Advertisement
Research Article

Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection

  • Monica E. Embers mail,

    members@tulane.edu (MEE); Philipp@tulane.edu (MTP)

    Affiliation: Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Stephen W. Barthold,

    Affiliation: Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California Davis, Davis, California, United States of America

    X
  • Juan T. Borda,

    Affiliation: Comparative Pathology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Lisa Bowers,

    Affiliation: Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Lara Doyle,

    Affiliation: Veterinary Medicine, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Emir Hodzic,

    Affiliation: Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California Davis, Davis, California, United States of America

    X
  • Mary B. Jacobs,

    Affiliation: Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Nicole R. Hasenkampf,

    Affiliation: Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Dale S. Martin,

    Affiliation: Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Sukanya Narasimhan,

    Affiliation: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America

    X
  • Kathrine M. Phillippi-Falkenstein,

    Affiliation: Veterinary Medicine, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Jeanette E. Purcell,

    Affiliation: Veterinary Medicine, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    Current address: Biologic Resources Laboratory, University of Illinois, Chicago, Illinois, United States of America

    X
  • Marion S. Ratterree,

    Affiliation: Veterinary Medicine, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Mario T. Philipp mail

    members@tulane.edu (MEE); Philipp@tulane.edu (MTP)

    Affiliation: Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America

    X
  • Published: January 11, 2012
  • DOI: 10.1371/journal.pone.0029914

Reader Comments (8)

Post a new comment on this article

A Paradigm Shift

Posted by inmacdonald on 13 Feb 2012 at 22:36 GMT

Re: Persistence of Borrelia burgdorferi in Rhesus Macaques

by inmacdonald » February 13th, 2012, 3:14 pm

The collective comments on the LymeNet Europe Forum (Persistence of Borrelia burgdorferi in Rhesus Macaques) above are provacative and might induce Primate scientists to design further studies to provide some additional insights.

I would like to attempt to dissect the molecular evidence gleaned from this paper.

Before doing that I point out a fact concerning Ceftiofur , which is a third generation cephalosporin
available to Veterinary practitioners. Ceftiofur is fully equivalent to Ceftriaxone in terms of its MIC/MBC actions in laboratory testing and in terms of its bioavailability an pharmacologic repertoire.
Link:
http://www.ijaaonline.com...(00)00184-9/abstract

In a previous thread on Primate Brain Borrelia infection
I offered a tabulation to demonstrate the intinsic superiority of the DECAL RT PCR
method (Narasimhan..et al/ Fikrig paper) which I think is orders of magnitude superior (over 160 ORF's examined) as opposed to the use of PCR for a single ORF , namely OspA (Pachner)

RT PCR probes for the RNA products of the borrelia transcriptome.
The authors in this paper point out that the detection of RNA derived from Borrelia genome
is superior to the detection of DNA using routine PCR, because RNA speaks to support
the presence of viable borrelia. (Please download all supplementary Data)

In Experiment 2,--- 5 primates are available for study.
RT PCR demonstrates the presence of Borrelia RNA [Osp A in tissues, and in organ tissue culture Pellets from heart,spleen,blood ] in five of five subjects.
Brain tissue was not examined.
Brain tissue examination is important in any autopsy molecular interrogation
of animals infected and subsequently receiving antibiotic therapy .
Narashimhan,S ....et at ../Fikrig.E in their Primate Borrelia Autopsy Transcriptome
demonstrated that multiple ORFs ( more than 60) were upregulated in Brain tissues, and that the
borrelia transcriptome profile in autopsy heart differed from the profile in Medulla oblongata.
Deep brain tissues, such as the Medulla, are particularly important in any autopsy
investigation, because neuroborreliosis is not restricted to the covering membranes of
the brain, namely the leptomeninges, which are inflammed in meningitis.
Neuroborreliosis has graduated from the initial reports of Dr. Allen Steere in the late
1970s-1980 time frame.
It is unfortunate, in my view, that some physicians only diagnose the Meningitis profle
from the 1980's.

Now, a word or two about inflammation in borrelia infected tissues. Dr Paul Duray
expertly demonstrated in the 1980's-90's a spectrum of inflammatory infiltrates in various body sites
in Lyme borreliosis. Inflammation when present is interesting and indicates a cellular
immune host response to the infection. There is no pattern in the tissue inflammation realm
with the possible exception of ACA and BL, which serves as a stand alone signpost that the condition is Lyme Borreliosis. Inflammation with concurrent detection of antibody titers in the ranges
which are acceptable for the diagnosis of Lyme borreliosis by current CDC Guidelines
has been used ( in the absence of tissue detection of the spirochete, or in the absence of
laboratory culture of borrelia burgdorferi from the host)
to define newer manifestations of Lyme Borreliosis ( ie other than EM,Carditis,Arthritis, and Meningitis). Inflammation and concurrent positive serology may not satisfy some skeptics
as quantum suffit for proof.
Over the years, it has become accepted that bona fide cases of Borrelia burgdorferi infection exist in immunocompetent human hosts
in which no microscopic inflammatory infiltrates are present.( The lack of inflammation in
mouse models of Borrelia infection of tendon tissue is a noteworthy feature of a separate thread
on this site.) Perhaps tendon tissue and collagen might provide sanctuary sites for borrelia.
The deep brain regions constitute a second possible sanctuary site for Borrelia.
In the past century,
animal inoculation of brain tissue for detection growth of African borrelia from human hosts
was the only research modality available,... Ie. the work of Dr F. Hawking, (Father of Dr Stephen Hawking) is informative for Mouse brain inoculaation of Cerebrospinalo fluid as a reliable laboratory method for the diagnosis of borrelia infection in human body fluids.

Autoimmune situations in chronic lyme borreliosis are an intriguing situation. Borrelia species
are capable of Lateral DNA transfer between strains (Horizontal DNA Transfer), and based on the Agrobacterrium tumafaciens
model of Dr Citovsky and colleagues at SUNY Stony Brook, Bacterial DNA from Agrobacterium
has been detected in Human tissue culture cells (HeLa cells). Bacterial transfer to eukaryotic cells
is the next great horizon for young investigatgors with molecular biology backgrounds .
If Borrelia DNA winds up in the nucleus
of human cells, the stage would be set for the production of Borrelia epitopes on the surfaces
of human cells in the infected human host, which would be dealt with by an Autoimmune host response. This is somewhere
between a hypothesis and a theorum, based on other dialogues on this forum, which dissect
the differences between Hypothesis and Theorums.
Scientific method is hypothesis testing, as we learned from our earliest education.

In order to rigorously evaluate the paper which is the subject of this thread, all of the
supplementary tabular data must be downloaded and cognitively incorpoprated into the total opus of the text.

Respectfully,

Alan B. MacDonald MD

No competing interests declared.