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resistance

E-interview with Dr. Vincent Corbel (Benin, 1976)

March 19, 2010 - 10:19 -- Bart G.J. Knols

Dr. Corbel is currently a senior researcher at IRD, and based at the CREC in Cotonou in Benin. Following five years of heading the WHO collaborating centre for the evaluation of new public health pesticides he moved to Benin where he undertakes highly interesting studies aimed at improving vector control across Africa.

PhD thesis: Experimental studies on the ecology and evolution of drug-resistant malaria parasites

January 26, 2010 - 14:39 -- Silvie Huijben

Drug resistance is a serious problem in health care in general, and in malaria treatment in particular, rendering many of our previously considered ‘wonder drugs’ useless. Recently, large sums of money have been allocated for the continuous development of new drugs to replace the failing ones. We seem to be one step behind the evolution of antimalarial resistance; is it possible to get one step ahead?

Evolutionary biology, evolution-proof insecticides and malaria control

December 11, 2009 - 13:49 -- Yannis Michalakis

Yannis Michalakis & François Renaud GEMI, CNRS-IRD UMR 2724, Montpellier, France Yannis.Michalakis@mpl.ird.fr, Francois.Renaud@mpl.ird.fr

 

Evolutionary thinking started pervading vector control strategies and planning since it was used to explain and manage insecticide resistance. More recently it has been used in the planning of GMMs (Genetically Modified Mosquitoes).

 

A new promising avenue was recently opened by Andrew Read and his colleagues.

Synthesis of 9-anilinoacridine triazines as new class of hybrid antimalarial agents.

November 18, 2009 - 13:00 -- Patrick Sampao
Author(s): 
Ashok Kumar, Kumkum Srivastava, S. Raja Kumar, S.K. Puri, Prem M.S. Chauhan
Reference: 
Bioorganic & Medicinal Chemistry Letters, Volume 19, Issue 24, 15 December 2009, Pages 6996-6999, doi:10.1016/j.bmcl.2009.10.010

There is challenge and urgency to synthesize cost-effective chemotherapeutic agents for treatment of malarianext term after the widespread development of resistance to CQ. In the present study, we synthesized a new series of hybrid 9-anilinoacridine triazines using the cheap chemicals 6,9-dichloro-2-methoxy acridine and cyanuric chloride.

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Cell-based optimization of novel benzamides as potential antimalarial leads.

November 18, 2009 - 12:57 -- Patrick Sampao
Author(s): 
Tao Wu, Advait Nagle, Tomoyo Sakata, Kerstin Henson, Rachel Borboa, Zhong Chen, Kelli Kuhen, David Plouffe, Elizabeth Winzeler, Francisco Adrian, Tove Tuntland, Jonathan Chang, Susan Simerson, Steven Howard, Jared Ek, John Isbell, Xianming Deng, Nathanael S. Gray, David C. Tully, Arnab K. Chatterjee
Reference: 
Bioorganic & Medicinal Chemistry Letters, Volume 19, Issue 24, 15 December 2009, Pages 6970-6974, doi:10.1016/j.bmcl.2009.10.050

Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan-kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its antiplasmodial activity. The evolution of this compound series leading to optimized candidates with good cellular potency against multiple strains as well as decent in vivo profile is described in this Letter.

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Mechanisms of Resistance; Characteristics of Genetic Hitchhiking around Dihydrofolate Reductase Gene Associated with Pyrimethamine Resistance in Plasmodium falciparum Isolates from India .

November 18, 2009 - 12:34 -- Patrick Sampao
Author(s): 
Vanshika Lumb, Manoj K. Das, Neeru Singh, Vas Dev, Wajihullah,4 and Yagya D. Sharma
Reference: 
Antimicrobial Agents and Chemotherapy, December 2009, p. 5173-5180, Vol. 53, No. 12, doi:10.1128/AAC.00045-09

Sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum has been widespread across continents, causing the major hurdle of controlling malaria. Resistance is encoded mainly by point mutations in P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) target genes. To study the origin and evolution of pyrimethamine resistance on the Indian subcontinent, microsatellite markers flanking the pfdhfr gene were mapped. Here we describe the characteristics of genetic hitchhiking around the pfdhfr gene among 190 P. falciparum isolates.

