CostsTelecoms helppave the wayto improvednet benefitsPage 2

Inside »

Fake drugs putpatients at riskCall for greaterpenalties forcounterfeitersPage 3

Within reachThe world’s firstmalaria vaccinecould be availablein a few yearsPage 4

The state of anation’s healthIndia struggles toassess its malariaburden accuratelyPage 4

ScienceResearchers testnew ways ofcontrolling thediseasePage 5

FT SPECIAL REPORT

FT Health Combating MalariaFriday April 25 2014 www.ft.com/reports | @ftreports

Success can be a dangerousthing in the world of globalhealth policy. Deaths frommalaria have fallen by 42 percent since 2000 and incidence

of the disease is down by a quarter.This is due in large part to a surge

of international financial support foranti-malaria efforts from just $100m in2000 to almost $1.84bn in 2012. An esti-mated 3.3m lives have been saved as aresult. Yet, far from trumpeting thesestatistics, leaders of the global cam-paign against malaria are worriedabout complacency.

“It is part of human nature thatpeople always want to move on to thenext thing,” says James Whiting,executive director of Malaria No MoreUK. “There is a danger that peoplethink malaria has been ‘done’ andstart to shift attention elsewhere.”

If this were to happen, says MrWhiting, the gains of the past decadecould quickly vanish. “Whenever I goto meet a politician to talk aboutfunding, I take a chart with me show-ing what happened the last timemomentum was lost,” he says.

“The first big push against malariamade huge progress between the 1950sand 1970s, but things stalled in the1980s and 1990s and you saw the dis-ease come surging back,” he adds.

There have already been warningsigns. A dip in deliveries of mosquitonets treated with insecticide – one ofthe most effective measures againstthe parasitic infection – was accompa-nied by a slowing of the decline inmalaria deaths in 2011 and 2012.

Even after years of progress,malaria remains one of the world’sbiggest killers, responsible for 627,000

deaths in 2012. About 90 per cent ofthese were in Africa and 460,000 ofthem were children under five.

“The fact that so many people aredying from mosquito bites is one ofthe greatest tragedies of the 21st cen-tury,” says Margaret Chan, director-general of the World Health Organisa-tion. “If political commitment wanes,the great progress that has beenachieved could be undone, in someplaces in a single transmissionseason.”

Much of the success of the past dec-ade has been driven by the GlobalFund to Fight Aids, Tuberculosis andMalaria – a consortium of govern-ments, international bodies and pri-vate donors set up to tackle three dis-eases that have ravaged Africa andother parts of the developing world.

Donor nations last year pledged$12bn to the Global Fund between2014 and 2016 – an increase of 30 percent from the $9.2bn donated over thetwo prior years, but short of the $15bntarget set by the fund’s leaders.

“We’re doing everything we can tokeep up the sense of urgency,” saysRay Chambers, the special envoyresponsible for financing the healthprogrammes within the UN’s Millen-nium Development Goals. “With a bigpush over the next two years, we cantry to get down to about 100,000[annual] childhood [malaria] deaths,from about 400,000 now. But fundingis a challenge.”

Strong economic growth in parts ofAfrica should help, by allowing localgovernments to spend more on healthand by lifting people out of thesqualid living conditions in whichmalaria prospers.

But Suprotik Basu, chief executiveof Mr Chambers’ team, says the dis-ease is still holding back economicdevelopment on the continent.

In parts of Ghana, for example,malaria treatment costs up to a quar-ter of household income for poorerpeople. Including lost productivity,the annual cost of malaria to Africa isestimated at $8bn-$12bn.

“Many African nations are oncourse to become middle-income coun-tries,” says Mr Basu. “We are doingeverything we can to break the back

Continued on Page 6One of the world’s biggest killers: 627,000 people died from malaria in 2012 PA

Researcherswarn victoryremains along way offThe biggest threat to the campaign againstmalaria is the perception that thewar hasalready beenwon, writesAndrewWard

When AngloGold Ashantibegan a malaria controlprogramme at its gold minein Obuasi in the Ashantiregion of southwest Ghanain 2005, the main local hos-pital was handling 6,800cases of the disease amonth.

Almost a decade later,and after an annual invest-ment of $1.5m, it has cutthat volume to about 100 amonth, and as low as 47 inMarch. “This is very posi-tive,” says Sylvester Seg-baya, director of the com-pany’s malaria control pro-gramme. “We’ve sharplyreduced the burden.”

Often nature works syner-gistically, generating prob-lems and solutions in thesame place. This applies togold mining, which oftenbrings large volumes of peo-ple close to areas ofstagnant water in humidclimates where mosquitoescan breed.

The industry risksharbouring – if not encour-aging malaria – throughartisanal mining processes,during which gold iswashed and sorted withwater, and more generallyby bringing employees intohigh-risk areas.

Yet both the mining com-panies and the preciousmetal itself can play animportant role in tacklingthe disease. The juxtaposi-tion of a lethal disease andlarge companies extractinggold is beginning to mobi-lise greater efforts to tacklemalaria.

With 2,500 of the malariacases among AngloGoldAshanti’s own employees adecade ago – amounting toa third of its workforce –there was a strong elementof self-interest in it doingmore.

With an average of threedays absence per infection,the company estimated itwas losing 7,500 man-days amonth and spending$660,000 a year on treat-

ment. Malaria causedabsenteeism from employ-ment and from schools inthe local community.

“Malaria from the veryword ‘go’ is a big problem,”Mr Segbaya says. “We sawit affecting the productivityof our employees and every-thing else. Even when staffgot back to work, they werenot as fit and strong as theyused to be, and had loweroutput. It was harming ouroperations.”

