[Leish-l] miltefosine for diffuse leishmaniasis

Tue Jul 12 08:05:48 BRT 2011

Dear Hannah,

May be the genetic differences between organisms inducers/non-inducers of
diffuse disease can be as discrete as one single SNP, in such a way that
only through sequencing we would detect it. The questions is: to sequence
the whole genome or to make a bet in certain genes?

Another point is if the diffuse disease caused by L. amazonensis and L.
aethiopica have the same underlying parasite mechanisms. Again, comparative
genomics of isolates of both species can give more hints.

I agree with you that both hosts and parasites contribute to the outcome,
but modern genomics is bringing so many new secrets of Leishmania that its
role will be seen as more important soon.

Your findings are very interesting. Do you have the pdf? Please check the
recent excellent paper of Cortez et al, 2011, right in the target.

My best regards, extended to Jennie,

Carlos.

2011/7/12 Hannah Akuffo <Hannah.Akuffo at sida.se>

>  Dear Carlos,****
>
> As with so many things the answer is more like “both” Parasite and host.
> There are proponents for the host being the most relevant and others for the
> parasite also playing a role.****
>
> ** **
>
> When it comes to *L. aethiopica* induced DCL my colleagues and I have done
> a series of laboratory studies that suggest that the parasite that causes
> DCL and that which causes LCL, induce different responses (cytokines,
> proliferation etc) *in vitro*. (example of publications *Akuffo HO,
> Fehniger TE, Britton S. Differential recognition of Leishmania aethiopica
> antigens by lymphocytes from patients with local and diffuse cutaneous
> leishmaniasis. Evidence for antigen-induced immune suppression. J Immunol.
> 1988 Oct 1;141(7):2461-6*. AND *Akuffo H, Maasho K, Blostedt M, Hojeberg
> B, Britton S, Bakhiet M. Leishmania aethiopica derived from diffuse
> leishmaniasis patients preferentially induce mRNA for interleukin-10 while
> those from localized leishmaniasis patients induce interferon-gamma. J
> Infect Dis. 1997 Mar;175(3):737-41*) Whether this is because the infecting
> organism is different or there are changes that occur in the parasite when
> they are in the host for some time, has not been studied.  However we have
> not been able to find genetic differences in the organisms derived from DCL
> versus those derived from LCL. (example of publication *Schönian G, Akuffo
> H, Lewin S, Maasho K, Nylén S, Pratlong F, Eisenberger CL, Schnur LF,
> Presber W. Genetic variability within the species Leishmania aethiopica does
> not correlate with clinical variations of cutaneous leishmaniasis. Mol
> Biochem Parasitol. 2000 Mar 5;106(2):239-48* ). ****
>
> ** **
>
> As we know, the low or non-existent cellular immune response in DCL is
> antigen specific but in a very small study we did show that the use of
> intra-lesional IL-2 did stimulate the local immune response and reduce the
> number of amstigotes (*Akuffo H, Kaplan G, Kiessling R, Teklemariam S,
> Dietz M, McElrath J, Cohn ZA. Administration of recombinant interleukin-2
> reduces the local parasite load of patients with disseminated cutaneous
> leishmaniasis. J Infect Dis. 1990 Apr;161(4):775-80*). ****
>
> ** **
>
> I hope this information sheds some light on your question to Jennie. There
> is so much more to understand about DCL.****
>
> Best regards****
>
> Hannah Akuffo****
>
> ** **
>
> ** **
>
> *From:* leish-l-bounces at lineu.icb.usp.br [mailto:
> leish-l-bounces at lineu.icb.usp.br] *On Behalf Of *Carlos Costa
> *Sent:* den 10 juli 2011 23:44
> *To:* Jennie Blackwell
> *Cc:* Leish-L
>
> *Subject:* 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
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>
> ** **
>
>    <cleu antes grav 13jan09.jpg>****
>
>  <cleu e nene.jpg>****
>
>  <cleu santada recorte.jpg>****
>
>  <cleu panturrilhas.jpg>****
>
>  <cleu palato.jpg>****
>
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> 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. ****
>
> ** **
>

-- 
*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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