<font color="#000000"><font size="4"><font face="verdana,sans-serif">Hi Gena,</font></font></font><div><font color="#000000"><font size="4"><font face="verdana,sans-serif"><br></font></font></font></div><div><font color="#000000"><font size="4"><font face="verdana,sans-serif">Thanks a lot for your offer. </font></font></font></div>
<div><font color="#000000"><font size="4"><font face="verdana,sans-serif"><br></font></font></font></div><div><font color="#000000"><font size="4"><font face="verdana,sans-serif">Our purpose is to work together with John and Abhay, who I know personally for a long time. May be the experience here will lead to broader application.</font></font></font></div>
<div><font color="#000000"><font size="4"><font face="verdana,sans-serif"><br></font></font></font></div><div><font color="#000000"><font size="4"><font face="verdana,sans-serif">I am forwarding your email to DNDi to see if they could help us in getting the machine into the country, since they have expertise in this kind of humanitarian treatment.</font></font></font></div>
<div><font color="#000000"><font size="4"><font face="verdana,sans-serif"><br></font></font></font></div><div><font color="#000000"><font size="4"><font face="verdana,sans-serif">My best regards,</font></font></font></div>
<div><font color="#000000"><font size="4"><font face="verdana,sans-serif"><br></font></font></font></div><div><font color="#000000"><font size="4"><font face="verdana,sans-serif">Carlos. </font></font></font></div><div><br>
<div class="gmail_quote">2011/7/12 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>
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<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">This is good to try.<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>
<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>
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<hr size="2" width="100%" align="center">
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<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:gzischke@thermosurgery.com" target="_blank">gzischke@thermosurgery.com</a> [mailto:<a href="mailto:gzischke@thermosurgery.com" target="_blank">gzischke@thermosurgery.com</a>] <br>
<b><span style="font-weight:bold">Sent:</span></b> Tuesday, July 12, 2011 12:47
PM<br>
<b><span style="font-weight:bold">To:</span></b> Carlos Costa; Abhay Satoskar;
John David; <a href="mailto:generhedin@thermosurgery.com" target="_blank">generhedin@thermosurgery.com</a><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>; Raimunda Sampaio; Dorcas Lamounier Costa;
Mark Nawacki; <a href="mailto:jurbina@mac.com" target="_blank">jurbina@mac.com</a>; Pierre BUFFET; <a href="mailto:joseanegodinho@yahoo.com.br" target="_blank">joseanegodinho@yahoo.com.br</a>; Robert
Vinson; Shyam Sundarmail; <a href="mailto:robertobadaro768@gmail.com" target="_blank">robertobadaro768@gmail.com</a>; Leish-L; Fernando
Koremblum; Chang, Kwang-Poo<br>
<b><span style="font-weight:bold">Subject:</span></b> RE: [Leish-l] miltefosine
for diffuse leishmaniasis</span></font><u></u><u></u></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>
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<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">Dear Dr. Costas,<u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">Thermosurgery is
committed to the research and treatment of leishmaniasis. We are pleased
to work with you and assist your patients. We can lend you an instrument
to use in your program. Our biggest hurdle is getting the equipment into
the country. If you work with an NGO or government agency that can assist
us in the importation that would be helpful. <u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">Lets discuss the
logistics to see if it is feasible to get you the equipment. I would
suggest that you work with Dr David and Dr Satoskar on the recommended
treatment protocol. <u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">We would want to
receive documentation regarding the use of the equipment and a paper so that we
can educate others on the value of this treatment. <u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u> <u></u></span></font></p>
</div>
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<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">Warm regards,<u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">gena<u></u><u></u></span></font></p>
</div>
<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u> <u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u> <u></u></span></font></p>
</div>
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<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">Gena
Zischke<br>
Business Development<br>
Thermosurgery Technologies, Inc.<br>
2901 <u></u><u></u>W. Indian School Rd.<u></u><u></u><br>
<u></u><u></u>Phoenix<u></u>, <u></u>AZ<u></u>
<u></u>85017<u></u><u></u><br>
Phone: (602) 264-7300<br>
<br>
<br>
The information in this communication is confidential. It is intended solely
for the addressee. Access to this communication by anyone else is unauthorized.
