4 Part 3: Sexual Transmission Of Lyme Disease - Is There Evidence?

This article is the continuation of "Part 2: Sexual Transmission of Lyme Disease - Is There Evidence?", our series on sexual transmission and contact studies involving Borrelia burgdorferi.

To review the content of the first article briefly: We discussed the fact that no human sexual transmission studies of Borrelia burgdorferi have been conducted to date and reviewed the outcomes of animal studies on contact transmission and sexual (venereal) transmission. Based on all studies which could be found, there was evidence that Borrelia burgdorferi may be transmitted between at least some animals either via exposure to infected urine or by consumption of raw milk. The possibility that animals could transmit Borrelia burgdorferi to each other via sexual intercourse has only been examined in a few controlled studies, no cases have been confirmed so far, and it remains an issue of speculation in studies where uninfected animals came in contact with infected ones and developed a positive of antibody response (and in some cases, even signs of infection).

What follows below is some notes on studies which are listed in Table 1 in "Part 2: Sexual Transmission of Lyme Disease - Is There Evidence?" as well as notes on additional papers on Borrelia burgdorferi transmission studies which were not included in that table as they were speculative and not based on controlled studies.

Additional Notes On Studies Included In Part Two's Table

The 1994 paper, "Distribution of Borrelia burgdorferi in host mice in Pennsylvania", is a study where samples are taken from ear tissue from mice from different counties around the state of Pennsylvania. When a sample was positive by darkfield microscopy and fluorescent-antibody testing, it was sent to the CDC for further evaluation.

In the discussion section of this paper, the authors state that a group tagged mice in one county which repeatedly tested negative before began to turn up positive during the winter in areas where no vector ticks had been found - and because of this, the authors speculate this group of mice may not have been infected by ticks. However, there is no evidence in their paper which confirms an alternative method of infection. Because of this, I wouldn't cite this paper to support a method of contact or sexual transmission of Lyme disease between mice. It is a mystery how one specific group of mice in Indiana County were infected during the winter.

I run into the same problem with the 1997 publication, "Tick-raccoon associations and the potential for Lyme disease spirochete transmission in the coastal plain of North Carolina". In it, the authors discover that while raccoons in the South are highly infected with Borrelia burgdorferi, none of the vector ticks which they find on them appear to have high spirochetal loads, and a low percentage of them are infected with Borrelia burgdorferi. The ticks which latch onto the raccoons the most are Amblyomma americanum - Lone Star ticks - and studies in the past showed they are incompetent vectors of Borrelia burgdorferi but are great at transmitting Ehrlichia and other pathogens.

The authors go on to speculate that maybe the raccoons are infected via urine, but also actually refer to the 1994 paper on host mice above, wondering if sexual or oral contact may be the cause for raccoons' high rate of Borrelia burgdorferi infection. There is no evidence here which confirms this method of transmission occurred in this study - it is just something the scientists are wondering about. More recent research supports the idea that Amblyomma americanum ticks are infected with other strains of Borrelia, and today raccoons in North Carolina may be infected with those - but at the time of this study, the raccoons' infections were considered unusual because the ticks collected did not appear to be full of spirochetes in general.

Relevant Reviews, Summaries, and Editorials Outside The Scope of Part Two's Table

One of the most cited papers on Borrelia, "Biology of Borrelia Species"(1986) by Dr. Alan Barbour and Dr. Stanley Hayes, quotes research on the presence of Borrelia spirochetes in urine dating back to 1938: Chung and Wei's "Studies on the transmission of relapsing fever in North China I. Observations on the mechanism of transmission of relapsing fever in man." In a short passage, they mention that "Spirochetes in the urine could enter the host through the mucous membranes of the conjunctiva, mouth, or nose". It is this early research which perhaps set the stage for stringent laboratory rules about how to handle Borrelia burgdorferi spirochetes - that and the knowledge that other spirochetes, Leptospira, could infect people through contact with urine.

In another paper not included in the table in Part 2, "Epidemiologic Studies of Lyme disease in horses and their public  health significance" there was passing mention of horse bite transmitting Lyme disease to a man in 1987 in Belgium. I am fortunate to have located the case study online describing the transmission of Lyme disease via a horse bite, "Horse Reservoir for Borrelia burgdorferi?" (Lancet, Apr. 25, 1987), and read the full text. It is an interesting case, in that it describes a man who was bitten on the neck by a horse with Lyme disease who went on to develop a erythema migrans (EM) rash and additional symptoms of Lyme disease shortly thereafter. No mention of the location of the rash was made in the case study, but had it stated it was directly at the bite site it would have strengthened the case for the infection being caused by the horse bite. As it stands, the history, timing of exposure, and clinical evidence do point to the possibility that a horse bite could have given this man Lyme disease - but this appears to be a rare case as I have not found other similar case studies.

A paper from 1991, "Borrelia burgdorferi: another cause of foodborne illness?" is an editorial letter which refers to studies mentioned in the table, and was written by researchers who questioned whether or not Borrelia burgdorferi was a risk to the food supply. They mention another study from 1990, "Thermal inactivation of Borrelia burgdorferi, the cause of Lyme disease," where it was discussed that refrigerated milk at 5° C contained viable Borrelia burgdorferi after 46 days and that high-temperature short-time (HTST) pasteurization may not kill all Borrelia burgdorferi in milk, thus raising questions as to whether the temperature should be raised and how much. The authors do not have an answer for their own questions - they only raise them for consideration.

The 1992 paper, "Lyme Borreliosis in dairy cattle" and 1994 paper, "Lyme Borreliosis in domestic animals" were not included in the table because both are overviews on Lyme disease studies on animals which refer to existing studies otherwise mentioned in the table and do not contain new experiments;  references used in one paper are also used in the other. In the first paper, references to finding spirochetes in cattle milk, urine, and colostrum are cited which are mentioned in the second. In the second paper, it is mentioned that cats have been infected via experimental inoculation of B. burgdorferi by intravenous, oral, and conjunctival routes. Both papers cite other papers already listed in the table, and as such, I have not included these two papers in the table order to avoid duplication of data.

While not directly addressed in the studies above,  pasteurization seems likely to reduce odds of Borrelia burgdorferi survival.

Studies listed in Table 1 indicate that spirochetes can turn up in urine, milk, and colostrum samples, but positive samples in these studies came from animals which have not been treated with antibiotics (which affect Lyme disease) and/or fluids such as raw milk which has not been pasteurized - which suggests that the possibility of human infection from consuming animal products is going to be extremely low because most meat is cooked and milk is pasteurized.

"Thermal inactivation of Borrelia burgdorferi, the cause of Lyme disease" is the only paper I've reviewed which suggests that milk should be pasteurized at a higher temperature to ensure all spirochetes are dead.

What happens to milk during pasteurization all depends on how it's pasteurized: High-temperature short-time (HTST) pasteurization is when milk is subjected to a temperature of 71.5 °C (160 °F) to 74°C (165 °F), for about 15 to 30 seconds. Low-temperature long-time treatment is when milk is pasteurized at 63 °C (145 °F) for 30 minutes. And ultra-pasteurization is when one heats milk or cream to 138 °C (280 °F) for 2 seconds to extend the refrigerated shelf life of milk from 60 to 90 days.

This of course raises the question: At what temperature does Borrelia burgdorferi die?

Porcella and Schwan wrote in 2001 that:

"In vitro cultivation of B. burgdorferi at various temperatures demonstrates that the spirochete replicates most quickly at 37 °C. An increase in temperature to 39 °C retards growth significantly, while a 24 hour exposure at 41 °C kills all spirochetes in the culture." 

According to a 2008 research study by Juliet Kim, "Differential Temperature Susceptibility and Survival of Borrelia burgdorferi and Borrelia hermsii":

"... on average, the Lyme disease bacterium had a higher survival at the higher temperatures than the relapsing fever agent, with a mean survival (95% confidence interval) of 1.62 (0.06– 43.6) X10-4 vs. 3.16 (1.02- 9.77) X10-4 at 50 °C and 38.3 (1.18- 1250) X10-6 vs. 1.96 (23.5- 16.3) X10-6 at 51 °C."

Laboratory techniques for semisolid plating of Borrelia burgdorferi require that samples do not exceed 52 °C, which is in the ballpark of the highest temperature on average that Borrelia burgdorferi die off in vitro in Kim's study.

It would seem either a lower temperature exposure of 41 °C over a longer duration is needed to kill all spirochetes or a higher temperature at shorter duration. Pasteurization is a minimum over 10 °C higher than these temperatures where spirochetes died off - so the question becomes how long can spirochetes survive at temperatures this high? Perhaps this is an issue requiring further research.

