Testing for infection
Scientific folk want evidence of causative agents to enable
disease; patients want focus on their symptoms, their illness, while science
works on the details. Both groups make equally valid points, but lives are at
risk and people are suffering.
The question of pathology testing is perhaps the most contentious issue
to emerge from this inquiry, and is at the root of the frequently-posed and
incessantly debated question: can Lyme disease be contracted in Australia? The
committee explored this issue at length in its interim report but found that
conclusive answers were elusive. In this, its final report, the committee aims
to identify a few areas where some progress may be made.
Evidence presented to the committee over the course of this inquiry
suggests three principal points of contention:
lack of an agreed definition and understanding of what constitutes Lyme-like
illness and how, if at all, it differs from Lyme disease.
over laboratory testing protocols and results when looking for the pathogens
responsible for Lyme disease.
lack of conclusive, accepted scientific evidence linking tick bites in
Australia to Lyme-like illness.
This chapter will examine all three.
Lyme, or Lyme-like?
The illnesses discussed throughout this inquiry are Lyme disease,
chronic Lyme disease and Lyme-like illness. The terms are often used
interchangeably, and generate considerable disagreement.
Classical Lyme disease
In its interim report, the committee outlined known epidemiological
facts about Lyme disease in detail.
Classical Lyme disease, or Lyme borreliosis, is a tick-borne disease caused
by a number of closely related species of Borrelia bacteria. Lyme
disease is recognised as one of the most common tick-borne diseases in humans,
and is known to be present in parts of the United States of America (US),
Europe and Asia. Lyme disease is named after the town of Lyme in Connecticut
where it was first recognised in the early 1970s.
There are a number of common species of Borrelia known to cause
Lyme disease. In the US, the most common of these is Borrelia burgdorferi.
Different species of Borrelia have been identified as Lyme pathogens in
Europe and Northern Asia, such as Borrelia afzelii and Borrelia
garinii. Although different, these species are related and referred to as
the 'Borrelia burgdorferi sensu lato complex'.
Chronic Lyme disease
If classical Lyme disease is understood to be an acute infection, one
that is treated with readily available antibiotics,
the concept of chronic Lyme disease, on the other hand, is a controversial one.
This is in part because the symptoms some patients experience after an acute
Lyme infection are not easily defined. As put by the Department of Health
In some patients, a post-treatment late Lyme disease syndrome
occurs, with patients experiencing non-specific symptoms like headache,
fatigue, and muscle and joint pain. These symptoms are generally not regarded
as persistence of active infection but more as post infectious problems.
There is much debate about whether post-infection symptoms constitute chronic
Lyme disease, whether such a disease even exists. This debate, as set out in
the committee's interim report, is not unique to Australia. Disagreement
revolves around whether an ongoing Borrelia infection can manifest as chronic,
debilitating illness once the acute state of infection has subsided:
The department is aware of the controversy in endemic areas
overseas about the diagnosis of chronic Lyme disease. That controversy which
focuses on persistent infection rather than post infectious sequelæ as the
cause of ongoing symptoms is relevant to the Australian context because the
Australian advocacy groups for a Lyme disease-like illness support the concept
of persistent infection.
Australian medical authorities do not support the use of the term
'chronic Lyme disease', nor do they accept that its associated symptoms are the
result of ongoing Borrelia infection:
The issue of chronic Lyme disease assumes that there is
persistent, active infection. That is what is so contentious. The mainstream
conventional position is that the sequelae that we see after an infection is
post-infectious and not active infection ... So, in Australia, like in many other
countries that we would be like-minded with in terms of medicine, the experts
in microbiology and infectious disease will not readily accept that there is chronic
Lyme disease or chronic persistent active infection. So, for that reason, and
because of the association between what is happening in Australia with chronic
Lyme disease, most of the medical profession expert in this field do not accept
that it is Lyme disease.
This view was, however, challenged by submitters such as Dr Mualla
McManus, a scientist with credentials and expertise in immunology,
pharmacology, pharmacy, neuroscience and molecular biology:
The significance of Borrelia infection is that once
you are infected with it, you have to be treated early so that it does not
disseminate. Once disseminated, it becomes chronic. It is very hard to
eradicate...after 20 years of antibiotic treatment on a patient, they took the
samples from the synovium, the knee joint, and they could actually identify the
Borrelia burgdorferi—after 20 years of treatment. So you are looking at
a unique pathogen that is emerging, but the problem with this pathogen is that
it is emerging very slowly.
The notion of chronic Lyme disease is also important to understanding
the debate around laboratory testing results, to be discussed later in this
Whereas Lyme disease is caused by known pathogens, and later stages of
infection are sometimes referred to as chronic Lyme disease, the term 'Lyme-like
illness' has been used to describe a constellation of symptoms thought to be caused
by a variety of tick-borne pathogens. As these symptoms are closely connected
to those exhibited by patients with classical Lyme disease, the terms 'Lyme
disease', 'Lyme-like illness' and 'chronic Lyme disease' are often used
interchangeably by patients and their advocates.
Public discourse on Lyme-like illness is problematic in part due to a
lack of agreement or understanding around terminology:
The department [Department of Health WA] notes that there is
no widely published or accepted definition of Lyme-like illness. It is not
possible, therefore, to determine the prevalence or geographical distribution
of Lyme-like illness in Australia or even to be certain that different groups
discussing Lyme-like disease are referring to the same concept.
