Born in Budapest, Hungary, Sept. 9, 1942, as son of Pal Bozsik and Maria Klinga; married to Marta Schleer, Dec. 4, 1968; children: Bela, Andras Pal, Attila Peter.
Member of N.Y. Acad. Sci.
Member of Society for Christian Physicians, Roman Catholic.
1960-61: Worker Lenin Metall. Works, Miskolc, Hungary.
1966: Graduated as MD from Semmelweis Med. U., Budapest.
1966-74: Pathologist St. Istvan Mcpl. Hosp., Budapest.
1974-99: Researcher. Nat. Inst. Hygiene, Budapest. A new method for evaluating the immunohemolytic activity of Complement with modified method was developed and new hypothesis for the structure of Membrane Attack Complex (C5b-C9) was constructed during 1974-1984. Based on the studies of the Complement system a new micro-method for complement fixation method was elaborated.
/ special work
and achievements regarding the subject of "Lyme borreliose"
1980-99: Head of the Serology laboratory at Johan Bela Nat. Inst. Hygiene; during that periode the laboratory did over 100000 serology tests for Borrelia burgdorferi, using different methods.
1999: Head of Lyme borreliosis center, St Rokus Hosp., Budapest, a position from which he had to retire in 1999.
1985: Proposing the since then worldwide accepted technical term for Lyme Disease and Related Disorders that is "Lyme Borreliosis"at the 2nd World Conference.
????: Proposing a diagnostic and therapeutic scheme for Lyme borreliosis seronegatives, and new hypothesis for pathogenesis of Lyme borreliosis respectively.
2002-2003/03: Researcher at Lyme borreliosis Clinic in Budapest.
2002: Patent 6689577. Special reagent (Dualdur) and procedure for the detection of pathogens, especially spirochetes from body fluids by microscopy.
Selected excerpts from the patent description:
"The laboratory diagnosis of borrelioses with different clinical
presentations is based primarily on the detection of spirochetes from
blood samples. This is easily accomplished in recurrent fever because
normally, there is a large number of B.recurrentis present. Besides,
other morphological properties of this pathogen (shown in the table
enclosed) and the fact that this pathogen is easy to stain also make its
detection easier. There are mild cases, however, when the symptoms
suggest the diagnosis of recurrent fever but the cell count is too low
for the conventional methods to detect the causative agent. To solve
this problem, the technique of microhematocrit concentration (double
centrifugation of blood samples) has been used since 1972. Microscopy is
superior in that the test result is not affected by the changing
antigenicity of Borreliae. [Goldsmid, J M. Mohamed: The use of
Microhematrocit Technic for the Recovery of Borrelia duttonii from the
Blood, Am. J. Clin. Pathol. 58:165-169 (1972)].
As mentioned above, morphological examination has long been included in the laboratory diagnosis of spirochetoses. If dark-field microscopy is employed, concentrated fluid samples do not need to be stained, which means that the long and thinspirochetes are not washed off the slides, which, in turn, increases sensitivity.
During the first stage of this infection, antibody production is slower than usual. Antibodies do not appear until weeks after the infection and are only rarely present throughout the whole course of the disease because titers keep changing and--after some time--they may become normal without any intervention. This makes it difficult to define the threshold titer. There is no clinically applicable threshold that could make a clear-cut distinction between those who are infected and those who are not. Besides, generation cycles of the causative agent cause a fluctuation of the early--IgM type--antibody titers. As far as we know, this is the only disease in which the causative agent blocks the production of the more specific and more effective IgG type antibodies, which normally follows the production of IgM. There are even cases of Lyme borreliosis in which only the early (IgM type) antibodies are present years after the infection.
What has been said so far affects all antibody assays. That is to say, comparative studies can only compare the sensitivity of the techniques in question.
Thus, it would be a big mistake to base the laboratory diagnosis of Lyme borreliosis on the traditional evaluation of a single test. Test results are sometimes considered non-specific in this case. The chances of non-specific reactions are known to be higher in spirochetoses but they can be avoided with traditional pre-test absorption, which removes the non-specific antibodies that could give a false reaction. If the test result is negative, physicians may doubt the validity of the patients' complaints and abandon the possibility of Lyme borreliosis even though antibody production may be inadequate or blocked, the technique employed may not be able to detect all antibodies or the threshold value may not be set correctly.
