[Leish-l] miltefosine for diffuse leishmaniasis
Pierre BUFFET
pierre.buffet at upmc.fr
Fri Jul 8 16:37:23 BRT 2011
Anthony,
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 Ethiopia 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 ?
Pierre
Anthony Bryceson <a.bryceson at doctors.org.uk> a écrit :
> Dear Carlos
> 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.
>
> 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.
>
> Hannah Akuffo has sent you the abstract relating to 3 patients
> treated by Sabawork Teklemariam in Addis Abeba. That article details
> this approach.
>
> 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.
>
> 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.
> 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.
>
> In a few patients with VL-HIV confection whom I treated in London,
> 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.
>
> 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.
>
> Robert Vinson is CEO of Paladin Labs, and would I am sure help you
> locate miltefosine. <rvinson at paladin-labs.com>
>
> Richard Chin is CEO of One World Health, and would, I am equally
> sure, help you locate paromomycin, should you consider that path.
> http://www.oneworldhealth.org/contact-us Phone: +1 415-421-4700
> Fax: +1 415-421-4747
>
> I wish you and Maria all the best in this venture.
> Anthony
>
>
> Dear Jennie
> 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.
> Sadly
> Anthony
>
>
> On 6 Jul 2011, at 20:04, Carlos Costa 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).
>>
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