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Chemotherapy and Experimental Models of Visceral Leishmaniasis

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Abstract

Visceral leishmaniasis (VL) is a neglected tropical parasitic disease in humans caused by protozoan parasite Leishmania donovani and transmitted to humans by the bite of an infected female sand fly, a haemoflagellate vector. According to WHO, every year 0.7–1 million leishmaniasis cases are reported globally, and over 20,000–30,000 deaths occur. Current anti-leishmanial drug (pentavalent antimonials, miltefosine, amphotericin B, pentamidine and paromomycin) therapy is fraught with several problems and causes serious adverse effects, which limit their clinical application. The emergence of drug resistance and non-availability of an effective vaccine(s) against leishmaniasis poses a serious challenge to leishmaniasis treatment and control. Environmental and socio-economic status of people like deforestation, global warming and poverty exacerbates both parasite survival and disease progression. Pentavalent antimonial-resistant strains of L. donovani are rampant in Bihar, a highly endemic zone of VL in India. Development of co-infections (HIV-VL and Malaria-VL) often leads to poor diagnosis and treatment. There are no proper prognostic and diagnostic markers for VL. Therefore, there is an urgent need for the development of new anti-leishmanial drugs for the treatment and control of devastating VL. Effective immunotherapy/immuno-chemotherapy is considered as a viable alternative to chemotherapy. Cytokines (granulocyte-macrophage colony-stimulating factor, interferon-γ and interleukin-12) both stand-alone and in combination with current anti-leishmanial drugs are being thought to reduce the drug resistance and useful in VL treatment. The development and availability of the reliable models for anti-leishmanial drug screening is very much warranted.

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References

  • Ab Rahman AK, Abdullah FH (2011) Visceral leishmaniasis (kala-azar) and malaria coinfection in an immigrant in the state of Terengganu, Malaysia: a case report. J Microbiol Immunol Infect 44:72–76

    Article  PubMed  Google Scholar 

  • Agrawal Y, Sinha A, Upadhyaya P, Kafle S, Rijal S, Khanal B (2013) Hematological profile in visceral leishmaniasis. Int J Infect Microbiol 2:39–44

    Article  Google Scholar 

  • Almeida R, D’Oliveira A Jr, Machado P, Bacellar O, Ko AI, de Jesus AR et al (1999) Randomized, double blind study of stibogluconate plus human granulocyte macrophage colony stimulating factor versus stibogluconate alone in the treatment of cutaneous leishmaniasis. J Infect Dis 180:1735–1737

    Article  CAS  PubMed  Google Scholar 

  • Asilian A, Jalayer T, Nilforooshzadeh M, Ghassemi RL, Peto R, Wayling S et al (2003) Treatment of cutaneous leishmaniasis with aminosidine (paromomycin) ointment: double-blind, randomized trial in the Islamic Republic of Iran. Bull World Health Organ 81:353–359

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bacellar O, Brodskyn C, Guerreiro J, Barral-Netto M, Costa CH, Coffman RL et al (1996) Interleukin-12 restores interferon-gamma production and cytotoxic responses in visceral leishmaniasis. J Infect Dis 173:1515–1518

    Article  CAS  PubMed  Google Scholar 

  • Badaro R, Nascimento C, Carvalho JS, Badaro F, Russo D, Ho JL et al (1994) Granulocyte-macrophage colony-stimulating factor in combination with pentavalent antimony for the treatment of visceral leishmaniasis. Eur J Clin Microbiol Infect Dis 13:23–28

    Article  Google Scholar 

  • Barbieri CL (2006) Immunology of canine leishmaniasis. Parasite Immunol 28:329–337

    Article  CAS  PubMed  Google Scholar 

  • Basu JM, Mookerjee A, Sen P, Bhaumik S, Sen P, Banerjee S et al (2006) Sodium antimony gluconate induces generation of reactive oxygen species and nitric oxide via phosphoinositide 3-kinase and mitogen-activated protein kinase activation in Leishmania donovani-infected macrophages. Antimicrob Agents Chemother 50:1788–1797

