Background: The Department of Medical Entomology’s (Westmead) website acknowledges that Lyme disease is the
“most frequently reported human tick-borne infection worldwide”, it goes on to say that “it has been reported from every continent (except Antarctica), although doubt remains as to whether it occurs in the southern hemisphere in general, and in Australia in particular”. This doubt is based on the fact that - “In 1988 at Westmead Hospital, a multidisciplinary investigation of putative LD in coastal New South Wales began, encompassing clinical, serological, vector and reservoir host studies”.
These components - clinical, serological, vector and reservoir host studies - are examined individually.
Clinical & Serological Studies
Westmead Website: http://medent.usyd.edu.au/fact/ticks.htm
"Despite clinical cases being reported from the early 1980's, there has been no confirmation that the disease occurs in Australia”.
Clinical
& Serological Studies
DME website: "Despite clinical cases being reported from the early 1980's, there has been no confirmation that the disease occurs in Australia.”
Russell et al 1994 (Pg 376): “The first Australian cases of a syndrome consistent with Lyme disease were reported from the Hunter Valley region of New South Wales in 1982. Further clinical cases were reported in 1986 from the south and central coast of NSW. In Queensland, in 1986-1989, the State Health Laboratories tested 1,247 patients for antibody response to B. burgdorferi, using an indirect fluorescent antibody test (IFAT), and reported 186 with positive (>64) titres”. In 1988 a serological diagnostic service for Lyme disease was started at Westmead Hospital. Enzyme linked immunosorbent assay (ELISA) for IgG and IFAT for IgG and IgM, were used with antigens derived from a North American strain (B31) of B. burgdorferi. From 1988 to 1992, specimens were tested from 2,446 patients referred with suspected clinical Lyme disease; only 66 (2.7%) showed positive results by both methods indicating possible Lyme disease”. These figures include seven patients infected outside Australia. More recent data from one of us (DD) indicate that to August 1993, 75 (2.2%) of 3458 local patients were positive for IgG by both methods. Less than 1% of the patients referred with suspected Lyme disease conformed with the United States national surveillance case definition for Lyme disease.”
DME webpage: The number of suspected cases referred to Westmead for testing by 1994 rose to 4,372. “From 1988 to 1994 at Westmead Hospital, 78 (1.8%) of 4,372 from local patients with suspected LD were positive for IgG by ELISA and IFAT. All 78 were tested by WB, using North American and European strains of Borrelia; 46 sera showed one or more bands. None, including those with putative late stage disease, showed more than 4 specific bands and thus were all negative by international criteria.”
When observing these test results, it becomes evident lightly more than two percent of the patients tested were positive, and less than one percent of the patients were positive by what the DME terms “international criteria”. It should be noted that the DME Website differs to what was published in the 1994 study, as it notes that “all were negative by international criteria”.
With so few patients testing positive, why then is there the insistence that Lyme is in Australia?
Lyme disease IS a CLINICAL Diagnosis
Clinical diagnosis is not a new phenomenon to the medical world. Diseases such as Parkinson’s, Alzheimer’s, Multiple Sclerosis and Motor Neurone all rely on the clinician’s interpretation of medical history, symptoms and response to treatment for diagnosis. As the underlying cause for most of these diseases is unknown, they do not have an available diagnostic test to definitively rule in or out the diagnosis. While the cause of Lyme disease is known, the current available testing methods are inadequate due to a number of reasons, including the diversity of the Borrelia bacteria that can cause Lyme disease and the lack of standardisation of testing methods, which renders the diagnosis of Lyme primarily as a clinical diagnosis that “may be” supported by blood tests.
In Australia, between 1988 and 1992, there were 2,446 patients suspected of Lyme disease who were tested at Westmead Hospital, NSW. By 1993, the number of suspected cases and tests had risen to 3,458 and again to 4,372 by 1994. Add to these figures the Queensland patients that a 1994 study of Russell et al. mentions and this indicates there were at least 6000 suspected cases of Lyme disease in Australia in 1994. There is no further information publicly available after this date to indicate whether or not the growth of new suspected cases continued to average approximately 1,000 per annum. With so many suspected clinical cases each year, it is baffling how it can be logically asserted that Lyme disease does not exist in Australia.