In a study made at a university in Vienna, Austria in 1985, Professor Stanek and his colleagues found that in artificially infected laboratory animals bacteremia could be detected using dark-field microscopy as well as conventional microscopy after Giemsa staining: the Borrelia burgdorferi sensu lato injected subcutaneously appeared in the circulation and remained detectable continuously. The number of bacteria detected was changing in seven to eight day cycles. They realized that the number of pathogens is changing and that in certain periods of the generation cycle spirochetes are more difficult to detect. [(Stanek, G.; Burger, I; Hirschl, A.; Wewalka, G.; Radda, A: Borrelia transfer by ticks during their life cycle Studies on laboratory animals. Zbl. Bakt. Mikrobiol. Hyg. A., 263: 29-33: 1986)]
In our experience, it is still possible to detect the pathogenic bacteria if there are less than 10 bacteria in a milliliter of centrifuged native blood samples. In comparison, the threshold for the detection of Lyme borreliosis with PCR, which is currently considered the most sensitive but can only be done in specially equipped laboratories, is between 40 and 100 germs per ml; besides, as many as possible primers specific to different sub-strains should be available.
It should be noted that further morphological, immunocytological and immunoserological examination of the centrifuged sample treated with the reagent according to the invention is also possible. Furthermore, it can also be utilized for PCR and cultivation. In the latter cases, filtering is recommended before concentrating the sample."
2004: The diagnostic method
was Patented in USA (Wikipatents, USPTO
). Read more about dr. Bozsik's method below and
????: Founder, Med, Sec. Head of the Hungarian Lyme Borreliosis Foundation, Budapest (http://lymenet.hu).
suggests, a new reagent has been developed that can slow
down the aging (membrane hardening) of human erythrocytes, leukocytes,
platelets and squamous epithelial cells in the samples. It has been
found that the reagent according to
the invention stops the amoeboid movement of leukocytes and the
fragmentation of platelets. Thus, myeloid figures are not formed. The
membrane of accidentally formed myeloid figures is also hardened.
Consequently, they do not even exhibit Brownian
movement; they simply float along. The movement and the cell division
of Borrelia burgdorferi sensu lato remained unaffected by the invented
reagent. This is how shedding could be observed, which had only been
noted in cell cultures." .... "The technique according to
the invention makes it possible to study the
current state of pathogenesis and determine the activity of Lyme
borreliosis in a given patient. A fast and reliable diagnosis can be
made even when serological tests are
negative. The reagent and the procedure according to the invention
provides reliable data to aid treatment (which is still controversial),
monitor treatment effects and predict relapses before the development
of humoral immune response or after it has
been blocked and all this is independent of autoimmune responses. "
.... Illustrative picture from abovementioned lecture:
test are not influenced by
either the genetic polymorphism or the phenotype of Borrelia
burgdorferi sensu lato (or the changes in either of these during the
pathogenesis of the disease), which is very important in Middle-Europe.
The test is also reliable in the cases when Lyme disease is caused by
new subspecies or immunological changes or when vaccination has
produced an antibody response. The theoretical sensitivity of this
procedure can be as high as one organism/ml. Concurrent PCR tests
appear to be less sensitive even nowadays. If
properly evaluated, it is the most sensitive of the direct tests and it
is also very reliable. It provides a tool to investigate natural
phenomena in a laboratory setting, which may help to gather new
information regarding the pathogenesis of Lyme disease.
In the microscopy, immobile cellular bodies are always seen in the background serving as controls of the moving Spirochetes.
DualDur® -treated normal or washed blood or Borrelia burgdorferi sensu lato cultures can also be used as controls. Indirect immunofluorescent assays using specific monoclonal antibodies kindly donated by prof. Barbour and Barbara Johnson prove that the Spirochetes are identical to Borrelia burgdorferi sensu lato. They were proven by electron microscopy in the last years with both negative staining and immuncytologic reactions.
This reagent provides conditions similar to the body, therefore the division of Spirochetes was detected several times; sometimes they were acting in pictures. You can see it in the following:
will be on the emerging combined
developed in 1990 and used widely with success in Hungary prescribed by
the members of the Therapeutic Workgroup of the Lyme Borreliosis
Foundation in Hungary. According
to our practice we can
tell you that the
following could not
in Middle Europe: “Conclusion
: Patients with
post-treatment chronic Lyme disease who have symptoms
but show no evidence of persisting Borrelia infection do not show
objective evidence of cognitive impairment. Additional antibiotic
therapy was not more beneficial than administering placebo."
Dr. W. Burgdorfer (left), Dr. B.P. Bozsik (in the middle) and colleague?
From personal / Internet group communications with dr. Bozsik:
Bozsik's own words on Borrelia burgdorferi Bleb's & Cysts - see more pictures of Borrelia spirochetes undergoing changes in the PDF:
tell You my opinion based on my morphological practice since 1986.
