Microbiology :: Tips from the Journals of the American Society for Microbiology

The following articles are featured in the upcoming issue of the Journals of the American Society for Microbiology: Novel H3N1 swine influenza virus identified in pigs in Korea; New treatment using human antibodies to target harmful toxins may protect against C. cifficile; and Guinea pig aerosol challenge presents new model for Q fever research in humans.

Novel H3N1 Swine Influenza Virus Identified in Pigs in Korea

For the first time, researchers from the U.S. and abroad have identified the H3N1 swine influenza virus in domestic pigs in Korea. They report their findings in the November 2006 issue of the Journal of Clinical Microbiology.

A highly infectious respiratory pathogen, the H3N1 influenza A virus is a new genetic reassortment of influenza viruses first identified in pigs in the U.S. in 2004. The virus can be found in birds and mammals (including humans and pigs), but is not generally transmissible between birds and humans. Pigs are believed to be susceptible to both origins resulting in them being deemed “mixing vessels” for the virus and ultimately reinforcing concerns of zoonosis and pandemic outbreaks.

In March and April of 2006 researchers isolated H3N1 influenza A viruses in pigs with respiratory diseases at two commercial swine farms in Korea. Further testing confirmed the H3N1 viruses presenting were reassortments of an H3 human-like virus and other genes from swine influenza viruses and that pig-to-pig and farm-to-farm transmission had occurred. Additionally, analysis of experimentally infected mice suggested the potential to transmit the virus between pigs and other mammalian hosts.

“We report here the first isolation and characterization of H3N1 swine influenza viruses from pigs with respiratory disease in Korea,” say the researchers. “Given the evidence that pigs can support the reassortment of influenza viruses from humans and other species, it is prudent that we enhance surveillance for atypical influenza viruses in pigs as part of overall pandemic preparedness efforts.”

(J.Y. Shin, M.S. Song, E.H. Lee, Y.M. Lee, S.Y. Kim, H.K. Kim, J.K. Choi, C.J. Kim, R.J. Webby, Y.K. Choi. 2006. Isolation and characterization of novel H3N1 swine influenza viruses from pigs with respiratory diseases in Korea. Journal of Clinical Microbiology, 44. 11: 3923-3927.)

New Treatment Using Human Antibodies to Target Harmful Toxins May Protect Against C. Difficile

A new therapeutic method using human antibodies to neutralize toxins was found to prevent Clostridium difficile-induced death in hamsters say researchers from New Jersey and Massachusetts. They report their findings in the November 2006 issue of the journal Infection and Immunity.

C. difficile is the leading cause of nosocomial antibiotic-associated diarrhea, often resulting from the administration of antibiotics such as clindamycin, ampicillin, or cephalosporins. C. difficile associated diarrhea (CDAD) effects approximately 300,000 patients per year in the U.S. alone. Treatment available to date includes discontinuation of the antibiotic causing the illness as well as administration of medication such as metronidazole or vancomycin. Although both methods offer initial relief, there is currently a 10 to 20% relapse rate among patients. Due to the recent emergence of more virulent C. difficile strains, in addition to increasing vancomycin resistance, researchers are focusing on new treatments and relapse prevention therapy.

In the study mice were used to isolate human monoclonal antibodies (HuMAbs) capable of neutralizing C. difficile toxins A and B. Researchers then tested anti-toxin A HuMAb CDA1 alone and in conjunction with anti-toxin B HUMAb MDX-1388 for the ability to protect hamsters from C.difficle-induced death and relapse prevention. Results showed that combination therapy reduced mortality from 100% to 45% in the primary disease model and from 78% to 32% in the relapse model.

“These human and animal studies, taken together, demonstrate the relevance of toxin-reactive antibodies in disease outcomes,” say the researchers. “Here we describe the characterization of a panel of neutralizing, fully human monoclonal antibodies (HuMAbs) directed against either toxin A or toxin B. HuMAb CDA1 (against toxin A) alone could protect hamsters from mortality, but significantly enhanced protection was observed when the antibodies were administered as a combination therapy.”

(G.J. Babcock, T.J. Broering, H.J. Hernandez, R.B. Mandell, K. Donahue, N. Boatright, A.M. Stack, I. Lowy, R. Graziano, D. Molrine, D.M. Ambrosino, W.D. Thomas, Jr. 2006. Human monoclonal antibodies directed against toxins A and B prevent Clostridium difficile-induced mortality in hamsters. Infection and Immunity, 74. 11: 6339-6347.)

Guinea Pig Aerosol Challenge Presents New Model for Q Fever Research in Humans

Clinical signs and pathological changes in guinea pigs following an aerosol challenge with acute Q fever were similar to those seen in human acute Q fever indicating an effective animal model of human disease say researchers from Texas A&M University. They report their findings in the November issue of the journal Infection and Immunity.

Q fever, caused by the bacterium Coxiella burnetti, generally infects humans through inhalation with as few as 10 organisms capable of causing disease. C. burnetti has a high degree of resistance to treatment agents and can remain infectious in contaminated soils for years. Due to its highly infectious nature, the Centers for Disease Control and Prevention has listed C. burnetti as a potential weapon of mass destruction reinforcing the need for a safe and effective vaccine. There is currently no licensed vaccine available in the U.S.

In the study select guinea pigs received a killed whole-cell Q fever vaccine after which all were infected with C. burnetti through inhalation of small-particle aerosols and evaluated 28 days postinfection. Noted clinical signs included fever, weight loss, respiratory difficulty and death with the degree and duration of response correlating with the dose of organism delivered. Those guinea pigs vaccinated prior to challenge with the highest dose of C. burnetti did not develop fever and were protected against lethal infection.

“The guinea pig aerosol challenge model presented here mimics both the clinical and pathologic changes seen in human acute Q fever and Q fever pneumonia cases and will provide an accurate and valuable tool for the study of the general pathogenesis of C. burnetti infection, for vaccine assessment, and for evaluations of host immune responses,” say the researchers.

(K.E. Russell-Lodrigue, G.Q. Zhang, D.N. McMurray, J.E. Samuel. 2006. Clinical and pathological changes in a guinea pig aerosol challenge model of acute Q fever. Infection and Immunity, 74. 11: 6085-6091.)

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