Prevention raceScientists face astruggle to find adengue vaccinePage 2

Inside »

Fighting theslow killersInterview: Ghana’sformer president,John KufuorPage 2

Poverty factorTropical diseasescan still have animpact in thedeveloped worldPage 3

A positiveknock-on effectResearch maylead to progressin the cancer fieldPage 3

Turning the tideSmall butco-operative stepsgo a long way withparasite problemPage 4

Thursday October 11 2012 www.ft.com/reports | twitter.com/ftreports

In remote parts of Congo, VictorKande struggles to help thousandsof people suffering from one of thecountry’s most unpleasant butobscure scourges. He is trying to

improve conditions for those withsleeping sickness, one of the mostunpleasant of a range of “neglected”tropical diseases.

“Our government has many prob-lems, and all attention is focused ondealing with cholera, Ebola andmalaria. Everyone sees and deals withthose,” says Mr Kande, a health offi-cial who struggles with lack of petrolfor boats and bikes to reach affectedvillages. “People with sleeping sick-ness die slowly in their houses out ofsight. It’s a rural and social illnessthat leaves people unable to work,stigmatised and regarded as mad.”

He has been working with theDrugs for Neglected Diseases Initia-tive, a non-profit research group inGeneva trying to improve decades-oldmedical techniques, which requirepainful spinal taps for diagnosis andarsenic-based injected medicines that

kill a tenth of the patients treated.Sleeping sickness (trypanosomiasis) isone of a number of so-called“neglected tropical diseases” (NTD),dubbed by Dr Peter Hotez, head of theSabin Vaccine Institute, “the mostimportant diseases you have neverheard of.” Their names are oftenunpronounceable, their symptoms al-most unimaginable, and their impacton individuals, communities andregional development incalculable.

According to the best statisticsavailable – and the data are extremelypoor – more than 1bn people in theworld are chronically infected by oneor more such NTD, and more thanhalf a million people a year die as aresult. Yet they receive scant supportfor research, prevention or treatment.

Prof David Molyneux at the Liver-pool School of Tropical Medicine esti-mates 0.6 per cent of internationaldevelopment assistance for healthgoes to NTDs compared with 42 percent for the “big 3” of HIV, tuberculo-sis and malaria.

One reason is that they affect the

poorest and most disenfranchised,principally in Africa, with little of thevisibility in richer nations of diseaseswhich occur in the west. Another isthat they often debilitate rather thankill, making their short-term impactless dramatic.

Yet growing research points to thebroader consequences of neglect. Soil-transmitted helminthiases (intestinalworms) and schistosomiasis (bilhar-zia), transmitted through snails, maycause physical stunting, slow intellec-tual development and impede chil-dren’s schooling and future ability towork productively.

Onchocerciasis and trachoma causeblindness, a further factor holdingback economic development and plac-ing a burden on those who contractthe diseases and their families.Greater study of the interaction ofanimal and human infections hashighlighted the impact on agriculturalproductivity of NTDs.

The good news today is that someare becoming less neglected. Referredto in ancient documents, studied by

scientists in the late 19th century, andalready dubbed “great neglected dis-eases” by Ken Warren at the Rockefel-ler Foundation in the 1980s, they haverisen to the priorities of donors andpolicymakers over the past decade.

There has been a surge in academicarticles in the past few years, andeven the creation of new journals,such as PlosNTDs. Funding forresearch into new “tools” has jumpedfrom $268m in 2007 to $460m last year,according to Policy Cures, a think-tank. Donors led by the US Agency forInternational Development, the UK’sDepartment for International Develop-ment and the Gates Foundation haveconsiderably stepped up support.

The activity reached a new peaklast January, when 13 pharmaceuticalcompanies signed up to the “LondonDeclaration” on NTDs, offeringexpanded donations of supplies ofdrugs with a theoretical commercialvalue of hundreds of millions of dol-lars a year that have the potential toprevent and treat many NTDs.

Some stress their corporate respon-

sibility, while others point to econo-mic self interest. “This is a long-terminvestment in the future middle class,”says Haruo Naito, head of Japanesedrugmaker Eisai, which pledged toproduce diethylcarbamazine for lym-phatic filariasis (elephantiasis), in theprocess expanding its brand name andexperience of manufacturing in Indiaand the UK.

Bill Foege, a veteran public healthexpert, who praises Merck as it cele-brates the 25th year of donations of itsdrug ivermectin for trachoma controlthis week, says: “This is becoming theway corporations operate. They do notsimply do it for good publicity orsome sort of tax break, but becausewhen you are competing for goodworkers, it makes a difference.”

He also points to the importance ofhigh-level advocacy among politiciansand chief executives inspired byformer US president Jimmy Carter,whose tireless efforts mean that dra-cunculiasis (guinea worm) could by2015 become only the second human

Continued on Page 2

Economicreality spursinterventionMore is being done to tackle ‘NTDs’as research reveals their impact oncountries’ growth, writes Andrew Jack

Children are tested for sleeping sickness in a WHO screening programme in sub-Saharan Africa Corbis

FT SPECIAL REPORT

FT HealthCombating Neglected Diseases

2 ★ FINANCIAL TIMES THURSDAY OCTOBER 11 2012

Combating Neglected Diseases

Source: Peter J. Hotez, The American Society of Tropical Medicine and Hygiene

Number of estimated global cases of tropical diseasesMillion

0 200 400 600 800

AscariasisTrichuriasisHookwormSchistosomiasis*AmebiasisDengue**MalariaLymphatic filariasisStrongylodiasis***TrachomaOnchocerciasisLiver fluke infection

Estimated annual number of global deaths fromtropical diseases’000

0 100 200 300 400 500 600 700

MalariaSchistosomiasis

Typhoid feverCholera

Hookworm infectionRabies

LeishmaniasisAmebiasis

DengueChagas disease

TrichuriasisFood-borne trematodiases

Leprosy

Estimates:

* Between 391–587

** Ranges between 70–500

*** Between 30–100

John Kufuor had long beenaware of the burden ofneglected diseases inGhana, but it took the visitof a foreign head of stateto mobilise his country’sgovernment into action.

