Study on efficacy and regulation of inflammatory factors with oseltamivir phosphate by different time series of interventions in a murine model of influenza A H1N1 virus infection / 中国药理学通报

Aim To compare the effects of different time sequence interventions on virus infected mice by using oseltamivir (Tamiflu) as a "tool drug" in view of the current situation of the too early the administration time of antiviral in vivo experiment, so as to provide a basis for selecting a reasonable model intervention time point for antiviral drug research. Methods Balb/c mice were randomly divided into six groups. The virus infection model was established by intranasal infection with influenza virus (0.25 TCID50). Tamiflu-1 group and Tamiflu-2 group were administered orally on 1st and 4th day after exposure. The body mass, survival rate, organ index, viral load and inflammatory factor content were measured. Results Compared with the blank control group, the body weight of the mice in the model group decreased and the lung index increased significantly (P < 0.05). The expression levels of 13 inflammatory factors in model 2 group were significantly different ( P < 0.05). Compared with the model-1 group ,the lung index and spleen index of the Tamiflu-1 group decreased significantly (P < 0.05). Compared with the mode-2 group,the lung index in the Tamiflu-2 group was significantly lower (P <0.05) ,and the thy-mus index was significantly higher (P<0.05). The viral load was 0. 03 times that of the model-2 group. The expression levels of 13 inflammatory factors were significantly different (P < 0. 05). Conclusions The symptoms of the mice in Scheme 2 are more obvious and stable after exposure. After administration, the lung inflammation damage is alleviated. Considering the latency, drug intervention is in line with the drug indications when the model animals show symptoms. It will be more reasonable and accurate whether in the model evaluation or drug evaluation.

Effect of Chuankezhi Injection on Prevention and Treatment of H1N1 Influenza Virus in Mice / 中国实验方剂学杂志

Objective: To evaluate the effect of Chuankezhi injection on mouse model of pneumonia induced by influenza A (H1N1) FM1 strain. Method: ICR mice were randomly divided into normal group, model group, tamiflu control group (27.5 mg·kg-1·d-1) and Chuankezhi injection group (1.5 mL·kg-1·d-1). In the death protection experiment, mice were infected with 2×half lethal dose (LD50) of influenza virus FM1.The Chuankezhi injection was given once a day for 4 days. The number of death animal within 14 days was counted. The mortality and the death protection rate were calculated. In the treatment experiment, mice were infected with 0.8×LD50 of influenza virus, and the Chuankezhi injection was given once a day for 4 days. On the 5th day after the infection, the levels of interleukin-8 (IL-8) in lung, prostaglandin E2 (PGE2) and vasopressin (AVP) in brain were tested by enzyme-linked immunosorbent assay (ELISA). The viral load of influenza virus in lung was tested by Real-time PCR. In the pre-treatment experiment, mice were given Chuankezhi injection once a day for 5 days. 1 hour after the last treatment, mice were infected with 0.8×LD50 influenza virus. 4 days after the infection, the lung index, spleen index, thymus index, and viral load in lung tissue were calculated. Result: Compared with normal group, the IL-8, PGE2 content, lung index and viral load in the lung tissue of model group were significantly increased (P2, and the viral load of influenza(PPPPConclusion: Chuankezhi injection could effectively prevent the mouse model of pneumonia induced by influenza A (H1N1) virus. The mechanism might be related to the reduction of inflammation and inhibiting viral replication.

Immunologic mechanisms of Yinhua Pinggan granule and San-ao decoction against influenza virus / 中国中药杂志

This paper aimed to investigate the effect of Yinhua Pinggan granule and San-ao decoction on the immunologic mechanisms of influenza viral pneumonia mice , in order to study the activity of the combined administration of different formulas on influenza A/H1N1 virus. The model of pneumonia was established in mice through nasal dropping influenza virus, and then divided randomly into five groups: normal control group, influenza virus model group, oseltamivir control group, Yinhua Pinggan granule group, and San-ao decoction group. The animals were put to death at the 5th day after gavage administration with the corresponding drugs. The contents in mice serum of TNF-α, IL-6 and IFN-γ were respectively measured by ELISA. The mRNA expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in lung tissues were respectively detected by RT-PCR. The protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues were determined by immunohistochemical analysis, respectively. According to the results, Yinhua Pinggan granule and San-ao decoction could significantly decrease the levels of TNF-α and IL-6, increase the level of IFN-γ in mice serum of lung tissues, significantly reduce the gene expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in influenza virus-infected mice lung tissues, and significantly reduce the protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues. Furthermore, the regulatory effect of Yinhua Pinggan granule was superior to that of San-ao decoction. In conclusion, Yinhua Pingan granule and San-ao decoction have the therapeutic effect on pneumonia mice infected by H1N1 virus . The anti-influenza mechanisms of Yinhua Pinggan granule and San-ao decoction may be the results of interactions by regulating the immunologic function of influenza virus-infected mice and TLR3/7 signaling pathway with multiple links of the gene and protein expressions. Moreover, the combined administration of warm-natured and cold-natured Yinhua Pinggan granule with the effects of detoxification and exhalation has a better effect than the single administration of warm-natured San-ao decoction.

