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KARL MCMANUS FOUNDATION (KMF) SUBMISSION TO THE SENATE COMMITTEE FOR LYME LIKE DISEASE IN

Karl McManus Foundation (KMF) was founded in memory of Karl who passed away from complications of tick borne diseases in 2010. The aim of KMF is to raise awareness of tick borne diseases, erode barriers to diagnosis and treatment by encouraging education and funding research in Australia. KMF is a crucial organisation with extensive knowledge and experience in tick borne diseases in Australia. KMF funds research in the Tick Borne Diseases Unit, School of Medical Sciences (Pharmacology), University of and has hosted tick borne diseases conferences with international plenary speakers in 2013-2015.

Current Directors of KMF are:

Emeritus Prof John Shine AO Emeritus Prof Graham Johnston Emeritus Professor Ted Martin Dr James Read Mr Gary Sanderfield Dr Mualla McManus-

This document is submitted by Dr Mualla McManus. The founding director of KMF

Committee Secretary Standing Committee on Health PO Box 6021 Parliament House ACT 2600

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Growing Evidence of an Emerging Tick Borne Disease that cause Lyme like illness for many Australian patients Overview

The Karl McManus Foundation (KMF) is currently the only charity in Australia funding research into tick-borne diseases including Lyme-like illness, and the only charity specifically advocating for education of health practitioners and for tick bite prevention campaigns to the public. The KMF believes that education of both health practitioners and the public is essential to prevent chronic tick-borne diseases from becoming established in Australia and, potentially, causing a significant public health burden. Research is absolutely essential in order to clarify the tick-borne disease situation in Australia.

What is Lyme disease, Lyme like disease?

Lyme disease, or Lyme-like disease, is a controversial topic in Australia because definitions vary between patients and health practitioners. There is no clear agreed definition of Lyme disease in Australia. The World Health Organisation (WHO) has an International Classification of Disease (ICD) code for Lyme disease which defines it as an infection common in the USA1, but in the rest of the world, the disease is termed “Borreliosis” 1, after the bacteria family (Borrelia) and genospecies identified as the causative agent of the disease in countries where it is recognised. However, people ill with Borrelia infection from a tick bite commonly have multiple pathogens 2 so even the Borreliosis terminology does not define this infection. The better terminology to describe this infection in Australia would be “Tick-Borne Diseases” (TBD) or “Tick-Borne Syndrome” (TBS), given that Australian ticks have been found to harbour the Borrelia responsible for relapsing fever 3 but the infectiousness of this particular genospecies of Borrelia in people has not been determined yet.

Not all Borrelia cause Lyme disease, only one genopspecies (B.burgdorferi sensu stricto) does. However, chronic relapsing fever infection can also cause Lyme-like illness symptoms. 4, 5, 9, therefore Australia’s Lyme-like infection can be referred to as “relapsing fever-like illness”. Other tick -borne pathogens like Bartonella, Babesia, Ehrlichia and Anaplasma, alone or with Borrelia, can also produce similar symptoms 2. Without the identification of tick-borne pathogen(s) that cause these Lyme-like illnesses it is very hard to reach any conclusions.

Overseas acquitted TBDs

Overseas-acquired Lyme disease is present in Australia and can be diagnosed appropriately 6. However diagnosis of other overseas-acquired Borrelia genospecies infections is very difficult. The focus on Lyme Borrelia in Australian ticks prevents proper diagnosis of overseas-acquired non-Lyme Borrelia infections.

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Australians are ardent travellers, particularly to Asia, the Middle East, Africa, South America and Europe. 9.2 million Australians travelled overseas between 2014 and 2015 7. Half a million Australians could be returning to Australia with TBDs if the 0.094% /year incidence of contracting TBD (USA, 300,000/year) 8 holds. Unfortunately, Australian health practitioners are not familiar with the signs and symptoms of TBDs, so most of these people are likely to be misdiagnosed with other diseases/illnesses such as chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME), other neurodegenerative diseases, or an undiagnosable illness.

In Australia, patients use the term “Lyme disease” to define almost every chronic infection, including every tick-borne infection they can think of. Without a clear definition, the way forward will be very difficult in Australia.

