Persistence

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Ability of bacteria to persist desptite treatment or immune function.

Repeated Chlamydia pneumonia infection, persistence, caridovascular disease, luteolin

I don't believe we have this linked to our Research Pages (Marie?). This is a brilliant dissertation from the Finnish group, some of the world's experts on Cpni as some of the faculty in Helsinki were part of the original group who discovered the very existence of Cpn.

This dissertation demonstrates a number of important findings:

  • Repeated infection with Cpn "...induced persistent chlamydial DNA and inflammation in lung tissue and development of mouse Hsp60 autoantibodies."
  • Repeated infection with Cpn "...significantly increased subendothelial lipid accumulation in the aortic sinus area."
  • That "A flavonoid, luteolin, was shown to effectively decrease the chlamydial load and inflammatory reactions in lung tissue." Note: luteolin is not the same as lutein.
  • Conventional antimicrobial treatments are not effectively to eradicate persistent infection.
Go to the link and you can download the whole thing in pdf form.
Experimental Chlamydia pneumoniae infection model: effects of repeated inoculations and treatment

Liisa Törmäkangas

Lääketieteellinen tiedekunta, Oulun yliopisto

Research shows standard antibiotic treatment does NOT kill persistant Chlamydia pneumoniae

This study does a nice job of demonstrating that standard antibiotic treatment with accepted antichlamydials does not get rid of persistent Chlamydia pneumoniae in cells. Note the date. It's been around for a while, and yet "modern" researchers in cardiovascular disease "persist" in treating with 14-30 days of zithi and pronouncing with medical authority that antibioticsi have not effect on Cpni induced cardiovascular events. Duh! There's still infection. Note too, it's from our old friend Hammerschlag who also has argued strenously against Cpn in MSi and Alzheimer's. Win one, loose one.

Antimicrob Agents Chemother. 2002 Feb;46(2):409-12.
Related Articles,  Links
 
Effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on Chlamydia pneumoniae in a continuous-infection Model.

Kutlin A, Roblin PM, Hammerschlag MR.

Department of Pediatrics, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203-2098, USA.

Persistent infectionsi with Chlamydia pneumoniae have been implicated in the development of chronic diseasesi, such as atherosclerosis and asthmai. Although azithromycin, clarithromycin, and levofloxacin are frequently used for the treatment of respiratory C. pneumoniae infections, little is known about the dose and duration of therapy needed to treat a putative chronic C. pneumoniae infection. In this study, we investigated the effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on the viability of C. pneumoniae and cytokinei production in an in vitro model of continuous infection. We found that a 30-day treatment with azithromycin, clarithromycin, and levofloxacin at concentrations comparable to those achieved in the pulmonary epithelial lining fluid reduced but did not eliminate C. pneumoniae in continuously infected HEp-2 cells. All three antibiotics decreased levels of interleukin-6 (IL-6) and IL-8 in HEp-2 cells, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms. The levels of IL-1beta, IL-4, IL-10, tumor necrosis factor alphai, and gamma interferon were too low to assess the effect of antibiotics. These data suggest that the dosage and duration of antibiotic therapy currently being used may not be sufficient to eradicate a putative chronic C. pneumoniae infection.

Chlamydia pneumoniae infection of brain cells

This pre-publication abstract is a remarkable piece of laboratory work. It strengthens the case for Cpni infection especially in MSi and Alzheimer's, and other brain diseasesi.

The two findings I've underlined which seem to have espeical importance is (1) the sensitivity of neuronal cells to infection, as big producers of EB'si, and their particular sensitivity to necrosisi (tissue death); and (2) the finding in microglial cells that they resist active replicating infection but appear to be potential reservoirs for persistant Cpn.

  Neurobiol Aging. 2006 Apr 16; [Epub ahead of print]

Chlamydia pneumoniae infection of brain cells: An in vitro study.

Boelen E, Steinbusch HW, van der Ven AJ, Grauls G, Bruggeman CA, Stassen FR.

Department of Medical Microbiology, CARIM (Cardiovascular Research Institute Maastricht), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands; Department of Cellular Neuroscience, EURON (European Graduate School of Neurosciences), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.

Inspired by the suggested associations between neurological diseases and infectionsi, we determined the susceptibility of brain cells to Chlamydia pneumoniae (Cpn). Murine astrocytei (C8D1A), neuronal (NB41A3) and microglial (BV-2) cell lines were inoculated with Cpn. Infection was established by immunofluorescence and real-time PCRi at various time points. Productive infection was assessed by transferring medium of infected cells to a detection layer. Finally, apoptosisi and necrosis post-infection was determined. Our data demonstrate that the neuronal cell line is highly sensitive to Cpn, produces viable progeny and is prone to die after infection by necrosis. Cpn tropism was similar in an astrocyte cell line, apart from the higher production of extracellular Cpn and less pronounced necrosis. In contrast, the microglial cell line is highly resistant to Cpn as the immunohistochemical signs almost completely disappeared after 24h. Nevertheless, significant Cpn DNA amounts could be detected, suggesting Cpn persistencei. Low viable progeny and hardly any necrotic microglial cells were observed. Further research is warranted to determine whether these cell types show the same sensitivity to Cpn in an in vivo setting.