Effect and mechanism of Mahuang Tang against influenza A/H1N1 virus / 中国中药杂志

To study the effect and underlying mechanism of Mahuang Tang against influenza A virus ， the influenza virus-infected Madin-Darby canine kidney(MDCK) cells were used as the carrier in this study to detect the median tissue culture-infective dose(TCID₅₀) of influenza A virus strains(A/PR8/34) on MDCK cells with cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and anti-influenza virus biosynthesis were used as two different administration methods， and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to determine the antiviral effective rate(ER)， median efficacious concentration(EC₅₀) and therapeutic index(TI) of Mahuang Tang. The quantitative Real-time polymerase chain reaction(RT-PCR) was used to measure virus load and the mRNA expression levels of TLR4， TLR7， MyD88 and TRAF6 in MDCK cells at 24， 48 h after the treatment. The experiment results indicated that TCID₅₀ of A/PR8/34 for MDCK cells was 1×10-4.32/mL. The EC₅₀ values of two different treatment methods were 4.92，1.59 g·L⁻¹ respectively， the TI values were 12.53， 38.78 respectively， and when the concentration of Mahuang Tang was 5.00 g·L⁻¹， ER values were 50.21%， 98.41% respectively， showing that Mahuang Tang can block influenza virus into the host cells and significantly inhibit their biosynthesis. Meanwhile， as compared with the virus group， the virus load was significantly inhibited in Mahuang Tang groups， and Mahuang Tang high and middle doses had the significant effect on decreasing the mRNA expression of TLR4， TLR7，MyD88 and TRAF6 at 24， 48 h after the treatment. It can be demonstrated that the mechanisms of Mahuang Tang against influenza A virus are related to the inhibition of influenza virus replication and the mRNA expression of correlative genes in TLR4 and TLR7 signaling pathways.

Improvement Effects of Qingre Jiedu Soft Capsule on Mice Infected by Influenza A H1N1 Virus / 中国药房

OBJECTIVE:To observe the antiviral effects of Qingre jiedu soft capsule(ADSC)against influenza A H1N1 virus in vivo,and to provide a experimental support for clinical therapy of influenza A H1N1 virus. METHODS:BALB/c mice were ran-domly divided into normal control group,model control group,positive drug high-dose,medium-dose and low-dose groups [oselta-mivir phosphate capsule,0.04,0.02,0.01 g/(kg·d)] and ADSC high-dose,medium-dose and low-dose groups [1.5,0.75,0.375 g/(kg·d)].Except for normal control group,others groups were given influenza A H1N1 virus with titer 1.6×10-5.2 via nasal cavity to induce poisoned mice model;6-8 h after modeling,they were given relevant medicine intragastrically,once a day,for 5 days. After medication,the change of body weight within 7 d were observed in mice;the mortality and death prevention rate within 15 d,mean survival days(MSDs)were calculated in mice.Other mice were selected and grouped,and they were given same drugs as above. 8 h after last medication,lung index and inhibition rate of lung index were determined in mice.RESULTS:In model control group,the body weight of mice decreased significantly since 5th day,and mice death was beginning to occur since 8th day(mortal-ity of 85.7% within 15 d);the lung index was increased significantly compared to normal control group (P<0.01). Both ADSC and oseltamivir phosphate capsule could slow down the decrease of body weight in mice,decreased the mortality and lung index of mice,and prolonged MSDs;the MSDs of mice in ADSC high-dose,positive drug high-dose and medium-dose groups were signifi-cantly higher than model control group(P<0.05),and lung index was significantly lower than model control group except that of ADSC low-dose group(P<0.05). CONCLUSIONS:ADSC has certain antiviral effect against influenza A H1N1 virus in vivo.