Summary of Findings From This Three Part Series

There is not one study to date which has been conducted which provides evidence sexual transmission of Borrelia burgdorferi, the spirochete which causes Lyme disease, occurs between humans. (I am reserving discussion on the Middelveen et al study for later - and so far the abstract does not indicate it is a transmission study.)

Far as is known, there is no study to date which has been conducted which provides evidence sexual transmission of Borrelia burgdorferi occurs between animals, either - and very few controlled studies on venereal transmission in animals have been completed (Are there more than three?).

There is some evidence that at least some animals under certain circumstances may contract infection with Borrelia burgdorferi through contact in some way. The two most plausible routes appear to be through exposure to urine and ingestion of raw milk.

Studies on pasteurization of raw milk and the temperature at which Borrelia burgdorferi lead one to believe that most if not all of Borrelia burgdorferi will die when raw milk is pasteurized - but I would like an expert spirochetologist to weigh in on this, though, and cover what is posted about laboratory plating requirements.

Researchers have at times speculated that sexual transmission of Borrelia burgdorferi may occur between animals, but there has been more speculation than there have been actual controlled studies to support this hypothesis.

Some of this speculation came about after finding out uninfected contact animals exposed to infected animals developed a positive antibody response for Borrelia burgdorferi as well as signs of infection. If sexual contact between these animals occurred, it was not recorded as having been observed in the holding pen/cage.

So, to answer the question about sexual transmission of Lyme disease between humans and also between animals: So far there is no evidence that it occurs. There are also few studies which test this possibility.

Thus ends another chapter in this ongoing notebook, Camp Other blog... I'm tired, I go crash now.

[Placeholder for references of all papers listed in this three part series to be added soon.]

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0 Part 2: Sexual Transmission Of Lyme Disease - Is There Evidence?

Syrian hamsters mating. From How to Breed
Syrian Hamsters on wikiHow.

This article is the continuation of "Part 1: Sexual Transmission Of Lyme Disease - Is There Evidence?", our series on sexual transmission and contact studies involving Borrelia burgdorferi.

To review the content of the first article briefly: We discussed three studies which are often used online to support the idea that Lyme disease could be a sexually transmitted disease between human patients. While two of those studies provided some evidence patients had spirochetal DNA in their bodily fluids, none of the studies provided evidence that Lyme disease is sexually transmitted by people. Setting aside the yet-to-be available Middelveen et al study, there are no studies to date which provide evidence that Lyme disease can be sexually transmitted in humans and there are very few studies which investigate this method of transmission in animals. We also had an introduction to Dr. Elizabeth Burgess' Lyme disease transmission studies, the criticism from Dr. Burgdorfer which they received, and took a glance at her study findings.

In Part 2 of this series, we'll be looking more closely at the results of  Dr. Burgess' studies and that of other researchers on contact transmission and the potential for sexual transmission of Lyme disease in animals.

The Tally So Far: Studies On Lyme Disease Sexual Transmission And Contact Transmission

So far, I have not located any studies on Lyme disease and sexual transmission in humans, and found only a few studies about human sexual secretions containing Borrelia burgdorferi DNA.

Is this lack of research on this method of transmission in people an oversight by researchers who are more focused on observing tickborne transmission? Or has the dominant view of researchers been that based on Lyme disease's pathogenesis, human sexual transmission of Borrelia burgdorferi is highly unlikely if not impossible - so why conduct more studies on it? Either way one answers, there is very little research on different transmission methods of Lyme disease in people.

What we do have are early animal studies which were designed to investigate the nature of Lyme disease transmission through various methods - methods such as: how much more effective needle inoculation was compared to tick bites in transmitting infection; injecting mice with the urine of infected cattle to see if they would get infected; a few studies where it was hoped animals would copulate and that one could determine if sexual transmission could occur.

To date, there are more animal studies which are about the potential for contact transmission of Borrelia burgdorferi -which means any kind of contact between animals either directly or indirectly via exposure to their blood, saliva, feces, urine, milk, or colostrum - than there are studies specifically about sexual or venereal transmission. It is the results of these early animal studies which were hoped would give one a better idea of whether or not other non-tickborne methods of transmission might also be possible in people, too.

Given the wide range of data available from different animal model transmission studies over a period of nearly fifteen years, I've decided to place them into a table to view them all in one place.

In general, the study data in the table below fall under the following five categories:

1. Evidence of the presence or absence of Borrelia burgdorferi in different bodily fluids of animals. These are not transmission studies. These are studies which demonstrate spirochetes or spirochetal DNA can be found in various secretions, but they do not show that such spirochetes or infection can be passed on to another host animal.
   
   
2. Evidence that the use of needle inoculation/subcutaneous injection of infected bodily fluids from animals can transmit Borrelia burgdorferi to uninfected animals and a tick was not required.
   
   
3. Evidence pointing to oral inoculation as a potential route of transmission. These are studies where the researcher deliberately tried to infect an animal with Borrelia burgdorferi (or a substance assumed to contain it) either orally or oronasally, then looked at the results.
   
   
4. Evidence supporting or rejecting sexual (venereal) transmission of Borrelia burgdorferi between studied animals.
   
   
5. Evidence suggesting that an uninfected animal became infected somehow by being housed in the same space as an animal already infected with Borrelia burgdorferi. These studies suggest that contact transmission may have occurred because no direct action was taken by the researcher to infect the control/uninfected animal, and no ticks were deliberately introduced to the control/uninfected animal.

For the purpose of focusing discussion, the table below mostly displays information related to the possibility of oral, contact, and sexual (venereal) transmission and not much transmission data via needle inoculation (though some of the studies also focus on that method of transmission and may be mentioned in passing).

Table 1: Evidence For The Presence of Borrelia Burgdorferi Infection Via Different Forms of Inoculation and Potential Contact Transmission