Incidence

The first term of reference in this submission is about the prevalence and geographic distribution of Lyme-lie illness in Australia. How can a disease that cannot be defined clinically, or be tested accurately and treated properly have prevalence or geographic distribution in Australia?10,11 Clinical trials in the 1990s showed that the northern suburbs of Sydney have high prevalence of Lyme-like illness, but the exact incidence was elusive 12. TBDs can be misdiagnosed due to non- specificity of symptoms so their prevalence is blurred. There are also no reliable tests to validate the clinical symptoms13.

For these reasons the process of diagnosis is problematic. Laboratory tests using indirect methods like serology or the T cell test, Elispot, are unreliable and can result in a false positive11. Immune dysregulation by Borrelia can also result in false negative results14. Tests based on DNA identification like polymerase chain reaction (PCR) tests have high specificity but a narrow spectrum so can miss unknown or rare genospecies. Presently the diagnostics of TBDs are problematic13

Current Research

Unfortunately, medical research investment is very minimal in Australia relative to the OECD. The government funding to date for TBD research has been a Bayer grant, matched by the Australian Research Council (ARC) to Murdoch University. The Tick-Borne Diseases Unit at the University of Sydney is funded entirely by the Karl McManus Foundation (KMF) through donations and fund raising activities. Research outcomes are delayed due to lack of funding. The KMF is the only charity in Australia currently funding research TBDS. Funding of TBDs research in Australia would clarify exactly which TBDs exist in Australia, erode barriers to recognition of these diseases, remove stigma about TBDs, and improve health outcomes for thousands of Australians.

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Tick-borne diseases research has been neglected in Australia over the last 25 years, and we now need to catch up with the rest of the world. There is a need to provide better funding for research, and this requires the National Health and Medical Research Council (NHMRC) and the ARC to be open to supporting tick-borne diseases research. The probability of having a successful NHMRC grant was 16% in 201359 NHMRC, but the probability of being successful for a TBDs grant is even less because of the controversy over the existence of TBDs and the structure of NHMRC. Urgent research is needed to identify tick-borne pathogens, and to diagnose and treat the diseases they cause.

Contraversy

The controversy surrounding TBDs, Lyme disease or Lyme-like disease arises from the non- specificity and multi-systemic nature of the clinical symptoms, the unreliability of laboratory tests and the anecdotal treatment protocols used for chronic TBD infections 15,16,10 .. The characteristics of Borrelia and its co-infections2 undermine the established microbiological principles. The Koch postulates 18 of were founded on only one pathogen producing specific symptoms with one antimicrobial treatment. Unfortunately TBDs do not fit these criteria, because they involve multiple infections 17 with delayed onset of symptoms which can create difficulties in early diagnosis and/or misdiagnosis, resulting in a need for multiple treatment modalities.

Discussion is urgently needed between interested parties to understand the best way to diagnose multiple pathogenic infections with non-specific, multi-systemic symptoms, and delayed onset, which are caused by polymorphic bacteria, such as Borrelia19. All stakeholders need to communicate with each other so that people who are ill can get appropriate diagnosis and treatment. These people cannot wait for research to identify Australian Borrelia; they need our help now. Treatment of overseas-acquired TBDs can be expedited by education of all health practitioners and the adoption of validated treatment protocols from overseas could be used to treat infections, because these protocols have been verified as being effective. The diagnostics in Australia should include testing for other Borrelia groups and better testing of co-infections like Babesia, Bartonella, Ehrlichia and Anaplasma and other zoonotic pathogens.

Sincerely

Dr Mualla McManus. B.Sci (Hons), MSc, B.Pharm, Ph.D Director, Karl McManus Foundation Honorary Associate University of Sydney, School of Medical Sciences (Pharmacology)

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1. Prevalence and Geographical Distribution of Lyme-like illness in Australia

Incidence

Lyme- like illness in Australia is an undefinable illness in that its causative agent is unknown and its diagnosis is not possible purely from clinical symptoms since these are non-specific and multi- systemic, and the diagnostics used here utilise the USA Lyme disease Borrelia proteins. Therefore an accurate estimate of the prevalence of Lyme-like illness in Australia is not possible. However, indirect estimates can be made based on tick-borne disease (TBD) prevalence in Europe and the USA. In the Netherlands, Germany, Austria and the USA, the prevalence of TBDs is 0.094%/year of the population. If we extrapolate to Australia (population 25million), that translates to approximately 200,000 people/year incidence. If TBDs are diagnosed and treated promptly, rapid recovery is possible. The onset of symptoms can be delayed so that connection to the tick bite can be lost. This can create confusion leading to misdiagnosis. Therefore, many people can go on to become chronically ill with TBDs and be misdiagnosed.

