Scientific publications 2009

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. 2009 July, 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.

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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 Globalization. PLoS 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 Frontières. PLoS Negl Trop Dis 3(7): e488. Click here to access full-text 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.
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An accompanying Lancet editorial calls the NECT study ‘more than a small victory over sleeping sickness‘.
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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.
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.
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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 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.
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Randomized, multicentre assessment of the efficacy and safety of ASAQ – a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria by 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.
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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.
Due 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.
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The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum by Sirima SB, Tiono AB, Gansané A, Diarra A, Ouédraogo A, Konaté AT, Kiechel JR,Morgan CC, Olliaro PL, Taylor WRJ. Malaria Journal 2009 Mar 16; 8:48.
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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 combination by 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.
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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.
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