Tackling Mal aria Interventions available today could lead to decisive gains in prevention and treatment—if only the world would apply them By Claire Panosian Dunavan

Long ago in the Gambia, West Africa, a two-year-old boy named Ebrahim almost died of . Decades later Dr. Ebrahim Samba is still reminded of the fact when he looks in a mirror. That is because his mother—who had already buried several children by the time he got sick—scored his face in a last-ditch effort to save his life. The boy not only survived but eventually became one of the most well-known leaders in Africa: Regional Director of the World Health Organization. Needless to say, scarification is not what rescued Ebrahim Samba. The question is, What did? Was it the particular strain of parasite in his blood that day, his individual genetic or immunological makeup, his nutritional state? After centuries of fighting ma- laria—and conquering it in much of the world—it is amazing what we still do not know about the ancient scourge, including what determines life and death in severely ill chil- dren in its clutches. Despite such lingering questions, however, today we stand on the threshold of hope. Investigators are studying malaria survivors and tracking many other leads in efforts to develop vaccines. Most important, proven weapons—princi- pally, insecticide-treated bed nets, other antimosquito strategies, and new combination drugs featuring an ancient Chinese herb—are moving to the front lines. In the coming years the world will need all the malaria weapons it can muster. Af- ter all, malaria not only kills, it holds back human and economic development. Tack- ling it is now an international imperative. A Villain in Africa four principal species of the genus Plasmodium, the parasite that causes ma- laria, can infect humans, and at least one of them still plagues every continent save Antarctica to a lesser or greater degree. Today, however, sub-Saharan Africa is not only the largest remaining sanctuary of P. falciparum—the most lethal species infecting humans—but the home of Anopheles gambiae, the most aggressive of the more than 60 mosquito species that transmit malaria to people. Every year 500 million falciparum infections befall Africans, leaving one million to two million dead—mainly children. Moreover, within heavily hit areas, malaria and its complications may account for 30 to 50 percent of inpatient admissions and up to 50 percent of outpatient visits. The clinical picture of falciparum malaria, whether in children or adults, is not pretty. In the worst-case scenario, the disease’s trademark fever and chills are followed by dizzying anemia, seizures and coma, heart and lung failure—and death. Those who survive can suffer mental or physical handicaps or chronic debilitation. Then there are people like Ebrahim Samba, who come through their acute illness with no residual ef- fects. In 2002, at a major malaria conference in Tanzania where I met the surgeon- turned–public health leader, this paradox was still puzzling researchers more than half a century after Samba’s personal clash with the disease.

BITE OF INFECTED MOSQUITO begins the deadly cycle of malaria—a disease that kills one million to two