    Article  CAS  Google Scholar 

  • Belosevic MI, Finbloom DS, Van Der Meide PH, Slayter MV, Nacy CA (1989) Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major. J Immunol 143:266–274

    CAS  PubMed  Google Scholar 

  • Broderson JR, Chapman WL, Hanson WL (1986) Experimental Visceral Leishmaniasis in the OwlMonkey. Vet Pathol 23:293-302

    Article  CAS  PubMed  Google Scholar 

  • Burgess AW, Camakaris JA, Metcalf DO (1977) Purification and properties of colony-stimulating factor from mouse lung-conditioned medium. J Biol Chem 252:1998–2003

    CAS  PubMed  Google Scholar 

  • Callahan HL, Portal AC, Devereaux R, Grogl MA (1997) An axenic amastigote system for drug screening. Antimicrob Agents Chemother 41:818–822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carvalho L, Luque-Ortega JR, Lopez-Martin C, Castanys S, Rivas L, Gamarro F (2011) The 8-aminoquinoline analogue sitamaquine causes oxidative stress in Leishmania donovani promastigotes by targeting succinate dehydrogenase. Antimicrob Agents Chemother 55:4204–4210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chalfie M (1995) Green fluorescent protein. Photochem Photobiol 62:651–656

    Article  CAS  PubMed  Google Scholar 

  • Chang KT, Dwyer DM (1978) Leishmania donovani hamster macrophage interactions in vitro: cell entry, intracellular survival, and multiplication of amastigotes. J Exp Med 147:515–530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW et al (2007) Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol 5:873

    Article  CAS  PubMed  Google Scholar 

  • Chattopadhyay A, Jafurulla M (2011) A novel mechanism for an old drug: amphotericin B in the treatment of visceral leishmaniasis. Biochem Biophys Res Commun 416:7–12

    Article  CAS  PubMed  Google Scholar 

  • Chunge CN, Gacmra G, Muigai R, Wasunna K, Rashid JR, Chulay JD et al (1985) Visceral leishmaniasis unresponsive to antimonial drugs III. Successful treatment using a combination of sodium stibogluconate plus allopurinol. Trans R Soc Trop Med Hyg 79:715–718

    Article  CAS  PubMed  Google Scholar 

  • Coleman RE, Edman JD, Semprevivo LH (1988) Leishmania mexicana: effect of concomitant malaria on cutaneous leishmaniasis. Development of lesions in a Leishmania-susceptible (BALB/c) strain of mouse. Exp Parasitol 65:269–276

    Article  CAS  PubMed  Google Scholar 

  • Costa S, Machado M, Cavadas C, do Ceu Sousa M (2016) Antileishmanial activity of antiretroviral drugs combined with miltefosine. Parasitol Res 2016(115):3881–3887

    Article  Google Scholar 

  • Croft SL, Seifert K, Yardley V (2006a) Current scenario of drug development for leishmaniasis. Indian J Med Res 123:399–410

    CAS  PubMed  Google Scholar 

  • Croft SL, Sundar S, Fairlamb AH (2006b) Drug resistance in leishmaniasis. Clin Microbiol Rev 19:111–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Rycker M, Hallyburton I, Thomas J, Campbell L, Wyllie S, Joshi D et al (2013) Comparison of a high-throughput high-content intracellular Leishmania donovani assay with an axenic amastigote assay. Antimicrob Agents Chemother 57:2913–2922

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dea-Ayuela MA, Rama-Iniguez S, Alunda JM, Bolas-Fernandez F (2007) Setting new immunobiological parameters in the hamster model of visceral leishmaniasis for in vivo testing of antileishmanial compounds. Vet Res Commun 31:703–717

    Article  CAS  PubMed  Google Scholar 

  • Dietze R, Carvalho SF, Valli LC, Berman J, Brewer T, Milhous W et al (2001) Phase 2 trial of WR6026, an orally administered 8-aminoquinoline, in the treatment of visceral leishmaniasis caused by Leishmania chagasi. Am J Trop Med Hyg 65:685–689