Patient advocacy groups, such as the Lyme Disease Association of
Australia, similarly recognise the lack of clear definition. From their
perspective, however, the semantic debate is unhelpful:
There is considerable contention around these two simple
words ‘Lyme’ and ‘disease’. On their own they do not offend, used together they
invoke very powerful, often emotive shifts in the demeanour, language and
behaviours of others. Depending on your perspective, we either have it in
Australia or we don’t – it's binary.
It is impossible to find a precise and consistent definition
of the term in Australia. It is used by the medical community to describe a
very specific strain of a biological organism, or sometimes organisms; even
they can’t decide. It is used by the rest of the world to describe a suite of
symptoms and infections caused by a number of organisms.
...We don’t know what people have. We do know that some people
become seriously ill, sometimes after the bite of a tick, and that their
symptoms closely resemble that of internationally defined Lyme disease.
Given that the pathogens which cause Lyme disease overseas are known,
Australian authorities are firm in the view that the term 'Lyme disease' is misused
in the local context. This is because the pathogens responsible for Lyme
disease overseas were identified some time ago, and have not been identified
The term is used to describe a variety of symptoms and
clinical features ranging from well-defined illnesses to non-specific chronic
symptoms. However, there is no evidence to indicate that infection with Borrelia
burgdorferi sensu lato, resulting in Lyme disease, has been acquired within
Australia. In addition, there is no convincing scientific evidence to date that
tick bites from native Australian ticks result in Lyme-like disease.
Critics of this position, however, challenge both the assertion that a) Borrelia
known to cause Lyme disease have not been found in Australia, and b) only
bacteria known to be part of the Borrelia burgdorferi sensu lato complex
can cause Lyme disease.
Lack of consensus on the name or
If symptoms of Lyme-like illness in Australia lack clear definition, its
cause is similarly very poorly understood and in dispute. As put by Dr McManus,
exclusive focus on Borrelia burgdorferi as a causative agent for
Lyme-like disease may be counterproductive:
We need to change our view. The government only thinks of
Lyme disease, and follows the CDC [US Center for Disease Control] criteria. I
have an explanation for Borrelia...There is Borrelia burgdorferi sensu
lato group, and a subset of that is Lyme disease Borrelia. There is
relapsing fever, which has over 20 genospecies known today. We have reptilian Borrelia,
but the infection has not yet been found in humans. So if we concentrate on
Lyme disease we are missing out on 80 per cent of other Borrelia
infections, and that is really dangerous. We are being short-sighted. Some of
the relapsing fever genospecies can produce 80 per cent of their infections
neurologically, but there is no research, because relapsing fever is a
poor-country disease. It is endemic in Africa, Asia, India, Indonesia and
Vietnam. All the focus is in Lyme disease; everyone makes such a fuss about it.
Lyme disease, Borrelia burgdorferi sensu stricto, is much easier to
treat that relapsing fever. This is something that has not been understood.
Dr Richard Horowitz, who spoke to the committee in a private capacity, suggested
that Lyme disease itself is far more complex than first imagined. The fact
that Lyme disease is still poorly understood, Dr Horowitz believes, contributes
in large part to the controversy over its diagnosis and treatment:
I think some of the controversy is happening because we are
not understanding the definition of what Lyme disease really is. The patients
that I see with Lyme disease do not just have Borrelia burgdorferi sensu
latu. What they end up having is many other species of bacteria, viruses and
parasites because the ticks are now containing many of these different species
and are rapidly spreading.
The evidence supplied by Dr Horowitz is not easily dismissed. He is one
of the founding members, as well as past president, of the International Lyme
and Associated Diseases Society (ILADS), has published a large number of
peer-reviewed articles on the subject and has engaged with a number of
governments—including the US, Chinese, UK, French and Belgian—on the subject of
Lyme and related diseases.
On the basis of his own research and that of others cited in his
submission, Dr Horowitz in fact advocates a move away from the term "Lyme
disease", submitting that the Lyme diagnosis fails to capture the chronic
symptoms and multiple infections exhibited by many patients:
One of the first and most basic problems we face is in
helping Australian patients is defining “chronic Lyme disease” or “Lyme-like
illness”. Patients with chronic symptoms who see me, either before or after
classical treatment for Lyme disease, have multifactorial causes for their
illness. I call this syndrome Lyme-MSIDS. MSIDS stands for Multiple Systemic
Infectious Disease Syndrome, and represents sixteen potential overlapping
medical problems contributing to persistent symptoms in the Lyme patient.
The first point on the MSIDS map is infections. Ticks are now
containing multiple bacterial, viral and parasitic infections which can be
transmitted simultaneously with Borrelia burgdorferi, the agent of Lyme
disease. Patients infected with Lyme disease and associated co-infections are
much sicker and resistant to standard therapies.
Dr McManus similarly pointed to multiple infections as an impediment to
straightforward diagnosis and treatment:
The scientific community is not in a state to understand the
multiple infections. Over 100 years ago, Koch's postulates were formulated to
say, 'You have one infection, one specific set of symptoms—we give you one
antibiotic.' That was the treatment. But then you come to something with four
or five infections—which one do you treat first? Which is the prominent one
that produced the symptoms?