Potential Clinical Significance/misdiagnosis TBDs like Lyme disease have been known to mimic the symptoms of many neurodegenerative diseases 20, 21, 22, 23, This may potentially explain the high incidence of Australians suffering from chronic fatigue syndrome (CFS; 72,000 - 432,000) 24, Parkinson’s disease (80,000, with a 17% increase in the last six years) 25, multiple sclerosis (MS; 23,700) 26, motor neurone disease (MND; 2000 with a 30% increase since 2000) 27 and dementia (380,000) 28. All of these diseases currently have no single identified cause and no cure, and 10% of incidences are attributed to genetics and 90% to environmental factors. What are some of these environmental factors, and could they include tick bites? Can tick pathogens contribute to the disease process? If these diseases had a purely genetic cause, the incidence would remain constant in the population.

Migratory Birds The geographic distribution of Lyme-like illness is hard to locate accurately because of the difficulty in diagnosis and the delayed onset of symptoms. However, ticks are vectors, like other arthropods, and their main form of transport round the globe is via birds. Therefore the demographics of TBDs can be linked to areas where bird migrations take place. For example, the areas under the Australasian flight path of coastal birds (shallow feeders)29 can have a high incidence of TBDs as ticks are carried by birds which feed on local fauna, which then can become reservoir animals that can continue to spread the pathogens via local arthropod vectors. This was suggested by a study by Professor Richard Barry of the University of Newcastle in the 1990s. His study found a high incidence of Borrelia infection in the northern beaches of Sydney and other coastal areas in northern NSW12. From this information we can surmise that coastal areas in Australia are likely to have a high incidence of TBDs, but more studies need to be done to obtain

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more reliable statistics. KMF is looking to sponsor a PhD scholarship studying the bird flight path between Siberia and Australia.

Climate Change There are also other factors that help in the spread and distribution of TBDs. Arthropods feeding on reservoir animals travel to different areas for food and shelter. Therefore changes in climate which result in variations in availability of food for the reservoir animals and their ticks can also change the demographics of TBDs not only in Australia but also globally 30, 31. Hence TBDs can occur in non-coastal areas. In addition, shallow feeders also fly to feed on inland lakes, therefore the spread of ticks/arthropods and TBDs in those areas of inland water ways can increase correspondingly.

In hot tropical climates where temperatures can remain optimal for tick or other arthropod reproduction (27-28degrees) throughout the year instead of being seasonal as is in the Northern hemisphere, can result in high arthropod numbers can reach high densities 31, 32 . High populations of arthropods mean a high incidence of human contact by vectors and therefore a high incidence of TBDs. So, is climate change affecting arthropod demographics? A study in the USA found an increase of 2°C degrees increase in mean temperature can increase the virulence of Borrelia in the MidWest of the USA 33, 31, 32.

Vectors Arthropods- Ticks Initially, Lyme disease Borrelia were thought to be transmitted by the black legged deer tick (Ixodes scapularis) 34. In addition Borrelia burgdorferi sensu lato group bacteria were thought to survive only in hard ticks, and relapsing fever Borrelia only in soft ticks. Hard ticks can have more than one host and usually feed longer (24-72 hours before they dislodge from their host) 35. Hard ticks also need to moult into the next stage of their life cycle with each feed. Soft ticks in contrast generally have short blood meals, indiscriminate hosts (e.g. birds), and flexible development cycles.35.

In the 1990s it was believed that Ixodes Holocylus could not harbour Borrelia bacteria36 .However, that was proven incorrect in 2015 when a relapsing fever type Borrelia was found from the gut of an Ixodes Holocylus by the Murdoch University team3. Recently, the relapsing fever pathogen, Borrelia miyomotoi discovered in Japan, was found to be pathogenic in humans37. Borrelia miyomotoi (relapsing fever) was found in hard ticks which is contrary to previous assumptions that only B.burgdorferi is found in hard ticks and relapsing fever Borrelia are found only in soft ticks. There is also another group of Borrelia, reptilian Borrelia, which is a hybrid of B.burgdorferi and relapsing fever Borrelia 38. All these different groups of Borrelia can potentially inhabit all arthropods and different gut environments and can produce different virulence in different geographical areas where there are high incidences of arthropod bites, which 6

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can result in a high incidence of TBDs. Demographic surveys need to be done to map the areas where there are high incidences of tick bites and human diseases in those areas initially then other blood sucking insects should be investigated.