From river blindness andburuli ulcer toelephantiasis, the countryhad plenty of healthproblems that affected itspoorest residents. Itharboured one of thelargest number of cases ofguinea worm outsideSudan, a diseaseenergetically targeted forglobal eradication byformer US presidentJimmy Carter through hisfoundation.

“President Carter hadvisited before I came topower with a technicalgroup of volunteers whotargeted guinea wormeradication,” Mr Kufuor,the former president ofGhana, recalls. “Thatfocused attention.

“During my tenure, hemust have visited four orfive times, travelling witha group of experts to someof the remotest parts up inthe north. He providedleadership, and we gotembarrassed remaining inthe capital.”

While guinea worm andother diseases were “slowkillers” that often escapedattention, he argues:“When the afflicted getrelief, they are empoweredto work productively.Children can go to schoolwithout suffering, to thebenefit of the nation.

“In government, thetopmost priorities aresecurity and health. If thepeople are not healthy,they can’t be productiveand the economy stalls.”

Although plenty ofattention and funding wentto other diseases, led byHIV, over the years, hesays: “The truth is thatthese neglected diseaseshave been there long

before the explosion ofHIV. The only difference isthey attacked the poorest,marginalised peoplewithout a voice.

“The fight must besustained against HIV, butwe want to bring alongsidethe fight against theseother diseases. For as littleas 50 cents per person ayear, we can make a greatonslaught.”

He stresses theimportance of cleandrinking water, andpartnerships with non-governmental organisationsto help tackle neglecteddiseases.

He also cites the broaderimpact of the pioneeringintroduction of healthinsurance in place of theprevious out-of-pockethealthcare system dubbed“cash and carry” by criticsthat offered scant supportfor the poor. “There is stillsome way to go, but Ibelieve Ghana is reallyshaping up,” he says.

Now he is bringing hisown gravitas as a formerpresident to try to do thesame for his peers acrossAfrica and beyond. Thisyear he was appointed asspecial envoy to the GlobalNetwork for NeglectedTropical Diseases.

Mr Kufuor has spenttime both travelling inAfrica and meeting donorselsewhere to stress theimportance of the cause.But how optimistic is heabout fresh support forlong unfulfilled pledges toboost health investmentacross the continent?

“Things are beginning tochange. The afflictedtended to be some of thepoorest, at the margins ofsociety. Now, withgovernments gettingaccountable throughdemocratisation, and theopening up of the worldthrough the IT revolution,governments are having tosit up.”

A little effortcan producegreat stridesInterviewJohn KufuorFormer president of Ghana

Andrew Jack hearswhat 50 cents can do

‘If the people arenot healthy, theycannot beproductive’

Voice for change: John Kufuor, special envoy AFP

disease eradicated, aftersmallpox. “When a head ofstate is interested, you canbet the minister of health isinterested,” he says.

One broader factor mobi-lising recent efforts hasbeen interest closer to homefor donors. Mr Hotez haslong highlighted the burdenof NTDs, such as helminthsand leishmaniasis, in thepoor rural and indigenouscommunities of NorthAmerica. Caroline Ansteyof the World Bank, anotherimportant funder, prefers todub NTDs not neglected dis-eases, but diseases ofneglected people.

Climate change and thegrowth in commerce meansthat some diseases – led bymosquito-transmitted den-gue – are now moving frompoorer to richer emergingcountries and into the USand western Europe. No sur-prise that much pharmaceu-tical industry investment –and not purely philanthro-pic support – is going into

Continued from Page 1 the search for a vaccine.But many difficultiesremain. Sustaining funding– let alone meeting a $2bngap by 2015 for currentinternational plans – is aparticular concern during aperiod of slower economicgrowth. Sabin trustee Bar-oness Hayman, who is keep-ing a nervous eye on arecent reshuffle in the Brit-ish government that couldchange priorities at Dfid,the official developmentagency, cautions: “We aregoing to have to work veryhard to keep up the momen-tum on funding. It would bea terrible shame if it wentbackwards.”

Dr Lorenzo Savioli, whoruns the NTD programmeat the World Health Organi-sation, says: “Outside theUS and the UK, few govern-ments are interested orunderstood how relevantthis is for poverty reduc-tion. We need the eurozoneand the yen zone involved.”

Prof Alan Fenwick, direc-tor of the SchistosomiasisControl Initiative at Impe-

rial College, London, saysfew African governmentsyet have their own budgetor staff for NTDs. He alsosays donors should care-fully examine the growingnumber of organisationsnow competing for support,stressing his own group’slow overhead, use of localrather than expatriate staff

and careful partnerships toavoid corruption.

Others call for efficienciesin other ways, includinggreater linkage betweenwell-established but under-funded NTD programmesand better-supported HIVand malaria projects.

Not all NTDs are receiv-ing equal attention in everycountry, and nor can they

be tackled in the same way.Some are more “tool-ready”than others, though mostwould benefit from freshdiagnostics and drugs.

“Mass drug administra-tion” – using a number ofdonated drugs in combina-tion preventatively like avaccine – is taking off, butremains hindered by poorco-ordination. Some ques-tion whether the approachis wise, arguing it may risktriggering drug resistanceand placing heavy strainson local communities andhealth systems.

