[Leish-l] Fwd: PRO/EDR> Leishmaniasis - India: miltefosine resistance

[jeffreyj at usp.br]

De: < promed at promedmail.org > 

> Data: domingo, 25 de outubro de 2015
> Assunto: PRO/EDR> Leishmaniasis - India: miltefosine resistance
> Para: promed-post at promedmail.org , promed-edr-post at promedmail.org

> LEISHMANIASIS - INDIA: MILTEFOSINE RESISTANCE
> *********************************************
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> Date: Thu 22 Oct 2015
> Source: Medical Xpress [edited]
> <
> http://medicalxpress.com/news/2015-10-resistance-drug-treatment-tropical-skin.html
> >

> Cutaneous leishmaniasis [CL] is an ulcerous skin disease caused by a
> tropical parasite [_Leishmania_ spp.], all forms of which can be
> treated with the drug miltefosine.

> Researchers from the National Institute of Pathology, Indian Council
> of Medical Research and Safdarjung Hospital in Delhi studied the
> responses of 86 patients treated with miltefosine over 18 months,
> which indicated a developing parasitic resistance to the drug,
> supporting a growing evidence base showing the rise of miltefosine
> resistance.

> The researchers studied 86 patients, all confirmed to have post
> kala-azar dermal leishmaniasis. Patients were initially treated with
> 50 mg 3 times daily for 60 days; however, some patients suffered
> gastrointestinal side-effects and were changed to a dose of 50 mg of
> miltefosine twice daily for 90 days. Due to the side effects, all
> patients from 2011 onwards were initiated onto this 2nd regime. The
> patients were followed for 18 months post-treatment and assessed
> monthly via a clinical and histopathological examination.

> 73 patients successfully completed the treatment and were cured. Four
> percent of patients suffered relapse in the 1st 12 months after
> treatment, while 15 percent relapsed in the 18 months following
> treatment, with a higher relapse rate seen in patients on the 60-day
> treatment regimen compared with the 90-day regimen. The number of
> parasites pre-treatment was found to be higher in the patients who
> later suffered a relapse.

> In 6 of the relapsed cases, the researchers tested the susceptibility
> of the parasites to miltefosine post-relapse and compared this with
> susceptibility of parasites pre-treatment. Following the relapse,
> parasites were shown to have significantly reduced sensitivity to the
> treatment, suggesting the development of resistance.

> Although all the patients in the study were cured through the use of
> miltefosine, the rate of relapse, along with the reduced drug
> susceptibility of the parasites following relapse, indicates that the
> development of drug resistance is a major concern. This indicates a
> pressing need for the development of new therapies or co-therapies to
> ensure the continued effective treatment of all forms of
> leishmaniasis.

> --
> Communicated by:
> ProMED-mail
> < promed at promedmail.org >

> [The study referred to in the text is: Ramesh V et al. Decline in
> Clinical Efficacy of Oral Miltefosine in Treatment of Post Kala-azar
> Dermal Leishmaniasis (PKDL) in India. PLoS Negl Trop Dis.
> 2015;9(10):e0004093.

> PKDL develops up to several years after treatment of visceral
> leishmaniasis and leishmania parasites can be found in the cutaneous
> lesions in PKDL. PKDL develops in 5-15 percent of treated kala-azar
> case-patients in India (Salotra & Singh. Challenges in the diagnosis
> of post kala-azar dermal leishmaniasis. Indian J Med Res.
> 2006;123:295-310), and in up to 50 percent of cases in the Sudan
> (Zijlstra & el-Hassan. Leishmaniasis in Sudan. Post kala-azar dermal
> leishmaniasis. Trans R Soc Trop Med Hyg. 2001;95(Suppl 1):S59-76).

> Miltefosine is usually used for treatment of cutaneous leishmaniasis
> and has recently been reported to be less effective against visceral
> leishmaniasis (Monge-Maillo & Lopez-Velez; Miltefosine for visceral
> and cutaneous leishmaniasis: drug characteristics and evidence-based
> treatment recommendations. Clin Infect Dis. 2015;60:1398-404). This
> is
> certainly a concern, as miltefosine is the only oral drug available
> for treatment of leishmaniasis. If resistance against miltefosine is
> developing as suggested in these studies, a rational strategy to
> prevent it could be not to use miltefosine as single drug but combine
> it with at least one other anti-leishmania drug. - Mod.EP

> A HealthMap/ProMED-mail map can be accessed at:
> < http://healthmap.org/promed/p/142 >.]

> [See Also:
> 2013
> ----
> Leishmaniasis - India (02): (JK): 20130910.1935488
> Leishmaniasis - India: (KL): 20130303.1568442
> 2012
> ----
> Leishmaniasis, visceral - India: (BR): 20120725.1214743
> 2011
> ----
> Leishmaniasis, visceral - India 20111007.3015
> 2008
> ----
> Leishmaniasis, visceral - India: RFI 20080928.3075
> Leishmaniasis, visceral - India: (Assam), susp., RFI 20080223.0736
> 2007
> ----
> Leishmaniasis, visceral - India (Mumbai) 20070430.1400
> 2004
> ----
> Leishmaniasis - India (Bihar) (02) 20040526.1418
> Leishmaniasis - Pakistan & India: background 20040201.0392
> Leishmaniasis - India (Andhra Pradesh) 20040124.0288
> Leishmaniasis - India (Bihar) (02): vectors 20040115.0167
> Leishmaniasis - India (Bihar) 20040114.0156
> 2000
> ----
> Leishmaniasis - India (Calcutta) (02) 20001026.1858
> Leishmaniasis - India (Calcutta) 20001022.1830]
> .................................................sb/ep/msp/dk
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