KP, do you have any idea about prices? Please send me the brand name to see if I can easily import them. Best wishes to Jean, Carlos<br><br><div class="gmail_quote">2011/7/10 Chang, Kwang-Poo <span dir="ltr"><<a href="mailto:KwangPoo.Chang@rosalindfranklin.edu">KwangPoo.Chang@rosalindfranklin.edu</a>></span><br>
<blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex;">
<u></u>
<u></u>
<u></u>
<div lang="EN-US" link="blue" vlink="blue">
<div>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">Carlos will undoubtedly go with those,
which are clinically acceptable and feasible for the sake of expediency. <u></u><u></u></span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"><u></u> <u></u></span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">In a separate message, the causative agent
was said to have been identified as L amazonensis. Thermosensitivity of this species
has been well-documented, suggestive of thermotherapy. There is already the
suggestion of hot bath. One-use heat pad/heat wrap available over-the-counter
in the <u></u><u></u>USA<u></u><u></u>
drug stores is just as innocuous to consider as some topical ointments
suggested.<u></u><u></u></span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"><u></u> <u></u></span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">KP<u></u><u></u></span></font></p>
<div>
<div class="MsoNormal" align="center" style="text-align:center"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">
<hr size="2" width="100%" align="center">
</span></font></div>
<p class="MsoNormal"><b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;font-weight:bold">From:</span></font></b><font size="2" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma">
<a href="mailto:leish-l-bounces@lineu.icb.usp.br" target="_blank">leish-l-bounces@lineu.icb.usp.br</a> [mailto:<a href="mailto:leish-l-bounces@lineu.icb.usp.br" target="_blank">leish-l-bounces@lineu.icb.usp.br</a>] <b><span style="font-weight:bold">On Behalf Of </span></b>Carlos Costa<br>
<b><span style="font-weight:bold">Sent:</span></b> Saturday, July 09, 2011
10:07 AM</span></font></p><font size="2" face="Tahoma"><div class="im"><br>
<b><span style="font-weight:bold">To:</span></b> Leish-L<br>
<b><span style="font-weight:bold">Cc:</span></b> Josh Berman;
<a href="mailto:dagobertosilveira@superig.com.br" target="_blank">dagobertosilveira@superig.com.br</a>; Dorcas Lamounier Costa; <a href="mailto:jurbina@mac.com" target="_blank">jurbina@mac.com</a>;
Pierre BUFFET; Robert Vinson; Raimunda Sampaio; Shyam Sundarmail;
<a href="mailto:robertobadaro768@gmail.com" target="_blank">robertobadaro768@gmail.com</a>; Mark Nawacki; Fernando Koremblum;
<a href="mailto:joseanegodinho@yahoo.com.br" target="_blank">joseanegodinho@yahoo.com.br</a><br>
</div><b><span style="font-weight:bold">Subject:</span></b> Re: [Leish-l] miltefosine
for diffuse leishmaniasis</font><u></u><u></u><p></p>
</div><div><div></div><div class="h5">
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
<p class="MsoNormal"><font size="4" color="black" face="Verdana"><span style="font-size:13.5pt;font-family:Verdana;color:black">Dear friends,</span></font><u></u><u></u></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="4" color="black" face="Verdana"><span style="font-size:13.5pt;font-family:Verdana;color:black">This is really a such
touching and motivated community, and leish-l is proving to be an excellent
tool for solving the leishmaniasis toughest problems throughout the world. The
word "together" sounds really powerful in such a cases.</span></font><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="4" color="black" face="Verdana"><span style="font-size:13.5pt;font-family:Verdana;color:black">What os showing up
from these kind emails is a face of science coming not only from the bench, the
hospitals, the field, but a science coming straight from the heart.</span></font><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">Let me summarize some of the
lessons and suggestions. Please correct me if I skip some.</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">1) Hot bath - <u></u><u></u>Teresina<u></u><u></u> is very hot, and hot showers are
rare here. However, we can easily provide her an electric shower. Should it be
a tube? How long the bath would last?</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">2) BCG - one or two shots.
