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-
1.
Alvar J, Velez ID, Herrero M, Desjeux P, Cano J, Janin J, den Boer M; WHO Leishmaniasis Control Team, 2012. Leishmaniasis worldwide and global estimates of its incidence. PLoS ONE 7: e35671.
-
2.
Guerin PJ, Olliaro P, Sundar S, Boelaert M, Croft SL, Desjeux P, Wasunna MK, Bryceson AD, 2002. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis 2: 494–501.
-
3.
Joshi A, Narain JP, Prasittisuk C, Bhatia R, Hashim G, Jorge A, Banjara M, Kroeger A, 2008. Can visceral leishmaniasis be eliminated from Asia? J Vector Borne Dis 45: 105–111.
-
4.
WHO, 2005. Expert Committee on Regional Strategic Framework for Elimination of Kala-azar from the South-East Asia Region (2005–2015). New Delhi: WHO regional Office for South-East Asia.
-
5.
Prajapati VK, Awasthi K, Gautam S, Yadav TP, Rai M, Srivastava ON, Sundar S, 2011. Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes. J Antimicrob Chemother 66: 874–879.
-
6.
Sundar S, Jha TK, Thakur CP, Engel J, Sindermann H, Fischer C, Junge K, Bryceson A, Berman J, 2002. Oral miltefosine for Indian visceral leishmaniasis. N Engl J Med 347: 1739–1746.
-
7.
Jha TK, Sundar S, Thakur CP, Bachmann P, Karbwang J, Fischer C, Voss A, Berman J, 1999. Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis. N Engl J Med 341: 1795–1800.
-
8.
Sundar S, Singh A, Rai M, Prajapati VK, Singh AK, Ostyn B, Boelaert M, Dujardin JC, Chakravarty J, 2012. Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use. Clin Infect Dis 55: 543–550.
-
9.
Rijal S, Ostyn B, Uranw S, Rai K, Bhattarai NR, Dorlo TP, Beijnen JH, Vanaerschot M, Decuypere S, Dhakal SS, Das ML, Karki P, Singh R, Boelaert M, Dujardin JC, 2013. Increasing failure of Miltefosine in the treatment of kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance. Clin Infect Dis 56: 1530–1538.
-
10.
Kumar D, Kulshrestha A, Singh R, Salotra P, 2009. In vitro susceptibility of field isolates of Leishmania donovani to Miltefosine and amphotericin B: correlation with sodium antimony gluconate susceptibility and implications for treatment in areas of endemicity. Antimicrob Agents Chemother 53: 835–838.
-
11.
Prajapati VK, Mehrotra S, Gautam S, Rai M, Sundar S, 2012. In vitro antileishmanial drug susceptibility of clinical isolates from patients with Indian visceral leishmaniasis–status of newly introduced drugs. Am J Trop Med Hyg 87: 655–657.
-
12.
Kulshrestha A, Bhandari V, Mukhopadhyay R, Ramesh V, Sundar S, Maes L, Dujardin JC, Roy S, Salotra P, 2013. Validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of Leishmania donovani. Parasitol Res 112: 825–828.
-
13.
Maurya R, Mehrotra S, Prajapati VK, Nylen S, Sacks D, Sundar S, 2010. Evaluation of blood agar microtiter plates for culturing Leishmania parasites to titrate parasite burden in spleen and peripheral blood of patients with visceral leishmaniasis. J Clin Microbiol 48: 1932–1934.
-
14.
Srivastava P, Prajapati VK, Vanaerschot M, Van der Auwera G, Dujardin JC, Sundar S, 2010. Detection of Leptomonas sp. parasites in clinical isolates of Kala-azar patients from India. Infect Genet Evol 10: 1145–1150.
-
15.
Bhandari V, Kulshrestha A, Deep DK, Stark O, Prajapati VK, Ramesh V, Sundar S, Schonian G, Dujardin JC, Salotra P, 2012. Drug susceptibility in Leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis. PLoS Negl Trop Dis 6: e1657.