Doctors do not know, we do not know. There are no clinical
trials, no investigations into it, because most of the research community
thinks that it is too hard to handle. Most of the research on Lyme disease or
any species of Borrelia looks at acute disease because it is easier to
follow. You have got one tick bit, you have got history and you can detect it
because the immune system is competent and you can follow it through and treat
it. But when it comes to chronic—I have talked to IDSA members; they do not
know what to do. ILADS try to treat with long-term antibiotics.
Where to from here?
Despite considerable disagreement around most aspects of tick-borne
illness in Australia, this inquiry also highlighted important areas of
agreement. The committee chose to focus on these, as they are a clear
indication that progress on the issue is possible.
Importantly, the committee noted a promising level of interest in
further research and examination of the issues from authorities, such as this
statement from the department indicating its preparedness to work towards
broadening and deepening understanding of tick-borne illness:
We acknowledge that the cause of these tick-bite-associated, chronic
debilitating symptoms may not be limited to a single bacterial species.
Parasitic and viral causes as well as environmental toxins should also be investigated.
As part of the department's work in communicable diseases in
states and territories, we are developing an awareness of newer genomic
technology that is using specimens from patients to look for bacterial and
viral nucleic acid, in an attempt to find commonalities in patient specimens.
It may reveal a common pathogen or pathogens which can be further considered.
The committee notes that the term 'Lyme-like illness' is in use to
describe a constellation of symptoms and what may very well be a number of
different illnesses. In the committee's view debate around what to call tick-borne
illness in Australia has impeded progress on establishing its cause and
optimising treatment. The scope of what scientists and clinicians are grappling
with—tick-borne infections, co-infections and post-infection symptoms—is not
yet well defined, but appears to be considerable. Australia's understanding of
what is in our ticks, and how it might be making some people sick, is clearly at
a very nascent stage.
The committee notes the department's commitment to exploring tick-borne
illness and identifying the pathogens involved:
Through regular communication and correspondence, the
department has gained a deeper appreciation and real concern for those
Australians experiencing these chronic debilitating symptoms, which they
associate with a tick bite. The department remains engaged with the patient and
medical community to continue to find, share and understand the evidence associated
with this medical conundrum. The department hopes our work with diagnostic pathology
and research communities will result in answers and relief for patients and
The committee is encouraged by this and calls on medical authorities to
engage with the research presented during the course of this inquiry.
Diagnosing Lyme disease
Diagnostic testing of samples—usually blood—taken from patients suspected
of having Lyme-like illness is perhaps the most controversial issue to emerge
from this inquiry, and one that evidence returned to time and again.
Much—if not most—of the evidence presented was contradictory, and most of
it was confidently articulated by qualified, experienced and respected
professionals. It is therefore necessary to establish from the outset that the
committee is not in a position to arbitrate a scientific debate. Instead, the
committee's objective is to broadly define the parameters of the disagreement
around laboratory testing, and identify how some progress can be made.
As outlined in the committee's interim report, a number of prominent and
experienced doctors have questioned the reliability of laboratory tests used to
diagnose or rule out Lyme-like illness—classical and chronic Lyme disease or
other Lyme-like illnesses. Broadly, the question can be seen from two
Lyme disease, caused by Borrelia bacteria, cannot be contracted in
Australia. This position is held by the Australian medical authorities and many
experts in relevant fields, and supported by the fact that accredited
Australian laboratories return negative results when testing for Lyme disease.
illness with considerable similarities to Lyme disease can and has been
contracted in Australia, and pathogens which cause Lyme disease do exist here.
This position is held by some doctors and scientists, and supported by the fact
that patients who have not travelled overseas have had positive laboratory test
results when tested for Lyme disease by some Australian and overseas
A key part of the matter is the issue of test quality—understanding which
testing protocol is optimal and how test results are to be interpreted.
This section will build on evidence already explored by the committee's
interim report. Evidence already examined by the interim report is only
referred to again where necessary.
The two-tier testing protocol
As previously described, classical Lyme disease is caused by a number of
known, closely related species of Borrelia bacteria. The Borrelia strains
known to cause Lyme disease in Europe, for example, are different to the strains
responsible for Lyme disease in the United States (US)—together the bacteria
make up the Borrelia burgdorferi sensu lato complex. It is antibodies to
these bacteria that most laboratories test for when doctors send patients for
pathology tests, looking to diagnose or rule out Lyme disease.
The committee's interim report detailed the protocol used for testing
In brief, most Australian laboratories accredited with the National Association
of Testing Authorities (NATA)
use a two-tier serological diagnostic protocol, as is also the case with
accredited US and European laboratories.
The first tier is most commonly an enzyme-linked immunosorbent assay
(ELISA). If the ELISA test returns a positive result, laboratories will then
conduct a Western blot test. The committee understands that laboratories can,
but will rarely run a Western blot test in the absence of a positive ELISA
This testing protocol is considered to be world-class and reliable.
Accredited laboratories using the protocol in Australia have only returned
positive results for Lyme disease acquired overseas, reinforcing the
understanding that the pathogens responsible for Lyme disease are not endemic
Seeking to understand the logic behind the two-tier testing system, the
committee questioned why the ELISA test was routinely performed first. Professor
Stephen Graves, spokesman on Lyme disease for the Royal College of Pathologists
Australasia, described how and why the two tiers of testing ensure accuracy:
The Western Blot assay is more “reliable" than the ELISA
in that it is more specific, at least when the IgG class of antibodies is being
tested for. This means it is less likely to give a false-positive result. i.e.
mis-call some other illness as Lyme Disease.