We will do it. Any hint about the intervals between the shots?</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">3) Previous drug therapy:
ImunoglucanTM (cell wall of <i><span style="font-style:italic">Saccharomyces
cerevisiae</span></i>), and saquinavir, after her delivery (</span></font></span><a href="http://www.ncbi.nlm.nih.gov/pubmed/18816190" target="_blank">Intracellular survival of
Leishmania species that cause visceral leishmaniasis is significantly reduced
by HIV-1 protease inhibitors.</a>).<u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">4) Besides miltefosine we got a
good hint where to find it (<u></u><u></u>Paladino<u></u>,
<u></u>Canada<u></u><u></u>), which
has excellent temporary effect (Zerpa et al, 2006), we should consider: </span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">a) lower/corrected doses of
paramomycin (Bryceson) - we have also to find the drug outside <u></u><u></u>Brazil<u></u><u></u>, since
it is not distributed/approved here; </span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">b) gamma-interferon (who
produces/sells it?).</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">c)
fluconazol/itraconazol/(voriconazol?).</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">d) amiodarone - <i><span style="font-style:italic">in vitro</span></i> testing does not sounds so good.</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">e) topic imiquimod (IxiumTM
cream) - apparently easy to find. concentration of 5%?</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">f) photodynamic therapy - with Dr.
Dagoberto Silveira, we are investigating where to do it around.</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">g) immunotherapy with suicide
photo-inactivated <i><span style="font-style:italic">Leishmania</span></i> (KP
Chang).</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">Please check what really seems
reasonable. My feeling is that most of the suggestions can be tried.</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">My warmest regards,</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><span><font size="5" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana">Carlos.</span></font></span><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
<div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">2011/7/8 Pierre BUFFET <<a href="mailto:pierre.buffet@upmc.fr" target="_blank">pierre.buffet@upmc.fr</a>><u></u><u></u></span></font></p>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Anthony,<br>
<br>
<br>
because there are only a few options left, would you consider at one point low
dose pentamidine (3 mg/kg every week or so, as you did in DCL patinets in <u></u><u></u>Ethiopia<u></u><u></u> in the
70s if I remember)? Could be used either to stabilize the situation before
starting on a coadministration, or as a maintenance after the
co-administration, in both cases with careful monitoring of kidney function ?<br>
<br>
<u></u><u></u>Pierre<u></u><u></u><br>
<br>
<br>
Anthony Bryceson <<a href="mailto:a.bryceson@doctors.org.uk" target="_blank">a.bryceson@doctors.org.uk</a>> a écrit :<u></u><u></u></span></font></p>
<div>
<div>
<blockquote style="border:none;border-left:solid #CCCCCC 1.0pt;padding:0in 0in 0in 6.0pt;margin-left:4.8pt;margin-right:0in">
<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Dear Carlos<br>
As you are well aware DCL is very difficult to treat. The big problem is that
the defect in specific CMI is more profound than that in VL and may never
recover, in contrast with the defect in VL which bounces back quickly.<br>
<br>
To have any chance of curing the patient, treatment should be monitored
by quantitative slit skin smears (as for splenic aspirates in VL) from multiple
pre-selected sites, every week or two weeks, and treatment continued until
negativity and for some weeks or months longer. When slit skin smears
become negative, hunt for any nodular or infiltrated lesions and take deep
biopsies and look for amastigotes there. Keep on hunting and smearing.