Simon Bush, head ofNTDs at Sightsavers, says:“Mass treatments are goingwell, but if we want tomove to elimination weneed to look at water, sani-tation and hygiene. That’salways been the weak link.”

Ambitious goals set foreradication of several NTDsin the coming years areunlikely if these issues arenot addressed. Medicinescan help, but are unlikelyto eliminate diseases of pov-erty alone.

Projects need co-ordinated approach

Andrew JackParmaceuticals Correspondent

Clive CooksonScience Editor

Alan RappeportUS Consmer IndustriesCorrespondent

Sarah MurrayFT Contributor

Denise RolandFT Contributor

Ian MossCommissioning Editor

Steve BirdDesigner

John WellingsPicture Editor

For advertising,please contactIan EdwardsPhone +44 020 7873 3272Fax +44 020 7873 4336Ian.Edwards@ft.com

Contributors » These are notneglected diseasesbut diseases ofneglected people

Genetic modification couldbe a powerful weaponagainst the mosquitoes thattransmit dengue.

Field trials, involving therelease of millions of sterileGM mosquitoes, have givenencouraging results in Bra-zil, Malaysia and GrandCayman island.

Oxitec, an Oxford univer-sity spinout company,developed the technology. A“dominant lethal gene”inserted into the Aedesaegypti mosquito enablesmales to fertilise females –

but their larvae die beforehatching.

If huge numbers of sterilemales are released – at least10 times more than the wildpopulation – they swampthe native males and matewith all available females,which fail to produce viableoffspring.

The large-scale release ofmale insects sterilised byradiation has been very suc-cessful in fighting agricul-tural pests such as fruit-flies, but irradiation doesnot work with mosquitoes,so Oxitec has pioneered thisalternative approach.

The first field trial wascarried out two years agoon Grand Cayman in theCaribbean, with resultspublished last month in thejournal Nature Biotechnol-ogy. The release of 3.3m

sterile male mosquitoesover 16 hectares for 23weeks resulted in an 80 percent reduction in thenumber of wild mosquitoes.

Luke Alphey, Oxitec chiefscientist, says: “Eighty percent reduction is an excel-lent result, especially aswild mosquitoes couldmigrate into the trial area.

“We should see evenstronger reduction in largeror more isolated areas. Webelieve this approach canbe used in many countriesto offer a more effective,greener solution to control-ling the Aedes aegypti mos-quito and reducing denguefever.”

Environmental groupsdispute the claim that GMinsects represent a greenersolution to mosquito con-trol. Helen Wallace, director

of GeneWatch UK, says theGrand Cayman data wereunconvincing.

“Staff would be betteremployed using the well-established public healthapproach of removing mos-quito breeding sites [water

containers] rather than inplacing GM mosquito larvaeat intervals across a site,”she says. “Plans to scale upreleases of GM mosquitoesin dengue-endemic Brazilshould be halted. Authori-

ties in other places wherereleases are planned, suchas Florida and Panama,would also stop and thinkagain.”

In fact, the technology isgathering momentum inBrazil. Dr Alphey says:“That is where the mainaction is at the moment.”

Oxitec is working withMoscamed, a Brazilian com-pany that already uses radi-ation-based sterile insecttechnology to control Medi-terranean fruitflies.

In July Moscamed openeda breeding facility whereproduction of Oxitec’s GMmosquitoes will be scaledup to produce enoughinsects for a trial in a townwith 50,000 inhabitants.

Although male Aedesaegypti mosquitoes do notbite, there were initially

some complaints during theGrand Cayman test that thelarge numbers releasedwere causing a nuisance.

But Dr Alphey says thesystem was then adjustedto release insects fartherfrom people’s homes and tosubstitute some of the adultmosquitoes with pupaefrom which adults emergeover a period. No furthercomplaints were received.

While Oxitec is focusingresources on Aedes aegypti,scientists believe the tech-nology could also stopAedes aldopictus (Asiantiger mosquito) which ismoving aggressively intosouthern Europe.

It is a secondary vectorfor dengue and transmitsother viruses that threatenhuman health, includingthe crippling chikungunya.

Ruining the mosquito’s sex life may payVector control

Work to halt lifecycle is promising,says Clive Cookson

80%Reduction in number of wildmosquitoes during trial

Abreakthrough in tacklingthe world’s most wide-spread mosquito-bornevirus is tantalisingly close,but disappointing results

from the latest vaccine trialserve as a reminder of the scale of thechallenge.

Dengue, also known as ‘break bonefever’ due to the excruciating painsuffered by its victims, afflicts 100mpeople across the globe every year,especially in the tropics.

The disease is on a northwardmarch via a resilient mosquito speciesarriving in cargo.

The first local transmissions inEurope were recorded in France andCroatia in 2010, and last month Greekhealth officials attributed the death ofan 80-year-old man to its first case ofdengue since the 1920s.

No cure exists, so treatment is lim-ited to relieving the agonising bone,muscle and joint pain that accompanythe fever. Few cases end in death, but500,000 people each year develop thesevere form. They have a one in 40chance of dying from its complica-tions, with children at most risk.

Although 2.5bn people are at risk ofinfection, the disease’s low death tollhas hidden its impact from the globalhealth community.

Dr Richard Mahoney, policy and

access co-ordinator of the dengue Vac-cine Initiative, a non-profit organisa-tion, says: “Dengue is different fromthe other neglected tropical diseases.

“It is a global problem affectingevery country in the tropics, and isspreading further – while the otherstend to be localised to very specificspots on the globe.”

