[Leish-l] : Re: miltefosine for diffuse leishmaniasis

Carlos Costa chncosta at gmail.com
Tue Jul 12 21:10:26 BRT 2011


Dear Gerlind,

I took a very fast look in PubMed in respect to the use of Rifampicin in CL.
Data shows an apparent advantage, but not something to be used alone. But in
a desperate situation it may be worthy to try.

One of your comment specially called my attention: the prolonged use of
miltefosine in VL HIV patients. If so, they had not developed resistance,
which is quite different from DCL. Again, is parasite playing a role? Does
L. amazonensis has a peculiar system to develop drug resistance?

Although treatment with miltefosine would lead to resistance, it is worthy
to try and see if new lesions do not develop in such a severity.

Kind regards,

Carlos.

2011/7/12 Gerlind Anders <Gerlind.Anders at gmx.net>

>
> Dea All,
>
> From my memories when I was in charge of Clinical trials with Miltefosine
> during 2005-2007 at Aeternazentaris in Germany:
>
> Nephrotoxicity was dose dependent (in early dose escalation studies).
> During Ph III-IV: elevated Creatinine (up to CTC-toxicity grade 3) values
> were reversible in nearly all cases. There was a case with accidental severe
> overdose, leaing to an irreversible damage.
> Nephrotoxicity during treatment was usually related to dehydration after
> vomiting and episodes of diarrhoea. After rehydration values normalized.
>
> It was common that VL patients started off with elevated creatinine levels
> which did normalize under effective miltefosine therapy.
>
> There were a number of individual examples of HIV/AIDS patients receiveing
> Miltefosine continuously for years without any kidney problems. (though at
> VL dosage, not CL dosage, data not pblished).
>
> I do not remmember the mechanism, this is in the preclinical/ toxicology
> records of the drug, to which there is hopefully some access via the current
> company(?).
>
> I think Shyam Sundar has the best overview on the real nephrotoxic
> potential over many years in thousands of patients, and he may want to
> comment.
>
> DCL: Miltefosine will most certainly give relief for 2-4 months but then
> its failure is nearly certain as well. (Sad to say, unless combined almost
> not worth trying).
>
> I think, but I am not sure, that DNDi has data on combination therapy
> toxicology (animal models).
>
> This is really a desparate case, and I am wondering whether Thalidomid is
> worth trying? (Not a nice drug, but also not sufficiently tested for this
> indication I think).
>
> There must be also patients (in East Africa/ India?) receiving
> Tuberculostatics eg. (Rifampicin) plus antileishmanial drugs, any clinical
> toxicity known from these combinations?
>
> Best regards,
> Gerlind Anders
>
>
>
>
>
>
> -------- Original-Nachricht --------
> > Datum: Mon, 11 Jul 2011 17:19:47 -0300
> > Von: Carlos Costa <chncosta at gmail.com>
> > An: jaime.soto at prodderma.com
> > CC: Leish-L <Leish-l at lineu.icb.usp.br>
> > Betreff: Re: [Leish-l] SPAM-LOW: Re:  miltefosine for diffuse
> leishmaniasis
>
> > Thanks, Jaime.
> >
> > From your review the drug is not eliminated by the kidneys, so there is
> no
> > need for dose adjustment. But we should be very careful with kidney
> > functions.
> >
> > Is there any information on the mechanism of renal lesion? Tubular?
> >
> > Best regards,
> >
> > Carlos.
> >
> > 2011/7/11 Jaime Soto <jaime.soto at prodderma.com>
> >
> > > Dear all,****
> > >
> > > ** **
> > >
> > > I received some days ago a specific question regarding miltefosine use
> > in
> > > patients with renal impairment. I delay my answer asking to other
> people
> > > because this is not an easy answer; this is the conclusion:****
> > >
> > > ** **
> > >
> > > “Miltefosine is mildly nephrotoxic [Soto. CID 2004; 38:1266–72] in
> > > leishmaniasis patients with normal renal function, Whether or not
> > > miltefosine would further diminish renal function in renally-impaired
> > > patients is not known. If renal function is already very low, however,
> a
> > > further effect on renal function might not be seen. ****
> > >
> > > ** **
> > >
> > > My personal view would be to not lower dosing because of a possible
> > adverse
> > > effect on the kidneys, specially because, in the specific case, full
> > dose
> > > could mean the difference between improving and failure.****
> > >
> > > ** **
> > >
> > > Regards from Bolivia,****
> > >
> > > ** **
> > >
> > > Jaime soto ****
> > >
> > >  ****
> > >
> > > ** **
> > >
> > > *De:* leish-l-bounces at lineu.icb.usp.br [mailto:
> > > leish-l-bounces at lineu.icb.usp.br] *En nombre de *Carlos Costa
> > > *Enviado el:* domingo, 10 de julio de 2011 05:44 p.m.
> > > *Para:* Jennie Blackwell
> > > *CC:* Leish-L
> > > *Asunto:* SPAM-LOW: Re: [Leish-l] miltefosine for diffuse
> > leishmaniasis***
> > > *
> > >
> > > ** **
> > >
> > > Hi Jennie,****
> > >
> > > ** **
> > >
> > > Thanks for the drug information. Now, I have to check the permission
> for
> > > its use in Brazil and how to justify its use to the public system in
> > order
> > > to be acquired by the government. Meanwhile, we are looking for
> > miltefosine,
