Follow DNDi on LinkedInFollow DNDi on TwitterFollow DNDi on Facebook

Scientific Publications

2014

Improving the quality of host country ethical oversight of international research: the use of a collaborative ‘pre-review’ mechanism for a study of fexinidazole for human African trypanosomiasis by Coleman CH, Ardiot C, Blesson S, Bonnin Y, Bompart F, Colonna P, Dhai A, Ecuru J, Edielu A, Hervé C, Hirsch F, Kouyaté B, Mamzer-Bruneel MF,  Maoundé D, Martinent E, Ntsiba H, Pelé G, Quéva G, Reinmund MC, Sarr SC, Sepou A, Tarral A, Tetimian D, Valverde O, Van Nieuwenhove S, Strub-Wourgaft N. Developing World Bioethics 2014, doi:10.1111/dewb.12068.
Click here to read the article / PDF

In vivo preliminary investigations of the effects of the benzimidazole anthelmintic drug flubendazole on rat embryos and fetuses by Longo M, Zanoncelli S, Messina M, Scandale I, Mackenzie C, Geary T, Marsh K, Lindley D, Mazué G. Reproductive Toxicology 2014, doi:10.1016/j.reprotox.2014.06.009.

  • Flubendazole, in a new formulation with high systemic bioavailability, has been proposed as a macrofilaricide against filarial diseases. The embryotoxic activity of a new oral flubendazole formulation was investigated. It did not interfere with rat embryofetal development.
Click here to access the article

Serum biomarkers predictive of cure in Chagas disease patients after nifurtimox treatment by Santamaria C, Chatelain E, Jackson Y, Miao Q, Ward BJ, Chappuis F, Ndao M. BMC Infectious Diseases 2014, doi:10.1186/1471-2334-14-302.
Click here to read the article / PDF

Population pharmacokinetics of mefloquine, administered as a fixed-dose combination of artesunate-mefloquine in Indian patients for the treatment of acute uncomplicated Plasmodium falciparum malaria by Jullien V, Valecha N, Srivastava B, Sharma B, Kiechel JR. Malaria Journal 2014, doi:10.1186/1475-2875-13-187.
Click here to read the article / PDF

Antitrypanosomal activity of fexinidazole metabolites, potential new drug candidates for Chagas disease by Bahia MT, Nascimento AF, Mazzeti AL, Marques LF, Gonçalves KR, Mota LW, Diniz LD, Caldas IS, Talvani A, Shackleford DM, Koltun M, Saunders J, White KL, Scandale I, Charman SA, Chatelain EAntimicrobial Agents and Chemotherapy 2014, doi:10.1128/AAC.02754-13
Click here to access the article

Modular multiantigen T cell epitope–enriched DNA vaccine against human leishmaniasis by Das S, Freier A, Boussoffara T, Das S, Oswald D, Losch FO, Selka M, Sacerdoti-Sierra N, Schönian G, Wiesmüller KH, Seifert K, Schroff M, Juhls C, Jaffe CL, Roy S, Das P, Louzir H, Croft SL, Modabber F, Walden P. Science Translational Medicine 2014, doi: 10.1126/scitranslmed.3008222
Click here to access the article

The role of modern drug discovery in the fight against neglected and tropical diseases by Burrows JN, Elliott RL, Kaneko T, Mowbray CE, Waterson D. Medicinal Chemistry Communication 2014, doi:10.1039/C4MD00011K
Click here to access the article

Nitroheterocyclic compounds are more efficacious than CYP51 inhibitors against Trypanosoma cruzi: implications for Chagas disease drug discovery and development by Moraes CB, Giardini MA, Kim H, Franco CH, Araujo-Junior AM, Schenkman S, Chatelain E, Freitas-Junior LH. Nature Scientific Reports 2014, doi:10.1038/srep04703.
Click here to read the article / PDF

Biological markers for evaluating therapeutic efficacy in Chagas disease, a systematic review by Pinazo MJ, Thomas MC, Bua J, Perrone A, Schijman AG, Viotti RJ, Ramsey JM, Ribeiro I, Sosa-Estani S, López MC, Gascon J. Expert Review of Anti-infective Therapy 2014, doi:10.1586/14787210.2014.899150.
Click here to read the article / PDF

Design, synthesis, ADME characterization and antileishmanial evaluation of novel substituted quinoline analogs
by Gopinath VS, Rao M, Shivahare R, Vishwakarma P, Ghose S, Pradhan A, Hindupur R, Sarma KD, Gupta S, Puri SK, Launay D, Martin D. Bioorganic & Medicinal Chemistry Letters 2014, doi:10.1016/j.bmcl.2014.03.065
Click here to access the article

The pharmacokinetics and acceptability of lopinavir/ritonavir minitab sprinkles, tablets and syrups in African HIV-infected children by Musiime V, Fillekes Q, Kekitiinwa A, Kendall L, Keishanyu R, Namuddu R, Young N, Opilo W, Lallemant M, Walker AS; Burger D, Gibb DM. JAIDS Journal of Acquired Immune Deficiency Syndromes 2014, doi: 10.1097/QAI.000000000000013.
Click here to access the article

Plasmodium falciparum clearance in clinical studies of artesunate-amodiaquine and comparator treatments in sub-Saharan Africa, 1999–2009 by Zwang J, Dorsey G, Mårtensson A, d’Alessandro U, Ndiaye JL, Karema C, Djimde A, Brasseur P, Sirima SB, Olliaro P. Malaria Journal 2014, doi:10.1186/1475-2875-13-114.
Click here to access the article / PDF

Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: first-in-human studies by Tarral A, Blesson S, Valverde Mordt O, Torreele E, Sassella D, Bray MA, Hovsepian L, Evène E, Gualano V, Felices M, Strub-Wourgaft N. Clinical Pharmacokinetics 2014, doi:10.1007/s40262-014-0136-3.
Click here to read the article / PDF

Communicating the AMFm message: exploring the effect of communication and training interventions on private for-profit provider awareness and knowledge related to a multi-country anti-malarial subsidy intervention by Willey BA, Tougher S, Ye Y, The ACTwatchGroup, Mann AG, Thomson R, Kourgueni IA, Amuasi JH, Ren R, Wamukoya M, Torres Rueda S, Taylor M, Seydou M, Blay Nguah S, Ndiaye S, Mberu B, Malam O, Kalolella A, Juma E, Johanes B, Festo C, Diap G, Diallo D, Bruxvoort K, Ansong D, Amin A, Adegoke CA, Hanson K, Arnold F and Goodman C. Malaria Journal 2014, doi:10.1186/1475-2875-13-46.
Click here to access the article / PDF

Poly(methacrylic acid) complexation of amphotericin B to treat neglected diseases by Les KA, Mohamed-Ahmed AHA, Balan S, Choi J, Martin D, Yardley V, Powell K, Godwin A, Brocchini S. Polymer Chemistry January 2014, doi:10.1039/C3PY01051A.
Click here to access the article

Safety and efficacy of single dose versus multiple doses of AmBisome® for treatment of visceral leishmaniasis in eastern Africa: A randomised trial
by Khalil EAG, Weldegebreal T, Younis BM, Omollo R, Musa AM, Hailu W, Abuzaid A, Dorlo TPC, Hurissa Z, Yifru S, Haleke W, Smith PG, Ellis S, Balasegaram M, EL-Hassan AH, Schoone GJ, Wasunna M, Kimutai R, Edwards T, Hailu A. PLOS Neglected Tropical Diseases 2014, 8(1): e2613. doi:10.1371.
Click here to read the article / PDF

2013

Two Analogues of Fenarimol Show Curative Activity in an Experimental Model of Chagas Disease by Martine Keenan, Jason H. Chaplin, Paul W. Alexander, Michael J. Abbott, Wayne M. Best, Andrea Khong, Adriana Botero, Catherine Perez, Scott Cornwall, R. Andrew Thompson, Karen L. White, David M. Shackleford, Maria Koltun, Francis C. K. Chiu, Julia Morizzi, Eileen Ryan, Michael Campbell, Thomas W. von Geldern, Ivan Scandale, Eric Chatelain, and Susan A. Charman. J Med Chem, December 2013
Click here to read the article / PDF

Safety, efficacy and population pharmacokinetics of fixed-dose combination of artesunate-mefloquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in India by Neena Valecha, Bina Srivastava, N.G. Dubhashi, B.H. Krishnamoorthy Rao, Ashwani Kumar, S.K. Ghosh, Jai Prakash Narayan Singh, J.R. Kiechel, Bhawna Sharma, V. Jullien,A.P. Dash, W.R.J. Taylor & Anupkumar R. Anvikar. J Vector Borne Dis, December 2013
Click here to read the article / PDF

PLOS and DNDi: A Decade of Open Access and NTD R&D
PLOS Medicine Collection,
December 2013
Click here to view the collection of open access articles

Design, synthesis and biological evaluation of 2-substituted quinolines as potential antileishmanial agents by Vadiraj S. Gopinath, Jakir Pinjari, Ravindra T. Dere, Aditya Verma, Preeti Vishwakarma, Rahul Shivahare, Manjunath Moger, Palusa Sanath Kumar Goud, Vikram Ramanathan, Prosenjit Bose, M.V.S. Rao, Suman Gupta, Sunil K. Puri, Delphine Launay, Denis Martin. Eur J Med Chem., November 2013
Click here to access the article

Towards a paradigm shift in the treatment of chronic Chagas disease by R. Viotti, B. Alarcón de Noya, T. Araujo-Jorge, M. J. Grijalva, F. Guhl, M. C. López, J. M. Ramsey, I. Ribeiro, A. G. Schijman, S. Sosa-Estani, F. Torrico and J. Gascon. Antimicrob Agents Chemother, November 2013
Click here to access the article

An Unfolding Tragedy of Chagas Disease in North America by Peter J. Hotez, Eric Dumonteil, Miguel Betancourt Cravioto, Maria Elena Bottazzi, Roberto Tapia-Conyer, Sheba Meymandi, Unni Karunakara, Isabela Ribeiro, Rachel M. Cohen, Bernard Pécoul. PLoS Negl Trop Dis., October 2013
Click here to read the article / PDF

Selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi by Martine Keenan, Paul W Alexander, Jason H Chaplin, Michael J Abbott, Hugo Diao, Zhisen Wang, Wayne M Best, Catherine J Perez, Scott MJ Cornwall, Sarah K Keatley, RC Andrew Thompson, Susan A Charman, Karen L White, Eileen Ryan, Gong Chen, Jean-Robert Ioset, Thomas W von Geldern & Eric Chatelain. Future Med Chem, October 2013
Click here to read the article / PDF

The drug and vaccine landscape for neglected diseases (2000—11): a systematic assessment by Dr Belen Pedrique MD, Nathalie Strub-Wourgaft MD, Claudette Some PharmD, Piero Olliaro MD, Patrice Trouiller PharmD, Nathan Ford PhD, Bernard Pécoul MD, Jean-Hervé Bradol MD. The Lancet Global Health, October 2013
Click here to read the article / PDF

Therapeutic efficacy of fixed dose artesunate-mefloquine for the treatment of acute, uncomplicated Plasmodium falciparum malaria in Kampong Speu, Cambodia by Rithea Leang, Sakun Ros, Socheat Duong, Visweswaran Navaratnam, Pharath Lim, Frédéric Ariey, Jean-René Kiechel, Didier Ménard and Walter RJ Taylor. Malaria Journal, September 2013.
Click here to read the article / PDF

Validation of Two Rapid Diagnostic Tests for Visceral Leishmaniasis in Kenya by Jane Mbui, Monique Wasunna, Manica Balasegaram, Adrian Laussermayer, Rashid Juma, Simon Njoroge Njenga, George Kirigi, Mark Riongoita, Roberto de la Tour, Joke van Peteghem, Raymond Omollo, François Chappuis. PLoS Negl Trop Dis., September 2013
Click here to read the article / PDF

Pharmacokinetics and pharmacodynamics utilizing unbound target tissue exposure as part of a disposition-based rationale for lead optimization of benzoxaboroles in the treatment of Stage 2 Human African Trypanosomiasis
by Stephen Wring, Eric Gaukel, Bakela Nare, Robert Jacobs, Beth Beaudet, Tana Bowling, Luke Mercer, Cyrus Bacchi, Nigel Yarlett, Ryan Randolph, Robin Parham, Cindy Rewerts, Jacob Platner and Robert Don. Parasitology, September 2013.
Click here to access the article

Complexes of Trypanosoma cruzi sterol 14alpha-demethylase (CYP51) with two pyridine-based drug candidates for Chagas disease: Structural basis for pathogen-selectivity by Tatiana Y. Hargrove, Zdzislaw Wawrzak, Paul W. Alexander, Jason H. Chaplin, Martine Keenan, Susan A. Charman, Catherine J. Perez, Michael R. Waterman, Eric Chatelain and Galina I. Lepesheva. J. Biol. Chem., September 2013.
Click here to access the article

Evaluating Chagas disease progression and cure through blood-derived biomarkers: a systematic review by Requena-Méndez A, López MC, Angheben A, Izquierdo L, Ribeiro I, Pinazo MJ, Gascon J, Muñoz J. Expert Review Anti-infective Therapy 2013, doi: 10.1586/14787210.2013.824718.
Click here to read the article

Novel 3-nitro-1H-1,2,4-triazole-based piperazines and 2-amino-1,3-benzothiazoles as antichagasic agents. by Papadopoulou MV, Bloomer WD, Rosenzweig HS, Kaiser M, Chatelain E, Ioset JR. Bioorg Med Chem., August 2013.
Click here to access the article

Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections by Rob Don and Jean-Robert Ioset. Parasitology, August 2013.
Click here to access the article

Benznidazole and Posaconazole in Experimental Chagas Disease: Positive Interaction in Concomitant and Sequential Treatments by Lívia de Figueiredo Diniz, Julio A. Urbina, Isabel Mayer de Andrade, Ana Lia Mazzeti, Tassiane Assíria F. Martins, Ivo Santana Caldas, André Talvani, Isabela Ribeiro, Maria Terezinha Bahia. PLoS Negl Trop Dis., August 2013.
Click here to access the article / PDF

An Improved Kilo-scale Synthesis of 2-Bromo-4-nitro-1H-imidazole: A Key Building Block of Nitroimidazole Drugs by Srinivasa Rao Pedada, Vijay S. Satam, Pawan J. Tambade, Srinivas A. Kandadai, Rama Mohan Hindupur, Hari Narayan Pati, Delphine Launay, and Denis Martin. Org. Process Res. Dev., August 2013.
Click here to access the article

Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial by Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, Pinoges L, Sundaygar T, Zolia YM, Jones JJ, Comte E, Bruneel A, Branger M, Jullien V, Carn G, Kiechel J, Ashley EA, and Guérin PJ, Malaria Journal, July 2013.
Click here to read the article / PDF

Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia by  Birgit Schramm, Parastou Valeh, Elisabeth Baudin, Charles S Mazinda, Richard Smith, Loretxu Pinoges, Timothy Sundaygar, Yah M Zolia, Joel J Jones, Eric Comte, Arnaud Bruneel, Michel Branger, Vincent Jullien, Gwenaelle Carn, Jean-René Kiechel, Elizabeth A Ashley and Philippe J Guérin, Malaria Journal, July 2013.
Click here to read the article / PDF

Report of the Post Kala-Azar Dermal Leishmaniasis (PKDL) consortium meeting, New Delhi, India, 27-29 June 2012 by Philippe Desjeux, Raj Shankar Ghosh, Pritu Dhalaria, Nathalie Strub-Wourgaft and Ed E Zijlstra. Parasites & Vectors, July 2013.
Click here to read the article

Effects of the benzimidazole anthelmintic drug flubendazole on rat embryos in vitro by Monica Longo, Sara Zanoncelli, Paolo Angelo Colombo, Michael Oscar Harhay, Ivan Scandale, Charles Mackenzie, Timothy Geary, Nicole Madrill, Guy Mazué. Reprod Toxicol., April 2013
Click here to access the article

Methodology of Clinical Trials Aimed at Assessing Interventions for Cutaneous Leishmaniasis by Olliaro P, Vaillant M, Arana B, Grogl M, Modabber F, Magill A. PLoS Negl Trop Dis., March 2013, Vol. 7, 3 (e2130).
Click here to read the article / PDF

The story of artesunate-mefloquine (ASMQ), innovative partnerships in drug development: case study by Wells S, Diap G and Kiechel J-R, Malaria Journal, February 2013
Click here to read the article / PDF

Serological and parasitological response in chronic Chagas patients 3 years after nifurtimox treatment by Jackson Y, Chatelain E, Mauris A, Holst M, Miao Q, Chappuis F, Ndao M, BMC Infectious Diseases, February 2013
Click here to read the article / PDF

Design, structure-activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi by Keenan, M., Alexander, P.W., Diao, H., Best, W.M., Khong, A., Kerfoot, M., Thompson, R.A., White, K.L., Shackleford, D.M., Ryan, E., Gregg, A.D., Charman, S.A., von Geldern, T.W., Scandale, I., Chatelain, E., , Bioorganic & Medicinal Chemistry, January 2013
Click here to access article

2012

Human African Trypanosomiasis in the Democratic Republic of the Congo: A Looming Emergency? by Hasker E, Lutumba P, Chappuis F, Kande V, Potet J, et al. PLoS Negl Trop Dis., December 2012, 6(12): e1950.
Click here to read the article / PDF

Liposomal amphotericin B as a treatment for human leishmaniasis, by. Expert Opinion on Emerging Drugs, December 2012, Vol. 17, No. 4 , Pages 493-510
Click here to read the article / PDF

In-Hospital Safety in Field Conditions of Nifurtimox Eflornithine Combination Therapy (NECT) for T. b. gambiense Sleeping Sickness by Schmid C, Kuemmerle A, Blum J, Ghabri S, Kande V, Mutombo W, Ilunga M, Lumpungu I, Mutanda S, Nganzobo P, Tete D, Mubwa N, Kisala M, Blesson S, Valverde Mordt O, PLoS Negl Trop Dis., November 2012, 6(11): e1920.
Click here to read the article / PDF

Identification of Compounds with Anti-Proliferative Activity against Trypanosoma brucei brucei Strain 427 by a Whole Cell Viability Based HTS Campaign by Sykes ML, Baell JB, Kaiser M, Chatelain E, Moawad SR, Ganame D, Ioset JR, Avery VM, PLoS Negl Trop Dis., November 2012, 6(11): e1896.
Click here to read the article / PDF

Fexinidazole: A Potential New Drug Candidate for Chagas Disease by Bahia MT, Mayer de Andrade I, Fontes Martins TA, da Silva do Nascimento AF, de Figueiredo Diniz L,Santana Caldas I, Talvani A, Bourdin Trunz B, Torreele E, Ribeiro I, PLoS Negl Trop Dis., November 2012
Click here to read the article / PDF

Access to Artemisinin-Combination Therapy (ACT) and other Anti-Malarials: National Policy and Markets in Sierra Leone Amuasi JH, Diap G, Blay Nguah S, Karikari P, Boakye I, Jambai A, Kumba Lahai W, Louie KS, Kiechel J-R, PLoS one, October 2012
Click to read PDF

Effect of the Affordable Medicines Facility—malaria (AMFm) on the availability, price, and market share of quality-assured artemisinin-based combination therapies in seven countries: a before-and-after analysis of outlet survey data by Tougher S, the ACTwatch Group, Ye Y, Amuasi JH, Diap G, et al. The Lancet, October 31 2012, 6(11): e1870.
Click to read article

Catechol Pyrazolinones as Trypanocidals: Fragment-Based Design, Synthesis, and Pharmacological Evaluation of Nanomolar Inhibitors of Trypanosomal Phosphodiesterase B1 by Orrling KM, Jansen C, Lan Vu X, Balmer V, Bregy P, Shanmugham A, England P, Bailey D, Cos P, Maes L, Adams E, van den Bogaart E, Chatelain E, Ioset JR, van de Stolpe A, Zorg S, Veerman J, Seebeck T, Sterk GJ, de Esch IJP, and Leurs R. J. Med. Chem., September 2012, 55 (20), pp 8745–8756
Click here to access the article

Pharmacological characterization, structural studies, and in vivo activities of
anti-Chagas disease lead compounds derived from tipifarnib
by Buckner FS, Bahia MT, Suryadevara PK, White KL, Shackleford DM, Chennamaneni NK, Hulverson MA, Laydbak JU, Chatelain E, Scandale I, Verlinde CL, Charman SA, Lepesheva GI, Gelb MH, Antimicrob Agents Chemother. 2012 September; 56(9):4914-21.
Click here to access the article

Genotoxicity profile of fexinidazole - a drug candidate in clinical development for human African trypanomiasis (sleeping sickness) by Tweats D, Bourdin Trunz B, Torreele E. Mutagenesis, September 2012, 27(5):523-32. 
Click here to access the article

Effect of artesunate-mefloquine fixed-dose combination in malaria transmission in Amazon basin communities by Santelli AC, Ribeiro I, Daher A, Boulos M, Marchesini PB, La Corte dos Santos R, Lucena MB, Magalhães I, Leon AP, Junger W, and Ladislau JL. Malaria Journal, 11:286, August 2012
Click here to read the article / PDF

Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis by  Dorlo TPCBalasegaram M, Beijnen JH, and de Vries PJ. Journal of Antimicrobial Chemotherapy, July 2012.
Click here to read the article

Sodium Stibogluconate (SSG) & Paromomycin Combination Compared to SSG for Visceral Leishmaniasis in East Africa: A Randomised Controlled Trial, by Musa A, Khalil E, Hailu A, Olobo J, Balasegaram M, et al.  PLoS Negl Trop Dis., 6(6): e1674. June 2012
Click here to read the article / PDF

An image-based high-content screening assay for compounds targeting intracellular 'leshmania donovani' amastigotes in human macrophages, by 
Siqueira-Neto JL, Moon S, Jang J, Yang G, Lee C, Moon HK, Chatelain E, Genovesio A, Cechetto J, Freitas-Junior LH. PLoS Negl Trop Dis.June 2012, 6(6): e1671.
Click here to read the article / PDF

Translational pharmacokinetics modelling and simulation for the assessment of duration of contraceptive use after treatment with miltefosineby Dorlo TPC, Balasegaram M, Lima MA, de Vries PJ, Beijnen JH, Huitema ADR. Journal of Antimicrobial Chemotherapy, doi: 10.1093/jac/dks164, May 10, 2012
Click here to read the article   / PDF

More efficient ways of assessing treatments for Neglected Tropical Diseases are required: innovative study designs, new endpoints, and markers effets, by Olliaro P, Vaillant M, Sundar S, Balasegaram M. PLoS Negl Trop Dis.May 2012, Vol 6, Issue 5, e1545
Read the article in PDF

Novel 3-Nitro-1H-1,2,4-triazole-Based Amides and Sulfonamides as Potential Antitrypanosomal Agents by Papadopoulou MV, Bloomer WD, Rosenzweig HS, Chatelain E, Kaiser M, Wilkinson SR, McKenzie C, and Ioset JR, Journal of Medicinal Chemistry, 2012 May, 55 (11), 5554-5565
Click here to read the article 

Analogues of Fenarimol Are Potent Inhibitors of Trypanosoma cruzi and Are Efficacious in a Murine Model of Chagas Disease by Keenan M., Abbott MJ, Alexander PW, Armstrong T, Best WM, Berven B, Botero A, Chaplin JH, Charman SA, Chatelain E, von Geldern TW, Kerfoot M, Khong A, Nguyen T, McManus JD, Morizzi J, Ryan E, Scandale I, Thompson RA, Wang SZ, White KL, J. Med. Chem., April 2012, 55 (9), pp 4189–4204.
Click here to read the article

Artesunate-amodiaquine fixed dose combination for the treatment of Plasmodium falciparum malaria in India by Anvikar AR, Sharma B,Shahi BH, Tyagi PK, Bose TK, Sharma SK, Srivastava P, Srivastava B, Kiechel JR, Dash AP, Valecha N. Malaria Journal, 30 March 2012, 11:97
Click here to read the article / PDF

Comparing changes in haematologic parameters occurring in patients included in randomized controlled trials of artesunate-amodiaquine vs single and combination treatments of uncomplicated falciparum in sub-Saharan Africa, by Zwang J, Ndiaye JL, Djimde A, Dorsey G, Martensson A, Karema C, Olliaro P. Malaria Journal, 25 January 2012
Click here to read the article / PDF

Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it? By Freitas-Junior LH, Chatelain E, Kim HA, Siqueira-Neto JL. International Journal for Parasitology: Drugs and Drug Resistance, Volume 2, January 2012
Click here to read the article 

2011

Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness
Kaiser M, Bray MA, Cal M, Bourdin Trunz B, Torreele E, and Brun R, Antimicrob Agents Chemother. 2011 Dec;55(12):5602-8. doi: 10.1128/AAC.00246-11. Epub 2011 Sep 12.
Click here to read the article

Kinetoplastid Parasites by Tomas von Geldern, Michael Oscar Harhay, Ivan Scandale and Robert Don 
Click here to read the article

Hematologic parameters in pediatric uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa by Olliaro P, Djimdé A, Dorsey G, Karema C, Mårtensson A, Ndiaye JL, Sirima SB, Vaillant M, Zwang J. Am J Trop Med Hyg. 2011 Oct;85(4):619-25. 
Click here to read the article

Novel 3-Nitro-1H-1,2,4-triazole-based Aliphatic and Aromatic Amines as anti-Chagasic Agents by Papadopoulou MV, Bourdin B, Bloomer WD, McKenzie C ,  Wilkinson SR, Prasittichai C, Brun R, Kaiser M, Torreele E. Journal of Medicinal Chemistry, Online, October 24, 2011
Click here to read the article

Who Is a Typical Patient with Visceral Leishmaniasis? Characterizing the Demographic and Nutritional Profile of Patients in Brazil, East Africa, and South Asia by Harhay M.o, Olliaro P.L, Vaillant M, Chappuis F, Lima M.A, Ritmeijer K, Costa C.H, Costa D.L, Rijal S, Sundar S, Balasegaram M. Am. J. Trop. Med. Hyg. 84(4), 2011, pp. 543–550
Click here to access the article

Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges by Shing Chang and Jean-Robert Ioset. Future medical chemistry, September 2011, Volume 3, Number 11
Click here to read the article in PDF

Synthesis of 2H- and 14C-labeled fexinidazole and its primary metabolites labeled with 2H by Fontana E, Pignatti A, Venegoni S, and Bray MA. The Journal of labelled compounds and radiopharmaceuticals. August 30, 2011.
Click here to read the article

Pediatric HIV - A Neglected Disease ? by Lallemant M, Chang S, Cohen R, and Pécoul R. The New England Journal of Medicine. 2011 August. 365:581-583.
Click here to read the article / PDF