2. Methods to Reduce the Stigma Associated with Lyme-like illness for patients, doctors and researchers.

Underlining reasons for Stigma

Stigma attached to Lyme-like illnesses comes partly from the undefinable characteristics of the disease and partly from the politicisation of the disease. This allows conflicting opinions of definitions, diagnosis and treatment protocols by interested parties to proliferate. The actual truth is unknown. The Lyme disease controversy arose in the USA in the 1980s and 1990s and continues today. Social media, together with the internet and the fact of Australia being an English speaking country like the USA, has enabled the controversy to transfer and take hold in Australia, despite the fact that Australian ticks have not been shown to harbour Lyme Borrelia to date.

History Lyme disease controversy is more intensive in Australia because of the 1994 study by Russell et al 39 which could not find Lyme disease Borrelia in Australian ticks. Patient advocate groups marketing the brand name “Lyme”, but not the disease, increase the stigma. There is also a lot of media attention on Lyme disease while other Borrelia infections like relapsing fever have been ignored. The media surge in Australia is driven by advocate groups that don’t understand the complexity of TBDs. There is a lot of misinformation on blogs and websites claiming to cure Lyme disease. Nothing about this infectious disease is straightforward. Everyone’s definition of Lyme disease is different. Sufferers find solace in forums and groups. In addition, the misdiagnosis and/or mistreatment of sufferers by the health practitioners who are not familiar TBDs continue to inflame the controversy and the stigma. Lyme disease has almost become a religion.

The controversy is compounded by difficulties in diagnosis, both clinically and by unreliable diagnostics40, 13, the unfamiliarity of Australian health practitioners with the signs and symptoms of TBDs, a lack of research and a lack of education of health practitioners meaning that even overseas-acquired non-Lyme Borrelia infections are not diagnosed appropriately.

Stigma can only be reduced by education and research. Educating health practitioners about the complexities of chronic persistent TBDs and the importance of early diagnosis and treatment can help to reduce the politicisation and misinformation surrounding TBDs.

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Educating the public about the dangers of tick/arthropod bites can prevent TBDs and hence the number of sufferers. Investigating the pathogens in Australian ticks and other arthropods, with the aim of identifying the causative agents which define the disease accurately will also help to reduce stigma.

3. The process for Diagnosis of Patients with a Lyme-like illness with a specific focus on the Laboratory Testing Procedures and Associated Quality Assurance Processes.

Diagnostics Diagnosis of TBDs is difficult not only clinically but also at the laboratory diagnostics level. Tests use indirect and direct methods. Indirect methods include serology, response from B cells13 and Elispot response from T cells41. Direct techniques utilise detection of bacteria DNA using PCR (polymerase chain reaction) 42, 43.

Indirect Techniques The use of indirect techniques like serology, based upon the production of antibodies by the patient, can be problematic if the patient has been ill for prolonged periods and is immune- dysregulated, i.e. their immune system is not making the right amount and type of antibodies required to be detected in an ELISA or an immunoblot assay14. There are so many different genospecies of Borrelia, but ELISA assays commonly use the proteins of the B31 strain of Borrelia burgdorferi sensu stricto, Lyme Borrelia or recombinant proteins. ELISA assays based upon Lyme Borrelia assume that they can detect all Borrelia bacteria; however, this may not be the case.

The C6 Antigen Assay- an evidence of the hypervariability of Borrelia genome TheC6 antigen region of the Lyme Borrelia genome is supposed to be the constant region (sequences conserved by all Borrelia) but the C6 antigen assay44 does not pick up Borrelia infections from Europe which are also in the B.burgdorferi sensu lato group. In fact the C6 antigen does not detect one third of USA patients who have Lyme Borrelia infection45.

The Borrelia genome is very highly mobile46 so one assay based upon one genospecies cannot be used to detect all Borrelia infections unlike other bacterial infections. A similar argument can be presented for T cell assays for immunodysregulation. The T cells of a chronically ill patient, when stimulated with Borrelia proteins, cannot produce sufficient interferon gamma to get a positive result 47, and therefore the result is a false negative.

