News From The Journals Of The American Society For Microbiology
Main Category: MRSA / Drug ResistanceAlso Included In: Infectious Diseases / Bacteria / Viruses; Biology / Biochemistry; Immune System / Vaccines
Article Date: 22 Aug 2007 - 20:00 PDT
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Phage Therapy May Control Staph Infections in Humans Including MRSA
Researchers from Italy have identified a bacteriophage active against Staphylococcus aureus, including methicillin-resistant strains, in mice and possibly humans. They report their findings in the August 2007 issue of the journal Antimicrobial Agents and Chemotherapy.
S. aureus is a highly flexible and potentially dangerous pathogen capable of causing skin abscesses, wound infections, endocarditis, osteomyelitis, pneumonia and toxic shock syndrome. Due to the organism's ability to live inside cells, emerging strains are increasingly resistant to antibiotics. Currently, forty to sixty percent of reported nosocomial S. aureus infections in the United States and the United Kingdom are multi-drug resistant with methicillin-resistant S. aureus carrying a significantly higher mortality rate.
A bacteriophage, or phage for short, is a virus that infects bacteria. In the study researchers identified the phage, MSa, and tested its activity against S. aureus in mice. Following simultaneous inoculation with both MSa and lethal and non-lethal doses of S. aureus results showed MSa rescued ninety-seven percent of mice from death and fully cleared mice of non-lethal bacterial infections.
"These results suggest a potential use of the phage for the control of both local and systemic human S. aureus infections," say the researchers.
(R. Capparelli, M. Parlato, G. Borriello, P. Salvatore, D. Iannelli. 2007. Experimental phage therapy against Staphylococcus aureus in mice. Antimicrobial Agents and Chemotherapy, 51. 8: 2765-2773).
New Smallpox Vaccine Candidates Demonstrate Superior Immune Response, Efficacy and Safety in Mice
The integration of an immune-enhancing protein into two new smallpox vaccine candidates elicited superior immune responses, efficacy and safety in mice say researchers from the U.S. They report their findings in the August 2007 issue of the Journal of Virology.
Following the declaration of global eradication of smallpox in 1979, vaccinations for the general public were discontinued. Today, the virus poses threat as an agent of biological warfare, leaving half of the worldwide population susceptible to serious disease or death in the event of an attack. Severe adverse effects resulting from the currently licensed Dryvax vaccine emphasize the need for new preventative methods.
Researchers developed two new vaccine candidates integrating the immune-enhancing protein Interleukin-15 (IL-15) and tested for efficacy in mice challenged with smallpox. Wyeth IL-15 included a strain of the vaccinia virus derived from the Dryvax vaccine and MVA IL-15 incorporated a modified strain of the vaccinia virus Ankara which is currently being considered as a substitute for the Dryvax vaccine. The Wyeth IL-15 vaccine resulted in a 1,000-fold reduction in lethality and highly increased cellular and humoral immune responses. Additionally, mice vaccinated with Wyeth IL-15 fully survived a lethal intranasal challenge ten months after vaccination. The second candidate MVA IL-15 also demonstrated greater immunogenicity and efficacy than Dryvax.
"By integrating IL-15 cytokine into Wyeth and MVA strains, we have developed two smallpox vaccine candidates with greater immunogenicity and efficacy yet with more-attenuated virulence than the currently licensed Dryvax vaccine suitable for contemporary populations," say the researchers.
(L.P. Perera, T.A. Waldmann, J.D. Mosca, N. Baldwin, J.A. Berzofsky, S.K. Oh. 2007. Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice. Journal of Virology, 81. 16: 8774-8783).
First Animal Model Developed for Oral Infection of Human Poliovirus
For the first time researchers have developed an animal model for oral poliovirus infection. They report their findings in the August 2007 issue of the Journal of Virology.
Poliovirus causes acute disease in the central nervous system in humans often resulting in paralysis. Due to its reemerging presence in developing countries researchers are reexamining the viruses' ability to spread among humans through oral ingestion and develop new preventative therapies accordingly.