Inhibitory effect of geniposide against influenza A/H1N1 virus / 中国药科大学学报

@#The aim of this study was to explore the protective effects of geniposide against Influenza A(H1N1)pdm09 virus in vitro and in vivo. In vitro, geniposide was administered as a precaution drug, a direct deactivation drug or a treatment drug at different doses. Peramivir was applied as a positive control. The quantitative colorimetric MTT assay was applied to test both the cytotoxicity of geniposide on Madin-Darby Canine Kidney(MDCK)cells and the cytopathogenic effect(CPE)of geniposide on MDCK cells infected by influenza A(H1N1)virus. The viral inhibitory rate of geniposide on NT0901 was also calculated. In vivo, we presented a mouse model of influenza A(H1N1)pdm09 virus infection. Geniposide(5, 10, or 20 mg/kg)or peramivir(30mg/kg)were used as treatment procedures. Lung index and the survival rate were calculated to evaluate the therapeutic effects of geniposide or peramivir on NT0901-infected mice. Haematoxylin and eosin(H&E)stain was used to access the pathological alterations of lung tissues. The study in vitro demonstrated that the TD50(median toxic dose)of geniposide was higher than 1 040 μmol/L. Besides, the EC50(concentration for 50% of maximal effect)of geniposide administered for precaution, direct deactivation and therapy were 91. 90, 96. 25, 87. 68 μmol/L, respectively. These results suggested that geniposide could block the damage of NT0901 on MDCK cells in a dose-dependent manner. The results in vivo showed that geniposide could significantly alleviate the lung index elevation and inflammatory responses in lung tissues induced by NT0901, reduce the mortality of infected mice and extend their survival time. In conclusion, our investigation indicates that geniposide is highly effective in inhibiting cytopathogenic effect and acute lung injury caused by influenza A(H1N1)pdm09 virus. Geniposide may be a potential therapeutic agent for the suppression of influenza virus.

Construction of microRNA Let-7b-mediated recombinant influenza A (H1N1) virus with mutated PB1 / 医学研究生学报

Objective Vaccination is a most effective method for the prevention of severe diseases caused by pandemic influenza and microRNA ( miRNA) mediated gene silencing has offered a novel approach to the construction of new vaccines.Our study aimed to construct a recombinant influenza A ( H1 N1 ) virus with the PB1 gene that carries the target fragment of miRNA Let-7b. Methods After comparing the sequence of the A/Nanjing/108/2009 H1N1 viral fragments with that of Let-7b, we selected PB1 as the optimal gene sequence, inserted the Let-7b binding target gene into PB1, ligated the modified fragments with pDP 2000, and named the recombinant plasmids pDP-mu-PB1 and pDP-sclb-PB1, respectively.We co-transfected the MDCK and 293T cells with the recombinant and other seven plasmids and injected the supernatant into the allantoic cavity of the chickenembryo for virus propagation, followed by detection of the virus by hemagglutination ( HA) assay and measurement of the viral titer by TCID50 .We amplified the viral cRNA by RT-PCR and identified the viruses by agarose gel electrophoresis and nucleotide sequence analysis. Results PB1 was the optimal sequence ( 83 bp -107bp) for the attenuation of viruses.The HA-titers of miRT-H1N1 and scbl-H1N1 were 1∶32 and 1∶64, and their viral loads were 4.68 ×105 and 7.94 ×104 TCID50/mL, respectively.Nucleotide sequence analysis showed the expected fragment in the rescued virus. Conclusion A recombinant strain vaccine was successfully constructed, which has laid the foundation for fur-ther assessment of virulence.

Influenza due to a Novel Influenza A (H1N1)/09 Virus.

The influenza A(H1N1) virus originating in Mexico has shaken the political, economical and health system of the whole world. It produces flu like symptoms in human body and is responsible for producing high morbidity than mortality.

Importancia de las imágenes y el diagnóstico etiológico en el paciente inmunocomprometido con afección del sistema nervioso central: Segunda parte / Importance of images and etiological diagnosis in the immunocompromised patient with central nervous system envolvement: Part II

We present the case of a 12-year-old boy with acute lymphocytic leukemia who developed pneumonia and multiple brain infarcts compatible with acute necrotic encephalitis. The infectious disease screening tests revealed influenza A H1N1 virus, Staphylococcus aureus in broncho alveolar lavage, E. coli and galactomannan antigen in blood. CNS influenza associated complications are reviewed. This case highlights the importance of magnetic resonance imaging as a diagnostic tool in the assessment of immunocompromised patients with CNS compromise and the value of brain biopsy in the final identification of an infectious disease etiology.

Escolar de 12 años de edad, con Leucemia Linfocítica Aguda en tratamiento que desarrolla una bronconeumonía bilateral, infartos cerebrales compatibles con encefalitis necrosante aguda. El estudio infectológico demostró más de una causas infecciosa que pudiera explicar su evolución destacando influenza A H1N1, Staphylococcus aureus meticilina sensible en lavado bronco alveolar, E. coli y galactomanano en sangre. Se revisa el compromiso del SNC por influenza A H1N1. Se destaca la importancia del uso de resonancia magnética nuclear al evaluar pacientes inmunocomprometidos con complicaciones neurológicas y el aporte de una biopsia cerebral en aclarar la etiología de este compromiso.

