The race againstdrug-resistant strainsPromising trials ofnew drugs offerfresh hopePage 5

FT Health Combating MalariaFT SPECIAL REPORT

www.ft.com/reports | @ftreportsFriday April 24 2015

Inside

The laws of attractionBiological-warfare tacticrelies on geneticallymodified insectsPage 2

Searching for thesilver bulletVolunteershelp vitalresearch intovaccinesPage 3

Testing timesThe start-ups developinga new generation ofdiagnostic toolsPage 4

Insecticides and theneed for innovationAs mosquito immunityto pyrethroids increases,alternatives are essentialPage 6

T his will be a decisive yearfor malaria. From the jun-gles of the Greater Mekongor the urban shanties ofHaiti, new tools and tactics

are being used to counter the spread ofthe disease and to alleviate its huge eco-nomicandhumancosts.

It still infects 200m people each yearand kills nearly 600,000, yet enormousprogress has been made since the startof the millennium — the death rate hashalvedandanestimated4.3mliveshavebeen saved but there are concerns overfundingand biological resistance.

Pedro Alonso, director of the WorldHealth Organisation’s global malariaprogramme, says: “Malaria has been asuccess story. The progress made isreally unprecedented. But we are at atipping point. We are worried aboutlosing the gains achieved over the pastdecade.”

Meanwhile, 19 countries are movingtowards elimination. Argentina is set tobe declared malaria-free this year, whileother nations including Sri Lanka andSaudiArabiaareclose.

Leaders of countries where malaria isendemic have stepped up their cross-border commitments spearheaded byorganisations such as the African Lead-ers’ Malaria Alliance and the Elimina-tion Eight of southern African countries

as well as the Asia Pacific LeadersMalaria Alliance. Some prominent busi-ness people have also increased sup-port, suchasAlikoDangote inNigeria.

Increased funding to disseminateexisting tools — including indoor resid-ual spraying and insecticide treated bednets, rapid diagnostic tests for accurateconfirmation of malaria and artemisi-nin-combination drug therapy for treat-ment — has helped strengthen the fightagainst the disease. New experimentalapproaches are also advancing. TheMedicines for Malaria Venture and itsacademic and pharmaceutical industrypartners report progress towards asingle-dosemalaria treatment.

GlaxoSmithKline’s RTS,S, a vaccine itis developing against the parasite, isbeing scrutinised regulators. Mean-while, Oxitec is developing geneticallymodifiedsterilemosquitoes toeradicatethe insects that transmit the infection.

There is fresh momentum on yetmore ambitious goals. The Bill &Melinda Gates Foundation is reviving adecades-old discussion about eradica-tion.“Thegreatdebatenowisamalaria-free world,” says Alan Magill, in chargeof work on the disease at the Seattle-based organisation. “Do we just acceptthe status quo or start to chart pathstowardsanewvision?”

Already the World Health Organisa-

tion is set to seek approval next monthfrom ministers of health at the WorldHealth Assembly in Geneva of a bolderplan for 2016-2030 that envisages elimi-nation of malaria in at least 35 morecountries, with a 90 per cent reductionindeathandinfection.

In the Greater Mekong, a growingnumber of studies have shown that theparasite has become resistant to artem-isinin and the other drugs with which itis combined on the Thai-Cambodiaborder. There are plans for a rapid shifttowards elimination of the disease usingtechniques including mass drug admin-istrationtotheentirepopulation.

Continuedonpage3

Fight intensifies against a killer diseaseDespite progress,existing treatments andpesticides are losingtheir effectiveness,saysAndrew Jack

Challenge:infrared trackingof multiplemosquitoesattempting toreach a humanvolunteerLiverpool School of TropicalMedicine/University ofWarwick

‘We are at atippingpoint.Weareworriedaboutlosing thegainsachievedover thepast decade’

2 ★ † FINANCIAL TIMES Friday 24 April 2015

The humble lightbulb is not oftencounted among the tools used to fightinfectious disease. But, as questionshang over the efficacy of the insecticide-treated mosquito net, some argue thatadditional measures — from innovativeindoor lighting to land reuse — will beneededtohalt thedisease’s spread.

Most agree that the distribution ofbed nets has been a success andaccounted for a large proportion of the4.3mlivessavedbetween2001and2013through all interventions monitored bytheWHO.

The nets have two functions. Theyprovide a protective barrier that shieldspeople from the insects. And whentreated with pyrethroid-based insecti-cides — which are less harmful to theenvironment and humans than otherproducts — they kill mosquitoes on con-tact, shrinkingtheirnumbers.

Yet, despite their success, it is becom-ing clear that nets cannot be the solesolution to arresting the spread ofmalaria.

First, a growing number of mosqui-toes are developing resistance to theinsecticides. Alternatives are beingdeveloped but getting them to marketwill taketime.

Others worry about the nets’ environ-mental impact. On the shores of LakeTanganyika, for example, one recentstudy found free bed nets being used forfishing in 87 per cent of the shorelinehouseholdsstudiedbytheLakeTangan-yika Floating Health Clinic, a non-gov-ernmentalorganisation.

The problem is that the finely meshednets catch far more fish than traditionalnets, threateningfishstocksanddamag-ing the lake’s ecosystem. Concerns havealso been raised about the potentialwater pollution the insecticide chemi-calscancausewhenthenetsareusedforfishing.

Moreover, even where nets are widelydistributed and being used for theirintended purpose, there is evidence thatmalariaratesarerising.

One surveillance study found this to

be the case in rural areas of Uganda. Inspite of the fact that bed nets were givento all children under 10, malaria inci-dence remained high and increasedoverthetwo-yearstudyperiod.

“We think Uganda is representative ofa lot of sub-Saharan Africa, where westill have a long way to go,” says PhilipRosenthal, a professor in the School ofMedicine at the University of California,San Francisco, which studies malaria inAfrica.

Such evidence, along with insecticideresistance and environmental worries,is prompting some to suggest that addi-tional measures must be used in con-junctionwithbednets.

For the lightbulb, it is early days. Butresearchers at the University of South-ern California believe that using indoor

lighting that is less attractive to insectsmeans fewer mosquitoes would bedrawntothe light.