PHOTOGRAPH BY RANDY HARRIS; PHOTOILLUSTRATIONmillion BY JEN CHRISTIANSEN people annually, mainly young children in sub-Saharan Africa. Tackling Mal awww.sciam.comria SCIENTIFIC AMERICAN 77 That is not to say we have learned and bacteria for which vaccines now ex- Scandinavia and the American Midwest. nothing in the interim regarding inborn ist, malaria vaccines may never carry the The events surrounding malaria’s exit and acquired defenses against malaria. same clout as, say, measles or polio shots, from temperate zones and, more recent- We now know, for example, that inher- which protect more than 90 percent of ly, from large swaths of Asia and South ited hemoglobin disorders such as sickle recipients who complete all recommend- America reveal as much about its peren- cell anemia can limit bloodstream infec- ed doses. And in the absence of a vac- nial ties to poverty as about its biology. tion. Furthermore, experts believe that cine, Africa’s malaria woes could con- Take, for example, malaria’s flight antibodies and immune cells that build tinue to grow like a multiheaded Hydra. from its last U.S. stronghold—the poor, up over time eventually protect many Leading the list of current problems are rural South. The showdown began in Africans from malaria’s overt wrath. drug-resistant strains of P. falciparum the wake of the Great Depression when Ebrahim Samba is a real-life example of (which first developed in South America the U.S. Army, the Rockefeller Founda- this transformed state following repeat- and Asia and then spread to the African tion and the Tennessee Valley Authority ed infection; after his early brush with continent), followed by insecticide resis- (TVA) started draining and oiling thou- death, he had no further malaria crises tance among mosquitoes, crumbling sands of mosquito breeding sites and and to this day uses no preventive mea- public health infrastructures, and pro- distributing quinine (a plant-based an- sures to stave off new attacks. (As a trop- found poverty that hobbles efforts to timalarial first discovered in South ical medicine doctor, all I can say is: prevent infections in the first place. Fi- America) to purge humans of parasites Don’t try this on safari, folks, unless you, nally, the exploding HIV/AIDS pan- that might otherwise sustain transmis- too, grew up immunized by hundreds of demic in Africa competes for precious sion. But the efforts did not stop there. malarial mosquitoes every year.) health dollars and discourages the use of The TVA engineers who brought hydro- Samba’s story also has another les- blood transfusions for severe malarial electric power to the South also regu- son in it. It affirms the hope that certain anemia. lated dam flow to maroon mosquito lar- vae and installed acres of screen in windows and doors. As ma- Malaria not only kills, it holds back human laria receded, the local econo- mies grew. and economic development. Then came the golden days of DDT (dichlorodiphenyltri- chloroethane). After military vaccines might one day mimic the pro- Where does this leave us? With chal- forces used the wettable powder to aeri- tection that arises naturally in people lenges, to be sure. But challenges should ally bomb mosquitoes in the malaria-rid- like him, thereby lessening malaria-re- not lead to despair that Africa will always den Pacific theater during World War II, lated deaths and complications in en- be shackled to malaria. Economic histo- public health authorities took the lead. demic regions. A different malaria vac- ry, for one, teaches us it simply isn’t so. Five years later selective spraying within cine might work by blocking infection houses became the centerpiece of global altogether (for a short time, at least) in Lessons of History malaria eradication. By 1970 DDT visitors such as travelers, aid workers or when i lecture about malaria to spraying, elimination of mosquito breed- military peacekeepers, whose need for medical students and other doctors, I ing sites and the expanded use of anti- protection is less prolonged. like to show a map of its former geogra- malarial drugs freed more than 500 mil- On the other hand, the promise of phy. Most audiences are amazed to learn lion people, or roughly one third of those vaccines should not be overstated. Be- that malaria was not always confined to previously living under malaria’s cloud. cause malaria parasites are far more the tropics—until the 20th century, it Sub-Saharan Africa, however, was complex than disease-causing viruses also plagued such unlikely locales as always a special case: with the exception of a handful of pilot programs, no sus- Overview/Where We Stand Today tained eradication efforts were ever mounted there. Instead the availability ■ Researchers are laboring to create vaccines that would prevent malaria of chloroquine—a cheap, man-made rel- or lessen its severity. ative of quinine introduced after World ■ But existing interventions could fight the disease now. They include War II—enabled countries with scant re- insecticide-treated bed nets, indoor spraying and new combination drugs sources to replace large, technical spray- based on an ancient Chinese herb. ing operations with solitary health work- ■ The question comes down to one of will and resources: In view of all the ers. Dispensing tablets to almost anyone competing scourges—in particular, HIV/AIDS—is the world ready to take with a fever, the village foot soldiers on malaria in its principal remaining stronghold, sub-Saharan Africa? saved millions of lives in the 1960s and 1970s. Then chloroquine slowly began