The company placedgreat emphasis on indoorresidual spraying to killand deter mosquitoes,carrying out programmesevery six months. Large-scale government pro-grammes had been carriedout several decades ago, butsince neglected.

It also launched larvicid-ing in selected places to killmosquito eggs. Morerecently, AngloGold hasensured that all suspectedcases are confirmed withtesting ahead of treatment.

It has begun to distributebed nets alongside govern-ment programmes, al-though Mr Segbaya saysthere is still some debate ontheir value at the company.

“The challenge we sawwas that people had theoption to use the nets or

not,” he argues. “We didn’twant to leave the results toindividual’s discretion. Datahave shown that people usethem only 40 or 50 per centof the time.”

However, the company’ssuccess in this area has ledto its appointment –unusual for a business – asthe principal recipient of agrant in Ghana for bed netdistribution by the GlobalFund to fight Aids, TB andMalaria. It also advises the

US President’s Malaria Initi-ative on insecticide spray-ing.

Just as importantly, thecompany has begun toexpand its programme to itsother mines in Ghana andthe various countries whereit operates, includingGuinea, Mali and Tanzania.

Its thinking has alsohelped inspire other miningcompanies to wage war onmalaria, including New-

mont of the US and Kinrossof Canada.

Critics say that largercompanies could be doingmore to tackle malaria, forinstance increasing thefocus on artisanal miningcommunities.

Many people also point tothe primary role of govern-ment in operating malariacontrol programmes.

Mr Segbaya says: “Theproblem is always that gov-ernment support has beenvery limited. We had to fol-low with the funding.”

In the absence of suffi-cient public sector financ-ing and activity, Mr Seg-baya says he is workingwith Ghana’s governmentto create “a national fundoverseen by high-profilepeople with integrity, andwith companies to maketheir contribution”.

Meanwhile, there isanother important role thatgold plays in the fightagainst malaria.

Trevor Keel, head of tech-nology at the World GoldCouncil, says the metal isan essential part of modernrapid diagnostic tests forthose infected with the par-asite. Some 200m kits aredistributed globally eachyear.

The malaria antibody isattached to gold nanoparti-cles during manufacture.These will attract anymalaria antigens in a bloodsample. That turns the par-ticles from red to purple,resulting in a “positive”two-line readout on thedevice.

“Without the gold, thesetests would be useless,”says Mr Keel.

His organisation is nowworking on support for thedevelopment of a new ther-mal contrast technologythat will improve the sensi-tivity of standard rapiddiagnostic tests.

More generally, gold itselfis finding new applications,both in diagnostics for awider range of diseases andeven in some treatments,such as for dysentery.

Gold may find a broaderrange of medical uses, whilethe businesses that extractit are mobilising to tacklethe malaria with whichmining can all too often beassociated.

Gold miner and the metal itselfhelp in fight against the diseaseCase study

Andrew Jack looksat how a businessin Ghana is takinga leading role

‘Governmentsupport has beenvery limited. Wehad to follow withthe funding’

Watchful: a mine worker at the Ashanti goldfields mine inObuasi, Ghana Reuters

2 ★ FINANCIAL TIMES FRIDAY APRIL 25 2014

FT Health Combating Malaria

Perhaps the reason MartinEdlund is optimistic aboutthe procurement and distri-bution of anti-malaria toolsis his experience in the field.

A co-founder of the charity MalariaNo More, he witnessed a successfulstep-change in malaria net distribu-tion in Senegal starting in 2008.

A year earlier, the World HealthOrganisation had changed the ruleson net coverage. While previously ithad recommended focusing distribu-tion efforts on pregnant women andchildren below the age of five, now itwas aiming for universal coverage.

That meant that the old practices –for example, handing out net vouch-ers at neonatal clinics – were nolonger sufficient. “How do you findadult males and give them thesenets,” Mr Edlund recalls asking.

There was no obvious mechanism,and yet the answer was, in the end,relatively simple: a walking census.

The group teamed up with thePeace Corps and began visitingvillages, finding out how many peoplelived in each, and telling them whenthey would be back with the appropri-ate number of nets. They even man-aged to reduce the problem of peopleselling the nets on rather than usingthem themselves by writing the nameof the head of household and thevillage on each.

In other words, the last mile – short-hand for the final steps a product orservice must take to reach the individ-uals who will use it – was less of aproblem than had been feared.

But Mr Edlund does not think thiswill always be the case. “You mightbe able to do a mass campaign withprevention tools, but not malaria dia-gnostics,” he explains.

“People need to be able to accessdiagnostic tools when and where theycome across a fever that might bemalaria.” However, he believes solu-tions to problems of access are not faroff.

Some of these come from the very

industry that gave rise to the term“last mile”: telecommunications.Thanks to widespread mobile phoneuse in African countries plagued bymalaria, experts hope for a future inwhich malaria infection could betracked in near real-time, and treatedaccordingly.

This falls into what the UN’s Popu-lation Fund describes as a “pull”model of distribution: demand-drivenand targeted. But technology shouldalso aid more traditional “push”approaches, under which govern-ments and charities roughly forecasthow much of a product will be neededin a certain area, then make sure theappropriate quantity is available.

Patrick Kuchar, malaria branchchief at the US Centers for DiseaseControl and Prevention, cites aproject in Tanzania that turned physi-cal vouchers for nets – slips of papereasily lost and hard to safeguardagainst counterfeiting – into elec-tronic codes delivered to phones andgood for one net per code. Other pilotprojects send health workers regulartext message reminders about, say,running a diagnostic test or urgingpatients to buy nets. Others send

messages directly to patients, alert-ing them when it is time to take adose of their prescribed medicine.