If you are not the intended recipient, any disclosure, copying, distribution or
any action taken or omitted to be taken in reliance on it, is prohibited and
may be unlawful. If you have received this communication in error, please
notify us immediately by return email, and destroy this communication and all
copies thereof, including all attachments. Thank you. Thermosurgery Technologies,
Inc.<br>
<br>
<br>
Fax: (602) 248-3809<u></u><u></u></span></font></p>
</div>
<blockquote style="border:none;border-left:solid blue 1.0pt;padding:0in 0in 0in 4.0pt;margin-left:3.95pt;margin-top:5.0pt;margin-bottom:5.0pt">
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<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">--------
Original Message --------<br>
Subject: Re: [Leish-l] miltefosine for diffuse leishmaniasis<br>
From: Carlos Costa <<a href="mailto:chncosta@gmail.com" target="_blank">chncosta@gmail.com</a>><br>
Date: Sun, July 10, 2011 4:23 pm<br>
To: "Chang, Kwang-Poo" <<a href="http://KwangPoo.Chang@rosalindfranklin.edu" target="_blank">KwangPoo.Chang@rosalindfranklin.edu</a>><br>
Cc: Josh Berman <<a href="mailto:Jbe9320457@aol.com" target="_blank">Jbe9320457@aol.com</a>>,
<a href="mailto:dagobertosilveira@superig.com.br" target="_blank">dagobertosilveira@superig.com.br</a>,<br>
Raimunda Sampaio <<a href="mailto:rsampaio@unb.br" target="_blank">rsampaio@unb.br</a>>,
Dorcas Lamounier Costa<br>
<<a href="http://dorcas.lc@gmail.com" target="_blank">dorcas.lc@gmail.com</a>>, Mark
Nawacki <<a href="mailto:mnawacki@paladinlabs.com" target="_blank">mnawacki@paladinlabs.com</a>>,<br>
<a href="mailto:jurbina@mac.com" target="_blank">jurbina@mac.com</a>, Pierre BUFFET <<a href="mailto:pierre.buffet@upmc.fr" target="_blank">pierre.buffet@upmc.fr</a>>,<br>
<a href="mailto:joseanegodinho@yahoo.com.br" target="_blank">joseanegodinho@yahoo.com.br</a>,
Robert Vinson <<a href="mailto:rvinson@paladinlabs.com" target="_blank">rvinson@paladinlabs.com</a>>,<br>
Shyam Sundarmail <<a href="mailto:Drshyamsundar@hotmail.com" target="_blank">Drshyamsundar@hotmail.com</a>>,<br>
<a href="mailto:robertobadaro768@gmail.com" target="_blank">robertobadaro768@gmail.com</a>,
Leish-L <<a href="mailto:Leish-l@lineu.icb.usp.br" target="_blank">Leish-l@lineu.icb.usp.br</a>>,
Fernando<br>
Koremblum <<a href="mailto:fkorembl@paladinlabs.com" target="_blank">fkorembl@paladinlabs.com</a>><br>
<br>
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<u></u><u></u></span></font></p>
<div>
<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">2011/7/10 Chang,
Kwang-Poo <<a href="mailto:KwangPoo.Chang@rosalindfranklin.edu" target="_blank">KwangPoo.Chang@rosalindfranklin.edu</a>><u></u><u></u></span></font></p>
<div link="blue" vlink="blue">
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<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. </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
<div>
<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.</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
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<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="2" color="navy" face="Arial"><span style="font-size:10.0pt;font-family:Arial;color:navy">KP</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
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<div class="MsoNormal" align="center" style="text-align:center"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black">
<hr size="2" width="100%" align="center">
</span></font></div>
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<p class="MsoNormal"><b><font size="2" color="black" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;color:black;font-weight:bold">From:</span></font></b><font size="2" color="black" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;color:black"> <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><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="2" color="black" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;color:black"><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><u></u><u></u></span></font></p>
</div>
<p class="MsoNormal"><b><font size="2" color="black" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;color:black;font-weight:bold">Subject:</span></font></b><font size="2" color="black" face="Tahoma"><span style="font-size:10.0pt;font-family:Tahoma;color:black"> Re: [Leish-l] miltefosine for diffuse leishmaniasis</span></font><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<div>
<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><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
<div>
<div>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<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><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
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<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><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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</div>
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<div>
<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">Let me summarize some
of the lessons and suggestions. Please correct me if I skip some.</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">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><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">2) BCG - one or two
shots. We will do it. Any hint about the intervals between the shots?</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">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><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><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></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">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><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">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><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">b) gamma-interferon
(who produces/sells it?).</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">c)
fluconazol/itraconazol/(voriconazol?).</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">d) amiodarone - <i><span style="font-style:italic">in vitro</span></i> testing does not sounds so good.</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
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<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">e) topic imiquimod