The difference is in the light’s colourtemperature, as measured through theKelvin scale. The researchers havefound that if lighting gives off a blue col-our wavelength, it is more attractive tocertain insect species, including mos-quitoes.

Using this knowledge, theteam worked with Philips,the conglomerate thatmakes lightbulbs, todevelop lamps with acolour wavelengththat attracted about20 per cent fewerinsects than off-the-shelfLEDbulbs.

“This could be anadditional tool to mini-mise their abundance inareas where you don’thave screens and glass win-dows but you need an insidelight,” says Travis Longcore,associateprofessorat theuni-versity’s Spatial SciencesInstitute. By the same token,he says, the current push toreplace kerosene lamps with

standard LEDs could increase thespread of malaria in some developingcountries if those lights give off coolerwavelengths. “In those situations, youshouldn’t be replacing a yellow lightwith a blue-ish light as it will attractmore insects.”

In addition to lighting, some arguethat improved housing must be part ofthe strategy to combat malaria. Whilelarge-scale trials of the effectiveness ofhousing measures have yet to be con-ducted, experience suggests that mos-quito-proofing homes by installing win-dowanddoorscreenscanbeeffective.

Between 1925 and 1927, for example,the British army reduced the incidenceof malaria in its barracks in Lahore,Pakistan, from 569 cases per 1,000 peo-ple to 45 after the barracks were mos-quito-proofedwithscreens.

In a report citing this and many otherearly studies, Habitat for Humanity, thehousing non-profit organisation, callsfor further exploration of the linkbetween housing improvement andmalariareduction.

Others point to the benefits of landusechanges.

Reclaiming swamps and plantingcrops on the land would reduce breed-ing sites, says William Jobin, a publichealth engineer who worked on largeirrigation and drainage systems in cen-tralSudan.

“Malaria dropped to barely measura-ble levels,” he says. “So the technique

works.”Of course, not all these

measures are free of con-troversy. Draining

swamps has implica-tions for ecosys-tems and biodiver-sity. Malaria-proofing houseswith screens canbe logistically

tricky and unaf-fordable for some

people. But while bednets will play an impor-

tant role in reducing thespread of malaria, it isbecoming clear that a

broader package of solu-tions isneeded.

“It’s not that things havegot worse, but things are notobviously getting better,”

says Prof Rosenthal. “Andthat tells us we need more

interventions.”

Time has come to cast net wideras pesticide resistance growsPrevention

As bed nets begin to losetheir effectiveness,researchers are comingup with new approaches,writes Sarah Murray

Fighting the blues: on awarmer wavelength

FT Health Combating Malaria

M alaria depends on a com-plex triangle of biologicalrelationships betweenthe Plasmodium parasiteandits twohosts:humans

and mosquitoes. Although most scien-tific attention in recent years hasfocused on attacking the parasite itselfthrough drugs and vaccines, the war onthe Anopheles mosquitoes, whichspread Plasmodium to people, is gather-ingpace.

But progress is threatened by the evo-lution of resistance against pyrethroids,the main class of insecticides used forbednetsandindoorspraying.

Genetic mutations can produce threedifferent types of resistance: metabolicresistance leads to enzymes that breakdown insecticides more efficiently; pen-etration resistance hardens the insects’outer cuticle so they absorb less chemi-cal; and target-site resistance reducesthe ability of the insecticide to target themosquito’s immunesystem.

In January, researchers from the Uni-versity of California, Davis, reported inProceedings of the National Academy ofSciences the emergence of a “super-mosquito” in Mali as a result of inter-breeding between Anopheles gambiae,the most important malaria carrier, andarelatedmosquito,A.coluzzii.

“It is ‘super’ with respect to its abilityto survive exposure to the insecticideson treated bed nets,” says Gregory Lan-zaro, who led the research team. Thestudy “provides convincing evidence

indicating that a man-made change inthe environment — the introduction ofinsecticides — has altered the evolution-ary relationship between two species, inthis case a breakdown in the reproduc-tive isolationthatseparates them.”

Such evidence is driving the growingeffort to develop entirely new insecti-cides, with the Innovative Vector Con-trolConsortiumleadingtheway.

Meanwhile, more fundamentalresearch into mosquito biology pro-ceeds apace. Recent work is uncoveringunsuspected relationships betweenmosquitoes’ DNA and behaviour. InNovember, the journal Science pub-lished two papers comparing thegenomes of 16 Anopheles species thatlive in different parts of the world withdifferingabilities totransmitmalaria.

The comparison shows that Anophe-les mosquitoes evolve very fast by insectstandards. Genes involved in reproduc-tionchangeparticularlyrapidly.

“These dynamic changes may offerclues to understanding the diversifica-tion of Anopheles mosquitoes: whysome breed in salty water while othersneed temporary or permanent pools offresh water, or why some are attractedto livestock while others will only feedon humans,” says Daniel Neafsey wholeads the Malaria Genome Sequencingand Analysis Group at the Broad Insti-tute inMassachusetts.

Follow-up research, which Sciencepublished online in February, focusedmore closely on the evolution of

Anopheles’ reproductive traits. Thefindings suggest that understanding theinsects’ sexual biology may producenew targets for malaria control. Forexample, the ability of Anopheles spe-cies to transmit malaria to humans isrelated to the amount of a steroid hor-mone called 20-hydroxyecdysone pro-ducedbymalemosquitoes.Blockingthehormonecouldprevent transmission.

Researchhasbeenpublishedthisyearon the chemical cues that prompt mos-quitoes to bite people. “Understandingthe molecular basis of mosquito attrac-tion and host choice is important for fig-uring out how you might prevent peoplefrom getting bitten in the first place,”says Audrey Odom of Washington Uni-versity inStLouis.

She is senior author of a paper pub-lished last month in the journal mBiothat shows how Plasmodium enhancesits transmission. It entices mosquitoesto take blood meals from infectedpeople by emitting molecules called ter-

penes. The discovery could lead to newdiagnostic tests for malaria, if the terpe-nes can be detected in patients’ sweat orbreath.

Another study, published in Januaryin the Journal of Chemical Ecology,showed carbon dioxide, the gas pro-duced by respiration, plays a central rolein mosquito biting. The insects do notrespond to human skin odours unlesssomeadditionalCO2ispresent, too.