PMID: 16621171 [PubMed - as supplied by publisher]

Long term NAC -- would it eventually eliminate C.Pn.?

Would NACi administered for a sufficient time eliminate C.Pn? Here's my reasoning:

The C.Pn. spreads in the body by means of Essential Bodies. NAC kills them.

The replicating body has to work in a cell -- and all cells eventually die, killing the replicating bodies in them (I think that's what I read.)

The Cryptic Body is kind of "out of the loop." Mysterious, but if it can't get energy from a cell, and it can't reproduce, what does it really do?

Does anyone know, or can they set me straight, please?

Ron 

Dr. Stratton Answers Some Questions:

In some recent correspondance with Dr. Stratton at Vanderbilt University, he kindly answered some of the questions which had formed as I've understood more about the combination antibiotic protocol and about Cpni. From the patient's perspective I wanted to correlate some observations about treatment reactions with his deeper understanding about the biology of the Cpn. I'll list the questions I put to him, and then his generous response below.

1.  In an earlier correspondance you had mentioned pulsing the INHi band metronidazolei together.
        * Why do that rather than take it continuously?
        * My understanding is that INH is one of the anti-replicatives, and the point is to use these continuously to drive the bug into the cryptic phase where it will be obliterated by the flagyl/tinii. Does INH act differently than the other antireplicatives?
        * I also understood that we use a dual abxi to prevent developing resistance. Why can we use INH alone without developing resistance?
 

Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment

Circulation. 2001 Sep 25;104(13):E75.

Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment.

Gieffers J, Fullgraf H, Jahn J, Klinger M, Dalhoff K, Katus HA, Solbach W, Maass M.

Institute of Medical Microbiology and Hygiene, Medical University of Lubeck, Lubeck, Germany.

BACKGROUND: Recovery of the intracellulari bacterium Chlamydia pneumoniae from atherosclerotic plaques has initiated large studies on antimicrobial therapy in coronary artery disease. The basic concept that antibiotic therapy may eliminate and prevent vascular infection was evaluated in vitro and in vivo by examining the antibiotic susceptibility of C pneumoniae in circulating human monocytes, which are thought to transport chlamydiae from the respiratory tract to the vascular wall. METHODS AND RESULTS: Blood monocytes (CD14+) from 2 healthy volunteers were obtained before and after oral treatment with azithromycin or rifampin and then inoculated with a vascular C pneumoniae strain and continuously cultured in the presence of the respective antibiotic. Progress of infection and chlamydial viability was assessed by immunogold-labeling and detection of C pneumoniae-specific mRNA transcripts. Circulating monocytes from patients undergoing treatment with experimental azithromycin for coronary artery disease were examined for C pneumoniae infection by cell culture. Antibioticsi did not inhibit chlamydial growth within monocytes. Electron microscopy showed development of chlamydial inclusion bodies. Reverse transcription-polymerase chain reaction demonstrated continuous synthesis of chlamydial mRNA for 10 days without lysis of the monocytes. The in vivo presence of viable pathogen not eliminated by azithromycin was shown by cultural recovery of C pneumoniae from the circulating monocytes of 2 patients with coronary artery disease. CONCLUSIONS: C pneumoniae uses monocytes as a transport system for systemic dissemination and enters a persistent state not covered by an otherwise effective antichlamydial treatment. Prevention of vascular infection by antichlamydial treatment may be problematic: circulating monocytes carrying a pathogen with reduced antimicrobial susceptibility might initiate reinfection or promote atherosclerosis by the release of proinflammatory mediators.

The immune system, atherosclerosis and persisting infection

Vestn Ross Akad Med Nauk. 2005;(2):17-22. Related Articles, Links

[The immune system, atherosclerosis and persisting infection]

[Article in Russian]

Pigarevskii PV, Mal'tseva SV, Seliverstova VG.

The paper demonstrates that lymph nodes situated in the vicinity of magistral blood vessels are the source of immune and inflammatory response to LDL as the main pathogenetic factor in atherosclerosis. The activation of T-cell-mediated immunity takes place in them at the very early stages of the disease, resulting in forming of CD4+T-lymphocytes, activated mononuclear cells and immunostabilizing B-lymphocytes. The cell changes in lymph nodes correlate with the severity of atherosclerotic lesions in the vessel intima and closely reflect the peculiarities of immune inflammation development in fatty streaks and atherosclerotic plaques in human atherogenesis. A paradoxical reaction was observed in cases with Chlamydia pneumoniae found in the wall of aorta and paraaortal lymph nodes. No evident immune response on the part of immunocompetent cells took place, but, on the contrary, the function of mononuclear cells, including T-lymphocytes, was suppressed. This phenomenon may be explained by the fact that intracellulari localization of Chlamydia pneumoniae hides it from immune system control or by the possible microorganism capability of direct immunosuppressive influence on lymphoid cells both in the blood vessel wall and in regional lymph nodes.

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