Bullying Borrelia

General or non-medical topics with information and discussion related to Lyme disease and other tick-borne diseases.
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tosho
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Location: Poland

Re: Bullying Borrelia

Post by tosho » Mon 14 Jan 2013 23:27

Henry wrote:Tosho: When you refer to TBDs, which specific infections are you including.
It depends on region, but the most commonly mentioned are: Bb, protozoals (like Babesia), Anaplasmas, and Bartonella. (transmission of Bartonella, according to the IDSA experts panel, is not likely, despite the fact that ticks carry these bacteria quite often. However, there are contrary opinions re: transmission: http://www.lymeneteurope.org/forum/view ... bartonella ).

Besides above mentioned, there are other pathogens. This is a quote from a National Institute of Public Health in Poland:
"Ticks are vectors of 130 species of viruses, 200 species of piroplasms, few species of filarias, fungis, 20 species of ricketsias, 20 species of spirochetes, and other bacterias."
http://www.pzh.gov.pl/page/index.php?id=1087&L=1
http://www.pzh.gov.pl/kleszcze/pge.php?mid=57

I think what may happen is that sometimes it is impossible for a physician or diagnostician to figure out which exactly TBDs a patinet is dealing with. Rather, they make an educated guess by using available tools and see how patient react to antimicrobial treatment.
By saying "infections soup" I meant a situation when a patient has more than one TBD at once.
Henry wrote:If you suspect one of the components of the soup to be Bartonella, then tell us how you would diagnose and treat that component. It would not be advisable to test for the presence of antibodies vs Bartonella since most people -- especially cat owners-- have such antibodies and the presence of such antibodies may only indicate past exposure, not active infection.
I agree, and at the same time I can't give you more detailed answer. Probably an experienced diagnostician would be able to say whether there are any possibilities to distinguish past vs active infection.

Henry wrote:In any event, most Bartonella infections -- except in immunocompromised individuals are self-resolving. For those infections that aren't, Bartonella is susceptible to treatment with doxycycline, the agent of choice for treating borreliosis. So, by treating with doxycycline you would be "killing two birds with one stone".
The problem is that when accompanied with other infections Bartonellosis may be more difficult to treat compared to the classic cat's scratch disease, which you describe.

RitaA
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Re: Bullying Borrelia

Post by RitaA » Tue 15 Jan 2013 0:07

Henry wrote:If you suspect one of the components of the soup to be Bartonella, then tell us how you would diagnose and treat that component. It would not be advisable to test for the presence of antibodies vs Bartonella since most people -- especially cat owners-- have such antibodies and the presence of such antibodies may only indicate past exposure, not active infection. In any event, most Bartonella infections -- except in immunocompromised individuals are self-resolving. For those infections that aren't, Bartonella is susceptible to treatment with doxycycline, the agent of choice for treating borreliosis. So, by treating with doxycycline you would be "killing two birds with one stone".
Henry,

Doesn't the lack of ability to distinguish between a past exposure and a current infection (whether Borrelia or Bartonella) strongly suggest that indirect tests that rely on solely on antibodies have an inherent limitation?

Although doxycycline is one of the medications used to treat a Bartonella infection, it looks like it may require a longer course of treatment than early Lyme disease. It also looks like a combination of medications may be the optimal treatment -- something that is rarely used by mainstream doctors to treat suspected Lyme disease. This is mostly hypothetical, I realize, since not everyone is convinced that Bartonella infections are actually transmitted by ticks. The evidence appears to be circumstantial, however there is at least one documented case where the person had no exposure to cats, but did have very clear evidence of a tick bite:

http://columbia-lyme.org/patients/tbd_bartonella.html
CSD is most often treated with tetracyclines, macrolides or aminoglycosides. For CNS infection, antibiotics that cross the blood brain barrier are necessary, and combination therapy is usually recommended, as it may have more efficacy. Among the recommended regimens are azithromycin or doxycycline in combination with rifampin, clarithromycin or a fluoroquinolone. The optimal length of therapy has yet to be determined, but most guidelines suggest that treatment should last for at least 4-6 weeks.
In more general terms, the antibody test for TB is now strongly discouraged by WHO (World Health Organization). With false positive and false negative test results, the TB antibody tests in question speak directly to the limitation of antibody testing upon which critical clinical decisions are then made:

http://www.who.int/mediacentre/news/rel ... index.html
WHO warns against the use of inaccurate blood tests for active tuberculosis

A substandard test with unreliable results

News release

20 July 2011 | GENEVA -The use of currently available commercial blood (serological) tests to diagnose active tuberculosis (TB) often leads to misdiagnosis, mistreatment and potential harm to public health, says WHO in a policy recommendation issued today. WHO is urging countries to ban the inaccurate and unapproved blood tests and instead rely on accurate microbiological or molecular tests, as recommended by WHO.