The virus has been on the rise formore than 70 years, but serious effortsby drug companies to create a denguevaccine – which experts agree wouldbe the single most effective tool incontrolling the disease – only gainedmomentum in the past two decades.

One reason is that the fever can becaused by four different virus strains.

Dr Jean Lang, R&D associate vice-president for Sanofi Pasteur, the com-pany leading the way towards creat-ing a vaccine, says: “Dengue is theonly disease with this feature – it’slike developing four vaccines for fourdifferent viruses.

“If dengue was a simple disease, wewould already have a vaccine. It typi-cally takes 10-15 years to bring a vac-cine to market – it’s an indication ofdengue’s complexity that it has beennearly 20 years already.”

If a new shot fails to protect againstone or more of the virus types, moredifficulties arise. Some studies haveshown that, if a patient becomes

immune to one strain, they faceincreased chances of developing thesevere form. It is unclear whetherinoculation with the weakened virusin the vaccine would have the sameeffect.

This stumbling block recentlytripped up researchers at Sanofi, whofound the candidate they were trial-ling only protected against three ofthe four virus types in a trial on 4,002children in Thailand.

Despite this setback, developershailed the trial as a milestone in aprocess started in 1994 when theFrench pharmaceutical group part-nered with a Thai research lab todevelop a candidate vaccine.

The intervening 18 years have seenSanofi become the first company totake a dengue vaccine to late-stagephase III clinical trials.

Dr Lang said that, although the lat-est results were surprising, the smalltrial size and the specific conditionsin Thailand may mean the results willnot be replicated in the much largerphase trials under way on 31,000 peo-ple across 10 Asian and Latin Ameri-can countries.

Sanofi remains confident. With atarget of going to market in 2015, ithas invested €350m in a factory withthe capacity to manufacture 100mdoses of vaccine a year.

The growing demand for a denguejab is attractive for big pharma, withSanofi forecasting €1bn in annualsales. Others are following, withGlaxo SmithKline and Merck amongthe companies testing rival vaccines.

While the most advanced versionuses the traditional technique ofusing a weakened form of the livevirus, alternative approaches of trig-gering an immune response using imi-tations of dengue are also beingtested.

Dr Mahoney says: “We do not knowwhether a live attenuated vaccine willbe successful, so it’s important that avariety of types are being looked at.

“Even if the Sanofi vaccine goes tomarket it will only be able to produceenough doses in its first year to meetdemand from Brazil alone. We predictthe global demand being one billiondoses per year.”

Dengue may not be considered aglobal health priority, but this has notprevented important progress frombeing made to rid the world of thedisease.

Dr Lang says: “It is a sign of howfar we have come that the WorldHealth Organisation now has a targetof halving the death rate and reducingincidence by 25 per cent by 2020.

“This chimes with my personalmantra: dengue – neglected no more!”

Science isfighting thedengue waron four fronts

Prevention Developing a vaccine againstdengue is especially difficult – but potentialbenefits are enormous, says Denise Roland

Testingoccupation:vaccinedevelopment atthe Sanofi Pasteursite in France

Vincent Moncorgé

On FT.com »

InteractivegraphicFocus onneglecteddiseases indifferent partsof the worldwww.ft.com/reports

FINANCIAL TIMES THURSDAY OCTOBER 11 2012 ★ 3

Combating Neglected Diseases

Impoverished parts of theUS remain a hotbed of rarediseases that many Ameri-cans have never heard of,with illnesses such as Cha-gas disease, Leishmaniasis,Trench fever, and Denguestill prevalent.

Appalachia, the Missis-sippi Delta and poor neigh-bourhoods in some citiesare especially vulnerable, assanitation and medicalsupervision is persistentlylacking.

“Tens of thousands, or insome cases, hundreds ofthousands of poor Ameri-cans harbour these chronicinfections, which representsome of the greatest healthdisparities in the UnitedStates,” Peter Hotez, a pro-fessor at The George Wash-ington University and theSabin Vaccine Institute,wrote in a recent study onthe subject.

Neglected diseases arelabelled as such because thepublic has little awarenessof them and drug compa-nies do not invest heavilyin treatments or vaccines.Public health officialsare especially focusedon the border regionbetween Mexico and Texas,where neglected tropicaldiseases such as hookwormand even vivax malariaoccur.

One neglected diseasethat is beginning to getincreased attention is Cha-gas, which some have calledthe “Aids of the Americas”because of its incubationtime and the challenge offinding a cure. According tothe Chagas Disease Founda-tion, the often fatal illnessaffects up to 20m people inLatin America and has beenimported to the US, creat-ing concerns about bloodand organ donations.

Chagas is usually trans-mitted through a triatominebug, or “kissing bug”,according to the US Centerfor Disease Control (CDC).The bug thrives under poorhousing conditions, such asmud walls and thatchedroofs, making those livingbelow the poverty line espe-cially vulnerable.

Untreated, Chagas canlead to heart and digestionproblems and ultimatelydeath.

The spread of neglecteddiseases, especially theinsect-borne variety, isincreasingly problematicbecause of globalisation,public health experts say.

Michael Osterholm, direc-tor of the Center for Infec-tious Disease Research andPolicy at the Universityof Minnesota, says thatincreased transport of cargoon ships and aeroplanes isaccelerating the spread ofinfectious diseases.

“We have really elimi-nated geographic barrierswith the modern transpor-tation system we have,”

Mr Osterholm says. “We aremoving mosquitoes aroundthe world every day incargo.”

The increased speed oftravel is exacerbating thiseffect, Mr Osterholm says,pointing to the quick spreadof swine flu in 2009, whichbecame a public healthscare.

The efficiency of the phar-maceutical sector’s supply

chain has also been shownto have drawbacks when itcomes to faulty medicine. Abad batch of methylpred-nisolone acetate is believedto have led to an outbreakof fungal meningitis justthis month.

