Louse-borne relapsing fever borreliae are transmissible in an 'invisible' form ..

- which possibly also may apply to other spirochetes?

The paradox: that an infectious agent, which relies mainly on transmission from one mammalian host to the next via a bloodsucking vector, but only rarely can be found visible in blood in its spirochetal form, can be explained by the socalled equally virulent 'invisible stage' desbribed by the authors below. This 'invisible stage' possibly corresponds to the L-form / cystic 'granule' form of the spirochetes as described by several authors:
Spirochetal-cysts.htm

The granule / cyst / L-form must be perfect for passive transportation in a moving fluid like blood - while the spirochetal form must be perfect for screwing itself into dense tissues like sinew ?

The time in 'invisible stage is apparently concurrent with the apyretic period as described by the authors below and is of mean 8-10 days duration for relapsing fever borreliae.
This corresponds very well to Brorson's much more recent observation that young cysts of Borrelia burgdorferi takes about 9 days to revert to its spirochetal form, while older cysts take longer about 4 weeks
1998-Brorson-cyst.htm

The implication of this is first of all that we need to look for the L-form of borreliae in blood instead of the spirochetal form.
As the spirochetaemia phase is known to correspond to the pyrexic phase, the immune system obviously reacts strongly to the spirochetal surface antigens, while it reacts much less to the L-form's surface antigens - thus the L-form probably do not contain all the same surface antigens as the spirochetal form does ?...
and from the pictures and investigations done on the spheroblast L-form / cyst form - it seems obvious that the L-form does not contain any flagella, hence do not stimulate formation of flagella-antibodies, so this may possibly be one of many explanations why exactly this antibody very often declines in Late borreliosis despite culture or PCR-proven persistent borreliosis ?

I asked LymeRICK friends just a few months ago: "Which antigens does the L-form contain then - how can we find out?
- because when we know which antigen the L-form expresses we can hopefully develop a staining method to directly visualize the L-forms in blood ?
and perhaps we can also create an ELISA-test that look for antibodies towards L-form surface-antigens, that possibly will be better for cases of chronic Lyme disease than the ELISA for flagella-antibodies.

Now - just a few months later this has indeed been done by Bowen Research and Training Institute, which have developed a DIRECT flourescent antibody staining technic for the L-forms of Borrelia burgdorferi, see Bowen RTI:
http://www.bowen.org/

A danish patient with a classic history of antibiotic responsive remitting-relapsing persistent Lyme borreliosis since 1996, has just tested positive on the Bowen test for Borrelia burgdorferi L-forms, babesia and smear also 'suggest' morulae of HME.
She was previously seropositive for Borrelia flagella-antibodies, but only for IgM-antibodies, while today she is SERONEGATIVE for both borrelial flagella IgM and IgG !!
See last picture in: Spirochetal-cysts.htm
This result gave basis for doing a pilot-study on danish patients with similar history.

That cysts of Borrelia garinii is INFECTIVE has been shown by Gruntar et al. summer 2001, see last reference below !!!!!

Marie Kroun, MD
April 2001, revised March 2002, revised july 2006

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Les Spirilles de la fievre recurrente sont-ils virulent aux phases successives de leur evolution chez le pou? Demonstration de leur virulence á un stade invisible.
Nicolle C, Blanc G. Compt. Rend. Acad. Sci., clviii, pp. 1815-1817, 1914
#14_01 RF virulence invisible.tif#
Authors describe transmission of relapsing fever by lice, that occur at a time, when no spirochetes are present in the louse i.e. transmission occur at an 'invisible stage. Later spirochetes appear.
Excerpts:
Les rèsultats positifs de nos expèriences prouvent la virulence du pou à la pèriode qui prècède immèdiatement la rèapparition des spirilles, c'est-à-dire à un stade invisible de l'èvolution de ceux-ci.
1'er au 4'e jour du repas infectant (rèactif singe): ni spirilles visibles, ni virulence
5'e, 6'e jours (rèactif singe): spirilles encore invisible, virulence.
7é au 9'e jour (rèactif homme): spirilles fins, virulence
10e jour et suivant (rèactif singe): spirilles adultes, non-virulence. Nous rappelons que, passè le 19'e jour, il n'est plus rencontre de spirilles chez le pou.