The ELISA assay is more sensitive than the Western Blot and
will detect almost all patients with antibodies to the Lyme bacteria, but it is
less specific and some of the antibodies it detects are not the result of Lyme
Disease. These are cross-reacting antibodies. The ELISA assay can therefore give
By going straight to a Western Blot assay, there is a
possibility that some Lyme cases could be missed, as it a less sensitive assay
than the ELISA.
The logic for this serological testing pattern is that the
ELISA is a “screening” assay that will detect all cases of Lyme Disease [ and
some non-case also ] and the Western Blot is a “specific” assay and will
differentiate the true Lyme cases from the non-Lyme cases, as it is a more
specific assay than the ELISA.
In practice however, both assays can give false positive
results and also false-negative results. By having the 2 assays the lab is more
likely to obtain the correct result.
If a lab went straight to the Western Blot assay they are
likely to miss some genuine cases of Lyme Disease.
However, a considerable number of submitters and witnesses questioned
the reliability of the protocol. These ranged from patients and their advocates,
to respected members of the medical and scientific community—each provided
evidence in stark contrast to that presented by Professor Graves. Their
positions can be broadly divided into two categories:
those who hold that the ELISA test is not sensitive enough, can
therefore only detect antibodies to Lyme disease in some patients, and cannot
rule infection out; and
those who hold that Lyme-like illness is in Australia caused by
an as-yet unidentified pathogen, perhaps a species of Borrelia unique to
Australia, and therefore testing for Borrelia which are endemic overseas
A small sample of the evidence presented in support of a move away from
ELISA-led testing is cited below.
Dr Peter Dobie, Secretary of the Australian Chronic Infectious and
Inflammatory Disease Society (ACIIDS), told the committee that Lyme disease and
Lyme-like illness were underdiagnosed in Australia due to over-reliance on
ELISA, which in his experience is not sensitive enough to detect the presence
[M]ost Australian pathology laboratories are doing the wrong
blood test for Lyme disease. This is one reason why Lyme disease and Lyme-like
illness are underdiagnosed in Australia. Most laboratories are using a test
called the ELISA test. This test is not sensitive enough to detect most cases
of this illness. There is a large body of scientific opinion that this test
should be abandoned because of the high rate of false negatives.
Mr Christopher Walker, Acting Chief Executive Officer of the Karl
McManus Foundation, was unequivocal in his assessment of the two-tier protocol:
The complicated nature of Borrelia infections makes it highly
possible for laboratory tests to miss an infection, for multiple reasons. One
of the biggest flaws in the current Australian Borrelia or Lyme disease testing
is the singularity presumption—that is, a presumption that a negative test
result is a positive confirmation that one does not have a Borrelia infection.
Permit me to repeat that: there is a presumption that a negative test result is
a positive confirmation that one does not have a Borrelia infection.
Dr Richard Horowitz similarly questioned the logic behind the protocol,
concluding that ELISA lacks the necessary sensitivity to detect ongoing
According to these guidelines, an immunoblot is not to be
performed if the ELISA is negative, despite the poor sensitivity of ELISA tests
ranging from 34 to 70.5%.
The problem with that is if you look at the scientific
literature carefully, the scientific literature is supporting that the ELISA
test is not reliable...these organisms can persist. I think the literature is
Dr McManus concurred, describing Borrelia as complex and
possessing a considerable capacity for mutation which makes testing difficult:
The testing is problematic because the bacteria Borrelia has
got very variable, hypervariable genomes. Basically, it can mutate inside you.
If I had a rat injected in one leg with one genome species of Borrelia and
I took blood from the other leg, I can get a different genospecies. That is not
normal; you do not normally find that. If I inject a rat with a staph.
aureus, or a golden staph, I get the golden staph, but a different strain,
not a different genospecies. The reason for this is that this bacteria: (1) can
mutate a lot; and (2) it as a lot of phages, or bacterial viruses. I can give
you an example. Golden staph has got only one phage, and it is very difficult
to eradicate from hospitals because of the way it develops a tolerance to all
the treatment protocols. You have a Borrelia, the burgdorferi one
in the US has 21 phages. That means it can dress itself in so many different
ways that it can hide in your body—it can change from vector to vector; it can
be in a tick; it can be in a deer; it can be in a human—because it has the
capacity to change itself so enormously. I do not think that is really
understood by the scientific community or by the clinicians.
The committee put this to Professor Graves. He indicated that having
hypervariable genomes was not particular to Borrelia, but instead could
be said of all microbes. He reiterated that the accuracy of the two-tiered
protocol in use by the majority of laboratories is not impeded by the hypervariable
This problem doesn’t apply to serological assays that detect
antibodies, as a wide variety of antibodies of different specificities that are
produced by a patient in response to an infectious agent.
Those persons who believe that Lyme Disease occurs in
Australia can always point to minor defects in certain assays that may result
in the assay not detecting the occasional patient with Lyme Disease due to a
rare variability in the patient or the bacterium. But this would not be the
case for the majority of patients and the fact that no genuine patients have
been detected, by a variety of laboratory assays, strongly points to the
conclusion that this infection [Lyme Disease] does not occur naturally in
The patients who claim to have Lyme Disease have something
else wrong with them, whether an infection transmitted by tick bite or not
remains to be seen. They clearly need help but giving them the wrong diagnosis
does not help them!
