Dr. Bartley Cryan:

I thank the committee for inviting me in to discuss the laboratory diagnosis of Lyme disease. I will outline a little about medical microbiologists, what we are and what we do. There are approximately 40 of us in the country fulfilling approximately 30 whole time equivalent posts. There are two or three of us in most of the major teaching hospitals scattered throughout the country.

Generally speaking, our job is to manage the laboratories in conjunction with the senior scientists, to develop the service and to engage in clinical liaison with our users. They are largely hospital physicians and surgeons as well as general practitioners. We are involved in infection control, antibiotic stewardship and teaching. Our main function is to ensure that the right tests are done and are available for our catchment population, that they are interpreted correctly and that we are available to advise the clinicians on putting the patients on the correct treatment as well as monitoring that treatment and any further investigations that are required.

I work as a consultant medical microbiologist in Cork University Hospital. I have been there since 1991. Of significance, my prior position was as a lecturer in the Charing Cross and Westminster Medical School, where I was associated with the Lyme disease reference facility. I wrote several publications there which I have referenced in my submission. The publication of most significance is Lyme disease in Ireland. Under the study we reviewed the available Irish data from 1986. It is of significance that several specialties and physicians in Ireland were actively searching for and investigating the diagnosis of Lyme borreliosis at that time. In total, 484 samples were sent to us. A total of 14% of these were positive by the initial screening assays but only 13% were formally confirmed by the western blot. These were spread throughout several specialties, largely neurology, rheumatology and dermatology. People were actively searching for diagnoses for Lyme disease at the time and continue to do so.

The Cork University Hospital medical microbiology laboratory is one of the largest in the country. We deal with almost 500,000 samples a year. Approximately 50% of our work comes from general practitioners and approximately 50% comes from the hospitals under what used to be the southern health board. We cater for a population of approximately 500,000.

We get many types of samples. One point of significance to the committee is that we deal with approximately 180,000 serology or virology samples per year. We run at approximately 1,000 Lyme disease serologies per year. Our testing tends to be seasonal, as is the nature of the illness. We tend to get most of these in the autumn. Of the 1,000 serologies that we examined in 2013 some 30 were confirmed positive cases. We send all our positive enzyme immunoassay tests, which we carry out in-house, to the rare and imported pathogens laboratory, which is the United Kingdom reference laboratory for Lyme disease. That laboratory carries out an enzyme-linked immunosorbent assay test. Then it does the western blots and report back to us.

As previously mentioned by Dr. Bonner, Lyme disease results from the transmission of Borrelia burgdorferi by hard bodies, Ixodes ticks. The ticks need to be attached to the patient for over 24 hours for transmission to occur. The disease was first identified by Steere et al in 1975 and the organism was identified by Willi Burgdorfer, who died recently, in 1981.

In the United States, where the disease is more numerous and of more significance, between 10% and 20% of untreated patients will go on to develop nervous system symptoms. Arthritis will develop in approximately half of those cases. Arthritis is far more common in the United States than in Europe and this is related to the different species. The common species in Ireland is Borrelia garinii, which tends to give rise to skin and neurological signs but rarely arthritis. Generally speaking, the Borrelia burgdorferi sensu stricto, the specific strain which occurs in the United States, is more pathogenic.

Traditionally, infections and all illnesses are diagnosed by eliciting the appropriate clinical signs and characteristic symptoms. Then, the diagnosis is confirmed by detecting or growing the implicated organism in the infected tissue. When we can do that, we can make a firm diagnosis of an illness. Unfortunately, organisms like Borrelia burgdorferi and spirochetes in general are difficult to grow. Therefore, we cannot apply the normal standards that we would apply in diagnosing infections. Instead, we must resort to looking for antibodies or activated cells to counteract these infections. This means we are looking for evidence of previous contact with the organism rather than actual disease. One of the other problems associated with serology is that it takes time for people to develop antibodies. In the case of Lyme disease it may take up to 30 days before antibodies are detectable in blood. Moreover, there may be cross-reactions, which is a common problem in spirochetal illnesses. There may be false positive results as well as results that may be true positive but which are not related to the actual symptoms that the patients are suffering from. Another problem with antibody-associated diagnoses is that the antibodies tend to remain positive for life. Generally speaking, we cannot use them as an indicator for adequate treatment and it is difficult to determine relapse or reinfection because the antibody levels will still be present.

The earliest clinical manifestation of Lyme is the pathognomonic erythema migrans. This is a circular red rash which spreads out from the area of the tick bite. Generally, it occurs within seven or eight days of the bite, but it can take up to 30 days to occur and it lasts for approximately a month.

It is seen in most infections, but if it is not in an obvious body site, the patient might not be aware of it. Approximately 30% of people who display chronic signs of Lyme infection have no evidence of having had erythema migrans. We see quite a lot of these cases in west Cork and County Kerry. General practitioners regularly send us serology which turns out to be negative. If we are told when we telephone them that the characteristic rash is present, a repeat serology is carried out approximately one month later. If the serology is positive at this point, a diagnosis can be made. Approximately 30% of patients with the rash will have a negative serology. Those who are well aware of this problem get over it by repeating the serology. People can have flu-like symptoms at the same time.

The guidelines we follow when diagnosing Lyme disease were proposed by the US Center for Disease Control and Prevention, the Infectious Diseases Society of America, the UK Health Protection Agency and the European Centre for Disease Prevention and Control. They are probably the most widely applied guidelines, certainly in the United States, the United Kingdom and elsewhere in Europe. In the two-pronged approach taken we initially do an enzyme-linked immunosorbent assay, ELISA, test which, if positive, we follow with an immunoblot test. I ask members of the committee to bear in mind the caveat that in early infections people may have a negative serology. If the clinical syndrome is suggestive, we always go back and recommend that a repeat serology be done.

When we get a positive result in the initial ELISA test, we telephone the doctor involved to discuss the case and make him or her aware that it will take approximately three weeks for the western blot results to come back from the reference laboratory in the United Kingdom. If the clinical syndrome at that stage is very suggestive of Lyme disease, a decision will frequently be made to treat the patient to eradicate the organism as quickly as possible and avoid long-term complications. When the western blot results are available, we contact the clinician again to discuss the case with him or her. As I mentioned, we might suggest a further serology at that stage. I reiterate that just 30 of the 1,000 samples we examined in 2013 were actually confirmed. We tend to see a peak of samples late in the summer.

Anecdotally, having spoken to clinicians, it seems that most Lyme infections tend to occur in Ireland. However, we also see many cases that originated in central Europe, Scandinavia and the west coast of the United States. We have an active neurological centre within the hospital. The neurologists regularly test patients for Lyme disease. If there is any suggestion of a positive Lyme disease serology in a neurological patient, we will always also examine his or her cerebral spinal fluid to confirm the diagnosis. Where Lyme arthritis is an issue, joint fluid may also be taken to confirm the diagnosis.

I will stop there. I will be happy to answer questions members might have.