Ring Cardé, entomology professor atthe University of California, Riverside,whose lab carried out the research, sug-gests mosquitoes use human smells tolocate the presence of people — and inparticular thehouseswherethey live.

“We already know that mosquitoeswill readily fly upwind towards humanskin odour. But landing, the final stageof host location which typically takesplace indoors, does not happen unless afluctuating concentration of carbondioxide indicates that a human host ispresent,”hesays.

War onAnophelesmosquitoesheats upResearch Scientists are learningmore about howthe insects target humans, writes Clive Cookson

Mosquito larvae: some breed in salty water, while others need fresh water—Alamy

Chemical insecticidesarethemainweaponsusedagainstmosquitoestoday,but futurecampaignscouldfocusonbiologicalwarfarewagedwithgeneticallymodified insects.

Oxitec,acompanyspunoutofOxforduniversity in2002, is theadvanceguardof thisapproach,usingtechnologythatinsertsa“dominant lethalgene” intomosquitoes. Itproduces lustybutinfertilemales thatmatewithallavailable females; theresulting larvaediebeforehatching.

Thestrategy, testedoverthepast fiveyears in fieldtrials inMalaysia, theCaymanIslands,PanamaandBrazil, istoreleaseenoughof thesesterilemalestoswampthenatives.Thatmeansreleasingmanymillionsof insects—thenumbermustbe10ormoretimeshigherthanthewildpopulation.

Oxitec is focusing itsresearchanddevelopmenteffortsonAedesaegypti,themosquitothat transmitsbothdenguefeverandthechikungunyavirusthat is spreadingrapidlyaroundthewarmerpartsof theworld.

HadynParry,chiefexecutiveofOxitec, says thecompany’sscientistshaveshownthat thesametechnologycanbeappliedtotheAnophelesmosquitoes that transmitmalaria,thoughconsiderable investmentwouldbeneededtoadapt it to their lifecycle.“Weknowthat it is feasible . . . butweareasmallcompanyandwedon’thavethefundingorresources,”hesays.

Thefour fieldtrialscarriedoutsofarwithOxitec’smodifiedAedesaegyptimosquitoes,knownasstrainOX513A,reducedthenumberofdisease-carryingmosquitoesbybetween93and96percent insixmonths,MrParryadds.

OX513Acontains twoaddedgenes.Oneisa fluorescentmarkergenethat

enablesscientists to identifyanyprogenyfromthereleasedmosquitoes,estimatepopulationsizesandmonitorpopulationsuppression.

Theothergene isdesignedtokill theirlarvae.But therehastobeawaytooverride it sothat themosquitoescanbebredforrelease.Thechosenantidote isthecommonantibiotic tetracycline,whichswitchesoff the lethalgene.

Thisuseof tetracycline isoneofseveralaspectsof thetechnologyonwhichOxitec’sopponentshaveseized.GeneWatchUKsaysmassproductionofGMinsects inbreedingfactoriescouldspreadantibioticresistance intotheenvironment.

Butaccordingtothecompany, theamountof tetracyclinerequiredtobreedOX513Amosquitoes is“insignificant”comparedwiththequantitiesusedforveterinary,agriculturalandmedicalpurposes.

MrParryconcedesthat the

technology iscontroversial. “Therewillalwaysbepeopleopposinguswhoareanti-GMinprinciple,”hesays.

Thecompanyhasmademostprogress inBrazil,where ithasreceivednational technicalapproval forcommercial releaseofOX513Afromthenationalbiosafetycommittee.

ItalsohopestobreakintotheUSmarketwithafieldtrial inFlorida.TheFoodandDrugAdministration iscurrentlyconsideringthatapplication.

MrParry insists that theOxitecapproachis farpreferable fromthesafetyandenvironmentalpointofviewtocontrollingmosquitoeswithtoxicpesticides.“It ishighlytargetedtotheone insectspecies thatcausesharmtohumans.Other insect life isuntouched,”hesays.“Oncethereleaseof theOxitecmosquitoes is stopped, themodificationdisappears fromthegenepoolandtheenvironment.”

Lethal gene relies onlaws of attractionGenetics

Impressive results asbiological warfare isdeployed to combat insects,reports Clive Cookson

Hadyn Parry:‘There will alwaysbe peopleopposing us whoare anti-GM inprinciple’

‘You shouldn’t bereplacing a yellow light witha blue-ish light’

Friday 24 April 2015 ★ FINANCIAL TIMES 3

FT Health Combating Malaria

I magine volunteering to be infectedwith a disease that kills nearly600,000 people a year. That is whatCeleste Farmer, a psychology stu-dent at the University of Queens-

land in Australia, agreed to do in orderto help researchers develop drugs totreatmalaria.

“I’m healthy, but there are plenty ofpeople out there who are not,” she says.“It is important for people to donatetheirbodies likethis tohelpothers.”

Ms Farmer is one of 230 volunteerswho have taken part in trials using the“challenge model”, in which healthyhuman subjects are infected with lowdoses of malaria to test the efficacy ofnewdrugtreatments.

Advocates say the trials, undertakenby the QIMR Berghofer MedicalResearch Institute and other globalinstitutes, are speeding up the delivery

of new anti-malaria drugs, saving phar-maceutical companies millions of dol-lars in R&D costs and providing hope forthe development of more effective vac-cines.

“While many new drugs and vaccinesare being developed, it is difficult todetermine which are the best to take toareas where malaria is a life-threateningdisease,” says James McCarthy, a profes-sor at QIMR. “Malaria is becoming moreresistant to existing treatments, whichmakes the speedy development of newdrugs vital. These trials are helping toachievethis,”hesays.

The World Health Organisationreports that there were about 198mcases in 2013, mostly in Africa, Asia andSouth America which led to an esti-mated584,000deaths.

Under QIMR’s challenge model, par-ticipants in the trials are injected with asample of malaria that is much less thantheamount thatreaches thebloodwhena human catches the disease from amosquitobite.

Volunteers are closely monitoredusing tests that measure the DNA ofmalaria parasites in the blood. This ena-bles researchers to treat the volunteersbefore they become ill. They can admin-ister trial drugs to monitor their effec-

tiveness at tackling the disease and cap-ture valuable information that can helpdeveloptreatments.