As for procurement, the costs ofprevention tools, diagnostics andmedicines fell significantly between2005 and 2012, according to a studypublished last year in the MalariaJournal.

However, higher prices and newproducts mean that procurement effi-ciencies will remain important.

Mr Kuchar says that technologyshould aid centralised buying, along-side help from the US President’sMalaria Initiative. It offers guidanceto charities and governments on howto forecast accurately the amount ofdrugs, diagnostic tests and nets theywill need, and how to procure themcentrally.

In turn, this gives manufacturersthe confidence to produce products inhigh enough numbers that they canachieve economies of scale.

It is not a marginal concern. Whilethe Roll Back Malaria campaign esti-mates the global cost for malaria con-trol and elimination peaked in2009-10, it does not expect total coststo fall much below $5bn before 2020,

roughly split between Africa andAsia, with much smaller amountsdemanded by the Middle East, Eurasiaand the Americas.

Within this, procurement costsremain significant – they are esti-mated to account for about 40 per centof the money put towards malaria bythe Global Fund, one of the world’smost important funding sources foranti-malaria measures.

Meanwhile, the team at Malaria NoMore is investigating the degree towhich individuals might start sharingthe burden.

Mr Edlund points out that many ofthe countries facing malaria alreadyshoulder the vast bulk of the costs astheir economies grow – a virtuous cir-cle, since the economic progresscomes at least in part on the back ofsuccesses so far in the fight againstmalaria.

As the middle class in these regionsgrows, too, might real marketsdevelop for some of these products?

“By now, hundreds of millions offamilies have owned nets and usedthem and seen the benefits,” MrEdlund says. “Would these families bewilling to pay for a net?

Telecoms help pave way to improved net benefitsCosts Increasedefficiency keeps theprice of preventiondown, saysRose Jacobs

‘Would thegrowingmiddleclasses bewillingto pay fora net?’

Building networks:distributingmosquito nets inUganda Alamy

FINANCIAL TIMES FRIDAY APRIL 25 2014 ★ 3

FT Health Combating Malaria

In 2012, customs officers in theAngolan port of Luanda decided toinspect a shipment of hi-fi speak-ers. Inside, they found large quan-tities of concealed drugs: not nar-

cotics but medicines offering just asmuch profit for their distributors –and potentially far greater harm fortheir purchasers.

The seizure contained 32m tablets ofpills labelled as Coartem, one of themost effective drugs against malaria(see separate article overleaf), butwhen analysed they were found tocontain no “active pharmaceuticalingredient” at all.

This high-profile case highlightedthe extent of counterfeiting. Largequantities of a product purporting tobe a life-saving medicine were to besold to patients. Yet they would havedone nothing to treat malaria, butrather exposed many to risk of death.

The Angola shipment was traced toGuangzhou, in China’s industrialheartland. Despite the country’s

pre-eminent role in developingartemisinin, one of the two activeingredients in Coartem, China is alsoby far the largest hub of counterfeitmanufacturing – especially formalaria treatments. Indian producershave also been identified as producingfake antimalarials.

Yet no prosecutions have takenplace in China, and few people havebeen brought to court anywhere elsefor counterfeit medicines in general –let alone faking malaria medicines.Most of the investigations that havetaken place have focused on higher-priced drugs for patients in richercountries such as cancer treatments.

Ironically, Coartem is available freeto a large number of patients acrossAfrica and other parts of the develop-ing world, thanks to substantial donorsupport from the Global Fund to FightAids, TB and Malaria, the US Presi-dent’s Malaria Initiative, and a rangeof other projects, companies and indi-viduals. That process has created a

powerful brand that unscrupulousintermediaries seek to exploit.

Andrew Jackson, head of global cor-porate security at Novartis of Switzer-land, the pharmaceutical group thatdeveloped and produces the treat-ment, says: “When you donate some-thing to governments or their agentsin many African countries, and it hasa certain street value, a lot is going toleak out of the system.”

He says that an important problemhas been the diversion of donatedCoartem from clinics to so as to sell itto patients – engineering a shortage ofsupplies where they are available freeand creating an alternative market forprivate vendors to exploit.

In the absence of a firmly controlledpharmacy distribution chain, or therequirement for doctors’ prescriptionsto help restrict access to regulatedoutlets, Coartem is available for sale.

That process may reduce the drug’seffectiveness even when it is genuine,since stocks lose their potency after

they have gone out of date, or if theyhave been transported and stored inhigh temperatures or humidity.

Pirated versions of a drug are amore serious problem. Counterfeitershave proved highly effective inproducing successive generations offakes to keep up with efforts by theoriginal producers to differentiatethem. Label changes, special charac-ters and even holograms are quicklycopied.

Amir Attaran, a professor at the lawand medicine faculties of the Univer-sity of Ottawa, is among those callingfor an international treaty andtougher national laws that wouldincrease the penalties for counterfeit

drugs. Penalties for fake medicines –unlike narcotics – are usually modestfines or criminal sentences and arenot a primary focus for law enforce-ment bodies.

He says international action hasstalled, not only because of the lack ofreliable information about the extentof the problem but also because ofdisputes over definitions.

Health experts have long beendivided on the distinction betweencheap, poorly manufactured “sub-standard” drugs and intentional coun-terfeits.

“I see this as a legal or criminalissue, and only secondarily a medicalone,” Prof Attaran says.

In the absence of tougher laws,donors, police and manufacturershave increased the exchange of infor-mation to identify and track counter-feiters.

Yet so far, only a small number ofprosecutions of intermediaries andsellers of fake antimalarials have

Call for greaterpenalties forpeddlers offake remedies

CounterfeitsFewpeople are being brought tocourt anywhere in theworld formanufacturinguseless copies of drugs, writesAndrew Jack

‘People will makemoney wherever thereis an opportunity’

Under scrutiny: Cambodian officials inspect a pharmacy in their continuing search for counterfeit drugs Getty

taken place in Africa, with no convic-tions against the real counterfeiters.