CDC International Criteria is Surveillance, NOT Clinical Criteria.
The “international criteria” to which Russell and others refer is that of the Centre for Disease Control (CDC) in the United States of America. It was developed for surveillance purposes, and not clinical or diagnostic purposes. The CDC Morbidity and Mortality Weekly Report (1) states: “This surveillance case definition was developed for national reporting of Lyme disease; it is NOT appropriate for clinical diagnosis” (pg 20) (Emphasis not added). The case definition includes serological results, “For the purposes of surveillance, the definition of a qualified laboratory assay…” (2).
Testimony by Paul Mead, Medical Epidemiologist with the CDC, given to the Connecticut Department of Public Health and the Connecticut Attorney General's Office at a hearing regarding CDC's Lyme Disease Prevention and Control Activities in 2004 (3) notes: “A clinical diagnosis is made for the purpose of treating an individual patient and should consider the many details associated with that patient's illness. Surveillance case definitions are created for the purpose of standardization, not patient care.” It also points out that: “No surveillance case definition is 100% accurate. There will always be some patients with Lyme disease whose illness does not meet the national surveillance case definition. For this reason, CDC has stated repeatedly that the surveillance case definition is not a substitute for sound clinical judgment. Given other compelling evidence, a physician may choose to treat a patient for Lyme disease when their condition does not meet the case definition.”
CDC Western Blot Criteria was developed for use in America (B. burgdorferi ss species)
The problem of testing and species variations of Borrelia has been historically documented. Just a few of the known problems are:
Advice for testing and the wording in the Fact Sheet, ‘Lyme Disease - Testing Advice for NSW clinicians’ (6) and the ‘Lyme Disease Fact Sheet’ by the Institute of Clinical Pathology and Medical Research (ICPMR), Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead (7), is very ambiguous. The ‘Lyme Disease - Testing Advice for NSW clinicians’ (6) implies that antigens from all three species are utilised in testing yet, based on the ICPMR fact sheet (7), it appears that only the blood/samples that are ELISA positive with B. burgdorferi species/antigens may qualify to be further tested on the Western Blot (and therefore with the inclusion of European antigens).
The ‘Lyme Disease - Testing Advice for NSW clinicians’ fact sheet notes: “The recommended testing strategy follows European and US-CDC guidelines for two-step serological testing with a screening immunoassay and a confirmatory immunoblot for antigens from Borrelia burgdorferi sensu lato genospecies (including B. afzelii, B. garinii)”.
The Institute of Clinical Pathology and Medical Research (ICPMR), Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead, Fact Sheet on Lyme Disease states : “The screening test is an ELISA to detect combined B. burgdorferi IgG and IgM. The sensitivity of this kit is as high as 100% but specificity may be only 68% (unpublished data). False positive results may occur when the patient has other spirochaete diseases such as syphilis, leptospirosis and relapsing fever or has mononucleosis, lupus erythematosis or rheumatoid arthritis.
All sera with positive or equivocal results on screening are tested by the Western immunoblot technique to determine specific IgG antibodies to particular proteins of B. burgdorferi (USA strain) and B. afzelii (European strain). At least five specific IgG immunoblot bands are required to confirm true Lyme disease after the first few weeks of infection (F. Dressler et al. J Infect Dis 1993;167:392-400 ) as recommended by the Second National Conference on Serologic Diagnosis of Lyme Disease, Centers for Disease Control,USA, 1994.”