Year	Publication	Oral Inoculation		Contact	Spirochetal DNA	Whole Cell Spirochetes	Antibody Test	Culture/ PCR Status
1986	Experimental inoculation of dogs with Borrelia burgdorferi	N		Y	n/a	N	IFA+ n=1/1 contact  exposed dog	no PCR completed
1986	Experimental inoculation of Peromyscus spp. with Borrelia burgdorferi: evidence of contact transmission	N		Y	n/a	+ n=1/1 blood, contact mouse	Exp 1: IFA+ n=2/2 contact mice; 4 log2, 6 log2 Exp 2: +n=10/10 contact mice 4 log2-6 log2 Burgess speculates local IgA reaction possible instead of systemic IgG	no PCR completed
1986	The prevalence and significance of Borrelia burgdorferi in the urine of feral reservoir hosts	n/a		n/a	n/a	+ n=2 urine, via darkfield +n=21/22 kidneys, positive correlation w/ Babesia presence	n/a	no PCR completed
1986	Suspected borreliosis in cattle	Y cat fed infected milk		n/a	n/a	+ n=2/6 urine, via darkfield	IFA+ +n=1/1 cat fed infected milk had 1:164 titer +n=5/5 mice 1:8-1:32 titers with sc inoculation of milk +n=5/5 mice 1:32-1:64 titers with sc inoculation of urine	- cultures negative in blood, urine, and milk no PCR completed
1987	Oral infection of Peromyscus maniculatus with Borrelia burgdorferi and subsequent transmission by Ixodes dammini	Y		N	n/a	+ n=1/10 blood, + n=1/10 organs +n=1/10 blood (tick-fed) +n=1/10 organs (tick-fed)	IFA+ +n=10/10 orally infected mice +n=10/10 mice from ticks that fed on orally infected mice; 6 orally infected mice developed symptoms	no PCR completed
1988	The urinary bladder, a consistent source of Borrelia burgdorferi in experimentally infected white-footed mice (Peromyscus leucopus)	n/a		N	n/a	- 0/15 urine samples + 2/15 blood samples + tissue samples: bladder, kidney, spleen	n/a	+ tissue culture, no PCR
1988	Clinical and serologic evaluations of induced Borrelia burgdorferi infection in dogs.	n/a		Y	n/a	n/a	IFA antibody + ELISA + n=1 control dog elevated + IgG	no PCR completed
1988	Borrelia burgdorferi infection in Wisconsin horses and cows	Y n=3 mice inoculated with cow urine		n/a	n/a	+ n=2/10 cow urine + n=2/3 colostrum - all milk samples	IFA+ IgG n=2/3 colostrum titer, n=1/3 cows ~1:512 n=2/3 mice 1:64; 1:28	samples cultured, no PCR completed
1989	Experimental inoculation of mallard ducks (Anas platyrhynchos) with Borrelia burgdorferi	Y n=4 ducks		n/a	n/a	+ n=1/4 cloaca secretion, + n=1/4 kidney	IFA+ n=3/4 kidneys of orally inoculated ducks; +n=1/4 mesentery	positive cultures, no PCR completed
1990	Experimental infection of the white-footed mouse with Borrelia burgdorferi	Y		n/a	n/a	+ n=1 blood	IFA+ all asymptomatic mice	tissue culture, no PCR completed
1991	Experimental infection of dogs with Borrelia burgdorferi	N		Y	n/a	+ n=1 urine, blood of contact dog	IFA+ +n=1 uninoculated dog near 1 infected dog both asymptomatic	no PCR completed
1991	Relative infectivity of Borrelia burgdorferi in Lewis rats by various routes of inoculation	Y oronasally		N	n/a	- n=0/13 oronsally infected - n=0/6 males venereally - n=0/7 females venereally	only needle inoculated rats +	n/a
1992	Experimentally induced infection of cats with Borrelia burgdorferi	Y n=2		n/a	n/a	+ n=2 blood smear; n=1 lung	n=2 orally inoculated IFA+ n=2 ocularly inoculated IFA+	no PCR completed
1993	Detection of Borrelia burgdorferi in Urine of Peromyscus leucopus by Inhibition Enzyme-Linked Immunosorbent Assay	N		n/a	+n=57/87 whole cells or subunits in urine	+ n=57/87 whole cells or subunits in urine	+IFA +ELISA +n=47/75 serum +n=57/87 antigens in urine	+n=50/87 tissue culture; +n=36/50 infected bladders no PCR completed
1994	Experimental infection of dogs with Borrelia burgdorferi	N		Y	n/a	+ n=1/4 infected dog blood, urine	IFA+ +n=1/1 control dog, 1:128 (max titer) +n=2/2 guinea pigs inoculated with urine, 1:128	no PCR completed
1994	Distribution of Borrelia burgdorferi in host mice in Pennsylvania	n/a		Y see notes part 3	n/a	+ n=112 isolations/1619 mice (from ear tissue)	IFA+ in tick-bitten mice see notes part 3	no PCR completed
1996	Lyme Borreliosis in the laboratory mouse	-		-	-	-	- see below	-
1996	Dissemination of Borrelia burgdorferi after experimental infection in dogs	N		n/a		- n=0/6 urine culture		- culture bladder PCR completed - urine
1997	Tick-raccoon associations and the potential for Lyme disease spirochete transmission in the coastal plain of North Carolina	n/a		Y see notes part 3	n/a	n/a	IFA+ see notes part 3	no PCR was completed
1998	Viable Borrelia burgdorferi in the urine of two clinically normal horses	n/a		n/a	n/a	+n=2/5 horses, urine	+	+PCR FA on urine samples
1999	Investigation of venereal, transplacental, and contact transmission of the Lyme disease spirochete, Borrelia burgdorferi, in Syrian hamsters	N		N	n/a	-n=0/6 female hamsters, -n=0/6 male hamsters infected venereally no mice contact infected	- IFA in 6/6 venereal test hamsters and all contact mice	- tissue samples, no PCR was completed

Table Key:

+ positive - negative

n= #/# number of samples or study animals infected or not infected out of the total studied

n/a not applicable to study or no data available in given paper


Notes On The Above Table

While every effort was made for this table to be comprehensive, it may not be complete. (If you know of any additional publications and data which apply, please comment below so that I may add the paper to this table.)

Note that certain papers which have been cited online pointing to different methods of contact transmission or evidence of Borrelia burgdorferi spirochetes or spirochetal DNA in bodily fluids were not included in the above table. This is because these specific papers were either review or editorial papers which cited more than one study already included in the above table, and I did not want to give the impression that additional studies were completed where the studies and findings were reproduced by another researcher. (I do, however, mention these papers in part 3 of this series on sexual transmission.)

Note also that in certain columns data is lacking or relies on older methods:

In some studies, antibody testing was not completed on animals because the research goal was to focus on finding evidence of Borrelia DNA and/or spirochetes in a given sample and not to measure antibodies in the host animal.

In the 1980's and early 1990's, PCR studies were not performed on many samples. This is because at the time PCR was a relatively recent invention, was at first a slow and labor intensive process, and not many researchers had access to it. Also, there was some discussion over what the best method was to use on specific samples, and it hadn't been completely determined yet.

Immunofluorescent antibody (IFA) assay testing was the primary method of testing samples for the presence of antibodies, rather than ELISA or Western blot. This method has been considered less sensitive than others, but given studies listed use one or more monoclonal antibodies specific to Borrelia burgdorferi (such as H5332, specific to North American OspA) the positive results obtained are noteworthy.

So What Do These Studies Indicate or Suggest?

1.  Contact transmission of Borrelia burgdorferi could occur between specific animals under specific conditions.

While there is some evidence that some animals can be experimentally infected with Lyme disease through an oral or ocular route, it is unclear if animals end up infected through these routes in the natural world. It's important to note that dosages and the method used in a laboratory experiment may not have their parallel in real life conditions. Optimally, observing how infections occur in the wild would be best - but it is difficult to study animals in the wild to determine exactly when and how they get infected.

What the data in this table reflects is that there is some evidence to suggest that contact transmission via urine may be a concern with some animals - particularly cattle and mice. One study on ducks points to the possibility of oral transmission, though no one has duplicated it thus far or extended additional transmission research to other kinds of birds.

Based on the studies reviewed, if a form of contact transmission can occur in animals, it appears to happen inconsistently and in low numbers of animals - and so far appears to happen more frequently in specific species. Perhaps repeat studies with larger groups of animal subjects would be helpful - or perhaps they would demonstrate that contact transmission still only occurs in relatively few subjects under narrowly defined conditions. We just don't know.

There is also some evidence that certain animals are highly unlikely to contract Lyme disease via contact transmission via urine, such as Lewis rats and Syrian hamsters.

Additional autopsy studies in such cases that demonstrate where spirochetes are found in infected animals can be useful as they can indicate why spirochetes were not likely to be found in urine based on which tissues spirochetes colonized.

2.  In some cases, it is not exactly clear how contact animals were infected in individual studies. All we know is they had positive antibody tests and some showed signs of infection.

Based on the studies within the above table, the following studies resulted in at least a positive IFA result in a contact animal, and in some cases evidence of spirochetal infection:

1. Experimental inoculation of dogs with Borrelia burgdorferi.
2. Experimental inoculation of Peromyscus spp. with Borrelia burgdorferi: evidence of contact transmission.
3. Clinical and serologic evaluations of induced Borrelia burgdorferi infection in dogs.
4. Experimental infection of dogs with Borrelia burgdorferi.
5. Distribution of Borrelia burgdorferi in host mice in Pennsylvania.
6. Tick-raccoon associations and the potential for Lyme disease spirochete transmission in the coastal plain of North Carolina.

Of these studies, the last two listed above contained speculation by the researchers about whether or not mice and raccoons could contract Lyme disease through other methods outside of a tick bite - and neither of those two studies were completed under lab conditions and had control animals.

As for the remaining four studies, there is no indication exactly how uninfected control animals ended up with positive antibody tests and signs of infection when in the presence of infected animals. Apparently it has happened - but how and why it happened in a number of these studies even when animals are in captivity is unclear.

It is the unknown method of contact transmission in such studies which has led to speculation by others that sexual transmission may have occurred between animals. However, without a definite confirmation that sexual contact was the route of transmission, what happened remains a mystery.

We do not have documentation in a number of cases of whether or not infected and contact animals were housed together indoors or outdoors, or if they were isolated from birds or other environmental factors which may have introduced infected ticks or Borrelia burgdorferi. Without more data, it is difficult to determine whether or not animals may have been infected via a different route.

All the same, there is research above which indicates point #1 - that animals can be infected by other animals' secretions, although how often it happens and how is a good question. So far, urine and raw milk ingestion appears to be a plausible mode of transmission between some animals.

3.  There haven't been many animal studies specifically focused on sexual or venereal transmission.

Based on the studies within the above table, the following studies were specifically focused on sexual or venereal transmission and their results:

Title	Sexual or Venereal Transmission?
Investigation of venereal, transplacental, and contact transmission of the Lyme disease spirochete, Borrelia burgdorferi, in Syrian hamsters	- negative
Relative infectivity of Borrelia burgdorferi in Lewis rats by various routes of inoculation	- negative
Lyme Borreliosis in the laboratory mouse	- negative

Of three papers where experiments were specifically designed to see if venereal transmission occurred between animals, the results of all three were negative.

Three seems like a very small number of studies, and they were only completed on rats, Syrian hamsters, and mice. If you, the reader, knows of any additional studies on sexual or venereal transmission of Lyme disease in animals which were not included here - please comment below with the title(s) and link(s) to the paper(s).