78 SCIENTIFIC AMERICAN DECEMBER 2005 HOW MALARIA SPREADS

MALARIA PARASITE n e e d s bo th hu man s a n d mo s q u i t o e s to pr o p a g a te it s e l f. Th i s c o mp l e x li f e c y c l e ha s hind er e d e f f o rt s I n th e mo s q u i t o ’s t o en g i n e e r a v a c c i n e tha t c a n c r u s h 5 g u t , th e game to c y te s d e v el o p in to gam e te s Anopheles the par asi te. C ur r en t v ac c ine r e s ear c h gambiae a n d f u s e to e v e n t ua l l y str a te g ie s f o c us o n th r e e st a g e s o f th e p r o d u c e an o o c y st tha t par a s i te’s li f e c y c l e (a, b and c), two in r eleas e s spor ozoi te s. t h e hu ma n an d on e in th e mo s q u i t o . T h e s e tr a v el to th e mo s qui to’s sali v ar y Sporozoite g la n d s , r ea d y to TO be tr ans f er r ed Oocyst UI SQ N in to an o th er O MA M HU Fertilization DE E W hil e f e e ding, victim SI ID N S a n in f e cte d f e ma l e I IN 1 Anopheles mo s q ui to pa s s e s Sporozoite s p o r o z o i te s o f th e malar ia parasite Plasmodium into Host’s liver Male t h e v i ct i m’s bl o o d st r ea m a gamete Female gamete c Wi t h i n 30 to 6 0 The Disease 2 minu te s , th e sp or o z oi te s en ter T h e r up t ur e o f in f e cte d bl o o d c ell s t h e v i ct i m’s li v e r c a u s e s ma la r ia’s f e v e r, c h i l l s an d p r o g r e s s i v e anemia . D ea th may o c c ur c ell s , w h er e th e y f r o m s e v e r e an e mia as w e l l a s c l o gg i n g r epr oduc e as ex ually , o f bl o o d v e s s e l s in th e br a i n , lu n g s an d f or ming tho u s and s o th er or gan s by par a s i ti z e d r e d bl o o d Liver cell o f mer o z oi te s , mo st c ell s . In pr e g nanc y , malar ia - lad en o f w h i c h ar e la te r Merozoites p la c en ta s r o b bab i e s o f g r o wth r el ea s e d in t o th e b e f o r e th e y ar e e v en b o r n blo o d str eam Eventually some 4 of the merozoites develop into male and Female gametocyte b female gametocytes, T he mer o z oi te s which can be ingested Male gametocyte 3 in v a d e r e d bl o o d by a previously Host’s c el l s and mu l ti p l y , uninfected mosquito red c a u s i n g th e c e l l s to taking a blood meal blood cell r up tur e, r eleasing ye t mor e mer o z oi te s . T he c yc le r ep ea t s

Vaccine Targets

a S P OR O Z OI T E : T he goal o f b ME R O Z O I T E : Va c c in e s ba s e d on mer o z o i te c G AMET O CYT E : S o - c alle d al tr ui stic game to c y te - s p o r o z oi te v a c c ine s is to a n t i g e n s le s s e n ma la r ia’s se v e r i t y by b a s e d v a c c i n e s do no t a f f e ct hu man di s ea s e b l o c k par a s i te s f r o m en ter ing or h o b b l i n g th e in v a s i o n of ne w ge n e r a t i o n s of b u t ar e de s i g n e d to e v o k e hu ma n an t i b o d i e s tha t g r o w i ng w i thi n hu ma n li v er c el l s r e d bl o o d ce l l s or by r e d u c i n g co m p l i c a t i o n s d er ail par a s i te de v el o p men t w i thin th e mo s q ui to

to fail against falciparum malaria. With necessities such as food and youngsters’ malaria remains entrenched because of little remaining infrastructure and ex- school fees, it fuels fertility because vic- poverty and, at the same time, creates pertise to counter Africa’s daunting mos- tims’ families assume they will always and perpetuates poverty. quito vectors, a rebound in deaths was lose children to the disease. On the re- virtually ordained. gional level, it bleeds countries of foreign Battling the Mosquito Along the way, economists learned investment, tourism and trade. Conti- years ago i thought everyone their lesson once again. Today in many nentwide, it costs up to $12 billion a knew how malaria infected humans: African households, malaria not only year, or 4 percent of Africa’s gross do- nighttime bites of parasite-laden Anoph-

JEN CHRISTIANSEN limits income and robs funds for basic mestic product. In short, in many places eles mosquitoes. Today I know better.

www.sciam.com SCIENTIFIC AMERICAN 79 MALARIA tiles were formally partnered. After pub- lic opinion swung against DDT, treating bed nets with a biodegradable class of insecticides—the pyrethroids—was the logical next step. It proved a break- through. The first major use of pyre- throid-treated nets paired with antima- larial drugs, reported in 1991, halved rden

bu mortality in children younger than five g a in the Gambia, and later trials, without sin a the drugs, in Ghana, Kenya and Burkina re Inc of malari Faso confirmed a similar lifesaving trend, plus substantial health gains in pregnant women. Moreover, with wide enough POVERTY use, whole families and communities benefited from the nets— even people who did not sleep under them. But insecticide-treated bed nets also have drawbacks. They work only if ma- laria mosquitoes bite indoors during sleeping hours—a behavior that is not universal. Nets make sleepers hot, dis- couraging use. Until recently, when Per- rden