> > > paramomycin, and alternative therapies.****
> > >
> > > ** **
> > >
> > > But if the immunosuppression is species specific do you think that a
> > > general stimulation would reverse it? Does anyone knows which is the
> > > mechanism behind the DCL induced immunosuppression? Parasite or host or
> > > both? ****
> > >
> > > ** **
> > >
> > > Cheers,****
> > >
> > > ** **
> > >
> > > Carlos.****
> > >
> > > 2011/7/7 Jennie Blackwell <jmb37 at cam.ac.uk>****
> > >
> > > Hello Carlos****
> > >
> > > ** **
> > >
> > > My memory from late 80s was that these patients responded well to
> > > interferon-gamma treatment. With all the moves to make drugs more
> > affordable
> > > for disease endemic countries, has it not been possible to consider
> this
> > > option?****
> > >
> > > ** **
> > >
> > > In psoriasis they use creams with Vitamin D. Has anyone ever tried this
> > for
> > > DCL?****
> > >
> > > ** **
> > >
> > > I'm sure this is going to elicit a round of responses - but you know
> I'm
> > > not a clinician so I would just be interested to know!****
> > >
> > > ** **
> > >
> > > Cheers, Jennie
> > >
> > > Jenefer M. Blackwell****
> > >
> > > TICHR, CCHR, UWA****
> > >
> > > Phone: +61 8 94897910****
> > >
> > > From my iPhone****
> > >
> > >
> > > On 07/07/2011, at 3:04, Carlos Costa <chncosta at gmail.com> wrote:****
> > >
> > > Dear all,****
> > >
> > > ** **
> > >
> > > 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 Maranhão State, Brazil, 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 Teresina.****
> > >
> > > ** **
> > >
> > > 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).****
> > >
> > > ** **
> > >
> > > Our hope now stands only in miltefosine, for oral chronic use, but the
> > drug
> > > is not licensed or available in Brazil yet (to my knowledge).****
> > >
> > > ** **
> > >
> > > 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 Brazil (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.****
> > >
> > > ** **
> > >
> > > 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.****
> > >
> > > ** **
> > >
> > > Hoping a little from friends, my kindest regards,****
> > >
> > > ** **
> > >
> > > Carlos.****
> > >
> > > ** **
> > >
> > > PS. Please understand that the pictures are allowed not for publication
> > or
> > > public presentation. Cleudimar permission is restricted to this
> > forum.****
> > >
> > > ** **
> > >
> > >
> > > --
> > > *Carlos H. N. Costa, MD, DSc.*****
> > >
> > > *President*****
> > >
> > > *Sociedade Brasileira de Medicina Tropical *****
> > >
> > > *(Brazilian Society of Tropical Medicine)*****
> > >
> > > *Instituto de Doenças Tropicais Natan Portella
> > > Universidade Federal do Piauí*****
> > >
> > > *Rua Artur de Vasconcelos 151-Sul*****
> > >
> > > *64049-750 Teresina-PI
> > > Brazil
> > > Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).
> > > *
> > > 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.
> > > 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. ****
> > >
> > > ** **
> > >
> > > <cleu antes grav 13jan09.jpg>****
> > >
> > > <cleu e nene.jpg>****
> > >
> > > <cleu santada recorte.jpg>****
> > >
> > > <cleu panturrilhas.jpg>****
> > >
> > > <cleu palato.jpg>****
> > >
> > > _______________________________________________
> > > Leish-l mailing list
> > > Leish-l at lineu.icb.usp.br
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> > >
> > >
> > >
> > >
> > > --
> > > *Carlos H. N. Costa, MD, DSc.*****
> > >
> > > *President*****
> > >
> > > *Sociedade Brasileira de Medicina Tropical *****
> > >
> > > *(Brazilian Society of Tropical Medicine)*****
> > >
> > > *Instituto de Doenças Tropicais Natan Portella
> > > Universidade Federal do Piauí*****
> > >
> > > *Rua Artur de Vasconcelos 151-Sul*****
> > >
> > > *64049-750 Teresina-PI
> > > Brazil
> > > Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).
> > > *
> > > 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.
> > > 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. ****
> > >
> > > ** **
> > >
> > > ** **
> > >
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> >
> > --
> > *Carlos H. N. Costa, MD, DSc.*
> > *President*
> > *Sociedade Brasileira de Medicina Tropical *
> > ***(Brazilian Society of Tropical Medicine)*
> > *Instituto de Doenças Tropicais Natan Portella
> > Universidade Federal do Piauí*
> > *Rua Artur de Vasconcelos 151-Sul*
> > *64049-750 Teresina-PI
> > Brazil
> > Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).
> > *
> > 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.
> > 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.
>
> --
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-- 
*Carlos H. N. Costa, MD, DSc.*
*President*
*Sociedade Brasileira de Medicina Tropical *
***(Brazilian Society of Tropical Medicine)*
*Instituto de Doenças Tropicais Natan Portella
Universidade Federal do Piauí*
*Rua Artur de Vasconcelos 151-Sul*
*64049-750 Teresina-PI
Brazil
Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).
*
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.
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.
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