TB can be wrongly diagnosed

Testing for active TB disease through antibodies or antigens found in the blood is extremely difficult. Patients can have different antibody responses suggesting that they have active TB even when they do not. Antibodies may also develop against other organisms which again could wrongly indicate they have active TB. In addition, different organisms share the same antigens, making tests results unreliable. These factors can result in TB disease not being identified or wrongly diagnosed.


A blood test for diagnosing active TB disease is bad practice

"In the best interests of patients and caregivers in the private and public health sectors, WHO is calling for an end to the use of these serological tests to diagnose tuberculosis," said Dr Mario Raviglione, Director of WHO Stop TB Department. "A blood test for diagnosing active TB disease is bad practice. Test results are inconsistent, imprecise and put patients' lives in danger."

Today's policy recommendation applies to blood tests for active TB. Blood tests for inactive TB infection (also known as dormant or latent TB) are currently under review by WHO.

New recommendation after 12 months of rigorous analysis

The new recommendation comes after 12 months of rigorous analysis of evidence by WHO and global experts. Ninety-four studies were evaluated - 67 for pulmonary tuberculosis (TB in the lungs) and 27 for extrapulmonary tuberculosis (TB elsewhere in other organs). Overwhelming evidence showed that the blood tests produced an unacceptable level of wrong results - false-positives or false-negatives - relative to tests endorsed by WHO.

Problems of misdiagnosis

The research revealed "low sensitivity" in commercial blood tests which leads to an unacceptably high number of patients wrongly being given the 'all clear' (i.e. a false-negative when in reality they have active TB). This can result in the transmission of the disease to others or even death from untreated tuberculosis. It also revealed "low specificity", which leads to an unacceptably high number of patients being wrongly diagnosed with TB (i.e. a false-positive when in reality they do not have active TB). Those patients may then undergo unnecessary treatment, while the real cause of their illness remains undiagnosed, which may then also result in premature death.

The inaccurate blood tests are costly

More than a million of these inaccurate blood tests are carried out annually to diagnose active TB, often at great financial cost to patients. Many patients pay up to US$ 30 per test. There are at least 18 of these blood tests available on the market. Most of these tests are manufactured in Europe and North America, even though the blood tests are not approved by any recognized regulatory body.

Selling substandard tests with unreliable results

"Blood tests for TB are often targeted at countries with weak regulatory mechanisms for diagnostics, where questionable marketing incentives can override the welfare of patients," said Dr Karin Weyer, Coordinator of TB Diagnostics and Laboratory Strengthening for the WHO Stop TB Department. "It's a multi-million dollar business centred on selling substandard tests with unreliable results."

This is the first time WHO has issued an explicit "negative" policy recommendation against a practice that is widely used in tuberculosis care. It underscores the Organization's determination to translate strong evidence into clear policy advice to governments.

Tuberculosis kills 1.7 million people every year, and is the major killer of people living with HIV. Improving the early and effective diagnosis of TB to ensure more lives are saved is a priority action for WHO and the international TB community. TB research is currently underway to bring better and more rapid tests that are easy to administer, effective and accurate.
I wonder how many other antibody tests will need to be examined in the coming years. Something tells me the problem isn't confined to TB testing.

Henry
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Re: Bullying Borrelia

Post by Henry » Tue 15 Jan 2013 0:12

Tosho: In all fairness, I must say that this is highly speculative since many of the symptoms are non-specific (not unique or diagnostic for any particular infection) and may not even be due to any sort of infectious disease at. That possibility is just as likely under such circumstances. If that possibility is the case, then one would be doing the patient a great injustice by treating him/her for an infectious disease for which there is no evidence. Some would call that malpractice. I know that you are sure in your mind and heart that this must be caused by an infectious agent of some sort; but, the possibility is just as likely that may not be the case.