bu maNet and Olyset—two long-lasting py- g y in rt rethroid-impregnated nets—became as

re available, nets had to be redipped every Inc of pove six to 12 months to remain effective. Fi- nally, at $2 to $6 each, nets with or with- out insecticide are simply unaffordable for many people. A recent study in Kenya MALARIA AND POVERTY cover common ground. Costs levied by the disease go far beyond expenditures on prevention and treatment to include lost income, investment and tourism found that only 21 percent of households revenue. Annual economic growth in countries with endemic malaria averaged 0.4 percent of had even one bed net, of which 6 percent per capita GDP between 1965 and 1990, compared with 2.3 percent in the rest of the world. were insecticide-treated. A summary of 34 surveys conducted between 1999 and Some highly intelligent residents of ma- with fishing nets: “Every man has a net 2004 reached an even more depressing laria-plagued communities still believe which he uses in the daytime for fishing, conclusion: a mere 3 percent of African that an evil spirit or certain foods cause but at night he finds another use for it: he youngsters were protected by insecticidal the illness, a fact that underscores yet an- drapes it over the bed.... Mosquitoes nets, although reports on the ground other pressing need: better malaria edu- can bite through any cover or linen blan- now suggest that use is quickly rising. cation. Nevertheless, long before Ronald ket ... but they do not even try to bite Insecticide resistance could also un- Ross and Giovanni Batista Grassi learned through the net at all.” Based on this dermine nets as a long-term solution: in the late 19th century that mosquitoes passage, some bed-net advocates view mosquitoes genetically capable of inac- transmit malaria, savvy humans were nets steeped in fish oil as the world’s ear- tivating pyrethroids have now surfaced devising ways to elude mosquito bites. liest repellent-impregnated cloth. in several locales, including Kenya and Writing almost five centuries before the It was not until World War II, how- southern Africa, and some anophelines common era, Herodotus described in ever, when American forces in the South are taking longer to succumb to pyre- The Histories how Egyptians living in Pacific dipped nets and hammocks in 5 throids, a worrisome adaptive behavior marshy lowlands protected themselves percent DDT, that insecticides and tex- known as knockdown resistance. Be- cause precious few new insecticides in- CLAIRE PANOSIAN DUNAVAN, a tropical medicine specialist at the David Geffen School of tended for public health use are in sight Medicine at the University of California, , is co-editor of a recently published (largely because of paltry economic in- Institute of Medicine report, Saving Lives, Buying Time: Economics of Malaria Drugs in an centives to develop them), one solution Age of Resistance. A graduate of , Northwestern University Medical is rotating other agricultural insecticides School and the London School of Hygiene and Tropical Medicine, she is an avid teacher on nets. Decoding the olfactory clues T H E A U T H O R

and clinician whose second career as a medical journalist spans nearly two decades. that attract mosquitoes to humans in the JEN CHRISTIANSEN; SOURCE: ROLL BACK MALARIA

80 SCIENTIFIC AMERICAN DECEMBER 2005 first place is another avenue of research salivary glands. If such insects succeed- DDT remains a valuable public health that could yield dividends in new repel- ed in displacing their natural kin in the tool in many settings in Africa and else- lents. (Ironically, a change in body odor wild, they could halt the spread of ma- where [see box below]. Applied to sur- when P. falciparum parasites are present laria parasites to people. Recently native faces, DDT is retained for six months or in the blood may also attract mosquito genes hindering malaria multiplication more. It reduces human-mosquito con- bites; according to a recent report, Ken- within Anopheles mosquitoes have been tact by two key mechanisms—repelling yan schoolchildren harboring gameto- identified, and genetically reengineered some mosquitoes before they ever enter cytes—the malaria stage taken up by strains of several important species are a dwelling and killing others that perch mosquitoes—drew twice as many bites now on the drawing board. Once they on treated walls after feeding. A stun- as their uninfected counterparts.) are reared in the laboratory, however, ning example of its effectiveness sur- How about harnessing the winged releasing these Trojan insects into the faced in KwaZulu-Natal in 1999 and creatures themselves to kill malaria par- real world poses a whole new set of chal- 2000. Pyrethroid-resistant A. funestus asites? In theory, genetic engineering lenges, including ethical ones. plus failing drugs had led to the largest could quell parasite multiplication be- Bottom line: for the time being, old- number of falciparum cases there since fore the protozoa ever left the insects’ fashioned, indoor residual spraying with the South African province launched its DDT: A Symbol Gone Awry In the 1950s a worldwide campaign to eradicate malaria had as its centerpiece the spraying of houses with DDT (dichlorodi- phenyltrichloroethane). In less than two decades, the pesticide enabled many countries to control the disease. In India, for example, deaths from malaria plummeted from 800,000 annually to almost zero for a time. Then, in 1972, the U.S. government banned DDT for spraying crops—although public health and a few other minor uses were excepted. Rachel Carson’s eloquent book Silent Spring, published a decade earlier, is often said to have sparked the ban. Carson meticulously charted the way DDT travels up the food chain in increasing concentrations, killing insects and some animals outright and causing genetic damage in others. ) DDT became a symbol of the dangers of playing God with nature, 1997 1999 2001 2003 MALARIA CASES DECLINED and the developed countries, having got rid of malaria within dramatically in KwaZulu-Natal 7,000 Annual maximum their borders, abandoned the chemical. Most of Europe followed al when the South African at photograph government sprayed dwellings

