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A Plan to Defeat NEGLECTED TROPICAL DISEASES The poorest people are not only poor. They are also chronically sick, making it harder for them to escape poverty. A new global initiative may break the vicious cycle BY PETER JAY HOTEZ

n the north of Burkina Faso, not far to the east of one KEY CONCEPTS of the best-known backpacker destinations in West Af- ■ A group of seven tropical I rica, the Bandiagara Escarpment in Mali, lies the town diseases, mostly caused by of Koumbri. It was one of the places where the Burkina parasitic worms, affl ict a Ministry of Health began a mass campaign fi ve years ago billion impoverished people to treat parasitic worms. One of the benefi ciaries, Abou- worldwide. They seldom bacar, then an eight-year-old boy, told health workers he kill directly but cause life- felt perpetually tired and ill and had noticed blood in his long misery that stunts urine. After taking a few pills, he felt better, started to children’s growth, leaves adults unable to function to play soccer again, and began focusing on his schoolwork their fullest, and heightens and doing better academically. the risk of other diseases. The Burkina Faso program, which treated more than two million children, was both a success story and an em- ■ Fortunately, they can be blem of the tragedy of disease in the developing world. For easily treated, often with a single pill. Various agen- want of very simple treatments, a billion people in the cies and foundations are world wake up every day of their lives feeling sick. As a collaborating to deliver result they cannot learn in school or work effectively. these drugs, although they Most people in richer countries equate tropical disease have reached only about with the big three—HIV/AIDS, and malar- 10 percent of the popula- ia—and funding agencies allocate aid accordingly. Yet a tion so far. group of conditions known collectively as neglected tropi- ■ The U.S. has its own ne- cal diseases (N T Ds) has an even more widespread impact . glected parasitic diseases They may not often kill, but they debilitate by causing se- Getty Images ONE TABLET of ivermectin per year / that affect millions of rural vere , malnutrition, delays in intellectual and cog- is enough to protect against river and urban poor. nitive development, and blindness. They can lead to hor- blindness. Health workers in the —The Editors rifi c limb and genital disfi gurement and skin deformities Ivory Coast have been battling

and increase the risk of acquiring HIV/AIDS and suffer- SANGOISSOUF AFP a resurgence of the disease.

90 SCIENTIFIC AMERICAN January 2010

www.ScientificAmerican.com SCIENTIFIC AMERICAN 91 [DISEASE STATS] THE GRISLY SEVEN The neglected tropical diseases comprise seven parasitic or bacterial that are common in impoverished areas.

DISEASE CASES CAUSE TRANSMISSION EFFECTS

Roundworm 800 million 5- to 14-inch-long Ascaris Soil ■ Malnutrition and intestinal obstruction in young children (Ascariasis) worms that live in the small ■ Child stunting intestine (shown actual size) ■ Impaired cognition

Whipworm 600 million 1- to 2-inch-long Trichuris Soil ■ Colitis and infl ammatory bowel disease () worms that live in the colon ■ Child stunting and impaired cognition (large intestine)

Hookworm 600 million 0.5-inch-long Necator Soil ■ Severe iron defi ciency anemia and protein malnutrition worms that live in the ■ “Yellow disease”(anemia) small intestine ■ Child stunting and impaired intellectual and cognitive development ■ Maternal morbidity and mortality in pregnancy

Schistosomiasis 200 million 0.5- to 1-inch-long blood Freshwater ■ Spiny eggs that damage the bladder, intestine or liver and cause infl ammation fl ukes that live in veins of ■ Chronic pain, anemia, malnutrition and stunting the bladder or intestines ■ Liver and intestinal fi brosis (for mansoni and S. japonicum) ■ Blood in urine, kidney disease, female genital (for S. haematobium)

Lymphatic 120 million 2- to 4-inch-long Wuchereria Mosquitoes ■ Leg swelling fi lariasis (LF) worms that live in the limbs, ■ Scrotum enlargement (elephantiasis) breasts and genitals ■ Disfi gurement