RitaA
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Joined: Thu 1 Jul 2010 8:33

Re: Bullying Borrelia

Post by RitaA » Tue 15 Jan 2013 0:21

http://www.hhmi.org/biointeractive/vlab ... index.html
The Virtual Immunology Lab

Howard Hughes Medical Institute

DIAGNOSIS OF DISEASE BASED ON IMMUNE RESPONSE—A VIRTUAL LABORATORY EXERCISE

Components of the immune system called antibodies are found in the liquid portion of blood and help protect the body from harm. Antibodies can be used also outside the body in a laboratory-based assay to help diagnose disease caused by malfunctions of the immune system or by infections.

This virtual laboratory will demonstrate how such a test, termed an enzyme-linked immunosorbent assay (ELISA), is carried out and some of the key experimental problems that may be encountered. Students will learn about the assay procedure and the equipment and materials that are needed. By completing this exercise, students will gain a better understanding of experimental design, key concepts in immunological reactions, and interpretation of data.

Concepts Covered

The basis of humoral immunity
The foundation for ELISA
Potential errors in conducting an ELISA
Sensitivity and specificity of a diagnostic test
Potential Experimental Problems

ELISA is used in many laboratories to determine whether a particular antibody is present in a patient's blood sample. Although the procedure is routine and straightforward, it involves a number of variables, such as reagent selection, temperature, volume measurement, and time, which if not adjusted correctly can affect subsequent steps and the test outcome. This virtual laboratory has been developed so that when a mistake is made, you will not get the correct answer. The program keeps track of errors made throughout the experiment and generates a report at the end.

Limitations of the Test

This general test has some important limitations.

First, a positive result correctly confirming the presence of antibody does not necessarily mean the patient is sick. The body can continue to produce antibodies even though the person may have had the disease earlier and recovered.

Second, people may be poor producers of antibody or may have some interfering substance in their blood. The amount of antibody, consequently, may be too low to measure accurately or may go undetected. This result is termed a false negative.

Third, a positive result may occur if an unrelated antibody reacts with the antigen nonspecifically.
Unlike a true-positive result where the specific antibody is detected, however, this positive reaction is false. Testing many patients and running tests more than once helps lab workers distinguish a true from a false result. To avoid simple experimental mistakes leading to incorrect results, scientists conduct tests using duplicate (or, sometimes, more than two) samples.

radicale
Posts: 134
Joined: Fri 4 May 2012 16:51

Re: Bullying Borrelia

Post by radicale » Tue 15 Jan 2013 0:25

http://cid.oxfordjournals.org/content/55/3/322
Fool's Gold: Why Imperfect Reference Tests Are Undermining the Evaluation of Novel Diagnostics: A Reevaluation of 5 Diagnostic Tests for Leptospirosis
Direk Limmathurotsakul1,2, Elizabeth L. Turner7, Vanaporn Wuthiekanun2, Janjira Thaipadungpanit2, Yupin Suputtamongkol5, Wirongrong Chierakul2,3, Lee D. Smythe6, Nicholas P. J. Day2,8, Ben Cooper2, and Sharon J. Peacock2,4,9

Abstract

Background. We observed that some patients with clinical leptospirosis supported by positive results of rapid tests were negative for leptospirosis on the basis of our diagnostic gold standard, which involves isolation of Leptospira species from blood culture and/or a positive result of a microscopic agglutination test (MAT). We hypothesized that our reference standard was imperfect and used statistical modeling to investigate this hypothesis.

Methods. Data for 1652 patients with suspected leptospirosis recruited during three observational studies and one randomized control trial that described the application of culture, MAT, immunofluorescence assay (IFA), lateral flow (LF) and/or PCR targeting the 16S rRNA gene were reevaluated using Bayesian latent class models and random-effects meta-analysis.

Results.The estimated sensitivities of culture alone, MAT alone, and culture plus MAT (for which the result was considered positive if one or both tests had a positive result) were 10.5% (95% credible interval [CrI], 2.7%–27.5%), 49.8% (95% CrI, 37.6%–60.8%), and 55.5% (95% CrI, 42.9%–67.7%), respectively. These low sensitivities were present across all 4 studies. The estimated specificity of MAT alone (and of culture plus MAT) was 98.8% (95% CrI, 92.8%–100.0%). The estimated sensitivities and specificities of PCR (52.7% [95% CrI, 45.2%–60.6%] and 97.2% [95% CrI, 92.0%–99.8%], respectively), lateral flow test (85.6% [95% CrI, 77.5%–93.2%] and 96.2% [95% CrI, 87.7%–99.8%], respectively), and immunofluorescence assay (45.5% [95% CrI, 33.3%–60.9%] and 96.8% [95% CrI, 92.8%–99.8%], respectively) were considerably different from estimates in which culture plus MAT was considered a perfect gold standard test.