The ICPMR fact sheet notes, “The screening test is an ELISA...The sensitivity of this kit is as high as 100% but specificity may be only 68% (unpublished data)”. Unmentioned is that the ELISA as a screening test is only as sensitive as to the antigen/species of Borrelia tested for and the sensitivity of this test can range from as low as 30% (depending on duration of infection) and which testing kits are used (8). Ang and others (2011) note “ELISAs and immunoblots for detecting anti-Borrelia antibodies have widely divergent sensitivity and specificity and immunoblots for detecting anti-Borrelia antibodies have only limited agreement” (9).
The statement in the ICPMR Fact Sheet “At least five specific IgG immunoblot bands are required to confirm true Lyme disease after the first few weeks of infection (F. Dressler et al. J Infect Dis 1993;167:392-400 )”, is also a little confusing for a various reasons: Its reliance on American (rather than European) WB interpretation; the time frame for testing positive; and the reference to “true” Lyme disease.
The European and US-CDC guidelines do recommend two-step testing;. however, despite being known since the 1990’s, what is not mentioned acknowledged or acted upon in Australian testing laboratories is that the European Western Blot (WB) criteria is very different. While the US surveillance criteria (10, 11) requires five bands (IgG) for a test to be considered positive, the WB criteria in Europe acknowledges that the immune response is lower in Borrelia species other than B. burgdorferi ss, and the requirement for a test to be considered positive is for one or two bands only, depending upon the species for which testing is being conducted (12).
Regardless of whether using American or European Western Blot interpretation, the length of time of IgG responses is not ‘set’ to the “first few weeks”. A few excerpts on this:
Craft, Fischer, Shimamoto and Steere (1986), whose article is referenced in the introduction in the Dressler et al paper to which the ICPMR fact sheet refers: “In 12 patients with early disease alone, both the IgM and IgG responses were restricted primarily to a 41-kD antigen. This limited response disappeared within several months...The IgG response in these patients appeared in a characteristic sequential pattern over months to years.” (13;pg 934).
Strle et al., (1996) states: “Our work also highlighted the continuing problems associated with use of serological methods for patients with early disease. Fewer than 50% of cases demonstrated seropositivity at any time within the first 2months” (14; pg 64).
Aguero-Rosenfeld et al., (1996) report on the serological results from Culture-Confirmed cases of Lyme: “Although 89% of the patients developed IgG antibodies as determined at a follow-up examination, only 22% were positive by the IgG IB criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors. (15; pg 1).
This raises the question, what exactly does the Centre for Infectious Diseases and Microbiology at Westmead define as, or refer to, when they say “true” Lyme disease? At the time of their study it was known that there were various species of Borrelia responsible for Lyme-like illness. For example, in 1994, Steere (who first ‘recognised’ Lyme disease) described “Lyme disease or Lyme borreliosis as the result of an infection from B. burgdorferi ss, B. afzelii or B. garinii” (16). It has also been long known that there are numerous other Borrelia species in the burgdorferi sensu lato complex that may cause Lyme disease (eg: 17-22), which the testing advice provided by Westmead does not appear to acknowledge or take into account in their testing procedures.
In an interview with Doctor Jeremy McAnulty, the Director of Health Protection with the New South Wales Department of Health in July 2010, Bronwyn Herbert asked whether the testing methods for Lyme disease in Australia were adequate. The reply from Jeremy McAnulty “Look they do seem to be and again we need to put in context who needs to be tested and when and the doctor’s decision and advice about that. But there is a specialist laboratory at Westmead that’s very expert in the range of tests that need to be done and can be done and they of course keep in contact with the experts around the world” (23).
This raises the following questions and concerns:
DME website: "Despite clinical cases being reported from the early 1980's, there has been no confirmation that the disease occurs in Australia.”
