David Warhurst

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Born 8th April 1938 at Aldershot where my father Charles, a male nurse, was with the RAMC on the outset of hostilities and was posted to Norway , later to go to the N. Africa , Sicily and Italy, travelling home through Europe at the end of the war. My mother Alice and I lived with her parents in Blackburn and soon moved to Leeds then Keighley in Yorkshire. (to be continued)....

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Arnaud Tarantola

UNiversité de la Nouvelle Calédonie

University of Oxford

University of Liverpool

Christine Kaseba

University of Zambia

Edwin Michael

Imperial College London

margaret pinder

Stefan Dongus

University of Basel, Switzerland

Johnson Matowo

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Papers by David Warhurst

Back-calculation of the number of inoculated Plasmodium falciparum parasites in a documented case of needlestick malaria in a French nurse

by Arnaud Tarantola and David Warhurst

Transactions of the Royal Society of Tropical Medicine and Hygiene, 2003

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Bioactive Compounds from Psychotria camponutans

by Pablo Solis and David Warhurst

Planta Medica, 1995

A new benzoquinone (1-hydroxybenzoisochromanquinone) and benz [g]isoquinoline-5, 10-dione have be... more A new benzoquinone (1-hydroxybenzoisochromanquinone) and benz [g]isoquinoline-5, 10-dione have been isolated from the woody parts of Psychotria camponutans, as a result of bioactivity-guided fractionation. The compounds were characterized by UV, IR, EI-mass, 1H-, and 13C-NMR, and HETCOR NMR spectroscopy. Both compounds, together with acetylbenzoisochromanquinone, showed in vitro strong activity against brine shrimp, KB cells, and chloroquine-resistant P. falciparum.

Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthetase and dihydrofolate reductase alleles in a large number of field samples of diverse origins

by ogobara doumbo, Marcel Tanner, and David Warhurst

Molecular and Biochemical Parasitology, 1997

Resistance of Plasmodium falciparum to antifolate chemotherapy is a significant problem where com... more Resistance of Plasmodium falciparum to antifolate chemotherapy is a significant problem where combinations such as Fansidar (pyrimethamine-sulfadoxine; PYR-SDX) are used in the treatment of chloroquine-resistant malaria. Antifolate resistance has been associated with variant sequences of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS), the targets of PYR and SDX respectively. However, while the nature and distribution of mutations in the dhfr gene are well established, this is not yet the case for dhps. We have thus examined by DNA sequence analysis 141 field samples from several geographical regions with differing Fansidar usage (West and East Africa, the Middle East and Viet Nam) to establish a database of the frequency and repertoire of dhps mutations, which were found in 60% of the samples. We have also simultaneously determined from all samples their dhfr sequences, to better understand the relationship of both types of mutation to Fansidar resistance. Whilst the distribution of mutations was quite different across the regions surveyed, it broadly mirrored our understanding of relative Fansidar usage. In samples taken from individual patients before and after drug treatment, we found an association between the more highly mutated forms of dhps and/or dhfr and parasites that were not cleared by antifolate therapy. We also report a novel mutation in a Pakistani sample at position 16 of DHFR (A16S) that is combined with the familiar C59R mutation, but is wild-type at position 108. This is the first observation in a field sample of a mutant dhfr allele where the 108 codon is unchanged.

Primaquine: Pharmacokinetics, metabolism, toxicity and activityedited by Walther H. Wernsdor fer and Peter I. Trigg UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, John Wiley & Sons, 1987. £18.50 (x + 164 pages) ISBN 0 4719 1182 8

Parasitol Today, 1987

WT441S1.pdb homology model for Plasmodium .falciparum Pf3D7_1343700 Community files, PlasmoDB 25.11.14

ABSTRACT Community files, PlasmoDB 25.11.14 Homology Model (WT441S1.pdb) of P. falciparum K13 Kel... more ABSTRACT Community files, PlasmoDB 25.11.14 Homology Model (WT441S1.pdb) of P. falciparum K13 Kelch propeller. Homology protein Model of Plasmodium falciparum K13 Kelch propeller sequence (Coding sequence PF3D7_1343700.) Made in Phyre2. (http:www.sbg.bio.ic.ac.uk/phyre2/PD2/) Kelley and Sternberg 2009. Protein structure prediction on the web: A case study.... Nat Protoc. 2009 4(3): 363-71 After preparation through PHYRE the side-chain rotamers in the final model were optimized using Andante (RE Smith et al. 2007. Andante: reducing side-chain rotamer search space during comparative modeling using environment-specific substitution probabilities. Bioinformatics, 23: (9) 1099-1105) Templates employed: 6 Templates for phyre model 2XN4 human Mayven KLHL2 Canning et al 2013 1X2R human keap1 Padmanabhan2006 2VPJ human KLHL12 Canning 2013 4ASC human kbtbd5 Canning 2013 1ZGK human keap1 Beamer et al 2005 2WOZ KRP1 rat Pseudopodial extension. Gray et al 2009 Total Q-MEAN Score: 0.730 (Z-Score =-0.44) I think this will be of interest to those working on modelling the P. falciparum and related Kelch propellers, as the beta strands of the classical propeller are retained. This work was carried out with the encouragement of Michael Miles and Colin Sutherland at the London School of Hygiene and Tropical Medicine, London WC1E 7HT UK. 2014-11-25 05:17:48 david warhurst london School of hygiene and tropical medicine Uploaded to Community files, PlasmoDB 25.11.14