Conclusions. Our findings show that culture plus MAT is an imperfect gold standard against which to compare alterative tests for the diagnosis of leptospirosis. Rapid point-of-care tests for this infection would bring an important improvement in patient care, but their future evaluation will require careful consideration of the reference test(s) used and the inclusion of appropriate statistical models.
More info on MAT:

http://tesla.rcub.bg.ac.rs/~lepto/lab/mat.html
...One should never depend entirely upon the serologic reactions of the patients serum in determining the infecting serotype.
A negative MAT reaction even on serial samples does not rule out the possibility of infection, since the patient may be infected with a serotype not included in the battery of antigens.
Furthermore early antibiotic treatment may suppress the development of leptospiral antibodies. Paradoxical reactions with certain strains act as a signal for an acute leptospirosis. Serodiagnosis of leptospirosis in not particularly difficult by MAT, but reliability depends on the availability of a large number of representative strains of Leptospira and on specialized experience.
Apart from the variables inherent in the serological tests the antibody response of the host to leptospiral infections is also variable.
The results must be considered for each individual case and evaluated in relation to all other, especially clinically and epidemiological data...
Of interest:

http://spirochetesunwound.blogspot.ca/2 ... ation.html
...You can see that the accuracy of alternative leptospirosis tests is underestimated when MAT (or MAT plus culture) is assumed to be the perfect reference test. Another implication of the study is that the prevalence of leptospirosis has been underestimated, at least in Thailand. The only other study to evaluate the performance of MAT by latent class analysis was conducted by the CDC here in the U.S almost a decade ago. In contrast to the Limmathurostsakul study, the CDC study determined that the sensitivity of MAT was high, at 98.2%. There were many differences between the two studies, including the patient population, the alternative tests evaluated, the time interval between collection of paired sera, and the number of serovars included for MAT. The poor performance of MAT in the Thailand study may therefore not be a universal finding...
The study by the CDC is found here:

http://jcm.asm.org/content/41/2/803
Evaluation of Four Commercially Available Rapid Serologic Tests for Diagnosis of Leptospirosis

Camp Other
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Re: Bullying Borrelia

Post by Camp Other » Tue 15 Jan 2013 0:50

Joanne60 wrote:Camp
At the IOM workshop Later in discussing reinfection and relapsing illness Ben Lufts response was - 100.30 mins in
Apologies for spelling but this was a copy from the automated transcript on the day.
But the nature of Lyme disease is it's a relapsing disease.

That's the very nature of you getting infected, very erythema myograms, having dissemination, separated by time, the disease comes back and it can give you cardiac abnormalities or abnormalities in your joint, that's a relapse.

That's a relapsing process.

The period of time is well-being with disease relapses, and that can occur in a cyclical manner.

You can have multiple episodes of relapse, and this can go on for years.

That's the natural history of the disease.

The natural history of disease ez is it's a relapsing disease.

It's also very interesting that even though you may have this disease, you can be reinfected with another -- with Lyme disease again, even though you've been previously infected.

I just wanted to clarify that.

http://www.tvworldwide.com/events/iom/1 ... t=0&live=0

Joanne, I saw that presentation, too and agree with the general statement that B. burgdorferi sensu latu causes a relapsing disease. But that said, when it comes to the most common usage in scientific research, the disease name associated with B. burgdorferi sensu latu is "Lyme disease" or "Lyme Borreliosis" and disease name associated with spirochetes designated as being relapsing fever spirochetes (such as B. hermsii or recurrentis) is "relapsing fever". To be technically correct and escape the distinction, patients with relapsing fever or Lyme disease are both suffering from Borreliosis.