(IxiumTM cream) - apparently easy to find. concentration of 5%?</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">f) photodynamic
therapy - with Dr. Dagoberto Silveira, we are investigating where to do it
around.</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">g) immunotherapy with
suicide photo-inactivated <i><span style="font-style:italic">Leishmania</span></i>
(KP Chang).</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">Please check what
really seems reasonable. My feeling is that most of the suggestions can be
tried.</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">My warmest regards,</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="5" color="black" face="Verdana"><span style="font-size:18.0pt;font-family:Verdana;color:black">Carlos.</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black">2011/7/8 Pierre BUFFET <<a href="mailto:pierre.buffet@upmc.fr" target="_blank">pierre.buffet@upmc.fr</a>></span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black">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 :</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<div>
<blockquote style="border:none;border-left:solid windowtext 1.0pt;padding:0in 0in 0in 6.0pt;margin-left:4.8pt;margin-top:5.0pt;margin-right:0in;margin-bottom:5.0pt;border-color:-moz-use-text-color -moz-use-text-color -moz-use-text-color rgb(204, 204, 204)">
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<div style="margin-bottom:12.0pt">
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black">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:</span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black">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>
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<p class="MsoNormal" style="margin-bottom:12.0pt"><font size="3" color="black" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;color:black"><u></u> <u></u></span></font></p>
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"><br>
<br clear="all">
<br>
-- <br>
</span></font><b><font color="black" face="Verdana"><span style="font-family:Verdana;color:black;font-weight:bold">Carlos H. N. Costa, MD, DSc.</span></font></b><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><b><font size="3" color="black" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;color:black;font-weight:bold">President</span></font></b><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><b><font size="3" color="black" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;color:black;font-weight:bold">Sociedade
Brasileira de Medicina Tropical </span></font></b><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><b><font size="3" color="black" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;color:black;font-weight:bold">(Brazilian
Society of Tropical Medicine)</span></font></b><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><b><font size="3" color="black" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;color:black;font-weight:bold">Instituto
de Doenças Tropicais Natan Portella<br>
Universidade Federal do Piauí</span></font></b><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
<div>
<div>
<p class="MsoNormal"><b><font size="3" color="black" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;color:black;font-weight:bold">Rua
Artur de Vasconcelos 151-Sul</span></font></b><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
</div>
<div>
<div>
<p class="MsoNormal"><b><font size="3" color="black" face="Verdana"><span style="font-size:12.0pt;font-family:Verdana;color:black;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 color="black" face="Verdana"><span style="font-family:Verdana;color:black"><br>
</span></font><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">Aviso: As informações contidas nesta
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<p class="MsoNormal"><font size="3" color="black" face="Times New Roman"><span style="font-size:12.0pt;color:black"> </span></font><font color="black" face="Verdana"><span style="font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><br>
<br clear="all">
<br>
-- <br>
<b><span style="font-weight:bold">Carlos H. N. Costa, MD, DSc.</span></b><u></u><u></u></span></font></p>
<div>
<p class="MsoNormal"><b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black;font-weight:bold">President</span></font></b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u><u></u></span></font></p>
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<p class="MsoNormal"><b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black;font-weight:bold">Sociedade
Brasileira de Medicina Tropical </span></font></b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black;font-weight:bold">(Brazilian
Society of Tropical Medicine)</span></font></b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black;font-weight:bold">Instituto
de Doenças Tropicais Natan Portella<br>
Universidade Federal do Piauí</span></font></b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u><u></u></span></font></p>
<div>
<p class="MsoNormal"><b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black;font-weight:bold">Rua
Artur de Vasconcelos 151-Sul</span></font></b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u><u></u></span></font></p>
</div>
<div>
<p class="MsoNormal"><b><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black;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 size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><br>
Aviso: As informações contidas nesta mensagem são CONFIDENCIAIS, protegidas
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<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black"><u></u> <u></u></span></font></p>
<div class="MsoNormal" align="center" style="text-align:center"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">
<hr size="2" width="100%" align="center">
</span></font></div>
<p class="MsoNormal"><font size="2" color="black" face="Verdana"><span style="font-size:10.0pt;font-family:Verdana;color:black">_______________________________________________<br>
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</blockquote>
</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>
</b><br><span style="font-size:x-small">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>
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