Some Researchers Weigh In On Non-Tick Methods Of Transmission

More has been said about the methods of transmission in mice than any other animal because mice are used more extensively in a lab environment for the study of Lyme disease than any other species.

In 1996, Dr. Stephen Barthold wrote "Lyme Borreliosis in the laboratory mouse"in the Journal of Spirochetal and Tick-Borne Disease. On pages 23-24, he states:

"There has been no evidence of contact transmission or detection of viable spirochetes in urine of laboratory mice. Lung, bladder, and kidney are frequently infected, but spirochetes in these tissues are present in the connective tissue of the serosa, subserosa, submucosa (bladder), and periarterial connective tissue (lung, kidney), rather than lumina of tubules, ureters, bladder, or airways."

Based on his research up to that point in time, mice were not transmitting spirochetes through their urine to uninfected mice, and spirochetes which were found in autopsies were deeply embedded in connective tissue and not lining the vessels or surface of ureters, bladders, or bronchial tubes. In other words, if live spirochetes were present, they would be highly unlikely to be found in urine.

His findings differ from those of Dr. Burgess, and those of Dr. Magnarelli.

Magnarelli et al in the paper, "Detection of Borrelia burgdorferi in Urine of Peromyscus leucopus by Inhibition Enzyme-Linked Immunosorbent Assay" determined that 57 out of 87 mice had either subunits or whole cell Borrelia burgdorferi in their urine.

Despite this high number, Magnarelli et al cited their own difficulties in detecting evidence of Lyme disease infection in mice consistently:

"For more than half of the field-collected mice tested, there was concordance in the results of the serum antibody, culture, and urine analyses. Similar results were records for four of five laboratory-bred mice inoculated with B. burgdorferi. However, there were discrepancies. B. burgdorferi antigens sometimes were detected in urine from field-collected mice without supportive data from antibody assays or culture work. This was particularly noticeable in animals captured during October and November, a period after peak nymphal I. scapularis population levels had been reached."

The authors also pointed out that antibody-positive serum and titers can be low especially during early infection, successful culturing of B. burgdorferi depended partially on the number of spirochetes present in host tissues, and that occasionally, serum antibody analyses and culturing results were positive, while urine antigen test results were negative - antigens may not always be released into urine.

In 2001, we have what may have been the last published words from Dr. Burgess on contact transmission in the book, "Infectious Diseases of Wild Mammals" published by Iowa State University Press, chapter 26. Authored by Dr. Richard Brown and Dr. Elizabeth Burgess, the chapter contains this quote:

"Although direct transmission may occur in some situations, it has not been easily substantiated (Mather et al 1991) and has yet to be shown as epidemiologically important." 

The authors supported the idea that direct transmission of spirochetes may occur between animals under certain circumstances - but it's not easy to provide evidence of what exactly happened and it occurs in only a very small number of cases.

More recently, in 2010, in the book, Borrelia: Molecular Biology, Host Interaction and Pathogenesis by Horizon Press, on p. 381, the most recent note on transmission stated:

"Mice are also susceptible to infection following intragastric inoculation of very high doses of B. burgdorferi N40, but there is no evidence for contact transmission (Barthold, 1991) or in utero (placental) transmission, although maternal infection may cause fetal death (Silver et al, 1995; Weis et al, 1997)."

Since our focus here is on contact, venereal, and oral transmission and not maternal/in utero (a topic worthy of a post in itself), it's notable that mice can be infected intragastrically based on Barthold's studies - though it takes high doses to do so, and it is a question how likely it is such doses would be found in nature. According to Burgess, Peromyscus are apparently susceptible to oral inoculation with B. burgdorferi, since oral infection with ~400 spirochetes resulted in sufficient spirochetemia to infect Ixodes (previously dammini) scapularis larvae.

That there has been a variety of study outcomes regarding mice, transmission, and inoculation routes leads to questions about whether or not it is not just species that matters when it comes to how Lyme disease affects the host - but also the individual genetic background of the host animal.

One should take note that anyone studying Borrelia burgdorferi in wild type mice should make sure they do not use mice which are naturally resistant to infection with Lyme disease due to a particular genetic variant of the antigen receptor TLR2, because such mice can greatly affect study outcome.

Could it be that the discrepancies Magnarelli et al found in their research was due in part to the presence of mice in their study group which had this genetic variant?

Future Directions

One question this raises for some reading along is how likely is it that Borrelia burgdorferi spirochetes can be found in human urine, and is there evidence of non-sexual transmission of Lyme disease between people? This is a question that will be discussed in an upcoming blog post, as there have been a number of studies on testing human urine samples for the presence of Lyme disease.

But the main question which kicked off this post is this one: Will we have any evidence in the near future that Borrelia burgdorferi can be sexually transmitted between partners?

So far, we do not, though a recent paper by Middelveen et al, "Isolation and Detection of Borrelia burgdorferi from human vaginal and seminal secretions" is the first publication to make the claim in its abstract that live motile spirochetes have been found in vaginal and seminal secretions, and that because two partners in the study share the same strain of Borrelia burgdorferi in their secretions, odds are greater than random chance that one partner passed Borrelia burgdorferi to the other.

For these claims, I currently have no evidence. And unfortunately, my ability to give the paper a thorough review is limited without access to the full text of the paper. Once the Middelveen et al paper is out of embargo and I have read the entire paper, it deserves its own future blog entry given how important this topic has become for many patients.

To sum up: Sexual transmission of tickborne diseases - is there evidence? Answer: Not so far. But existing studies to date provide evidence that oral inoculation and urine transmission may occur in a few cases in animals.

Questions For Further Discussion:

• Why did different researchers have different results when it comes to the issue of contact transmission?
  
  
• How much did animal species play a role in the outcome?
  
  
• Why is it in a number of cases, uninfected animals exposed to infected animals had positive antibodies for Borrelia burgdorferi but were culture negative and no spirochetes could found in tissues post-mortem?
  
  
• How did duration of untreated infection in the host relate to the odds of finding spirochetal DNA or a spirochete in a given sample?
  
  
• How did the timing of testing of the host animal relate to the odds of finding spirochetal DNA or a spirochete in a given sample?
  
  
• How do methods and materials and test conditions affect outcomes (e.g. urine acids can lyse cells) ?
  
  
• How did the researchers demonstrate they had ruled out or eliminated other potential methods of transmission via experimental design?
  
  
• What - if any - connection is there between nonsexual modes of Lyme disease transmission and a sexual one?

Coming up next:

Part 3: Sexual Transmission Of Lyme Disease - Is There Evidence?

The next post will include notes on some of the above studies mentioned in the table and
additional studies which have been cited when mentioning transmission methods of
Borrelia burgdorferi. The temperature at which Borrelia burgdorferi dies
off will also be discussed in relationship to pasteurization.

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Attribution-NonCommercial-ShareAlike 3.0 Unported License.

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1 Part 1: Sexual Transmission Of Lyme Disease - Is There Evidence?

Male and female Ixodes ricinus ticks mating. 

A number of patients with Lyme disease have wondered if there is any other way to contract Lyme disease other than a tick bite. It's not an uncommon question to ask, given that not everyone remembers getting a tick bite, and nymphs are so small they can bite and infect someone without anyone ever knowing they were there.

Of all the questions which lead one to pause for a moment regarding the possible methods of transmission of Lyme disease, it has to be this one: Can Lyme disease be sexually transmitted between partners?

This is an interesting question, and the overwhelming majority of researchers and medical professionals out there have stated that no, Lyme disease cannot be sexually transmitted between people.

They will state other forms of transmission can occur outside of a tick bite: Borrelia burgdorferi, the bacteria which causes Lyme disease, could be transmitted between ticks while they are mating (sexual transmission of relapsing fever spirochetes also occurs between ticks). It could be transmitted between ticks during co-feeding on the same mammal. It could be passed from a mother to her child's placenta in utero during pregnancy, and in some cases, to the fetus itself. But they will state that thus far, there is no evidence that Lyme disease can be sexually transmitted between mammals including humans.

My Initial Thoughts On The Issue Of Sexual Transmission

I didn't care much about answering the sexual transmission question when I first contracted Lyme disease. Partly because I was so sick, sex was the last thing on my mind, and I wasn't up to having any. Yeah, sad but true. For the most part, I concerned myself with treatment, rest, and getting better.

Time and again, it's clear the question about whether or not Lyme disease can be sexually transmitted is important to others as it has been raised in support groups, on online patient fora, in chat rooms, and at conferences. So it's a question that keeps coming back, and now that a new abstract by Middelveen et al has been making the rounds concerning sexual transmission of Lyme disease, the topic has become the focus of discussion by the media and among patients yet again.