The committee noted the contradictory evidence.
Dr Richard Schloeffel, Chairperson of ACIIDS, challenged the role which
has been ascribed to laboratory testing, making the point that pathology should
only be used to confirm a doctor's clinical assessment, not the other way
around. The tests most commonly used, Dr Schloeffel, stated, were of little use
in patients who are immunosuppressed:
The tests are not good enough. The bugs are varied. There are
viruses, parasites and bacteria. Pathology is very secondary. Sure, do no harm,
but do not lie to your patient that they are not sick because the test was
This was supported by Ms Jennie Burke, Director of Australian Biologics,
who clarified how the devastating effect Borrelia has on patients'
immune system makes detection through ELISA, which looks for an immune
With tests that rely on an immune response, again Borrelia is
difficult, as it has a devastating effect on the patient's immune system, which
may lead to abhorrent effects in tests. With other infections you would expect
the patient to produce IgM antibodies in the initial stage and, three to six
months later, the antibodies to seroconvert to IgG antibodies. With Borrelia,
however, patients may show no antibodies at all. They may not seroconvert and
can remain IgM positive for greater lengths of time than usual.
Australian Biologics does not use the two-tier protocol to detect Borrelia
infection. This is explored below.
Other testing protocols
There are a number of laboratories which do not use the two-tier testing
protocol, and which have reported positive results for Australian patients who
have never travelled to known Lyme-endemic areas overseas. The laboratories
doctors prefer to use are:
Australian Biologics Testing Services, a Sydney-based laboratory
which is not yet accredited with NATA;
ArminLabs, a German laboratory with a focus on Lyme disease which
is in the process of accreditation with the German accreditation body, Deutsche
Infectolab in Germany, which is accredited by DAkkS;
IGeneX, a US-based laboratory which specialises in Lyme Disease
and associated tick-borne diseases.
Australian Biologics offers three types of testing for Borrelia—DNA
testing, or Polymerase Chain Reaction (PCR), an immunoblot test imported from
Germany, and EliSpot testing, also from Germany. Australian Biologics uses
these tests because of a perceived lack of sensitivity of ELISA testing:
Earlier ELISA testing was known to have poor sensitivity
whereas the newer ImmunoBlot assays using recombinant antigens have a much
higher level of sensitivity. The EliSpot Lymphocyte Transformation Test is
useful to show if an infection is active.
A submission from Australian Biologics explains that the PCR test is the
gold standard for the detection of bacterial infection:
PCR is one of the most sensitive methods utilised to detect
microbial pathogens in clinical specimens. This is particularly necessary when
specific pathogens, difficult to culture in vitro or are known to be of low
level in blood, tissue and other samples, are to be detected. The diagnostic value
of PCR is known to be significant.
False positives vs false negatives
The committee held an additional public hearing partly with the aim of
clarifying the apparent discordance in test results obtained from different
laboratories, however this failed to provide conclusive answers.
In short, evidence on the presence of Borrelia in Australia was once
again contradictory. However, two laboratories testing for the same infection
but getting different results cannot both be right—it is an issue of false
positives versus false negatives.
When asked about the rate of false negatives of ELISA, Professor Graves
assured the committee the tests have a high degree of sensitivity and are not
likely to miss infections. On the contrary, it appears ELISA is more likely to
return a false positive than false negative:
Probably close to zero as it is a very sensitive assay and
won’t miss many cases. However, many of the “positive” results will not be
genuine Lyme Disease as the assay has poor specificity.
In my lab, the Australian Rickettsial Reference Laboratory,
the genuine cases of Lyme Disease that we have diagnosed [all in travellers
returning from overseas and infected in endemic countries] the ELISA assay has
always been positive.
Professor Graves suggested that Australian Biologics must be getting
false positive results:
I would never refer a specimen to a nonaccredited laboratory
so I never refer specimens to Jenny because I do not think that her laboratory
is doing the tests properly. I think she is getting a lot of false positives.
That is where the difference is. I hear everybody laughing but that is the
bottom line. I think that she is putting out a lot of false positives for Lyme
disease, mycoplasma and whatever so I do not have confidence in her testing;
therefore, I would not refer to her.
However, the committee noted that there is no concrete evidence to
support the conclusion that Australian Biologics is returning false positives.
The committee sought to clarify, through a question taken on notice,
whether testing protocols used by Australian Biologics were peer reviewed:
Yes, we have swapped samples (both positives and negatives)
with the Reference Laboratory for Borreliosis in the Czech Republic. We
detected all the samples they sent us and they detected all the samples we sent
them. The six research papers on Borrelia to which we contributed used our PCR
testing and the same samples were also tested by Prof Eva Sapi at New Haven
University. Prof. Sapi is well known for her work on Borrelia. We have also
had correlations in PCR testing with Professor Vett Lloyd at Mt. Alison
University and since 2012 we have participated in a Quality Assurance Programme
offered by QCMD (Quality Control Molecular Diagnostics), based at Glasgow
University. We now have 5 years of results showing 100% correct detection of
Borrelia through QCMD. Dr. Peter Mayn published “Clinical Determinants of Lyme
Borreliosis, babesiosis, bartonellosis, anaplasmosis, and ehrlichiosis in an
Australian cohort” in 2014 (paper is attached) which compared our testing to
that of Igenex. Our positivity rate for Borrelia was given as 59% and Igenex
as 58%. This is very good confirmation of both laboratories’ testing.