The injectable steroid

that is used to treat backpain was thought to haveoriginated in a compound-ing pharmacy in Massachu-setts and quickly spread tosicken people in six states,killing five.

Meanwhile, outbreakssuch as the West Nile virusin several states andHantavirus in YosemiteNational Park have raisedawareness that rare dis-eases can still be deadly inthe US. Earlier this monththe CDC said there hadbeen 169 West Nile virus-re-lated deaths so far this yearand nearly 4,000 cases. Thatputs 2012 on pace to be theworst year for the virussince 2003.

Many experts argue thatglobal warming is to blamefor the spread of West Nile.At a press conference inAugust, Lyle Petersen,director of the CDC’s divi-sion of vector-borne infec-tious diseases, said the unu-sually hot summer had“fostered conditions favour-able to the spread of WestNile virus to people”.

Poor hit hardest bychronic infectionsUnited States

Tropical diseasescan still be deadly inthe west, explainsAlan Rappeport

Triatoma dimidiata: a blood-sucking insect that spreads Chagas disease AFP

Place a map of the preva-lence of HIV in Africa nextto one showing the less wellknown condition of urogeni-tal schistosomiasis, andthere is a striking overlap.It is just one example of thebroader impact of neglectedtropical diseases.

While the connectionsbetween many conditionsmay be poorly studied, thepotential for saving moneyand improving health by co-ordinating the efforts ofthose fighting them is sub-stantial. Experts arguesharing just a fraction ofthe generous support tofight the Big Three of HIV,TB and malaria to tacklemore neglected diseasescould reduce the burden ofboth sets of conditions.

One measure would begreater support for deworm-ing with drugs alreadydonated. Female genitalulcers caused by schisto-somiasis are associatedwith a substantial increasein transmission of HIV.

And several studies haveargued helminth infectionsincrease HIV viral load andthe likelihood of mother-to-child transmission. Theworms boost the chance ofcontracting TB, increasethe risk any infection willbe more severe and lessresponsive to therapy andalso exacerbate anaemia inchildren and pregnantwomen, adding to the deathtoll from malaria.

A second measure wouldbe to enhance malaria bednet distribution by tappinginto the infrastructure cre-ated by projects such as theGlobal Programme to Elimi-nate Lymphatic Filariasisand the African Programmefor Onchocerciasis Control.

These community-based

initiatives using local vol-unteers with governmentsupport tend to be wellaccepted compared withintensive one-off malariabed net campaigns. Usingthem would increase thelikelihood that nets wouldbe used to protect againstmalaria, while also helpingprotect from other insect-borne diseases includinglymphatic filariasis.

But Prof David Molyneuxfrom the Liverpool Schoolof Tropical Medicine says:“The malaria communitydoes not want to either hearor listen, it seems.”

The former head of theGlobal Alliance to Elimi-nate Lymphatic Filariasis,he has lobbied over a dec-ade for joint working. As hewrote in the Lancet in 2009:“Although further researchmight be needed to examine

the effect of linkingneglected tropical diseasesand malaria control onsome of the weaker healthsystems in Africa and else-where, we believe that theevidence for combiningthese two approaches is suf-ficiently mature to scale upcombined neglected tropicaldisease and malaria controlinitiatives immediately.”

He is still waiting.The Global Fund to Fight

Aids, TB and Malaria, thelargest multilateral redis-tributing funds, said itbelieved its financing didhelp strengthen health sys-tems more broadly in recipi-ent countries, allowingthem to tackle other condi-tions. But a spokesman saidthere was no current directsupport: “NTDs do not fallwithin our mandate.”

Joint approachis still a dreamLinkage

Synergy would helpin tackling diseases,writes Andrew Jack

The potential forsaving money andimproving healthby co-ordinationis substantial

Neglected Tropical Diseasesis a convenient name for adisparate group of infec-tions that hardly exist inthe developed world but

affect more than a billion people inthe poorest regions of Africa, Asia andSouth America. However the labelmay be misleading in two ways,according to Professor Simon Croft ofthe London School of Hygiene andTropical Medicine. First, he says:“Many of the diseases are no longer soneglected.”

Medical science is paying moreattention to them, helped by increasedfunding from the pharmaceuticalindustry, governments and charities.Policy Cures, a health charity thattracks spending on R&D, says $460mwas invested on 12 neglected tropicaldiseases in 2011 – up from $418m in2010 and just $268m in 2007.

The other reason is the label sug-gests more similarities between thediseases than exist. Prof Croft, head ofthe LSHTM faculty of infectious andtropical diseases, says: “Lumpingthem together conceals their diversityfrom the viewpoint of medical science.They pose different challenges, andthey are at different stages of develop-ment when it comes to diagnosis andtreatment.”

The diseases can be grouped intobroad categories, according to the

pathogen responsible for the infectionand the vector that transmits it.There are four main types of patho-gen: helminths (wormlike parasites),trypanosomes (protozoan parasites),bacteria, and viruses. A range of flies,mosquitoes, snails, bugs and othercreatures transmit the diseases – andresearchers are working on ways totackle both vectors and pathogens.

Even within each pathogen group,the diseases vary greatly in the waythey respond to treatment. Anti-helminthic drugs – mainly derivedfrom veterinary medicines developedto deworm animals – are much moreeffective against some worms thanothers. “For some helminthic diseasesthe cure rate is 90 per cent, for othersit is much lower,” says Prof Croft.

