[Serum, lymph node and testicular concentrations of penicillin in 31 healthy or syphilitic rabbits treated with penicillin].
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Biomedical subjects
Publications and source records attributed to P Collart.
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For lack of being able to grow Treponema pallidum, the only method which allows us to study the biology of this germ and the physiopathology of this infection lies in researches in experimental syphilis. After pointing out the different aspects of Treponema pallidum, either with light microscopy or electron microscopy, the authors review the different kinds of reproduction suggested by syphiligraphs, the recent trials to cultivate the treponema, and the processes of elimination. Then, they examine the biological properties and the antigenic structure of T.p. as it has been established by comparison with cultivable spirochetes. To end with, the authors show that both the TPI test and the FTA test are two very specific reactions; these tests mean nothing but the fact that the patient has been in contact with the antigens of Treponema pallidum and the quantitative tests cannot be considered as expressing the infectious potential capacity.
For lack of being able to grow Treponema pallidum, the only possibility that we have to study its biological behavior is to have recourse to experimentation upon animals. The stade comprising primary and secondary syphilis is characterized by visible "warning signals" which are not serious for the patient himself. But all their importance lies in the fact that they reveal the dissemination of T. pallidum inside the whole body. Thus, the healing alone or the disappearance of the lesion does not necessarily mean that it is cured. As a matter of fact, after that phase, infection may proceed "á bas bruit", as a chronic affection, which will come to light later, 10 to 15 years or more after the primary stage, as a visceral phase involving mainly cardiovascular or central nervous system. Those impairments cannot then be cured. Now, during that long period of latency, we are totally without any absolute criterion of "bacteriological sterilization", for we do not know precisely the physio-pathological meaning of these numerous serological reactions which are at out disposal and subsequently we are obliged to interpret them through divergent opinions because these techniques are not established on scientific method but are based upon empiric knowledges.
Can penicillin be considered as an infallible treatment for syphilis? Some practitioners have hoped and even believed that this antibiotic would be able to eradicate this infection. To support their thesis, they have put forward an uniform standard therapeutic plan capable of being applied to any stage of the disease and which is based upon the following syllogism: a) all T.p. would divide every 30-33 hours. b) a level of penicillinemia of 0.03 IU/ml would destroy all Treponema when they divide. c) thus, a penicillin therapy administered 3 times giving such levels in serum during a period of 33 hours would produce a bacteriological sterilization of the infected organism. But statistics have shown that these conceptions were wrong. As a matter of fact: 1) every biological research has clearly proved that it is wrong to assert such a rhythm of division for all T.p. Since this multiplication is submitted to a succession of factors that we know more or less well, thus, during the latency phase, T.p. vegetate inside the tissues without apparently multiplying so quickly. 2) For lack of being able to cultivate T.p., it is not possible to state which is the activity level of penicillin on this germ. 3) Finally, the kinetic elimination of penicillin varies extremely, particularly depending on the drug which is used with patients, and on the localization of these germs. All experimental and clinical studies agree and insist on the fact that penicillin therapy must be given early in the infection, at a prolonged and high dose; results having to be estimated on the serological answers, especially with repeated TPI and FTA tests. As far as the late phases of the disease are concerned, for lack of being able to cultivate T. pallidum and because we do not have any absolute criterion of any bacteriological sterilization, the serological answers being often positive, circumspection has always to be a rule: it is better to admit what we do not know rather than to assert without any proof.
The problem of immunity in Syphilis is a very complex problem which is tightly bound to healing. But for lack of being able to grow T. pallidum and as we are without any absolute criterion of bacteriological sterilization, the only method we have to be able to consider this study is to have recourse to experimentation upon animals. Two theories had been proposed to give an explanation about this phenomenon occurring during a late treated syphilis: on one side, for Kolle, Evers and Neisser, immunity in syphilis would be due to a premunition given by the only persistence in the organism of T.p. having still kept all their virulence. On the other hand, as far as Chesney and Kemp are concerned it would be a true immunity, obtained before the application of any therapeutic treatment, but which is not due to persistence of T.p. in tissues. However, recent works have proved, and this has been confirmed by several searchers, that a penicillin therapy, even at a high dose, given six months after the infection outset, is no longer able of destroying all T.p. Immunity in syphilis would then be due to a modification of tissular receptivity kept by the persistence of T.p. vegetating in the organism in a commensal state. As far as the nature of this immunity is concerned, all the present research would lead to prove that this refractory state would not be due to tumoral properties, but more likely to tissular properties and probably to cell mediated phenomena. Similar research carried out in man has created an opportunity to demonstrate these facts similar to those observed in experimentations upon animals. They particularly prove that a persistent serology over a long period is not due to a "cicatrice sérologique" (Serological marker) but to the keeping of T.p. in a quiescent state. However, it is a more or less relative immunity which is concerned, depending upon a very large number of factors that are far from being elucidated.