-
16.
Leprohon P, Legare D, Raymond F, Madore E, Hardiman G, Corbeil J, Ouellette M, 2009. Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum. Nucleic Acids Res 37: 1387–1399.
| Past two years | Past Year | Past 30 Days | |
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| Abstract Views | 31 | 31 | 5 |
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In vitro Susceptibility of Leishmania donovani to Miltefosine in Indian Visceral Leishmaniasis
Vijay Kumar Prajapati
Vijay Kumar Prajapati
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP, India; Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium; National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India; Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium
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Smriti Sharma
Smriti Sharma
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP, India; Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium; National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India; Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium
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Madhukar Rai
Madhukar Rai
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP, India; Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium; National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India; Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium
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Bart Ostyn
Bart Ostyn
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP, India; Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium; National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India; Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium
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Poonam Salotra
Poonam Salotra
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP, India; Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium; National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India; Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium
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Manu Vanaerschot
Manu Vanaerschot
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP, India; Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium; National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India; Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium
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Jean-Claude Dujardin
Jean-Claude Dujardin
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP, India; Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium; National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India; Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium
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Shyam Sundar
Shyam Sundar
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP, India; Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium; National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India; Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium
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Promastigote miltefosine (MIL) susceptibility was performed on Leishmania donovani isolates from Indian patients with visceral leishmaniasis treated with MIL. Isolates that were obtained before the onset of MIL treatment, after completion of treatment (29th day), or at the time of treatment failure, were screened using in vitro promastigote assay. The MIL susceptibility of the pre-treatment isolates (N = 24, mean IC50 ± SEM = 3.74 ± 0.38 μM) was significantly higher than that of the post-treatment group (N = 26, mean IC50 ± SEM = 6.15 ± 0.52 μM; P = 0.0006) but was similar in the cured patients (N = 22, mean IC50 ± SEM = 5.58 ± 0.56 μM) and those who failed treatment (N = 28, mean IC50 ± SEM = 4.53 ± 0.47 μM). The pre/post-treatment results thus showed a 2-fold difference, whereas isolated from cured versus failed patients showed a similar susceptibility, suggesting that this higher tolerance is not responsible for MIL-treatment failure. Our work highlights the need for careful monitoring of MIL susceptibility for implementation in national VL elimination programs.
Author Notes
Financial support: This work was funded by Kaladrug-R (grant no. EC-FP7-222895, www.leishrisk.net/kaladrug), Directorate-General for Development Cooperation of the Belgian Government (framework agreement 03 - project 3.04 Visceral Leishmaniasis Control), Sitaram Memorial Trust, Muzaffarpur. Author V.K.P. is thankful to Indian Council of Medical Research, New Delhi, India for providing research fellowship. S.S. has received grant support for clinical trials and travel funds to attend scientific meetings from Paladin Labs, Institute for One World Health, and GlaxoSmithKline, and his institute has received grants from Bharat Serum and Vaccine Ltd.
Authors' addresses: Vijay Kumar Prajapati, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, E-mail: vijay84bhu@gmail.com. Bart Ostyn, Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium, E-mail: Bostyn@itg.be. Poonam Salotra, National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India, E-mail: salotra@vsnl.com. Manu Vanaerschot, Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium, E-mail: Mvanaerschot@itg.be. Jean-Claude Dujardin, Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium, and the Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium, E-mail: Jcdujardin@itg.be. Smriti Sharma, Madhukar Rai, and Shyam Sundar, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India, E-mails: smritibhardwaj87@gmail.com, rai_madhukar@sify.com, and drshyamsundar@hotmail.com.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Alvar J, Velez ID, Herrero M, Desjeux P, Cano J, Janin J, den Boer M; WHO Leishmaniasis Control Team, 2012. Leishmaniasis worldwide and global estimates of its incidence. PLoS ONE 7: e35671.
-
2.