So I started investigating the issue of sexual transmission of Lyme disease, and while I came across a number of stories online where patients are convinced either they were infected by their spouse or had infected their spouse - actual studies regarding this phenomenon have been lacking. In reading of all the documentation on Lyme disease transmission I could get a hold of prior to writing this entry, I found one patient blog which offered a good layperson's summary of the literature regarding Lyme disease and sexual transmission: "Sexual Transmission of Lyme disease" on A Lyme Disease Journal by J. Mankoff.

Ms. Mankoff writes about the difficulty in finding scientific papers on Lyme disease sexual transmission studies using both animal and human models - and unfortunately, my own experience mirrored hers.

In doing the research for this post, I initially learned the following things about publications to date:

• Setting aside Middelveen et al's recent abstract for now, there has not been one published study which provides any evidence that live spirochetes can be passed on from one human to another through sexual intercourse or sexual contact.
• There is scant evidence that spirochetal DNA can be found in human seminal and vaginal secretions.
• There is limited evidence that spirochetal DNA can be found in human breast milk.
• There are animal studies which demonstrate uninfected animals placed in the same cages with infected animals can develop antibody responses to Borrelia burgdorferi.
• There are animal studies which demonstrate that animals infected with spirochetes do not pass them on to uninfected animals in the same cage.
• There are animal studies which indicate that the bladder and kidneys can be very good locations from which to culture spirochetes.
• There are animal studies which indicate spirochetal DNA can be high in urine samples.
• There are animal studies which indicate spirochetal DNA can be absent in urine samples.

When you look at this list, you'll notice that I went from discussing sexual transmission of Lyme disease to looking for spirochetes in sexual fluids and breast milk to looking for spirochetes in urine - probably not the direction anyone imagined I'd go. But that's because to date, more studies have been completed which indicate spirochetes are present in urine than studies which indicate spirochetes appear in sexual fluids - so I'm going to end up talking about those studies, too.

Evidence of Borrelia burgdorferi - Lyme disease DNA - in human semen and vaginal secretions

So far, while there is research which indicates Borrelia burgdorferi DNA has been found in samples of vaginal and seminal secretions, there is no research to date which has conclusively shown that live motile Borrelia burgdorferi spirochetes have been passed from one partner to another.

The distinction between having evidence of Borrelia burgdorferi DNA and having live motile Borrelia burgdorferi spirochetes is an important one: Having Borrelia burgdorferi DNA is like holding a strand of my hair in your hand - whereas having a live, motile Borrelia burgdorferi spirochete is like having me sitting in your living room drinking a beer. Hair DNA is a part of me, but it isn't all of me.

This distinction is important to remember when reviewing one of the most frequently cited papers online on the presence of Borrelia burgdorferi DNA in human vaginal and seminal secretions, "Recovery of Lyme Spirochetes by PCR in Semen Samples of Previously Diagnosed Lyme Disease Patients" presented by Dr. Gregory Bach at the 14th International Scientific Conference on Lyme Disease in April, 2001.

Unfortunately, when I reviewed all the major online repositories (Google Scholar, PubMed, Oxford Journals, etc.), this paper and its abstract was not listed anywhere and a general search outside of repositories did not point to any peer-reviewed sources. I eventually tracked down a copy of the abstract on Jenna's Lyme Blog, and am reproducing it here (with minor typo corrections) to make a few comments on it:

Recovery of Lyme Spirochetes By PCR In Semen Samples of Previously Diagnosed Lyme Disease Patients (2001)

Lyme disease, being a spirochete with pathology similar to syphilis, is often found difficult to treat due to the spirochete invading sanctuary sites and displaying pleomorphic characteristics such as a cyst (L-form). Because a significant portion of sexually active couples present to my office with Lyme disease, with only one partner having a history of tick exposure, the question of possible secondary (sexual) vector of transmission for the spirochete warrants inquiry.

Additionally, sexually active couples seem to have a marked propensity for antibiotic failure raising the question of sexually active couples re-infecting themselves through intimate contact.

METHODS:

Lyme spirochetes/DNA have been recovered from stored animal semen. Recovery of spirochete DNA from nursing mother’s breast milk and umbilical cord blood by PCR (confirmed by culture/microscopy), have been found in samples provided to my office.

RESULTS:

Surprisingly, initial laboratory testing of semen samples provided by male Lyme patients (positive by western blot/PCR in blood) and the male sexual partner of a Lyme infected female patient were positive approximately 40% of the time.

PCR recovery of Lyme DNA nucleotide sequences with microscopic confirmation of semen samples yielded positive results in 14/32 Lyme patients (13 male semen samples and 1 vaginal pap).

ALL positive semen/vaginal samples in patients with known sexual partners resulted in positive Lyme titers/PCR in their sexual partners. 3/4 positive semen patients had no or unknown sexual partners to be tested. These preliminary findings warrant further study. Currently a statistical design study to evaluate the possibility of sexual transmission of the spirochete is being undertaken.

Our laboratory studies confirm the existence of Lyme spirochetes in semen/vaginal secretions. Whether or not further clinical studies with a larger statistical group will support the hypothesis of sexual transmission remains to be seen. A retrospective clinical study is also underway.

We are reviewing the medical records, collecting semen samples of patients who were previously diagnosed with current and previously treated Lyme disease are being asked to provide semen, pap, and blood samples for extensive laboratory testing.

CONCLUSION:

With the initially impressive data, we feel the subsequent statistical study on the sexual transmission of the Lyme spirochete will illuminate a much broader spectrum of public health concerns associated with the disease than the originally accepted tick borne vector.

At first glance, someone reading this study may get excited: Hey, they found evidence of Lyme disease bacteria in semen and vaginal fluid. But on further reading, it becomes clear that the paper focuses on PCR recovery of Lyme DNA nucleotide sequences and the results of western blots - not whole spirochetes.

There are unanswered questions about this study based on the abstract: We don't know what kind of microscopic confirmation was conducted and why it was mostly conducted on semen. We don't know if patients had other possible routes of exposure to spirochetes. We don't know if the DNA sequences recovered matched between sexual partners. We don't know whether any of the patients who were sampled had recently taken antibiotics and if the spirochetal DNA that was detected was the result of their bodies trying to purge a massive die-off of spirochetes. What kind of treatment patients in the study had received so far is an unknown.

I would agree with one message in the conclusion - that additional studies on spirochetal DNA or spirochetes in sexual fluids could be informative and help confirm or deny these findings.

But finding Lyme disease Borrelia burgdorferi DNA alone in secretions is not evidence that spirochetes can be transmitted - it can be much like finding dead viral particles leaving the body of someone who recently had the flu.

And in the case of figuring out who gave a flu to who, if Jane gets the flu - she may or may not have passed on the flu to John in her office. John could have picked it up from someone else or from fomites on a doorknob. Without more data, there's no compelling evidence to suggest that his active infection traces back to Jane in particular.

The difference with a study on the sexual transmission of Lyme disease compared to transmission of the flu is that one has to demonstrate not only that the person contracted Lyme disease from a specific partner through sexual contact but one also has to provide evidence that the person did not somehow contract Lyme disease from a tick bite or by a different nonsexual mode of transmission.

To my knowledge, further clinical studies with a larger statistical group have not been conducted by Dr. Bach to support his hypothesis about Lyme disease and sexual transmission, and his 2001 study abstract leaves the reader with unanswered questions.

Here is another paper which examines Borrelia burgdorferi in human samples - but not semen or vaginal secretions:

Detection of Borrelia burgdorferi DNA by polymerase chain reaction in the urine and breast milk of patients with Lyme Borreliosis (1995)

Abstract

Current laboratory diagnosis of Lyme borreliosis relies on tests for the detection of antibodies to Borrelia burgdorferi with known limitations. By using a simple extraction procedure for urine samples, B. burgdorferi DNA was amplified by a nested PCR with primers that target the specific part of the flagellin gene. To control possible inhibition of the enzyme (polymerase), a special assay using the same primers was developed. We examined 403 urine samples from 185 patients with skin manifestations of Lyme borreliosis. Before treatment, B. burgdorferi DNA was detected in 88 of 97 patients with Lyme borreliosis. After treatment, all but seven patients became nonreactive. Six of these seven persons suffered from intermittent migratory arthralgias or myalgias, and one from acrodermatitis chronica atrophicans. Two of 49 control patients with various dermatologic disorders and none out of 22 presumably healthy persons were reactive in the PCR. In addition to urine, breast milk from two lactating women with erythema migrans was tested and also found reactive. Borrelia burgdorferi DNA can be detected with high sensitivity (91%) by a nested PCR in urine of patients with Lyme borreliosis. In addition, this test can be a reliable marker for the efficacy of treatment.