There has also been much discus-sion – in developed and poorer coun-tries alike – of the use of bar codesand other detection systems, com-bined with scanners and mobilephones to verify unique numbers as away to authenticate medicines.

Some experts question their value,and say that they create a false senseof security, can be circumvented andmay not work at all in rural areas.

“Everyone thinks technology iscool,” says Mr Jackson. “But weshould invest heavily in enforcement,inspection and intelligence exchange.

“We are certainly seeing more andmore diverted and fake Coartem. Peo-ple will make money wherever thereis an opportunity.”

In the meantime, he says, improvededucation for patients about the risksof counterfeits is needed. “Peoplehave blind trust in the drugs theybuy, but they are not all OK.”

4 ★ FINANCIAL TIMES FRIDAY APRIL 25 2014

Mao Zedong may seem anunlikely hero of the bat-tle against malaria. Dur-ing his leadership ofChina in the 1960s, uni-

versities were shut down and scien-tists banished to the countryside aspart of the Cultural Revolution.

But an exception was made for aresearch programme into treatmentsfor malaria, which was ravaging thearmy of Beijing’s North Vietnameseallies during their jungle battles withUS-backed South Vietnam.

An effective drug was developedusing a chemical compound calledartemisinin extracted from the sweetwormwood plant – a herb used inChinese medicine for centuries.

It took until the late 1990s for thetreatment to gain wider usage, whenNovartis of Switzerland bought theChinese patent for an artemisinin-based combination therapy (ACT)with a cure rate of 95 per cent.

The Basel-based drugmaker hadoriginally eyed its potential as apremium-priced product to sell totourists and countries’ militaries butin 2001 agreed to make it available tothe World Health Organisation and itspartners at cost price. Since then,Novartis has supplied more than 600mtreatments on a non-profit basis inmore than 60 countries, with manymillions more treatments comingfrom generic producers.

Coartem, Novartis’s brand name forthe drug, remains one of the mostimportant weapons in the fightagainst malaria and has played a bigrole in the 42 per cent drop in deathsfrom the disease since 2000.

However, there are fears its daysmay be numbered because of signs ofrising resistance to the treatment insoutheast Asia. ACT-resistant strainsof the Plasmodium parasite responsi-ble for malaria have been detected inCambodia, Myanmar, Thailand, Viet-nam and Laos.

The big fear is that these strainscould spread to India or Africa. TheWHO has warned this could have“dire” consequences and imperilprogress made over the past 15 years.

“Given the ever-increasing levels ofpopulation movement in Asia and thePacific, the geographic scope of theproblem could widen quickly, posing ahealth security risk for many coun-tries in the region,” the WHO said.

With the clock ticking on artemisi-nin-based drugs, the race is on todevelop a new generation of treat-ments.

Novartis announced last Novemberthat it had discovered a potential newdrug based on a class of compoundscalled imidazopyrazines, in a researchprogramme backed by the WellcomeTrust and Medicines for MalariaVenture.

Initial studies have shown it has thepotential to block the plasmodiumparasite at an earlier stage of infec-tion and to stop it recurring. Thiswould give it an important advantageover existing treatments, which areonly effective against the disease atits most acute stage.

Thierry Diagana, head of theNovartis Institute for Tropical Dis-eases, says the breakthrough “couldprovide a path towards elimination ofthe disease”. However, there are years

of work ahead before a medicine willbe patented.

In the meantime, GlaxoSmithKlineis hoping to provide an alternative byoffering the first vaccine againstmalaria. After 30 years of work, GSKplans to seek European regulatoryapproval for its RTS,S vaccine thisyear.

If successful, the WHO has indi-cated it could make a recommenda-tion on the vaccine next year, clearingthe way for its adoption by govern-ments across Africa and othermalaria-hit regions.

In clinical trials, the vaccine cutincidence of the disease among youngchildren aged between five and 17months by nearly half, and amonginfants aged six to 12 weeks by abouta quarter.

These success rates are much lowerthan those associated with otherchildhood vaccines and the trialresults were a disappointment tosome in the health community whohad been hoping for a “silver bullet”.

But Allan Pamba, head of GSK ineast Africa, who has been closelyinvolved in development of thevaccine, says a success rate of nearlyhalf is more than enough to justify itsadoption given the number of livesthis could save.

An estimated 627,000 people world-wide died from malaria in 2012 – mostof them children under the age of fivein Africa.

“The antimalarial drugs we haveare great, but resistance is growing,”says Mr Pamba. “We need new tools.”

So far, GSK has invested about$350m on development, with another

$260m to come in the final push tolaunch.

The UK-based company has said theprice will be based on the cost ofproduction plus 5 per cent, with theprofit ploughed back into furtherresearch and development on tropicaldiseases.

“We could have put these resourcesinto developing another Viagra or sta-tin or diabetes drug, any of whichwould have promised a much surerreturn on investment,” says MrPamba. “The only rationale for devel-oping this product is its socialimpact.”

GSK cites its malaria work as evi-dence of a broader commitment toAfrica, which also includes donationsof drugs to fight neglected tropicaldiseases such as soil-transmittedhelminth infections and affordableaccess programmes for its HIV drugs.

For a company battered in the pastyear by allegations of corruption inChina and several other countries, thelaunch of the world’s first malariavaccine would help enhance GSK’sglobal image.