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Direct Techniques- Direct assays using PCR theoretically would be very sensitive and can identify the Borrelia accurately. However the efficacy of PCR is dependent on the primers used 42. With a highly variable genome it is very hard to have a primer sequence that is common to all Borrelia. Usually PCR assays can detect already identified genospecies but rarer and unknown genospecies can be missed.

Dissemination and Persistence Borrelia are micro-anaerobic (need low oxygen environment to grow) bacteria and the most common tissue for sampling is blood, which is not an ideal environment for Borrelia to reside in unless tick-borne co-infections invade red blood cells (RBC) and cause RBC damage and hamper oxygen transport48. In tissues where there is no direct blood supply, like the joints and the central nervous system (CNS) protected pockets of micro-anaerobic environments can be created conducive for Borrelia survival and persistence in tissues 49

In order to improve the efficacy of diagnostics, multiple techniques need to be used to identify Borrelia. Therefore serology/ ELISPOT, along with PCR may be needed, together with tissue sampling.

In Australia diagnostic efficacy can be improved greatly once the Australian tick pathogen (s) in Australian ticks is/are identified. Current tests should also include relapsing fever Borrelia detection. The sooner diagnostic efficacy is improved the better, but can only be achieved by improved research funding.

Overseas Acquired TBDs However, for those who have travelled overseas to areas endemic with other Borrelia infections, such as relapsing fever or reptilian Borrelia, the present NATA approved laboratory testing with ELISA first, then Western blot designed for Lyme disease, is inappropriate. There need to be better tests designed for relapsing fever Borrelia like GLPQ 50, 51 ELISA assays, or PCR.

Patients with an overseas travel history need to be tested for all potential TBDs of the regions they have travelled in, and not be tested only for Lyme Borrelia or Borrelia burgdorferi sensu lato.

The Australian medical system follows the CDC USA 2 tier testing for Lyme disease, very closely; it is appropriate for Lyme disease but not for other Borrelia infections. We should be aware of that and take a global perspective and consider testing for other Borrelia infections.

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4. Evidence of investments in contemporary research into Australian pathogens specifically acquired through the bite of a tick and including other potential vectors

Currently the only government funding for TBDs research is held by Murdoch University through a Bayer grant of $100,000/year for 3 years which is matched with an ARC grant. The research at the Tick Borne Diseases Unit, School of Medical Sciences, University of Sydney, is funded entirely by the Karl McManus Foundation 52. So far $1million has been spent on creation of TBD Unit at University of Sydney. Half of the set up costs were donated by Dr Mualla McManus.

The current state of research funding is not conducive for expediting research results which can benefit everyone. There are no funded clinical research programs. Ticks are the most common vector for transmission of Borrelia bacteria, but transmission by other arthropod vectors cannot be ruled out as the sources of infection are reservoir animals like kangaroos, wombats, deer, rats, foxes, mice etc.

Acute Lyme disease, in contrast to chronic TBDs, is easily diagnosable and treatable. There are approved treatment protocols from the Infectious Diseases Society of America (IDSA) 53 and Europe 54. However, chronic TBDs are complex to diagnose and complex to treat due to immunodysregulation and likely misdiagnosis and tissue damage.40

The current health system in Australia is also geared to diagnose and treat acute conditions while chronic diseases solutions have not produced positive outcomes. Neurodegenerative diseases have also been increasing at an alarming rate: motor neurone disease (MND) has increased by 40% since 2000, and Parkinson’s disease by 17%. These diseases have no single identified cause or a cure and are thought have 10% genetic and 90% environmental factor contribution. Common investigations into these diseases investigate genetic factors and potential breakthroughs are based upon a band aid approach rather than on finding the cause of these disease.

There needs to be a change in the way research into chronic diseases is funded. The funding system can be biased towards acute infectious diseases (e.g. Swine flu, bird flu). Currently it is expected that emerging infectious diseases need to comply with the Koch postulates as noted above, but TBDs do not fit this postulate paradigm of one pathogen/one treatment option. TBDs have nonspecific, multi-systemic symptoms, multiple infections, and need multiple treatment modalities. In summary there is not much research into TBDs in Australia due to lack of funding and politicisation.

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5. Potential investment into researching the bite of a tick and including other potential vectors.