This study indicates that spirochetal DNA could be easily detected in urine using nested PCR, though today this is not a testing method for Lyme disease which is regularly used (and indeed there have been mixed reviews on how effective the use of urine is in testing for Lyme disease). While human breast milk was found to be reactive in PCR, it's important to note that no motile, whole spirochetes were recorded as being found.

While interesting, this paper does not provide evidence that Lyme disease is sexually transmitted. It only has the potential to raise - but not answer - questions about the viability of spirochetes in urine and breast milk. Additional studies would have to be completed to determine that live, whole spirochetes are present in urine and breast milk, and that transmission of spirochetes can occur via human breast milk and urine.

Others have cited a 1995 paper online as evidence pointing to Borrelia burgdorferi surviving in semen: "Viability of Borrelia burgdorferi in stored semen". That line of thinking is erroneous,  however, and to clear up the matter here:

This paper is not about Borrelia burgdorferi being found surviving in semen - it's about seeing if Borrelia burgdorferi which is manually added to semen from different animals (bull, ram, and dog) is a useful storage method. Storing Borrelia burgdorferi in semen samples is then compared to storing them in Barbour-Stoenner-Kelly (BSK) medium. Nothing in this study is relevant to providing evidence about Borrelia burgdorferi from an actual infection showing up in the host animal's semen. (And yes, I agree this is a weird experiment, and wonder what the authors were thinking when designing it - perhaps that semen's components may be nutritious for spirochetes and easier to use than BSK.)

These studies are the top three studies often cited by some to support the position that Lyme disease can be sexually transmitted between humans - however, the first two only provide some evidence that Borrelia burgdorferi DNA can be found in semen, vaginal fluid, and breast milk - while the third is only about using animal semen to store spirochetes for research purposes.

The EC Burgess Studies

One oft-cited researcher who investigated various routes of transmission of Borrelia burgdorferi in animal models was Dr. Elizabeth Burgess. Notes taken from a lecture by Tom Grier, microbiologist, at Lac Court Oreilles Convention Center said in reference to Dr. Burgess:

"Dr Elizabeth Burgess, DMV at Madison: her work has been overlooked for decades.

Her preliminary work showed that the Borrelia species of spirochete possessed some mechanism and ability to penetrate mucous membranes suggesting transmission in cattle could be through urine–to- mouth contact putting cattle at a risk, besides just ticks.

Dr Burgess’ work was harshly and unjustly criticized without investigation or inspection. A decade later we see that Borrelia is a champion at penetrating mammalian blood vessels and endothelial cells that line the blood vessels. How hard is it to imagine mucosa capillaries in cattle are exposed targets for Borrelia to penetrate on contact? Since the introduction of the veterinary Lyme vaccines, we hear little about entire herds of cattle and horses being infected."

And it's true - Dr. Burgess' work was criticized.  Some of this criticism was mentioned in an article on Lyme disease from 1989 which was published in the New York Times:

Dr. Elizabeth Burgess of the University of Wisconsin's School of Veterinary Medicine has suggested the possibility of direct spread through contaminated urine.

But other experts expressed deep skepticism about her proposal, saying further studies are needed. They also say the disease probably would not follow a seasonal pattern if the spirochete were transmitted in this way. 

''If this were true, then virtually every veterinarian and every farmer would have Lyme disease,'' said Dr. Willy Burgdorfer, scientist emeritus at the Public Health Service laboratory in Montana. Dr. Burgdorfer led the team that in 1981 isolated the spirochete, which was named for him.

That same article later goes on to discuss the possibility of ticks spreading Lyme disease via migratory birds, with Dr. Burgdorfer then saying that ''just because they can be carried on birds does not mean that ticks will spread to every corner of the country.''

Since this article's publication in 1989, numerous scientific studies have provided evidence that migratory birds spread infected ticks to various corners of the country as well as to neighboring Canada. Dr. Burgdorfer has presumably revised his view on the role of migratory birds in spreading Lyme disease given these studies.

But as of this writing, it is unknown if his criticism of Dr. Burgess remains the same. And to some degree, Dr. Burgdorfer's statement on record at the New York Times is interesting from a historical perspective because in 1989, he had co-authored a paper with Dr. Tom Schwan about the utility of culturing Lyme disease from mouse bladders and how spirochetes were not found in the urine of the mice they studied - but by 1998, he co-authored a paper about tickborne relapsing fever, citing a Linnemann et al paper from 1978 mentioning that Borrelia spirochetes could be found in the urine of human patients with acute relapsing fever.

One interesting note about Dr. Burgdorfer's paper co-authored with Dr. Schwan: He cited an earlier 1986 study by Bosler and Schultze, "The prevalence and significance of Borrelia burgdorferi in the urine of feral reservoir hosts" (mentioned in table in part two of this blog post) where 50% of the mice studied from Shelter Island had evidence of Borrelia burgdorferi in urine, but it was thought the reason that they were that highly spirochetemic was because 95% of the mice were also infected with Babesia.

With this knowledge, I wonder if at some point years after his interview with the NYT, if Dr. Burgdorfer sat down with Dr. Burgess and discussed her work over a cup of coffee while they were both working on the Journal of Spirochetal and Tick-borne Diseases for the now retired Lyme Disease Foundation, and what conclusions they shared regarding the presence of spirochetes in urine samples. Did they discuss the role of Babesia in the presence of greater spirochetemia and spirocheturia in mice?

But I digress...

What did Burgess study? Burgess was known for her work on two infections - primarily duck plague virus, caused by anatid herpesvirus 1 - and Borrelia burgdorferi infections in a wide range of animals from cats and dogs to livestock; from black bears to coyotes. She was first author on 20 papers and co-author on 16 additional papers that I could find. This was her career, her lifeblood, and a record of her work can be viewed on Google Scholar.

Her most notable works related to Borrelia burgdorferi transmission in animals are:

• 1986 Experimental inoculation of dogs with Borrelia burgdorferi 
• 1986 Experimental inoculation of Peromyscus spp. with Borrelia burgdorferi: evidence of contact transmission 
• 1987 Oral infection of Peromyscus maniculatus with Borrelia burgdorferi and subsequent transmission by Ixodes dammini
• 1988 Borrelia burgdorferi infection in Wisconsin horses and cows
• 1989 Experimental inoculation of mallard ducks (Anas platyrhynchos) with Borrelia burgdorferi
• 1992 Experimentally induced infection of cats with Borrelia burgdorferi

I tried to track down Dr. Burgess to ask her about her work, but this task was not successful; she appears to have retired and does not have an active online presence. However, I was able to acquire copies of the full text of her papers for my own review.

Dr. Burgess' studies suggest that contact transmission from infected animals to uninfected animals can and does occur, though not consistently - and that even if there is no evidence of spirochetes being transferred from infected animals to uninfected animals, that uninfected animals housed with infected animals develop a positive antibody response to Borrelia burgdorferi. Her research also indicates that spirochetes can be found in animal urine and it is suggested that oral contact with that urine could lead to infection.

Her findings - now as they were then - have been considered by some to be controversial. Other researchers have conducted similar experiments and their results conflicted with those of Burgess. Or  they had negative results after running similar experiments using different animal models - which indicates that perhaps the ability for an animal to either transmit Borrelia burgdorferi via oral/urine contact or contract it that way is entirely species dependent.

Coming up next:

We'll take a closer look at suspected cases of contact transmission between animals infected with Borrelia burgdorferi and uninfected animals, and how these cases may have led to the question of whether or not sexual transmission of Lyme disease between animals occurred in Part 2 of "Sexual Transmission Of Lyme Disease - Is There Evidence?"

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4 Commentary: Slate's Article On Romney & Lyme Disease

It seems like over the past two weeks, every time I turned around, there's a new article about Mitt Romney and chronic Lyme disease. How much mileage from one topic can the media get? You would think by now they would have moved on, but today The Day decided it was going to post yet another rehashing about this subject.

Well, if they get to rehash, then so do I. I have some things to say in response to the Slate's article, "Why Is Romney Campaigning on Medical Quackery?", even though it's not the most recent in this set of offerings.

And again, I'd like to make one request of the media at large:

Can you please investigate more deeply the issue of people with persisting symptoms after delayed or initial antibiotic treatment for Lyme disease?

And not just spout out the same tired phrase that clinical trials to date have not shown that the use of long term antibiotics has been effective for the treatment of chronic Lyme disease (or what the CDC and other organizations call "Post Lyme Disease Syndrome")?

But I digress...

On to eviscerating the Slate...