The critical component of anyhuman-challenge model is that an exist-ing drug has to work 100 per cent to res-cue the volunteer who has beeninfected. This is one of the reasons thatthe model works well in the case ofmalaria.

“This method reduces costs, increasesthe speed of drug testing and provides a

valid path to develop new malariadrugs,” says Prof McCarthy. “By usingthis method, we have [ruled out] threetrial drugs at an earlier stage than wouldnormally be possible. The data we col-lect also enable us to guide the dosageapplied in larger fieldstudies.”

None of the participants in the trials,which have continued for several years,have become ill, say the researchers — apositive outcome which they attributeto intensive monitoring and the timelydeployment of proven drugs to kill themalaria parasites in the blood beforetheybecomearisk.

“I did have a headache at one stagebut that may just have been the hospitalenvironment,” says Ms Farmer. “I hadcomplete trust inthemedicalpeople.”

The challenge-model research hasattracted support from Medicines forMalaria Venture (MMV), a Switzerland-based non-profit agency. A big interna-tional donor will shortly be announcedbythe institute.

Tim Wells, chief scientific officer atMMV, says: “QIMR learns lots about thebasic immunology of malaria — it’s avaluable resource, and . . . James’s [ProfMcCarthy’s] team has learnt a lot abouthow the human body deals with low lev-elsof infection.”

MMV and pharmaceutical companypartners provide the new drug com-pounds, which are tested by QIMR. Itnow has three molecules moving intofull clinical development — and MMVpicked the dose to be applied for two ofthe drugs based on data provided by theQIMRteam.

“It saved us a year at least, which isimportant knowing that we urgentlyneed new treatments,” says Mr Wells.“Weknowreallyearlyoninaproject if itworks. That gives us the confidence tomove quickly into the big clinical stud-ies in Africa, which are expensive andalsocomplicated.”

The “silver bullet” for researchersis the development of a 90-100 percent effective vaccine for malaria. Thecurrent vaccine in phase III trials isexpected to be only 30-50 per centprotective. Groups working on vaccinesare making progress and the dataprovided by the challenge model arebuilding knowledge on how one shouldwork.

“Too often people prefer to fund big“pivotal” clinical trials based on notenough science,” says Mr Wells. “Butwhat is important is that we understandthe human biology of the vaccinesbeforewestartdoingbigclinical trials.”

Human trials speed up delivery of vaccinesR&D Australian drugtrial research on healthyvolunteers is attractinginternational donors,writes Jamie Smyth

Challenge model: James McCarthywith one of the drug-test volunteers

The aim is a $4bn decade-long effortto wipe out the parasite in the regionwhere resistance to drugs has emergedin the past and further resistance risksspreading around the world today. Thedanger is malaria’s ability to adapt —there are well documented past failuresof widespread elimination programmesthat ultimately only spurred resistance.Migrant and often clandestine workerson contested borders in the region willaddtothecomplications.

Stillmoretroubling,notably inAfrica,is a growing pattern of resistance toexisting insecticides used to sprayindoors and to impregnate bed nets.Manufacturers and academic teams areworking on alternatives, but areconcernedatslowprogress

Luke Lucas, in charge of global vectorcontrol at Sumitomo Chemical, says:“It’s like we are steaming on the Titanictowards the iceberg but having to waituntil we sink and large numbers of peo-ple die before there is a willingness tochange.” He and others raise the alarmabout counterfeit, substandard andinappropriate insecticides, bed nets anddrugs thataccelerateresistance.Despiteinternational guidelines against the useof “monotherapy” artemisinin drugs,for instance, eight countries still author-ise their use and two dozen Indian com-paniesmanufacturethem.

In the absence of stronger publichealth systems, there are also continuedworries about the role of the privatemedical sector.

But if tougher controls and incentivesfor appropriate use of newer technolo-gies are important, so are more targetedapproaches to stretch existingresources further. Nigeria and theDemocratic Republic of Congo aloneaccount for 40 per cent of total globalmalaria deaths each year, yet progresshasbeenslow.

In Haiti, older chloroquine drugsremain effective while bed nets are lessuseful than elsewhere, given that mos-quitoes inHaiti tendtobiteearlier in the

Continued frompage1

evening. That suggests the need for dif-ferent approaches to malaria in differ-ent locations.

Increased funding will be fundamen-tal tocontinuedprogress.

The WHO’s own plan envisages thatannual spending on malaria needs torise from $2.5bn currently to $6.5bn by2020and$9bnby2030.

In September, the UN general assem-bly is set to adopt Sustainable Develop-ment Goals to replace the MillenniumDevelopment Goals (MDGs) that expireat the end of 2015. The fear is that thenew objectives will distract attentionfrom health in general and malaria in particular.

Ray Chambers, the businessman andUN secretary-general’s special envoy forfinancing the health MDGs and the fightagainst malaria, says: “We’ve beenworking hard to retain quantifiable andmeasurable outcomes. We’re a bit con-cerned about the number of additionaldraftgoalsandhowtokeepthefocus.”

Whatever the outcomes, there aregrowing calls for fast-growing emergingeconomies with a significant malariaburdentopaymorethemselves.

Tocomplicatematters, there isdebateabout the explanations for reducedmalaria cases in recent years, and hencehow best to respond in the future. Casenumbers in parts of Africa began fallingbefore the big upsurge in funding fromthe early 2000s. That implies otherfactors than health programmes — suchas infrastructure and broader economicand social development — were at leastpartly responsible for the decline incases.

“We need to think more about joiningforces with other sectors,” says Fatou-mataNafo-Traoré,headof theRollBackMalaria partnership. “Construction andsmall-scale irrigation create breedingsites for mosquitoes. Improvinghousing, education and tacklingmalaria through tourism ministriesareall important.”

In the fight against malaria, healthresponsesalonewillnotbeenough.

