Scientific Publications - Malaria

2011

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
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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
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Standardised versus actual white cell counts in estimating thick film parasitaemia in African children under five. by 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
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Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand by S. Krudsood1, S. Looareesuwan1, P. Wilairatama1, W. Leowattana1, N. Tangpukdee, K. Chalermrut, S. Ramanathan, V. Navaratnam, P. Olliaro, M. Vaillant, J. R. Kiechel, W. R. J. Taylor. Tropical Medicine & International Health. Volume 16, Issue 4, pages 458–465 , April 2011
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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 J. Malaria 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.
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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.
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2010

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.
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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.
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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.
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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.
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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.
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2009


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.)
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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.
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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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More Information on ASAQ

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.
A new fixed-dose combination of artesunate (AS) and amodiaquine (AQ) was tested for the first time in a field study comparing its efficacy and safety with the corresponding non-fixed combination. Conducted in Burkina Faso children suffering from P. falciparum malaria, the study incorporated a new, simplified, age-based dosing regimen with the fixed-dose combination. The results show that the AS and AQ, one of  the artemisinin-based combinations (ACT) recommended by the WHO, is highly efficacious and well tolerated.
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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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2008

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.
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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
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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.
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2007

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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Accessibility and affordability of malaria intervention, treatment and prevention in Africa by Koech DK. Afr J Health Sci. 2006;13(1-2):i.
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2004

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.
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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.
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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.
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2003

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.
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1999

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