"Let’s play doctor. A patient comes to you with joint pain, difficulty concentrating, anxiety, poor attention, and mood swings. You might run a series of tests to rule out a persistent infection or other disorder. If your patient lives in a tick- and Lyme-disease-infested area, you would be wise to test for the bacterium Borrelia burgdorferi and, if detected, prescribe a course of antibiotics. But suppose the tests come back negative and there is little evidence that your patient was bitten by a tick or was infected with the Lyme disease bacterium. If you are a good doctor, and you are, you might explore a diagnosis of depression, a disease that afflicts almost 10 percent of the population at any given time."

Okay, I'm going to respond to this with, "let's NOT play doctor", because it's not within our training and expertise to give medical advice if we are blogging or writing for online magazines and we are not doctors - or even if we are doctors, and have not actually seen the patient in question before making a diagnosis.

But as we are talking about some hypothetical case here - patient X - and not a real person, then I'm going to use patient X to discuss hypotheticals.

First, joint pain, difficulty concentrating, anxiety, poor attention, and mood swings can be indicative of any of a number of disorders. The doctor is correct to consider different diagnoses, and rule out or rule in anything which may be causing these symptoms. They can be related to some rheumatoid or autoimmune disorder, exposure to certain toxic substances, stress, immunological problems, and other conditions. Patient X may even have more than one condition which is producing these symptoms and need proper diagnosis and treatment.

I would not automatically leap to the conclusion that depression is the disease that is happening - and even so, depression can be a symptom of another underlying condition such as hypothyroidism, hormonal imbalance, or serious vitamin deficiency.

Let's reexamine this portion, and part of the succeeding paragraph:

"But suppose the tests come back negative and there is little evidence that your patient was bitten by a tick or was infected with the Lyme disease bacterium. [...] If you are a doctor who believes that the CDC and NIH have misrepresented carefully vetted clinical trial data about the diagnosis and treatment of Lyme disease, however, you might diagnose your patient with chronic Lyme disease and prescribe an intensive, long-term, side-effect-laden, mega-dose of antibiotics."

First of all, is clinical trial data about the diagnosis and treatment of Lyme disease the only data on which a medical practitioner should base their diagnosis and treatment of tickborne diseases in a particular individual patient?

The problem is this soundbite doesn't even begin to offer an overview of why a medical practitioner would think that maybe - just maybe - someone with a negative test for Lyme disease might still have Lyme disease. Or how it is that diagnosing Lyme disease can be a difficult task at times for any doctor.

The words chosen that follow - "prescribe an intensive, long-term, side-effect-laden, mega-dose of antibiotics" - reflect the judgment of the writer on how people with Lyme disease are treated without the writer actually investigating which antibiotics are used at which dosage for how long, nor how long-term antibiotic treatment for Lyme disease compares with long-term antibiotic treatment for other conditions, nor even what happens to those who have Lyme disease who do not receive long-term antibiotic treatment.

The costs and benefits of antibiotic treatment in general are not weighed and shared, so all it can be is a negative description of this treatment without investigating the long term outcomes of case-by-case studies of those patients who are either receiving it or where such treatment has been withheld.

On to another part of the article...

"As a Slate story pointed out years ago, chronic Lyme disease—not the persistent effects of a long-term bacterial infection but a collection of mysterious symptoms—has powerful supporters. Advocates for the diagnosis tend to blame the medical establishment for not taking them seriously enough."

Here I have a problem with this description of the condition, because it's not reflecting reality.

No one seems to really understand entirely what chronic Lyme disease is and what causes it. No one.

The CDC and IDSA have said that Lyme disease cannot become a chronic and persisting infection after a certain minimum allotment of antibiotic treatment, and offer up the hypothesis that any symptoms beyond this treatment are a (potentially autoimmune) condition known as Post Lyme Disease Syndrome (PLDS). However, this is a hypothesis, and thus far there are no treatment trials which put this hypothesis to the test.

If this hypothesis is so strongly supported, then why are federally funded treatment trials currently being conducted which are about providing evidence for Lyme disease as a persisting infection? Why is there a study currently recruiting which is entitled, "Searching For Persistence In Infection In Lyme Disease"? And why has another study been conducted in Europe, known as the "Persistent Lyme Empiric Antibiotic Study Europe (PLEASE)"?

This doesn't sound like the issue of what causes chronic Lyme disease's persisting symptoms is settled. If so, treatment trials which address this devastating autoimmune condition would outweigh clinical trials on Lyme disease. If one searches for clinical trials for treating Post Lyme Disease Syndrome, the total sum is zero.

To add to this, why is it that the researchers who completed the most recent research on persisting Lyme disease infection in non-human primates concluded this at the end of their recent publication, "Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection"?:

"Our studies do however offer proof of the principle that intact spirochetes can persist in an incidental host comparable to humans, following antibiotic therapy. Additionally, our experiments uncover residual antigen associated with inflammatory foci. Whether persistent spirochetes or spirochetal antigen can cause PTLDS remains unanswered."

That chronic Lyme disease is a mystery is true. That one can readily come to the conclusion that it is not a persistent infection under any circumstances, in any situation, has yet to be established - just as these symptoms being caused an autoimmune condition has yet to be established.

But the content of Slate's article and that of others is very negative about the hypothesis of persisting infection without any specific evidence to strongly back an alternative explanation - or refute the evidence provided in a study such as Embers et al, above.

To continue...

"In 2008, the attorney general of Connecticut investigated the Infectious Diseases Society of America, a 50-year-old organization with more than 9,000 physician and scientist members, for misrepresenting the science of Lyme disease. Not to be outdone, Virginia Gov. Bob McDonnell assembled a governor’s task force on Lyme disease. He appointed Michael Farris as its chair. Farris is a lawyer and the chancellor of Patrick Henry College, aka God’s Harvard, whose motto is “For Christ and for Liberty” and whose “Statement of Faith” holds that the “Bible in its entirety” is “inerrant.” The school isn’t known for its biology department"

You know, we can argue this one until the cows come home. I honestly am not too keen that politicians are getting involved with medical debates - even though I as a patient want more recognition for my condition and more research for it.

What I want is more recognition from the medical profession, and for there to be programs put in place to help those of us with chronic Lyme disease. And what I really want is for someone with an understanding of the disease who has researched it extensively - and has suffered with it long term themselves - to come forward and represent me and other patients; to work from a desire to find the truth about what is causing our symptoms.

I do not need to see another advisory board, appointed chair, or politician try to defend my condition without a more intimate and thorough understanding of it. And I definitely do not need to see my condition being used in a political free-for-all from any side, from any party or special interest group, in order to try to gain more votes.

I find Slate's use of pulling out an appointed chair who is not big on science and who oversees a college with a statement of faith which holds the Bible as being infallible as being a diversion from the issue at hand: the issue of whether or not Borrelia burgdorferi can be a persistent infection.

All we see is an obvious character to take issue with if one is on the side of science and skepticism and wants an easy target to use to rail against the chronic Lyme disease issue... Of course those who are scientifically minded and skeptics are not going to take the word of an evangelical young earth creationist as being one educated about Lyme disease.

On the other hand, if we take one governor and one evangelical chair out of the picture, who do we have left that could have been interviewed instead? How about some scientists, for example? What about Dr. John Aucott of John Hopkins University, Dr. Stephen Barthold of UC Davis, Dr. Monica Embers of Tulane University, Dr. Straubinger, Dr. Brian Fallon of Columbia University, and others who have been studying Borrelia burgdorferi? They have nothing to lose by being asked for their opinion, being neither in politics, nor making money directly off treating patients, or nor working directly for the IDSA. Why doesn't Slate ask them about their scientific opinion on the cause of chronic Lyme disease?

But Slate doesn't do this. Slate goes for low-hanging fruit to support its diatribe against chronic Lyme disease - with the primary goal of denigrating Romney's attempts to appeal to voter subgroups and to support their characterization of Romney as being anti-science.

The mistake Slate makes is in conflating Romney's anti-science leanings with chronic Lyme disease as a condition which does not have enough evidence to support it. The two topics are issues which deserve independent examination.

Onward and upward...

"But the task force seems to have bought into the conspiracy theory that the infectious disease establishment is maliciously interfering with proper treatment. It states: “There is no scientific basis for concluding that 30 days or less of antibiotics is sufficient treatment for every case of Lyme disease.” Again, tell it to the Centers for Disease Control and Prevention."

I am not one of those people who will sit here and spout conspiracy theories. Refer to my page, What To Expect Here, if you have any questions. But there is the issue of oversimplifying and dumbing down the issues involved with properly treating Lyme disease - which is exactly what this article is doing.