Changing patterns of malaria during 1996-2010 in an area of moderate transmission in southern Senegal by Brasseur P, Badiane M, Cisse M, Agnamey P, Vaillant MT, Olliaro PL.  Malaria J. 2011 Jul 25;10:203. 
Click here to read the article

Kinetoplastid Parasites by Tomas von Geldern, Michael Oscar Harhay, Ivan Scandale and Robert Don 
Click here to read the article

SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis by Jacobs R.T, Nare B, Wring S.A, Orr M.D, Chen D, Sligar J.M, Jenks M.X, Noe R.A, Bowling T.S, Mercer L.T, Rewerts C, Gaukel E, Owens J, Parham R, Randolph R, Beaudet B, Bacchi C.J, Yarlett N, Plattner J.J, Freund Y, Ding C, Akama T, Zhang Y-K, Brun R, Kaiser M, Scandale I, Don R. PLoS Negl Trop Dis. 2011 June. e1151.
Click here to read the article  / PDF

Potential Drug Development Candidates for Human Soil-Transmitted Helminthiases by Olliaro P, Seiler J, Kuesel A, Horton J, Clark J.N, Don R, Keiser J. PLoS Negl Trop Dis. 2011 June. 5(6): e1138. 
Click here to read the article / PDF

Kinetoplastid Parasites by Tomas von Geldern, Michael Oscar Harhay, Ivan Scandale and Robert Don 
Click here to read the article

Kinetoplastid Parasites by Von Geldern T, Harhay MO, Scandale I and Don R. Top Med Chem. DOI: 10.1007/7355_2011_17 
Click here to read the article

Innovative public-private partnerships to maximize the delivery of anti-malarial medicines: lessons learned from the ASAQ Winthrop experience by Bompart F, Kiechel J-R, Sebbag R, Pecoul B. Malaria Journal. May 2011, 10:143doi:10.1186/1475-2875-10-143
Click here to read the article

Challenges of controlling sleeping sickness in areas of violent conflict: experience in the Democratic Republic of Congo by Tong J, Valverde O, Mahoudeau C, Yun O, Chappuis F. Conflict and Health. May 2011, 5:7 doi:10.1186/1752-1505-5-7
Click here to read the article

1-Aryl-4-nitro-1H-imidazoles, a new promising series for the treatment of human African trypanosomiasis 
by Bourdin Trunz B, Jędrysiak R, Tweats D, Brun R, Kaiser M, Suwiński J and Torreele E. European Journal of Medicinal Chemistry, available online 5 February 2011, doi: 10.1016/j.ejmech.2011.01.071
Nitroimidazoles are a well-known class of antibacterial and antiprotozoal drugs but in spite of the widespread clinical and veterinary use of these drugs, this family has been stigmatized in part due to associated genotoxicity problems. Here we report the synthesis, the anti-trypanosomal activity and a structure–activity relationship (SAR) study of a series of about fifty 1-aryl-4-nitro-1H-imidazoles, with an emphasis on selected in vivo active molecules. Compounds 4-nitro-1-{4-(trifluoromethoxy)phenyl}-1H-imidazole and 1-(3,4-dichlorophenyl)-4-nitro-1H-imidazole are promising leads for the treatment of human African trypanosomiasis (HAT or sleeping sickness), including the fatal stage 2 of the disease, for which new treatments are urgently needed.
Click here to read the article

The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership by Lacaze C, Kauss T, Kiechel J-R, Caminiti A, Fawaz F, Terrassin L, Cuart S, Grislain L, Navaratnam V, Ghezzoul B, Gaudin K, White N.J, Olliaro P, Millet P. Malaria Journal. May 2011, 10:142doi:10.1186/1475-2875-10-142
Click here to read the article

Standardised versus actual white cell counts in estimating thick film parasitaemia in African children under fiveby Olliaro P, Djimdé A, Karema C, Mårtensson A, Ndiaye JL, Sirima SB, Dorsey G, Zwang J. Tropical Medicine & International Health. May 2011. 16(5):551-4. doi: 10.1111/j.1365-3156.2011.02738.x
Click here to read the article

Drug discovery and development for neglected diseases: the DNDi model by Chatelain E and Ioset J-R. Drug Design, Development and Therapy, 2011 March, Vol. 5, 175-181.
Click here to read the article 

Access to artesunate-amodiaquine, quinine and other anti-malarials: policy and markets in Burundi by Amuasi JH, Diap G, Blay-Nguah S, Boakye I, Karikari PE, Dismas B, Karenzo J, Nsabiyumva L, Louie KS, Kiechel JMalaria Journal 2011, 10:34 (10 February 2011) doi:10.1186/1475-2875-10-34
Conclusions: 
AS-AQ was widely available and affordable in the public and NGO markets of hard-to-reach post-conflict communities in Burundi. However greater accessibility and affordability of policy recommended anti-malarials in the private market sector is needed to improve country-wide policy uptake.
Click here to read the article / PDF

Registering New Drugs for Low-Income Countries: The African Challenge by Moran M, Strub-Wourgaft N, Guzman J, Boulet P, Wu L, Pecoul B. PLoS Medicine, 2011 February, Vol. 8, Issue 2, e1000411.
Click here to read the article / PDF
More about the Regulatory process in the African context here

Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand by Krudsood S, Looareesuwan S, Wilairatama P, Leowattana W, Tangpukdee N, Chalermrut K, Ramanathan S, Navaratnam V, Olliaro P, Vaillant M, Kiechel J-R, Taylor V.R.J. Tropical Medicine and International Health, 2011 January, doi:10.1111/j.1365-3156.2010.02714.x. 
Click here to read the article
/ PDF

Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial by Sundar S, Sinha P.K, Rai M, Verma D.K, Nawin K, Alam S, Chakravarty J, Vaillant M, Verma N, Pandey K, Kumari P, Lal C.S, Arora R, Sharma B, Ellis S, Strub-Wourgaft N, Balasegaram M, Olliaro P, Das P, Modabber F. Lancet, 2011 January, DOI:10.1016/S0140-6736(10)62050-8. 
Click here to read the article / PDF

2010

Fexinidazole – A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness by Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazué G, Bray M A, Pécoul B. PLoS Negl Trop Dis., 2010 December, Vol. 4, Issue 12, e923. 
Human African trypanosomiasis (HAT) is a fatal parasitic disease caused by trypanosomes. Current treatment options for HAT are scarce, toxic, no longer effective, or very difficult to administer, in particular for the advanced, fatal stage of the disease (stage 2, chronic HAT). Here it is shown that fexinidazole, a 2-substituted 5-nitroimidazole rediscovered by the Drugs for Neglected Diseases initiative (DNDi) after extensive compound mining efforts, could be a short-course, safe and effective oral treatment for both acute and chronic HAT and that could be implemented at the primary health care level.
Click here to read the article

Leishmaniasis vaccines: past, present and future by F. Moddaber. International Journal of antimicrobial agents, 2010 Nov;36 Suppl 1:S58-61. 
No vaccine exists against any form of leishmaniasis. Because recovery from infection is usually accompanied by a strong immunity and because it is possible to protect experimental animals against live challenge, hope for the development of a vaccine for humans has been high. However, leishmaniasis is a disease of the poor and the market for a vaccine is very limited. Until a few years ago, with minimal resources, only a pragmatic approach was possible for testing the first-generation vaccines (i.e. killed whole parasites). Recently, funding has become available for developing defined second-generation vaccines, including recombinant proteins and DNA constructs. With new adjuvants also being developed there is new hope, and several new vaccines are in development against leishmaniasis.
Click here to read the article

Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study by Musa A, Younis B, Fadlalla A, Royce C, Balasegaram M, wasunna M, Hailu A, Edwards T, Omollo R, Mudawi M, Kokwaro G, El-Hassan A, Khalil E. PLoS Negl Trop Dis., 2010 October, 4(10):e855 
A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days.
Click here to read the article

Geographical Variation in the Response of Visceral Leishmaniasis to Paromomycin in East Africa: A Multicentre, Open-Label, Randomized Trial by Hailu A, Musa A, Wasunna M, Balasegaram M, Yifru S, Mengistu G, Hurissa Z, Hailu W, Weldegebreal T, Tesfaye S, Makonnen E, Khalil E, Ahmed O, Fadlalla A, El-Hassan A, Raheem M, Muellerm, Koummuki Y, Rashid J, Mbui J, Mucee G, Njoroge S, Manduku V, Musibi A, Mutuma G, Kirui F, Lodenyo H, Mutea D, Kirigi G, Edwards T, Smith P, Muthami L, Royce C, Ellis S, Alobo M, Omollo R, Kesusu J, Owiti R, Kinuthia J, for the Leishmaniasis East Africa Platform (LEAP) group. PLoS Negl Trop Dis., 2010 October, 4(10):e709 
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.
Click here to read the article

Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial by Smithuis F, Kyaw Kyaw M, Phe O, Win T, Phyo Aung P, Pyay Phyo Oo A, Naing A L, Yee Nyo M, Htun Myint N Z, Imwong M, Ashley E, Lee S J, White N J. The Lancet Infectious Diseases, 2010 September, Vol. 10, Issue 10, Pages 673 - 681. 
The Artemisinin-combination therapy (ACT) is recommended as first-line treatment of P. falciparum malaria worldwide, and fixed-dose combinations are preferred by WHO. This study aimed to compare effectiveness of all four WHO-recommended fixed-dose ACTs (artesunate–mefloquine, artesunate–amodiaquine, dihydroartemisinin–piperaquine, artemether–lumefantrine) and a loose tablet combination of artesunate and mefloquine in Burmese adults and children. Artesunate–mefloquine provided the greatest post-treatment suppression of malaria.
Click here to read the article / PDF

Cost-Effectiveness Analysis of Combination Therapies for Visceral Leishmaniasis in the Indian Subcontinent by Meheus F, Balasegaram M, Olliaro P, Sundar S, Rijal S, Faiz Md. Al, Boelaert M. PLoS Negl Trop Dis., 2010 September, 4(9):e818 
Visceral leishmaniasis is a systemic parasitic disease that is fatal unless treated. The article assesses the cost and costeffectiveness of alternative strategies for the treatment of visceral leishmaniasis in the Indian subcontinent. In particular it examines whether combination therapies are a cost-effective alternative compared to monotherapies.
Click here to read the article

Nature Outlook Chagas Disease supplementNature Supplement, 2010 June, Vol. 465, No. 7301 suppl. ppS3-S22
Chagas disease is one of the most neglected of the tropical diseases, yet millions of people are infected with it. There are only two available drugs to treat it, both of which are more than 40 years old and neither of which is ideal. As the global population has become more internationally mobile, Chagas disease has spread from Latin America to become a worldwide threat. This Outlook highlights some of the progress in understanding and treating Chagas disease over its 101 years of recent history and outlines the challenges still to be met.

 

New fixed dose artesunate/mefloquine for treating multidrug resistant Plasmodium falciparum in adults – a comparative phase IIb safety and pharmacokinetic study with standard dose non-fixed artesunate plus mefloquine by Krudsood S, Looareesuwan S, Tangpukdee N, Wilairatama P, Phumratanaprapin W, Leowattana W, Chalermrut K, Ramanathan S, Navaratnam V, Olliaro P, Vaillant M, Kiechel JR, Taylor WRJ. AAC, 2010 June, doi:10.1128/AAC.01187-09  
A new fixed dose artesunate (AS)/mefloquine (MQ) was assessed in adults, hospitalized for 28 days, with uncomplicated, drug resistant falciparum malaria.
Click here to read the article / PDF 

NECT Is Next: Implementing the New Drug Combination Therapy for Trypanosoma brucei gambiense Sleeping Sickness by Yun O, Priotto G, Tong J, Flevaud L, Chappuis F. PLoS Negl Trop Dis., 2010 May, 4(5):e720 
In April 2009, a new treatment option for second-stage T. b. gambiense HAT, nifurtimox-eflornithine combination therapy (NECT), was added to the WHO Essential Medicines List (EML). In the current context, NECT stands as the most promising first-line treatment for second-stage T. b. gambiense HAT. The article describes the developments and challenges in rolling out and implementing NECT in HAT-endemic areas.
Click here to read the article

Pharmacokinetics and Comparative Bioavailability of Artesunate and Mefloquine Administered Separately or as a Fixed Combination Product to Healthy Volunteers and Patients with Uncomplicated Plasmodium falciparum Malaria by Olliaro P, Ramanathan S, Vaillant M, Reuter S, Evans A, Krudsood S, Looareesuwan S,
Kiechel J-R, Taylor W, and Navaratnam V. Journal of Bioequivalence & Bioavailability, 2010 May, Volume 2(3): 059-066.
The pharmacokinetics of artesunate, dihydroartemisinin, the artesunate metabolite and predominant species and mefloquine were assessed in a single-dose, randomised, crossover design study in healthy volunteers and in a multiple-dose, randomised, parallel group study in patients with uncomplicated falciparum malaria.
Click here to read the article