Des periodes de latence du Spirille chez le malade atteint de fievre recurrente.
Sergent E, Foley H. Compt. Rend. Acad. Sci. 1914, clviii, pp. 1926-1928
Authors find that the infectious agent of recurrent fever must be in the blood in a very small non-spirochetal, but still very infectious form for (6-) 8-10 (-16) days, concurrent with the apyretic phase.
Excerpts:
Ce fait est favorable à l'idèe d'une évolution périodique du virus dans l'organisme apyrétique du convalescent, évolution qui aurait une durée de 8 à 10 jours en moyenne, comme l'intervalle d'apyrexie. Cette évolution se continuerait simplement chez le singe inoculé.
En conclusion, le virus de la fièvre récurrente existe, dans le sang circulant, depuis le début jusqu'à la fin de la première période d'apyrexie, sans que les spirilles y soient décelables pendant ce temps à l'examen microscopique. Le virus doit donc revêtir, au cours de l'apyrexie, une autre forme d'évolution très petite.
Nous avons constaté dès 1908 des faits analoques avec le même virus de la fièvre récurrente dans le corps des poux.

De la periode de latence du spirille chez le Pou infecté de fievre recurrente.
Sergent E, Foley H. Compt. Rend. Acad. Sci. 1915, clix, pp. 119-122
Authors have previously found (1908) that material from crushed lice that had been feed blood meal on a recurrent fever sick and filtered was still infectious despite the fact that no spirochetes could be seen in the inoculation material.
In this work authours examines lice for spirochetes from the first day and up to 14-16 days after the blood meal; they find that during the first 8 days after the infectious meal, spirochetes can not be visualized, but thereafter a growing number of spirochetes reappear.
They conclude that the infectious agent must be in a very small form that is equally infectious and that the infectious agent changes to this form during the apyretic periods between relapses and that this peiod in man is of a mean of 8 days duration.
Excerpts:
Nous aviouns déjà vu, en 1908, que le liquide de broyage du corps d'un Pou nourri 6 jours auparavent sur un malade de fièvre re´currente avait étè infectant pour le singe, bien que ce liquide de broyage placé en totalité une lame et une lamelle et très minutieusement examiné à frais avant l'inoculation ne montrât aucun Spirille. .....
En conclusion, pendant les 8 jours qui suivent le repas infectant, le corps des Poux ne conyient pas de Spirilles; ceux-ci rèapparaissent ensuite. Cette rèapparition a été vue, por la première fois, en 1912, par C. Nicolle et ses collaborateurs. Mais, comme nous l'avons signalè déjà en 1908 (1), en 1910 (2) et en 1911 (3), les Poux des 8 premiers jours, qui ne renferment aucun Spirille visible, contiennent cependent un virus infectant.
Nous sommes donc conduits à admettre que le virus de la fièvre récurrente, outre sa forme spirillaire, peut revêtir une autre forme très petite, également virulente. Il prendre cette forme, soit dans les périodes d'apyrexie qui séparent les accès de récurrente chez 'Homme, soit dans la période qui suit le repas infectant chez le Pou. L'évolution de cette forme très petite dure chez l'Homme, comme chez le Pou, 8 jours en moyenne. L'existence d'un cycle évolutif est un argument en faveur du rattachement du Spirille de la fièvre récurrente aux Protozoires.

Conversion of Borrelia garinii cystic forms to motile spirochetes in vivo.
Gruntar I, Malovrh T, Murgia R, Cinco M. APMIS. 2001 May;109(5):383-8. PMID: 11478686
Abstract:
Cystic forms (also called spheroplasts or starvation forms) and their ability to reconvert into normal motile spirochetes have already been demonstrated in the Borrelia burgdorferi sensu lato complex. The aim of this study was to determine whether motile B. garinii could develop from cystic forms, not only in vitro but also in vivo, in cyst-inoculated mice. The cysts prepared in distilled water were able to reconvert into normal motile spirochetes at any time during in vitro experiments, lasting one month, even after freeze-thawing of the cysts. Motile spirochetes were successfully isolated from 2 out of 15 mice inoculated intraperitoneally with cystic forms, showing the infectivity of the cysts. The demonstrated capacity of the cysts to reconvert into motile spirochetes in vivo and their surprising resistance to adverse environmental conditions should lead to further studies on the role and function of these forms in Lyme disease.