But Mr Pamba says the project isabout much more than public rela-tions. As Africa’s economy develops,GSK is increasingly looking at thecontinent’s commercial potential. Thecompany last month announced plansto invest £130m in Africa over thenext five years to boost manufactur-ing capacity.

By reducing the $12bn annual costof malaria to the African economy,GSK hopes to hasten the day when itcan treat the continent like anordinary market.

Race is on to find new treatmentsDrugs The threat of drug resistance spreading has prompted a hunt for fresh remedies, saysAndrewWard

Improving situation: thanks to advancements in the treatment of malaria, since 2000 there has been a 42 per cent drop in the number of deaths from the disease Alamy

‘Thegeographicscope of theproblemcouldwidenquickly’

FT Health Combating Malaria

In 1987, I started work onan ambitious project todevelop a vaccine againstmalaria.

In the 1980s, as vaccineshelped tackle killerdiseases such as polio andmeasles, hopes were highthat a similar approachcould end the deadly cycleof malaria.

While huge progress hasbeen made during the pastdecade, thanks to bed nets,better treatments anddiagnostic tools, it stillclaims hundreds ofthousands of lives eachyear – mostly youngAfrican children.

The need for newapproaches is as relevantnow as it was then.

It is exhilarating to thinkthat nearly 30 years later,this may finally be withinreach. The investigationalvaccine we have beenworking on is being testedin late-stage trials acrossAfrica.

We will submit thevaccine for assessment bythe European MedicinesAgency this year. All beingwell, the world might haveits first vaccine againstmalaria in a few years.

Setting out on a careeras a molecular biologist in1984, I’d planned to headinto academia. But a jobadvert caught my eye,offering the chance to joina group developing ahepatitis B vaccine.

My application wassuccessful and became partof the team that createdthe first vaccine based ongenetic engineeringtechnology.

When I was asked threeyears later to lead amalaria vaccine project Ijumped at the chance. Ididn’t think I would stillbe working on it threedecades later. But malariais tough to crack.

It is caused by a parasiterather than a bacterium orvirus. Parasites are expertsat evading the body’simmune system. Novaccine exists against anyhuman parasite anywhere.

The malaria parasite canalter its appearance andcomposition to avoiddetection.

Once in the body, itspends minutes in thebloodstream before hidingin the liver, where itbecomes harder to target.

There it differentiatesand replicates beforebursting into the blood-stream, invading anddestroying red blood cellsand causing symptomsfrom headaches toseizures and, alltoo often,death.

Ourapproachfocused onadvances inmolecularbiology andimmunologyto target themalaria parasitebefore and duringliver cell infection.

We trialled ourcandidatevaccine inhealthy adultvolunteers inthe US then,with proof

of concept in hand, inAfrica, starting in adultsand progressing towardstesting in children.

Data from a late-stagetrial that is still inprogress suggest thecandidate vaccine canalmost halve the numberof malaria cases inchildren aged five to 17months, on top ofreductions from bed netsand other tools.

This seems modest, buteach year there are morethan 100m malaria cases inAfrican children underfive. Easing this diseaseburden would haveenormous human, socialand economic benefits.

The other big challengeis financing. In the late1990s, ready to startclinical trials in Africa, weunderstood the cost ofdeveloping this vaccinewould be hundreds ofmillions of dollars. Thosewho would eventually usethe vaccine – children inAfrica – could not beexpected to pay for it.

We have been fortunate.Not only has the supportand commitment ofGlaxoSmithKline beenconstant, but we found away of sharing the costand risk by joining withthe Path Malaria VaccineInitiative, a non-profitgroup, to develop thevaccine.

The partnershipcontinues and is one of thebedrocks of the project, asare our multiplecollaborations with leadingAfrican scientists. Thistype of public-privatepartnership could be amodel for similar projects.

If the candidate vaccineis approved andrecommended by globaland national public healthpolicy makers, we need tomake sure it reaches thepeople who need it.

Having it sit on a shelfbecause it is too expensivewould be unthinkable forme and for the hundreds ofresearchers in Africa, theUS and Europe.

After three decades offighting malaria, I’mretired, but certainly nottired. I’m still a consultantto the project. Innovationagainst malaria does notend here.

The RTS,S candidatevaccine is not perfect and,if approved, it will need tobe implemented with otherantimalarial measures.

We will always need tolook for better approachesto stay ahead and, I hope,to make malaria history.

Joe Cohen PhD is anadviser to the malariavaccine project at GSK

An effectivevaccinemay atlast be in sightOpinionJOE COHEN

In the early 1950s, India,newly independent fromBritish rule, went on theoffensive against malaria,with a well-coordinated pro-gramme to spray the insec-ticide DDT in areas withhigh levels of the disease toprevent the mosquitoesbreeding.

The results were soencouraging – a 99 per centdrop in reported cases –that in 1958 New Delhirenamed its programme theNational Campaign for theEradication of Malaria, opti-mistic that mosquito-borneillness could be eliminated.

Instead, the programmefaltered, because of lack ofpublic co-operation, weakmorale among sprayingteams and inadequatesupervision.

Mosquitoes developedresistance to DDT andmalaria bounced back witha vengeance, rising to apeak of about 6.5m reportedcases in 1976.

“Gradually, the systemgot corrupted,” says DrManish Kakkar, head ofzoonotic diseases at thePublic Health Foundationof India. “There werereversals and resurgence.”

Today, India’s govern-ment claims to be makingrenewed strides in malariacontrol. The World HealthOrganisation estimates thatby 2015 India’s malariaincidence and fatalitieswill be down to 50-70 percent of their 2002 levels.

But with serious ques-tions about the credibilityof official data – and fewsigns of an intensive, long-term effort to reduce mos-quito breeding – healthexperts say malaria stillthreatens the lives of many.