Close Relationship between the 2009 H1N1 Virus and South Dakota AIV Strains / 中国病毒学·英文版

Although previous publications suggest the 2009 pandemic influenza A(H1N1)virus was reassorted from swine viruses of North America and Eurasia, the immediate ancestry still remains elusive due to the big evolutionary distance between the 2009 H1N1 virus and the previously isolated strains. Since the unveiling of the2009 H1N1 influenza, great deal of interest has been drawn to influenza, consequently a large number of influenza virus sequences have been deposited into the public sequence databases. Blast analysis demonstrated that the recently submitted 2007 South Dakota avian influenza virus strains and other North American avian strains contained genetic segments very closely related to the 2009 H1N1 virus, which suggests these avian influenza viruses are very close relatives of the 2009 H1N1 virus. Phylogenetic analyses also indicate that the2009 H1N1 viruses are associated with both avian and swine influenza viruses circulating in North America. Since the migrating wild birds are preferable to pigs as the carrier to spread the influenza viruses across vast distances, it is very likely that birds played an important role in the inter-continental evolution of the 2009 H1N1virus. It is essential to understand the evolutionary route of the emerging influenza virus in order to find a way to prevent further emerging cases. This study suggests the close relationship between 2009 pandemic virus and the North America avian viruses and underscores enhanced surveillance of influenza in birds for understanding the evolution of the 2009 pandemic influenza.

Impacto de la obesidad en pacientes con neumonía grave por virus influenza A/H1N1: estudio multicéntrico chileno / Impact of obesity with severe pneumonia by influenza A/H1N1 virus: a Chilean multicenter study

En la primera pandemia del siglo XXI por virus influenza A/H1N1, una importante proporción de paciente que desarrollaron neumonía y Falla Respiratoria Aguda (FRA) eran obesos. La obesidad ha sido propuesta como un factor de riesgo que aumenta la morbimortalidad; sin embargo, hay controversia al respecto. Objetivo: evaluar el impacto de la obesidad en complicaciones, estadía y/o mortalidad en pacientes adultos graves por virus influenza A/H1N1. Estudio observacional y multicéntrico realizado en 17 UCIs de Chile durante el periodo mayo-agosto 2009. Fueron incluidos en el estudio solo paciente con infección por virus Influenza A/H1N1 confirmada o probable. Los paciente obesos (IMC>30) fueron comparados con pacientes no obesos. Resultados: De un total de 136 pacientes incluidos en el estudio, 64 (47 por ciento) fueron obesos y de estos 13 obesos mórbidos (BMI >40). Los pacientes obesos tienen mayor frecuencia de: comorbilidades, ventilación mecánica y complicaciones. La estadía en UCI y en el hospital fue más prolongada en pacientes obesos (18,1+/-15 vs. 10,9+/-10,2, p=0,002 y 27,2+/-24,7 vs17,7 +/- 14,6, p=0,01 respectivamente). La mortalidad fue mayor en pacientes obesos (36 por ciento vs. 19,4 por ciento; OR 2,32; IC95 por ciento 1,07-5,05, p=0.035). El estudio de regresión logística encuentra que la FOM es un factor pronóstico independiente de mortalidad en pacientes obesos. Conclusiones: Los pacientes obesos con neumonía grave por virus influenza A/H1N1 tienen una mayor morbi-mortalidad y prolongación de su estadía en UCI y en el hospital. El desarrollo de FOM en pacientes obesos es un factor de mal pronóstico.

In the first pandemic of the 21st century due to influenza A/H1N1 virus, a significant proportion of patients who developed pneumonia and acute respiratory failure (ARF) were obese. Obesity has been proposed as a risk factor that increases morbidity and mortality, however, there is controversy about it. Objective: To determine the impact of obesity on complications, stay and / or mortality in adult patients with severe influenza A/H1N1 virus. Multicenter observational study conducted in 17 ICUs of Chile during the period May to August 2009. Were included only patients with influenza A/H1N1 virus infection confirmed or probable. Obese patients (BMI> 30) were compared with non obese patients. The results: Of a total of 136 patients included in the study, 64 (47 percent) were obese and of these 13 morbidly obese (BMI> 40). Obese patients have a higher frequency of: comorbidities, mechanical ventilation and complications. The stay in ICU and hospital was longer in obese patients (18.1 +/- 15 vs. 10.9 +/- 10.2, p = 0.002 and 27.2 +/- 24.7 vs17, 7 +/- 14.6, p = 0.01 respectively). Mortality was higher in obese patients (36 percent vs. 19.4 percent, OR 2.32, 95 percent CI 1.07 to 5.05, p = 0,035). The logistic regression analysis found that the MOF is an independent predictor of mortality in obese patients. Conclusions: Obese patients with severe pneumonia due to the influenza A/H1N1 virus have a high morbidity and mortality and prolonged stay in ICU and hospital. MOF development in obese patients is a poor prognostic factor.

