My father is ill with Brucella (abortis, I am told) and has not
responded to treatment with conventional antibiotics.

We are seeking information which could lead to recovery (he has been
unable to leave his bed for most of these two years).

Satisfactory would be, in order of importance: 

A) Detailed information about cutting-edge therapeutic approaches,
complete with contact details for the doctors involved. This does not
include information about doctor Cascio and his coleagues in Italy
(Cascio A, Scarlata F, Giordano S, Antinori S, Colomba C, Titone L.),
which has already been provided in a separate question by pafalala-ga,
but other information from Italy is good, as we have heard from
several sources that there have been recent successes in that country.

B) Support groups for Brucella patients, preferably english-speaking,
with full contact details.

C) Literature about the disease, in english, and written for the layman.

If satisfactory information can be provided for this fee, we are
willing to increase the fee for all additional information which can
directly help to achieve our goal: to see our father able to walk,
work, and live his life normally.

---

Request for Question Clarification by pafalafa-ga on 05 Jul 2004 14:26 PDT

Hello,

I've been looking into your question, but haven't found enough
information (yet) to constitute an answer.  However, there are two
site I want to make you aware of, in case you haven't seen them yet.

One is from the Texas Dept. of Health:

http://www.tdh.state.tx.us/ideas/brucella/factsheet/

and it offers a synopsis of treatment regimes.  I wanted to make sure
you were aware of all of these, and have considered them:

=====

Treatment: The treatment of choice for brucellosis is doxycycline 100
mg po q 12 hours for 6 weeks and streptomycin 1 gm IM qd for the first
3 weeks. This regimen is particularly indicated for patients with
complications such as spondylitis. Doxycycline 100 mg bid po plus
rifampin 600 mg qd po for a minimum of six weeks may also be used. In
children, serious infections are treated with streptomycin 15 mg/kg
intramuscularly twice daily (up to 2 grams/day) or gentamicin 2.5
mg/kg every 8 hours plus ciprofloxacin 15 mg/kg/day or rifampin 20
mg/kg/day in 2 divided doses. Oral trimethoprim/sulfamethoxazole 10
mg/kg/day (of trimethoprim), doxycycline, or tetracycline can be used
to treat less serious infections. For central nervous system
infections, a third generation cephalosporin plus rifampin is
appropriate.

=====

Another site worth visting is this infectious diseases site:

http://www.cbel.com/infectious_diseases/

which lists about ten sites on Brucellosis that they consider to be
the best out there.



I'll continue looking around on this, and will let you know if I find
anything that appears useful.  In the mean time, give me whatever
feedback you can about the above sites, to let me know if they are
useful, or if they are covering old ground that you are already
familiar with.

All the best,

pafalafa-ga

---

Request for Question Clarification by pafalafa-ga on 05 Jul 2004 14:38 PDT

Also, here's one of the infrequent mentions I've come across about
actual theraputic trials for brucellosis patients:


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14719211

I've excerpted a bit of the abstract, below.  But in essence, the
authors are saying that:  (1) three-drug combination therapies are far
more effective than the standard two-drug combos, and (2) extended
drug therapy is more effective than the standard length of therapy.

The article was written by Dr. Miedany, and his email address is given as: 
miedanycrd@yahoo.com


J Rheumatol. 2003 Dec;30(12):2666-72.

  
Human brucellosis: do we need to revise our therapeutic policy?

El Miedany YM, El Gaafary M, Baddour M, Ahmed I.

Department of Rheumatology and Rehabilitation, Ain Shams University, 2
Italian Hospital, St. Abbassia, Cairo 11381, Egypt.

OBJECTIVE: To identify risk factors of relapse among patients with
osteoarticular brucellosis.

METHODS: In a prospective cohort study, we investigated 90 patients
with diagnosis of brucellosis... Thirty-five patients received
combination therapy of 2 drugs (rifampicin + cotrimoxazole or
doxycycline), while 55 patients received a combination of 3 drugs
(streptomycin + rifampicin + doxycycline)...

