Miltefosine, an Oral Agent, for the Treatment of Indian Visceral Leishmaniasis

Jha, T K; Sundar, Shyam; Thakur, C.P.; Bachmann, Peter; Karbwang, Juntra; Fischer, Christina; Voß, Andreas; Berman, Jonathan

doi:10.1056/nejm199912093412403

Cited by 410 publications

(280 citation statements)

References 19 publications

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“…Combinations of SSG and paromomycin have shown to be efficient and safe in India , Sudan (Seaman et al, 1993), and Kenya (Chunge et al, 1990) but paramomycin has yet to be registered for VL treatment and its future production and cost remain unclear. Other possible combinations could include in future trials conventional or liposomal amphotericin B as well as miltefosine, an oral drug showed to be very efficient in India when used alone for 4 weeks (Jha et al, 1999;Sundar et al, 2000b). Miltefosine was registered for the treatment of VL in India in 2002 and a phase IV trial will take place in India and Nepal in the coming year.…”

Section: Discussionmentioning

confidence: 99%

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

Rijal

Chappuis

Singh

et al. 2003

Transactions of the Royal Society of Tropical Medicine and Hygi

114

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Sodium stibogluconate (SSG) is the first-line therapy for visceral leishmaniasis (VL) in south-eastern Nepal. Recent studies from the neighbouring state of Bihar, India, have shown a dramatic fall in cure rates with treatment failure occurring in up to 65% of VL patients treated with SSG. A prospective study was conducted at a tertiary-level hospital located in south-eastern Nepal from July 1999 to January 2001. Parasitologically proven kala-azar patients with no previous history of treatment for VL were treated with SSG 20 mg/kg/d for 30 d which was extended to 40 d in those with persistent positive parasitology. Of the 110 patients who completed SSG therapy and were assessed at 1 and 6 months, definite cure was achieved in 99 patients (90%) and SSG failure occurred in 11 patients (10%). Except for the presence of hepatomegaly and a lower platelet count there was no clinical or laboratory baseline characteristic associated with treatment failure. A significantly lower cure rate (76%, P= 0.03) was observed in patients from the district of Saptari, which borders the antimony-resistant VL areas of Bihar. The efficacy of SSG as a first-line treatment for VL in south-eastern Nepal was still satisfactory, except for the patients living closer to the antimony-resistant VL areas of India. These findings indicate that the spread of resistance to antimonials is already taking place in Nepal and that a policy to control further spread should be urgently implemented.

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Section: Discussionmentioning

confidence: 99%

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

Rijal

Chappuis

Singh

et al. 2003

Transactions of the Royal Society of Tropical Medicine and Hygi

114

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“…Hexadecylphosphocholine (miltefosine; Miltex), one of the first of this class to undergo clinical evaluation, had evidence of immunomodulatory and antitumor activity in model systems (1)(2)(3). Although low oral bioavailability, gastrointestinal, and hemolytic toxicities limited its clinical development as an anticancer agent, it is approved for use in Europe for topical treatment of cutaneous lymphomas and breast cancer metastases (4) and has activity against visceral leishmaniasis despite low oral absorption (5).…”

Section: Introductionmentioning

confidence: 99%

In vitro Combination Treatment with Perifosine and UCN-01 Demonstrates Synergism against Prostate (PC-3) and Lung (A549) Epithelial Adenocarcinoma Cell Lines

Dasmahapatra¹,

Didolkar²,

Alley

et al. 2004

Clinical Cancer Research

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Purpose: Antineoplastic agents often achieve antitumor activity at the expense of close to unacceptable toxicity. One potential avenue to improve therapeutic index might combine agents targeting distinct components of the same growth regulatory pathway. This might lead to more complete modulation of the target pathway at concentrations lower than those associated with limiting adventitious toxicities from either agent alone.

