On May 1st two of LDA’s trustees spent a very productive day at Porton discussing the move with Dr Tim Brooks, Consultant Medical Microbiologist and his staff.

The RIPL is intending to improve the information on the Lyme Borreliosis web pages and Dr Brooks has asked for input from LDA to help in compiling a set of frequently asked questions and answers. The team has also agreed to participate in LDA’s James Lind Alliance PSP documenting the uncertainties in Lyme disease diagnosis and treatment and to involve LDA in research that it is hoped will be undertaken in due course.

It will take the RIPL some time to fully take over: the team needs to be able to handle more than 1,000 Lyme disease tests a month and considerably more during the approaching peak months. The current plan is to start testing at Porton at the beginning of June.

The reference laboratory will run the same C6 ELISA from Immunetics. The immunoblot, however, is to be a mechanised strip blot from a German company, Viramed Biotech, which means the result will no longer depend on subjective, manual reading. This test is designed for use in Europe and is based predominantly (though not exclusively) on the highly antigenic Pko strain of Borrelia afzelii.

Patients need to be aware that the staff at the RIPL will not take phone calls from patients about test results – all requests for information need to come from the patient’s doctor as the HPA has a policy of not revealing confidential information about patients in response to an unverifiable phone call.

The HPA and LDA aim to work together as much as is possible and this first meeting was a very good start. It has been agreed that a second meeting will be convened for 6 months’ time to monitor progress.

*  The Rare and Imported Pathogens Laboratory (RIPL) at HPA Microbiology Services Porton was known until Nov 2011 as the Special Pathogens Reference Unit (SPRU). From 2005 to 2009, SPRU operated as part of the Novel and Dangerous Pathogens Department at the Health Protection Agency (HPA) Centre for Emergency Preparedness and Response (CEPR), then later as part of the Medical Affairs department. RIPL now operates as part of the Specialist Microbiology Services subdivision of HPA Microbiology Services.

RIPL provides a clinical diagnostic service for rare and/or imported pathogens like pathogenic arboviruses, haemorrhagic fever viruses and a number of Hazard Group 3 bacterial pathogens including rickettsiae, Coxiella burneti and Bacillus anthracis.

In March 2011 the Netherlands Journal of Medicine published a review (Tired of Lyme borreliosis. Coumou et al) which seemed intended to help Dutch physicians cope with the many people who believe they may have Lyme disease. The review says that in long lasting manifestations of Lyme disease the sensitivity of serology approaches 100% and that after adequate treatment there is no benefit of additional antibiotics.

In the same issue was an editorial (The challenge of Lyme disease: tired of the Lyme wars. Kullberg et al) This editorial points out that serological diagnosis of Lyme disease has its limitations and that the results from the Klempner trials cannot rule out the efficacy of longer term antibiotics. The authors state that

“Thus, there is a need for well-designed studies on this subject, rather than misusing outcomes of underpowered trials of disputed quality to either defend or deny the possible effect of antimicrobial therapy.”

The editorial also raised the issue of adequate treatment:

 “Indeed, if ‘adequate’ signifies that the microorganism has been eradicated and the immune system has come to rest, the problem has been solved, but the issue rather is whether treatment has been ‘adequate’ or not in patients who continue to feel ill.”

This editorial was very balanced and positive, however, some people couldn’t let it rest there. In the January 2012 edition, Klempner, Halperin, Baker, Shapiro, O’Connell, Fingerle and Wormser put their names to an editorial (Lyme borreliosis: the challenge of accuracy) in which they defend the Klempner trials and say that they

“did not find any evidence, based on over 700 samples from 129 patients that were examined by culture and polymerase chain reaction (PCR) assays, for persistent B. burgdorferi sensu stricto infection in patients with persistent symptoms after treatment for Lyme borreliosis.”

This was too much for LDA because the Klempner trials had specifically excluded any PCR positive cases, so however many samples they took from people included in the trials, they weren’t going to find B burgdorferi.

LDA’s chairman and medical director sent a letter to the journal which has been published in the April issue (Lyme disease – the challenge for patients. Huyshe-Shires & Pearson).

All the articles are freely available on the Netherlands Journal of Medicine website.

Although screening tests for Lyme disease will continue to be the responsibility of local and regional laboratories, a new confirmatory immunoblot will be introduced at Porton. The new test will be a strip blot with fully automated processing of the strips: detecting the intensity of the bands and accurately comparing this with the control cutoff. The previous western blot was read by hand: subjectively separating and judging varying shades of grey.

Dr Sue O’Connell, previous head of the LBU at Southampton, retired on Friday March 30th; as, coincidentally, did the Head of Emerging Infections and Zoonoses in the Department of Health who has been responsible for Ministers’ responses on Lyme disease over at least the last two governments.

New lab, new test, new gatekeeper.

This well-written and moderate article from the US, seeking research into the unknown areas of optimum length of treatment, best drugs to use and so on, caught our eye precisely because it was so well written and moderate, despite the writer experiencing and sharing her frustration and confusion about the battles within the medical profession about how to handle Lyme disease. We applaud the writer and thought it worth sharing with our own web audience.