Due to the human digestive tracts' low sensitivity to the poliovirus, no previous rodent model tracking oral infection has been developed. In the study mice carrying the human poliovirus receptor gene and lacking the interferon receptor gene (IFNAR) were sensitive to an oral challenge of the poliovirus. Nine days following the challenge the mice had died and the virus was detected in their small intestines and digestive tracts. Mice expressing the interferon receptor gene were found to be much less sensitive to virus.
"These results suggest that IFNAR plays an important role in determining permissivity in the alimentary tract as well as the generation of virus-specific immune responses to poliovirus via the oral route," say the researchers. "Thus, hPVR-Tg/IfnarKO are considered to be the first oral infection model for poliovirus."
(S. Ohka, H. Igarashi, N. Nagata, M. Sakai, S. Koike, T. Nochi, H. Kiyono, A. Nomoto. 2007. Establishment of a poliovirus oral infection system in human poliovirus receptor-expressing transgenic mice that are deficient in alpha/beta interferon receptor. Journal of Virology, 81. 15: 7902-7912).
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Source: Carrie Patterson
American Society for Microbiology
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Phage Therapy & Superbugs
posted by Bill on 23 Aug 2007 at 6:05 pmChoosing to let patients with superbug infections die rather than phage them!!!!
It is my humble opinion that the antibiotic-resistance superbug crisis is the mother of all regulatory-scientific-medical-environmental misadventures; however, the absurdity of the superbug crisis consists of the fact that it can be demonstrated that we had technology, namely bacteriophage therapy, long before we created the antibiotic-resistance superbug crisis through massive abuse of antibiotics and other antimicrobials. Additionally many politicians, bureaucrats, scientists and members of the public health community are or should be well informed about phage therapy which can cure many superbug infections. In spite of a voluminous literature attesting to the scientific validity, safety and medical effectiveness of phage therapy (see http://www.phage.org and find phage therapy references), there are still phage therapy deniers who would resist the careful deployment of these weapons of mass-destruction for specific pathogens in the war with superbugs.
What is Phage Therapy? Prior to the discovery and widespread use of antibiotics, bacterial infections were treated worldwide by the administration of bacteriophages. Bacteriophages or phages are highly specific viruses that invade bacterial cells and, in the case of lytic phages, disrupt bacterial metabolism and cause the bacterium to die. Interestingly it was the French-Canadian microbiologist, Felix d'Herelle, while working at the Institute Pasteur in Paris in 1917 who is credited with discovering and promoting phage therapy. While the use of phage therapy was discontinued in the West soon after the discovery of antibiotics they continued to be utilized in Eastern Europe and today many infections untreatable with antibiotics can be treated in clinics in Georgia (Europe) and Poland. Once one accepts the fact that it requires microscopes to see the world of bacteria and bacteriophages, phage therapy may be compared to any biological control methodology and can conceptually be described as: What a cat is to a mouse the right bacteriophage is to a specific bacterium or superbug. Phage therapy has been going on in nature as a balancing force in the evolution of microbes for a long time. Medical phage therapy is simply the intervention by humans to ensure that the balance is in favour of bacteriophages over susceptible bacterial pathogens! While there is considerable expertise on phage therapy in Canada at the research level, as can be substantiated by googling phage therapy ("pages from Canada" only), medical phage therapy is not currently approved or practised in Canada; however, according to a letter signed by the former federal health minister phage therapy can be made available legally to Canadian patients under the Special Access Program of our Food & Drugs Act! Additionally, there are moral and ethical reasons for making phage therapy available since Canada appears to be a member of The World Medical Association which states: "In the treatment of a patient, where proven prophylactic, diagnostic and
therapeutic methods do not exist or have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic measures, if in the physician's judgement it offers hope of saving life." ( see below for quote source ).