“The danger is stillthere,” says Amit Sengupta,co-convener of the People’sHealth Movement India, anon-governmental organisa-tion. “It isn’t something youcan be complacent about.”

India’s National VectorBorne Disease ControlBoard says malaria inci-dence has fallen from about3m cases a year in the mid-1990s to some 1m in 2012.

It also says deaths havedropped from an average of1,050 a year for 16 yearsfrom 1995 to 519 in 2012.

But these numbers areacknowledged seriously tounderreport incidence and

fatalities, as officials onlycount those cases confirmedby a test at a governmenthealth facility.

Many malaria patients inrural India – whether theyrecover or succumb – aretreated by local private doc-tors or never see a healthworker at all, and so do notappear on the government’sradar for official testing anddiagnosis.

“Everybody accepts thatif you only rely on databased on cases that smearpositive, you would misssomething by an order ofmagnitude of 10 to 100times,” says Dr Sengupta.

Some of India’s worstaffected areas are conflictzones such as Chhattisgarh– where radical Maoistrebels control vast swathsof territory and the govern-ment has little presence –or remote border areas.

“It’s difficult to obtaininsights into the malariaprogramme in India,” saysDr Kakkar. “It’s a casewhere the information isnot only deficient, but thereare questions about thecredibility of what is availa-ble.”

India’s true malaria bur-den is a matter of intensedebate. The WHO estimatesmalaria kills 15,000 Indiansannually. But researchersworking on the innovativeMillion Deaths Survey –which used so-called

“verbal autopsies” to assignlikely causes to 122,000unexplained deaths in Indiafrom 2001 to 2003 – say thereal toll is far higher.

In a 2010 article in TheLancet, the Million Deathssurvey researchers said amore “plausible” range was125,000 to 277,000 fatalities ayear, mostly in rural areas.

New Delhi, however, hasquestioned the accuracy ofverbal autopsies, which userelatives’ recollections of aperson’s fatal illness tomake a postmortem diagno-sis, and argued malariadeaths are overestimated.

Meanwhile, a govern-ment-appointed panel devel-oped a method for estimat-ing malaria deaths thatresulted in a sharply higherfigure than the current offi-cial estimate. But healthofficials are planning a fur-ther study on the methodol-

ogy, which is unlikely to beaccepted for at least a year.

India is not alone instruggling accurately toassess its malaria burden.The WHO says just 14 percent of global malaria casesare detected and reportedthrough official surveil-lance systems. In turn,these are too weak andinconsistent even to reflectmalaria trends in countriesaccounting for about 85 percent of the global burden.

While some professionalseven question whetherIndia’s malaria trend isdeclining, others sayresearch suggests incidenceand death are falling.

In recent years, artemisi-nin combination therapyand rapid diagnostic testshave been more widelyavailable, improving treat-ment success rates.

But Dr Sengupta warns

India’s current declinecould be part of a cycle oftemporary “small victories”followed by renewedmalaria resurgence, unlessthere is a more determined,concerted effort to controlmosquito breeding.

He also notes a worryingrise in the more dangerousfalciparum malaria as a per-centage of all Indianmalaria cases.

“Marginally, the healthsystem has improved withnew drugs and rapid diag-nostic tests being used,” hesays. “It’s an infusion oftechnology that temporarilygives you an edge. But theparasite is also moving tooutwit you.

“If you can put in placepublic health measures thateliminate places where mos-quitoes breed, you wouldprobably see a more perma-nent secular change.”

Statistics fail to reveal the true picture of India’s healthAsia

More accuratereporting is needed,writes Amy Kazmin

‘Technology givesa temporary edge,but the parasiteis also movingto outwit you’

Still battlingon: Dr JoeCohen

FINANCIAL TIMES FRIDAY APRIL 25 2014 ★ 5

FT Health Combating Malaria

From the biological point ofview, malaria is a particularlycomplex disease. It is causedby an unusual pathogen, theprotozoan Plasmodium para-

site, which has an extremely involvedlifestyle shuttling between two hosts:mosquitoes and humans.

This triangular complexity involv-ing protozoa, people and insectspresents a formidable problem to sci-entists looking for new treatments.But it can also be seen as an opportu-nity, because there are potentiallymore points of attack than for simplerdiseases. And these can be illumi-nated by new molecular techniquessuch as genomics and proteomics.

One of the most urgent jobs is todiscover how and why Plasmodiumbecomes resistant to artemisinin,which has been the most effectiveantimalarial drug available.

In January, an international teamannounced a breakthrough in thejournal Nature, after using a batteryof technologies to identify a geneticmarker of artemisinin resistance.

The scientists first created a Plas-modium strain in the laboratory thatresisted high levels of artemisinin andcompared its DNA with the non-resist-ant parent strain. This revealed a spe-cific mutation in a gene called K13that marked the resistant parasite.Then field work in Cambodia, whereartemisinin resistance is emergingmost strongly, showed that the sameK13 mutation characterised the phe-nomenon in the wild.

Chris Plowe of the University ofMaryland summarised the importanceof the discovery. “This new markergives us a tool that will make it possi-ble to map the distribution of artem-isinin resistance very quickly,” hesays. “There are a number of impor-tant research questions that need tobe answered, but in the meantimeknowing the distribution of K13 resist-ant genotypes will be very useful inplanning malaria elimination efforts.”

Another important example of thecontribution that a battery of high-tech approaches can make to under-standing malaria was published inNature in February. Scientists fromGlasgow University and the WellcomeTrust Sanger Institute have identifiedthe factor that Plasmodium must pro-duce to begin the process of passing

from human to mosquito. Blockingthis essential step in the parasite’s lifecycle could open the way to drugsthat prevent transmission of malaria.