Population Pharmacokinetics and Pharmacodynamic considerations of Amodiaquine and Desethylamodiaquine in Kenyan Adults with uncomplicated malaria receiving the Artesunate-Amodiaquine combination therapy by Jullien V, Ogutu B, Juma E, Carn G, Obyono C, and Kiechel J-R. Antimicrobial Agents and Chemotherapy. 2010 April 5. 01496-09.
Amodiaquine (AQ) is an antimalarial drug that was frequently combined with artesunate (AS) for the treatment of uncomplicated malaria due to Plasmodium falciparum and is now available as a fixed dose combination. Despite its widespread use, the simultaneous  pharmacokinetics of AQ and its active metabolite, desethylamodiaquine (DAQ) were not characterized to date in patients. The pharmacokinetics of AQ and DAQ were therefore investigated in 54 adult patients receiving the AS/AQ combination by the use of a population approach. AQ followed a 1-compartment model with first-order absorption and elimination as well as a first-order and irreversible transformation  into DAQ, which in turn followed a 2-compartment model with first-order elimination from its central compartment. Mean AQ apparent clearance and distribution volume were 3410 L/h and 39200 L respectively. Mean terminal elimination half-life of DAQ was 211 h. Bodyweight was found to explain the interindividual variability of the apparent volume of distribution of AQ and the elimination rate constant of DAQ. A new dosage form consisting in a fixed dose combination of AS and AQ was found to have no effect on the pharmacokinetic parameters of AQ and DAQ. All patients achieved parasite clearance within 4 days following the initiation of the treatment, which prevented the investigation of the possible relationship between DAQ exposure and treatment outcome. This study provided the first simultaneous pharmacokinetic model for AQ and DAQ.
Click here to access the full article | PDF

"Manifesto" for Advancing the Control and Elimination of Neglected Tropical Diseases by Hotez P. and Pecoul B. In PLoS Negl Trop Dis. 2010 May, Vol. 4, Issue 5, e 718
The "manifesto" is meant to mobilise the global community to increase financial support for Neglected Tropical Diseases. All NTDs are "tool ready" but also "tool deficient" as for many diseases tools are suboptimal, incomplete or inadequate. Thus, increased investments in R&D are urgently needed. The eight-point "manifesto" published as an editorial in PLoS NTDs is co-authored by Peter Hotez, President of the Sabin Vaccine Institute, and Bernard Pécoul, Executive Director of DNDi.
Click here to read the article   

Antileishmanial High-Throughput Drug Screening Reveals Drug Candidates with New Scaffolds by Siqueira-Neto J L, Song O-R., Oh H, Sohn J-H, Yang G, Nam J, Jang J, Cechetto J, Lee C B, Moon S, Genovesio A, Chatelain E, Christophe T, Freitas-Junior L H. PLoS Negl Trop Dis., 2010 May, Volume 4, Issue 5.
Drugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need for new drugs as a treatment solution for this neglected disease. Here we show the development and implementation of an automated high-throughput viability screening assay for the discovery of new drugs against Leishmania. Assay validation was done with Leishmania promastigote forms, including the screening of 4,000 compounds with known pharmacological properties. In an attempt to find new compounds with leishmanicidal properties, 26,500 structurally diverse chemical compounds were screened. A cut-off of 70% growth inhibition in the primary screening led to the identification of 567 active compounds. Cellular toxicity and selectivity were responsible for the exclusion of 78% of the pre-selected compounds. The activity of the remaining 124 compounds was confirmed against the intramacrophagic amastigote form of the parasite. In vitro microsomal stability and cytochrome P450 (CYP) inhibition of the two most active compounds from this screening effort were assessed to obtain preliminary information on their metabolism in the host. The HTS approach employed here resulted in the discovery of two new antileishmanial compounds, bringing promising candidates to the leishmaniasis drug discovery pipeline.
Click here to read the article

Anti-malarial market and policy surveys in sub-Saharan Africa by Diap G, Amuasi J, Boakye I, Sevcsik A-M, and Pecoul B. Malaria Journal Supplement, BioMed Central 2010 April, 9(1):S1
Following the development by DNDi and the FACT partners of the ASAQ fixed-dose combination, according to WHO recommendations (easy to use, affordable, field adapted and non-patented), and despite the fact that ASAQ fixed-dose combination is registered and available in more than 25 African endemic countries and eligible for Global Fund and other international funding, general access to ACTs for patients is still inadequate. 
At the recent meeting (Sept 18, 2009) on public and private market and policy survey: ‘Antimalarial market and policy surveys in sub-Saharan Africa’, a validated methodology for these surveys in two countries (Sierra Leone and Burundi) was discussed. Real-life data were presented in a highly interactive brainstorming session among key stakeholders, in a time when market issues for malaria are at the top of the international agendas.
Click here to read the article

In vitro and in vivo experimental models for drug screening and development for Chagas disease by Romanha A J, de Castro S L, de Nazaré Correia Soeiro M, Lannes-Vieira Ribeiro I, Talvani A, Bourdin B, Blum B, Olivieri B, Zani C, Spadafora C, Chiari E, Chatelain E, Chaves G, Calzada J E, Bustamante J M, Freitas-Junior L H, Romero L I, Bahia M T, Lotrowska M, Soares M, Andrade S G, Armstrong T, Degrave W, de Araújo Andrade Z. Mem Inst Oswaldo Cruz, 2010 March, Vol. 105 (2): 233-238
Although the occurrence of acute cases of Chagas disease has declined, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of a workshop held in Rio de Janeiro, Brazil, in November 2008: the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease.
Click here to read the article

Combination therapy for visceral leishmaniasis by van Griensven J, Balasegaram M, Meheus F, Alvar J, Lynen L, Boelaert M. In Lancet Infect Dis 2010; 10: 184–94
Combination therapy for the treatment of visceral leishmaniasis has increasingly been advocated as a way to increase treatment efficacy and tolerance, reduce treatment duration and cost, and limit the emergence of drug resistance. The authors reviewed the evidence and potential for combination therapy, and the criteria for the choice of drugs in such regimens.
Click here to access the article / PDF

2009

Developments in the treatment of visceral leishmaniasis by den Boer M. L, Alvar J, Davidson‌ R. N, Ritmeijer‌ K, Balasegaram M. In Expert Opinion on Emerging Drugs, 2009 Sept, 14; 3, 395-410.
Visceral leishmaniasis (VL) is one of the most neglected parasitic diseases causing large scale mortality and morbidity among the poorest of the poor in the Indian subcontinent and Africa. Objective: This review aims to describe the potential and the (lack of) current impact of newly developed treatments on the control of VL. It describes how the problem of an empty research pipeline is addressed, and discusses the emerging threat of incurable HIV/VL coinfection. Methods: The literature was searched for drugs used in VL. Conclusion: Research and development of VL drugs has received a financial boost but no new drugs are expected in the next 5 years. Only three new and highly effective treatments have been licensed in the past 10 years. These remain, however, largely inaccessible as VL control programs in the developing world are lacking. This is deserving of immediate and urgent attention, especially in the context of the rapidly expanding HIV/VL coinfection.
Click here to access the article

Population pharmacokinetics of artesunate and amodiaquine in African children by Stepniewska K, Taylor W, Sirima S.B, Ouedraogo E.B, Ouedraogo A, Gansane A, Simpson J.A, Morgan C.C, White N.J, Kiechel J-R. Malaria Journal 2009 Aug 20, 8:200.
Pharmacokinetic (PK) data on amodiaquine (AQ) and artesunate (AS) are limited in children, an important risk group for malaria. The aim of this prospective population pharmacokinetic study of AS and AQ was to evaluate the PK properties of “ASAQ”, a newly developed and registered fixed dose combination (FDC) of AS and AQ in African children. Conducted in 70 children aged six months to five years, the study utilized population PK models for dihydroartemisinin (DHA) and desethylamodiaquine (DeAq), the principal pharmacologically active metabolites of AS and AQ, respectively, and total artemisinin anti-malarial activity. Relative bioavailability between products was compared by estimating the ratios (and 95% CI) between the areas under the plasma concentration-time curves (AUC). The bioavailability of the co-formulated AS-AQ FDC was similar to that of the separate tablets for desethylamodiaquine, DHA and the total anti-malarial activity. These data support the use this new AS-AQ FDC in children with acute uncomplicated falciparum malaria.
Click here to access the full article on the website / PDF

Efficacy of artesunate-amodiaquine for treating uncomplicated P. falciparum malaria in Sub-Saharan Africa: a multi-centre analysis by Zwang J, Olliaro P, Barennes H, Bonnet M, Brasseur P, Bukirwa H, Cohuet S, D'Alessandro U, Djimde A, Martensson A, Yeka A, Karema C, Guthmann J-P, Hamour S, Ndiaye J-L, Rwagacondo C, Sagara I, Same-Ekobo A, Sirima S, van den Broek I, Taylor W, Dorsey G, Randrianarivelojosia M. Malaria Journal 2009 Aug 23; 8:203.
This multi-centre analysis led by Julien Zwang at the Shoklo Malaria Research Unit addresses the efficacy of artesunate-amodiaquine, a very important candidate for the treatment of uncomplicated malaria globally. The analysis of patient-level data examining the efficacy of AS&AQ compared with local standard therapy, makes a strong case for the use of AS&AQ in all transmission settings. The analysis, sponsored by DNDi, has pooled data from 26 drug studies in a majority of paediatric malaria cases in sub-Saharan Africa identified through a systematic search and has focused on efficacy as safety will be reported separately. While not without limitations, this analysis contributes to the evidence base as to the proper use of ACTs, particularly the AS&AQ combination, and has provided results consistent with the recently published Cochrane systematic review and meta-analysis on ACTs (including AS&AQ.)
Click here to access the full article

Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial by Priotto G, Kasparian S, Mutombo W, Ngouama D, Ghorashian S, Arnold U, Ghabri S, Baudin E, Buard V, Kazadi-Kyanza S, Ilunga M, Mutangala W, Pohlig G, Schmid C, Karunakara U, Torreele E, Kande V. In Lancet. 2009 July; 374:56-64.
This pivotal Phase III study assessed the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) for second-stage disease compared with the gold-standard regimen of eflornithine in 287 patients at four HAT treatments centres in the Republic of the Congo and the Democratic Republic of Congo. The results showed NECT to be comparable with eflornithine in efficacy (>90% cure in both treatment arms at 18-month follow-up) and to be well tolerated. Patient follow-up at 18 months after treatment was 93%, which is exceptionally high for these types of studies in HAT and further contributes to the robustness of the study. In comparison with eflornithine, NECT is easier to administer, more affordable and with simpler logistics, and potentially protective against the emergence of resistant parasites. The authors conclude that NECT represents an improved alternative for stage 2 HAT treatment and is suitable for first-line use in HAT control programmes. 
Click here to access the full article / PDF

An accompanying Lancet editorial calls the NECT study ‘more than a small victory over sleeping sickness‘.
Click here to access the full article / PDF

Randomized, multicentre assessment of the efficacy and safety of ASAQ – a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malariaby Ndiaye J-L, Randrianarivelojosia M, Sagara I, Brasseur P, Ndiaye I, Faye B, Randrianasolo L, Ratsimbasoa, Forlemu D, Moor V A, Traore A, Dicko Y, Dara N, Lameyre V, Diallo M, Djimde A, Same-Ekobo A, Gaye O. Malaria Journal 2009 Jun 8; 8:125.
Click here to access the full article

A Business Plan To Help The ‘Global South’ In Its Fight Against Neglected Diseases by Frew S.E, Liu V.Y, and Singer P.A., Health Affairs, 2009, Vol. 28, 6:1760-73
Featured ArticleAlthough neglected tropical diseases (NTDs) threaten the health of those living in the developing world, innovation directed toward addressing NTDs is comparatively meager. Health biotechnology firms in rapidly growing economies in the global South are developing and selling vaccines, diagnostics, and therapeutics for these diseases to local markets. In this paper the authors identify a pipeline of sixty-two NTD products from seventy-eight “Southern” companies. They also propose creation of a Global Health Accelerator—a new nonprofit organization whose mission would be to support and help grow this Southern source of affordable innovation for NTDs.
Click here to access the article

Drug discovery for neglected diseases: View of a public-private partnership by Chatelain E, Don R. In Antiparasitic Antibacterial Drug Discovery by Paul M. Selzer (Ed); 2009 Apr: Wiley-Blackwell.
In answer to the lack of modern and effective drugs for diseases such as human African trypanosomiasis (HAT; sleeping sickness) and Chagas disease which present no financial viability for the pharmaceutical industry, new models of drug discovery have been developed.
Drug discovery for neglected diseases: View of a public-private partnershipThe Drugs for Neglected Diseases initiative (DNDi) has adopted a model closely related to that of a virtual biotechnology company for identifying and optimizing drug leads. 
Click here to download the full manual [PDF]


Tolerability and pharmacokinetics of non-fixed and fixed combinations of artesunate and amodiaquine in Malaysian healthy normal volunteers by Navaratnam V, Ramanathan S, Wahab MSA, Hua GS, Mansor SM, Kiechel JR, Vaillant M, Taylor WRJ, Olliaro P. Eur J Clin Pharmacol 2009 Apr 30. 
Tolerability and pharmacokinetics of non-fixed and fixed combinations of artesunate and amodiaquine n Malaysian healthy normal volunteersDue to limited pharmacokinetic data available for the combination artesunate + amodiaquine, which is used widely to treat uncomplicated malaria, this study examined the bioavailability and tolerability of a fixed and loose combination of artesunate + amodiaquine with a 2×2 cross-over design in 24 healthy volunteers. The authours concluded that both combinations were well tolerated and had comparable pharmacokinetic profiles, and that differences are unlikely to be clinically relevant. 
Click here to download the full article [PDF]
More Information on ASAQ

Drug Screening for Kinetoplastid Diseases: A Training Manual for Screening in Neglected Diseases by Ioset JR, Brun R, Wenzler T, Kaiser M, Yardley V. DNDi and Pan-Asian Screening Network 2009 Apr: 74pp. 
The production of this research manual is one of the deliverables of the Pan-Asian Network for Drugs for Neglected Diseases from Natural Substances. This comprehensive manual is a practical and user-friendly guide for essays Drug discovery for neglected diseases: View of a public-private partnershipavailable to screen natural products against pathogens responsible for some of the neglected diseases. It brings recommendations and protocols related to these essays, describes the principles of good scientific practice, and lists information about materials requested for the essays, institutions using them as well as key references. 
Click here to download the full manual [PDF]

New, Improved Treatments for Chagas Disease: From the R&D Pipeline to the Patients by Ribeiro I, Sevcsik AM, Alves F, Diap G, Don R, Harhay MO, Chang S, Pecoul B. In PLoS Negl Trop Dis. 3(7): e484.
This policy paper outlines the urgent need for new treatments for Chagas, examines barriers to development and evaluation of new drugs, and reports on progress in bringing new treatments to patients. Part of a Chagas disease series published by PLoS NTD, this paper focuses on the efforts of DNDi and others to develop and make available better-adapted diagnostic and treatment tools. Published upon the occasion of the 100th anniversary of Chagas disease, this article also mentions a newly launched campaign, www.treatchagas.org, to increase awareness about Chagas disease, and is joined in the series by an editorial covering the unfinished public health agenda and a research article on MSF’s 10-year experience of treating Chagas disease in Latin America. 