Fightintensifiesagainst akiller disease

‘It saved us a year at least,which is important, knowingwe need new treatments’Chief scientific officer, MMV

ContributorsAndrew JackEditor of FirstFT,former pharmaceuticals correspondent

Clive CooksonScience editor

Andrew WardPharmaceuticals correspondent

Jamie SmythAustralia correspondent

Andrew BoundsEnterprise editor, Manchester

Sarah MurrayFT contributor

Emma BoydeCommissioning editorSteven BirdDesignerAndy MearsPicture editor

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$2.5bnThe amountspent globallyevery yearfighting malaria

$6.5bnThe annualamount WHOestimates willneeded by 2020

4 ★ FINANCIAL TIMES Friday 24 April 2015

FT Health Combating Malaria

Little Ahmed was restless and febrile ashe sweated profusely in his woodenbed. His temperature soared despitehis mother Amina rubbing him downwith a towel soaked in water. “It ismalaria,” she said, pressing on his chinto help him swallow a syrup from alocal medicine store.

Such is the plight of the average poorfamily with no access to insecticide-treated bed nets and decent livingconditions. To ease their suffering andbring attention to their plight is whythis week we mark World Malaria Day.

The day has been set aside for healthadvocates and individuals around theworld to raise awareness of malaria asa disease that is preventable andtreatable, and to mobilise action toend its ravages.

This year, the burning question iswhat more can we do collectively andwhat specifically is the role of theprivate sector, of which I am a part, tohelp eliminate the disease?

I have chosen to be a part of thisglobal effort because in the past 20years I have witnessed scores ofchildren afflicted by the scourge ofmalaria. Studies show that Nigeria hasa quarter of the world’s disease burdenand reports more deaths from thedisease than any other country.

In Nigeria, each year malaria isresponsible for killing an estimated300,000 children and contributes tomore than 4,000 maternal deaths. It isalso the leading cause of absenteeism,resulting in loss of productivity at workand school.

An estimated 97 per cent ofNigerians are at risk from malaria, andhalf of adults suffer at least oneinfection every year. Malaria accountsfor 60 per cent of outpatient visits and30 per cent of hospitalisations.

The Nigerian economy loses some$2.4bn annually from malaria-relatedabsenteeism and treatment costs. Inaddition to the direct costs to businessand the economy, it inflicts indirectdamage through the deterioration ofhuman capital, the loss of savings,investments and tax revenues. This isclearly too high a price.

Because malaria is so prevalent andmany people can easily seek an over-the-counter cure, many people havebecome desensitised to the debilitatingeffects of the disease.

What works for prevention is the useof insecticide-treated bed nets andspraying affected areas. We also knowthe value of systematic testing withrapid diagnostic tests to ensure onlypeople with malaria are given anti-malaria drugs; and that artemisinin-combination drugs cure the disease.

Over the past 10 years, thegovernment of Nigeria and its partnershave committed huge amounts ofmoney to bring malaria under control.Although these efforts have reducedprevalence by more than 8 per cent,much more needs to be done.

As the founding patron and funder ofthe Private Sector Health Alliance ofNigeria (PSHAN), I have focused on

mobilising business leaders in Nigeriato leverage their capabilities, advocacy,innovation and resources to supportthe government in scaling up coverageof simple cost-effective, life-savinginterventions across the value chain,including financing, manufacturingand distributing life-savingcommodities.

Through my foundation, I have andcontinue to contribute funds tosupport the government-led NationalMalaria Elimination Programme,and other non-governmentalorganisations including the ClintonHealth Access Initiative to whichwe gave $500,000 to test seasonalmalaria chemoprevention (withantimalarials) in the north of Nigeria,which has proven successful.

This effort should now be replicatedand scaled up with support fromothers. The Dangote Foundation willcontinue to advocate increasedawareness and commitment as the bestapproach to eliminate malaria entirelyfrom Nigeria.

As the malaria ambassador forNigeria, I will continue to use my voiceto attract attention to the fight againstthe disease. I will be a part of the globalcampaign using social media,television, newspapers and radio toraise awareness of malaria and itsprevention.

As we come together on WorldMalaria Day, I urge every individual,group, conglomerate and communitynot just to join the fight but to sustainthe battle against malaria by takingpractical steps to prevent the healthproblems it causes and to safeguardour collective future.

Aliko Dangote is president and chiefexecutive of Dangote Group. He is malariaambassador for Nigeria, presides over theDangote Foundation and is foundingpatron of the Private Sector HealthAlliance of Nigeria.

Theplight of victims and losses to theeconomyhave been a call to action

GUEST COLUMN

AlikoDangote

Bed-nets: their use has reduced rates of infection — William Daniels/Malaria Consortium

97 per cent of Nigerians areat risk frommalaria, and halfof adults suffer at least oneinfection every year

H alf a century ago, theDominican Republic andHaiti combined forces in abold but ultimately unsuc-cessful initiative: to elimi-

nate malaria from the island of Hispani-ola. Now, despite continuing politicaltensions, they are uniting again for afreshattempt.

“There is longstanding interest in His-paniola to make it a malaria-freeregion,”saysPatrickKachur, chiefof theUS Centers for Disease Control and Pre-vention, which is working on the pro-gramme. “Both countries are interestedand,politically, there is thewill.”

Yet the experience of recent years —and the limited resources available —highlight the need for a more targetedapproach.

Malaria and the mosquitoes thatcarry it were probably brought to theCaribbean by slaves in the late 15th cen-tury. Plantation agriculture helped itsspread by creating stagnant pools ofwaterallowingmosquitoes tobreed.

Today, the island of Hispaniola is thelastplace intheregionwherethediseaseis endemic, and its continued presencehas periodically led to cases spreadingto nearby countries such as Jamaica.There are an estimated 15,000-30,000cases a year in Haiti, and fewer than 50deaths.

In the 20th century, malaria in muchof the Caribbean and Central Americawas tackled by a mixture of extensivespraying with the pesticide DDT to killmosquitoes, combined with swampdrainage. Then, US funding for suchprogrammes diminished in the 1960s,slowing the momentum. Widespreaduse of DDT also went out of fashion,reflectingenvironmentalconcerns.

While the Dominican Republic hadcut annual infections to just 21 by 1968,Haiti — already falling behind its neigh-

bour economically and politically —struggled to keep pace, in turn provid-ing a way for malaria to spread backacross theborder.