Uso de oseltamivir durante la pandemia de gripe a (H1N1): análisis de las reacciones adversas reportadas al sistema nacional de farmacovigilancia de ANMAT / Use of oseltamivir during influenza A (H1N1) pandemic: analysis of adverse reactions reported to the ANMAT national pharmacovigilance system

INTRODUCCIÓN: Oseltamivir es un medicamento antiviral usado para profilaxis y tratamiento de la gripe. Sus efectos adversos son conocidos a través de los ensayos clínicos y por la experiencia adquirida en la última epidemia de gripe aviar. Dentro de las reacciones más graves se han reportado casos de anafilaxia, eventos cutáneos y manifestaciones psiquiátricas como alucinaciones, delirium e ideación suicida. OBJETIVO: en julio de 2009, el departamento de Farmacovigilancia de ANMAT lanzó el Plan Nacional de Farmacovigilancia para Drogas Antivirales con el objetivo de recolectar mayor información de seguridad de estos medicamentos durante su uso masivo, con especial atención a las manifestaciones cutáneas, hepáticas y neuropsiquiátricas. MÉTODOS: se analizaron todas las notificaciones recibidas durante junio - noviembre de 2009. Los datos considerados fueron: sexo, edad, notificador, modalidad terapéutica, severidad, clasificación delefecto adverso principal e imputabilidad asignada. RESULTADOS: serecibieron 179 notificaciones, la mayoría asociadas a la modalidad tratamiento. Las reacciones adversas más reportadas involucraron al sistema gastrointestinal, siendo en su mayoría leves y autolimitadas. Con respecto a los casos psiquiátricos reportados, su severidad y variabilidad obliga a prestar especial atención a estas notificaciones. Se reportaron además casos de prolongación del Intervalo QTc, evento no descripto previamente en la literatura. CONCLUSIÓN: Dada la escasa experiencia en la Argentina y el estrecho perfil de seguridad de este fármaco, es indispensable continuar con una vigilancia activa del mismo.

INTRODUCTION: Oseltamivir is an antiviral drug used for profhylaxis and treatment of influenza. Adverse effects are known through clinical trials and in large part by the experience gained after its use in the last outbreak of avian influenza in Asia. Among the most serious reactions are reported cases of anaphylaxis, cutaneous events and psychiatric symptoms such as hallucinations, delirium and suicidal behaviour. OB JECTIVE: in line with various international regulatory authori ties, during July 2009, the ANMAT through Pharmacovigilance Department launched the National Pharmacovigilance Plan for antiviral drugs used for prophylaxis and treatment of the pandemic H1N1 influenza virus. The plan called for reporting any signs or symptoms, paying particular attention to the cutaneous, hepatic and neuropsychiatric symptoms. METHOD:we analyzed all reports received during June to November 2009. The data considered were: sex, age, notifier, therapeutic modality, severity, classification of main side effect and imputation assigned. RESULTS: 179 notifications were received, most associated with treatment modality. As can be seen world wide, in Argentina, the great majority of reported adverse reactions involve the gastrointestinal system, being mostly mild and self-limiting. Given the variability and severity of psychiatric cases reported it is very important to pay close attention to these reports. Reported cases include the QTc interval prolongation, an event not previously described in the literature. CONCLUSIONS: it is essential to continu e with proactive monitoring of this drug because of the limited current experience and the benefits/ risks ratio of the safety profile of this drug.

Análisis descriptivo de los casos de gripe A (H1N1) notificados durante la pandemia de 2009 en la Región Sanitaria V de la Provincia de Buenos Aires, Argentina / Descriptive analysis of cases of Influenza A (H1N1) reported durig the pandemic of 2009 in the Health Region V of the province of Buenos Aires, Argentina