Sometimes, at the end of all this, evidence of CMI may appear, and cure becomes
a possibility. I am sure that the method of treating is more important than the
choice of drug - so long of course that the parasite is susceptible to the
drug.<br>
<br>
Hannah Akuffo has sent you the abstract relating to 3 patients treated by
Sabawork Teklemariam in Addis Abeba. That article details this approach.<br>
<br>
Do you know the species of Leishmania causing Maria's DCL, and its
sensitivities? In Addis Abeba parasites were cultured from two of the patients
and sensitivities determined and isobolograms drawn to look for synergy. The
isolates were sensitive to paromomycin and sodium stibogluconate was
synergistic. It would be worth while to make cultures before you start any new
treatment and have the isolate tested in this way. I expect that you have a lab
that could do this; if not, Simon Croft might be able to advise.<br>
<br>
Miltefosine has been very successful in a number of situations in South
American CL and showed promise for DCL, but patients relapsed despite
prolonged treatment.<br>
1. Zerpa O, Ulrich M, Blanco B, et al. Diffuse cutaneous leishmaniasis responds
to miltefosine but then relapses. Br J Dermatol. 2007;156:1328-1335.<br>
<br>
In a few patients with VL-HIV confection whom I treated in <u></u><u></u>London<u></u><u></u>, miltefosine worked well at first, but
the patients relpased while still on treatment and drug resistance was supected
but not tested. Miltefosine has a pharmacokinetic profile with a long tail that
might make it susceptible to the devlopment of resistance, especially if the
therapeutic window for a given isolate was narrow. So you might want to think
about adding a second drug to go with miltefosine from the beginning. I am not
sure what might be the best drug for combination; perhaps Josh Berman might
have an opinion. It is of course essential to ensure contraception.<br>
<br>
You could also consider the combination of paromomycin and low dose SSG. In
view of Maria's poor renal function you might need to modify the dose of
paromomycin and to monitor function.<br>
<br>
Robert Vinson is CEO of Paladin Labs, and would I am sure help you locate
miltefosine. <<a href="mailto:rvinson@paladin-labs.com" target="_blank">rvinson@paladin-labs.com</a>><br>
<br>
Richard Chin is CEO of One World Health, and would, I am equally sure,
help you locate paromomycin, should you consider that path. <a href="http://www.oneworldhealth.org/contact-us" target="_blank">http://www.oneworldhealth.org/contact-us</a>
Phone: +1 415-421-4700 Fax: +1 415-421-4747<br>
<br>
I wish you and Maria all the best in this venture.<br>
Anthony<br>
<br>
<br>
Dear Jennie<br>
Immunotherapy proved rather disappointing in VL. It seems that the patient
needs a decent immune response in the first place to benefit from
immuno-boosting.<br>
Sadly<br>
Anthony<br>
<br>
<br>
On 6 Jul 2011, at 20:04, Carlos Costa wrote:<u></u><u></u></span></font></p>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt">Dear all,<br>
<br>
Maria Cleudimar has cutaneous diffuse leishmaniasis due to Leishmania
amazonensis. She used to be a long time patient form Dr. Jackson Costa, in the
countryside of <u></u><u></u>Maranhão State<u></u>,
<u></u>Brazil<u></u><u></u>, since
she was 10 years old, after a disease that started when she was just five. Now,
she is under my and Dorcas care, at the age of 30, living in the city of <u></u><u></u>Teresina<u></u><u></u>.<br>
<br>
Her long time DCL does not respond to the treatment antimonium anymore.
Although we still prescribe liposomal amphotericin B at very low dose
(3mg/kg/once a week), her situation is deteriorating progressively, her renal
function does not allow any additional dosing since creatinine is presently
above 3mg/dL, and previous biopsy had shown tubular damage apparently secondary
to the drug, without evidence of amyloidosis. We tried several combinations of
different drugs, without success. Her situation worsened a lot during her
recent pregnancy (the baby is eight months old now).<br>
<br>
Our hope now stands only in miltefosine, for oral chronic use, but the drug is
not licensed or available in <u></u><u></u>Brazil<u></u><u></u>
yet (to my knowledge).<br>
<br>
With her permission I attached some of her pictures, hoping to sensitize
critical people in order to help me to get miltefosine and the permission for
prescription in <u></u><u></u>Brazil<u></u><u></u>
(or any other oral drug with promising efficacy, and without nephrotoxicity, if
known). Moreover, we need to know about the dose adjustment for the renal
impairment, and how long the drug could safely be used.<br>
<br>
One picture shows her face before treatment, and another after the pregnancy,
with the baby. One shows the situation of her thighs, another the calf of the
leg and the last one the infiltration of the palate.<br>
<br>
Hoping a little from friends, my kindest regards,<br>
<br>
Carlos.<br>