It is generally said that after a tick bite, the IgM response develops first, followed by the IgG response. The Health Protection Agency (HPA) states

“The chances of a positive test in early infection range from about 30% in the first two weeks to about 80% by six weeks, and the positivity rate increases further with duration of active infection.”

That implies a steady increase in antibodies, but HOW DO WE KNOW?

In an ideal world (for research purposes) one would want to follow individual patients before treatment, taking repeated blood tests over a period of months in order to study the immune response. That clearly cannot be done as it involves withholding treatment.

The next best is to study several patients with a known time between tick bite and the first blood sample. This is precisely what a recent German paper reports, and the results are very interesting.

This paper documents successive blood test results of a group of German patients with erythema migrans. A western blot was used, as the authors found it to be more sensitive than an ELISA test (which in itself is an interesting conclusion).

The first test was at a known period after a tick bite, ranging from 1 week to more than 10 weeks after the bite. The results show what appears to be an undulating early immune response, with IgM immune reaction peaking at 5 weeks, then declining and showing a second peak at week 9 before declining again.

Similarly, the IgG reaction showed a first peak at 4 weeks, a second peak at 8 weeks followed by another decline.

Of the patients first tested at more than 10 weeks post bite only 10% were IgM positive and 33% IgG positive. However, at only 4 weeks post bite 75% of patients had been IgG positive. This does not indicate a smooth increase in in antibodies.

The authors conclude:

“So, we suggest that a single serological finding is a snap shot and gives evidence of an infection. On the other hand, the true infection might be missed by negative immune response, as might be the case in about 40% seronegative EM patients.”

At the moment, in the absence of an erythema migrans (the characteristic rash which should always be treated regardless of test result) patients with, say, an equivocal test in early infection, followed by a negative test a few weeks later, would be unlikely to be given treatment unless they or their doctors persisted with further testing in the hope of getting a positive test. Given the confidence in the tests currently expressed by the HPA, that is unlikely to happen.

This research paper shows that we have to be much more careful when drawing conclusions from blood test results. Remember – only about half of patients see an erythema migrans and doctors are heavily reliant on test results.

What happens beyond 10 weeks? Does the immune response continue undulating?

Is a blood test always a snapshot?

The full paper is available on-line.

Wessel M, Lynøe N, Juth N, et al. The tip of an iceberg? A cross-sectional study of the general public’s experiences of reporting healthcare complaints in Stockholm, Sweden. BMJ Open 2012;2:e000489. doi:10.1136/ bmjopen-2011-000489

Sweden has a Patients’ Advisory Committee, similar in function to the UK PALS (Patient Advice and Liaison Service) and in Stockholm, as in the UK, the number of complaints is increasing. The study sample was small, and the results may not be generalizable to other countries, however, this paper states what is probably a universal finding -

“The general aim of authorities’ administration of complaints is to improve patient safety and efficiency in healthcare. The patients’ motives for filing a complaint might, however, differ; they may also concern a wish for an explanation, someone to be accountable for what happened, financial compensation or receiving an apology.”

The study was designed

• to test the hypothesis that patients’ complaints about adverse events related to negative encounters in healthcare are under-reported
• to study the barriers to filing complaints
• to see whether the trust in and experience of healthcare are related.

Of the random sample of 1500 patients in Stockholm in 2008, 992 completed questionnaires were returned: 58% from women and 42% from men. Out of these:

• 23 (2.7%) had complained about the quality of their encounters
• 159 (18.5%) said they had legitimate reasons to complain, but had chosen not to.

Of those who had reasons to file a complaint but did not do so, one-third reported that they had low trust in healthcare. This can be compared with those who had no reason for filing a complaint; nine of the 10 had high trust in healthcare.

The top reasons for not filing a complaint were:

• I did not have the strength (39)
• I did not know where to turn (18)
• It makes no difference anyway (17)
• I had other priorities (14)
• It was too difficult (13)
• I was afraid of the consequences (8)
• I did not have time to do it (8)
• The damage was already done (5)

The authors conclude that in Stockholm healthcare complaints regarding encounters reveal only the tip of an iceberg and if trust in healthcare is jeopardised by negative encounters, it seems important also to examine more carefully the bottom of the iceberg, that is, to study those who do not file complaints.

Because of this the National Guidelines Clearinghouse (NGC) in the USA requires that American guidelines are reviewed every 5 years. The IDSA guidelines of 2006 are due for renewal but have been re-submitted without change and re-instated on the NGC website until 2015. It seems that NGC have allowed this because they believe that the guidelines underwent review in 2010 – the date of publication of the final report of the Lyme Disease Review Panel of the IDSA.

In fact the IDSA specifically states, on the webpage where you can find the final report, “The Review Panel was not charged with updating or rewriting the 2006 Lyme Guidelines.  Any recommendation for update or revision to the 2006 Lyme Guidelines would be conducted by a separate IDSA group.”