Additional observation: I think it's more reasonable to make a comparison of B. burgdorferi sl to relapsing fever spirochetes in terms of behavior and survival strategies rather than compare B. burgdorferi sl to Treponeme spirochetes. Reason being that relapsing fever spirochetes are also tickborne, and having the tick as an intermediary in infection triggers an immune cascade which differs from that which occurs with a Treponeme infection. Why patients and patient advocates continue to compare Lyme disease to syphilis when a comparison to relapsing fever is genetically closer and more similar to Lyme disease is something I do not understand.
Last edited by Camp Other on Tue 15 Jan 2013 2:15, edited 1 time in total.

tosho
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Re: Bullying Borrelia

Post by tosho » Tue 15 Jan 2013 1:14

Henry wrote:Tosho: In all fairness, I must say that this is highly speculative since many of the symptoms are non-specific (not unique or diagnostic for any particular infection) and may not even be due to any sort of infectious disease at. That possibility is just as likely under such circumstances. If that possibility is the case, then one would be doing the patient a great injustice by treating him/her for an infectious disease for which there is no evidence. Some would call that malpractice. I know that you are sure in your mind and heart that this must be caused by an infectious agent of some sort; but, the possibility is just as likely that may not be the case.
A lot of symptoms of TBDs (if not most) are non-specific, thus the diagnosis may be difficult. And that is why differential diagnosis is so important. When you have a patient that had tick bite(s), was previously healthy, became chronically ill, has negative work-up for other diseases, and so on..., then, the probability that this patient suffers of infections transmitted by a tick(s) is meaningful.

Lorima
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Re: Bullying Borrelia

Post by Lorima » Tue 15 Jan 2013 15:47

Camp Other wrote:Additional observation: I think it's more reasonable to make a comparison of B. burgdorferi sl to relapsing fever spirochetes in terms of behavior and survival strategies rather than compare B. burgdorferi sl to Treponeme spirochetes. Reason being that relapsing fever spirochetes are also tickborne, and having the tick as an intermediary in infection triggers an immune cascade which differs from that which occurs with a Treponeme infection. Why patients and patient advocates continue to compare Lyme disease to syphilis when a comparison to relapsing fever is genetically closer and more similar to Lyme disease is something I do not understand.
CO,
I take your point that it's worth comparing relapsing fever borreliosis and Lyme borreliosis, from a scientific standpoint.

What makes the analogy with syphillis more useful, IMHO, is that doctors, and the general public, know a lot more about syphillis than relapsing fever. The point of an analogy, is to explain something people don't know about, by comparing it to something they do know about. If you compare it to something else people don't know about, in this case relapsing fever borreliosis, you're simply confusing them further.

If you have the idea that doctors all know (or "should" know) about relapsing fever, I'd think again. It's true that the name might tip them off that there's something "relapsing" about it, which is indeed one of the important points about Lyme borreliosis that the analogy is meant to convey. But even if they pick up on that and look into it, they will find that the relapses of RF occur within a short period of time (weeks and months), according to textbook-level (i.e. superficial) knowledge. The important thing to convey about Lyme borreliosis is that it seems to disappear: the patient seems to be fully recovered, but actually they are in a latent stage comparable to that of syphillis, which every doctor knows often lasts for years or even decades, before the "tertiary stage" manifests itself. Furthermore, the tertiary stage often is completely neurological. Every doctor knows this, off the top of his/her head (and a large proportion of educated laypeople know this too).

That is the value of syphillis, as an analogy to help doctors and the public understand Lyme borreliosis.
"I have to understand the world, you see."
Richard Feynman

Henry
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Re: Bullying Borrelia

Post by Henry » Tue 15 Jan 2013 16:12

I refer those who persist in making analogies between Lyme disease and tick relapsing fever to this reference which clearly distinguishes between both diseases ( http://www.cdc.gov/relapsing-fever/). Comparing Lyme disease to syphilis is also hazardous and inappropriate. Although both diseases are caused by spirochetes, the pathology is very different; that is the major reason why Treponema pallidum -- the spirochete that causes syphilis -- is placed in a different GENUS than Borrelia burgdorferi. The genetic relationship of T. pallidum is closer to T. denticola than to B. burgdorferi; although T. denticola is a common inhabitant of the oral cavity and is one of the agents involved in gingivitis, it doesn't cause syphilis. So, forget all of these stupid analogies that only serve to "muddy the waters" and cause more confusion.

Incidentally, relapsing tick fever is easily cured by a short course of oral antibiotics; it is characterized by a pattern of 3-4 cycles that occurs at regular -- not irregular-- seven day intervals -- and then, no more (most likely because immunity develops). Some forms of late syphilis can be cured by penicillin . Most likely, this erroneous concept of "relapsing Lyme disease" was taken from the cancer literature.