Since 2009, a fresh effort has beenlaunched in conjunction with the twocountries’ ministries of health and theCarter Center, a charity founded byformerUSpresident JimmyCarter.

Its International Task Force for Dis-ease Eradication concluded that elimi-nation was technically feasible, medi-callydesirableandeconomicallybenefi-cial. The aim, with estimated total fund-ing requirements of $194m, is to endmalariaonHispaniolaby2020.

Jean Frantz Lemoine, head of Haiti’smalaria control programme, says hebelieves the elimination objective isworth pursuing, but he remains cau-tious about whether the scale of addi-tional fundingrequired isachievable.

According to the World MalariaReport 2014, support dropped from arecent peak of $8m in 2004 to almost

zero in 2010, rising again since, but stillto less than $4m in 2013. The good newsis that in Haiti the parasite remains sen-sitive to chloroquine — a cheap andwidely available medicine — as opposedto many other parts of the world whereit is ineffective.

Furthermore, the introduction inrecent years of rapid diagnostic tests hasshown that malaria may in fact be lesscommon in Haiti than was thought. Butit has also demonstrated the poor qual-ity of reporting. That highlights theneed for more accurate compilation oftest results to focus efforts where theyareneeded,using tools suchas textmes-sagingandgeospatialmapping.

“Haiti offers a chance to use currenttools with new strategies rather thancurrent tools with the current strategy,”says Alan Magill from the Bill & MelindaGates Foundation, which has helpedfund the new programmes. “A simpleredirectionto targetwhere thedisease iswillmakeahugedifference.”

There are other particularities ofmalaria intheregion.

According to the CDC, in Africa mos-quitoes typically bite overnight andindoors, while people are sleeping. InHaiti, by contrast, they tend to bite ear-lier in the evening, between 5.30pm and9pm. They also typically do so largelyoutdoors, or fly outdoors after bitinginside, rather than lingering on internalwallsorceilings.

That means insecticide-treated bednets — despite being widely funded anddistributed by donors in the country —are not particularly effective either inprotecting people from being bitten orin killing mosquitoes. Indoor residualspraying with insecticide may alsoprove lesseffectivethanelsewhere.

Instead, specialists are examininghow to provide “mass drug administra-tion”, the idea being pre-emptivelyto provide drugs to populations at highriskof infection, inaneffort toeliminatetheparasiteandstopitcirculating.

Haiti revives eradication aimCase studyRecent experience andlimited funding pointto the need for amoretargeted approach,writesAndrew Jack

Fumigation: a Haitian government worker sprays pesticide to kill mosquitoes in Port-au-Prince — Hector Retamal/Getty

Next-generation technologies are aboutto transform the diagnostics landscape,with far-reaching implications formalariareduction.

Rapid diagnostic tests (RDTs) havealready brought quick results to manymore people, but new variants offergreater accuracy, which could be criticalin the fight against malaria. They willnot only help prevent indiscriminateuse of antimalarial drugs but coulduncover more victims with very mildinfections who are unwittingly helpingtospreadthedisease.

RDTs have played a critical role. Car-ried out cheaply, they do not requireclinicswithsophisticatedequipment.

“The biggest achievement of the pastcouple of years has been the increase inthe use of rapid diagnostic tests,” saysIveth González, head of the malaria pro-gramme at the Foundation for Innova-tive New Diagnostics (Find). But shesays that the accuracy of the tests needsto be improved. “The current rapid testis not sensitive enough to detect verylowlevelsof infection,”sheexplains.

Factors ranging from low-qualitymanufacturing or exposure to high tem-peratures during transport and storagemean the tests often vary in quality. Toaddress this, Find has been workingwith the World Health Organisation andothers on a programme to improve thequalityof thetests.

Now, a number of researchers andstart-ups are using next-generationtechnologies to develop alternative teststhat are cheap and fast but also able todetect lowlevelsof infection.

At Path, the Seattle-based non-profitorganisation, the Diagnostics forMalaria Elimination TowardEradication (Diameter) project isseeking to identify sensitive tests that

could be commercialised at low cost.US-based Disease Diagnostic Group, amedical device company, is developinga reusable test that aims to detectmalaria with 94 per cent accuracy inless than a minute. At a projected cost of$0.25, the test can make a diagnosisbeforesymptomsappear.

The test relies on a magnet and a laserpointer in a handheld device thatdetects the hemozoin crystals releasedbyparasites toassess infection levels.

Magnets are also the tool for research-ers at MIT and Singapore’s NationalResearch Foundation, where they havefound a way to use magnetic resonancerelaxometrytodetecthemozoin.

Meanwhile, Nanobiosym, a start-upbased in Cambridge, Massachusetts, hasdeveloped what it calls Gene-RADARtechnology to detect any disease in amatterofminutesbydecodingDNAandRNA genetic information from a bloodsample on a nano-chip inserted into amobiledevice.

“You hit the button and the machineanalyses the blood at DNA and RNAlevel, depending on what virus you arelooking for. It tells you if it is present andhow much of it there is,” explains Anita

Goel, chairman and chief executive ofNanobiosym. “And quantification is thegoldstandard.”

Start-ups and researchers are notalone in seeking new malaria diagnos-tics. GE is working with Global Good — acollaboration between Bill Gates andIntellectual Ventures, a privately heldinvention capital company — to developan affordable testing kit to detect thepresence of low levels of malaria in peo-plewithoutsymptoms.

“The most important thing is findingpeople who have not been properlytreated because they can carry for manymonths,” says David Bell, who leadsIntellectual Ventures’ work on globalhealthtechnology.

Tests get cheaperandmore sensitiveTechnology

Rapid diagnosis couldhelp detect victims withlow-grade infections who areunwittingly spreading thedisease, says Sarah Murray

RDT: communityhealth workers arealready usingmobile phones tohelp with testingand data collection

Friday 24 April 2015 ★ FINANCIAL TIMES 5

FT Health Combating Malaria

F or years, researchers havebeen hunting for a vaccineto protect people againstmalaria. But what about avaccine that could stop mos-

quitoes fromtransmittingthedisease?That is one of the approaches being

worked on by the Malaria Vaccine Initi-ative, an offshoot of the Seattle-basedPath health charity and backed by theBill&MelindaGatesFoundation.