RESULTS: All patients continued treatment beyond the usual 6 week
period previously recommended. Relapse occurred in 59.3% in patients
who received treatment for 5 months or less, while relapse occurred in
7.9% among those who received treatment for more than 5 months...Sixty
percent of patients who received combination therapy of 2 drugs had
relapse, while there was no relapse in patients who received 3 drugs
in combination...

CONCLUSION: Extending treatment for longer than previously recommended
(6 weeks) resulted in an incidence of relapse significantly lower than
for shorter courses of treatment...



Again, let me know if this is useful information, or if it covers
familiar ground for you.

pafalafa-ga

---

Request for Question Clarification by pafalafa-ga on 10 Jul 2004 06:25 PDT

donovanski-ga,

When you have a chance, perhaps you can let me know if the links I
posted are on the right track in terms of the information you are
looking for.  This would help me or another researcher continue to
pursue an answer to your question.

pafalafa-ga

---

Clarification of Question by donovanski-ga on 11 Jul 2004 13:56 PDT

Pafalafa, so far what you have turned up looks like new ground to me,
I don't know what my father may have previously found, I will contact
him shortly and give you the information as to which of the leads we
would want you to pursue further. As it stands I don't really want any
other researcher on the case at this stage, seeing how you have made
such a good start, so do what you have to in order to keep this, or
let me know what I should do so as to give you the exclusive or
whatever its called.
Good work.
donovanski.

---

Request for Question Clarification by pafalafa-ga on 11 Jul 2004 14:04 PDT

Hello again.

Thanks for the update here.  You don't need to do anything in
particular to direct this question exclusively to me, since your
remarks already make clear that you would like to do so.

I'm glad to learn that there may be some useful information here for
your father.  Once you have some feedback on what additional
information might be helpful, let me know, and I'll continue working
on this.

Please be aware that there does not seem to be a great deal of ongoing
research regarding brucellosis in humans.  I don't want to
unrealistically raise expectations for you or your father.  However,
I'm certainly willing to keep plugging away to find whatever is in
print, and available for you to look at.

I look forward to hearing back from you.

pafalafa-ga

---

Clarification of Question by donovanski-ga on 11 Jul 2004 16:07 PDT

hi pafalafa,

The sites found here : http://www.cbel.com/infectious_diseases/
plus the texas dept of health all mention the same treatment: rifampin
+ doxycycline, this type of sites we have found a plenty, and shed
little new light.

The site from egypt:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14719211
is more interesting, and covers new ground. Especially interesting is
the mention of NO RELAPSE. Also the fact that it is recent. Pre-2002
information is less likely to be of use, and Pre-2000 is almost
certainly useless.

We are also interested in finding support groups, particularly online
ones, and books written for the man on the street.

Thank you for all your efforts so far,

donovanski.

donovanski-ga,

Thank you for your patience in awaiting the answer I have posted here.
 I have included below a good number of sources of information on
brucellosis, several of which represent cutting-edge treatment
research.

Let me know if you need anything beyond what I've posted here, and
best of luck to you and your father.

pafalafa-ga


==========

I have repeatedly found the emedicine.com site to be one of the best,
most professional sources of information available on the web
regarding medical conditions.  The information is not dumbed-down, but
is presented with care in a manner that is accessible to
non-professionals.   Their page on Brucellosis is here:


http://www.emedicine.com/neuro/topic42.htm


and I would encourage you to read it in its entirety.  I've excerpted
the gist of the section on treatment:

-----

Initial treatment of patients presenting with acute
meningoencephalitis usually entails treatment for herpes encephalitis,
until that entity has been excluded. In some instances, treatment
under the presumption that partially treated meningitis is the cause
of illness may entail the use of appropriate antibiotics, until that
possibility also is excluded. Once a brucellar infection has been
presumed or established as the cause of acute illness, treatment for 2
weeks with the combination of tetracycline and rifampicin (Rifampin)
is the standard therapy. Whether this treatment influences recovery
from meningoencephalitis, which usually occurs over several days with
or without such treatment, is not clear. However, this treatment is
aimed at preventing the development of chronic manifestations.
Streptomycin has been combined with tetracycline in the treatment of
some serious cases of brucellosis.