The researchers identified a regula-tory protein that triggers the develop-ment of male and female forms ofPlasmodium. These specialised sexualcells, called gametocytes, are responsi-ble for infecting the mosquito and ini-tiate transmission of the disease.

Any drug developed to disable this

transmission switch is likely to be an“altruistic intervention”, taken byinfected adults to prevent them pass-ing on the disease. Researchersbelieve parents would agree to do sofor the sake of their children.

Vaccines are one of the most activefields of malaria science, as research-ers look for improvements on RTS,S,the only product that has shown someefficacy in extensive clinical trials (seeJoe Cohen, Page 4). While public

health experts welcome RTS,S theyrecognise that more effective “second-generation vaccines” will be needed ifhumanity is ever to achieve thedream of eliminating malaria.

The World Health OrganisationMalaria Vaccine Technology Road-map, published last November, lists 27vaccine candidates in clinical trials.

One promising example at Oxforduniversity is a vaccine that enlists thecellular arm of the human immune

system to attack Plasmodium, gener-ating CD8 T-cells. Most other vaccinesrely on the antibodies they raise,rather than on immune cells.

The Oxford candidate combinesattenuated doses of two viruses, onederived from a chimpanzee commoncold virus and the other from a strainof the old smallpox vaccine.

If trials of the Oxford vaccine inAfrica this year give encouragingresults, it may be combined withRTS,S to give a vaccine that attacksmalaria on both fronts, with antibod-ies and killer T-cells.

Another approach focuses on Plas-modium’s residence in mosquitoesrather than in people. Last year,researchers at Michigan State Univer-sity reported in the journal Sciencethat they had established a stable andinheritable bacterial infection inmalaria-transmitting Anopheles mos-quitoes that makes them immune toPlasmodium parasites.

The Wolbachia bacteria are in effectacting as a vaccine to prevent malar-ial infection of the mosquitoes.

In the Michigan experiment, thePlasmodium-preventing infection withWolbachia bacteria passed down 34generations of mosquito before thestudy ended. The idea is that a Wol-bachia-infected strain of mosquito,once released, will spread bacteriathrough the wild insect population.But extensive field testing will berequired to confirm that it works.

A study at Pennsylvania State Uni-versity, published in February inNature Scientific Reports, showed theeffects of Wolbachia infection varyconsiderably with environmental con-ditions, particularly temperature.

“Much of the work on the Wol-bachia-malaria interaction has beenconducted under highly simplified lab-oratory conditions,” says CourtneyMurdock of Penn State. “These resultssuggest that the development of thispromising control technology requiresan improved understanding of howmosquitoes, Wolbachia and malariaparasites will interact in diversetransmission settings.”

Similar comments could be madeabout much of the promising researchinto this most complex of diseases.

A long and winding road leads fromgreat work in the lab to effectivedeployment in the field.

Complexity of life-cycle also offers opportunitiesScience Newmethods of controlling the spread of the disease are being tested, but they need time to be developed, reportsClive Cookson

The triangular complexityinvolving protozoa, peopleand insects presentsa formidable problem

A trial in Kenya: vaccine research is one of the most active fields of malaria science Reuters

6 ★ FINANCIAL TIMES FRIDAY APRIL 25 2014

FT Health Combating Malaria

of this disease over the nextfive to 10 years, so we cangradually hand over thebaton to national govern-ments as the problembecomes more managea-ble.”

Mr Chambers reportsgrowing interest from com-panies in Africa to co-operate with anti-malariaprogrammes as a way tohelp boost development.

He cites the case of asafari tourism company insouthern Africa that isworking with local healthagencies, motivated by adesire to declare its basemalaria-free to attract for-eign visitors.

Mr Whiting says research-ers have estimated that, by2035, the world economywill see a return of $208bnon the international invest-ment in fighting malaria.With an insecticide-treatedbed net costing just £3 toprotect a family of four forfour years, campaigners saythe programme is one of themost cost-effective in globalhealth.

Mosquito net ownershipin sub-Saharan Africa hasrisen from about 3 per centof the population in 2000 tojust over half, helpingreduce malaria mortalityrates among children byabout 54 per cent.

Other measures haveincluded insecticide spray-ing, improved diagnostictests and widened distribu-tion of antimalarial drugs.

“All the donors haveagreed there must be nobacksliding, because thatwould put at risk the gainsfrom all the investment putin so far,” says Mr Basu.

“If you take your eye offthe ball even for a fewmonths, malaria comesroaring back,” he explains.

The biggest donors to theGlobal Fund have been theUS, which pledged $4bn inthe latest financing roundlast December, the UK($2.7bn), France ($1.5bn)

Continued from Page 1 and Japan ($800m). The Bill& Melinda Gates Founda-tion, run by the Microsoftfounder and his wife, under-scored its powerful role bydonating up to $500m.

Mr Chambers says risingpowers such as China, Indiaand Brazil have started toshow more interest in glo-bal health challenges asthey grow in stature.

China, in particular, hasan increasing commercialstake in Africa that couldencourage it to take a big-ger role.

“In the next several yearsI expect we will see the Briccountries standing shoulderto shoulder with the tradi-tional donor nations,” saysMr Chambers.

Just under a third of Glo-bal Fund resources hasbeen allocated to fightingmalaria over the next twoyears, with half going toHIV/Aids and 18 per cent toTB. “These diseases are

interconnected, because ifyou are infected with one,you become more vulnera-ble to the others,” says MrBasu.

Another threat toprogress comes from resist-ance to antimalarial drugsand insecticides. Drugresistance has so far beenlimited to southeast Asia,but scientists fear it couldspread through infectedtravellers.

