Chronic persistent Lyme Disease (LD) or chronic Borreliosis

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
Lorima
Posts: 914
Joined: Mon 29 Oct 2007 20:47

Re: Chronic persistent Lyme Disease (LD) or chronic Borrelio

Post by Lorima » Thu 20 Sep 2012 7:32

Chuck,

Sorry, my sentence was awkward. I just meant that the two Osps were regulated in the tick, before transfer to the host.

I said I was going to ignore early transmission, but of course once I started thinking about it, I couldn't. It's like "don't think of an elephant."  :)

Did you notice the relevant thread that Cobwebby resurrected? 

http://www.lymeneteurope.org/forum/view ... &t=94#p225

There's a good eye-witness story from the late Joe Hamm, about partially fed ticks, abandoning a dead deer in favor of its killer.

Claudia provided an abstract to a 1993 ( watershed year in Lyme history) paper by Shih and Spielman describing experiments with partially fed ticks (see below). They don't think they're extremely rare, and they see the importance of that with regard to both prevention and, I presume, diagnosis. After 1993 (when Steere's influential paper on "the overdiagnosis of Lyme disease" persuaded the mainstream to work on preventing diagnosis rather than improving it) this observation of early transmission would have been out of favor, and followups might have been difficult politically.

http://www.ncbi.nlm.nih.gov/pmc/article ... 3-0052.pdf

J Clin Microbiol. 1993 Nov;31(11):2878-81.
Accelerated transmission of Lyme disease spirochetes by partially fed vector ticks.
Shih CM, Spielman A.
Source
Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts 02115.

Abstract
To determine how rapidly Lyme disease spirochetes (Borrelia burgdorferi) can be transmitted by partially fed vector ticks (Ixodes dammini), attached nymphs were removed from their hosts at various intervals post-attachment and subsequently permitted to re-feed to repletion on noninfected mice. We confirm previous reports that ticks deposit Lyme disease spirochetes in the skin of their hosts mainly after 2 days of attachment. Those that have been removed from a host within this interval can reattach and commence feeding. Spirochete-infected nymphs that have previously been attached to a host for 1 day become infectious to other hosts within another day. Noninfected nymphs acquire infection from spirochete-infected hosts within a day of attachment and become infectious to other hosts 3 to 5 days later. Virtually all ticks transmitted infection when reattaching after first feeding for 2 days. We conclude that partially fed nymphal ticks transmit spirochetal infection more rapidly than do ticks that have never been attached to a host and that infected ticks become infectious before they molt.
PMID: 8263171 [PubMed - indexed for MEDLINE] PMCID: PMC266148 Free PMC Article
Transmission of spirochetal infection from partially fed nymphs to their hosts depends on the capacity of a tick to acquire spirochetes early in the feeding process as well as its ability to reattach to another host. We found that spirochetal infection is efficiently acquired within the first day of feeding and that ticks can reinfest new hosts. We found that nymphs do detach spontaneously from free-ranging mice in thelaboratory, perhaps as frequently as 15% of the time. Indeed, about a tenth of questing nymphs in nature seem to be distended (24), and reattachment by partially fed subadult ticks commonly occurs (1, 9, 12).

Our observation of accelerated transmission by ticks that fed transiently on infected hosts suggests certain unexpected events in the life cycle of these spirochetes. We believe that this acceleration is not due to contaminative transmission because reattachment was delayed for several days. The previously observed phase of rapid multiplication (17) may be accompanied by spirochetal dissemination. Such disseminated infection normally is followed by a period of spirochete destruction that eliminates all but those spirochetes that survive in the lumen of the gut. Indeed, disseminated infections in nonfeeding ticks have occasionally been encountered during the course of fine-structural studies (6, 27).Such hemocelic spirochetes may become nonviable by the time that the tick has molted, and this persistence may reflect some failure of clearance by the inflammatory system of the tick. Lyme disease spirochetes, then, transiently disseminate soon after they are ingested by vector ticks. 
     
Exposure to vector ticks infected by the agent of Lyme disease generally occurs during outdoor activities associated with recreation or employment (19, 22). In one study at a site at which Lyme disease was endemic, vector deer ticks were found on or near the well-maintained lawns of the home of a patient with Lyme disease (8). Spirochetal infection was detected in 33% of the nymphs and 55% of the adults. Indeed, vector ticks feeding on infected hosts may detach prematurely because of grooming or host-derived antitick immunity (4, 5, 25, 26). These partially fed ticks may already have acquired spirochetal infection and avidly seek other hosts. Pet ownership appears to be a risk factor for human Lyme disease (10, 23), and this may reflect contact with ticks that have detached from a cat or dog within the household, Although the natural frequency of such partially fed nymphs has not been determined, they may present a particularly great risk of transmission of spirochetes.  
edited: Claudia provided this reference, not cave76 as I said before. I fixed it.
Last edited by Lorima on Thu 20 Sep 2012 21:39, edited 1 time in total.
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Claudia
Posts: 1448
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Location: Connecticut, USA

Re: Chronic persistent Lyme Disease (LD) or chronic Borrelio

Post by Claudia » Thu 20 Sep 2012 14:22

A very interesting paper that combines some of the information and some of the cited studies on this thread and on the thread "Duration of tickfeeding before removal on transmission of Bb" http://www.lymeneteurope.org/forum/view ... p?f=5&t=94.

A lot of unknowns, variables, and different studies that still need to be done: much complexity involved with this topic of transmission time and infection.

