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Virol J. 2013 Mar 16;10:88. doi: 10.1186/1743-422X-10-88.

Experimental infection with a Thai reassortant swine influenza virus of pandemic H1N1 origin induced disease.

Charoenvisal N1, Keawcharoen J, Sreta D, Tantawet S, Jittimanee S, Arunorat J, Amonsin A, Thanawongnuwech R.

Author information

1Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Henri-Dunant Rd, Bangkok 10330, Thailand.

Abstract

BACKGROUND:

Following the emergence of the pandemic H1N1 influenza A virus in 2009 in humans, this novel virus spread into the swine population. Pigs represent a potential host for this virus and can serve as a mixing vessel for genetic mutations of the influenza virus. Reassortant viruses eventually emerged from the 2009 pandemic and were reported in swine populations worldwide including Thailand. As a result of the discovery of this emergent disease, pathogenesis studies of this novel virus were conducted in order that future disease protection and control measures in swine and human populations could be enacted.

METHODS:

The pandemic H1N1 2009 virus (pH1N1) and its reassortant virus (rH1N1) isolated from pigs in Thailand were inoculated into 2 separate cohorts of 9, 3-week-old pigs. Cohorts were consisted of one group experimentally infected with pH1N1 and one group with rH1N1. A negative control group consisting of 3 pigs was also included. Clinical signs, viral shedding and pathological lesions were investigated and compared. Later, 3 pigs from viral inoculated groups and 1 pig from the control group were necropsied at 2, 4, and 12 days post inoculation (DPI).

RESULTS:

The results indicated that pigs infected with both viruses demonstrated typical flu-like clinical signs and histopathological lesions of varying severity. Influenza infected-pigs of both groups had mild to moderate pulmonary signs on 1-4 DPI. Interestingly, pigs in both groups demonstrated viral RNA detection in the nasal swabs until the end of the experiment (12 DPI).

CONCLUSION:

The present study demonstrated that both the pH1N1 and rH1N1 influenza viruses, isolated from naturally infected pigs, induced acute respiratory disease in experimentally inoculated nursery pigs. Although animals in the rH1N1-infected cohort demonstrated more severe clinical signs, had higher numbers of pigs shedding the virus, were noted to have increased histopathological severity of lung lesions and increased viral antigen in lung tissue, the findings were not statistically significant in comparison with the pH1N1-infected group. Interestingly, viral genetic material of both viruses could be detected from the nasal swabs until the end of the experiment. Similar to other swine influenza viruses, the clinical signs and pathological lesions in both rH1N1 and pH1N1 were limited to the respiratory tract.

Can there be a natural supplement to saturation by O2 procedure of the infected lungs in place of non-available extra-corporeal membrane oxygenation (ECMO)?

Referral to an Extracorporeal Membrane Oxygenation Center and Mortality Among Patients With Severe 2009 Influenza A(H1N1) 

JAMA. 2011;306(15):1659-1668. doi:10.1001/jama.2011.1471.

October 7, 2011 — The 2009 H1N1 influenza pandemic caused a surprisingly high number of deaths in young adults, but extracorporeal membrane oxygenation (ECMO) may have played a key role in keeping alive critically ill patients with acute respiratory distress syndrome in the United Kingdom, according to a cohort study. The new study was published online October 5 in JAMA, to coincide with its presentation at the European Society of Intensive Care Medicine in Berlin, Germany.

In a matched pairs analysis of patients with severe respiratory failure as a result of the H1N1 pandemic influenza, investigators found that twice as many non-ECMO-referred patients died when they were not referred for ECMO compared with those who were referred to 1 of 4 ECMO centers, accepted, and transferred.

Eighty patients were transferred to one of 4 UK ECMO centers during the 2009 to 2010 influenza A H1N1 pandemic; 69 of the patients (86.3%) received ECMO, and 22 (27.5%) died. All patients were critically ill and were part of a longitudinal cohort study, the Swine Flu Triage study. "The unique value of this study lies in the homogeneity of the patients with H1N1-related ARDS and the matching methods used," writes a research team led by Moronke A. Noah, MRCS, from Heartlink ECMO Centre, Glenfield, Hospital, Leicester, United Kingdom.

Rigorous matching using 3 matched pair analyses was intended to rule out differences in demographic, physiologic, or comorbidity factors that affect outcome. These included age, extent of hypoxemia, organ dysfunction, pregnancy, obesity, and the use of other ventilator strategies. Patients ranged in age between 28 and 46 years.

The death rate for discharge was 52.5% for non-ECMO-referred patients vs 23.7% for ECMO patients (relative risk [RR], 0.45; 95% confidence interval [CI], 0.26 - .79; P = .006), using individual matching; 46.7% vs 24.0% (RR, 0.51; 95% CI, 0.31 - 0.84; P = .008) using propensity score matching; and 50.7% vs 24.0% (RR, 0.47; 95% CI, 0.31 - 0.72; P = .001) using GenMatch matching. Patients who were not referred for ECMO had a higher rate of early deaths than ECMO-referred patients, using all 3 matched pairs analyses.

All patients who were transferred for ECMO survived the transfer. Adverse effects associated with ECMO included hemorrhaging complications, including intracranial hemorrhage (n = 8), cesarean delivery wound hematoma (n = 5), cannula site hematoma (n = 3), hemothorax (n = 4), and minor upper airway bleeding (n = 9).

The study is unlikely to resolve the exact place of ECMO in clinical care for patients with severe ARDS related to H1N1, explained William Checkley, MD, PhD, assistant professor of medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland, in an interview with Medscape Medical News. Dr. Checkley, who authored a companion editorial, said: "Even though the data are very enticing, it is an observational study. We need better evidence. Next to consider is a randomized controlled trial."

Dr. Checkley praised the "very elegant matching methods," but also drew attention to the "high cost of the technology, the need for 24-hour resource intensive support, hence the need for better guidelines and a more rigorous study design.... What the study did not disentangle is whether the improved outcomes could be a center effect, an effect of highly specialized care, much higher case volume, and experience." The generalizability of the study is also at issue because the patients were younger than many patients who became critically ill during the influenza pandemic. In addition, the authors and Dr. Checkley noted that previous studies have shown that treatment with ECMO costs twice as much as conventional ventilator care.

Pauline K. Park, MD, associate professor of surgery and codirector of the Surgical Intensive Care Unit at the University of Michigan Health System, Ann Arbor, told Medscape Medical News: "The signal is very strong that the ECMO-referral strategy led to higher survival" in patients with severe H1N1-associated ARDS.

Dr. Park also said that "even though the study did not determine whether the ECMO, the timing of the intervention, or the overall care contributed to the improved survival, it does suggest that regional centers of critical care expertise can have a positive influence on patient outcomes." When asked to comment about the cost of ECMO, she said: "The hospital costs are always higher when the patient survives. Moreover, in a previous UK study, the cost of ECMO per quality adjusted life year was consistent with other commonly accepted medical treatments. ECMO was offered only to patients who were felt to be failing lower-cost conventional treatment."