versus intramuscular trivalent inactivated seasonal influenza vaccine in lung transplant recipients.

BACKGROUND: In this study we compared the immunogenicity of influenza vaccine administered intradermally to the standard intramuscular vaccination in lung transplant recipients. METHODS: Patients were randomized to receive the trivalent inactivated seasonal 2008-9 influenza vaccine containing either 6 μg (intradermal) or 15 μg (intramuscular) of hemagglutinin per viral strain. Immunogenicity was assessed by measurement of geometric mean titer of antibodies using the hemagglutination-inhibition (HI) assay. Vaccine response was defined as a 4-fold or higher increase of antibody titers to at least one vaccine antigen. RESULTS: Eighty-five patients received either the intradermal (n = 41) or intramuscular (n = 44) vaccine. Vaccine response was seen in 6 of 41 patients (14.6%) in the intradermal vs 8 of 43 (18.6%) in the intramuscular group (p = 0.77). Seroprotection (HI ≥1:32) was 39% for H1N1, 83% for H3N2 and 29% for B strain in the intradermal group vs 28% for H1N1, 98% for H3N2 and 58% for B strain in the intramuscular group (p = 0.36 for H1N1, p = 0.02 for H3N2, p < 0.01 for B). Mild adverse events were seen in 44% of patients in the intradermal group and 34% in the intramuscular group (p = 0.38). CONCLUSIONS: Immunogenicity of the 2008-9 influenza vaccine given intradermally or intramuscularly was overall poor in lung transplant recipients. Novel strategies for influenza vaccination in this population are needed.

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.