Camp Other
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Re: Bullying Borrelia

Post by Camp Other » Tue 15 Jan 2013 18:03

Henry wrote:I refer those who persist in making analogies between Lyme disease and tick relapsing fever to this reference which clearly distinguishes between both diseases ( http://www.cdc.gov/relapsing-fever/). [...]
I don't find that to be the best link on the CDC site for making comparisons between Lyme disease and relapsing fever. This page is more appropriate for that purpose:

Vector Interactions and Molecular Adaptations of Lyme Disease and Relapsing Fever Spirochetes Associated with Transmission by Ticks
http://wwwnc.cdc.gov/eid/article/8/2/01 ... rticle.htm

I don't see why one wouldn't immediately want to make comparisons - they're their closest relative, genetically speaking, and have more similarities to each other than to Treponema.

Here's the section on species comparisons:
Species Comparisons

From the observations reviewed above, one phenomenon shared by B. burgdorferi and B. hermsii is the synthesis of OspC and Vsp33 at the time these spirochetes are transmitted by tick bite. DNA and amino acid sequence analysis also shows that these proteins are homologous (51) and that antisera produced to the two proteins are cross-reactive (51–53). Several other species of Borrelia also contain a related gene or protein recognized with either Northern or Western blot (53). Therefore, this family of surface proteins may be shared by all species of borreliae, which are spirochetes defined, in part, by their requirement for an arthropod vector for transmission. Our hypothesis is that these proteins are involved in the transmission of these spirochetes from tick to vertebrate host.

The temporal synthesis of OspC and Vsp33 during spirochete infection in ticks is strikingly different between B. burgdorferi and B. hermsii, but appears to be adaptive to ixodid versus argasid ticks, which have considerably different feeding behaviors. Most nymphal I. scapularis take 3 to 4 days to feed whereas O. hermsi feed to repletion in only 15 to 90 minutes. In free-living, unfed I. scapularis, B. burgdorferi is usually found only in the midgut and OspC is not expressed. However, following tick attachment B. burgdorferi replicates, downregulates OspA, disseminates from the midgut to salivary glands, synthesizes OspC, and is transmitted via the saliva after 2 to 4 days of feeding.

An increase in temperature and the ingestion of blood, environmental cues associated with a free-living tick having attached and begun to feed on a host, stimulate a subpopulation of B. burgdorferi to transiently synthesize OspC during feeding. If OspC is required for transmission of B. burgdorferi by tick bite, there is ample time, because of the slow feeding behavior of Ixodes ticks, for both the dissemination of spirochetes from the midgut to the salivary glands and the novel synthesis of OspC. Numerous studies have shown that humans and experimental animals infected by tick bite seroconvert to OspC early, demonstrating that this protein is expressed in mammals for some undetermined period.

In free-living, unfed O. hermsii, the distribution of B. hermsii in these ticks and their expression of Vsp33 are just the opposite, with spirochetes established in the salivary glands and nearly all expressing Vsp33. In the scenario with O. hermsi feeding for only minutes after encountering a host, there is no time for spirochetes to disseminate out of the midgut, penetrate the salivary glands to the salivary duct, and also synthesize a new Osp that may facilitate (or be required for) transmission. Hence B. hermsii is in a constant state of readiness for transmission that is comparable to the phenotype and localization displayed by B. burgdorferi only briefly during a few days of attachment by I. scapularis (Figure 4).

The phenotypic changes and dissemination shown by B. burgdorferi during transmission by tick bite point to several possible functions for OspC: dissemination from the midgut, infection of the salivary glands, or successful colonization in the mammal following delivery into the feeding lesion in the dermis. Because the changes in protein synthesis and movement of the spirochetes occur rapidly in the nymphal ticks, identifying the precise time when OspC is produced in relation to the spirochetes’ movement in the tick is difficult to determine by microscopy. Quantitative reverse transcription-PCR may help increase sensitivity through detecting specific gene transcripts in different tick tissues sampled a different times. However, the events shown by B. hermsii during its dissemination in the tick are much more protracted and may shed some light on the function of OspC, Vsp33, or other proteins.

Because it takes approximately 3 weeks or more for B. hermsii to disseminate and become established in the salivary glands of O. hermsi, immunofluorescent staining of these spirochetes in tick tissues at successive intervals after infection has recently shown that B. hermsii can infect the salivary glands before the upregulation of Vsp33. At least for this relapsing fever spirochete, Vsp33 does not appear to be needed either for dissemination from the gut or invasion of the salivary glands.