    Article  CAS  PubMed  Google Scholar 

  • Dostalova A, Volf P (2012) Leishmania development in sand flies: parasite-vector interactions overview. Parasit Vectors 5:276–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dube A, Gupta R, Singh N (2009) Reporter genes facilitating discovery of drugs targeting protozoan parasites. Trends Parasitol 25:432–439

    Article  CAS  PubMed  Google Scholar 

  • Dumas C, Muyombwe A, Roy G, Matte C, Ouellette M, Olivier M et al (2003) Recombinant Leishmania major secreting biologically active granulocyte-macrophage colony-stimulating factor survives poorly in macrophages in vitro and delays disease development in mice. Infect Immun 71:6499–6509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frezard F, Demicheli C, Ribeiro RR (2009) Pentavalent antimonials: new perspectives for old drugs. Molecules 14:2317–2336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallin JI, Farber JM, Holland SM, Nutman TB (1995) Interferon-γ in the management of infectious diseases. Ann Intern Med 123:216–224

    Article  CAS  PubMed  Google Scholar 

  • Ghosh M, Roy K, Roy S (2013) Immunomodulatory effects of antileishmanial drugs. J Antimicrob Chemother 68:2834–2838

    Article  CAS  PubMed  Google Scholar 

  • Gomes LI, Gonzaga FM, de Morais-Teixeira E, de Souza-Lima BS, Freire VV, Rabello A (2012) Validation of quantitative real-time PCR for the in vitro assessment of antileishmanial drug activity. Exp Parasitol 131:175–179

    Article  CAS  PubMed  Google Scholar 

  • Guevara P, Pinto-Santini D, Rojas A, Crisante G, Anez N, Ramirez JL (2001) Green fluorescent protein-tagged Leishmania in phlebotomine sand flies. J Med Entomol 38:39–43

    Article  CAS  PubMed  Google Scholar 

  • Ha DS, Schwarz JK, Turco SJ, Beverley SM (1996) Use of the green fluorescent protein as a marker in transfected Leishmania. Mol Biochem Parasitol 77:57–64

    Article  CAS  PubMed  Google Scholar 

  • Hailu A, Van der poll to, Berhe N, Kager PA (2004) Elevated plasma levels of interferon (IFN)-γ, IFN-γ inducing cytokines, and IFN-γ inducible CXC chemokines in visceral leishmaniasis. Am J Trop Med Hyg 71:561–567

    Article  CAS  PubMed  Google Scholar 

  • Haldar AK, Sen P, Roy S (2011) Use of antimony in the treatment of leishmaniasis: current status and future directions. Mol Biol Int 2011:1–23

    Article  Google Scholar 

  • Halim MA, Alfurayh O, Kalin ME, Dammas S, Al-Eisa A, Damanhouri G (1993) Successful treatment of visceral leishmaniasis with allopurinol plus ketoconazole in a renal transplant recipient after the occurrence of pancreatitis due to stibogluconate. Clin Infect Dis 16:397–399

    Article  CAS  PubMed  Google Scholar 

  • Hamerlinck FF, Van Gool T, Faber WR, Kager PA (2000) Serum neopterin concentrations during treatment of leishmaniasis: useful as test of cure? FEMS Immunol Medl Microbiol 27:31–34

    Article  CAS  Google Scholar 

  • Hamill RJ (2013) Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs 73:919–934

    Article  CAS  PubMed  Google Scholar 

  • Hamza T, Barnett JB, Li B (2010) Interleukin 12 a key immunoregulatory cytokine in infection applications. Int J Mol Sci 11:789–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Handman E, Burgess AW (1979) Stimulation by granulocyte-macrophage colony-stimulating factor of Leishmania tropica killing by macrophages. J Immunol 122:1134–1137

    CAS  PubMed  Google Scholar 

  • Hasker E, Singh SP, Malaviya P, Picado A, Gidwani K, Singh RP et al (2012) Visceral leishmaniasis in rural Bihar, India. Emerg Infect Dis 18:1662–1664