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC308935/
Infect Immun. 2003 December; 71(12): 6943–6952.
doi: 10.1128/IAI.71.12.6943-6952.2003
PMCID: PMC308935

Temporal Analysis of Borrelia burgdorferi Erp Protein Expression throughout the Mammal-Tick Infectious Cycle
Jennifer C. Miller,* Kate von Lackum, Kelly Babb, Jason D. McAlister, and Brian Stevenson

ABSTRACT
Previous immunological studies indicated that the Lyme disease spirochete, Borrelia burgdorferi, expresses Erp outer surface proteins during mammalian infection. We conducted analyses of Erp expression throughout the entire tick-mammal infectious cycle, which revealed that the bacteria regulate Erp production in vivo. Bacteria within unfed nymphal ticks expressed little to no Erp proteins. However, as infected ticks fed on mice, B. burgdorferi increased production of Erp proteins, with essentially all transmitted bacteria expressing these proteins. Mice infected with B. burgdorferi mounted rapid IgM responses to all tested Erp proteins, followed by strong immunoglobulin G responses that generally increased in intensity throughout 11 months of infection, suggesting continued exposure of Erp proteins to the host immune system throughout chronic infection. As naive tick larvae acquired B. burgdorferi by feeding on infected mice, essentially all transmitted bacteria produced Erp proteins, also suggestive of continual Erp expression during mammalian infection. Shortly after the larvae acquired bacteria, Erp production was drastically downregulated. The expression of Erp proteins on B. burgdorferi throughout mammalian infection is consistent with their hypothesized function as factor H-binding proteins that protect the bacteria from host innate immune responses.

[snippets]
B. burgdorferi within transmitting nymphal ticks. Two previous studies demonstrated that B. burgdorferi within engorged nymphal ticks produces detectable levels of erp transcripts or Erp proteins (23, 25). However, in those two studies, the ticks were examined for Erp expression either after completion of feeding or at only one time point during feeding. The present study represents the first analysis to accurately and quantitatively pinpoint the time frame of Erp expression during nymphal tick feeding and B. burgdorferi transmission.
B. burgdorferi in nymphal tick bite sites.
A caveat to studies such as those described above is that bacteria examined within the midgut of a feeding tick are those that did not make the trip from the midgut to the salivary glands and then into the skin of the host. Thus, they are not necessarily representative of the population of successfully transmitted bacteria. Taking this into account, we utilized double-labeling immunofluorescence techniques to examine skin taken from the nymphal tick bite sites at various time intervals during spirochete transmission. After 24 and 48 h of feeding, almost 100% of the spirochete population in each tick bite site skin sample was Erp positive. After 72 h of tick feeding, detectable Erp expression by spirochetes within the skin samples appeared to drop slightly, with over 80% of bacteria producing detectable levels of Erp proteins (Fig. ​(Fig.2A2A to C).
We consistently detected B. burgdorferi within the skin of mice at the tick bite sites within 24 h of tick attachment. Several other researchers have observed bacteria in the tick bite wound after a similarly short time of attachment (4, 27, 39, 40, 49). At first glance, these data seem to contradict results of other studies indicating that ticks must feed for at least 48 h before transmitting Lyme disease (13, 41, 51). However, a review of those reports indicates that, while efficiency of transmission greatly increases after 2 days of tick feeding, occasional infections were observed even when ticks fed for less time. Thus, it appears that during the first day or two of feeding, either very few bacteria are transmitted and are readily eliminated by the immune systems of most hosts or most of those bacteria transmitted are physiologically unable to establish disseminated infection.

4. Alekseev, A. N., L. A. Burenkova, I. S. Vasilieva, H. V. Dubinina, and S. P. Chunikhin. 1996. Preliminary studies on virus and spirochete accumulation in the cement plug of ixodid ticks. Exp. Appl. Acarol. 20:713-723. [PubMed]

27. Hodzic, E., S. Feng, K. J. Freet, D. L. Borjesson, and S. W. Barthold. 2002. Borrelia burgdorferi population kinetics and selected gene expression at the host-vector interface. Infect. Immun. 70:3382-3388. [PMC free article] [PubMed]

39. Ohnishi, J., J. Piesman, and A. M. de Silva. 2001. Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks. Proc. Natl. Acad. Sci. USA 98:670-675. [PMC free article] [PubMed]

40. Piesman, J. 1993. Dynamics of Borrelia burgdorferi transmission by nymphal Ixodes dammini ticks. J. Infect. Dis. 167:1082-1085. [PubMed]

49. Shih, C.-M., and A. Spielman. 1993. Accelerated transmission of Lyme disease spirochetes by partially fed vector ticks. J. Clin. Microbiol. 31:2878-2881. [PMC free article] [PubMed]
Tangentially related, I thought this was very interesting about IgM in later stages of infection:
Intriguingly, IgM antibodies directed against ErpA/I/N were stronger and of longer duration than those produced in response to ErpL or ErpQ, peaking at 3.5 months of infection, declining, and periodically increasing in the later stages of infection (Fig. ​(Fig.3A).3A). IgG titers produced in response to all examined Erp proteins also varied over time, and often increased, suggestive of continued stimulation of the immune systems throughout duration of the infection (Fig. ​(Fig.3C).3C). These fluctuations are even more dramatic when ELISA results for each mouse were considered individually (Fig. 3B and D and data not shown).

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Spanky
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Re: Chronic persistent Lyme Disease (LD) or chronic Borrelio

Post by Spanky » Thu 20 Sep 2012 17:40

From the above citation:
Thus, it appears that during the first day or two of feeding, either very few bacteria are transmitted and are readily eliminated by the immune systems of most hosts or most of those bacteria transmitted are physiologically unable to establish disseminated infection.


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