( 6,000 the U.S. in banning the pesticide for agricultural applications with DDT and later also treated in the 1970s. ulu-N 5,000 patients with an artemisinin- waZ For sub-Saharan Africa, where malaria still rages, these 4,000 based combination treatment (graph). One of the few African decisions have meant the loss of a valuable weapon. Most s in K 3,000 countries there go without DDT not because they have se countries wealthy enough to Ca

AfricanPictures.net fund its own program, it did not banned it themselves—in fact, it is allowed for public health a 2,000

ari have to rely on aid from donors uses in most areas of the world where malaria is endemic— l 1,000

Ma reluctant to use the chemical. but because wealthy donor nations and organizations are 0 The eaves of a typical African resistant to funding projects that would spray DDT even house, such as those in the

); KAREN DUTHIE in responsible ways. DDT spraying begins photograph, provide many Many malaria researchers think DDT should be given New drug treatment begins points of entry for mosquitoes. graph ( another look. In addition to being toxic to mosquitoes, they note, it drives the insects off sprayed walls and out of doors some 1,100 kilograms of DDT over four weeks. Spraying the before they bite, and it deters their entry in the first place. It is a interior surfaces of a house, in contrast, would require roughly

IOM REP OR T toxin, irritant and repellent all rolled into one. Moreover, it lasts half a kilogram, applied once or twice a year. twice as long as alternatives, and it costs a quarter as much as DDT alone will not save the world from malaria; for instance, the next cheapest insecticide. spraying houses works only against mosquitoes that bite The chemical’s deadly trajectory through the food chain had indoors. Effective drugs for patients already infected are its roots in massive agricultural spraying (mainly of cotton essential, as are other measures to control mosquitoes. But fields)—not in its much more moderate use inside dwellings to most malaria health professionals support the targeted use of repel mosquitoes. Dusting a 100-hectare cotton field required DDT as an important part of the tool kit. —The Editors JEN CHRISTIANSEN; SOURCE:

