Influenza A H1N1pdm 2009 Virus in Paraguay: Nucleotide Point Mutations in Hemagglutinin and Neuraminidase Genes are not Associated with Drug Resistance.

Influenza virus is associated with upper respiratory tract infections. The fourth influenza pandemic was declared in 2009. The aim of this study was to determine the genetic variability of the 2009 H1N1 pandemic virus circulating in Paraguay. Nasal swabs were collected from 181 patients with flu symptoms managed at the Hospital of the Medical School in Asunción, Paraguay, between August and October 2009. Virus detection was carried out by real-time reverse transcription-polymerase chain reaction, followed by sequencing of the hemagglutinin and neuraminidase genes, and phylogenetic analysis. H1N1pdm09 was detected in 14.9% (27/181) of the suspected cases. Analysis of 13 samples showed that these viruses the clustered in a single genetic group. Neither the mutation related to exacerbation of disease (D239G in hemagglutinin) nor that related to antiviral resistance (H275Y in neuraminidase), both detected in neighboring countries, were found. This genetic analysis of H1N1pdm09 will help to understand the spread of the disease.

Oseltamivir-resistant influenza A(H1N1) pdm09 virus: first reported case from India

Background: Recent studies on antiviral susceptibiliy from South-East Asia,Europe and the United States have shown sporadic neuraminidase inhibitor (NAI)resistance in A(H1N1)pdm09 viruses. We undertook a study to evaluate NAIresistance in these viruses isolated in India.Methods: Pandemic influenza viruses, isolated from 2009 to 2013, along withclincal samples were genetically analysed for known resistance markers in theneuraminidase (NA) gene. Clinical samples (n=1524) were tested for H275Y (N1numbering; H274Y in N2 numbering) mutation by real time reverse transcriptasePCR (rRT-PCR). One hundred and ten randomly selected resistant and sensitiveviruses were analysed by phenotypic assay.Results: All but one of the 2013 A(H1N1)pdm09 isolates were sensitive tooseltamivir. Genetic analysis of this isolate as well as the original clinical materialshowed that the presence of H275Y mutation was responsible for reducedsusceptibility to oseltamivir in the patient. This was confirmed by phenotypic assay.Conclusion: The emergence of a pandemic influenza strain resistant to oseltamiviremphasizes the need for monitoring antiviral resistance as part of the NationalInfluenza Programme in India

Pandemic influenza A (H1N1) 2009: epidemiological analysis of cases in a tropical/semi-arid region of Brazil

Introduction The year 2009 marked the beginning of a pandemic caused by a new variant of influenza A (H1N1). After spreading through North America, the pandemic influenza virus (H1N1) 2009 spread rapidly throughout the world. The aim of this study was to describe the clinical and epidemiological characteristics of cases of pandemic influenza in a tropical/semi-arid region of Brazil. Methods A retrospective study analyzed all suspected cases of pandemic influenza (H1N1) 2009 reported in the Ceará State through the National Information System for Notifiable Diseases during the pandemic period between 28 April, 2009 and November 25, 2010. Results A total of 616 suspected cases were notified, 58 (9.4%) in the containment phase and 558 (90.6%) in the mitigation phase. Most cases were of affected young people resident in the City of Fortaleza, the largest urban center in the State of Ceará. The most frequent symptoms presented by the cases with confirmed infection were fever, cough, myalgia, arthralgia, and nasal congestion. Mortality rate was 0.0009/1,000 inhabitants and lethality was 5.6%. Deaths were observed only in the mitigation phase. Mortality rates were similar for both sexes but were higher in the age group under 5 years. Conclusions The study suggests that the influenza A (H1N1) pandemic in this tropical/semi-arid region had a lower magnitude when compared to states in the Southern and Southeastern regions of Brazil. .

Genome Stability of Pandemic Influenza A (H1N1) 2009 Based on Analysis of Hemagglutinin and Neuraminidase Genes.