A particular challenge for scientistsfighting helminthic diseases such asonchocerciasis and lymphatic filaria-sis is to kill the adult worms. Drugssuch as Merck’s ivermectin can elimi-nate the larval stages relatively easilybut adults can survive and live formany years, producing new larvaethat continue to transmit disease.

In addition to chemical drugs, scien-tists are working on vaccines to blockthe transmission of tropical diseases.For a few helminthic diseases inwhich farm animals harbour theinfection, inoculation of livestock maybe sufficient. But for most diseases

new human vaccines are needed –they have been called “anti-povertyvaccines”, because they promise to liftpeople out of hardship by improvingtheir health. New vaccines for thehookworm infections leishmaniasisand schistosomiasis are in early clini-cal trials, while candidate vaccines foronchocerciasis (river blindness) andChagas disease are still in pre-clinicalresearch. Most of the vaccine work isbeing carried out by public sector andnon-profit organisations, such as theSabin Vaccine Institute and InfectiousDisease Research Institute in the US.The pharmaceutical industry’sinvolvement is much greater when itcomes to the development of newdrugs. The funding figures from Pol-icy Cures show a spectacular increasein corporate investment in neglectedtropical disease treatments in recentyears – from $25m in 2007 to $178m in2011. This investment has beenfocused particularly on dengue, whichreceives more research funding thatany other neglected disease.

This year three drug companies –Abbott of the US, AstraZeneca of theUK and Astellas of Japan – signedagreements to collaborate on researchwith the non-profit Drugs forNeglected Diseases Initiative (DNDi)based in Geneva. AstraZeneca, forexample, will provide DNDi with15,000 chemicals which will be

screened at Institut Pasteur Korea foractivity against the trypanosomic dis-eases leishmaniasis, Chagas diseaseand sleeping sickness. Any “hits” willthen be assessed for their potential asstarting points for future medicines.

Meanwhile significant results con-tinue to emerge from academicresearch. The latest, published thismonth in the Biochemical Journal,points the way to a new approach totreating leishmaniasis. Scientists fromEdinburgh University in the UK andthe US National Institutes of Healthhave created a chemical that blocks akey enzyme in the parasite responsi-ble for the disease, after testing300,000 possible drug molecules.

The Leishmania parasite needs theenzyme, pyruvate kinase or PYK, forthe glycolysis process that convertssugars into energy. Without it, theparasite dies. What makes the discov-ery particularly interesting is that ithas implications far beyond tropicaldiseases, neglected or otherwise.

A very similar biological pathwayoperates in human tumours, whichalso need PYK to convert food intoenergy to support their growth, saysHugh Morgan of Edinburgh Univer-sity. Research into leishmaniasis maytherefore also lead to a new way oftreating cancer. That would be anunexpected spin-off for research intoneglected tropical diseases.

Funds sharpen scientific focusResearch The response to exotic parasites may underpin future cancer treatments, writes Clive Cookson

Waiting for a breakthrough: volunteers for dengue clinical trials at the Ratchaburi hospital near Bangkok, Thailand Sanofi Pasteur

Most of thevaccinework iscarried outby publicsector andnon-profitgroups

169Number of West Nile virusrelated deaths in the US

4 ★ FINANCIAL TIMES THURSDAY OCTOBER 11 2012

Combating Neglected Diseases

With cases of guineaworm disease downfrom 3.5m in 21 coun-tries in 1986 to a matterof hundreds in four

African countries today, the neareradication of this painful and debili-tating disease is being celebrated as aglobal health success story. However,unlike many disease eradication pro-grammes, no drugs or immunisationswere available. Progress in this fighthas depended on aggressive advocacyefforts at every level of society.

Guinea worm disease, dracunculia-sis, is a parasitic disease that spreadswhen people drink contaminatedwater containing a water flea that ishost to the guinea worm larvae.

These larvae hatch in the digestivetract and, roughly a year later, theworm – which can be up to 120 centi-metres long – emerges from the body,often through the lower limbs.

In an attempt to relieve the excruci-ating pain and burning sensationcaused as the worm exits their bodies,people immerse themselves in water,at which point it releases thousandsmore larvae. Anyone drinking fromthis water source becomes infected.

What makes the disease difficult tobattle is no symptoms are apparent inthe sufferer until the fully grownworm emerges from the body.

In addition, health workers facelogistical problems. DieudonnéSankara, an epidemiologist in theWorld Health Organisation’s guineaworm eradication programme, says:“This disease occurs in places that arevery remote. It’s very difficult tomake contact with these people –there’s no access, no roads and theyare very neglected.”

However, in the campaign’s earlystages the challenge lay closer tohome – convincing health ministriesand international agencies that thiswas a battle worth fighting.

Donald Hopkins, vice-president ofhealth programmes at Carter Center,the human rights group that has ledefforts to eradicate guinea worm,says: “The disease was so obscure. Itwas in the back of beyond and peopleweren’t paying attention to it.”

Moreover, in the 1980s, when effortsto eliminate guinea worm began, theWorld Health Organisation had

recently declared smallpox eradicated– a victory that coincided with shift-ing priorities in global health policy.

Dr Hopkins says: “Single-diseaseeradication had gone out of fashion.

“The mantra in the early days ofthe guinea worm programme wasprimary healthcare and an integratedapproach that would provide healthfor all by the year 2000 – that was animpediment to getting the focus on toguinea worm eradication.”

Having convinced governments and

agencies that guinea worm could –and should – be eradicated, the nextchallenge was persuading affectedcommunities to change behaviour.

While temephos, a larvicide, can beused to treat water, killing the fleasthat host the larvae, the primarystrategy is ensuring people living inendemic areas do not drink contami-nated water and, if infected, do notbathe in water used for drinking.