www.sciam.com SCIENTIFIC AMERICAN 81 malaria-control program years ago. Re- Artemisia annua, a medicinal herb once tered human trials in 2004. Another introduction of residual spraying of used as a generic fever remedy in ancient promising tactic that could bypass bo- DDT along with new, effective drugs China. Artemisia-derived drugs (collec- tanical extraction or chemical synthesis yielded a 91 percent drop in cases within tively termed “artemisinins”) beat back altogether is splicing A. annua’s genes two years. malaria parasites more quickly than any and yeast genes into Escherichia coli, other treatment does and also block then coaxing pharmaceuticals out of the Treating the Sick transmission from humans to mosqui- bacterial brew. The approach was pio- antimosquito measures alone toes. Because of these unequaled advan- neered by researchers at the University cannot win the war against malaria— tages, combining them with other effec- of California, Berkeley. better drugs and health services are also tive antimalarial drugs in an effort to Preventing, as opposed to treating, needed for the millions of youngsters prevent or delay artemisinin resistance malaria in highly vulnerable hosts—pri- and adults who, every year, still walk the makes sense, not just for Africa’s but for marily African children and pregnant malaria tightrope far from medical care. the entire world’s sake. After all, there is women—is also gaining adherents. In Some are entrusted to village herbalists no guarantee malaria will not return the 1960s low-dose antimalarial pro- and itinerant quacks. Others take pills of someday to its former haunts. We know phylaxis given to pregnant Nigerians unknown manufacture, quality or effi- it can victimize global travelers. In recent was found, for the first time, to increase cacy (including counterfeits) bought by years P. falciparum–infected mosquitoes their newborns’ birthweight. Currently family members or neighbors from un- have even stowed away on international this approach has been superseded by a regulated sources. In Africa, 70 percent flights, infecting innocent bystanders full course of sulfadoxine-pyrimeth- of antimalarials come from the informal within a few miles of airports, far from amine taken several times during preg- private sector—in other words, small, malaria’s natural milieu. nancy, infancy and, increasingly, child- roadside vendors as opposed to licensed Yet there is a hitch to the new combi- hood immunization visits. Right now clinics or pharmacies. nation remedies: their costs—currently the recipe works well in reducing infec- tions and anemia, but once re- sistance truly blankets Africa, An ancient disease that is both preventable and curable the question is, What preven- tive treatment will replace sul- still claims at least one million lives every year. fadoxine-pyrimethamine? Al- though single-dose artemisi- nins might seem the logical Despite plummeting efficacy, chlo- 10 to 20 times higher than Africa’s more answer at first blush, these agents are roquine, at pennies per course, remains familiar but increasingly impotent ma- not suitable for prevention, because the top-selling antimalarial pharmaceu- laria drugs—are hugely daunting to most their levels in blood diminish so quickly. tical downed by Africans. The next malaria victims and to heavily affected And repeated dosing of artemisinins in most affordable drug in Africa is sulfa- countries. Even if the new cocktails were asymptomatic women and children—an doxine-pyrimethamine, an antibiotic more modest in price, the global supply untested practice so far—could also yield that interferes with folic acid synthesis of artemisinins is well below needed lev- unsuspected side effects. In an ideal by the parasite. Unfortunately, P. falci- els and requires donor dollars to jump- world, prevention equals vaccine. parum strains in Africa and elsewhere start the 18-month production cycle to are also sidestepping this compound as grow, harvest and process the plants. Where We Stand on Vaccines they acquire sequential mutations that Novartis, the first producer formally there is no doubt that creating will ultimately render the drug useless. sanctioned by the WHO to manufacture malaria vaccines that deliver long-last- Given the looming specter of drug re- a co-formulated artemisinin combina- ing protection has proved more difficult sistance, can lessons from other infec- tion treatment (artemether plus lume- than scientists first imagined, although tious diseases guide future strategies to fantrine), may not have enough funding progress has occurred over several de- beef up malaria drug therapy? In recent and raw material to ship even a portion cades. At the root of the dilemma is ma- decades resistant strains of the agents re- of the 120 million treatments it once laria’s intricate life cycle, which encom- sponsible for , leprosy and hoped to deliver in 2006. passes several stages in mosquitoes and HIV/AIDS triggered a switch to two- The good news? Cheaper, synthetic humans; a vaccine effective in killing and three-drug regimens, which then drugs that retain the distinctive chemis- one stage may not inhibit the growth of helped to forestall further emergence of try of plant-based artemisinins (a perox- another. A second challenge is malaria’s “superbugs.” Now most experts believe ide bond embedded in a chemical ring) complex genetic makeup: of the 5,300 that multidrug treatments can also com- are on the horizon, possibly within five proteins encoded by P. falciparum’s ge- bat drug resistance in falciparum malar- to 10 years. One prototype originating nome, fewer than 10 percent trigger ia, especially if they include a form of from research done in the late 1990s en- protective responses in naturally ex-