The impact of TBDs on many chronic diseases is likely to be significant, given that TBDs are easily misdiagnosed. Research investment into TBDs needs to be increased significantly given that the incidence of chronic diseases is increasing. Most treatments available for TBDs treat the symptoms but not the cause. This results in ever-increasing costs to the healthcare budget.

The Medicare system can be used to encourage the diagnosis of TBDs in Australia and also to gather important statistics from the time of the tick bite being recorded, the tick being removed, the patient being tested and disease progression (this method is being trialled in the Netherlands)55

In developed countries, a large portion of the health budget is used for funding the ever-increasing number of chronic illnesses with poor outcomes for sufferers. There needs to be greater research investment into the cause of chronic diseases from the environmental multifactorial angle.

Chronic TBDs can be misdiagnosed as one of a number of conditions, including: chronic fatigue syndrome [CFS]/myalgic encephalomyelitis [ME] 56, multiple sclerosis [MS] 21, motor neurone disease [MND] 20, Parkinson’s disease, 22 and dementia23. Ninety percent of neurodegenerative diseases have an environmental cause and 10% have a genetic cause such as a mutation of a gene57. As TBDs can mimic the symptoms of neurodegenerative diseases, screening for TBDs in patients suffering from neurodegenerative diseases and differential diagnosis should be encouraged.

Savings to the health care and social security budgets would be substantial if medications used to treat TBDs (including Lyme disease/relapsing fever) were subsidised by the Pharmaceutical Benefits Scheme, allowing better access to treatments, and therefore recovery, for Australian patients. Timely diagnosis of TBDs would result in a significant reduction in disability and ongoing health care costs.

The Karl McManus Foundation having funding research for 5 years can see the huge impact of tick borne diseases on health and accordingly have taken the significant step and commenced the process of forming the Karl McManus Institute (KMI) to augment and expand the investigation of the multifactorial causes and design and validate unique treatment protocols including clinical research into tick borne diseases. A funding process applicable to other research institutes like the Garvan Institute would expedite the applied research results to benefit all TBD patients.

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Incidence of Neurodegenerative Diseases in Australia

Disease Incidence Cost Other CFS/ME24 72,000- 482,000 $525million Parkinson’s disease25 80,000 $7.6 Billion 17% increase last 6 years MS26 23,700 $2Billion MND27 Approx. 2000 ?$500million 30% increase since 2000 Dementia58 342,000 $1.9Billion 1% of GDP in 2050 Total cost is over $10 billion

A 30% increase in MND and 17% increase in Parkinson’s disease suggest that environmental causes are contributing to the growth of these diseases in Australia. Ticks are considered the second most important vectors of zoonotic diseases after mosquitos. Yet understanding of ticks and tick pathogens is limited, especially their potential contribution to chronic diseases. If the incidence of neurodegenerative disease were reduced by a mere 10% there would be a saving of over $1 billion to the health care budget. If the savings for the social security budget is added, the total saving is even greater.

6. The signs and symptoms Australians with Lyme-like illness are enduring and the treatment they receive from medical professionals

Signs and symptoms of Australian tick borne diseases vary between patients involving different tissues, changing in severity and can be of intermittent in nature. Australia has high incidence of neurological symptoms which is in contrast to Lyme disease which is predominantly arthritic. TBDs can have neurological symptoms similar to dementia, paralysis like MND, gut symptoms like Crohn’s disease, dermatological manifestations which can be hard to diagnose, respiratory symptoms like chronic obstructive airway disease etc. With so many varied symptoms it would be difficult for health practitioners to diagnose it accurately. They can dismiss the symptoms as being conversion disorder, CFS and other diseases. Health practitioners need training in diagnosis and treatment of TBDs.

Acute Lyme disease can be diagnosed early and treated effectively. Treatment protocols are widely accepted by IDSA, ILADS and other infectious diseases societies in Europe. However, treatment for chronic persistent TBDs is complex, and there are no established treatment protocols for these diseases. There is no clear protocol, for example, on the duration of treatment with antibiotics (3 months? 6 months? 9 months?), or which co-infection to treat first? There are currently no validated answers to these questions.