It is not true that every case of Lyme disease is sufficiently treated with 30 days or less of antibiotics. Most acute cases are sufficiently treated with 30 days or less, but even when looking at the IDSA's guidelines themselves, they state that up to 10% of all acute Lyme disease patients experience treatment failures. These patients must be retreated and investigated for presence of tickborne coinfections. Also, a certain percentage of patients will have Lyme arthritis, which even Allen Steere treats with two months of oral antibiotics - and if symptoms are still present, a third month of IV antibiotics as well.

I can offer a number of cases where IDSA infectious disease doctors themselves have given individual patients with Lyme disease more than 30 days of antibiotics without thinking too hard, but cannot do so in detail because it would violate HIPAA practices. But these patients are out there, and have been helped by more than 30 days of antibiotics by patients treated by the IDSA's own specialists.

To add to this, there are those outliers with late stage Lyme disease and chronic Lyme disease who do not respond as well to treatment as early acute cases do. These patients have not been studied anywhere nearly enough, in part because fewer cases in these categories are diagnosed - but also because these patients' conditions are not as well understood or always as easily diagnosed to begin with because the obvious, early acute symptoms like a bull's eye rash are missing.

The Slate article continues...

"Another treatment point is telling: “We received substantial testimony from lay witnesses that they had been successfully treated with long-term antibiotics.” Pro tip: the plural of anecdote is not data. Just because someone signed up to address a public portion of the task force meeting does not mean their understanding or explanation of their own medical care is accurate or relevant."

I've said before that I know that the plural of anecdote is not data. And I understand that someone's own experience of their own medical care is not admissible as treatment for everyone.

But then, I've never made the claim that it was, anywhere... I've only made the statement that I think it is possible some people might need longer courses of antibiotics than the guidelines suggest are needed. How long, I think depends on the patient and their condition (genetics, underlying conditions, coinfections, etc).

But that is not for me to judge. I'm not a doctor, and we're talking about individual cases here... If IDSA doctors have the clinical leeway to make decisions to treat individual patients with more than 30 days worth of antibiotics and have it be covered by insurance, well, so then do other doctors - including my own primary care physician and someone who calls themselves an LLMD. The keyword in the document they published, after all, is guidelines.

If that's not happening and insurers are not covering additional treatment for patients when doctors authorize it, then that's an issue that Slate and other publications should be investigating.

To continue...

"I don’t mean to make fun of people who are suffering from what they think is chronic Lyme disease. Their symptoms are real, and they deserve help. But giving them a phantom diagnosis and making them part of a crusade to bring truth to medicine just perpetuates the idea that the symptoms they describe must be part of a complex, classic disease."

Look, this is all fine and good to hold this opinion. However, consider that I don't see enough evidence supporting an alternative diagnosis. The CDC, as you've cited, mentions Post Lyme Disease Syndrome. And yet, this is just a hypothesis and it has yet to graduate to being theory.

Just because the outcome of three clinical trials for long term antibiotic treatment on some patients with chronic Lyme disease showed that continued treatment did not permanently alleviate symptoms once treatment stopped does not mean that there isn't a persistent infection present.

And if Post Lyme Disease Syndrome is a genuine condition, with what may very well be its own genuine biomarkers for it - then as its own separate disease complex, it requires its own research arm and treatment for it.

Now Slate, are you saying PLDS doesn't exist, either, and you're going to flake on this illness which has scientific evidence to back its existence and call it depression?

Of course - because the next thing out of Slate's mouth is this:

"It’s much more likely to be depression, and depression is treatable."

Here we go with the depression, again.

Funny you should say this. Because I have had episodic depression. And I will tell you: Episodic depression was a fucking walk in the park compared to Lyme disease.

There simply is no comparison between the two, other than, well, having Lyme disease has made me feel depressed because it totally changed my life and not for the better.

Why would someone who could work full time at a high paying salary who had lots of friends and opportunity to travel the world a lot give that up to stay at home on the sofa with constant headaches and fatigue and hardly see anyone or go anywhere? To be seriously broke and give up on one's dream of owning a home?

The Lyme disease made me depressed. I don't have depression here as a separate clinical entity all on its own.

And depression, in my experience, never gave me a tick bite, an EM rash, high fevers, swollen lymph nodes, visible joint swelling, paresthesias, and a stocking and glove pattern of neuropathy on my feet.

I challenge you to ask any therapist if they think these symptoms are signs of depression. They'll tell you what they told me: "Your illness is not in your head; you have a genuine physical illness. See a doctor, but see me to deal with the depression that being ill can bring on if you need it."

And seriously... While taking antidepressants can help people with depression, if there is an organic cause for one's depression, such as infection, that needs to be treated first. One only needs to look at cases of psychiatric presentations of Lyme disease - however controversial they are - to at least ask if it isn't a possibility based on the patient's clinical history and limited response to common antidepressants.

Ask those chronic Lyme disease patients who have already taken antidepressants and have seen therapists just how well they have done. Ask. Quite a number of us have already tried exactly what some doctors suggested we do, when they thought we had depression and that is why we felt as crappy as we have. Either they're wrong, or partly wrong, or the drugs they prescribe us just aren't doing the trick.

Depression. Ha. If it is depression, well, then where are the clinical trials where antidepressants and long term antibiotics are used to treat chronic Lyme disease, so we can see the outcome? How about a third treatment arm with therapy alone? At least you'll give us patients a space of our own to swear at and curse modern medicine for not doing more for us.

There's more...

"As the CDC gently points out, mentioning other diagnoses that have been favorite catch-alls, “Your doctor may want to treat you in ways similar to patients who have fibromyalgia or chronic fatigue syndrome. This does not mean that your doctor is dismissing your pain or saying that you have these conditions. It simply means that the doctor is trying to help you cope with your symptoms using the best tools available."

And no one knows what exactly causes fibromyalgia or chronic fatigue syndrome. Obviously XMRV has been taken off the table as a cause for chronic fatigue syndrome - but some other virus or another agent may be the cause of this condition.

In any case, neither of these conditions have clear etiology, so you could be trading one mystery for another. None of which are well understood. And all of which are treated symptomatically, and all of which the drugs prescribed (with the exception drugs such as Lyrica, which is the first drug specifcally prescribed to treat fibromyalgia - which also has the unfortunate side effect of potentially causing suicidal behavior) are being offered based on an educated guess that they might work and, well, patient anecdote. They're prescribed off-label for these mysterious conditions of unknown etiology.

So how is treating chronic Lyme disease with antibiotics any different in this respect, until more research comes in on how to better treat it? Until we better understand the cause?

It may be that while long term antibiotic use for everyone with persisting symptoms may not hold up in small scale clinical trials that it may hold up in individual situations for particular patients with specific backgrounds - backgrounds which may not have been widely represented in the trials which have been held to date. Often it takes years for a wider population using a given drug or treatment regimen to expose its side effects and benefits - the outcomes are not always obvious at first.

And the last bit from the Slate:

"Disregarding my own advice about not taking an anecdote as data, I have my own story about chronic Lyme disease. A friend of one of my brothers had been suffering for years from headaches, fatigue, a sense of despair, a belief that she wasn’t worthy of her job or her boyfriend. She was diagnosed with chronic Lyme disease and was treated with antibiotics, which were ineffective. What she wasn’t treated for, and could have been, was severe depression. She killed herself."

I am very sorry for your loss, no matter what the cause. This is the tragic loss of one woman's life, and it may have been prevented.

I don't know, though, and I don't know the full story either way. I only have your anecdote.

She could have had undiagnosed Lyme disease. She could have had depression. She could have had something else entirely. She could have had more than one problem which included depression.

If depression is a concern, I recommend anyone with any illness see a therapist because in many cases therapy is equally as effective as antidepressants. And if that doesn't help, cautiously try out an antidepressant that is neuroprotective if no other biological or organic cause can be found for the depression. But certainly, if one continues to have the same symptoms while on antidepressants and begins an empiric course of antibiotics later and finds those symptoms begin to lift, well, then go with what works and maybe science does not immediately have all the answers. Sometimes symptoms which appear psychiatric in nature can have an infection as their cause.

So, anyway...

Whether or not persistent bacteria is the cause of all or some patients' symptoms, in my opinion, is still up for grabs. And at this point, many patients have either made the decision to ignore the results of the three small clinical trials which have been completed, or beg for more research on treatment to help us, or both.

I am a pro-science, pro-research person with a history of skepticism. I am skeptical about my own damn disease. And yet, no one has given me any particular advice in mainstream medicine or science as to what to do about it.

You might want to send your money directly to UC Davis or Tulane University for private research instead. But don't come kvetching to me that I'm running off to an LLMD because my primary care provider referred me to one.*

That's just more complaining - rather than addressing the root of the problem in the first place. Those of us in pain can only wait so long and do nothing for so long...

* True story.

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