<br>
PS. Please understand that the pictures are allowed not for publication or
public presentation. Cleudimar permission is restricted to this forum.<br>
<br>
<br>
--<br>
Carlos H. N. Costa, MD, DSc.<br>
President<br>
Sociedade Brasileira de Medicina Tropical<br>
(Brazilian Society of Tropical Medicine)<br>
Instituto de Doenças Tropicais Natan Portella<br>
Universidade Federal do Piauí<br>
Rua Artur de Vasconcelos 151-Sul<br>
64049-750 Teresina-PI<br>
<u></u><u></u>Brazil<u></u><u></u><br>
Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).<br>
<br>
Aviso: As informações contidas nesta mensagem são CONFIDENCIAIS, protegidas
pelo sigilo legal, por direitos autorais e destinadas exclusivamente à pessoa
ou organização para a qual a mensagem foi destinada.<br>
Warning: This message is meant only for the intended recipient of the
transmission. It is forbidden any unauthorized use, alteration,
reproduction and distribution. If you are not the correct recipient, please
notify us immediately by return e-mail and delete this message from your
system.<br>
<br>
<cleu antes grav 13jan09.jpg><cleu e nene.jpg><cleu santada
recorte.jpg><cleu panturrilhas.jpg><cleu
palato.jpg>_______________________________________________<br>
Leish-l mailing list<br>
<a href="mailto:Leish-l@lineu.icb.usp.br" target="_blank">Leish-l@lineu.icb.usp.br</a><br>
<a href="http://lineu.icb.usp.br/cgi-bin/mailman/listinfo/leish-l" target="_blank">http://lineu.icb.usp.br/cgi-bin/mailman/listinfo/leish-l</a><u></u><u></u></span></font></p>
<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</blockquote>
<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><br>
<br>
<u></u><u></u></span></font></p>
</div>
</div>
</div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><br>
<br clear="all">
<br>
-- <br>
</span></font><b><font face="Verdana"><span style="font-family:Verdana;font-weight:bold">Carlos H. N. Costa, MD, DSc.</span></font></b><u></u><u></u></p>
<div>
<p class="MsoNormal"><b><font size="3" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;font-weight:bold">President</span></font></b><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><b><font size="3" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;font-weight:bold">Sociedade Brasileira de Medicina
Tropical </span></font></b><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><b><font size="3" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;font-weight:bold">(Brazilian Society of Tropical Medicine)</span></font></b><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><b><font size="3" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;font-weight:bold">Instituto de Doenças Tropicais Natan
Portella<br>
Universidade Federal do Piauí</span></font></b><u></u><u></u></p>
<div>
<p class="MsoNormal"><b><font size="3" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;font-weight:bold">Rua Artur de Vasconcelos 151-Sul</span></font></b><u></u><u></u></p>
</div>
<div>
<p class="MsoNormal"><b><font size="3" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;font-weight:bold">64049-750 Teresina-PI<br>
<u></u><u></u>Brazil<u></u><u></u><br>
Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).<br>
</span></font></b><font face="Verdana"><span style="font-family:Verdana"><br>
</span></font><font size="2" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana">Aviso: As informações contidas nesta mensagem são
CONFIDENCIAIS, protegidas pelo sigilo legal, por direitos autorais e destinadas
exclusivamente à pessoa ou organização para a qual a mensagem foi destinada.<br>
Warning: This message is meant only for the intended recipient of the
transmission. It is forbidden any unauthorized use, alteration,
reproduction and distribution. If you are not the correct recipient, please
notify us immediately by return e-mail and delete this message from your
system. </span></font><u></u><u></u></p>
</div>
</div>
<p class="MsoNormal"><font size="3" face="Times New Roman"><span style="font-size:12.0pt"><u></u> <u></u></span></font></p>
</div>
</div></div></div>
</div>
</blockquote></div><br><br clear="all"><br>-- <br><font face="verdana, sans-serif"><b>Carlos H. N. Costa, MD, DSc.</b></font><div><font face="verdana, sans-serif"><b>President</b></font></div><div><span style="font-family:verdana, sans-serif"><b>Sociedade Brasileira de Medicina Tropical </b></span></div>
<div><b><span style="font-family:verdana, sans-serif"></span></b><span style="font-family:verdana, sans-serif"><b>(Brazilian Society of Tropical Medicine)</b></span></div><div><font face="verdana, sans-serif"><b>Instituto de Doenças Tropicais Natan Portella<br>
Universidade Federal do Piauí</b></font><div><font face="verdana, sans-serif"><b>Rua Artur de Vasconcelos 151-Sul</b></font></div><div><font face="verdana, sans-serif"><b>64049-750 Teresina-PI<br>Brazil<br>Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).<br>
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