Table Of ContentMilestones in Drug Therapy
Series Editors
Michael J. Parnham, University Hospital for Infectious Diseases, Zagreb, Croatia
Jacques Bruinvels, Bilthoven, The Netherlands
Advisory Board
J.C. Buckingham, Imperial College School of Medicine, London, UK
R.J. Flower, The William Harvey Research Institute, London, UK
A.G. Herman, Universiteit Antwerpen, Antwerp, Belgium
P. Skolnick, National Institute on Drug Abuse, Bethesda, MD, USA
Forfurther volumes:
http://www.springer.com/series/4991
.
Henry M. Staines Sanjeev Krishna
l
Editors
Treatment and Prevention
of Malaria
Antimalarial Drug Chemistry, Action and Use
VolumeEditors
DrHenryM.Staines Prof.SanjeevKrishna
CentreforInfectionandImmunology CentreforInfectionandImmunology
DivisionofClinicalSciences DivisionofClinicalSciences
StGeorge’s,UniversityofLondon StGeorge’s,UniversityofLondon
CranmerTerrace CranmerTerrace
LondonSW170RE LondonSW170RE
UnitedKingdom UnitedKingdom
[email protected] [email protected]
SeriesEditors
Prof.MichaelJ.Parnham,Ph.D.
VisitingScientist
Research&ClinicalImmunologyUnit
UniversityHospitalforInfectiousDiseases“Dr.FranMihaljevic´”
Mirogojska8
HR-10000Zagreb
Croatia
Prof.Dr.JacquesBruinvels
Sweelincklaan75
NL-3723JCBilthoven
TheNetherlands
ISBN978-3-0346-0479-6 e-ISBN978-3-0346-0480-2
DOI10.1007/978-3-0346-0480-2
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Preface
Malariaisadevastatingdiseasethatextractshugehealthandeconomiccostsfrom
the poorestcountriesin endemicregions. Malariaiscaused by single celled para-
sites, belonging to the genus Plasmodium that have infected humans (and related
primates)forthousandsofyears.Initsdifferentspecificandclinicalguises,malaria
isoneofthestrongestselective forcestohaveshapedourrecentevolution.These
parasites have already evaded one attempt at eradication in the mid twentieth
century. Now, there are renewed attempts to control and eventually eradicate
whatremainsoneoftheworld’sbiggestkillers.
Withambitiousnewtargetssettoreducetheglobalburdenofmalaria,wemust
urgently develop new tools for disease control, as well as optimising and re-
evaluating our current tools. An indispensable part of controlling malaria is the
capability of treating the disease effectively, despite the ability of this highly
mutableparasitetodevelopresistancesoonerorlatertoallclassesofantimalarials.
Understandingofhowantimalarialdrugsmightwork,howbesttousethemandhow
toassessforresistancetothemhasexpandedconsiderablyinthepastfewyears.This
bookaimstocapturetheserecentadvancesinourunderstandingofallantimalarial
classes,anddiscusshowthisinformationispertinentfortreatingpatients.
The introductory chapter details the disease, its current political, financial and
technical context, alongside the policies and tools required to make eradication a
possibility.Subsequentchapterscoverthehistory,chemistry,mechanismsofaction
andresistance,preclinicalandclinicaluse,pharmacokineticsandsafetyandtolerabil-
ityofourcurrentantimalarialdrugarmamentarium.Eachchapterreflectstheunique
perspectives of its expert authors, and often describes new ideas and directions for
study. There is particular emphasis on artemisinins (and related next generation
peroxides)thathavebecomethefrontlinetreatmentformalaria,aspartofartemisi-
nin-basedcombinationtherapies(ACTs).Theartemisininsmayhavebecomeestab-
lishedinACTsinthepastdecade,buttheyarenowbeingchallengedbythepotential
forresistancethathasrecentlybeendescribedandisonlyjustbeingdefined.
Other chapters authoritatively discuss our antimalarial drug development pipe-
lineandhowthisisbeingshapedbypublic/privatepartnerships;molecularmarkers
vii
viii Preface
of antimalarial drug resistance, their use in monitoring treatment failures and the
insights they provide into the action of these drugs; malaria prevention strategies,
includingchemoprophylaxis,wheretheriskofcatchingmalariaisbalancedagainst
the risk of side effects of drugs and the critical use of diagnostics to improve the
identificationofmalariaandtorefinetreatmentstrategies.
Thetreatmentandpreventionofmalariaisafascinatingandcomplexsubject–
made all the more interesting now that malaria eradication is back on the global
agenda.Wehopethatreaderswillbestimulatedbythisvolumeandthattheymay
finditscontentsusefulindealingwithmalaria.
London,UnitedKingdom HenryM.Staines
SanjeevKrishna
Contents
AntimalarialDrugsandtheControlandEliminationofMalaria ......... 1
KarenI.Barnes
4-Aminoquinolines:Chloroquine,Amodiaquine
andNext-GenerationAnalogues ............................................. 19
PaulM.O’Neill,VictoriaE.Barton,StephenA.Ward,
andJamesChadwick
CinchonaAlkaloids:QuinineandQuinidine ............................... 45
DavidJ.Sullivan
8-Aminoquinolines:PrimaquineandTafenoquine ......................... 69
NormanC.WatersandMichaelD.Edstein
Other4-Methanolquinolines,AmylAlcoholsandPhentathrenes:
Mefloquine,LumefantrineandHalofantrine ............................... 95
FrancoisNosten,PenelopeA.Phillips-Howard,
andFeikoO.terKuile
Antifolates:Pyrimethamine,Proguanil,Sulphadoxine
andDapsone .................................................................. 113
AlexisNzila
Naphthoquinones:Atovaquone,andOtherAntimalarials
TargetingMitochondrialFunctions ........................................ 127
AkhilB.Vaidya
Non-AntifolateAntibiotics:Clindamycin,Doxycycline,
AzithromycinandFosmidomycin ........................................... 141
SanjeevKrishnaandHenryM.Staines
ix
