Wednesday, April 30, 2014

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?

"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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Sunday, April 27, 2014

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 burgdorferievidence 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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