Professor Graves suggested that his laboratory and Ms Burke's might do
well to compare the assays they use in order to ascertain why they are getting
What usually happens in a situation like this is that
different labs will compare their assays so we would take a common QAP, quality
assurance process, sample. They would go to different laboratories and be
tested to see whether or not they are getting the same results. That is how we
normally do it. There may be, say, just for argument's sake, six or seven
different assays for detecting antibodies for Lyme disease used in Australian
laboratories. They will all have slightly different sensitivities and
specificities but on the whole most of them will give the same answer—positive
if it is truly positive or negative if it is truly negative. That is how we do
it. Strictly speaking, what we should do is Jennie [Ms Burke, Director,
Australian Biologics] and I should exchange specimens and methodologies and see
why we are not getting the same results.
Representatives of the Karl McManus Foundation suggested that some of
the confusion could be alleviated if laboratories stated the parameters and
limitations of their results when these are provided.
Clarity around these issues may be within reach, however. As noted in
the committee's interim report, the department has contracted the National
Serology Reference Laboratory (NSRL) to conduct a review of serological assays
used to diagnose Lyme disease. The review is looking at assays used in
Australia and overseas.
The NSRL provided an update on the status of the review:
We have received approximately 650 specimens from the
collaborators in UK, Germany, US and Australia, along with the results the
collaborators obtained for those specimens.
We have collected 308 specimens prospectively from Australian blood
donors who have not travelled outside Australia.
The collaborators have informed us of the serology assays they
use to test for Lyme Disease.
NRL has purchased sufficient of each of these assays to test all
collaborator and blood donor specimens on all assays.
We are in the process of testing the specimens now.
The specimens are being tested in a blind manner. By that I mean
that the specimens are labelled with an NRL identifier, not the identifier from
the collaborator. Therefore we do not know the origin of the specimens or the
results obtained by the collaborators as we are testing them. Therefore we
cannot say anything at the moment about what the results are showing.
This inquiry has highlighted what is now decades-old disagreement on whether
classical Lyme disease can be contracted in Australia. The committee
acknowledges evidence provided by Australian medical authorities indicating
that accredited laboratories—following established best-practice testing
processes—have not found classical Lyme disease in Australian patients, with
the exception of those who most likely contracted the disease overseas. This is
what leads many in the medical profession to the conclusion that classical Lyme
disease is not endemic to Australia.
However, while ever the issue of test quality remains contentious, the
committee warns against ruling out the possibility that these bacteria are
endemic to Australia. The committee is not satisfied that enough has been done
to examine testing processes used by laboratories such as Australian Biologics.
In the absence of such examination, the committee does not support an a
priori conclusion that those test results are false positives.
Furthermore, the very fact that the reliability of the two-tiered
testing protocol for Lyme disease is being questioned by respected doctors and
scientists is, in the committee's view, reason enough for authorities to give
careful consideration to these doctors' concerns. This notwithstanding, acknowledging
the controversy does not in itself constitute proof of the inadequacy of the
two-tiered testing protocol. The committee notes that work on developing new
tests for Lyme disease is underway overseas and urges Australian medical
authorities to remain appraised of the development of these tests.
The committee notes the NSRL review currently underway with interest. It
is the committee's hope that this review will be conducted in a transparent
manner and its findings published as anticipated. The committee expects that
this review will provide some much-needed, conclusive answers, and enable the
discourse on testing protocols to progress beyond the current impasse.
What is in our ticks?
Ticks in Australia, like ticks elsewhere, harbour a microcosm of
bacteria, viruses and other pathogens. To reiterate, the department states that
bacteria responsible for Lyme disease have not been identified in Australian
ticks, and discovering such a bacterium is necessary before an evidence-based
conclusion about the existence of Lyme disease in Australia—or a related
illness—can be made:
The conclusive finding of a bacterium that could cause Lyme
disease or a Lyme disease-like illness in Australia has yet to be made. Such a
finding would put beyond doubt the existence of Lyme disease, or a Lyme
disease-like illness in Australia.
Many submitters and witnesses concurred with this position, and
suggested an alternative explanation: that another, as yet unidentified
pathogen, may be the likely cause of tick-borne illness in Australia.
Others however challenged the assertion that bacteria causing Lyme
disease were not present in Australian ticks, providing evidence to support
Both positions are explored below.
Is Lyme Borreliosis endemic in
The committee was provided with excerpts from doctoral research dating
back to the early 1990s which alludes to the likely presence in Australian
ticks of Borrelia associated with Lyme disease. The objectives of the research
were as follows:
- To determine whether
Australian ticks carry and transmit spirochaetes related to Borrelia
- To develop a specific and
sensitive sero-diagnostic test to assess whether or not there is a correlation
between clinical illness and the presence of Borrelia burgdorferi
specific antibodies in likely Australian LB [Lyme Borreliosis] candidates.
- To access the distribution
of LB along the East Coast of Australia.