Click here to access full-text article.  
Although the occurrence of acute cases of Chagas disease has declined, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of a workshop held in Rio de Janeiro, Brazil, in November 2008: the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease.
Click here to read the article

Related articles in the series:
•    Franco-Paredes C, Bottazzi ME, Hotez PJ (2009). The Unfinished Public Health Agenda of Chagas Disease in the Era of GlobalizationPLoS Negl Trop Dis 3(7): e470. 
Click here to access full-text article.  
•    Yun O, Lima MA, Ellman T, Chambi W, Castillo S, et al. (2009). Feasibility, Drug Safety, and Effectiveness of Etiological Treatment Programs for Chagas Disease in Honduras, Guatemala, and Bolivia: 10-Year Experience of Médecins Sans FrontièresPLoS Negl Trop Dis 3(7): e488. 
Click here to access full-text article. 


 Drug discovery for neglected diseases: View of a public-private partnership by Chatelain E, Don R. In Antiparasitic Antibacterial Drug Discovery by Paul M. Selzer (Ed); 2009 Apr: Wiley-Blackwell.
In answer to the lack of modern and effective drugs for diseases such as human African trypanosomiasis (HAT; sleeping sickness) and Chagas disease which present no financial viability for the pharmaceutical industry, new models of drug discovery have been developed.
Drug discovery for neglected diseases: View of a public-private partnership The Drugs for Neglected Diseases initiative (DNDi) has adopted a model closely related to that of a virtual biotechnology company for identifying and optimizing drug leads.
Click here to download the full manual [PDF]


Drug Screening for Kinetoplastid Diseases: A Training Manual for Screening in Neglected Diseases by Ioset JR, Brun R, Wenzler T, Kaiser M, Yardley V. DNDi and Pan-Asian Screening Network 2009 Apr: 74pp. 
The production of this research manual is one of the deliverables of the Pan-Asian Network for Drugs for Neglected Diseases from Natural Substances. This comprehensive manual is a practical and user-friendly guide for essays available to screen Drug discovery for neglected diseases: View of a public-private partnershipnatural products against pathogens responsible for some of the neglected diseases. It brings recommendations and protocols related to these essays, describes the principles of good scientific practice, and lists information about materials requested for the essays, institutions using them as well as key references. 
Click here to download the full manual [PDF]

Validation of high performance liquid chromatography-electrochemical detection methods with simultaneous extraction procedure for the determination of artesunate, dihydroartemisinin, amodiaquine and desethylamodiaquine in human plasma for application in clinical pharmacological studies of artesunate-amodiaquine drug combinationby Lai CS, Nair NK, Muniandy A, Mansor SM, Olliaro PL, Navaratnam V. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Feb 15; 877(5-6):558-62.
With the expanded use of the combination of artesunate (AS) and amodiaquine (AQ) for the treatment of falciparum malaria and the abundance of products on the market, comes the need for rapid and reliable bioanalytical methods for the determination of the parent compounds and their metabolites. While the existing methods were developed for the determination of either AS or AQ in biological fluids, the current validated method allows simultaneous extraction and determination of AS and AQ in human plasma. The method is sensitive, selective, accurate, reproducible and suited particularly for pharmacokinetic study of AS–AQ drug combination and can also be used to compare the bioavailability of different formulations, including a fixed-dose AS–AQ co-formulation.
Click here to access the full article 

Dosing accuracy of artesunate and amodiaquine as treatment for falciparum malaria in Casamance, Senegal by Brasseur P, Agnamey P, Gaye O, Cisse M, Badiane M, Vaillant M, Taylor WR, Olliaro P. Trop Med Int Health. 2009 Jan; 14(1):79-87.
Several products of artesunate plus amodiaquine (AS + AQ) are being deployed in malaria-endemic countries for treating uncomplicated falciparum malaria but dosing accuracy and consequential effects on efficacy and tolerability have not been examined. Patients were treated and followed by research teams or local health centre staff in Casamance, Senegal. AS + AQ was given as: (i) loose combination (AS 50 mg, AQ 200 mg), dosed on body weight, or (ii) co-blistered product (AS 50 mg, AQ 153 mg) dosed by weight or age. It was concluded that Artesunate is easier to dose than AQ. Currently available age-dosed, co-blistered AS + AQ tends to overdose AQ and is less well tolerated than loose tablets. 
Click here to download the full article [PDF]

2008

Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial by Gomes M.F, Faiz M.A, Gyapong J.O, Warsame M, Agbenyega T, Babiker A, Baiden F, Yunus E.B, Binka F, Clerk C, Folb P, Hassan R, Hossain M.A, Kimbute O, Kitua A, Krishna S, Makasi C, Mensah N, Mrango Z, Olliaro P, Peto R, Peto T.J, Rahman M.R, Ribeiro I, Samad R, White N.J, for the Study 13 Research Group. The Lancet. 2008 Dec 8; 373:9663.
Won the "Best Research Paper of the year" award provided by the BMJ
Click here to access the article 

New lycorine-type alkaloid from Lycoris traubii and evaluation of antitrypanosomal and antimalarial activities of lycorine derivatives by Toriizuka Y, Kinoshita E, Kogure N, Kitajima M, Ishiyama A, Otoguro K, Yamada H, Omura S, Takayama H. Bioorg Med Chem. 2008 Dec 15; 16(24): 10182-9. Epub 2008 Oct 30.
A new lycorine derivative LT1 was isolated from the aerial part and bulbs of Lycoris traubii Hayward (Amaryllidaceae). Its structure including absolute configuration was established by spectroscopic analysis and semi-synthesis to be 1-O-(30S)-hydroxybutanoyllycorine. Some lycorine ester derivatives including LT1 were examined for their inhibitory activity against Trypanosoma brucei brucei, the parasite associated with sleeping sickness, and against Plasmodium falciparum, the causative agent of malaria. 
Click here to access the full article

New lycorine-type alkaloid from Lycoris traubii and evaluation of antitrypanosomal and antimalarial activities of lycorine derivatives by Toriizuka Y, Kinoshita E, Kogure N, Kitajima M, Ishiyama A, Otoguro K, Yamada H, Omura S, Takayama H. Bioorg Med Chem. 2008 Dec 15; 16(24): 10182-9. Epub 2008 Oct 30.
A new lycorine derivative LT1 was isolated from the aerial part and bulbs of Lycoris traubii Hayward (Amaryllidaceae). Its structure including absolute configuration was established by spectroscopic analysis and semi-synthesis to be 1-O-(30S)-hydroxybutanoyllycorine. Some lycorine ester derivatives including LT1 were examined for their inhibitory activity against Trypanosoma brucei brucei, the parasite associated with sleeping sickness, and against Plasmodium falciparum, the causative agent of malaria. 
Click here to access the full article

Natural Products for Neglected Diseases: A Review by Ioset JR. Current Organic Chemistry. 2008 May; 12 (8): 643-666. 
Neglected diseases are responsible for high mortality and morbidity each year in low-income countries. Due to the lack of vaccines and of safe, effective and affordable treatments, there is an urgent need to reinforce the existing therapeutic arsenal against these killers. One of the main opportunities is through the discovery of new molecules from natural origin. The gaps identified in the R&D process aiming to deliver new medicines for neglected diseases however also apply to natural products. A key review of the most promising antiprotozoal molecules recently discovered from natural resources is presented here together with a critical update on their current development status.

The Story of ASAQ: the first antimalarial product development partnership success by Pécoul B, Sevcsik A-M, Amuasi J, Diap G, Kiechel J-R. Health Partnerships Review, Global Forum for Health Research, Geneva, 2008 May: 77-83.    
ASAQ, the new fixed-dose combination of artesunate (AS) and amodiaquine (AQ), is now available to treat malaria throughout sub-Saharan Africa. It is the first drug developed by the FACT (fixed-dose, artemisinin-based combination therapy) partners, and its development can serve as a model for future drug development to treat neglected diseases. The article describes the rationale and the process behind the development; the partners involved in the development, production and promoting availability; and the steps taken in the registration and postregistration phases to ensure that ASAQ reaches the populations who can most benefit from it.
Click here to download the full article [PDF]

2007

Nifurtimox-Eflornithine Combination Therapy for Second-Stage Trypanosoma brucei gambiense Sleeping Sickness: A Randomized Clinical Trial in Congo by Priotto G, Kasparian S, Ngouama D, Ghorashian S, Arnold U, Ghabri S, Karunakara U. Clinical Infectious Diseases 2007 Dec; 45: 1435-1442.
Current treatment options for patients with second-stage disease are either highly toxic or impracticable in field conditions. The article compares the efficacy and safety of the nifurtimox-eflornithine drug combination with the standard eflornithine regimen for the treatment of second-stage disease. The nifurtimox-eflornithine combination appears to be a promising first-line therapy for second-stage sleeping sickness. 
Click here to download the full article [PDF]

The Challenges of Chagas Disease - Grim Outlook or Glimmer of Hope? By Tarleton RL, Reithinger R, Urbina JA, Kitron U, Gürtler RE. Plos Med 2007 Dec; 4 (12): 1852-1857. 
Despite estimates of up to 15 million existing cases and 50,000–200,000 new infections per year, funding for research, prevention, and control has been limited, and therapeutic options remain unsatisfactory. Consequently, several editorials and perspectives have recently drawn attention to Chagas disease and T. cruzi [8–10]. While these papers highlighted the impact of this disease on public health in the Americas, and rightly pointed out that major achievements have been made in its control, they failed to emphasize several key challenges that are currently undermining these achievements and that must be urgently addressed in order to move to the next stage: ensuring the long-term and sustainable control of this devastating disease. 
Click here to download the full article [PDF]

Efficacy and safety of artesunate plus amodiaquine in routine use for the treatment of uncomplicated malaria in Casamance, southern Senegal by Brasseur P, Agnamey P, Gaye O, Vaillant M, Taylor WR, Olliaro PL. Malar J. 2007 Nov 15; 6:150.
Artesunate plus amodiaquine (AS+AQ) was used to treat slide-proven Plasmodium falciparum-infected patients of all ages in the Oussouye district, Casamance, Senegal, over a period of six years (2000 to 2005). AS+AQ in combination was highly efficacious and well-tolerated in this area and justifies the decision to use it as first line treatment. Long-term monitoring of safety and efficacy should continue. 
Click here to download the full article [PDF]

An analytical method with a single extraction procedure and two separate high performance liquid chromatographic systems for the determination of artesunate, dihydroartemisinin and mefloquine in human plasma for application in clinical pharmacological studies of the drug combination by Lai CS, Nair NK, Mansor SM, Olliaro PL, Navaratnam V. J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Oct 1; 857(2): 308-14. 
The combination of two sensitive, selective and reproducible reversed phase liquid chromatographic (RP-HPLC) methods was developed for the determination of artesunate (AS), its active metabolite dihydroartemisinin (DHA) and mefloquine (MQ) in human plasma. The method was found to be suitable for use in clinical pharmacological studies. 
Click here to access the full article

Nature Outlook Neglected Diseases Supplement by various authors. Outlook: Neglected diseases 2007 Sep (449) , No. 7159 pp157-182
Tropical diseases affect more than one billion people, yet there are few effective treatments. And despite much research activity, scientific innovations with therapeutic potential are not making it out of the laboratory. The articles in this Outlook examine what can be done to stimulate the development of effective medicines and deliver them to the people who need them most. 
Click here to download the full supplement [PDF] - (Nine chapters in PDF)

Kala-Azar Outbreak in Libo Kemkem, Ethiopia: Epidemiologic and Parasitologic Assessment by Alvar J, Bashaye S, Argaw D, Cruz I, Aparicio P, Kassa A, Orfanos G, Parreno F, Babaniyi O, Gudeta N, Canavate C, Bern C. Am J Trop Med Hyg. 2007 Aug; 77(2): 275-82. 
In May 2005, visceral leishmaniasis (VL) was recognized for the first time in Libo Kemkem, Ethiopia. In October 2005, a rapid assessment was conducted using data from 492 patients with VL treated in the district health center and a household survey of 584 residents of four villages. Local transmission resulted from multiple introductions, is now well established, and will be difficult to eradicate. 
Click here to download the full article [PDF]

Artesunate – amodiaquine for the treatment of uncomplicated malaria by Sirima SB, Gansane A. Expert Opin Investig Drugs. 2007 Jul;16(7): 1079-85.
Without an effective vaccine for the prevention of malaria, a fundamental component of the strategy for the control of this disease is based on prompt and effective treatment. An important step is the recent registration in Morocco (the country where the drug is manufactured) of a fixed combination of artesunate plus amodiaquine by the Drugs for Neglected Diseases initiative with sanofi-aventis as the industrial partner. 
Click here to access the full article