A partir de la transmisión sostenida del virus de Gripe A(H1N1) en distintos países, la Organización Mundial de la Salud declaró el comienzo de la primera pandemia de influenza del siglo XXI el 11de junio de 2009. En Argentina, la región sanitaria V de la provincia de Buenos Aires fue una de las primeras afectadas en todo el país. OBJETIVO:realizar un análisis descriptivo de las notificaciones registradas de los casos de Gripe A (H1N1) en dicha región hasta el 20 de septiembre de 2009. MÉTODO: se trabajó con fuentes secundarias. La confirmación de casos (PCR en tiempo real) fue realizada en instituciones autorizadas. Variables consideradas: casos sospechosos, confirmados y fallecidos, sexo, edad, municipios, antecedentes epidemiológicos, embarazadas, fecha de inicio de síntomas y circulación viral por semana epidemiológica. RESULTADOS: se registraron 1.332 notificaciones de casos sospechosos y 949 confirmados. El mayor número de confirmados se registró en los municipios de Gral. San Martín (94), San Isidro (90), Pilar (85) y Vicente López (80). Las semanas epidemiológicas 23, 24 y 25 registraron la mayor cantidad de casos confirmados. Los grupos de edad que más confirmados aportaron fueron: de 5 a 9 años (121), 1 a 4 (89) y 10 a 14 (75) (cuya mediana de edad fue de 30 años). Se registraron 64 casos confirmados fallecidos. La tasa más alta de mortalidad específica por grupo de edad correspondió a menores de un año. Se registraron 9 casos confirmados en embarazadas y una puérpera, 5 de ellas fallecieron. CONCLUSIÓN: todos los municipios presentaron casos confirmados y 11 reportaron fallecidos. El pico de la epidemia se adelantó en una semana al registrado a nivel nacional y la mediana de edad en fallecidos fue más baja que la de todo el país. El análisis de mortalidad mostró un mayor riesgo para varones, embarazadas y menores de un año.

From the sustained transmission of influenza virus A (H1N1) in different countries, the World Health Organization declared the beginning of the first influenza pandemic of the twenty first century on June 11, 2009. In Argentina, the Health Region V of the Province of Buenos Aires was one of the first affected across the country. OBJECTIVE: to conduct a descriptive analysis of notifications of cases of Influenza A (H1N1) in that region until September 20, 2009. METHODS: we worked with secondary sources. The confirmation of cases (real-time PCR) was carried out in authorized institutions. Variables considered: suspected cases, confirmed and diseased, sex, age, municipalities, epidemiological history, pregnant, date of on set of symptoms and viral movement by epidemiological week. RESULTS: there were 1.332 notifications of suspected cases and 949 confirmed. The highest number of confirmed cases was in the municipalities of Gral. San Martin (94), San Isidro (90),Pilar (85) and Vicente López (80). The epidemiological weeks 23,24 and 25 showed the highest number of confirmed cases. Giventhe age group, which contributed more confirmed cases was that of 5-9 years (121), followed by 1-4 (89) and 10-14 (75). The median age was 30 years. There were 64 confirmed cases dead. The high estrate of cause-specific mortality by age group accounted for less than one year. There were nine conf irmed cases in pregnant and puerperal women, five of them died. CONCLUSION: all municipalities had confirmed cases and 11 confirmed deaths reported. The peak of the epidemic one week a head of the national and the medianage was lower than the registered for the rest of the country. The analysis of mortality showed a higher risk for men, pregnant women and children under one year.

Evaluation of the Efficacies of Rapid Antigen Test, Multiplex PCR, and Real-time PCR for the Detection of a Novel Influenza A (H1N1) Virus / 대한진단검사의학회지

BACKGROUND: In April 2009, a novel influenza A (H1N1) virus was detected in the US, and at the time of conducting this study, H1N1 infection had reached pandemic proportions. In Korea, rapid antigen tests and PCR assays have been developed to detect the H1N1 virus. We evaluated the efficacies of rapid antigen test, multiplex PCR, and real-time PCR for detecting the H1N1 virus. METHODS: From August to September 2009, we tested 734 samples obtained from nasopharyngeal swab or nasal swab using rapid antigen test (SD Influenza Antigen, Standard Diagnostics, Inc., Korea) and multiplex PCR (Seeplex FluA ACE Subtyping, Seegene, Korea). We also tested 224 samples using the AdvanSure real-time PCR (LG Life Sciences, Korea) to compare the results obtained using real-time PCR with those obtained using multiplex PCR. Furthermore, 99 samples were tested using the AdvanSure real-time PCR and the AccuPower real-time PCR (Bioneer, Korea). RESULTS: In comparison with the results of multiplex PCR, the sensitivity and specificity of the rapid antigen test were 48.0% and 99.8%, respectively. The concordance rate for multiplex PCR and the AdvanSure real-time PCR was 99.6% (kappa=0.991, P=0.000), and that for the AdvanSure real-time PCR and the AccuPower real-time PCR was 97.0% (kappa=0.936, P=0.000). CONCLUSIONS: The rapid antigen test is significantly less sensitive than PCR assay; therefore, it is not useful for H1N1 detection; however multiplex PCR, the AdvanSure real-time PCR, and the Accu-Power real-time PCR can be useful for H1N1 detection.