Ashley Birkett, director of the initia-tive, says such “transmission-blocking”vaccines could become a powerfulweapon against malaria by disabling theparasites thatcausethedisease.

This approach would not preventa vaccinated person from contractingmalaria. But it would trigger antibodiesin the parasite that would stop it beingpassed on to other people by mosqui-toes.

This would be especially useful inreducing the many instances of asymp-tomatic malaria carriers, who spreadthe disease without knowing theyhave it. “Many people do not feel sickbut are infecting mosquitoes all daylong,” Mr Birkett says. “Transmission-blocking vaccines would break thatcycle.”

Vaccines of this kind have shownpromise in early trials but remain yearsaway from production for sale. The factthat Mr Birkett and other leadingmalariaresearchersareplacingsomuchhope in them reflects the limitations ofotherapproachestriedsofar.

This assessment may sound undulynegative considering that the world’sfirst malaria vaccine is on the cusp of approval. GlaxoSmithKline, the UK-based drugmaker, is hoping for a greenlight this year from the European Medi-cines Agency for the vaccine, known asRTS,S.

Mr Birkett, whose organisationhelped GSK develop the product, says RTS,S is an “important first milestone”but it “was never going to be a magicbullet”.

In clinical trials, the vaccine cut infec-tions by almost half in children agedbetween five months and 17 months andbyaboutaquarter inyoungerbabies.

Some in the global health communityhave expressed disappointment thatthese prevention rates were not higherafter 30 years of work on the vaccine.Mr Birkett says such sentiments aremisplaced.

“We all want 99 per cent efficacy butwe have to be realistic. These are goingtobe incremental steps. Ifwecanreduceincidence by 50 per during the first fiveyears of life when children are most vul-nerable that would be a big step for-ward.”

If approved by European regulators,the next step would be a recommenda-tion from the World Health Organisa-tion for its use. It would then be up tocountries in Africa and other malaria-prone regions to decide whether toadopt thevaccine.

GSK has made clear that it sees RTS,S

asaprimarilyhumanitarianrather thancommercial product. It says the pricewill cover the cost of manufacturingplus a profit of about 5 per cent to bereinvested inresearchanddevelopmentfor further vaccines against malaria andotherneglectedtropicaldiseases.

Mr Birkett says RTS,S must be thebeginning not the end of the story.“We’re taking a portfolio approachrather than putting all our eggs in onebasket,”headds.

Other organisations are also enteringthe race. One of the most promising andadvanced alternatives to RTS,S is beingdeveloped by a Maryland-based biotechcompany called Sanaria. Its vaccine,known as PfSPZ, successfully com-pleted early-stage clinical trials lastyear.

Only three of 15 participants whoreceived a high dose of the vaccine

developed malaria after being exposedto infectedmosquitoes.

Mr Birkett says the speed with whichpotential Ebola vaccines have beenrushed into clinical trials from a stand-ing start shows what can be achievedwhen the global community commitsfunding and attention to a health chal-lenge.

He would like to see a similar pushagainst malaria — a disease that killsmore people around the world in a weekthanEbolahaskilled inthepastyear.

“We need to build a whole suite ofinnovations including better diagnos-tics and better vector control, but thekey missing ingredient has been a vac-cine,” says Mr Birkett. “We can battlethe parasite with drugs and bed nets buteventually the parasite catches up. Webelieve the long-term solution has to bevaccinationanderadication.”

Researchershope vaccinescan work onseveral frontsProgressThe firstmalaria vaccinewill be amilestonebut not amagic bullet, explainsAndrewWard

High hopes: a baby is injected as part of a malaria vaccine trial — Joseph Okanga/Reuters

Artemisinin has been used to treatmalaria since at least 1596, when LiShizhen, a Chinese medical scholar,recommended that the plant extractshould be given to infected patients inthe form of a tea.

Four centuries later, artemisinin,derived from the sweet wormwoodplant, remains the key ingredient inone of the most commonly usedmalaria treatments.

Modern artemisinin-basedmedicines were developed by theChinese military in the 1960s to helpprotect North Vietnamese soldiersfrom the disease during their junglebattles with US-backed SouthVietnam. The drug wascommercialised by Novartis ofSwitzerland in the 1990s andartemisinin-based combinationtherapies (ACTs) have since become amain line of defence against malaria.About 260m courses are distributedeach year.

However, like other treatmentsbefore it, ACTs are being graduallyblunted as drug-resistant strains ofmalaria spread through parts ofSoutheast Asia. If these were to reachAfrica, where the bulk of global casesare concentrated, the big gains madeagainst the disease in recent decadescould be quickly lost.

This explains the mounting urgencybehind efforts to develop a newgeneration of malaria medicines. “Newtreatments must be developed thatattack the malaria parasites in novelways in case resistance against currenttreatments spreads,” says RogerWaltzman, who is leading thedevelopment of an experimentalNovartis drug called KAE609.

In a study among 21 patients inThailand published last year,researchers saw “rapid parasiteclearance” after the medicine wastaken. This included some people withthe ACT-resistant strain.

Nick White, professor of tropicalmedicine at Mahidol University inThailand and lead author of the studyfindings, said KAE609 was “the firstnew antimalarial drug candidate with acompletely novel mechanism of action

to reach phase II clinical developmentin 20 years”.

Novartis has predicted that, iffurther trials prove successful,KAE609 could be ready for market by2018.

The drug is one of two experimentalantimalarials under development byNovartis in collaboration with theMedicines for Malaria Venture (MMV),a Swiss non-profit group. Sanofi ofFrance, GlaxoSmithKline of the UK andTakeda of Japan are among othersworking with the public-privatepartnership. They were joined thismonth by Merck Serono, thepharmaceuticals arm of Germany’sMerck group, when it agreed to workwith MMV on an experimental drugdiscovered at the University ofDundee in Scotland. Timothy Wells,chief scientific officer at MMV, said thecompound “holds great promise”.