Pragmatic and Principled: DNDi's Approach to IP Management by Banerji J and Pecoul B. Intellectual Property Management in Health and Agricultural Innovation: A Handbook of Best Practices (eds. A Krattiger, RT Mahoney, L Nelsen, et al.) 2007.
DNDi's mission is to develop safe, effective, and affordable new drugs for patients suffering from neglected diseases and to ensure equitable access to these drugs. DNDi believes that intellectual property (IP) rights should not pose a barrier to access to these medicines, and that a balanced approach to IP management is therefore critical. DNDi's IP policy articulates the organization’s approach to IP and ensures that products are accessible and affordable to patients who need them most. DNDi recognizes the reality of IP and seeks to implement its humanitarian mission using best, pragmatic practices for IP management. DNDi has already demonstrated that this is feasible, having successfully negotiated with both private and public sector institutions.
Click here to access the full article

Consultative meeting to develop a strategy for treatment of cutaneous leishmaniasis. Institut Pasteur, Paris, 13–15 June, 2006 by Modabber F, Buffet PA, Torreele E, Milon G, Croft SL. Kinetoplastid Biol Dis. 2007 Apr 24; 6:3.
A meeting was organized by Drugs for Neglected Diseases initiative (DNDi) and the Institute Pasteur (IP), Paris, to review the treatment for all forms of cutaneous leishmaniasis (CL) and to propose a strategy for the development of new efficacious and affordable treatments. Short and long-term objectives and activities were defined as a part of meeting recommendations. 
Click here to download the full article [PDF]

Consultative meeting to develop a strategy for treatment of cutaneous leishmaniasis. Institut Pasteur, Paris, 13–15 June, 2006 by Modabber F, Buffet PA, Torreele E, Milon G, Croft SL. Kinetoplastid Biol Dis. 2007 Apr 24; 6:3.
A meeting was organized by Drugs for Neglected Diseases initiative (DNDi) and the Institute Pasteur (IP), Paris, to review the treatment for all forms of cutaneous leishmaniasis (CL) and to propose a strategy for the development of new efficacious and affordable treatments. Short and long-term objectives and activities were defined as a part of meeting recommendations. 
Click here to download the full article [PDF]

Antimalarial efficacy and drug interactions of the novel semi-synthetic endoperoxide artemisone in vitro and in vivo by Vivas L, Rattray L, Stewart LB, Robinson BL, Fugmann B, Haynes RK, Peters W, Croft SL. J Antimicrob Chemother. 2007 Apr; 59(4): 658-65. Epub 2007 Mar 2.
The in vitro and in vivo efficacy and drug–drug interactions of the novel semi-synthetic endoperoxide artemisone with standard antimalarials were investigated in order to provide the basis for the selection of the best partner drug. Artemisone represents an important addition to the repertoire of artemisinin combination therapies currently in use, as it has enhanced antimalarial activity, improved bioavailability and stability over current endoperoxides. 
Click here to download the full article [PDF]

L’ASAQ, une avancée dans la lutte contre le paludisme by Kiechel JR, Pecoul B. Med Trop 2007; 67: 109-110. 
This editorial (in French) presents ASAQ, a fixed-dose combination of artesunate and amodiaquine launched in March 2007 by Drugs for Neglected Diseases initiative (DNDi) and sanofi-aventis. The combination is aimed for treating uncomplicated falciparum malaria in malaria-endemic countries in Africa. 
Click here to download the full article [PDF]

Neglected diseases: progress in drug development by Croft SL. Curr Opin Investig Drugs. 2007 Feb;8(2):103-4. 
Click here to access the full article

Topical buparvaquone formulations for the treatment of cutaneous leishmaniasis by Garnier T, Mantyla A, Jarvinen T, Lawrence MJ, Brown MB, Croft SL. J Pharm Pharmacol. 2007 Jan; 59(1):41-9.
As the part of a study to develop buparvaquone (BPQ) formulations for the treatment of cutaneous leishmaniasis, the topical delivery of BPQ and one of its prodrugs from a range of formulations was evaluated. The results confirm that BPQ and its prodrug 3-POM-BPQ can penetrate the skin from several formulations, making them potentially interesting candidates for further investigation of topical formulations using in-vivo models of cutaneous leishmaniasis. 
Click here to access the full article

Topical buparvaquone formulations for the treatment of cutaneous leishmaniasis by Garnier T, Mantyla A, Jarvinen T, Lawrence MJ, Brown MB, Croft SL. J Pharm Pharmacol. 2007 Jan; 59(1):41-9.
As the part of a study to develop buparvaquone (BPQ) formulations for the treatment of cutaneous leishmaniasis, the topical delivery of BPQ and one of its prodrugs from a range of formulations was evaluated. The results confirm that BPQ and its prodrug 3-POM-BPQ can penetrate the skin from several formulations, making them potentially interesting candidates for further investigation of topical formulations using in-vivo models of cutaneous leishmaniasis. 
Click here to access the full article

2006

Use of weight-for-age-data to optimize tablet strength and dosing regimens for a new fixed-dose artesunate-amodiaquine combination for treating falciparum malaria by Taylor WR, Terlouw DJ, Olliaro PL, White NJ, Brasseur P, ter Kuile FO. Bull World Health Organ. 2006 Dec;84(12):956-64.
The objective of this study was to test a novel methodology to define age-based dosing regimens for the treatment of malaria with a new, user-friendly, blister-packaged fixed-dose combination of artesunate and amodiaquine. The proposed method to use weight-for-age reference data from countries where malaria is endemic is a useful tool for designing age based dosing regimens for antimalarial drugs for drug registration and field use. 
Click here to download the full article [PDF] 

Miltefosine: issues to be addressed in the future by Berman J, Bryceson AD, Croft S, Engel J, Gutteridge W, Karbwang J, Sindermann H, Soto J, Sundar S, Urbina JA. Trans. R. Soc. Trop. Med. Hyg. 2006 Dec;100 Suppl 1:S41-4. Epub 2006 Jun 5.
Future issues that need to be addressed for miltefosine are efficacy against non-Indian visceral leishmaniasis, efficacy in HIV-coinfected patients, efficacy against the many forms of cutaneous and mucosal disease, effectiveness under clinical practice conditions, generation of drug resistance and the need to provide a second antileishmanial agent to protect against this disastrous event, and the ability to maintain reproductive contraceptive practices under routine clinical conditions. 
Click here to access the full article

Miltefosine — discovery of the antileishmanial activity of phospholipid derivatives by Croft SL, Engel J. Trans R Soc Trop Med Hyg. 2006 Dec;100 Suppl 1:S4-8. Epub 2006 Aug 14. Review.
Miltefosine (hexadecylphosphocholine, ImpavidoTM), a novel antiprotozoal drug used for the treatment of visceral and cutaneous leishmaniasis, was identified and evaluated independently in the early 1980s as a potential anticancer drug in Germany and as an antileishmanial drug in the UK. Miltefosine is active against most Leishmania species, including those that cause cutaneous disease. 
Click here to download the full article [PDF] 

An open label randomized comparison of mefloquine–artesunate as separate tablets vs. a new co-formulated combination for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand by Ashley EA, Lwin KM, McGready R, Simon WH, Phaiphun L, Proux S, Wangseang N, Taylor W, Stepniewska K, Nawamaneerat W, Thwai KL, Barends M, Leowattana W, Olliaro P, Singhasivanon P, White NJ, Nosten F. Trop Med Int Health. 2006 Nov;11(11):1653-60.
Delivering drugs in a fixed combination is essential to the success of the strategy of artemisinin-based combination therapy. This prevents one drug being taken without the protection of the other, reducing the chance of emergence and spread of drug resistant strains of Plasmodium falciparum. A new fixed combination of mefloquine plus artesunate has been developed. This was compared with the conventional regimen of separate tablets for the treatment of uncomplicated multidrug resistant falciparum malaria. 
Click here to download the full article [PDF] 

Evaluation of Azasterols as Anti-Parasitics by Gros L, Lorente SO, Jimenez CJ, Yardley V, Rattray L, Wharton H, Little S, Croft SL, Ruiz-Perez LM, Gonzalez-Pacanowska D, Gilbert IH. J Med Chem. 2006 Oct 5;49(20):6094-103.
In this article, the design and synthesis of some novel azasterols is described, followed by their evaluation against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donoVani, and Plasmodium falciparum, the causative agents of human African trypanosomiasis, Chagas disease, leishmaniasis, and malaria, respectively. Some of the compounds showed anti parasitic activity. 
Click here to access the full article

Liposomal Amphotericin B for the Treatment of Visceral Leishmaniasis by Bern C, Adler-Moore J, Berenguer J, Boelaert M, den Boer M, Davidson RN, Figueras C, Gradoni L, Kafetzis DA, Ritmeijer K, Rosenthal E, Royce C, Russo R, Sundar S, Alvar J. Clin Infect Dis. 2006 Oct 1;43(7):917-24. Epub 2006 Aug 28.
During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit groups in East Africa. The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs. 
Click here to download the full article [PDF]

Endemic tropical diseases: comtemporary health problem due to abandoned diseases in the developing world by Ohta N. Kansenshogaku Zasshi. 2006 Sep;80(5):469-74. Review. 
There are two kinds of infectious diseases in the world; diseases being paid attention and neglected diseases. The former diseases include HIV/AIDS, tuberculosis and malaria, the latter group include many parasitic, fungal, bacterial and some of viral infections. "Neglected Infectious Diseases", which have been renamed as Endemic Tropical Diseases by WHO, are endemic in the developing world are not newly appeared diseases, but diseases affecting humans in these decades. However, those diseases were not recognized as serious health problems because of socio-economical and/or scientific reasons. Considering that issues of "Neglected Infectious Diseases" are urgent to be solved and also are challenging for modern medicine and medical sciences, researchers in the developed countries including Japan should make efforts to promote more active researches in this field. 
Click here to access the full article 

New Azasterols against Trypanosoma brucei: Role of 24-Sterol Methyltransferase in Inhibitor Action by Gros L, Castillo-Acosta VM, Jimenez Jimenez C, Sealey-Cardona M, Vargas S, Manuel Estevez A, Yardley V, Rattray L, Croft SL, Ruiz-Perez LM, Urbina JA, Gilbert IH, Gonzalez-Pacanowska D. Antimicrob Agents Chemother. 2006 Aug; 50(8):2595-601.
A series of azasterol derivatives, designed as potential inhibitors of the Δ24 –sterol methyltransferase enzyme (24-SMT), were synthesized and evaluated for their activities against parasitic protozoa. We conclude that the designed compounds act at sites other than 24-SMT in Trypanosoma brucei. 
Click here to download the full article [PDF]

In-vitro and in-vivo studies on a topical formulation of sitamaquine dihydrochloride for cutaneous leishmaniasis by Garnier T, Brown MB, Lawrence MJ, Croft SL. J Pharm Pharmacol. 2006 Aug;58(8):1043-54.
The efficacy of topical formulations of the 8-aminoquinoline, sitamaquine dihydrochloride, in both in vitro and in in-vivo models of cutaneous leishmaniasis is reported. 
Click here to access the full article

Population Pharmacokinetic Assessment of a New Regimen of Mefloquine Used in Combination Treatment of Uncomplicated Falciparum Malaria by Ashley EA, Stepniewska K, Lindegardh N, McGready R, Hutagalung R, Hae R, Singhasivanon P, White NJ, Nosten F. Antimicrob Agents Chemother. 2006 Jul;50(7):2281-5.
A fixed artesunate-mefloquine combination, comprising three daily doses of 8 mg of mefloquine/kg of body weight and 4 mg of artesunate/kg, has been developed recently. This study was designed to construct a population pharmacokinetic model describing this new dosage regimen of mefloquine given as loose tablets together with artesunate. This new regimen is well tolerated and results in an equivalent therapeutic response. 
Click here to download the full article [PDF] 

Accessibility and affordability of malaria intervention, treatment and prevention in Africa by Koech DK. Afr J Health Sci. 2006;13(1-2):i.
Click here to access the full article

To Fully Tackle the Gang of Four, Needs-Driven R&D is Essential by Torreele E, Royce C, Don R, Sevcsik AM, Croft S. PLoS Med. 2006 Jun;3(6):e282; author reply e284.
In this correspondence, the authors address the challenges set to the global health audience to address neglected tropical diseases affecting the poor and powerless in resource-poor settings. To tackle the gang of four, adequate and field-adapted health tools must be available, and governments must prioritize needs-driven R&D for those diseases where no such tools exist. 
Click here to download the full article [PDF]

New initiatives against Africa’s worms by Fenwick A. Trans R Soc Trop Med Hyg. 2006 Mar;100(3):200-7. Epub 2005 Dec 15. 
Since 1999, the funding available for the control of diseases of poverty (neglected diseases) has increased mainly due to leverage resulting from donations by the Bill and Melinda Gates Foundation and loans from the World Bank. Many countries have embarked on control programmes on a national scale due to drug donation by pharmaceutical companies through vertical programmes. 
Click here to access the full article 

Global framework on essential health R&D by Chirac P and Torreele E. Lancet. 2006 May 13;367:1560-1. 
One of the critical issues to be discussed at the next World Health Assembly ( Geneva , May 22-26) will be a resolution about a global framework on essential health research and development. Over the past years, the crisis in research and development in the worldwide pharmaceutical industry, and in particular the absence of research and development for new medicines targeting diseases that mainly affect people in developing countries (neglected diseases), has become a global concern. 
Click here to download the full article [PDF]

