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"Endotoxicity" of the Lyme disease spirochete.
Fumarola, D; Munno, I; Miragiotta, G
Infection. Vol. 11, no. 6, 345 p. 1983.
A treponema or a Borrelia -like spirochete recently isolated from Ixodes ticks has been implicated as the etiologic agent of lyme disease, as systemic illness characterized by an inflammatory skin disorder (erythema chronium migrans). Apart from these reports, virtually nothing is known about the factor(s) responsible for disease production by the causative organism. Since many members of the spirochetes exhibit an endotoxin-like activity, the authors have investigated the activity of the lyme disease spirochete in the Limulus endotoxin assay in order to learn more about the organism's biological profile. Although only whole cells were tested, the strain was consistently positive in the Limulus lysate assay at a concentration of 1:10 super(5) bacteria per ml. The presence of an endotoxin-like property may explain in part the virulence of the organisms during infection in humans and the variable severity of the illness.
Journal of Experimental Medicine, Vol 175, 1207-1212, Copyright © 1992 by Rockefeller University Press
Detection of plasma tumor necrosis factor, interleukins 6, and 8 during the Jarisch-Herxheimer Reaction of relapsing fever
Y Negussie, DG Remick, LE DeForge, SL Kunkel, A Eynon and GE Griffin
Division of Communicable Diseases, St. George's Hospital Medical School, London, United Kingdom.
The Jarisch-Herxheimer Reaction (J-HR) is a clinical syndrome occurring soon after the first adequate dose of an antimicrobial drug to treat infectious diseases such as Lyme disease, syphilis, and relapsing fever. Previous attempts to identify factors mediating this reaction, that may cause death, have been unsuccessful. We conducted a prospective trial in Addis Ababa, Ethiopia on 17 patients treated with penicillin for proven louse-borne relapsing fever due to Borrelia recurrentis to evaluate the association of symptoms with plasma levels of tumor necrosis factor (TNF), interleukins 6, and 8 (IL-6 and -8). 14 of the 17 (82%) patients experienced a typical J-HR consisting of rigors, a rise in body temperature (1.06 +/- 0.2 degrees C) peaking at 2 h, leukopenia (7.4 +/- 0.6 x 10(-3) cells/mm3) at 4 h, a slight decrease, and then rise of mean arterial blood pressure. Spirochetes were cleared from blood in 5 +/- 1 h after penicillin. There were no fatalities, but constitutional symptoms were severe during J-HR. Plasma TNF, IL-6, and -8 were raised in several patients on admission, but a seven-, six-, and fourfold elevation of these plasma cytokine concentrations over admission levels was detected, respectively, occurring in transient form coincidental with observed pathophysiological changes of J-HR. Elevated plasma cytokine levels were not detected in the three patients who did not suffer J-HR. We conclude that the severe pathophysiological changes characterizing the J-HR occurring on penicillin treatment of louse-borne relapsing fever are closely associated with transient elevation of plasma TNF, IL-6, and -8 concentrations.
.Proposed mechanisms and preventative options of Jarisch–Herxheimer reactions
* M. W. Pound*†*Department of Pharmacy Practice, Campbell University School of Pharmacy, Buies Creek, NC,†Department of Pharmacy, Cape Fear Valley Health System, Fayetteville, NC and PharmD BCPS and
* D. B. May*‡*Department of Pharmacy Practice, Campbell University School of Pharmacy, Buies Creek, NC,‡Department of Pharmacy, Duke University Medical Center, Durham, NC, USA PharmD BCPS
*Department of Pharmacy Practice, Campbell University School of Pharmacy, Buies Creek, NC,
†Department of Pharmacy, Cape Fear Valley Health System, Fayetteville, NC and
‡Department of Pharmacy, Duke University Medical Center, Durham, NC, USA
Melanie W. Pound, Department of Pharmacy Practice, Campbell University School of Pharmacy, PO Box 1090, Buies Creek, NC 27506, USA. Tel.: 910 609 6688; fax: 910 609 7548; e-mail: email@example.com
Objective: To review the aetiologies and preventative methods associated with Jarisch–Herxheimer reactions (JHR).
Data sources: Ovid Medline® (1966–June Week 1 2004) was utilized to assess biomedical literature; a review of the bibliographies of articles was also performed.
Data synthesis: JHR often occurs with the treatment of spirochete infections. However, the mechanism by which the reaction takes place is not clearly defined.
Conclusion: Studies suggest with conflicting evidence that the JHR is caused by release of endotoxin-like material from the spirochete as well as cytokine elevation in the body. It appears the type of drug and the rate of spirochete clearance from the body have little effect on the incidence of the reaction. Many pretreatment options have been explored with limited efficacy with the exception of anti-tumour necrosis factor antibodies
Burrascano claims: "It has been observed that symptoms will flare in cycles every four weeks. It is thought that this reflects the organism's cell cycle, with the growth phase occurring once per month (intermittent growth is common in Borrelia species). As antibiotics will only kill bacteria during their growth phase, therapy is designed to bracket at least one whole generation cycle. This is why the minimum treatment duration should be at least four weeks. If the antibiotics are working, over time these flares will lessen in severity and duration. The very occurrence of ongoing monthly cycles indicates that living organisms are still present and that antibiotics should be continued.
With treatment, these monthly symptom flares are exaggerated and presumably represent recurrent Herxheimer-like reactions as Bb enters its vulnerable growth phase then are lysed."