The research project was initiated in 1989 and concluded in 1994. It
began with a focus on the Manning Valley in New South Wales (NSW), but expanded
to include the Sydney and Hunter Valley regions of NSW as well.
The paper concluded that Lyme Borreliosis does exist indigenously in
Australia, because patients who had never left Australia tested positive for Borrelia
antigens and displayed corresponding clinical symptoms.
Based on these findings, Dr Wills called for further research into:
- Development of suitable
cultural conditions for the growth and maintenance of Australian B.
- The molecular characteristics
of Australian strains of B. burgdorferi so that a taxonomical comparison
with existing genospecies can be obtained.
- A more exact definition of
the clinical manifestations of Australian Lyme disease and the immunological
responses of patients.
- Determination of
epizootiology of LB in Australia, and the importance of LB in Australian wild
and domestic animal populations.
It is unknown to what extent this research has been pursued or reviewed.
The department did, however, address this research in a scoping study conducted
in 2013, concluding that the results were unable to be replicated:
To this date, there has only been one report of Borrelia
species being found in I. holocyclus ticks, but the cultures were not
confirmed and were unsustainable (Wills and Barry 1991).... Spirochaetes
morphologically similar and antigenically related to Borrelia burgdorferi
were cultured from the gut contents of I. holocyclus and Haemophysalis
spp. ticks by Wills and Barry (1991), but the cultures weren’t sustainable
and these results have not been able to be repeated from ticks collected more
The committee notes that the department does not conclusively rule out
the presence of classical Lyme disease in Australia. Instead, the department
expresses a more nuanced position, stating that there is no evidence to suggest
the presence of the bacteria:
[T]he likelihood that Australia has an indigenous form of
classical Lyme disease is questionable, given that a causative micro-organism
with a competent vector is yet to be found. Whether a form of tick-borne human
borreliosis exists in Australia is yet to be determined.
A different Borrelia?
Some witnesses suggest that—accepting that Lyme disease is caused by
members of the Borrelia burgdorferi sensu lato complex which have not
been found in Australia—a different species of Borrelia might be present
On that basis, I would like to say that as far as I can
see—from the patients' clinical symptoms, from the scientific research and from
the preliminary results from the tick-borne disease unit—we do not have Borrelia
burgdorferi, or Lyme disease, in Australia. What we have is a unique Borrelia
infection. The problem with this disease is the symptoms are non-specific, so
not every single Lyme patient ends up with the same set of symptoms. It is very
hard to diagnose clinically. You can check the literature: every single
publication will say the same thing. In the US they ask for a history of tick
bite, and in certain areas like Connecticut it is common to have an EM rash, or
the 'bull's-eye' rash, so diagnosis is easier. But in Australia the
symptomology is much broader, and there are a lot more neurological symptoms.
So you will end up with patients having seizures, patients having MS-like
symptoms, patients having atypical Parkinson—atypical. Most of their symptoms
are atypical, so a classical neurologist cannot put them in the perfect box of
multiple sclerosis or whatever they are familiar with.
The plausibility of this theory is supported by other evidence. Dr
Horowitz pointed out that identification of new strains of Borrelia is
progressing at a rapid rate, suggesting that there may be far more species of Borrelia
than are currently identified:
So with inadequate diagnostic testing, and with the multiple
species of bacteria and parasites that are spreading with environmental toxins,
the problem is that with over 100 strains of Lyme borreliosis in the United
States and 300 strains worldwide, although most of them are not pathogenic, we
are finding new species every two years. There have been 15 new Borrelia
species discovered in the last 20 years. The problem is that the testing has a
difficult time keeping up with it.
The committee notes that, as Dr Horowitz states above, most of the new
species found are not pathogenic, they will not cause illness in humans.
However, the identification of new strains of Borrelia, as well as other
bacteria, in ticks around the world, including Australia, is of considerable
significance to this inquiry, as it is possible that some will be found to be
The department noted the recent discovery of new Borrelia species
in some Australian ticks, but cautioned against premature conclusions in the
absence of thorough research:
The department welcomes the finding of new Borrelia
species from ticks found on echidnas. This new Borrelia probably
represents a new clade.
It is different from the Borrelia in the Lyme disease group, the
relapsing fever group and the reptile group. While this is a significant
finding, it is important not to jump to conclusions. Whether these
micro-organisms cause disease in humans requires research into transmission and
human pathogenicity. The same research group has been able to readily identify Borrelia
burgdorferi sensu lato species in ticks collected from endemic areas
overseas. This demonstrates that, to date, with state-of-the-art technology,
there remains no evidence of a cause of classical Lyme disease in Australian
ticks. The Australian government has previously highlighted, in the scoping
study it commissioned, the importance of research not only in ticks but also in
patients, and of the need to draw evidence-based connections, if they exist.
The committee looks at research underway in the next section.
The committee notes contradictory evidence received on the subject of Borrelia
in Australian ticks, and reiterates that it is beyond the scope of this
inquiry to establish whether Borrelia species which may cause Lyme
disease are to be found in Australian ticks. The committee acknowledges the prevailing
view that contracting Lyme disease in Australia is not possible, that our ticks
have been studied and found not to harbour known Lyme disease-causing
However, the committee also notes that evidence challenging this
position has been presented during this inquiry. The committee refers
particularly to the research of Dr Michelle Wills, which has been provided in
evidence by more than one submitter, with consent from Dr Wills. The committee
is persuaded that steps should be taken by the medical authorities to conduct a
review of this evidence afresh if this has not already been done. To be
authoritative and conclusive, such a review must be conducted by an
independent, qualified team of scientists, with its methodology and results
published in full.