    Article  PubMed  PubMed Central  Google Scholar 

  • Heinzel FP, Schoenhaut DS, Rerko RM, Rosser LE, Gately MK (1993) Recombinant interleukin 12 cures mice infected with Leishmania major. J Exp Med 177:1505–1509

    Article  CAS  PubMed  Google Scholar 

  • Islam MZ, Itoh M, Mirza R, Ahmed I, Ekram AS, Sarder AH et al (2004) Direct agglutination test with urine samples for the diagnosis of visceral leishmaniasis. Am J Trop Med Hyg 70:78–82

    Article  PubMed  Google Scholar 

  • Jha TK (1983) Evaluation of diamidine compound (pentamidine isethionate) in the treatment of resistant cases of kala-azar occurring in North Bihar. India Trans R Soc Trop Med Hyg 77:167–170

    Article  CAS  PubMed  Google Scholar 

  • Jha TK, Sundar S, Thakur CP, Felton JM, Sabin AJ, Horton J (2005) A phase II dose-ranging study of sitamaquine for the treatment of visceral leishmaniasis in India. Am J Trop Med Hyg 73:1005–1011

    Article  CAS  PubMed  Google Scholar 

  • Kamhawi S (2006) Phlebotomine sand flies and Leishmania parasites: friends or foes? Trends Parasitol 22:439–445

    Article  PubMed  Google Scholar 

  • Kaur A, Kinhikar AG, Singh PP (2004) Bioimmunotherapy of rodent malaria: co-treatment with recombinant mouse granulocyte-macrophage colony-stimulating factor and an enkephalin fragment peptide Tyr-Gly-Gly. Acta Trop 91:27–41

    Article  CAS  PubMed  Google Scholar 

  • Kima PE, Soong L (2013) Interferon gamma in leishmaniasis. Front Immunol 4:156–160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kip AE, Balasegaram M, Beijnen JH, Schellens JH, de Vries PJ, Dorlo TP (2015) Systematic review of biomarkers to monitor therapeutic response in leishmaniasis. Antimicrob Agents Chemother 59:1–4

    Article  PubMed  CAS  Google Scholar 

  • Kolaczinski JH, Reithinger R, Worku DT, Ocheng A, Kasimiro J, Kabatereine N et al (2008) Risk factors of visceral leishmaniasis in East Africa: a case-control study in Pokot territory of Kenya and Uganda. Int J Epidemiol 37:344–352

    Article  PubMed  Google Scholar 

  • Kumar R, Engwerda C (2014) Vaccines to prevent leishmaniasis. Clin Transl Immunol 3:3–9

    Article  CAS  Google Scholar 

  • Lafuse WP, Story R, Mahylis J, Gupta G, Varikuti S, Steinkamp H et al (2013) Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen. PLoS One 8:59509

    Article  CAS  Google Scholar 

  • Lindoso JA, Cota GF, da Cruz AM, Goto H, Maia-Elkhoury AN, Romero GA et al (2014) Visceral leishmaniasis and HIV coinfection in Latin America. PLoS Negl Trop Dis 8:3136–3144

    Article  Google Scholar 

  • Loiseau PM, Cojean S, Schrevel J (2011) Sitamaquine as a putative antileishmanial drug candidate: from the mechanism of action to the risk of drug resistance. Parasite 18:115–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loria-Cervera EN, Andrade-Narvaez FJ (2014) Animal models for the study of leishmaniasis immunology. Rev Inst Med Trop Sao Paulo 56:1–11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maarouf M, de Kouchkovsky Y, Brown S, Petit PX, Robert-Gero M (1997) In vivo interference of paromomycin with mitochondrial activity of Leishmania. Exp Cell Res 232:339–348

    Article  CAS  PubMed  Google Scholar 

  • Maltezou HC (2009) Drug resistance in visceral leishmaniasis. Biomed Res Int 2010:1–8

    Google Scholar 

  • Mastroianni A (2004) Liposomal amphotericin B and rHuGM-CSF for treatment of visceral leishmaniasis in AIDS. Infez Med 12:197–204

    CAS  PubMed  Google Scholar 

  • Matte C, Marquis JF, Blanchette J, Gros P, Faure R, Posner BI et al (2000) Peroxovanadium-mediated protection against murine leishmaniasis: role of the modulation of nitric oxide. Eur J Immunol 30:2555–2564

