[Leish-l] miltefosine for diffuse leishmaniasis

[Hannah Akuffo]

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<mailto: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