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Evidence of multiple pyrethroid resistance mechanisms in the malaria vector Anopheles gambiae sensu stricto from Nigeria

October 25, 2009 - 17:39 -- Bart G.J. Knols
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Author(s): 
T.S. Awolola, O.A. Oduola, C. Strode, L.L. Koekemoer, B. Brooke, H. Ranson
Reference: 
Transactions of the Royal Society of Tropical Medicine and Hygiene, Volume 103, Issue 11, November 2009, Pages 1139-1145, doi:10.1016/j.trstmh.2008.08.021

 Pyrethroid insecticide resistance in Anopheles gambiae sensu stricto is a major concern to malaria vector control programmes. Resistance is mainly due to target-site insensitivity arising from a single point mutation, often referred to as knockdown resistance (kdr). Metabolic-based resistance mechanisms have also been implicated in pyrethroid resistance in East Africa and are currently being investigated in West Africa. Here we report the co-occurrence of both resistance mechanisms in a population of An. gambiae s.s. from Nigeria.

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The distribution of insecticide resistance in Anopheles gambiae s.l. populations from Cameroon: an update

October 25, 2009 - 17:32 -- Bart G.J. Knols
Author(s): 
Hamadou N.M. et al.
Reference: 
Transactions of the Royal Society of Tropical Medicine and Hygiene, Volume 103, Issue 11, November 2009, Pages 1127-1138, doi:10.1016/j.trstmh.2008.11.018

Insecticides are a key component of vector-based malaria control programmes in Cameroon. As part of ongoing resistance surveillance efforts, Anopheles gambiae s.l. female mosquitoes were exposed to organochlorine (DDT), a carbamate (bendiocarb), an organophosphate (malathion), and three pyrethroids (deltamethrin, lambda-cyhalothrin and permethrin) in WHO bioassay test kits.

Carbamate and organophosphorous compounds could thus be used as alternatives in locations in Cameroon where pyrethroid-resistant populations are found.

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Insecticide resistance and its association with target-site mutations in natural populations of Anopheles gambiae from eastern Uganda

October 25, 2009 - 17:27 -- Bart G.J. Knols
Author(s): 
Urvashi Ramphul, Thomas Boase, Chris Bass, Loyce M. Okedi, Martin J. Donnelly, Pie Müller
Reference: 
Transactions of the Royal Society of Tropical Medicine and Hygiene, Volume 103, Issue 11, November 2009, Pages 1121-1126, doi:10.1016/j.trstmh.2009.02.014

Insecticide resistance in Anopheles gambiae threatens the success of malaria vector control programmes in sub-Saharan Africa. In order to manage insecticide resistance successfully, it is essential to assess continuously the target mosquito population. Here, we collected baseline information on the distribution and prevalence of insecticide resistance and its association with target-site mutations in eastern Uganda.

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Distribution of pyrethroid and DDT resistance and the L1014F kdr mutation in Anopheles gambiae s.l. from Burkina Faso (West Africa)

October 25, 2009 - 17:23 -- Bart G.J. Knols
Author(s): 
K.R. Dabiré, A. Diabaté, M. Namountougou, K.H. Toé, A. Ouari, P. Kengne, C. Bass, T. Baldet
Reference: 
Transactions of the Royal Society of Tropical Medicine and Hygiene, Volume 103, Issue 11, November 2009, Pages 1113-1120, doi:10.1016/j.trstmh.2009.01.008

This study reports on the distribution of pyrethroid and DDT resistance and the L1014F knockdown resistance (kdr) mutation in Anopheles gambiae s.l. populations from 21 localities in three different climatic zones of Burkina Faso from August to October 2006. These results have practical significance for malaria vector control programs.

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