Antimalarial drugs I: Biological backgrounds, experimental methods ods and drug resistanceedited by W. Peters and W. H. G. Richards, Springer-Verlag, 1984. DM296/$110.40 (xviii + 484 pages) ISBN 3 540 12616 3

Trends Pharmacol Sci, 1985

warhurst&Folwell1968growthrate

Warhurst, 1973

Antimalarial drugs II: Current antimalarials and new drug development

Trends in Pharmacological Sciences, 1985

Schizontocidal antimalarials

Transactions of the Royal Society of Tropical Medicine and Hygiene, 1990

Detection of Giardia in human jejunum by the immunoperoxidase method. Specific and non-specific results

Transactions of the Royal Society of Tropical Medicine and Hygiene, 1985

Rabbit antiserum to cultured trophozoites of Giardia intestinalis (G. lamblia) was used to detect... more Rabbit antiserum to cultured trophozoites of Giardia intestinalis (G. lamblia) was used to detect organisms in jejunal biopsies using the PAP immunoperoxidase technique. In 30 sections examined from seven cases of giardiasis associated with histological changes in malabsorption, trophozoites were seen in the lamina propria in one instance, although they were otherwise seen in the intestinal lumen and surface mucus. One anti-Giardia serum reacted with the neutrophil polymorphs in all infected jejunal biopsies, and in jejunal and rectal biopsies from patients not suffering from giardiasis. The reaction with Giardia and with polymorphs could be absorbed out using washed Giardia trophozoites but not with preparations of bacteria.

Fifth annual malaria meeting of the British Society for Parasitology

International Journal for Parasitology, 1994

Treatment of uncomplicated malaria:[Letter to editor: Authors reply]

Malaria (CDROM, 3rd Edition)

Introduction to malaria

Antibiotic Resistance from Genes to Global Prevalence, Oct 31, 2010

Advances in mode of action of antimalarials and resistance mechanisms - part 1 of 2

Antibiotic Resistance from Genes to Global Prevalence, Nov 6, 2013

Laboratory Procedures for Diagnosis of Malaria

Acanthamoeba keratitis―Resistance to medical therpy

Eye, 1990

Successful medical therapy of Acanthamoeba keratitis has been reported with combination therapy; ... more Successful medical therapy of Acanthamoeba keratitis has been reported with combination therapy; topical Brolene and neomycin. Resistance has not so far been identified as a problem, but was the basis for recurrent disease observed in a patient with bilateral infection. Eradication of amoebae was finally achieved following prolonged topical therapy and two corneal grafts in each eye. Topical anti-amoebic therapy with paromomycin, benzethonium chloride, clotrimazole and R11/29 (a phenanthridinium compound), was continued for three months post-operatively. No further recurrences occurred during 14 months&#39; follow-up. Drug sensitivities were performed for three isolates of Acanthamoeba sp (group II) which demonstrated the development of resistance to Brolene and arsenic. In addition, the resistant isolates were temperature-sensitive mutants which would not grow at temperatures above 30 degrees C. This could explain &#39;culture-negative&#39; results in some cases of clinical recurrence when incubation of laboratory samples had only been performed at 37 degrees C.

Rational use of drugs against Plasmodium falciparum

Transactions of the Royal Society of Tropical Medicine and Hygiene, Jul 1, 2001

Recent studies on resistance to blood schizontocides in Plasmodium falciparum give a rational bas... more Recent studies on resistance to blood schizontocides in Plasmodium falciparum give a rational basis for the use of artemisinins combined with arylaminoalcohols for the treatment of uncomplicated chloroquineresistant malaria in Africa. In areas where such combinations are introduced, there is reason to believe that the continued use of chloroquine in the community will help protect the new drugs from resistance. In view of several laboratory studies, combinations of artemisinins with antifolates or chloroquine pose a risk of antagonistic interaction. This can be avoided by use of the artemisinin and the companion drug sequentially.

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