Emergence of HA mutants during influenza virus pneumonia.

During the influenza pandemic of 2009, the number of viral pneumonia cases showed a marked increase in comparison with seasonal influenza viruses. Mutations at amino acid 222 (D222G mutations) in the virus hemagglutinin (HA) molecule, known to alter the receptor-recognition properties of the virus, were detected in a number of the more severely-affected patients in the early phases of the pandemic. To understand the background for the emergence of the mutant amino acid D222G in human lungs, we conducted histological examinations on lung specimens of patients from Mexico who had succumbed in the pandemic. Prominent regenerative and hyperplastic changes in the alveolar type II pneumocytes, which express avian-type sialoglycan receptors in the respiratory tract of severely affected individuals, were observed in the Mexican patients. An infection model utilizing guinea pigs, which was chosen in order to best simulate the sialic acid distribution of severe pneumonia in human patients, demonstrated an increase of D222G mutants and a delay in the diminution of mutants in the lower respiratory tract in comparison to the upper respiratory tract. Our data suggests that the predominance of avian-type sialoglycan receptors in the pneumonic lungs may contribute to the emergence of viral HA mutants. This data comprehensively illustrates the mechanisms for the emergence of mutants in the clinical samples.

Socioeconomic factors influencing hospitalized patients with pneumonia due to influenza A(H1N1)pdm09 in Mexico.

BACKGROUND: In addition to clinical aspects and pathogen characteristics, people's health-related behavior and socioeconomic conditions can affect the occurrence and severity of diseases including influenza A(H1N1)pdm09. METHODOLOGY AND PRINCIPAL FINDINGS: A face-to-face interview survey was conducted in a hospital in Mexico City at the time of follow-up consultation for hospitalized patients with pneumonia due to influenza virus infection. In all, 302 subjects were enrolled and divided into two groups based on the period of hospitalization. Among them, 211 tested positive for influenza A(H1N1)pdm09 virus by real-time reverse-transcriptase-polymerase-chain-reaction during the pandemic period (Group-pdm) and 91 tested positive for influenza A virus in the post-pandemic period (Group-post). All subjects were treated with oseltamivir. Data on the demographic characteristics, socioeconomic status, living environment, and information relating to A(H1N1)pdm09, and related clinical data were compared between subjects in Group-pdm and those in Group-post. The ability of household income to pay for utilities, food, and health care services as well as housing quality in terms of construction materials and number of rooms revealed a significant difference: Group-post had lower socioeconomic status than Group-pdm. Group-post had lower availability of information regarding H1N1 influenza than Group-pdm. These results indicate that subjects in Group-post had difficulty receiving necessary information relating to influenza and were more likely to be impoverished than those in Group-pdm. Possible factors influencing time to seeking health care were number of household rooms, having received information on the necessity of quick access to health care, and house construction materials. CONCLUSIONS: Health-care-seeking behavior, poverty level, and the distribution of information affect the occurrence and severity of pneumonia due to H1N1 virus from a socioeconomic point of view. These socioeconomic factors may explain the different patterns of morbidity and mortality for H1N1 influenza observed among different countries and regions.

Reducing occurrence and severity of pneumonia due to pandemic H1N1 2009 by early oseltamivir administration: a retrospective study in Mexico.

BACKGROUND: Anti-viral treatment has been used to treat severe or progressive illness due to pandemic H1N1 2009. A main cause of severe illness in pandemic H1N1 2009 is viral pneumonia; however, it is unclear how effective antiviral treatment is against pneumonia when administered >48 hours after symptom onset. Therefore, we aimed to determine how time from symptom onset to antiviral administration affected the effectiveness of antiviral treatment against pneumonia due to pandemic (H1N1) 2009. METHODS/PRINCIPAL FINDINGS: A retrospective medical chart review of 442 patients was conducted in a hospital in Mexico. Subjects had tested positive for pandemic H1N1 2009 virus by real-time reverse-transcriptase-polymerase-chain-reaction and were administered oseltamivir. Median time from symptom onset to oseltamivir administration was 5.0 days (range, 0-43). 442 subjects, 71 (16.1%) had severe pneumonia which required mechanical ventilation, 191 (43.2%) had mild to moderate pneumonia, and 180 (40%) did not have pneumonia. Subjects were divided into four groups based on time to oseltamivir administration: ≤2, 3-7, 8-14, and >14 days. Severity of respiratory features was associated with time to treatment, and multivariate analysis indicated that time to oseltamivir administration was associated with severity of respiratory features. A proportional odds model indicated that 50% probability for occurrence of pneumonia of any severity and that of severe pneumonia in patients who would develop pneumonia reached at approximately 3.4 and 21 days, respectively, after symptom onset. Patients with a shorter time to oseltamivir administration were discharged earlier from the hospital. CONCLUSIONS: Earlier initiation of oseltamivir administration after symptom onset significantly reduced occurrence and severity of pneumonia and shortened hospitalization due to pandemic H1N1 2009. Even when administered >48 hours after symptom onset, oseltamivir showed considerable potential for reducing pneumonia. Application of these results would benefit patients affected by future influenza pandemics.

[Clinical and sociological prospectives on pandemic (H1N1) 2009].

A new pandemic influenza A (H1N1) virus has emerged and rapidly spread throughout the world. The clinical and pathological findings associated with severe illness in Pandemic (H1N1) 2009 and the risk factors are similar to the high pathogenic avian influenza (H5N1). The effective treatment methods for severe influenza in Pandemic (H1N1) 2009 could strongly refer to the treatment method for human H5N1 infection. In this article, the experiences, the investigation and our collaboration studies for Pandemic (H1N1) 2009 in Mexico and Avian Influenza (H5N1) in Vietnam and the examination for the past pandemic influenza will be described. The effective treatments for critical pneumonia caused by influenza will be discussed from the medical, regional and global point-of-view which can be applied to any type of pandemic influenza.