Discovery of Trypanocidal Compounds by Whole Cell HTS of Trypanosoma brucei by Mackey ZB, Baca AM, Mallari JP, Apsel B, Shelat A, Hansell EJ, Chiang PK, Wolff B, Guy KR, Williams J, McKerrow JH. Chem Biol Drug Des. 2006 May;67(5):355-63.
One potentially rapid and cost-effective approach to identifying and developing new trypanocidal drugs would be high throughput-screening of existing drugs already approved for other uses, as well as clinical candidates in late development. A screen was performed in a collection of 2160 FDA approved drugs, bioactive compounds and natural products to identify hits that were cytotoxic to cultured Trypanosoma brucei at a concentration of 1lM or less. From the screen, 35 hits from seven different drug categories were identified. 
Click here to download the full article [PDF]

Mechanisms of experimental resistance of Leishmania to miltefosine: Implications for clinical use by Perez-Victoria FJ, Sanchez-Canete MP, Seifert K, Croft SL, Sundar S, Castanys S, Gamarro F. Drug Resist Updat. 2006 Feb-Apr;9(1-2):26-39. Review.
Miltefosine (hexadecylphosphocholine, MIL), registered as Impavido®, has become the first oral drug for the treatment of visceral and cutaneous leishmanasis. MIL is a simple molecule, very stable, relatively safe and highly efficient in clinical trials. However, MIL requires a long treatment course (28 days) and has a long half-life (around 150 h), which might accelerate the emergence of drug resistance in case of inadequate use. 
Click here to download the full article [PDF]

No drugs in an age of plenty: urging governments to redress the balance by Torreele E. Interdisciplinary Science Reviews. 2006 Mar;31(1):3-8. 
35,000 people die every day from diseases that disproportionately affect the poor in Latin America, Africa, and Asia , and that have been neglected by the pharmaceutical industry and governments. Although scientific knowledge exists to develop new treatments, political will and the profit-driven pharmaceutical model have not sufficiently supported these efforts. Instead, it has been left to generous philanthropic efforts, but this is unsustainable. Public leadership and support is urgently needed. 
Click here to download the full article [PDF]

Aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of Trypanosoma brucei as lead trypanocidal agents by Vicik R, Hoerr V, Glaser M, Schultheis M, Hansell E, McKerrow JH, Holzgrabe U, Caffrey CR, Ponte-Sucre A, Moll H, Stich A, Schirmeister T. Bioorg. Med. Chem. Lett. 2006 May 15;16(10):2753-7. Epub 2006 Mar 3.
The protozoan parasite Trypanosoma brucei causes Human African trypanosomiasis, which is fatal if left untreated. Due to the toxicity of currently used drugs and emerging drug resistance, there is an urgent need for novel therapies. The major trypanosome papain-like cysteine protease expressed by the parasite (e.g., rhodesain in T. b. rhodesiense) is considered an important target for the development of new trypanocidal drugs. 
Click here to download the full article [PDF]

Current scenario of drug development for leishmaniasis by Croft SL, Seifert K, Yardley V. Indian J Med Res. 2006 Mar; 123(3):399-410. Review.
As part of research to identify better treatments for VL and cutaneous leishmaniasis (CL), alternative and potentially cheaper formulations of amphotericin B, alklyphosphocholines other than miltefosine and improved formulations of paromomycin for CL have been identified. The process for discovery and development of new antileishmanials would also benefit from improved models, for example, transfected parasites, and non invasive methods of measuring parasite load in rodent models of infection. 
Click here to download the full article [PDF]

Inhibition of Trypanosoma cruzi Hexokinase by Bisphosphonates by Hudock MP, Sanz-Rodriguez CE, Song Y, Chan JM, Zhang Y, Odeh S, Kosztowski T, Leon-Rossell A, Concepcion JL, Yardley V, Croft SL, Urbina JA, Oldfield E. J Med Chem. 2006 Jan 12;49(1):215-23.
Hexokinase is the first enzyme involved in glycolysis in most organisms, including the etiological agents of Chagas disease (Trypanosoma cruzi) and African sleeping sickness (Trypanosoma brucei). The T. cruzi enzyme is unusual since, unlike the human enzyme, it is inhibited by inorganic diphosphate (PPi). 
Click here to access the full article 

Drug resistance in leishmaniasis by Croft SL, Sundar S, Fairlamb AH. Clin Microbiol Rev. 2006 Jan;19(1):111-26. 
Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. It is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy. 
Click here to download the full article [PDF]

In Vitro and In Vivo Interactions between Miltefosine and Other Antileishmanial Drugs by Seifert K, Croft SL. Antimicrob Agents Chemother. 2006 Jan;50(1):73-9.
The interaction of miltefosine with amphotericin B, sodium stibogluconate, paromomycin, and sitamaquine was assessed in vitro and additionally for the first three combinations in vivo. 
Click here to download the full article [PDF]

Situational analysis of leishmaniases research in Kenya by Tonui WK. Afr J Health Sci. 2006;13(1-2):7-21.
Leishmaniasis has been known to be endemic in parts of Kenya from as far back as early in the 20th century. Since 1980, the Kenya Medical Research Institute (KEMRI) has spearheaded research on leishmaniases research in Kenya focusing on various aspects including characterization of Leishmania species, biology, and ecology of sand fly vectors, development of biological strategies for sand fly control, identification of animal reservoirs, diagnosis, new treatment strategies, new chemotherapeutic agents, and vaccine-related studies. 
Click here to access the full article

Chemotherapy in the Treatment and Control of Leishmaniasis by Alvar J, Croft S, Olliaro P. Adv. Parasitol. 2006; 61:223-74. 
Drugs remain the most important tool for the treatment and control of both visceral and cutaneous leishmaniasis. Although there have been several advances in the past decade, with the introduction of new therapies by liposomal amphotericin, oral miltefosine and paromomycin (PM), these are not ideal drugs, and improved shorter duration, less toxic and cheaper therapies are required. 
Click here to access the full article

2005

Antitrypanosomal, Antileishmanial, and Antimalarial Activities of Quaternary Arylalkylammonium 2-Amino-4-Chlorophenyl Phenyl Sulfides, a New Class of Trypanothione Reductase Inhibitor, and of N-Acyl Derivatives of 2-Amino-4 Chlorophenyl Phenyl Sulfide by Parveen S, Khan MO, Austin SE, Croft SL, Yardley V, Rock P, Douglas KT. J Med Chem. 2005 Dec 15;48(25):8087-97.
Quaternization of the nitrogen atom of 2-amino-4-chlorophenyl phenyl sulfide analogues of chlorpromazine improved inhibition ~40-fold (3’,4’-dichlorobenzyl-[5-chloro-2 phenylsulfanylphenylamino)-propyl]-dimethylammonium chloride inhibited trypanothione reductase from Trypanosoma cruzi with a linear competitive Ki value of 1.7 ( 0.2 íM). The phenothiazine and diaryl sulfide quaternary compounds were also powerful antimalarials, providing a new structural framework for antimalarial design. 
Click here to access the full article

Government action needed to step up research and development for world's most neglected diseases by Pecoul B. Expert Rev Anti Infect Ther. 2005 Dec;3(6):841-3. 
Neglected and most neglected diseases affect millions of people in the world's poorest countries, yet we do not have safe, affordable, and field-adapted vaccines, diagnostics and drugs to tackle them. 
Click here to download the full article [PDF]

Chemotherapy of trypanosomiases and leishmaniasis by Croft SL, Barrett MP, Urbina JA. Trends Parasitol. 2005 Nov;21(11):508-12. 
New formulations, therapeutic switching of the established drugs amphotericin B and paromomycin, and the serendipitous discovery of miltefosine have markedly improved leishmaniasis chemotherapy in the past 21 years. The situation for the two trypanosomiases has been less encouraging. However, the appearance of not-for-profit product-development partnerships offers a new paradigm for bringing new drugs to patients. 
Click here to download the full article [PDF]

Chemotherapy of trypanosomiases and leishmaniasis by Croft SL, Barrett MP, Urbina JA. Trends Parasitol. 2005 Nov;21(11):508-12. 
New formulations, therapeutic switching of the established drugs amphotericin B and paromomycin, and the serendipitous discovery of miltefosine have markedly improved leishmaniasis chemotherapy in the past 21 years. The situation for the two trypanosomiases has been less encouraging. However, the appearance of not-for-profit product-development partnerships offers a new paradigm for bringing new drugs to patients. 
Click here to download the full article [PDF]

Public-private partnership: from there to hereby Croft SL. Trans R Soc Trop Med Hyg. 2005 Oct; 99 Suppl 1:S9-14. 
Major changes in research and development (R&D) for drugs to treat tropical and neglected diseases have occurred in the past five years. Public-private partnerships have proved that they can move compounds quickly through the R&D pipeline. The challenge is to ensure that the products are delivered to the people who need them and to ensure that scientists in endemic countries are involved in the whole process. 
Click here to download the full article [PDF]

Advances in leishmaniasis by Murray HW, Berman JD, Davies CR, Saravia NG. Lancet. 2005 Oct 29-Nov 4;366(9496):1561-1577.
Diagnosis relies on visualising parasites in tissue or serology; culture and detection of parasite DNA are useful in the laboratory. Despite tangible advances in diagnosis, treatment, and basic scientific research, leishmaniasis is embedded in poverty and neglected. Current obstacles to realistic prevention and proper management include inadequate vector (sandfly) control, no vaccine, and insufficient access to or impetus for developing affordable new drugs. 
Click here to access the full article

Control of mucocutaneous leishmaniasis, a neglected disease: results of a control programme in Satipo Province, Peru by Guthmann JP, Arlt D, Garcia LM, Rosales M, de Jesus Sanchez J, Alvarez E, Lonlas S, Conte M, Bertoletti G, Fournier C, Huari R, Torreele E, Llanos-Cuentas A. Trop Med Int Health. 2005 Sep;10(9):856-62. 
Mucocutaneous leishmaniasis (MCL) is an important health problem in many rural areas of Latin America, but there are few data on the results of programmatic approaches to control the disease. We report the results of a control programme in San Martin de Pangoa District, which reports one of the highest prevalences of MCL in Peru. 
Click here to download the full article [PDF]

Preparation of transition-state analogues of sterol 24-methyl transferase as potential anti-parasitics by Lorente SO, Jimenez CJ, Gros L, Yardley V, de Luca-Fradley K, Croft SL, A Urbina J, Ruiz-Perez LM, Pacanowska DG, Gilbert IH. Bioorg. Med. Chem. 2005 Jul, 13: 5435-5453.
In this paper we discuss the design, synthesis and evaluation of potential transition state analogues of the enzyme D24(25)-methyltransferase (24-SMT). This enzyme is essential for the biosynthesis of ergosterol, but not required for the biosynthesis of cholesterol. A series of compounds were successfully synthesised in which mimics of the S-adenosyl methionine co-factor were attached to the sterol nucleus. 
Click here to access the full article 

Visceral Leishmaniasis: New Health Tools Are Needed by Hailu A, Musa A.M, Royce C, Wasunna M. PLoS Med. 2005 Jul; 2(7):e211. 
Visceral leishmaniasis (VL), commonly known as kala azar, from the Hindu vernacular, is a human systemic disease caused by parasitic protozoan species of the genus Leishmania. Transmitted by the bite of the tiny and seemingly innocuous female phlebotomine sandfly, the parasite enters macrophages, where it multiplies and establishes the infection. 
Click here to download the full article [PDF]

DNDi in the British Medical Journal, July 2005: Prioritising Neglected Diseases Related to Poverty by Rhona MacDonald. BMJ. 2005 Jul; 331:12. 
Bernard Pécoul, director of the Drugs for Neglected Diseases Initiative, tells Rhona MacDonald how his organisation is hoping to help millions of people living in poverty worldwide. 
Click here to download the full article [PDF]

Drugs for Neglected Diseases Initiative. Wasunna KM. Afr J Health Sci. 2005 Jan-Jun;12(1-2):i-ii. 
Click here to access the full article

The sensitivity of clinical isolates of Leishmania from Peru and Nepal to miltefosine by Yardley V, Croft SL, De Doncker S, Dujardin JC, Koirala S, Rijal S, Miranda C, Llanos-Cuentas A, Chappuis F. Am J Trop Med Hyg. 2005 Aug;73(2):272-5.
Clinical isolates of Leishmania, from visceral leishmaniasis (VL) cases in Nepal and from cutaneous leishmaniasis (CL) cases in Peru, were cultured using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) to type species and strain. The study demonstrates a notable difference in the intrinsic sensitivity of Leishmania species to miltefosine in vitro. 
Click here to download the full article [PDF]

Preparation of transition-state analogues of sterol 24-methyl transferase as potential anti-parasitics by Lorente SO, Jimenez CJ, Gros L, Yardley V, de Luca-Fradley K, Croft SL, A Urbina J, Ruiz-Perez LM, Pacanowska DG, Gilbert IH. Bioorg. Med. Chem. 2005 Jul, 13: 5435-5453.
In this paper we discuss the design, synthesis and evaluation of potential transition state analogues of the enzyme D24(25)-methyltransferase (24-SMT). This enzyme is essential for the biosynthesis of ergosterol, but not required for the biosynthesis of cholesterol. A series of compounds were successfully synthesised in which mimics of the S-adenosyl methionine co-factor were attached to the sterol nucleus. 
Click here to access the full article

