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By Dean L. Winslow, MD, FACP, FIDSA, Chairman, Department of Medicine, Santa Clara Valley, Medical Center; Clinical Professor, Stanford University School of Medicine, Associate Editor of Infectious Disease Alert. Dr. Winslow is a consultant for Siemens Diagnostic.
Synopsis: As of April 29 Chinese health officials have reported 126 cases of human infection due to Influenza A (H7N9) of whom 24 (19%) died. No sustained human-to-human transmission has been documented to date.
Source: Centers for Disease Control and Prevention. Emergence of Avian Influenza A(H7N9) Virus Causing Severe Human Illness — China, February–April 2013. MMWR 2013; 62: 366-371.
Since February of this year Chinese health authorities have documented 126 human cases of a recently-identified “avian” Influenza A (H7N9). Of these cases, 24 (19%) died of disease. Of the laboratory confirmed cases 77% followed exposure to live birds (chickens or ducks). The majority of cases were clustered in Zhejiang, Shanghai, and Jiangsu. The median age of patients was 61 years. Only 4 children have been reported. The majority of patients (76%) had at least one underlying health condition. Most of the confirmed cases had severe respiratory illness. Among those requiring hospitalization death was due to acute respiratory distress syndrome (ARDS) or multi-organ system failure. In a detailed follow up study of 1689 contacts of 82 patients with confirmed infection, Chinese public health officials found no evidence of sustained human-to-human transmission. However, three small family clusters of infection were documented making limited human-to-human transmission possible.
The saga of novel respiratory pathogens causing severe illness in humans continues. Beginning in 2009 we had pandemic Influenza A (H1N1) which displayed particular virulence in younger patients, last year we had a large outbreak of Hantavirus pulmonary syndrome in individuals staying in Curry Village cabins in Yosemite, and this year we have had cases of severe respiratory illness due to a novel coronavirus in the Middle East. This latest outbreak of a new strain of “bird flu” is of interest. A study published in May of this year reported on sequencing of the genome of the virus isolated from three fatal cases of H7N9 infection.1 A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses.
The significance of these findings is yet to be determined. It should be remembered when thinking about influenza that essentially all influenza is “avian” since birds are the “normal” host for this virus. However other domestic animals (particularly swine) and humans can be infected by many of these viruses as well. Of the influenza viruses which have caused pandemics in humans, all are characterized by efficient human-to-human transmission. While many of the recent “avian” influenza viruses including H5N1 a few years ago, and H7N9 this year have caused severe infection in humans, it has been fortunate that neither of these viruses possessed the ability to cause efficient human-to-human transmission. Host range, tissue tropism and pathogenicity are generally felt to be related to differences in sialyl glycan binding. However the specific genetic determinants needed to cause efficient human-to-human transmission are not well-characterized despite our employment of sophisticated molecular techniques. The scary thing about these cases of severe influenza in humans caused by these “avian” strains is that influenza virus has an amazing ability to form reassortant viruses and co-infection with different strains of influenza in “mixing vessel” animals such as swine, is common. A preliminary report also demonstrated that oseltamivir resistance developed on therapy in 3 Chinese patients who had severe disease due to H7N9 who required ECMO support.2
1. Gao R, et al. Human infection with a novel avian-origin Influenza A (H7N) virus. New Eng Jrl Med 2013; 368: 1888-1897.
2. Hu Y, et al. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet 2013;DOI:10.1016/S0140-6736(13)61125-3.