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Some healthcare practitioners are trying to treat complex TBDs using overseas protocols. Some of these protocols are anecdotal, some are not. This is one area that needs extensive research to validate. Furthermore, Australian TBDs do not present with the same symptoms as those from the USA or Europe. Therefore there needs to be urgent research to provide the microbiological (screening for all potential arthropod-borne pathogens) and pathological status (immune dysregulation that is induced by both single pathogens and combinations of pathogens, including past infectious history and genetic weaknesses) of chronic tick borne infections in Australia. Using this information, better treatment protocols can be designed and validated.

Clinical and scientific research need to be integrated together for research findings to be applied clinically and validated. The Karl McManus Institute (KMI) will be able to validate all treatment protocols for each patient with extensive base line testing of immunological, physiological and pathological parameters. To provide expedited results special funding allocations are needed so that this cohesive research can be undertaken.

The KMI, like other research institutes, will focus on TBDs and other arthropod-borne diseases investigating both clinical and scientific research. We would therefore like to propose that the KMI to be incorporated into an act of Parliament for guaranteed funding.

7. Any other related matters As the controversy of Lyme-like disease in Australia arises from lack of knowledge by health practitioners and a misunderstanding between patients and health practitioners about their disease definition. Lack of knowledge could be addressed if Australian medical colleges introduced compulsory continuing education programs on TBDs, so that overseas-acquired TBDs can be differentially diagnosed. With this education, Australian TBDs could also be differentially diagnosed...

In addition, we need to take a global perspective and be familiar with the way TBDs are diagnosed and treated in the non-English speaking world, where valuable lessons can be learned.

There also needs to be a good tick bite prevention campaign for the public, in order to prevent a continual increase in the numbers of Australians suffering both chronic and acute TBDs. . In particular, there need to be policies and procedures on the prevention of tick and other arthropod bites, tick removal and prophylactic treatment, in areas where people have occupational exposure to tick and other arthropod bites.

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In order to get an accurate picture of the prevalence of TBDs in Australia, funds should be allocated to collect data on TBDs. In order to establish the data collection, TBDs should be made a notifiable disease.

Executive Summary

 The prevalence of tick-borne diseases (TBDs) is not possible to determine due to delayed onset of non-specific, multi-systemic symptoms, unreliable diagnostics, and an unknown causative agent in Australia. There is anecdotal geographical distribution but demographic studies are needed to validate these regions.  Stigma is produced by politicisation of the disease arising from its undefinable characteristics, unknown causative agent, unreliable diagnostics and non-validated treatment protocols. With so many unknown factors, conflicting opinions and multiple definitions, stigma continues to propagate. Education can allow differential diagnosis by increasing familiarity. Research outcomes can reduce stigma by defining the disease and treatment protocols and eliminating assumptions.  Multiple diagnostic techniques are needed to diagnose chronic TBDs where there appears to be significant immune dysregulation. Hence indirect diagnostics based on serology or T cell responses need to be interpreted with caution. Direct diagnostics, such PCR, and indirect techniques need to be combined to improve diagnosis. Co- infection diagnostics need to be improved to enable identification of the particular co- infective pathogen that is creating the predominant symptoms.  Diagnostic developers need to understand the high variability of the Borrelia genome and to develop diagnostics for each geographical region separately, and not expect antibodies for recombinant proteins of B31 B.burgdorferi to be cross-reactive with antibodies to other Borrelia burgderferi sensu lato proteins. Testing bodies in indeterminate geographical regions should be acutely aware of this factor.  Research into TBDs in Australia has been lacking for the last 25 years. There is an urgent need to provide specific funding for research into these diseases.  Resolution of the controversy of TBDs in Australia needs urgent and specific funding. Only through identification of the causative agents of Australian TBDs can politicisation be removed. The Clinical Advisory Committee on Lyme Disease (CACLD) identified 12 research areas that are needed to understand, diagnose and treat Australian TBDs. This research would include investigating reservoir animals like foxes and kangaroos and vectors like ticks, sand flies, mosquitos and other blood sucking insects.

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 Signs and symptoms can vary between, which can make diagnosis very difficult. Australia has a greater proportion of patients with neurological symptoms compared with the USA.  There is an urgent need for all stakeholders to communicate with one another to agree on the definition of TBDs and to move forward objectively.  Education and research are the way forward.

Dr Mualla McManus. B.Sci (Hons), MSc, B.Pharm, Ph.D Director, Karl McManus Foundation Honorary Associate University of Sydney, School of Medical Sciences (Pharmacology)

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