There are sources ofencouragement too, includ-ing a promising new treat-ment under development byNovartis and a vaccinefrom GlaxoSmithKline.

“If we keep up this rate ofprogress over the next fiveto six years, we will start toget into more challengingterritory of eradication inmany countries,” says MrWhiting. “That last mile isalways the hardest.”

Experts say victoryis a long way off

Even the most predictableproblems cannot always beaverted. Ahead of a WorldHealth Organisation (WHO)endorsed, internationally em-

braced and remarkably successfulpush to fight malaria with insecticide-treated mosquito nets – an effort thatstarted in earnest about a decade ago– some scientists had qualms.

The history of medicine has shownthat successive generations of bugstend to develop resistance to chemi-cals designed to kill them – and do sowith greater speed and ease whenthey are up against only one type ofpoison.

Yet only one class of insecticides,those made of pyrethroid, a compoundwith low toxicity for mammals buthigh toxicity for insects, was beingused on the nets.

The reason for this was simple: theWorld Health Organisation hadapproved only one insecticide andthat was pyrethroid-based. Thechances of another meeting thegroup’s standards were low.

“A number of people thought wejust didn’t have the time [to wait foran alternative],” says Janet Heming-way, a professor at the LiverpoolSchool of Tropical Medicine, pointingout the challenge of finding chemicalsthat not only had the right levels oftoxicity, but also suitable longevityand the ability to bleed into polyesternetting.

The clock was ticking. By 2004,malaria was claiming 1.8m lives ayear, according to an analysis byresearchers at the Institute for HealthMetrics and Evaluation at the Univer-sity of Washington, in Seattle. Insecti-

cide-treated nets were the most effec-tive means available for prevention.

In 2007, the WHO extended its rec-ommendations for net usage frompregnant women and young childrento universal coverage in malarialregions, contributing significantly,experts agree, to a more than 40 percent reduction in malaria mortalityrates globally since 2000.

But insecticide resistance poses aserious threat to this success, says theWHO. Resistance has been identifiedin 64 countries, or nearly two-thirds ofthose suffering from malaria trans-mission. India and sub-Saharan Africaare the worst affected.

The degree to which this is increas-ing infection and death rates – or willin the future – is less clear.

A team of researchers, including MsHemingway, recently conducted areview of studies investigating therelationship, but hesitated to drawconclusions given the wide range ofmethods and standards of research.

Patrick Kuchar, malaria branchchief at the US Centers for DiseaseControl and Prevention, points outthat it may be “we are seeing resist-ance in more places because we’relooking for it in more places”.

Torn nets add complications. “Ini-tially, we were expecting that the lifeof the insecticide would be the limit-ing factor of their practical, usefullifespan and what we’re finding nowis that their physical integrity failsbefore the insecticide is entirely usedup,” says Mr Kuchar.

The WHO has recommended imme-diate action to tackle resistance toinsecticides, whose presence greatlyenhances the effectiveness of bed

nets. Unfortunately, that is easier saidthan done. According to Ms Heming-way, development of non-pyrethroidinsecticides for this kind of malariacontrol was “something of a cottageindustry” for many years.

This was, in part, because the focusof agricultural insecticide researchswitched from creating chemicals thatare sprayed and kill bugs on contactto those delivered via plants thattarget insects’ digestive systems.Potential profits for a bug spray tofight disease are not sufficient toattract much industry interest.

Public-private partnerships areattempting to address the problem,but viable alternatives to pyrethroid-treated nets are still six to sevenyears off, according to Ms Heming-way. In the meantime, spraying insec-ticides in homes and other buildingsmay grow in importance, despite itbeing less practical to deliver thannets. This is because, while pyrethroidis used most often in such spraying,other insecticides have also beenapproved. Scientists hope that, by

taking pyrethroid in and out of use,resistant bugs will die out, since theywill lack the competitive advantagethey possess in pyrethroid’s presence.

More broadly, as the favouritemeans of fighting malaria – the bednet – faces waning effectiveness, diag-nostic tools and treatment will play amore important role. But preventionmeasures remain essential.

“The nets are effective in most situ-ations,” says Mr Kuchar. “They con-tinue to provide a barrier mechanism,and you build that culture of net useand acceptability in people, so whenthe next generation of nets comealong, they’ll be ready for them.”

And so – for all their faults – pyre-throid-treated nets are not being aban-doned. In fact, funding for themremains a key concern for expertsmost alert to the problem of insecti-cide resistance.

Ms Hemingway points out that uni-versal net coverage in Africa requiresdelivery of 150m nets a year. In 2012,the global community did not managehalf that number.

Favoured wayto fight diseasefaces increasedresistanceInsecticides An alternative to impregnatedbed nets has yet to be found, saysRose Jacobs

Cover up: nets arestill proving to beeffective in mostsituations Getty

$500mAmount donated by theGates Foundation

Source: WHO * Midpoint estimates FT graphic

Malaria hotspots

Indonesia

Burkina Faso

Ghana Mozambique Tanzania

Uganda

Dem. Rep. of Congo

IndiaSudanNigeria

5.6m

48.0m

5.0m 8.9m

19.0m

180,000

17,0005,600

20,000

28,000

9,40021,00018,000

69,000

17,000

5.6m8.3m7.0m

17.0m

6.9m

= One million cases = Number of deathsThe 10 countries with the highest number of malaria cases 2012*

Clive CooksonScience editor

Andrew JackDeputy analysis editor

Rose JacobsFreelance writer

Amy KazminSouth Asia correspondent

Andrew WardPharmaceuticalscorrespondent

Aban Contractor, AdamJezard, Hugo GreenhalghEditors

Andy MearsPicture editor

Steven BirdDesigner

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