Russell et al 1994 (Pg 376): “The first Australian cases of a syndrome consistent with Lyme disease were reported from the Hunter Valley region of New South Wales in 1982. Further clinical cases were reported in 1986 from the south and central coast of NSW. In Queensland, in 1986-1989, the State Health Laboratories tested 1,247 patients for antibody response to B. burgdorferi, using an indirect fluorescent antibody test (IFAT), and reported 186 with positive (>64) titres”. In 1988 a serological diagnostic service for Lyme disease was started at Westmead Hospital. Enzyme linked immunosorbent assay (ELISA) for IgG and IFAT for IgG and IgM, were used with antigens derived from a North American strain (B31) of B. burgdorferi. From 1988 to 1992, specimens were tested from 2,446 patients referred with suspected clinical Lyme disease; only 66 (2.7%) showed positive results by both methods indicating possible Lyme disease”. These figures include seven patients infected outside Australia. More recent data from one of us (DD) indicate that to August 1993, 75 (2.2%) of 3458 local patients were positive for IgG by both methods. Less than 1% of the patients referred with suspected Lyme disease conformed with the United States national surveillance case definition for Lyme disease.”
DME webpage: The number of suspected cases referred to Westmead for testing by 1994 rose to 4,372. “From 1988 to 1994 at Westmead Hospital, 78 (1.8%) of 4,372 from local patients with suspected LD were positive for IgG by ELISA and IFAT. All 78 were tested by WB, using North American and European strains of Borrelia; 46 sera showed one or more bands. None, including those with putative late stage disease, showed more than 4 specific bands and thus were all negative by international criteria.”
When observing these test results, it becomes evident lightly more than two percent of the patients tested were positive, and less than one percent of the patients were positive by what the DME terms “international criteria”. It should be noted that the DME Website differs to what was published in the 1994 study, as it notes that “all were negative by international criteria”.
With so few patients testing positive, why then is there the insistence that Lyme is in Australia?
- Lyme disease is a clinical diagnosis: Suspected clinical cases averaging around 1,000 patients per year (since the 1980’s) is indicative that there is a urgent need for further research into why there are so many “suspected” cases of Lyme each year.
- CDC International criteria are for surveillance purposes, not clinical diagnostic criteria.
- Due to species variations of the Borrelia bacteria responsible for Lyme disease/Borreliosis, the “international criteria” are not recommended for use outside of America (where B. burgdorferi ss is not the primary species underlying Lyme). While the European, US-CDC surveillance criteria requires two tier testing – ELISA, then Western Blot (WB) – the interpretation of a positive WB is vastly different on each continent.
Lyme disease IS a CLINICAL Diagnosis
Clinical diagnosis is not a new phenomenon to the medical world. Diseases such as Parkinson’s, Alzheimer’s, Multiple Sclerosis and Motor Neurone all rely on the clinician’s interpretation of medical history, symptoms and response to treatment for diagnosis. As the underlying cause for most of these diseases is unknown, they do not have an available diagnostic test to definitively rule in or out the diagnosis. While the cause of Lyme disease is known, the current available testing methods are inadequate due to a number of reasons, including the diversity of the Borrelia bacteria that can cause Lyme disease and the lack of standardisation of testing methods, which renders the diagnosis of Lyme primarily as a clinical diagnosis that “may be” supported by blood tests.
In Australia, between 1988 and 1992, there were 2,446 patients suspected of Lyme disease who were tested at Westmead Hospital, NSW. By 1993, the number of suspected cases and tests had risen to 3,458 and again to 4,372 by 1994. Add to these figures the Queensland patients that a 1994 study of Russell et al. mentions and this indicates there were at least 6000 suspected cases of Lyme disease in Australia in 1994. There is no further information publicly available after this date to indicate whether or not the growth of new suspected cases continued to average approximately 1,000 per annum. With so many suspected clinical cases each year, it is baffling how it can be logically asserted that Lyme disease does not exist in Australia.
CDC International Criteria is Surveillance, NOT Clinical Criteria.
The “international criteria” to which Russell and others refer is that of the Centre for Disease Control (CDC) in the United States of America. It was developed for surveillance purposes, and not clinical or diagnostic purposes. The CDC Morbidity and Mortality Weekly Report (1) states: “This surveillance case definition was developed for national reporting of Lyme disease; it is NOT appropriate for clinical diagnosis” (pg 20) (Emphasis not added). The case definition includes serological results, “For the purposes of surveillance, the definition of a qualified laboratory assay…” (2).
