|
Dr. Michelle Alfa
Principal Investigator, Infectious Diseases
Canadian Centre for Agri-food Research In Health and Medicine
Research Focus
The Infectious Diseases Lab focuses on research in the area of Nosocomial (hospital acquired) infections. The two primary areas of research interest include:
- 1) Clostridium difficile associated diarrhea and
- 2) Medical device associated infections.
The project related to C.difficile targets development of interventions that can break the cycle of transmission from spores of C.difficile in the environment that act as a reservoir, as well as development of therapeutics that could prevent patients from acquiring the infection and/or treat those who have the infection. The C.difficile therapeutic program is part of the CCARM initiative and is based on the concept of utilizing egg immunoglobulins (IgY) as a means of “passive immunization” to prevent and/or treat the toxin mediated infection.
The project related to medical device infections is related to improving the efficacy of cleaning and preventing biofilm buildup in medical devices such as flexible endoscopes.
Why is this work important?
Currently hospital acquired C.difficile associated disease (CDAD) affects more people than all other enteric bacteria combined. CDAD is most commonly hospital acquired, but it can also be community acquired. Approximately 25% of patients who develop CDAD will have a recurrence of their infection after treatment is stopped. The increased length of hospital stay, along with adverse outcomes (especially in elderly patients) and possible death make this a significant pathogen that we urgently need to control and develop alternative therapeutics that will be effective in either preventing or curing this serious infection.
Infections associated with improperly reprocessed medical devices are not common – but when they do occur – they often affect a large number of patients. Flexible endoscope procedures are becoming very wide-spread (e.g. colonoscopy to evaluate patients for rectal cancer) as such any problem associated with a flexible endoscope could potentially affect a large number of people. Since you cannot see inside the endoscope channels – it is important to ensure that the reprocessing is being done properly and that the device is truly safe to use on the next patient. Flexible endoscopes cannot be steam sterilized so other methods are used for disinfection that do not provide a wide margin of safety. Ensuring these medical devices are safe for use on patients is an important focus to ensure patients do not loose confidence in the medical system.
What techniques and equipment are used in this laboratory?
Our lab has developed and utilizes tissue culture assays to evaluate the biological activity of C.difficile Toxin A and Toxin B. In addition, we utilize the “human gut” model to follow the impact of the microbial ecosystem on maintaining control of C.difficile replication and toxin production. In addition a number of molecular assays are used that include PCR, PFGE and sequencing.
For the medical device studies we have a wide range of narrow lumen reprocessors and flexible endoscope reprocessors that are used for our studies or are under development. The use of the MBEC pin model to study biofilm buildup has provided a valuable approach to understanding lack of disinfectant efficacy against microbes embedded in biofilm buildup.
Staff in the research centre working on Dr. Alfa’s research projects include: Nancy Olson, and Iram Fatima.
About Dr. Michelle Alfa
Dr. Alfa undertook her B.Sc. in Microbiology from the University of Manitoba, her M.Sc. in Microbiology at the University of New South Wales in Sydney, Australia and her Ph.D. in Medical Microbiology at the University of Alberta. She is board certified as a Clinical Microbiologist with the Canadian College of Microbiologists. She is currently a Clinical Microbiologist with the Diagnostic Services of Manitoba as well as a Professor in the Dept of Medical Microbiology at the University of Manitoba.
Dr. Alfa has been involved in the teaching of undergraduate students, graduate students and, medical students for over 16 years. She has been awarded outstanding teacher awards as well as the the “Distinguished Microbiologist” award from the Canadian College of Microbiologists. Dr. Alfa has over 70 peer-reviewed publications and book chapters and holds a USA patent for an artificial test soil that she developed. Dr. Alfa has also provided numerous National and International presentations on her research findings.
For more information, contact:
Dr. Michelle Alfa
[t] 235-3498
This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
In Detail
Egg-citing Alternative Therapy for Infectious Diarrhea
Nosocomial (hospital acquired) infections pose a significant challenge within healthcare as this type of infection is preventable. Clostridium difficile associated diarrhea (CDAD) is the most common infectious cause of diarrhea in hospitals. CDAD is caused by the vegetative form of the organism that produces toxins (C.difficile can exist as a spore form that is metabolically inactive so does not produce toxin and is not damaged by antibiotics). Indeed, CDAD (predominantly a nosocomial infection) causes more diarrhea infections per year than ALL other enteric pathogens combined (e.g. Salmonella spp, Shigella spp, E.coli O157:H7, Campylobacter spp which are predominantly community-acquired infections).
CDAD occurs when traditional antibiotic therapy is used because of some other underlying infectious disease. C.difficile is resistant to many of these antibiotics
and therefore is not killed whereas many of the other microbes that are part of the normal flora of gut are killed. This upsets the normal microbial balance in the gut thereby allowing C.difficile to overgrow. If the C.difficile strain is toxigenic, it can cause diarrhea and inflammation in the bowel which can progress to severe damage to the gut that can ultimately lead to death. In the recent outbreak in Quebec rapid progression to serious disease and an increase death rate were the hallmark of CDAD. Treatment of C.difficile infection is based on using specific antibiotics that the organism is susceptible to. Recurrence of CDAD disease once therapy is completed is common occurring in about 30% of patients. Recurrences are thought to be due to the ability of C.difficile to form spores that are not affected by any antibiotic as they are metabolically inactive. Once the vegetative form is killed by the specific therapy and antibiotic treatment is stopped then the spore can outgrow to form another source of vegetative organism that then produces toxin and CDAD recurs.
Dr. Alfa’s research program is directed towards reducing the spread of nosocomial pathogens such as CDAD by developing alternative therapeutics that would be capable of preventing, or treating CDAD and/or reducing recurrences of CDAD. The primary objective is to use specific antibodies that are delivered by a natural food product (e.g. egg yolks) to the gut of a person in a manner that will protect the person from infectious pathogens such as C.difficile. This type of therapy is referred to as “passive immune therapy” because the antibodies that are protective are not produced by the person but provided from some outside source. This is similar to how new born babies are protected from infectious diseases within the first few months of life because they have circulating antibodies that were originally derived from their mothers blood prior to birth or are receiving maternal antibodies from their mothers milk. These maternally derived antibodies are short-lived. The objective would be to mimic this type of immune therapy to provide a similar type of short-lived protection to patients who enter healthcare facilities to reduce their risk of acquiring CDAD.
An advantage of this type of therapy is that it does not induce antibiotic resistance because it does not target the bacterial replication the way that antibiotics do. Immune therapy provides a “tag” that binds to the specific organism and either directly inactivates it (e.g. binds to critical site on toxin and prevents the toxin from acting) or helps the body’s own immune system rapidly eliminate the organism through the phagocytosis killing process. This means it can be used “in addition” to any underlying antibiotic therapy but will not contribute to creation of “super-bugs” that are resistant to many antibiotics.
Egg yolks have a high concentration of antibodies. The specificity of what these antibodies are directed against can be controlled by immunizing the hen with antigens that ensure the antibodies in the yolk are targeted to the infectious agent (or critical subcomponents of the bacteria). Dr. Alfa’s preliminary work indicates that this approach can be used for CDAD. The primary objective of Dr. Alfa’s project is to characterize how to effectively deliver the egg yolk antibodies in a way that either prevents CDAD from developing – or helps eradicate the infection once it has developed. One major aspect of the research program is to determine if the immune therapy alone (i.e. without antibiotic therapy) is sufficient to prevent or treat CDAD – or whether antibiotics targeted at the vegetative organism are still needed. In addition it is hoped that the use of immune therapy will reduce or eliminate the risk of relapse after antibiotic therapy is completed.
|