A discussion of phage therapy is currently very timely, not only because too many patients are dying of superbug infections; but also because of the recent release of the Canadian film: Killer Cure: The Amazing Adventures of Bacteriophage and the June 2006 release of the book by Thomas Haeusler entitled, Viruses vs. Superbugs, a solution to the antibiotics crisis? ( see http://www.bacteriophagetherapy.info ) - both are available at Ottawa libraries. Additionally, the record of an excellent questions-and-answers session with Dr. Roger Johnson of the Public Health Agency of Canada can be found at http://meristem.com/topstories/ts06_08.html .
Further, the phage therapy file has dramatically changed during the last few months because the US Food and Drug Administration (FDA) has amended the US food additive regulations to provide for the safe use of a bacteriophage preparation on ready-to-eat meat and poultry products as an antimicrobial agent against Listeria monocytogenes (see http://www.fda.gov/OHRMS/DOCKETS/98fr/02f-0316-nfr0001.pdf ). This excellent submission evaluation changes the scientific validity of phage therapy from Eastern European science, which, sadly, too many of us Westerners dismiss with hubris and bias as not credible, to approved and supported by the all-knowing and all-seeing FDA at least for ready-to-eat meats. An enlightening FDA questions-and-answers document can be found at http://www.cfsan.fda.gov/~dms/opabacqa.html .
Superbugs are everybody’s business because superbugs make everybody their business and every North American should study the above references because sooner or later everybody will be faced with an infection or know a relative or friend who will be suffering or dying with one. Withholding such treatment from patients when antibiotics are failing ought to be a crime; however, those who have the money, knowledge and time to travel when faced with an infection where antibiotics are failing may be able to get phage therapy treatment in Georgia ( http://www.phagetherapycenter.com ) or Poland - http://www.aite.wroclaw.pl/phages/phages.html . A record of a trip to Georgia to get phage therapy treatment by UK citizens can be seen at http://www.relax-well.co.uk/news.html .
What is even more surprising and frustrating is that an American company, Phage International Inc., ( http://www.phageinternational.com ) would probably be willing and able to set up a phage therapy clinic in any country if the right regulatory climate existed. A recent article describing how foreigners from many countries are treated at their Phage Therapy Center in Tbilisi, Georgia can be found at http://www.phagetherapycenter.com/doc/sjbizjournal.pdf .
Since January 1, 2000 as many 87,000 Canadians may have died of superbug bacterial infections and there is not even a memorial for them, although some people are starting to wear blue ribbons in memory of superbug victims. Would it not be nice if the Canadian governments, public health officials and media got together and funded the Felix d'Herelle Center for Phage Therapy to provide the phage therapy treatment option for patients when antibiotics fail and we have nothing left to offer them?
P.S.: WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI PARAGRAPH 32:
"In the treatment of a patient, where proven prophylactic, diagnostic and
therapeutic methods do not exist or have been ineffective, the physician,
with informed consent from the patient, must be free to use unproven or new
prophylactic, diagnostic and therapeutic measures, if in the physician's
judgement it offers hope of saving life, re-establishing health or
alleviating suffering. Where possible, these measures should be made the
object of research, designed to evaluate their safety and efficacy. In all
cases, new information should be recorded and, where appropriate, published.
The other relevant guidelines of this Declaration should be followed."
FROM: The World Medical Association:
http://www.wma.net/e/policy/b3.htm - and
http://www.aite.wroclaw.pl/phages/phages.html
Reason Why Phage Therapy Is Not Available
posted by Debra on 4 Apr 2011 at 2:02 pmThe reason that phage therapy is not available to the Western world is quite simple...money. Vancomycin's cost, used to treat multi-resistant bacterial strains in the gut, is astronomical.
Phage therapy, on the other hand, is not exconomically feasible. The pharmaceutical lobby is successful.
http://wn.com/Phage_Therapy_for_MRSA_cheaper_than_antibiotics
Is this a moral and ethical issue? Most certainly. So how am I qualified to make this judgement? Well, I have a severe bacterial gut infection and have researched every available avenue, to no avail. Can I afford to travel to Tblisi, Georgia for treatment? Very hard, but may have to do this to save my life. Shame on you, those of you who manage to control the antibiotic monopoly in our medical system.
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