Testimony by Paul Mead, Medical Epidemiologist with the CDC, given to the Connecticut Department of Public Health and the Connecticut Attorney General's Office at a hearing regarding CDC's Lyme Disease Prevention and Control Activities in 2004 (3) notes: “A clinical diagnosis is made for the purpose of treating an individual patient and should consider the many details associated with that patient's illness. Surveillance case definitions are created for the purpose of standardization, not patient care.” It also points out that: “No surveillance case definition is 100% accurate. There will always be some patients with Lyme disease whose illness does not meet the national surveillance case definition. For this reason, CDC has stated repeatedly that the surveillance case definition is not a substitute for sound clinical judgment. Given other compelling evidence, a physician may choose to treat a patient for Lyme disease when their condition does not meet the case definition.”
CDC Western Blot Criteria was developed for use in America (B. burgdorferi ss species)
The problem of testing and species variations of Borrelia has been historically documented. Just a few of the known problems are:
- “The
presence of at least 3 different species in Europe renders the diagnosis of
Lyme Borreliosis by serological testing complicated and difficult” (4)
- “The antibody response is more limited in
European Borrelia species; with these
lower responses leaving the specificity and sensitivity of serodiagnostic tests
lower” (4)
- “….it
is clear from all accumulated studies on Lyme Borreliosis serology that serological testing should be used as
a support of clinical diagnosis rather than a confirmation” (5: Pg S195).
Advice for testing and the wording in the Fact Sheet, ‘Lyme Disease - Testing Advice for NSW clinicians’ (6) and the ‘Lyme Disease Fact Sheet’ by the Institute of Clinical Pathology and Medical Research (ICPMR), Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead (7), is very ambiguous. The ‘Lyme Disease - Testing Advice for NSW clinicians’ (6) implies that antigens from all three species are utilised in testing yet, based on the ICPMR fact sheet (7), it appears that only the blood/samples that are ELISA positive with B. burgdorferi species/antigens may qualify to be further tested on the Western Blot (and therefore with the inclusion of European antigens).
The ‘Lyme Disease - Testing Advice for NSW clinicians’ fact sheet notes: “The recommended testing strategy follows European and US-CDC guidelines for two-step serological testing with a screening immunoassay and a confirmatory immunoblot for antigens from Borrelia burgdorferi sensu lato genospecies (including B. afzelii, B. garinii)”.
The Institute of Clinical Pathology and Medical Research (ICPMR), Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead, Fact Sheet on Lyme Disease states : “The screening test is an ELISA to detect combined B. burgdorferi IgG and IgM. The sensitivity of this kit is as high as 100% but specificity may be only 68% (unpublished data). False positive results may occur when the patient has other spirochaete diseases such as syphilis, leptospirosis and relapsing fever or has mononucleosis, lupus erythematosis or rheumatoid arthritis.
All sera with positive or equivocal results on screening are tested by the Western immunoblot technique to determine specific IgG antibodies to particular proteins of B. burgdorferi (USA strain) and B. afzelii (European strain). At least five specific IgG immunoblot bands are required to confirm true Lyme disease after the first few weeks of infection (F. Dressler et al. J Infect Dis 1993;167:392-400 ) as recommended by the Second National Conference on Serologic Diagnosis of Lyme Disease, Centers for Disease Control,USA, 1994.”
The ICPMR fact sheet notes, “The screening test is an ELISA...The sensitivity of this kit is as high as 100% but specificity may be only 68% (unpublished data)”. Unmentioned is that the ELISA as a screening test is only as sensitive as to the antigen/species of Borrelia tested for and the sensitivity of this test can range from as low as 30% (depending on duration of infection) and which testing kits are used (8). Ang and others (2011) note “ELISAs and immunoblots for detecting anti-Borrelia antibodies have widely divergent sensitivity and specificity and immunoblots for detecting anti-Borrelia antibodies have only limited agreement” (9).
