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 Let's put testing under the microscope!

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Join date : 2016-01-07

Let's put testing under the microscope! Empty
PostSubject: Let's put testing under the microscope!   Let's put testing under the microscope! EmptySat Jun 11, 2016 11:07 am

Typically, those of us with IC/PBS originally present to our doctors with classic UTI symptoms.  A sample is sent off for testing and returns with a negative finding.   With this in mind, should  UTI testing methods, thresholds and criteria be the first thing to go under the microscope?    

I’m not a science person, so this is my layperson’s understanding of the science behind testing.  Labs around the world use the concepts of Koch’s Postulates (a set of scientific rules) to determine proof of bacterial causation when testing for UTIs.  Although these rules have been considered a useful benchmark for nearly 130 years, newer findings of bacterial species and behaviours (ie polymicrobial infection) have proven its limitations.  With the acceptance that Koch’s Postulates has such limitations, should we be questioning it as a ‘standard of proof’ to absolutely rule out causative agents when it comes to testing for UTIs in the first instance?  

For those who don’t know about Koch’s Postulates, it’s a set of scientific criteria first formulated in the late 1880s by German physician, Robert Koch.  These rules date back before Australian women were given the right to vote, so this gives an idea of the historical period.  Koch determined that if a pathogen was responsible for causing a disease, it must:

• be found in all cases of the disease;
• be isolated from the host and grown in pure culture;
• reproduce the original disease when introduced into a susceptible host; and
• be found present in the experimental host so infected.

Although following Koch’s Postulates has successfully proven causation (and ultimately, led to a cure) for many infectious diseases, it has growing limitations that are being recognised as technologies develop.  For example, Koch’s Postulates do not apply to infections such as cholera and leprosy, they do not apply to cell wall deficient bacteria, they do not apply to polymicrobial infections and they do not apply to viruses.  To try to bring Koch’s Postulates into the 21st century, a new molecular version was developed that considers genes and virulence factors.  

Based on the concepts of Koch’s Postulates, (which are used all day, every day, in labs around the world), to determine a positive urinary tract infection there must be a PURE GROWTH of a KNOWN URINARY PATHOGEN.    The growth must multiply to the point of reaching a set COLONY COUNT, which was determined by Edward Kass in the late 1950s.

I’ll break this down further for discussion.

PURE GROWTH:  There’s a gap in this rule when considering polymicrobial infections.  A polymicrobial infection is one that involves more than one bacterial species, or it can be a combination of two non-pathogenic bacteria that come together to become pathogenic, or it can be a mix of bacteria, fungus, virus or mould that give each other the pathogenic edge (Brogden, 2005).  

Koch’s Postulates assume that an infection of the urinary tract must involve only one bacterial species.  If more than one bacterial species is cultured from the urine sample, it’s reported as ‘no significant growth’, ‘mixed growth of no significance’ or often even written-off as contamination.   Kass, also working on the assumption that urine is sterile, discriminated between pathogens and contaminants by establishing a measurable threshold, based on unproven rules that defined a contaminant (Malone-Lee, J,  2014).  

When my results kept coming back with ‘no significant growth’, I spoke to the head microbiologist.  He told me at this particular lab, no significant growth usually meant more than one bacteria grew during the process and was considered contamination.  Despite my forms requesting all bacterial growth be reported, the lab would not do this.  When I quizzed the microbiologist further on the possibility of polymicrobial urinary infections, he dismissed this by saying polymicrobial infections could ‘sometimes’ apply to elderly people, as they are riddled with bacteria.

Q.  What evidence did Koch have that proved infections are caused by only a single organism?
Q. Could following these concepts of Koch’s postulates be wrongly ruling out legitimate polymicrobial infections of the urinary tract on a daily basis?  

A KNOWN URINARY PATHOGEN:  We’re learning hot off the press that urine is not sterile and, surprisingly, the bladder contains a community of bacteria that are being likened to the protective bacterial communities found in the gut.  This is being referred to as FUM - Female Urinary Microbiome (Wolfe, A & Bruabaker, L, 2015).  

Q. Given the recent discovery of FUM, should we now be questioning the existing criterion that determines known urinary pathogen?