Reduction of Influenza A (H1N1) Virus Through a Leukoreduction Filter / 대한수혈학회지

BACKGROUND: Leukoreduction can reduce the risk of HLA alloimmunization, recurrent febrile nonhemolytic transfusion reactions, and several transfusion-transmitted infectious diseases, including cytomegalovirus infection. Transmission of the new influenza A (H1N1) virus through transfusion may be a concern. We evaluated the effect of filtration with a leukoreduction filter on H1N1 genomes. METHODS: To evaluate the effect of filtration by a leukoreduction filter on H1N1 genomes, we analyzed pre- and post-filtered samples from nasopharyngeal swabs and 10 positive plasma samples using real time RT-PCR. RESULTS: The 10 samples (nasopharyngeal swabs and plasma) contained H1N1 RNA, and filtration with a leukoreduction filter reduced these levels (threshold cycle values from 31.42+/-2.06 to 38.84+/-1.47 in nasopharyngeal swabs, from 35.63+/-2.19 to 39.38+/-2.65 in plasma samples). CONCLUSION: Filtration with a leukoreduction filter can reduce H1N1 genome levels, but may not be completely sufficient for total eradication of this pathogen.

Genetic Evolution of Neuraminidase Gene of Influenza A/H1N1 Virus / 中山大学学报(医学科学版)

[Objective]This study was designed to investigate the genetic evolution of the neuraminidase(NA)gene of seasonal A/H1N1 and 2009 novel A/H1N1 inflilenza virus,and discuss the genetic variation of influenza A virus.[Methods]The virus strains were separately isolated from the clinical samples collected in 2006 and 2009,and then identified as seasonal A/H1N1 and novel A/H1N1.The full length of the NA gene of these strains was amplified by RT-PCR.Then the genetic evolution and mutations of important functional sites were analyzed.[Results]The homology of NA gene between the 2009 novel A/H1N1 isolates and 2006 seasonal A/H1N1 isolates was low(77.9%～78.8%),so was the homology of NA gene between the 2009 novel A/H1N1 isolates and representative strains of different periods and 1979-2001 WHO recommended vaccine strains(78.1%～79.3%).But compared with the WHO recommended vaccine strains of 2009 novel A/H1N1,the homology reached more than 99%.The genetic evolution analysis revealed that NA gene of 2009 novel A/H1N1 had the closest genetic relationship with the swine influenza A virus(A/swine/Belgium/1/1983)from Eurasian Iineage,and some of the antigenic sites and neuraminidase active sites of NA gene of seasonal A/H1N1 were mutated after 2005.[Conclusion]The NA gene of 2009 novel A/H1N1 may originate from Eurasian Iineage of swine influenza virus.The variation of NA gene of seasonal A/H1N1 has occurred in a certain degree.Hence,it is very necessary to continuously monitor the variant of influenza A virus.

Swine Influenza A (H1N1) Infection in Renal Transplant Recipients / 대한이식학회지

BACKGROUND: Novel H1N1 influenza A was a pandemic disease in 2009. However, limited data are available on renal transplant recipients undergoing long-term immunosuppression who contracted novel H1N1 influenza A. METHODS: We analyzed 2,345 patients who had been tested with H1N1 swab real-time reverse transcriptase-polymerase chain reaction test (rRT-PCR) between May 2009 and February 2010. Of them, 30 were kidney recipients who underwent kidney transplantation between April 1979 and 2, May 2009 before the first diagnosis of H1N1 influenza A in Korea. The clinical characteristics, treatment, and outcome of renal transplant recipients with confirmed H1N1 influenza were reviewed retrospectively. RESULTS: A total of 1,543 (66.7%) general patients were swine influenza A confirmed. Of the 30 transplant patients, 19 (63.3%) were confirmed with swine influenza A. The mean age of the general patients at diagnosis of swine influenza A was younger than that of renal recipients (16.5+/-16.1 vs. 39.7+/-11.5 years, P<0.0001). More patients died in the transplant group than in the general patient group even after oseltamivir (Tamiflu) treatment. When comparing the cured group with the dead group of transplant patients, the dead group had a longer duration between symptom manifestation and the beginning of treatment than the cured group (7 [5-7] vs. 2 [1-14] days, P=0.007). The dead group presented more complications such as pneumonia (P=0.009). CONCLUSIONS: H1N1 influenza A can cause severe illness in kidney transplant recipients. We suggest that early diagnosis and treatment with an antiviral agent produces good results in kidney transplant recipients as in the general population.