Dr Sankara says: “That’s easy tosay, but difficult to do.” The strength

of traditional local beliefs has nothelped. Affected communities oftensaw the disease as a curse or afflictionover which they had no control.

Dr Hopkins says: “They didn’t likehaving guinea worm but thought theyunderstood why they had it. They didnot understand that it was comingfrom their drinking water and that itwas in their power to do somethingabout it – people coming from theoutside often underestimated thestrengths of those traditional beliefs.”

This has meant showing people howthe disease spreads and persuadingthem to distrust all water sourcesexcept those they know to be clean.

In this respect, a powerful tool is asimple glass jar, used to scoop waterfrom contaminated ponds and demon-strate to onlookers what it contains.

Convincing affected communities totake action to help themselves hasalso been critical. Dr Hopkins says:“The unsung heroes in all of this werethe village volunteers, who were will-ing and able to help educate theirneighbours,”

Yet while guinea worm is poised tobe the next human disease aftersmallpox to be eradicated, the laststages of the battle will be thetoughest. Because of the way thedisease spreads, one case can lead todozens, with symptoms only appear-ing a year or more after infection.

This means employing a strategy Dr

Hopkins calls “redundant surveil-lance”. With cash for anyone report-ing a confirmed case, everyone in thecommunity becomes a surveillanceagent.

And because the offer of cash cancreate reporting incentives, generat-ing false positives, absence of reportedcases over a certain period can beaccepted with greater confidence (tobe declared free of guinea-worm, acountry must report no indigenouscases, through active surveillance, forat least three calendar years).

This community-based strategy haslessons to offer those running manykinds of health campaigns.

Dr Sankara says: “What we’re doingwill shape other programmes in theyears to come.

“And, for guinea worm diseaseeradication, one critical thing hasbeen using local manpower andempowering communities to take careof their own health.”

Tide may be turning against guinea wormEradication Simple, practical steps involving communities have been vital in the fight against this debilitating parasite, says Sarah Murray

Drawn out: thefight to banish theworm has been along one

AFP

It took several years tomove from academic ideathrough the political proc-ess to the drafting of regula-tory small-print, but aninnovative funding modelfor research into neglected

diseases has finally come ofage. The “priority reviewvoucher” provides incen-tives to companies to dis-cover treatments, howeveruptake so far has been slow.

A law in 2007 in the USpaved the way for thevoucher, inspired by asimple idea: the prospect ofearlier launch and greatersales of a “mainstream”drug by a pharmaceuticalcompany could persuadethem to develop treatmentsfor neglected tropical dis-eases, on which the finan-cial returns are scant.

For any neglected diseasetreatment approved by theUS Food and Drug Adminis-tration, companies can nowreceive an accelerated deci-sion – within six months –on the safety and efficacy ofany other experimentalmedicine in their pipelines,potentially halving theusual deadline of 10 monthsor more after submission.

Rather than extendingthe expiry date of a patent,the voucher offers the pros-pect of a front-loaded exten-sion by launching severalmonths earlier than usual.

David Ridley, associateprofessor at Duke Univer-sity Fuqua School of Busi-ness, and one of those whofirst described the conceptof the voucher in 2006, esti-mates the value at $200m-300m.

In practice, only onevoucher has so far beenissued and that in unusualcircumstances: it wasgranted in 2009 to Novartisof Switzerland for Coartem,a highly effective malariadrug that had already beenapproved by the FDA andregulators internationally

and was used across Asiaand Africa. It took a furthertwo years before the com-pany decided how toredeem it, seeking acceler-ated review for Ilaris, itsexperimental treatment forgouty arthritis. While the

regulators honoured theirdeadlines, they ultimatelyruled against approving thedrug, rendering the voucherworthless.

Novartis said it choseIlaris “because of the signif-icant unmet need” andrefused to comment on theoutcome.

“I’m not disappointedand I’m not surprised,”says Mr Ridley. “The valueis not a huge amount forbig pharma, but we hopethe voucher will nudgesome of them. It is oneof many mechanisms and

still has great potential.”He points out that revisedUS regulatory legislationthis year has extendeda similar voucher to rarepaediatric cancers, reducingthe application fee and cut-ting the notice periodrequired by a company sig-nalling its intention to filefor a priority review.

He hopes similar changeswill apply to neglected dis-eases, and that the defini-tion will be extended toother ailments previouslyexcluded, including tropicaldisease Chagas. In a survey

last month of drug develop-ers, Bio Ventures for GlobalHealth, a non-profit groupencouraging research forneglected diseases, sug-gested the voucher was auseful incentive.

The FDA proved that itrespected the terms, even ifCoartem was an unusualcase and Ilaris ultimatelyfailed to benefit.

With five vaccines andthree drugs in late-stageclinical trials that couldbe eligible, the voucher’sbest days may yet beahead.

Glory days for a plan to reward research hover in the distancePriority review vouchers

Scheme designed toencourage researchhas had few takers,says Andrew Jack

The voucher offersthe prospect oflaunching a drugearlier than usual

Roy Vagelos took a historicdecision nearly fourdecades ago that paved theway for a new era in effortsto tackle neglected tropicaldiseases. It set a high stand-ard not only for his com-pany but the entire pharma-ceutical sector in drugdonations for the poor.

In 1975 when Bill Camp-bell, a researcher at Merckin the US, saw during testsin the laboratory that hiscompany’s drug ivermectinfor deworming cattle hadthe potential to work inhumans, he had gone to MrVagelos, the then head ofresearch, who authorisedthe costly and lengthyclinical trials to prove it.

By the time the resultsfinally demonstrated that itwas safe and effective intreating onchocerciasis –river blindness – a dozenyears later, Mr Vagelos hadstepped up to becomeMerck’s chief executive.