The standard treatment for chronic neurobrucellosis entails triple
therapy. The 3 agents may be selected from a group of agents that
includes rifampicin, doxycycline, gentamicin, streptomycin, and
ciprofloxacin.

One common combination used in adolescents or adults includes oral
rifampicin (600-900 mg/d) and doxycycline (100-200 mg/d) for 3 months,
combined for the first 6 weeks of therapy with 0.5-1 g of streptomycin
administered intramuscularly.

Emphasis has been placed on the importance of including an
aminoglycoside in the combined therapy for chronic neurobrucellosis;
gentamicin may be substituted for streptomycin. However, these agents
probably should not be employed in patients with acute
brucellosis-induced deafness or in patients who have impaired renal
function. Doses of all selected medications must be adjusted in
children weighing less than 40 kg, in elderly patients, or in patients
with renal or hepatic abnormalities.

Duration and effectiveness of therapy should be judged on clinical and
radiological grounds rather than on the basis of changes in antibody
titer.

Patients have been treated with antibiotic courses lasting for only 8 weeks. 

The addition of methylprednisolone may be beneficial in patients with
severe or diffuse CNS involvement, cranial neuropathies, optic
neuritis or other MS-like presentations, or arachnoiditis


-----

The emedicine section on Brucellosis was written by Dr. Robert S Rust,
Jr, MD, Thomas E Worrell Jr Professor of Epileptology and Neurology at
the University of Virginia.

Dr. Rust's web page can be found here:


http://www.healthsystem.virginia.edu/people/dop/dopDetail.cfm?drid=541


Note that his email is included, along with other contact information.


==========



Oddly enough, concern about the possible use of brucella bacteria as a
bioterrorism weapon has spurred the creation of some reports that
summarize what is known about treatment options.  The best of the lot
appears to be this 2002 European report at:


http://www.emea.eu.int/pdfs/human/bioterror/8.Brucellosis.pdf


It summarizes treatment options, and offers detailed accounts of the
utility of five drugs used in the treatment of the disease. Included
in the report are summaries of:


--doxycycline

--rifampicin

--gentamicin

--streptomycin

--TMP-SMX



==========

A book, written with the lay patient in mind, is available that covers
all aspects of brucellosis, and can be ordered from this site:



http://www.icongrouponline.com/health/Brucellosis.html
The Official Patient's Sourcebook on BRUCELLOSIS


I can't recommend the book, since I am not familiar with its contents,
but I wanted to make sure you were aware of its availability.


==========


The BruNet site, that I mentioned in my earlier comments to your
question, includes a list of some of the world's leading authorities
on brucellosis:


http://www.moag.gov.il/brunet/contact.asp


A number of the contacts on this list appear to have largely an
animal/veterinary orientation to the disease, but there are also
included a number of professionals with expertise in brucellosis in
humans.

In particular, I would call to your attention:


Dr. Ottorino Cosivi
Division of Emergence and Other Communicable Diseases 
Disease Surveillance and Control 
World Health Organization 
Avenue Appia, 20 CH-1211 Geneva 27 Switzerland

cosivio@who.ch 
+41-22-791-25-31
+41-22-791-48-93



Dr. Michael J. Corbel
Division of Bacteriology 
National Institute for Biological Standards and Control 
Blanche Lane South 
Mimms Potters Bar 
Hertfordshire EN6 3QG United kingdom 

mcorbel@nibsc.ac.uk
(0)1707-654753 (ext. 450)
(0)1707-663796



Dr. Gershon Keren
Infectious disease Consultant 
Director Kupat Holim "Leumit" 
Tel Aviv Area Israel 