COLONY COUNTS:   For diagnostic purposes, a bacteria is only considered a pathogen if it grows to a certain measure during the culturing process.  This is known as a colony forming unit (cfu).  The adoption of the cfu came from Kass’ 1950s study of 74 women with acute pyelonephritis (a kidney infection).  He then backed up his findings with another study of pregnant women with severe acute pyelonephritis.   From these two studies, he determined a (widely criticised) diagnostic measure for pathogenic bacteria to be held at 10^5 cfu.  

Alongside basing this benchmark on those with severe, acute kidney infections, Kass didn’t consider variables associated with low bacterial counts, such as difficulties in growing certain bacteria outside the body (i.e. cell wall deficient bacteria).  He also didn’t take into account that some bacteria are slow growing (i.e. S. saprophyticus), or the concentration of the urine sample (Franz, M & Horl, WH, 1999).  Scientists and researchers have criticised Kass’ threshold as insensitive and questioned its suitability as a diagnostic criterion (Stamm, 1982; George, N., 2004; Khasriya, 2009).

Q. Could ignoring these valid variables impact on reaching the colony count set in the lab and possibly lead to  false negative results?

To summarise, these are my questions again:

1. Given that new technologies, like PCR testing, are proving Koch’s Postulates to be even less applicable than originally believed, should we be questioning the accuracy of using Koch’s Postulates in determining bacterial causation in things such as UTI testing?

2. What evidence did Koch have that proved infections are caused by only a single organism?

3. Could following concepts of Koch’s postulates be wrongly ruling out legitimate polymicrobial infections of the urinary tract?

4. Given the recent discovery of the female urinary microbiome (FUM), should we be questioning the existing criterion that determines known urinary pathogen?

5. Could ignoring valid variables (like urine concentrations/fluid intake, slow growing bacteria and bacteria that are difficult to grow in a lab) impact on reaching the currently accepted bacterial colony count that determines a positive growth?
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Posts : 92
Join date : 2016-01-07

Let's put testing under the microscope! Empty
PostSubject: Re: Let's put testing under the microscope!   Let's put testing under the microscope! EmptyWed Jun 29, 2016 7:21 am

I found this opinion piece online that questions the validity of the urine testing methods currently used - it's from Professor James Malone-Lee in the UK, Feb 2016. I'll paste the section on dipsticks and cultures, but there's more to read about treatments for over active bladder (OAB) and other regular testing offered by urologists, if anyone's interested:

The title is: Botox for your bladder… and other incontinence treatments that work. Many regular remedies are worse than useless, warns a leading specialist

"The checking of urine for infection is another vale of tears. If a doctor or nurse dips a test stick into your urine and it turns positive for leucocytes or nitrites, then the nature of the test means that you definitely have a urinary-tract infection. But if the test is negative, the sensitivity is such that there is no justification for claiming you do not have an infection. If your urine is then sent to the lab for culture and a microbe is isolated, it’s likely that this microbe is contributing to your distress. But if the culture is negative it is again wrong to claim this proves an absence of infection; the culture is too insensitive. For these reasons, negative tests are unhelpful and a cause of terrible suffering. Many women with the appropriate symptoms are dismissed as not suffering from an infection when they do in fact have one. This controversial view is supported by much published literature. I am sorry to record this, because in doing so I identify a worrying deficiency in our diagnostic protocols, but the evidence is out there for everyone to read. Science points to clinical history and examination as the best means of finding a diagnosis.

"In writing about miserable symptoms that needlessly blight the lives of too many people, I am critical of the approaches to care that are currently promoted and knowingly risk opprobrium. However, the published evidence persuades me that we should re-evaluate current practices and in many cases replace them.

"I am close to retirement now and I do not believe that this critical reappraisal will come easily from the clinical professions or the health service bureaucracies. I am, however, optimistic. The most impressive change in medicine I have seen in my career is the freedom, gifted by the internet, for patients to become well informed about their own conditions. They can form themselves into campaign and support groups of similarly affected peers and these can be an astonishingly powerful force. Thus, if you are suffering from urinary symptoms, I encourage you towards the Cystitis and Overactive Bladder Foundation (COB) website where the various forums provide more wisdom than I can offer.

"By banding together like this, informed sufferers can campaign for the right to receive rational care, rooted in the practical wisdom of medicine’s ethical history, with technology deployed only when appropriate and after diligent forethought."

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