Constrictive Pericarditis Accompanied by Swine-Origin Influenza A (H1N1) Infection

Swine-origin influenza A (H1N1) is caused by a new strain of the influenza virus. The disease has spread rapidly and was declared a pandemic in April, 2009. So far, however, there is a scarcity of information regarding the complications of swine influenza. A report of the disease in the winter of 2009 in the Southern Hemisphere found that the most common manifestations of influenza A virus infection are upper respiratory tract infection and pneumonia. Although there may be an association between fulminant myocarditis and Swine influenza, cardiovascular complications resulting from swine Influenza A infection are exceedingly rare. We report a case of acute constrictive pericarditis in a healthy subject infected by the swine-origin influenza A (H1N1) virus.

Manifestações da infecção pelo novo vírus influenza A (H1N1) na tomografia computadorizada de tórax / Manifestations of infection by the novel influenza A (H1N1) virus at chest computed tomography

OBJETIVO: Descrever as alterações na tomografia computadorizada de tórax de casos comprovados de infecção pelo novo vírus influenza A (H1N1). MATERIAIS E MÉTODOS: Três observadores avaliaram, em consenso, nove tomografias computadorizadas de pacientes com infecção pelo vírus influenza A (H1N1) comprovada laboratorialmente. A idade dos pacientes variou de 14 a 64 anos (média de 40 anos), sendo cinco do sexo masculino e quatro do sexo feminino. Quatro pacientes eram previamente hígidos, quatro eram transplantados renais e uma era gestante à época do diagnóstico. Foram avaliadas a presença, a extensão e a distribuição de: a) opacidades em vidro fosco; b) nódulos centrolobulares; c) consolidações; d) espessamento de septos interlobulares; e) derrame pleural; f) linfonodomegalias. RESULTADOS: As alterações mais frequentemente encontradas foram opacidades em vidro fosco, nódulos centrolobulares e consolidações, presentes em nove (100 por cento), cinco (55 por cento) e quatro (44 por cento) dos casos, respectivamente. Derrames pleurais e linfonodomegalias foram menos comuns, ocorrendo em apenas dois (22 por cento) dos casos estudados. CONCLUSÃO: Os achados mais comuns nos casos de infecção pelo novo vírus influenza A (H1N1) foram opacidades em vidro fosco, nódulos centrolobulares e consolidações. Estas alterações não são típicas ou únicas a este agente, podendo ocorrer também em outras infecções virais ou bacterianas.

OBJECTIVE: The objective of this study was to describe chest computed tomography findings in confirmed cases of infection by the novel influenza A (H1N1) virus. MATERIALS AND METHODS: Computed tomography studies of nine patients with laboratory-confirmed infection by the novel influenza A (H1N1) virus were consensually evaluated by three observers. The sample of the present study included five male and four female patients with ages ranging from 14 to 64 years (mean, 40 years). Four of the patients were previously healthy, four were kidney transplant recipients and one was pregnant at the time of diagnosis. Presence, extent and distribution of the following findings were evaluated: a) ground-glass opacities; b) centrilobular nodules; c) consolidation; d) interlobular septa thickening; e) pleural effusion; f) lymphadenopathy. RESULTS: The most frequent findings were ground-glass opacities, centrilobular nodules and consolidations, present in nine (100 percent), five (55 percent) and four (44 percent) of cases, respectively. Pleural effusions and lymphadenopathy were less common findings, occurring in only two (22 percent) of the cases. CONCLUSION: Ground-glass opacities, centrilobular nodules and consolidation were the most frequent findings in cases of infection by the novel influenza A (H1N1) virus. These changes are not typical or unique to this agent and may also occur in other viral or bacterial infections.

Successful treatment of a patient with severe H1N1 Flu anti multiple organ dysfunction syndrome / 中华急诊医学杂志

Objective To investigate the causes of severe H1N1 Flu with multiple organ dysfunction, and measures to reduce mortality. Method The data of the patient, who was diagnosed as severe H1N1 Flu and mul-tiple organ dysfunction syndrome in First People's Hospital Affiliated to Shanghai Jiaotong University in September 2009, were retrospectively analyzed. The patient was male, 35 year-old, obese, high fever, sore throat, cough, progressive dyspnea, severe hypoxemia and hypotension. Effective measures were carried out, including protective lung ventilation, recruitment maneuver, vasopressor support, limited fluid resuscitation, appropriate corticosteroid, anfiviral plasma, anticoagulafion and antiviral medicine (Oseltamivir)in early stage and full dose. Results After one-month intensive care, clinical symptoms was improved obviously, oxygen pressure reached 74 mmHg without oxygen supply, CT scan showed diffused interstitial ehange. Neuromyopathy developed at approximately 3 weeks after the onset of H1N1. Conclusions H1N1 Flu can develop in healthy adults, and obesity is one of the inde-pendent risk factors. Effective measures should be taken as soon as possible to reduce the mortality.