Influenza A virus (H1N1), which arose in 2009, constituted the fourth pandemic after the cases of 1918, 1957, and 1968. This new variant was formed by a triple reassortment, with genomic segments from swine, avian, and human influenza origins. The objective of this study was to analyze sequences of hemagglutinin (n=2038) and neuraminidase (n=1273) genes, in order to assess the extent of diversity among circulating 2009-2010 strains, estimate if these genes evolved through positive, negative, or neutral selection models of evolution during the pandemic phase, and analyze the worldwide percentage of detection of important amino acid mutations that could enhance the viral performance, such as transmissibility or resistance to drugs. A continuous surveillance by public health authorities will be critical to monitor the appearance of new influenza variants, especially in animal reservoirs such as swine and birds, in order to prevent the potential animal-human transmission of viruses with pandemic potential.

Low Level of Cross-Reactive Antibodies to Pandemic Influenza (H1N1) 2009 Virus in Humans in Pre-Pandemic Period in Maharashtra, India.

In India, the first outbreak of pandemic influenza (H1N1) 2009 (H1N1pdm) was reported from Panchgani, Maharashtra, in June 2009. Studies from several countries have revealed different levels of pre-existing immunity to H1N1pdm 2009 in various age groups. This study was undertaken using age-stratified pre-pandemic human sera to understand baseline cross-reactivity of antibodies against H1N1pdm. Using cut off antibody titers 20 and 40, overall cross-reactivity was 2.1 and 0.9% respectively by microneutralization assay; 1.2% and 0.7% by haemagglutination inhibition assay, respectively. Results showed higher baseline antibodies and cross-reactive antibodies in the 0-19 age group whereas the elderly age group (≥60) showed no cross-reactivity to H1N1pdm. The higher baseline and cross-reactive antibodies in 0-19 years age group could be because of higher positivity to seasonal H1N1 in that age group. Overall, low level of cross-reactive antibodies to H1N1pdm virus were found in humans in pre-pandemic period in Maharashtra, India.

A Case of Oseltamivir-Resistant Pandemic Influenza (H1N1 2009) in a Patient with Acute Myeloid Leukemia / 감염과화학요법

Oseltamivir is the drug of choice for patients with pandemic influenza (H1N1 2009). However, sporadic cases of oseltamivir resistance have been described worldwide. Up to March 2010, a total of 11 strains (2.2% of tested isolates) of oseltamivir-resistant pandemic influenza (H1N1 2009) have been discovered in South Korea. We report a case of 46-year-old man with acute myeloid leukemia in whom an oseltamivir-resistant pandemic (H1N1) 2009 virus was isolated. Despite high dose oseltamivir therapy for 10 days he had persistent symptoms and showed positive results in repeated real-time RT-PCR for pandemic influenza (H1N1 2009) virus from nasopharyngeal specimen. The patient improved eventually after oseltamivir was replaced by zanamivir inhalation.

Early Extracorporeal Membrane Oxygenation in a Patient with Pandemic Influenza (H1N1 2009) and Acute Respiratory Distress Syndrome / 감염과화학요법

Despite advanced technologies in intensive care, pandemic influenza (H1N1 2009) can rapidly progress to acute respiratory distress syndrome (ARDS) and cause death in a small subset of patients. Extracorporeal membrane oxygenation (ECMO) is expected to provide adequate gas exchange, to reduce ventilator-induced lung injury and, eventually, to improve outcome in these patients. A previously healthy, young female received mechanically ventilatory support because of rapidly progressive respiratory failure caused by 2009 H1N1 influenza. As she failed to respond to high ventilatory support, ECMO was instituted at 6 hours after admission. We describe detailed course of case and literature review on ECMO, helping physicians make a decision to initiate ECMO in patients with influenza-related ARDS.

A Fetal Case of Pandemic Influenza (H1N1 2009) by the Aggravated Heart Faiure / 감염과화학요법

On April, 2009, pandemic influenza (H1N1 2009) emerged in the United States at first. Clinical outcomes of this infection are reported as ranging from self-limited illness to respiratory failure or death. There were more than 250 deaths due to pandemic influenza until March 2010. Influenza-related deaths occurred in the elderly and in patients with underlying medical conditions. Most of the critically ill patients showed severe hypoxia and acute respiratory distress syndrome and required ventilator care. We experienced a 70-year-old man presenting with pandemic influenza (H1N1 2009) with heart failure. He was treated with antival agents, ventalator and extracorporeal membrane oxygenation. But his heart function was aggravared and resulted in his death.