82 SCIENTIFIC AMERICAN DECEMBER 2005 and four, the years when African chil- lished the Roll Back Malaria partner- dren are most susceptible to dying from ship. In 2000 the G8 named malaria as the disease. The formula used in this one of three pandemics they hoped to clinical trial (the most promising to date) curb, if not vanquish. The United Na- included multiple copies of a P. falci- tions subsequently created the Global parum sporozoite protein fragment fused Fund to Fight AIDS, Tuberculosis and to a hepatitis B viral protein added for Malaria and pledged to halt and reverse extra potency. Even so, subjects required the rising tide of malaria within 15 years. three separate immunizations, and the In 2005 the World Bank declared a re- period of protection was short (only six newed assault on malaria, and President months). Realistically, the earliest that George W. Bush announced a $1.2-bil- an improved version of the vaccine lion package to fight malaria in Africa known as RTS,S (or any of its roughly over five years, using insecticide-treated EBRAHIM SAMBA, who recently retired as the three dozen vaccine brethren currently in nets, indoor spraying of insecticides and WHO’s Regional Director for Africa, still bears clinical development) might come to combination drug treatments. More re- delicate hatch marks incised on his cheeks market is in 10 years, at a final price tag cently, the World Bank has begun look- at the age of two, when he was close to death from severe malaria. that leaves even Big Pharma gasping for ing for ways to subsidize artemisinin air. Because of the anticipated costs, pub- combination treatments. As this issue of posed individuals—the question is, lic-private partnerships such as the Se- Scientific American went to press, the Which ones? On top of that, several attle-based Malaria Vaccine Initiative Bill and Melinda Gates Foundation an- arms of the human immune system—an- are now helping to fund ongoing trials. nounced three grants totaling $258.3 tibodies, lymphocytes and the spleen, There is just one more thing to keep in million to support advanced development for starters—must work together to mind about malaria vaccines. Even when of a malaria vaccine, new drugs and im- achieve an ideal response to malaria vac- they do become available—with any luck, proved mosquito-control methods. cination. Even in healthy people, much sooner rather than later—effective treat- Despite these positive steps, the dol- less populations already beset with ma- ments and antimosquito strategies will lars at hand are simply not equal to the laria and other diseases, such responses still be needed. Why? First of all, because task. Simultaneously with the announce- do not always develop. rates of protection will never reach any- ment from the Gates Foundation, a ma- So far most experimental P. falci- where near 100 percent in those who ac- jor new analysis of global malaria re- parum vaccines have targeted only one of tually receive the vaccines. Other malar- search and development funding noted malaria’s three biological stages—sporo- ia-prone individuals, especially the rural that only $323 million was spent in zoite, merozoite or gametocyte [see box African poor, may not have access to the 2004. This amount falls far short of the on page 79], although multistage vac- shots at all. Therefore, at least for the fore- projected $3.2 billion a year needed to cines, which could well prove more effec- seeable future, all preventive and salvage cut malaria deaths in half by 2010. Per- tive in the end, are also planned. Some of measures must remain in the arsenal. haps it is time to mobilize not only ex- the earliest insights on attacking sporozo- perts and field-workers but ordinary folk. ites (the parasite stage usually inoculated Investing in Malaria At roughly $5, the price of a lunch in the into humans through the mosquito’s pro- once again the world is coming U.S. could go a long way toward pur- boscis) came in the 1970s, when investi- to terms with the truth about malaria: chasing an insecticide-treated bed net or gators at the University of Maryland the ancient enemy still claims at least one a three-day course of artemisinin combi- found that x-ray-weakened falciparum million lives every year while, at the nation treatment for an African child. sporozoites protected human volunteers, same time, imposing tremendous physi- In considering their potential return albeit only briefly. Presumably, the vac- cal, mental and economic hardships. on investment, readers might also recall cine worked by inducing the immune sys- Given our current tools and even more a small boy with scars on his cheeks who tem to neutralize naturally entering para- promising weapons on the horizon, the made it through malaria’s minefield, sites before they escaped an hour later to time has come to fight back. then devoted his adult life to battling dis- their next way station, the liver. The past decade has already wit- ease. Decades from now, how many oth- The demonstration that antibodies nessed significant milestones. In 1998 er children thus spared might accom- artificially elicited against sporozoites the WHO and the World Bank estab- plish equally wondrous feats? could help fend off malaria prompted further work. Three decades later, in MORE TO EXPLORE 2004, efforts bore fruit when a sporozo- What the World Needs Now Is DDT. Tina Rosenberg in New York Times Magazine, pages 38–43; ite vaccine more than halved serious epi- April 11, 2004. sodes of malaria in 2,000 rural Mozam- Medicines for Malaria Venture: www.mmv.org/

©WHO/P. VIROT bican children between the ages of one World Health Organization, Roll Back Malaria Department: www.who.int/malaria

www.sciam.com SCIENTIFIC AMERICAN 83