It is important to realise that the review panel did make many recommendations for changes to the guidelines and, despite the press headlines at the time, the panel members disagreed on some very fundamental points. See LDA’s 2010 comment on the final report. It should also not be forgotten that papers have been published during the last 3 years since the panel was convened and science has moved on.

Why does this matter to the UK? Because IDSA guidelines are referenced and recommended by official bodies in the UK including the Health Protection Agency (HPA) and the British Infection Association (BIA).

The IDSA review panel stated in its final report that “caution should be used in extrapolating results from European studies to North American patients, due to the well-established microbiological and clinical distinctions in Lyme Borreliosis on the two continents.” European guidelines all recognise the lack of evidence for treatment recommendations – see our guidelines page for details – but it seems that IDSA carries more weight with UK clinicians.

Patients have lost confidence in organisations that are responsible for protecting their health. And doctors? How do doctors retain confidence if those who provide them with guidelines to use ignore their own rules as the IDSA is doing?

A petition has been raised in the USA by LymeDisease.org (formerly the Californian Lyme Disease Association) to request that the outdated guidelines be removed. If you feel that guidelines matter, and should not be listed if they are known to be out of date, read this petition and consider signing.

IDSA guidelines are referenced across the world: this is an international petition.

The random samples of ticks were from dogs inspected at veterinary surgeries across the UK. Samples positive for Borrelia burgdorferi, the bacteria that cause Lyme disease, were found in ticks from Scotland to the Southwest of England and other places in between.

This study was well designed and a large number of dogs surveyed across a very wide geographical area. The vets’ surgeries were not just in “hot spots” and were in towns as well as country areas. Dogs were inspected throughout the season of March to October. So this was a good attempt to get closer to the real numbers of infected ticks.

4 species of ticks were identified: The sheep tick (Ixodes ricinus), the hedgehog tick (I. hexagonus), the fox tick (I. canisuga) and the ornate cow tick (Dermacentor reticulatus).

Some ticks were too damaged to be tested for Borrelia, but of those that were tested, the ospA gene of Borrelia species was detected in 2.3%. The researchers did not identify the bacteria down to genospecies level, but their test would have detected all genospecies of Borrelia burgdorferi sensu lato, including the lesser studied ones.

Of the positive samples, 15 were from I. ricinus and 2 from I. hexagonus. No positive samples were found among the I. canisuga or D. reticulatus. The positive sample is too small to draw any conclusions on relative prevalence except that both the sheep tick and the hedgehog tick carry B. burgdorferi.

In total 3534 dogs were examined by the vets and 810 were carrying at least one tick. The sheep tick was identified in 72.1% cases, the hedgehog tick in 21.7% and the fox tick in 5.6% cases. Five samples of the ornate cow tick were also received by the researchers. None of the dogs with infected ticks had recently been abroad, so these were UK acquired ticks.

A previous study (Ogden et al 2000), using a different survey method, identified ticks collected from UK cats and dogs and found a higher proportion (39%) were hedgehog ticks. That study found that the hedgehog tick was more frequently carried by cats and the sheep tick by dogs.

What pet do you have?

Hedgehog ticks and fox ticks are not very often counted in surveys, as many surveys rely on blanket dragging over the ground in known countryside habitats for the sheep tick. Hedgehog and fox ticks (the latter also found on badgers) live in the burrows of their hosts but will sometimes drop off their host as it walks through a town garden or park.

Town dwellers, beware!

As LDA continues to point out, Lyme disease is not just a problem of a few countryside “hot spots”.

Visit our YouTube channel to see an interview with Faith Smith at the LDA conference in September 2011.

The study focussed on 3 neurological conditions (Parkinson’s disease, multiple sclerosis and motor neurone disease). However, the study found, through literature reviews and focus groups with charities, patients and carers, that there were similar issues for people with other neurological conditions.

In 2005 the National Service Framework for Long-term Conditions introduced by the Department of Health focused on people with neurological conditions. At that time it noted a range of problems faced by people with neurological conditions and a series of requirements were put in place to improve the service. Since then spending on neurological services has increased but none the less, the study found that progress in implementing the Framework has been poor and significant problems with current services remain.

The study concluded:

“In summary, our report notes a range of systemic issues limiting service improvements for people with neurological conditions including

• poor data on prevalence of neurological conditions; 
• poor information for patients and carers about services;
• poor knowledge of neurological conditions among health
  professionals;
• performance measures that create cycles of referral–discharge–referral;
• little integration between health and social services;
• and skilled workforce shortages.”

The Neurological Alliance issued a press release following the report and this has been picked up by the BBC.

Hope is the thing with feathers
That perches in the soul,
And sings the tune without the words
And never stops at all,

And sweetest in the gale is heard;
And sore must be the storm
That could abash the little bird
That kept so many warm.

I’ve heard it in the chillest land,
And on the strangest sea;
Yet never in extremity,
It asked a word of me.

Emily Dickinson (1830-1886)