2004

New Drugs for Neglected Diseases: From Pipeline to Patients by Bernard Pécoul. PLoS Med. 2004 Oct; 1(1):e6. Epub 2004 Oct 19. 
In wealthy countries,state-funded research has yielded breakthroughs in molecular biology,chemistry,and engineering.These advances have been taken up by the pharmaceutical industry and applied to drug development for a growing range of illnesses and conditions.As a result, patients have access to new drugs that are better tolerated, more specific,and more effective than old ones. 
Click here to download the full article [PDF]

Novel Azasterols as Potential Agents for Treatment of Leishmaniasis and Trypanosomiasis by Lorente SO, Rodrigues JC, Jimenez Jimenez C, Joyce-Menekse M, Rodrigues C, Croft SL, Yardley V, de Luca-Fradley K, Ruiz-Perez LM, Urbina J, de Souza W, Gonzalez Pacanowska D, Gilbert IH. Antimicrob Agents Chemother. 2004 Aug;48(8):2937-50.
This paper describes the design and evaluation of novel azasterols as potential compounds for the treatment of leishmaniasis and other diseases caused by trypanosomatid parasites. The compounds prepared showed activity at micromolar and nanomolar concentrations when tested against Leishmania spp. and Trypanosoma spp. The compounds were also found to be active against the bloodstream form (trypomastigotes) of Trypanosoma brucei rhodesiense, a causative agent of African trypanosomiasis. 
Click here to download the full article [PDF]

Novel Azasterols as Potential Agents for Treatment of Leishmaniasis and Trypanosomiasis by Lorente SO, Rodrigues JC, Jimenez Jimenez C, Joyce-Menekse M, Rodrigues C, Croft SL, Yardley V, de Luca-Fradley K, Ruiz-Perez LM, Urbina J, de Souza W, Gonzalez Pacanowska D, Gilbert IH. Antimicrob Agents Chemother. 2004 Aug;48(8):2937-50.
This paper describes the design and evaluation of novel azasterols as potential compounds for the treatment of leishmaniasis and other diseases caused by trypanosomatid parasites. The compounds prepared showed activity at micromolar and nanomolar concentrations when
tested against Leishmania spp. and Trypanosoma spp. The compounds were also found to be active against the bloodstream form (trypomastigotes) of Trypanosoma brucei rhodesiense, a causative agent of African trypanosomiasis. Click here to download the full article [PDF]

Synthesis and antileishmanial activity of novel buparvaquone oxime derivatives by Mantyla A, Rautio J, Nevalainen T, Vepsalainen J, Juvonen R, Kendrick H, Garnier T, Croft SL, Jarvinen T. Bioorg Med Chem. 2004 Jul 1;12(13):3497-502.
Novel oxime derivatives (2, 3 and 5) of buparvaquone (1) and O-methyl-buparvaquone (4) were synthesized and their in vitro activities against Leishmania donovani, the causative agent of visceral leishmaniasis (VL), were determined. Buparvaquoneoxime (2) was also studied as a bioreversible prodrug structure of buparvaquone (1). 
Click here to access the full article

Efficacy of therapeutic combinations with artemisinin derivatives in the treatment of non complicated malaria in Burundi by Ndayiragije A, Niyungeko D, Karenzo J, Niyungeko E, Barutwanayo M, Ciza A, Bosman A, Moyou-Somo R, Nahimana A, Nyarushatsi JP, Barihuta T, Mizero L, Ndaruhutse J, Delacollette C, Ringwald P, Kamana J. Trop Med Int Health. 2004 Jun; 9(6): 673-9. 
Faced with the problem of resistance to chloroquine and sulfadoxine-pyrimethamine, the Ministry of Public Health of Burundi decided to study the efficacy of two artemisinin-based combinations, the fixed combination of artemether-lumefantrine and the combination of amodiaquine + artesunate. During a consensus workshop, the Ministry of Public Health agreed on the combination of artesunate and amodiaquine as the first line drug for the treatment of uncomplicated falciparum malaria in Burundi including epidemic outbreak. 
Click here to download the full article [PDF] 

Combined antimalarial therapy using artemisinin by Majori G. Parassitologia. 2004 Jun;46(1-2):85-7. 
The existing armamentarium of drugs for the treatment and prevention of malaria is limited primarily by resistance (and cross-resistance between closely related drugs). However, most of these drugs still have a place and their life-span could be prolonged if better deployed and used, and also by rationally combining them based on pharmacodynamic and pharmacokinetic properties. Newer compounds are also being developed. The nature of malaria disease and its prevalence in the developing world call for innovative approaches to develop new affordable drugs and to safeguard the available ones. 
Click here to access the full article

Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review by Olliaro PL, Taylor WR. J Postgrad Med. 2004 Jan-Mar; 50(1):40-4. Review.
The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. This review will summarise current antimalarial drug developments and outline recent clinical research that aims to bring artemisinin-based combinations to those that need them most. 
Click here to download the full article [PDF]

Design and synthesis of peptidomimetic protein farnesyltransferase inhibitors as anti-Trypanosoma brucei agents by Ohkanda J, Buckner FS, Lockman JW, Yokoyama K, Carrico D, Eastman R, de Luca-Fradley K, Davies W, Croft SL, Van Voorhis WC, Gelb MH, Sebti SM, Hamilton AD. J Med Chem. 2004 Jan 15;47(2):432-45.
On the basis of the structure of the CVIM tetrapeptide substrate of mammalian protein farnesyltransferase, a series of imidazole-containing peptidomimetics was designed and synthesized, and their inhibition activity against Trypanosoma brucei protein farnesyltransferase (TbPFT) was evaluated. 
Click here to access the full article 

2003

Leishmaniasis-current chemotherapy and recent advances in the search for novel drugs by Croft SL, Coombs GH. Trends Parasitol. 2003 Nov;19(11):502-8
The chemotherapy currently available for leishmaniasis is far from satisfactory. Resistance to the pentavalent antimonials, which have been the recommended drugs for the treatment of both visceral (VL) and cutaneous leishmaniasis (CL) for >50 years, is now widespread in India. Although new drugs have become available in recent years for the treatment of VL, treatment problems remain. The search for new drugs continues. Many potential drug targets have been identified in biochemical and molecular studies, and some have been validated. Attempts to exploit these targets are in progress. 
Click here to download the full article [PDF] 

Antimalarial compounds: from bench to bedside by Olliaro PL, Taylor WR. J Exp Biol. 2003 Nov;206(Pt 21):3753-9. 
The emergence and spread of drug-resistant malaria parasites is the major threat to effective malaria control. Experience has shown that resistance eventually curtails the life span of antimalarial drugs. If measures are not applied to contain resistance, the investment put into the development of new drugs will be squandered. This review will summarise current antimalarial drug developments and outline recent clinical research that aims to bring artemisinin-based combinations to those that need them most. 
Click here to download the full article [PDF]

Recent advances in research and control of malaria, leishmaniasis, trypanosomiasis and schistosomiasis by Croft SL, Vivas L, Brooker S. East Mediterr Health J. 2003 Jul;9(4):518-33. Review.
In the Eastern Mediterranean Region of the World Health Organization (WHO), malaria, schistosomiasis, leishmaniasis and trypanosomiasis are the parasitic diseases of major importance. Our review focuses on recent advances in the control and treatment of these diseases with particular reference to diagnosis, chemotherapy, vaccines, vector and environmental control. 
Click here to access the full article

Initiative launched to develop drugs for neglected diseases by Frankish H. Lancet. 2003 Jul 12; 362(9378):135. 
A new initiative that aims to develop drugs to tackle diseases that affect the world's poorest people was launched in Geneva on July 3. The Drugs for Neglected Diseases Initiative (DNDi) aims to identify drugs to combat diseases such as trypanosomiasis, visceral leishmaniasis, and Chagas disease, which affect more than 350 million people every year. 
Click here to access the full article

2002

Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda by Guérin P. et al, August 2002, Lancet Infect Dis 2002; 2 : 494–501. 
Visceral leishmaniasis is common in less developed countries, with an estimated 500 000 new cases each year. Because of the diversity of epidemiological situations, no single diagnosis, treatment, or control will be suitable for all. This article reviews the current situation and perspectives for diagnosis, treatment, and control of visceral leishmaniasis, and lists some priorities for research and development. 
Click here to download the full article [PDF]

Reflection & Reaction by Alimuddin Zumla, Lancet Infect Dis 2002 July, 2:393. 
Recent global partnership initiatives have focused on stimulating further interest in the development and provision of drugs for the world's top three killer infectious diseases: AIDS/HIV, malaria, and tuberculosis. The “most neglected” diseases (where there are no affordable, effective, easy to use medicines available) continue to cause significant morbidity and mortality in developing countries. This paper is a short introduction to a series of articles outlining research and development priorities for sleeping sickness, visceral leishmaniasis and malaria. 
Click here to download the full article [PDF] 

The world's most neglected diseases. Ignored by the pharmaceutical industry and by public/­private partnerships by Yamey G, Torreele E. BMJ. 2002 Jul 27;325(7357):176-7.
The article discusses issues about the “most neglected” diseases as still being ignored not just by the pharmaceutical industry but also by public-private partnerships. 
Click here to download the full article [PDF] 

Drug development for neglected diseases: a deficient market and a public-health policy failure by Trouiller, P. et al., June 2002, Lancet, 359: 2188–94. 
There is a lack of effective, safe, and affordable pharmaceuticals to control infectious diseases that cause high mortality and morbidity among poor people in the developing world. This paper analyses outcomes of pharmaceutical research and development over the past 25 years, and reviews current public and private initiatives aimed at correcting the imbalance in research and development that leaves diseases that occur predominantly in the developing world largely unaddressed. 
Click here to download the full article [PDF] 

Treatment of human African trypanosomiasis—present situation and needs for research and development by Legros, D. et al., Lancet Infect Dis 2002 2: 437–40. 
Human African trypanosomiasis (sleeping sickness) re-emerged in the 1980s. However, little progress has been made in the treatment of this disease over the past decades. Research and development efforts must be made for the development of new compounds. At the same time, on a long term basis, ambitious research programmes for new compounds must be supported to ensure the sustainable development of new drugs. 
Click here to download the full article [PDF] 

2001

Neglected diseases of global importance by Ford N, Torreele E. JAMA. 2001 Dec 19;286(23):2943-4.
In this letter to the editor, the authors raise the need of increased responsibility from the private and public sectors in order to ensure that people’s health needs are met, and the importance of non-for-profit drug development initiatives to address the imbalance in the burden of infectious diseases between rich and poor countries. 
Click here to download the full article [PDF]

Drugs for neglected diseases: a failure of the market and a public health failure? By Trouiller P, Torreele E, Olliaro P, White N, Foster S, Wirth D, Pecoul B. Trop Med Int Health. 2001 Nov;6(11):945-51. Review.
Infectious diseases cause the suffering of hundreds of millions of people, especially in tropical and subtropical areas. Effective, affordable and easy-to-use medicines to fight these diseases are nearly absent. Although science and technology are sufficiently advanced to provide the necessary medicines, very few new drugs are being developed. An urgent reorientation of priorities in drug development and health policy is needed. New and creative strategies involving both the public and the private sector are needed to ensure that affordable medicines for today's neglected diseases are developed. 
Click here to download the full article [PDF]

Public-private partnerships for health: their main targets, their diversity, and their future directions. Widdus R. Bull World Health Organ. 2001;79(8):713-20. Epub 2001 Oct 24.
The global burden of disease, especially the part attributable to infectious diseases, disproportionately affects populations in developing countries. Inadequate access to pharmaceuticals plays a role in perpetuating this disparity. A large variety of public-private partnerships, combining the skills and resources of a wide range of collaborators, have arisen for product development, disease control through product donation and distribution, or the general strengthening or coordination of health services. Suggestions are made for public, private, and joint activities that could help to improve the access of poor populations to the pharmaceuticals and health services they need. 
Click here to download the full article [PDF]

Fatal imbalance: the crisis in research and development for drugs for neglected diseases by MSF Campaign for access to medicine, Drugs for Neglected Diseases working group
Click here to downlad the full report [PDF]

Availability and affordability of treatment for Human African Trypanosomiasis by Etchegorry MG, Helenport JP, Pecoul B, Jannin J, Legros D. Trop Med Int Health. 2001 Nov;6(11):957-9.
Human African Trypanosomiasis (HAT) is a re-emerging disease whose usual treatments are becoming less efficient because of the increasing parasite resistance. Availability of HAT drugs is poor and their production in danger because of technical, ecological and economic constraints. 
Click here to download the full article [PDF]

1999

Antiparasitic agents: challenges of sleeping sickness, hopes for malaria by Croft SL. Curr Opin Infect Dis. 1999 Dec; 12(6):557-8. 
Click here to access the full article

Antiparasitic agents: challenges of sleeping sickness, hopes for malaria by Croft SL. Curr Opin Infect Dis. 1999 Dec; 12(6):557-8. 
Click here to access the full article

Access to Essential Drugs in Poor Countries – A Lost Battle ? ” by Pécoul, B. et al., JAMA, January 27, 1999—Vol 281, No. 4. 
This article focuses on the problems of access to quality drugs for the treatment of diseases that predominantly affect the developing world: (1) poor-quality and counterfeit drugs; (2) lack of availability of essential drugs due to fluctuating production or prohibitive cost; (3) need to develop field-based drug research to determine optimum utilization and remotivate research and development for new drugs for the developing world; and (4) potential consequences of recent World Trade Organization agreements on the availability of old and new drugs. 
Click here to download the full article [PDF]

Except for images, films and trademarks which are subject to DNDi’s Terms of Use, content on this site
is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Switzerland License