    Article  CAS  PubMed  Google Scholar 

  • Mohapatra S (2014) Drug resistance in leishmaniasis: newer developments. Trop Parasitol 4:4–9

    Article  PubMed  PubMed Central  Google Scholar 

  • Moore EM, Lockwood DN (2010) Treatment of visceral leishmaniasis. J Global Infect Dis 2:151–158

    Article  CAS  Google Scholar 

  • Moreno J, Alvar J (2002) Canine leishmaniasis: epidemiological risk and the experimental model. Trends Parasitol 18:399–405

    Article  PubMed  Google Scholar 

  • Munoz DL, Robledo SM, Kolli BK, Dutta S, Chang KP, Muskus C (2009) Leishmania (Viannia) panamensis: an in vitro assay using the expression of GFP for screening of antileishmanial drug. Exp Parasitol 122:134–139

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Murray HW (2000) Suppression of posttreatment recurrence of experimental visceral leishmaniasis in T-cell-deficient mice by oral miltefosine. Antimicrob Agents Chemother 44:3235–3236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murray HW, Hariprashad J (1995) Interleukin 12 is effective treatment for an established systemic intracellular infection: experimental visceral leishmaniasis. J Exp Med 181:387–391

    Article  CAS  PubMed  Google Scholar 

  • Murray HW, Hariprashad JU, Fichtl RE (1993) Treatment of experimental visceral leishmaniasis in a T-cell-deficient host: response to amphotericin B and pentamidine. Antimicrob Agents Chemother 37:1504–1505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murray HW, Montelibano C, Peterson R, Sypek JP (2000) Interleukin-12 regulates the response to chemotherapy in experimental visceral leishmaniasis. J Infect Dis 182:1497–1502

    Article  CAS  PubMed  Google Scholar 

  • Nacher M, Carme B, Sainte Marie D, Couppie P, Clyti E, Guibert P et al (2001) Influence of clinical presentation on the efficacy of a short course of pentamidine in the treatment of cutaneous leishmaniasis in French Guiana. Ann Trop Med Parasitol 95:331–336

    Article  CAS  PubMed  Google Scholar 

  • Nieto A, Dominguez-Bernal G, Orden JA, De La Fuente R, Madrid-Elena N, Carrion J (2011) Mechanisms of resistance and susceptibility to experimental visceral leishmaniosis: BALB/c mouse versus Syrian hamster model. Vet Res 42:39–51

    Article  PubMed  PubMed Central  Google Scholar 

  • Okwor I, Uzonna JE (2013) The immunology of Leishmania/HIV co-infection. Immunol Res 56:163–171

    Article  CAS  PubMed  Google Scholar 

  • Olobo JO, Gicheru MM, Anjili CO (2001) The African Green Monkey model for cutaneous and visceral leishmaniasis. Trends Parasitol 17:588–592

    Article  CAS  PubMed  Google Scholar 

  • Ota H, Takashima Y, Matsumoto Y, Hayashi Y, Matsumoto Y (2008) Pretreatment of macrophages with the combination of IFN-γ and IL-12 induces resistance to Leishmania major at the early phase of infection. J Vet Med Sci 70:589–593

    Article  CAS  PubMed  Google Scholar 

  • Patel TA, Lockwood DN (2009) Pentamidine as secondary prophylaxis for visceral leishmaniasis in the immunocompromised host: report of four cases. Tropical Med Int Health 14:1064–1070

    Article  CAS  Google Scholar 

  • Perez LE, Chandrasekar B, Saldarriaga OA, Zhao W, Arteaga LT, Travi BL et al (2006) Reduced nitric oxide synthase 2 (NOS2) promoter activity in the Syrian hamster renders the animal functionally deficient in NOS2 activity and unable to control an intracellular pathogen. J Immunol 176:5519–5528