More research is needed
Scientific research will play a critical part in identifying the
pathogen, or pathogens, responsible for tick-borne illness in Australia. The
committee's interim report outlined research currently underway. This was
explored further at an additional hearing, with new evidence presented by Professor
Peter Irwin, representing the Vector- and Water-borne Pathogen Research Group
at Murdoch university, on recently discovered potential pathogens:
Since the appearance of Professor Ryan and Dr Oskam before
the committee, we have further characterised a number of bacteria which, in our
opinion, represent potential candidates for tick-borne pathogens in Australia.
These include Neoehrlichia, Anaplasma, Ehrlichia and Borrelia.
Our work with Borrelia has confirmed that it is a unique Australian
species. It is distinct from both the Lyme disease group and the relapsing
fever disease group. Similar work with other bacterial species also reveals a
unique phylogeny. Our conclusion, based on the evidence so far, is that
Australian ticks harbour a relatively unique set of bacteria and therefore
these are unknown to medical science in terms of their capacity to cause
Professor Irwin has emphasised that it is not appropriate to link these
newly identified bacteria to illness in humans.
The next logical step in this research, Professor Irwin advised, will be to
look at which, if any, of the newly identified organisms found in Australian
ticks can be transmitted to humans. This, Professor Irwin concludes, is critical
to determining causation.
Professor Irwin further explained that after potential pathogens are
identified, work will need to be done to assess the impact these may have on
There are several phases in this research. Ours is to form
the building blocks of what is here in the ticks. The whole determination of
disease causation by which of those bugs could cause disease in people is a
further set of work that will require quite significant epidemiological type
We are actually intending to start work in that space. We
intend to apply for an NHMRC grant next year—in the next main funding round—to
support this work. We are starting to gather together collaborators—doctors in
various parts of Australia who see patients with tick bites. We want to
investigate them in a longitudinal fashion to follow those patients into the
Professor Irwin reported having received a new grant which will fund
some studies over the next three years, but called for an urgent increase in
funding through the National Health and Medical Research Council (NHMRC):
The NHMRC is the most relevant funding agency. However, an
understanding of the importance, or relevance, of research into
Lyme-disease-like illness may not be appreciated by all the reviewers and
independent experts. We are aware of a grant application on this topic that was
recently rejected by the NHMRC that scored relatively poorly for the category
of 'significance'. I note also that Professor Kelso explained the NHMRC funding
process in her submission to the committee in April, and I am encouraged by her
comments that the NHMRC is putting in place targeted calls for research, which
may recognise the priorities of not only government but also the wider
Australian community. I believe that funding for research into tick-borne
diseases in Australia is urgently needed.
Research is also underway at the tick-borne diseases unit at Sydney
University, which is currently conducting a study looking at whether ticks in
Australia carry Borrelia or similar bacteria. The committee notes that
the research has not been published yet, but that conclusive, direct evidence
of Borrelia known to cause Lyme disease has not been found, but that
other Borrelia have been found.
Professor Irwin and Dr Ann Mitrovic
both extrapolated a further conclusion from the research already conducted:
serological testing currently available, discussed earlier in this chapter, is
quite likely ill-equipped to identify infection by the pathogens most likely at
play in Australia:
I heard the end of the discussion previously on serological
testing, and, to my mind, it somewhat completely misses the point—that all the
tests that are available at the moment are developed against known bacteria and
disease. That is what they are designed for. I believe the Australian situation
is completely different. We have organisms here that may be causing disease—we
do not know what they are yet; we are working on that. In order to develop
tests that are going to be more specific for what we have going on here, we
need to isolate those organisms and develop tests from them.
In making the same point, Dr Mitrovic brought the committee back to the
issue of laboratory testing. In the US and Europe, where new strains of Borrelia
are being discovered, these are not able to be detected by tests looking for
infection with the Borrelia burgdorferi sensu lato complex.
The committee notes evidence indicating that international bodies are
expanding definitions around Lyme disease to include more than one strain of Borrelia
and a number of co-infections.
The committee notes evidence outlined above indicating that unique
pathogens have already been identified in Australian ticks, and that pathology
tests currently conducted in Australia are not designed to look for those
newly-identified pathogens. The committee is of the view that funding should be
made available for this research to continue and be expanded as a matter of
The committee is persuaded that it is possible that these unique
pathogens may be causing Lyme-like illnesses and therefore further work is
urgently needed to identify these pathogens and links to Lyme-like illnesses.
The committee however urges caution against extrapolating too much from
the discovery of possible new pathogens, supporting the department's view that
nothing should be assumed without further research.
The committee recommends that the Australian Government Department of
Health engage with stakeholders following the publication of the National
Serology Reference Laboratory review to discuss the findings of the review and
any bearing those may have on testing for Lyme disease in Australia.
The committee recommends that the Australian Government increase funding
for research into tick-borne pathogens as a matter of urgency. This funding
- funding for research on pathogens which may cause infection;
funding for research on whether newly-identified pathogens can
cause illness in humans; and
funding for the development of diagnostic tests which can detect
infection by any newly-identified pathogens endemic to Australia.
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