Three Reinfection Cases of the Pandemic Influenza (H1N1 2009) / 감염과화학요법

Infection with influenza virus results in acquisition of immunity, preventing reinfection with the homologous virus. Although reinfection following primary infection is rare, its incidence depends on immunity of human body, antigenic diversity of influenza virus, and the presence of outbreak in the community. During the pandemic influenza (H1N1 2009), a child and two women were reinfected by H1N1 influenza virus several weeks after the primary infection, and they were successfully treated again by oseltamivir. This case series will provide additional information on diagnosis, treatment, and prevention of the pandemic influenza (H1N1 2009).

Clinical Characteristic of Respiratory Tract Infections in Children during Pandemic Influenza (H1N1 2009) in Korea / 감염과화학요법

BACKGROUND: Since initial emergence on pandemic influenza (H1N1 2009) in Mexico on March 2009, the first case of pandemic influenza (H1N1 2009) occured on 2 May 2009 in Korea. We describe the clinical characteristics of childhood patients from pandemic influenza (H1N1 2009) and other concurrent respiratory pathogens during early phase of the pandemic influenza in Korea. MATERIALS AND METHODS: We have retrospectively studied 959 patients under age of 15 years who have visited Department of Emergency Medicine for a diagnostic test of pandemic influenza (H1N1 2009) or treatment of flu-like illness between May and September of 2009. The pandemic influenza (H1N1 2009) was detected via real-time RT-PCR and other respiratory viruses were detected via multiplex RT-PCR. RESULTS: A total of 959 patients visited Department of Emergency Medicine at Severance Hospital. Of them, 562 were tested; 124 (12.7%) were positive for pandemic influenza (H1N1 2009). Confirmed patients of pandemic influenza (H1N1 2009) were relatively older than non-H1N1 patients (7.5 years of age vs 4.6 years, P<0.001). Among histories or symptoms of patients with flu-like illness, contact history (80%) with another patient with pandemic influenza (H1N1 2009) was an important clue of the infection in early phase of pandemic. Comparing with hospitalized patients with respiratory tract infections due to other causes, lower ESR (32.9+/-23.5 mm/hour vs 11.5+/-9.2 mm/hour), hyperkalemia (4.2+/-0.3 mmol/L vs 5.2+/-3 mmol/L) and hyponatremia (137.2+/-2.5 mmol/L vs 124+/-40.5 mmol/L) were significant laboratory finding and higher cholesterol and GTP were noticed in pandemic influenza (H1N1 2009). Ten confirmed patients with pandemic influenza (H1N1 2009) were hospitalized due to pneumonia and all of them were resolved without any complication. CONCLUSIONS: Respiratory tract infections were caused not only by pandemic influenza (H1N1 2009) virus but also various respiratory viruses. Hospitalized patients, confirmed as pandemic influenza (H1N1 2009), showed a good prognosis. Age and contact history were distinct features and could be an important clue to differentiate causes in patients with febrile respiratory symptoms.

Laboratory Confirmatory Rate of Pandemic Influenza (H1N1 2009) Virus in Korean Households with Index Case / 감염과화학요법

BACKGROUND: Influenza transmission in households a subject of renewed interest especially in pandemic situation. We performed this study to investigate the laboratory-confirmatory rate in household contacts with index cases of pandemic influenza (H1N1 2009). MATERIALS AND METHODS: For three months from 1 September and 29 November 2009, people who had a history of close contact with confirmed cases of pandemic influenza (index case) were recruited. The information on the study participants was collected using a standardized questionnaire. Presence of the pandemic influenza (H1N1 2009) infection was confirmed by real-time reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: A total of 113 index cases and 141 household contacts were investigated. One hundred and four index cases (92.0%) were younger than 20 years. The median age of household contacts was 40 years. Twenty eight household contacts (19.8%) had acute respiratory illness (ARI). Overall, 10.6% of enrolled household contacts were positive in RT-PCR for pandemic influenza (H1N1 2009). The positive rate of household contacts with ARI was 25.0% and it was 7.1% in household contacts without ARI. The positive rate was significantly higher in children and young adults under 30 years (28.3%) compared with that in household contacts older than 30 years (8.3%). CONCLUSIONS: This results showed a significant role of mild symptomatic or asymptomatic pandemic influenza (H1N1 2009) patients as a virus carriers in households.