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.]



4 comments:

  1. I submit the following for your consideration:

    http://www.aldf.com/Letter_to_the_editor_of_AFMR_for_ALDF_website_3.10.14.pdf

    ReplyDelete
  2. Hi Anonymous, and welcome to Camp Other blog:

    You wrote:

    "I submit the following for your consideration:

    http://www.aldf.com/Letter_to_the_editor_of_AFMR_for_ALDF_website_3.10.14.pdf"


    Read it, and considered it. Much of the content found at that link doesn't conflict with that which I have written in this three part series. I already mentioned that three studies on Lewis rats, Syrian hamsters, and mice on contact transmission and in particular sexual (venereal) transmission were negative. These to my knowledge are the only controlled studies on sexual transmission in an animal model. If I am incorrect, and you know of more, please share citations in comments.

    None of those three studies negates the fact that there have been studies where uninfected control animals kept near animals infected with Borrelia burgdorferi ended up with positive antibody tests and in some cases, signs of infection. It has been speculated in such cases that sexual transmission might have occurred - although this is only speculation because animal behavior was not studied closely in these cases so far as is known based on the content of the papers mentioned in Table 1 in "Part 2: Sexual Transmission Of Lyme Disease - Is There Evidence?".

    Even if sexual transmission does not occur, these studies - as well as Burgess' and others - point to cases where small numbers of animals may have been infected via exposure to urine or raw milk. One can debate over whether these studies were conducted under stringent conditions which removed other possibilities of tickborne infection, based on experimental design, but many of the papers as written do not describe efforts to eliminate all possible access to tick exposure even if they had been put in place.

    They may have, they may not have - and this is an additional reason why people question the outcomes of these studies. The question is: Why would one decide not to take them at face value? It's a reasonable question, and if there is something within a given paper itself which indicates that experimental design was flawed and that is why a contact animal became infected with Lyme disease - then that is important to know. But in a number of cases there isn't information which would imply to the reader that experimental design was flawed.

    The fairest thing to do under the circumstance would be to find the researchers in question and ask them how their animal housing was arranged and where any specimen ticks might have been kept and their own efforts at tick checks on their person before entering the animals' enclosure. Then reproduce those circumstances if they seemed relatively free of the risk of accidental exposure to ticks via some environmental exposure or via a lab tech. Then repeat the original experiment, faithfully, and see what the results are.

    If this is done with a number of these studies and the results are the same or similar - we still have contact animals which have positive antibody tests for Lyme disease and signs of infection - then it's clear that transmission is occurring in some way which is not via a tick bite. There are only a few ways this can potentially happen.

    Dr. Richard Feynman said it's important to duplicate experiments to confirm their validity. I see no reason why that couldn't be done here.


    CO

    ReplyDelete
  3. Anonymous,

    One more thing, or two:

    I can't fairly comment on the Middelveen et al paper until I have read the full text. But as I've said above, based on the abstract it does not appear to be a transmission study anyway, so as far as I know, it does not specifically provide evidence that sexual transmission has occurred. It could provide evidence whole live motile spirochetes can be found in sexual secretions - and that's something I would like to know more about.

    Either way, an experiment has yet to be conducted which demonstrates sexual transmission occurs between human partners - and that is very hard to do, because it is difficult to eliminate all possible exposure to ticks for most people. They would have to live in the equivalent of Biodome and be in a highly controlled environment for a long period of time where nothing from the outside could get in, and everything inside the Biodome had been thoroughly checked before being added.

    CO

    ReplyDelete
  4. Comment for anyone reading:

    Does anyone know if more experiments were completed which demonstrated that mouse urine (and the urine of other animals) had more spirochetes in them if the mouse was coinfected with Babesia?

    Refer back to http://campother.blogspot.com/2014/03/part-1-sexual-transmission-of-lyme.html and reread what is said there about early studies on mice with both Borrelia burgdorferi infection and Babesia infection, and how spirochetes were found in urine under those circumstances.

    ReplyDelete

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