While new drugs may be on the way,artemisinin-based treatments willcontinue to play an important role foryears to come. Sanofi last yearlaunched an ACT using semi-syntheticartemisinin to reduce dependence onvolatile supplies of the sweetwormwood plant. The Frenchcompany said it had capacity toproduce 50-60 tonnes a year of theingredient using genetically modifiedyeast, enough to meet a third ofannual global need.AW

Drugs New treatment could be ready by 2018

Nick White: reports ‘rapid parasiteclearance’ from a new treatment

6 ★ FINANCIAL TIMES Friday 24 April 2015

FT Health Combating Malaria

A t the turn of the millen-nium, health experts hit ona way to reduce the scourgeof malaria in the develop-ing world. Distribute cheap

bed nets impregnated with pyrethroidinsecticides to as many households aspossible,andsprayhomesregularly.

It worked well. Human death rateshave almost halved while mosquitoeswere killed in untold numbers: exceptfor the tiny numbers immune to pyre-throids.

Those mosquitoes survived andbecame more prevalent. That growingresistance has left scientists and manu-facturers in a race to develop new insec-ticides.

The World Health Organisation esti-mates that without new approaches, anextra120,000peoplewilldieeachyear.

The Innovative Vector Control Con-sortium (IVCC), a disease research cen-tre, says: “Resistance can occur at a lowfrequency for many years until a tippingpoint is reached, when resistance risesextremely rapidly, which can result incatastrophic failure of an intervention.We are almost at that point in manycountries insub-SaharanAfrica.”

The IVCC, based at the LiverpoolSchoolofTropicalMedicine intheUK, isa not-for-profit organisation that workswith companies such as Syngenta,Bayer, BASF, Sumitomo, Dow andDuPont to develop products that canhelpcontroldiseasessuchasmalaria.

Professor Janet Hemingway, directorof the of the School and an expert onmosquito behaviour, presides oversome of the most advanced researchanywhere intomalariaanditscarriers.

“Everyone is confident we will pro-duce new insecticides in five to 10 years’time. The problem is we do not havevery much beyond pyrethroids untilthen,”shesays.

Syngenta and the IVCC last year wonWHO approval for Actellic 300CS, aspray for houses that is an organophos-phate rather than a pyrethroid. Itrequires only one treatment per seasonbut is between five and 10 times moreexpensivethanapyrethroid.

The WHO is trialling nets with a com-binationof insecticides,hopingtheywillwork on resistant mosquitoes. Anothernew design has insecticide impregnatedinto yarn before the net is woven ratherthan sprayed after it is made, increasingefficacy.Butcostscouldmount.

“There is nothing as cheap as pyre-throids,” says Prof Hemingway. “It isgoing to be more expensive and peoplewill have to factor that into their[donor]programmes.”

Sumitomo Chemical has alreadywarned of increased costs. Luke Lucas,

business development manager for itsmalaria programme, says that differentinsecticidesshouldberotated.

The company’s latest product, OlysetPlus, includes a pyrethroid but alsopiperonyl butoxide that can killresistant insects.

“We see Olyset Plus as an interimsolution,” says Mr Lucas. “Of course,with all the research and developmentthatgoes into it, thenetwill costmore.

“Where resistance levels are seen tostart to rise it’s incumbent on thosepeople to put pressure locally to say‘What other solutions have we?’” Headds that options could include larvi-cides, space sprays and residual indoorsprays.

Another priority is to reduce the useby farmers of pyrethroids to kill otherpests, says Kobie Hyacinthe Toé, a PhDstudent who has been testing anotherSumitomo product, the Olyset Duo, inBurkinaFaso.

Farmers use the same insecticide toprotect their rice and cotton crops. Therice and cotton fields are where mos-quito larvae are found, increasing thelikelihood of the adult insects becomingresistant. “We need the ministry ofhealth and [the ministry of] agriculturetoworktogether,”hesays.

Olyset Duo uses a pyrethroid insecti-cide and a chemical that prevents mos-quitoes laying eggs, which will stop newresistantones fromhatching.

The trial is in its first year, with morethan 60,000 nets distributed. Earlysigns are encouraging, says Mr Toé.However, he says malaria deaths in thecountryare increasing.

“Becausethenumberofmosquitoes isnot very high, people sometimes gowithout thebednet.”

Phil McCall, of the Liverpool School,believes products can save money bybeing smarter. He has been studyingmosquito behaviour, rigging a hut inAfrica with motion-sensitive camerasthatallowresearchers torecordthe flightpattern of a mosquito heading for a vic-tim. Early findings could help net designby concentrating insecticide on thoseareas the insectsvisitmost frequently.

Prof Hemingway says donors areinvesting in resistance-free alternatives.“Themessage isgettingthrough.”

Race against time to kill resistant mosquitoesInsecticides Scientistsandmanufacturersmust innovate to avoida catastrophe in thedecades to come,saysAndrew Bounds

Countries with ongoing transmission of malaria

No ongoing malariatransmission or n.a.

Less than 1

10–501–10

More than 10050–100

2013

Confirmed malaria casesper 1,000 population

Nigeria and Democratic Republic of Congo alone account for 40 per cent of global deaths from malaria each year

Experts plan mass use of the latest drugs in the Greater Mekong to elminate malaria and fight growing resistance

FT graphic Source: World Malaria Report 2014

Malaria in numbers

0

0.5

2005 13 2005 13

1.0

1.5

WHO African region Other WHO regions

DomesticInternational

Trends in funding$bn

Children* infected withP. falciparum

P. falciparum infections in sub-Saharan Africa

Countries with highest numberof P. falciparum infections

Per centEstimated number of people (m) Number of people infected, 2013 (m)

0

10

20

30

0

50

100

15040

20002000 1313

0 5 10 15 20 25 30 35

02 04 06 08 10

Africa

Eastern Mediterranean

Central Africa

East & southern AfricaWest Africa

* Aged 2-10 years

02 04 06 08 10

DR CongoUganda

MozambiqueBurkina Faso

GhanaMali

GuineaNiger

Nigeria

Malawi

Eastern Mediterranean Central AfricaEast & southern Africa West Africa

Americas 800

Western Pacific 3,300

Estimated malaria deaths2013

528,000Africa

Eastern Mediterranean 11,000

South-east Asia 41,000

‘There is nothing as cheapas pyrethroids . . . it is goingto bemore expensive’