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“…Within 12 As skin lesions were also gaining size, treatment with miltefosine, a phosphocholine analog that has proven successful in treating visceral leishmaniasis (6) and is highly effective against acanthamoebae in vitro (7,8), was initiated topically as a solution, 60 mg/mL, 1 drop applied directly to each skin lesion 2 times a day. After dramatic improvements of the skin lesions were observed within only 3 weeks (Figure 1, panel C), our patient began peroral miltefosine 100 mg/day (2.5 mg/kg); all other drugs except the tuberculostatic 5-drug regimen were stopped.…”

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confidence: 99%

Successful Treatment of DisseminatedAcanthamoebasp. Infection with Miltefosine

Aichelburg¹,

Walochnik²,

Assadian³

et al. 2008

Emerg. Infect. Dis.

107

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We report on an HIV-negative but immunocompromised patient with disseminated acanthamoebiasis, granulomatous, amoebic encephalitis, and underlying miliary tuberculosis and tuberculous meningitis. The patient responded favorably to treatment with miltefosine, an alkylphosphocholine. The patient remained well with no signs of infection 2 years after treatment cessation.A 25-year-old man from India, who had been living in Austria for 7 years and had no previous history of major illnesses, was brought by ambulance to the hospital for dyspnea, cough, fever, and weight loss. During neurologic examination, a hearing impairment was suspected. The patient was unable to walk because of severe ataxia. Skin examination showed several necrotic ulcers with purulent discharge and black eschars, measuring 0.5 cm to 3 cm, located on the skull, back, neck, and arms ( Figure 1, panels A and B). Miliary tuberculosis (TB) of the lungs, liver, spleen, and kidneys was suspected on the basis of chest radiography and computed tomography (CT) of chest and abdomen. Ziehl-Nielsen (ZN) staining for acid-fast bacilli in sputum, bronchial secretions, and lavage obtained through bronchoscopy was negative. PCR for Mycobacterium tuberculosis in bronchial secretions and serum was positive. Culture on Loewenstein agar resulted in growth of nonresistant M. tuberculosis after 31 days. Blood cultures were negative for aerobic/anaerobic bacteria, mycobacteria, and fungi. Results of serologic tests were negative for Aspergillus, Candida, Cryptococcus, Histoplasma, Blastomyces, and Coccidioides spp. Severe immunosuppression with a CD4+ lymphocyte count of 182 cells/μL made HIV infection probable, but HIV testing results were negative. Cranial CT showed multiple small enhancing lesions in cerebral cortex and underlying white matter, pons, midbrain, and around most of the cisterns. On magnetic resonance imaging (MRI), the lesions appeared as high T2 signal areas that enhanced heterogeneously or in a ringlike manner. These fi ndings were compatible with the diagnosis of meningoencephalitis with intracerebellar abscess formation.Cerebrospinal fl uid (CSF) obtained through lumbar puncture was negative for Toxoplasma gondii, Encephalitozoon cuniculi, and Enterocytozoon bieneusi by PCR and for Trypanosoma gambiense by indirect hemagglutination assay. Staining and antigen testing (enzyme immunoassay) for Cryptococcus neoformans was negative, as was Treponema pallidum antibody testing. No viruses (herpes simplex 1 and 2, varicella zoster, enterovirus) could be detected by PCR. Cultures were negative for aerobic/ anaerobic bacteria and fungi. ZN staining detected acid-fast bacilli that were confi rmed to be nonresistant M. tuberculosis after culture for 38 days. PCR for M. tuberculosis was positive. An Acanthamoeba-specifi c PCR (1) and DNA sequencing of the PCR product showed Acanthamoeba genotype T2 (corresponding to group III). High immunoglobulin (Ig) G (2,000) and IgM (1,000) titers against Acanthamoeba spp. could be demonstrated serologically. The organism ...

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Miltefosine, an Oral Agent, for the Treatment of Indian Visceral Leishmaniasis

Abstract: Orally administered miltefosine appears to be an effective treatment for Indian visceral leishmaniasis.

Cited by 410 publications

References 19 publications

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

In vitro Combination Treatment with Perifosine and UCN-01 Demonstrates Synergism against Prostate (PC-3) and Lung (A549) Epithelial Adenocarcinoma Cell Lines

Successful Treatment of DisseminatedAcanthamoebasp. Infection with Miltefosine

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