039244292@doar.net 
972 3 6970479
972 3 6969158 




Prof. Pablo Yagupsky
Laboratory of Bacteriology 
Soroka Medical Center 
P.O.Box 151 Beer Sheva 84101 Israel 

frances@bgumail.bgu.ac.il
972-7-6400507
972-7-6403541




Prof. Ignicio Moriyon
Departmento de Microbiologia Universidad de Navarra 
Aptdo. 177, 31080 Pamplona Spain 

imoriyon@unav.es 
34-48-425600
34-48-425649




Dr. Axel Cloeckaert
Brucellosis Unit Pathologie Infectieuse et Immunologie 
INRA - Centre de Recherches de Tours 
37380 Nouzilly France 

cloeckae@tours.inra.fr
33-2-47-42-78-72
33-2-47-42-77-79



Prof. R. Diaz
Director Department of Microbiology 
University of Navarra 
Apartado 4.209 SP-31080 Pamplona Spain 

rdiaz@unav.es 
+34-948-296292
+34-948-172294




Prof. Edward J. Young 
Depatments of Medicine and Microbiology & Immunology 
Baylor College of Medicine and 
Infectious Diseases Section Veterans Affairs Medical Center 
2002 Holcombe Blvd. Houston, Texas 77030 USA 

young.edward_j@houston.va.gov 
(713)794-7589
(713)794-7670


 

==========


I also wanted to bring to your attention this document:


http://www.cdc.gov/ncidod/EID/vol3no2/corbel.htm
1st International Conference on Emerging Zoonoses -- Brucellosis: an Overview


Although dated 1997, it includes a good, concise overview of the
thinking at the time about treatments for brucellosis in humans:


=====

Treatment 

Despite extensive studies over the past 15 years, the optimum
antibiotic therapy for brucellosis is still disputed. The treatment
recommended by the World Health Organization for acute brucellosis in
adults is rifampicin 600 to 900 mg and doxycycline 200 mg daily for a
minimum of 6 weeks (59). Some still claim that the long-established
combination of intramuscular streptomycin with an oral tetracycline
gives fewer relapses (60). There is some evidence of physiologic
antagonism between rifampicin and tetracyclines, but recent studies
suggest that the two regimens have very similar results given adequate
time. Quinolones in combination with rifampicin seem as effective as
either of these regimens (61). Controlled clinical trials with other
antibiotics, including new macrolides and ß-lactams, have either give
inferior results or involved too few patients for proper evaluation.

Infections with complications, such as meningoencephalitis or
endocarditis, require combination therapy with rifampicin, a
tetracycline, and an aminoglycoside (62). Rifampicin has been
recommended as the treatment of choice for uncomplicated disease in
children, with cotrimoxazole as an alternative. Both are associated
with a high relapse rate if used singly, and best results are achieved
by using them in combination (63). Co-trimoxazole is an alternative
but also has a high relapse rate. A combination of the two agents
gives the best results.


==========

The World Health Organization has done a lot of work on brucellosis --
Dr. Ottorino Cosivi, on the contact list, above -- is the WHO person
who apparently heads up their brucellosis work.

The WHO website ordinarily maintains a brucellosis fact sheet at:



http://www.who.int/mediacentre/factsheets/fs173/en/index.html
Fact sheet N?173 -- Brucellosis 


but at the moment, their site says:  "This fact sheet is being
updated. For further information, please e-mail
mediainquiries@who.int".

You many want to check this site periodically for an update, or
contact them for further information.

 
The archived factsheet (from 1997) can be seen here:


http://web.archive.org/web/20021213095000/www.who.int/inf-fs/en/fact173.html


and includes the following:


======

Treatment: Antibiotics are effective against Brucella. However,
Brucella is localized intracellularly like certain other
micro-organisms (e.g., Mycobacterium tuberculosis), and requires the
association of more than one antimicrobial for several weeks.

Possible drug resistance Antimicrobial resistant strains of Brucella
are reported; however, their clinical implications are not yet fully
understood. Some of the commonly-used antimicrobials for brucellosis
treatment (i.e. Rifampicin and Streptomycin) are also first line drugs
for the treatment of tuberculosis. The present worldwide occurrence of
multi-drug resistant strains of pathogenic Mycobacterium tuberculosis
poses the urgent question of an alternative treatment for brucellosis,
using antimicrobial agents not employed for tuberculosis.

