Monday, March 10, 2014

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

Female and male Ixodes ricinus ticks mating
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?"



1 comment:

  1. Thank you so much for exploring this topic thoroughly and with a research-oriented perspective. I honestly wish I could read it more thoroughly and respond to you better but I'm currently having one of those weeks where bite-sized chunks are easier to digest than large amounts of text and where I'm making hilarious (and sometimes scary) spelling substitutions. I've bookmarked all three of your posts and will be coming back to these when my brain feels up to the task, but just wanted to pass along my appreciation in the mean time. I think I want to join Camp Other myself when/if I get my former synthesizing skills back! Hope things are going well for you in 2015.

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