Guerin PJ, Olliaro P, Sundar S, Boelaert M, Croft SL, Desjeux P, Wasunna MK, Bryceson AD, 2002. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis 2: 494–501.
-
3.
Joshi A, Narain JP, Prasittisuk C, Bhatia R, Hashim G, Jorge A, Banjara M, Kroeger A, 2008. Can visceral leishmaniasis be eliminated from Asia? J Vector Borne Dis 45: 105–111.
-
4.
WHO, 2005. Expert Committee on Regional Strategic Framework for Elimination of Kala-azar from the South-East Asia Region (2005–2015). New Delhi: WHO regional Office for South-East Asia.
-
5.
Prajapati VK, Awasthi K, Gautam S, Yadav TP, Rai M, Srivastava ON, Sundar S, 2011. Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes. J Antimicrob Chemother 66: 874–879.
-
6.
Sundar S, Jha TK, Thakur CP, Engel J, Sindermann H, Fischer C, Junge K, Bryceson A, Berman J, 2002. Oral miltefosine for Indian visceral leishmaniasis. N Engl J Med 347: 1739–1746.
-
7.
Jha TK, Sundar S, Thakur CP, Bachmann P, Karbwang J, Fischer C, Voss A, Berman J, 1999. Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis. N Engl J Med 341: 1795–1800.
-
8.
Sundar S, Singh A, Rai M, Prajapati VK, Singh AK, Ostyn B, Boelaert M, Dujardin JC, Chakravarty J, 2012. Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use. Clin Infect Dis 55: 543–550.
-
9.
Rijal S, Ostyn B, Uranw S, Rai K, Bhattarai NR, Dorlo TP, Beijnen JH, Vanaerschot M, Decuypere S, Dhakal SS, Das ML, Karki P, Singh R, Boelaert M, Dujardin JC, 2013. Increasing failure of Miltefosine in the treatment of kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance. Clin Infect Dis 56: 1530–1538.
-
10.
Kumar D, Kulshrestha A, Singh R, Salotra P, 2009. In vitro susceptibility of field isolates of Leishmania donovani to Miltefosine and amphotericin B: correlation with sodium antimony gluconate susceptibility and implications for treatment in areas of endemicity. Antimicrob Agents Chemother 53: 835–838.
-
11.
Prajapati VK, Mehrotra S, Gautam S, Rai M, Sundar S, 2012. In vitro antileishmanial drug susceptibility of clinical isolates from patients with Indian visceral leishmaniasis–status of newly introduced drugs. Am J Trop Med Hyg 87: 655–657.
-
12.
Kulshrestha A, Bhandari V, Mukhopadhyay R, Ramesh V, Sundar S, Maes L, Dujardin JC, Roy S, Salotra P, 2013. Validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of Leishmania donovani. Parasitol Res 112: 825–828.
-
13.
Maurya R, Mehrotra S, Prajapati VK, Nylen S, Sacks D, Sundar S, 2010. Evaluation of blood agar microtiter plates for culturing Leishmania parasites to titrate parasite burden in spleen and peripheral blood of patients with visceral leishmaniasis. J Clin Microbiol 48: 1932–1934.
-
14.
Srivastava P, Prajapati VK, Vanaerschot M, Van der Auwera G, Dujardin JC, Sundar S, 2010. Detection of Leptomonas sp. parasites in clinical isolates of Kala-azar patients from India. Infect Genet Evol 10: 1145–1150.
-
15.
Bhandari V, Kulshrestha A, Deep DK, Stark O, Prajapati VK, Ramesh V, Sundar S, Schonian G, Dujardin JC, Salotra P, 2012. Drug susceptibility in Leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis. PLoS Negl Trop Dis 6: e1657.
-
16.
Leprohon P, Legare D, Raymond F, Madore E, Hardiman G, Corbeil J, Ouellette M, 2009. Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum. Nucleic Acids Res 37: 1387–1399.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 31 | 31 | 5 |
| Full Text Views | 458 | 131 | 4 |
| PDF Downloads | 117 | 32 | 2 |