...The Mediterranean Zoonoses Control Programme (MZCP) of WHO is
coordinating a study on the evaluation of new treatment regimes for
human brucellosis...


{NOTE:  I conducted a search for the MZCP program, but did not uncover
any very recent or very useful information].


==========


Several fairly recent studies of the effectiveness of various
treatments for brucellosis are cited here:


http://216.239.51.104/search?q=cache:jEmN0FX9nwAJ:bvs.insp.mx/componen/svirtual/calidad/ncalidad.asp%3Fida%3D1110%26seccion%3DZoonosis+treatment++human+brucellosis+2002..2005&hl=en

and include:

 
Treatment of human brucellosis 
J Med Liban 2000 Jul-Aug;48(4):255-63  


Azithromycin and gentamicin therapy for the treatment of humans with brucellosis. 
Clin Infect Dis 2001 Feb 1;32(3):506-9  
  

Ciprofloxacin and rifampicin versus doxycycline and rifampicin in the
treatment of brucellosis
Eur J Clin Microbiol Infect Dis 1999 Aug;18(8):535-8 
  

Quinolones in treatment of human brucellosis: comparative trial of
ofloxacin-rifampin versus doxycycline-rifampin
Antimicrob Agents Chemother 1993 Sep;37(9):1831-4 


Each title can be clicked on to read a full abstract of the studies. 
In particular, the Ciprofloxacin study concludes:

"Ciprofloxacin and rifampicin treatment for brucellosis is as
effective as the standard regimen of doxycycline and rifampicin and
offers the advantage of a shorter duration of treatment..."


==========


Lastly, the National Library of Medicine operates a site called "PubMed" at:



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi



which is your best source of information for keeping up-to-date on the
latest publications regarding brucellosis.


I conducted a search on:


[ brucellosis human treatment ]


which returned more than 1,000 relelvant articles, some of them hot
off the presses.   Here are a few you should be aware of:





http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15214959

BMC Infect Dis. 2004 Jun 23;4(1):18
Ofloxacin plus Rifampicin versus Doxycycline plus Rifampicin in the
treatment of brucellosis: A randomized clinical trial


Karabay O, Sencan I, Kayas D, Sahin I.

The combination therapies recommended by the World Health Organization
for treatment of brucellosis are doxycycline plus rifampicin or
doxycycline plus streptomycin. Although highly successful results have
been obtained with these two regimens, relapse rates as high as 14.4%.
The most effective and least toxic chemotherapy for human brucellosis
is still undetermined. The aim of the present study was to investigate
the efficacy, adverse effect and cost of ofloxacin plus rifampicin
therapy, and doxycycline plus rifampicin therapy and evaluate in the
treatment of brucellosis.

...Conclusions Ofloxacin plus rifampicin therapy has advantages of
shorter treatment duration and provided shorter course of fever with
treatment and it is as effective as doxycycline plus rifampicin
therapy.


==========



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14598939

J Chemother. 2003 Oct;15(5):466-71. 


Comparison of five antimicrobial regimens for the treatment of
brucellar spondylitis: a prospective, randomized study.

Bayindir Y, Sonmez E, Aladag A, Buyukberber N.

Inonu University, Medical Faculty, Department of Infectious Diseases,
Malatya, Turkey. yasarb@inonu.edu.tr

In a prospective and randomized study, we compared the efficacy of
five antimicrobial regimens for treatment of 102 patients with lumbar
brucellar spondylitis. Patients were randomly assigned to receive
antimicrobial combination therapy. ...22 patients received
streptomycin 1 g/day i.m. for 15 days and doxycycline 100 mg every 12
h orally for 45 days plus rifampicin 15 mg/kg per day in a single
morning dose orally for 45 days (SDR)...there was a maximum good
response (100%) and no relapse in the SDR group. In conclusion, a
combination of doxycycline, streptomycin, and rifampicin can be
recommended as therapy for brucellar spondylitis and to reduce relapse
rates.