He bounced his ownboard into an unprece-dented pledge: free suppliesof the drug (branded asMectizan) for as long as it

was needed for the disease,backed with fundingthrough a partnership forits distribution.

Brenda Colatrella, head ofcorporate responsibility,says: “Merck didn’t have apresence where thosepopulations lived in some ofthe remotest parts of Africaand Latin America, andthose who needed itcouldn’t afford to buy it atany price.”

Her department overseesa programme that thismonth is celebrating its25th year, with more than1bn treatments provided.

Bill Foege, a healthexpert credited with devis-ing the strategy that led tothe eradication of smallpox,helped plan the programme.

He says: “It launched anentire new chapter in globalhealth. It was a watershed.We now take it for grantedthat corporations are goingto do this sort of thing. It’llnever turn around and goin the other direction.”

The latest such efforttook place at the LondonDeclaration in January,during a meetinginitiated by theBil l andMelinda GatesFounda t i on ,when morethan ad o z e np h a r m a -c e u t i c a lcompanies

stepped up donations ofdrugs to help eliminate aseries of neglected diseases.

Taking part was Merck ofGermany, which agreed toraise its annual donation ofpraziquantel tablets for theschistosomiasis parasitefrom 25m to 250m.

Sir Andrew Witty, chiefexecutive of GlaxoSmithKline, which has pledgedunlimited supplies of alben-dazole from new productionlines to treat helminths andlymphatic filariasis, says:“This is an extremelyhuman issue. When you area company that, throughhard work, good fortuneand luck, has control andinsight into certain technol-ogies, and a talent base toapply and develop it, it’sour job to figure out how toshare that.”

But such donations areonly the start. Distributionremains difficult, notably intrying to ensure a series ofdrugs from different compa-nies arrive together to behanded out in local commu-nity campaigns.

Andy Wright, director ofGSK’s disease programme,says: “There are lots ofcomplaints on the groundthat co-ordination is notright yet, although thedirection of travel is right.”

Adrian Hopkins, his coun-terpart at Merck, alsopoints to concern about“orphan” countries such asthe Central African Repub-lic, where few large donorsare present to provide sup-port and distribution. Healso cautions that moremonitoring will be required:“For eradication, we needmore work in the field,detailed epidemiology andfollow-up.”

Drug companies mayhave made great strides indonating medicines, butmaximising the value oftheir gifts has yet to beachieved.

Companies strive for betteroutcomes from donationsCorporate efforts

Big pharma isstepping up efforts toaid poorer nations,says Andrew Jack

Roy Vagelos,former Merck chief

When Eisai signed up latelast year to a new interna-tional system designedto share details of itslibrary of experimentaldrug compounds with exter-nal researchers tacklingneglected diseases, it soonsparked interest.

It quickly became notonly the first Japanesepharmaceutical group tojoin the Re:Search initiativeof the World IntellectualProperty Organization, butone of the first to formallyclaim a successful match(albeit negotiations werealready under way before itjoined).

The company handedover details of seven com-pounds which it believedhad potential value, includ-ing E6020. Last month, theSabin Vaccine Institute inthe US signed a deal to test

its value as an adjuvant toboost the immune responseto two of its experimentalvaccines, for Chagas diseaseand leishmaniasis.

“Adjuvants are superhard to come by becausethey are closely guarded bythe major vaccine manufac-turers,” says Peter Hotez,president of the Sabin Insti-tute.

“It’s a real hurdle in thevaccine space to haveaccess to adjuvants. It’ssomething we struggle withfor each of our vaccines, soit’s great that Eisai pro-vided that access.”

Re:Search is the latest ina series of such multi-and bilateral initiativesdesigned to “crowd source”and pool internationalexpertise in the effort toboost neglected diseaseresearch. Companies shareinformation and agree tolicense any compounds,charging no royalty in theiruse in research and nonefor their eventual commer-cialisation in the world’sleast developed countries.

Some companies havepursued neglected diseaseresearch in-house, includingNovartis through its

specialist tropical diseaseinstitute in Singapore andGlaxoSmithKline (GSK) inSpain. But a number,including both GSK andPfizer have opened theirinternal drug compoundlibraries to outside academ-ics in the hunt for neglecteddisease treatments.

Others have formed pub-lic-private partnerships,combining expertise andfunding with additionaldonor support, such as theDrugs for Neglected Dis-eases Initiative, which origi-nally regarded co-operationwith the pharmaceuticalindustry with suspicion, buthas since signed up to workwith a number of compa-nies for different diseases.

So far, the output of suchnon-profit product develop-ment partnerships – mostfocused on a single disease– has been modest, oftenpicking “low hanging fruit”such as fixed-dose combina-tions of existing therapiesor reformulations to make

them easier to take. Thatpartly reflects the lengthyperiods required for drugand vaccine testing.

It also highlights the diffi-culties of finding the fund-ing for costly research, witha surge in costlier late-stagetrials just as austerity bites.Paul Herrling from Novartishas proposed a new hybridmodel that would pooldonor support across arange of diseases and organ-isations, with an expertcommittee deciding themost merit-worthy projectacross a wide-ranging port-folio.

That has met resistancefrom different funders andscientists reluctant to giveup their own preferredprojects, and questioningthe qualifications of such abroader expert group. Butfor many diseases for whichtreatments remain ineffec-tive, greater research co-operation still will berequired if much furtherprogress is to be made.

A sharedway forwardoffers hope

Research

Global co-operationmay provide many ofthe answers, writesAndrew Jack

Research at the Novartis Institute in Singapore Bloomberg

Convincing affectedcommunities to takeaction to help themselveshas also been critical