    Article  CAS  PubMed  Google Scholar 

  • Perez-Victoria JM, Bavchvarov BI, Torrecillas IR, Martinez-Garcia M, Lopez-Martin C, Campillo M et al (2011) Sitamaquine overcomes ABC-mediated resistance to miltefosine and antimony in Leishmania. Antimicrob Agents Chemother 55:3838–3344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Porrozzi R, Pereira MS, Teva A, Volpini AC, Pinto MA, Marchevsky RS et al (2006) Leishmania infantum-induced primary and challenge infections in rhesus monkeys (Macaca mulatta): a primate model for visceral leishmaniasis. Trans R Soc Trop Med Hyg 100:926–937

    Article  CAS  PubMed  Google Scholar 

  • Rosenthal E, Marty P, del Giudice P, Pradier C, Ceppi C, Gastaut JA et al (2000) HIV and Leishmania coinfection: a review of 91 cases with focus on atypical locations of Leishmania. Clin Infect Dis 31:1093–1095

    Article  CAS  PubMed  Google Scholar 

  • Rybniker J, Goede V, Mertens J, Ortmann M, Kulas W, Kochanek M et al (2010) Treatment of visceral leishmaniasis with intravenous pentamidine and oral fluconazole in an HIV-positive patient with chronic renal failure—a case report and brief review of the literature. Int J Infect Dis 14:522–525

    Article  Google Scholar 

  • Sah SP, Sharma SK, Rani S (2002) Kala azar associated with malaria. Arch Pathol Lab Med 126:382–383

    PubMed  Google Scholar 

  • Saha B, Saini A, Germond R, Perrin PJ, Harlan DM, Davis TA (1999) Susceptibility or resistance to Leishmania infection is dictated by the macrophages evolved under the influence of IL-3 or GM-CSF. Eur J Immunol 29:2319–2329

    Article  CAS  PubMed  Google Scholar 

  • Saraiva EM, de Figueiredo Barbosa A, Santos FN, Borja-Cabrera GP, Nico D, Souza LO, de Oliveira Mendes-Aguiar C et al (2006) The FML-vaccine (Leishmune®) against canine visceral leishmaniasis: a transmission blocking vaccine. Vaccine 24:2423–2431

    Article  CAS  PubMed  Google Scholar 

  • Schriefer A, Barral A, Carvalho EM, Barrel-Nettom (1995) Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis. Clin Exp Immunol 102:535–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seifert K, Croft SL (2006) In vitro and in vivo interactions between miltefosine and other antileishmanial drugs. Antimicrob Agents Chemother 50:73–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sereno D, Roy G, Lemesre JL, Papadopoulou B, Ouellette M (2001) DNA transformation of Leishmania infantum axenic amastigotes and their use in drug screening. Antimicrob Agents Chemother 45:1168–1173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singal P, Singh PP (2005) Leishmania donovani amastigote component-induced colony-stimulating factor production by macrophages: modulation by morphine. Microbes Infect 7:148–156

    Article  CAS  PubMed  Google Scholar 

  • Singh N, Dube A (2004) Fluorescent Leishmania: application to anti-leishmanial drug testing. Am J Trop Med Hyg 71:400–402

    Article  CAS  PubMed  Google Scholar 

  • Singh N, Kumar R, Gautam S, Singh OP, Gidwani K, Rai M et al (2014) Leishmania specific CD4 T cells release IFN-γ that limits parasite replication in patients with visceral leishmaniasis. Int J Infect Dis 21:158–166

    Article  Google Scholar 

  • Stauber LA, Franchino EM, Grun J (1958) An eight-day method for screening compounds against Leishmania donovani in the golden hamster. J Eukaryot Microbiol 5:269–273

    CAS  Google Scholar 

  • Suman Gupta, Nishi (2011) Visceral leishmaniasis: experimental models for drug discovery. Indian J Med Res 133:27–39

    Google Scholar 

  • Sundar S, Chatterjee M (2006) Visceral leishmaniasis-current therapeutic modalities. Indian J Med Res 123:345–352

    CAS  PubMed  Google Scholar 

  • Sundar S, Olliaro PL (2007) Miltefosine in the treatment of leishmaniasis: clinical evidence for informed clinical risk management. Ther Clin Risk Manag 3:733–740