==========




http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12875523

Scand J Infect Dis. 2003;35(5):337-8. 

Biotypes and antimicrobial susceptibilities of Brucella isolates.

Bodur H, Balaban N, Aksaray S, Yetener V, Akinci E, Colpan A, Erbay A.

Infectious Diseases and Clinical Microbiology Clinic, Ankara Numune
Training and Research Hospital, Ankara, Turkey. hbodur2@ttnet.net.tr


41 Brucella strains isolated from blood and cerebrospinal fluid
cultures were identified to species level ...According to the 90%
minimal inhibitory concentration (MIC90) values, the most active agent
was doxycycline (MIC90 0.064 microg/ml), followed by ciprofloxacin
(MIC90 0.25 microg/ml), trimethoprim-sulfamethoxazole and ceftriaxone
(MIC90 0.38 microg/ml). Rifampin exhibited the highest MIC90 value
(0.75 microg/ml).


==========



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12868551

J Chemother. 2003 Jun;15(3):248-52

Treatment of human brucellosis with rifampin plus minocycline.

Cascio A, Scarlata F, Giordano S, Antinori S, Colomba C, Titone L.

AILMI (Associazione Italiana per la Lotta contro le Malattie
Infettive) c/o Scuola di Specializzazione in Malattie Infettive
Universita di Messina, Via Consolare Valeria n.1, 98125 Messina,
Italy. acascio@unime.it


In order to evaluate the efficacy and tolerability of a high
intravenous dose of rifampin plus oral minocycline (administered daily
for 3 weeks) for the treatment of acute brucellosis, we
retrospectively reviewed the outcome of 239 consecutive patients...the
combination used resulted in 100% response and a relapse rate lower
than 2%.


==========


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12674788

Antibiot Khimioter. 2002;47(10):3-7

Duisenova AK, Kurmanova KB, Kurmanova GM.

Scientific Center of Hygiene and Epidemiology, Almaty State Institute
of Prolonged Education, Republik of Kazakhstan, Almaty.

With the aim to estimate the clinical and immunological efficiency of
the ciprofloxacin (cifloxinal) 105 patients with acute (51), subacute
(19) and chronic (35) brucellosis were studied...Ciprofloxacin in a
dose 500 mg bid within 14 days in acute stage and 20 days in chronic
stage of disease essentially reduced duration of local inflammatory
processes of brucellosis with simultaneous treatment of the chronic
infection focus, provides good proximate and distant outcomes of
treatment. Ciprofloxacin can be considered as an alternative drug for
the treatment of brucellosis, more effective (clinically and
immunologically) than a combination of two antibiotics: doxycycline
and rifampicin.


==========


There are many many more articles at the PubMed site -- including a
great number dealing with specific types of complications of
brucellosis - that may be of interest to you.


I hope I have touched all the bases of the topics you are interested
in having more information about.  I looked extensively for
brucellosis support groups, but did not find any -- perhaps this is
something you might want to consider starting up yourself.

If you find you would like additional information on anything
mentioned here, just say the word.  Post a Request for Clarification
to let me know how I can help your further, and I am at your service.

All the best...

pafalafa-ga



search strategy:  Searched Google and PubMed for [ brucellosis human
treatment ] and [ brucellosis support group ]

I am well satisfied with the quality and quantity of useful
information which pafalafa-ga has found, sifted and sorted.

As a beginning, there is a small thing that your family can pay
attention to, in terms of food.

There is a sugar called erythritol.  It is being used as "sugar
substitute" and also used as a sweetener in prepared foods.

You don't want your father to have much of that; therefore, read
labels and avoid it.

It is not possible to avoid it entirely, but you can at least stay
away from it somewhat.

I am not one of the Google "answerers" but if I come across any other
useful information, I'll pass it along.

donovanski-ga,

Thanks so much for your kind and generous feedback.  Hope all goes
well with you and yours.

paf