There are no cyst-forms as all ball-like morphology has always some material in them. They could be differentiate according to the following :
1. Gemma has DNA and could be further cultivated. This possibility was never proved by Garon and Dorward – Personal communication. If yes, it is the spore, until it is a sporoid structure.
2. Macromolecular immunocomplexes (blebs) contain Antigen-Antibody-Complement beside different extracellular material and Osp-s and they never could be used for cultivations. These forms could be developed during cultivation as leading character of B.burgdorferi as other Borrelias do. They are shedding both in the body and in the cultivation media.
3. So-called Spheroplasts or L-forms are developing during the effect of cell-wall-damaging antibiotics, and Lforms are caused by a process of herniation. They could also have DNA, but there is no hypothetical possibility of
4. Further damaged structures could be detected, which are the final product of protoplasma fragmentation inside of the Spirochetes – that is the granulation. It is hard to prove their extracellular presence as the so-called coccoid forms, except DNA hybridization.
5. Different forms of the intact B.burgdorferi were demonstrated in cultivation by Aberer and Duray and those of dividing Spirochete by me.
6. Ghost could be appeared as a final state of the reorganization process of B.burgdorferi after lytic damage
Do not forget the Dictionaries:
Gemma \Gem"ma\, n.; pl. Gemm[ae]. [L., a bud.]
1. (Bot.) A leaf bud, as distinguished from a flower bud.
2. (Biol.) A bud spore; one of the small spores or buds in the reproduction of certain Protozoa, which separate one at a time from the parent cell.
Detailed you can find in
lectures hold at the Anniversary
Congress of Lyme Borreliosis Foundation in Budapest in
2000 about the DualDur® reagent and method and the Hypothesis
based on the results got with this
method. The complete summary could be
downloaded at www.lymenet.hu
(letoltheto anyagok) and further information
from now http://lymerick.net/videomicroscopy.htm
All of my investigation was made in native human blood samples with Dark-field microscopy.
More from the conference website: Information to patients about Lyme borreliosis (10 pages, English version), Questionnaire (1 page, English version, Word DOC), Bozsik (2000) PPT on Therapy and Bozsik (2000) PPT on Diagnosis.
PS: I have never prescribed as I am a retired pathologist, but proposed to use and our colleagues are using tinidazol with our combined treatment schedule with better effect than without it to be demolish Gemma-s. I wish to know your proposal for patients with sensitivity to “azols”. Alinia? Plaquenil? Have you practice with it? Crossreaction with other antibiotics? Thanks You in advance, Bela
Dear Colleagues and Members of the list!
Binding antibody to the protein-band of 41 means appearance of LB either in the past or in the days. Other positive binding help us to evaluate a firm positive reaction. Perhaps the formerly reagents could not avoid the cross-reaction, so there were period of time with the need of clinical differentiations. Sometimes a one-shot abx treatment causes decapitation of the immune-response and develops LB seronegativa with a weak or no reaction even to p41. Seropositivity otherwise means only that LB exists.
The indication of the
treatment belongs to the clinical symptoms at this moment. – The only
absolute indication of the treatment is the PCR positivity of the biting tick.
[??? why do you NOT mention PCR positive on PATIENT SAMPLE?].
The substrain(s) determination gives a good data for the personal antibiotic treatment-schedule in the Carpathian Basin and Europe, too. There are further subgroups of Borrelia burgdorferi sensu stricto with different pathogenicity, which could also differ in their sensitivity to antibiotics.
Think of the extreme genetic plasticity and adoptability of Borrelia burgdorferi sensu lato we should prescribe combined antibiotics not allow the adoptation of the causative agent.
There is a possibility to
investigate Bbsl in blood using DualDur® reagent and method to help
with further data the clinicians. This reagent and method was developed in 1986.
You can see the demo video at the lower end of the page for http://lymerick.net/videomicroscopy.htm with some words on my video: http://lymerick.net/Sheffield2005/Bozsik/Dualdur.wmv
This method gives a possibility for further analysis of Borrelia burgdorferi sensu lato in similar condition to the body. Summarizing: there are two main and different chapters in Lyme borreliosis.
1. Diagnosis of LB according to laboratory investigations
2. Indication of treatment according to the activity of clinical symptoms
Of course there are several not classified parts both of diagnosis and indication of treatment, especially in the process of the development of a personal schedule for treatment.
3. The differential diagnosis of other TBD should be introduced into these processes…
This article was proof read by and further comments made by Dr. Bozsik (October 2007), but some of the excerpts has been added since.