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sundar S, Rai M (2002) Laboratory diagnosis of visceral leishmaniasis. Clin Diagn Lab Immunol 9:951–958

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sundar S, Rosenkaimer F, Lesser ML, Murray HW (1995) Immunochemotherapy for a systemic intracellular infection: accelerated response using interferon-γ in visceral leishmaniasis. J Infect Dis 171:992–996

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Rai M, Chakravarty J, Agarwal D, Agrawal N, Vaillant M et al (2008) New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine. Clin Infect Dis 47:1000–1006

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Agrawal N, Arora R, Agarwal D, Rai M, Chakravarty J (2009) Short-course paromomycin treatment of visceral leishmaniasis in India: 14-day vs 21-day treatment. Clin Infect Dis 49:914–918

    Article  CAS  PubMed  Google Scholar 

  • Tavora LG, Nogueira MB, Gomes ST (2015) Visceral leishmaniasis/HIV co-infection in Northeast Brazil: evaluation of outcome. Braz J Infect Dis 19:651–656

    Article  PubMed  Google Scholar 

  • Tewary P, Saxena S, Madhubala R (2006) Co-administration of IL-12 DNA with rORFF antigen confers long-term protective immunity against experimental visceral leishmaniaisis. Vaccine 24:2409–2416

    Article  CAS  PubMed  Google Scholar 

  • Wadhone P, Maiti M, Agarwal R, Kamat V, Martin S, Saha B (2009) Miltefosine promotes IFN-γ-dominated anti-leishmanial immune response. J Immunol 182:7146–7154

    Article  CAS  PubMed  Google Scholar 

  • Wasunna MK, Rashid JR, Mbui J, Kirigi G, Kinoti D, Lodenyo H et al (2005) A phase II dose-increasing study of sitamaquine for the treatment of visceral leishmaniasis in Kenya. Am J Trop Med Hyg 73:871–876

    Article  CAS  PubMed  Google Scholar 

  • Weiser WY, Van Niel AN, Clark SC, David JR, Remold HG (1987) Recombinant human granulocyte/macrophage colony-stimulating factor activates intracellular killing of Leishmania donovani by human monocyte-derived macrophages. J Exp Med 166:1436–1446

    Article  CAS  PubMed  Google Scholar 

  • WHO (2015) Media centre Leishmaniasis. Leishmaniasis Fact sheet No375, 1–5.

    Google Scholar 

  • Wolday D, Akuffo H, Fessahaye G, Valantine A, Britton S (1998) Live and killed human immunodeficiency virus type-1 increases the intracellular growth of Leishmania donovani in monocyte-derived cells. Scand J Infect Dis 30:29–34

    Article  CAS  PubMed  Google Scholar 

  • Yared S, Deribe K, Gebreselassie A, Lemma W, Akililu E, Kirstein OD et al (2014) Risk factors of visceral leishmaniasis: a case control study in north-western Ethiopia. Parasit Vectors 7:470–480

    Article  PubMed  PubMed Central  Google Scholar 

  • Zvulunov A, Klaus S, Vardy D (2002) Fluconazole for the treatment of cutaneous leishmaniasis. N Engl J Med 347:370–371

    Article  PubMed  Google Scholar 

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Acknowledgements

The author is thankful to Prof. R. R. Akkinepally, Director, National Institute of Pharmaceutical Education and Research (NIPER), S. A. S. Nagar for encouragement and help. The financial assistance from NIPER is greatly acknowledged.

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  1. Centre of Infectious Diseases, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S. A. S. Nagar, Punjab, India

    Ganesh Yadagiri & Prati Pal Singh

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  1. Centre of Infectious Diseases, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S. A. S. Nagar, Punjab, India

    Prati Pal Singh

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Yadagiri, G., Singh, P.P. (2018). Chemotherapy and Experimental Models of Visceral Leishmaniasis. In: Singh, P. (eds) Infectious Diseases and Your Health. Springer, Singapore. https://doi.org/10.1007/978-981-13-1577-0_5

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