Additional species of Borrelia and their expression of Osps associated with transmission need to be examined. If the OspC, Vsp33, or other proteins are required for transmission by ticks, we anticipate finding homologs to these proteins in other species associated with their transmission. Other relapsing fever spirochetes in Ornithodoros ticks, B. anserina in Argas ticks, and other borrelia associated with ixodid ticks will be fruitful tick-spirochete associations to study. A comparison of borrelial genomes will also be helpful when such sequences become available. Finally, with important advances being made recently to inactivate and introduce genes in these spirochetes (54,55), experiments to examine the importance of specific proteins in various steps of the transmission cycle are on the horizon.
Where there are unanswered questions - for me at least - are the relapsing fever spirochetes which are NOT in Ornithodoros ticks but now found in hard bodied ticks including Ixodes ticks. What role do they play in tick-spirochete associations? Where are they found throughout the tick's body? How quickly do they disseminate into salivary glands or are they there most of the time? I simply don't know, but I think this is something important to know for disease transmission purposes.
Incidentally, relapsing tick fever is easily cured by a short course of oral antibiotics; it is characterized by a pattern of 3-4 cycles that occurs at regular -- not irregular-- seven day intervals -- and then, no more (most likely because immunity develops). Some forms of late syphilis can be cured by penicillin . Most likely, this erroneous concept of "relapsing Lyme disease" was taken from the cancer literature.
I know about the fast repetitive cycles where relapsing fever shows up in the blood. But does it always happen that the infection is cleared or can it be latent? I thought I'd already cited literature here which provided evidence it can be latent in the mammalian host and it is unknown how often this occurs.

Why do you think Dr. Ben Luft is mischaracterizing Lyme disease as a relapsing disease? He is a key researcher of Lyme disease and its variability. Why would he draw from cancer literature to make such an association (and where, if you can be more precise - how is Borrelia similar to cancer, because I've never heard of this conceptual link you're making?)

Isn't there some evidence Lyme disease does relapse, but on a slower timescale than relapsing fever spirochetes found in soft bodied ticks? Aren't there at least two recorded bacterial peaks in early infection with Lyme disease recorded - one at week 5, then another around week 9-10? Or would you not consider these peaks to be relapses?

What about its antigenic variation cycles throughout infection? I would consider their similarity in antigenic variation cycles to be a good comparison - even if the genetic mechanism behind how RF spirochetes do it differs from the mechanism for how LD spirochetes do it.
Comparing Lyme disease to syphilis is also hazardous and inappropriate. Although both diseases are caused by spirochetes, the pathology is very different; that is the major reason why Treponema pallidum -- the spirochete that causes syphilis -- is placed in a different GENUS than Borrelia burgdorferi. The genetic relationship of T. pallidum is closer to T. denticola than to B. burgdorferi; although T. denticola is a common inhabitant of the oral cavity and is one of the agents involved in gingivitis, it doesn't cause syphilis. So, forget all of these stupid analogies that only serve to "muddy the waters" and cause more confusion.
Pathology is different, genetically different in a number of ways - agreed. Here's a good ref for anyone interested:

Comparative Genome Analysis of the Pathogenic Spirochetes Borrelia burgdorferi and Treponema pallidum
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC97324/

I particularly find this passage from the above paper to be fascinating, regarding hortizontal gene transfer from other bacteria (archaea) and also (!) eukaryotes:
In spite of the high level of conservation in the translation apparatus, we did detect a few interesting examples of evolutionary divergence between the two species. One notable case was the prolyl-tRNA synthetase from B. burgdorferi, where phylogenetic analysis strongly suggested that the enzyme in B. burgdorferi has been acquired from a eukaryotic source by the xenologous displacement mechanism (78). The other aminoacyl-tRNA synthetases are strongly conserved between the spirochetes, but phylogenetic analysis provided evidence for likely ancient horizontal transfers into the ancestor of spirochetes accompanied by displacement of the original gene. One well-studied case in this category is class I lysyl-tRNA synthetase, which apparently was acquired from the archaea (37, 78); similar evidence of archaeal origin was obtained for the two subunits of phenylalanyl-tRNA synthetase (78). By contrast, the synthetases for arginine, glutamate, methionine, isoleucine, and serine showed evidence of likely horizontal transfer from eukaryotic sources (78).

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