The statement in the ICPMR Fact Sheet “At least five specific IgG immunoblot bands are required to confirm true Lyme disease after the first few weeks of infection (F. Dressler et al. J Infect Dis 1993;167:392-400 )”, is also a little confusing for a various reasons: Its reliance on American (rather than European) WB interpretation; the time frame for testing positive; and the reference to “true” Lyme disease.
The European and US-CDC guidelines do recommend two-step testing;. however, despite being known since the 1990’s, what is not mentioned acknowledged or acted upon in Australian testing laboratories is that the European Western Blot (WB) criteria is very different. While the US surveillance criteria (10, 11) requires five bands (IgG) for a test to be considered positive, the WB criteria in Europe acknowledges that the immune response is lower in Borrelia species other than B. burgdorferi ss, and the requirement for a test to be considered positive is for one or two bands only, depending upon the species for which testing is being conducted (12).
Regardless of whether using American or European Western Blot interpretation, the length of time of IgG responses is not ‘set’ to the “first few weeks”. A few excerpts on this:
Craft, Fischer, Shimamoto and Steere (1986), whose article is referenced in the introduction in the Dressler et al paper to which the ICPMR fact sheet refers: “In 12 patients with early disease alone, both the IgM and IgG responses were restricted primarily to a 41-kD antigen. This limited response disappeared within several months...The IgG response in these patients appeared in a characteristic sequential pattern over months to years.” (13;pg 934).
Strle et al., (1996) states: “Our work also highlighted the continuing problems associated with use of serological methods for patients with early disease. Fewer than 50% of cases demonstrated seropositivity at any time within the first 2months” (14; pg 64).
Aguero-Rosenfeld et al., (1996) report on the serological results from Culture-Confirmed cases of Lyme: “Although 89% of the patients developed IgG antibodies as determined at a follow-up examination, only 22% were positive by the IgG IB criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors. (15; pg 1).
This raises the question, what exactly does the Centre for Infectious Diseases and Microbiology at Westmead define as, or refer to, when they say “true” Lyme disease? At the time of their study it was known that there were various species of Borrelia responsible for Lyme-like illness. For example, in 1994, Steere (who first ‘recognised’ Lyme disease) described “Lyme disease or Lyme borreliosis as the result of an infection from B. burgdorferi ss, B. afzelii or B. garinii” (16). It has also been long known that there are numerous other Borrelia species in the burgdorferi sensu lato complex that may cause Lyme disease (eg: 17-22), which the testing advice provided by Westmead does not appear to acknowledge or take into account in their testing procedures.
In an interview with Doctor Jeremy McAnulty, the Director of Health Protection with the New South Wales Department of Health in July 2010, Bronwyn Herbert asked whether the testing methods for Lyme disease in Australia were adequate. The reply from Jeremy McAnulty “Look they do seem to be and again we need to put in context who needs to be tested and when and the doctor’s decision and advice about that. But there is a specialist laboratory at Westmead that’s very expert in the range of tests that need to be done and can be done and they of course keep in contact with the experts around the world” (23).
This raises the following questions and concerns:
- If
Westmead’s laboratory is in contact with experts around the world, why does
their advice with regards to Lyme disease and testing procedures ignore over
half the literature in the world?
- Why
is the Australian laboratories first line of testing looking for B. burgdorferi ss species, especially
when outside of America it is not the most commonly found species of Borrelia? For example, in a 2005 meta
analysis of studies in Europe, it was noted that the afzelii, garinii, and valaisiania were more common than sensu
stricto (21). In Asia, the presence of B.
burgdorferi ss was not found (and then only in animals) until 2011 (22).
- With
so many species of Borrelia being
found worldwide, why are Westmead official’s adamant a species of borrelia
underlying Lyme cannot possibly be in Australia, denying any further government
research for the last twenty years?
For the Full Review (including references) a downloadable PDF Format: Please see the Research Link.