Onchocerciasis 30–40 1- to 20-inch-long Black fl ies ■ Microfi lariae (larvae) in the skin and eyes million Onchocerca worms living ■ Onchocerca skin disease in nodules under the skin ■ Blindness

Trachoma 60–80 intracellular Poor , ■ Blindness million bacteria house fl ies

[THE AUTHOR] ing complications during pregnancy. They not more coordinated and systematic way. Over the only result from poverty but also help to perpet- past half a decade the Bill & Melinda Gates Peter Jay Hotez became interested uate it. Children cannot develop to their full po- Foundation, the Dubai-based sustainable devel- in medicine as child when he read Paul De Kruif’s classic book Microbe tential, and adult workers are not as productive opment fund Legatum, and the U.S. and British

Hunters and asked his parents for as they could be. governments have committed serious money, ); a microscope. He went on to obtain Such diseases are not confi ned to developing while major pharmaceutical companies have ) worms both a Ph.D. and an M.D., specializ- nations. I estimate that millions of Americans donated urgently needed NTD drugs. But the ing in parasitology. He now chairs living in poverty also suffer from NTD-like in- battle has only begun. the department of microbiology, woman crying woman ( immunology and fections. Parasitic diseases such as cysticercosis, WILSON CAT ); ( , and toxocaria- Like Leeches in Your Gut at George Washington University. Hotez Hotez is president of the Sabin sis occur with high frequency in our inner cities, The scale and extent of the global NTD problem Institute, a member of the post-Katrina Louisiana, other parts of the Mis- are hard to take in. Almost every destitute per- Institute of Medicine of the Nation- sissippi Delta, the border region with Mexico, son living in sub-Saharan , Southeast Asia al Academies of Science, and co-founder of the Global Network and Appalachia [see box on page 94]. and Latin America is infected with one or more for Neglected Tropical Diseases. NTDs have plagued humankind for thou- of these diseases. The illnesses last years, decades Redux Pictures MARIELLA Redux ); FURRER sands of years. Historians have found accurate and often even a lifetime. The seven most com- descriptions of many of them in ancient texts as mon NTDs have the most devastating impact. diverse as the Bible, the Talmud, the Vedas, the Three of them are caused by parasitic worms, woman and child writings of Hippocrates, and Egyptian papyri. also known as helminths, that live in the intes- ( What is new, however, is that donors, drugmak- tines. The large common roundworm, which re- ers, health ministries in low- and middle-in- sults in ascariasis, affl icts 800 million people come countries, the World Health Organization and the whipworm, which results in trichuriasis, (WHO), and public-private partnerships are 600 million people. These helminths rob chil- ERIK LESSER S. Pictures Redux linking their efforts to combat the NTDs in a dren of nutrients, stunting their growth. Even COURTESY OF GW MEDICAL CENTER MARKETING AND COMMUNICATIONS (

92 SCIENTIFIC AMERICAN January 2010 learning in school. More than 40 million preg- nant women are also infected with hookworm, rendering them vulnerable to or addi- tional blood losses in childbirth. Their babies AREAS TREATMENT MAJOR CONTROL PROGRAMS are born with low birth weights [see “Hook- Asia, Africa, Americas Albendazole, mebendazole WHO, Children Without Worms, worm ,” by Peter J. Hotez and David I. Deworm the World Pritchard; Scientific American, June 1995]. Schistosomiasis is the next most common NTD. It is caused by parasitic worms known as schistosomes that live in the veins draining the Asia, Africa, Americas Albendazole, mebendazole WHO, Children Without Worms, intestines or bladder. More than 90 percent of Deworm the World the 200 million cases occur in sub-Saharan Af- rica, with another few million cases in Asia, Africa, Americas Albendazole, mebendazole WHO, Children Without Worms, and several other countries. Female schisto- Deworm the World, Sabin Vaccine Institute somes release eggs equipped with tiny spears that invade and damage organs, including the Mostly in Africa; Praziquantel Schistosomiasis Control Initiative intestine and liver or the bladder and kidneys, remainder in Brazil, depending on the species. Roughly 100 million East Asia, Middle East school-aged children and young adults pass blood in their urine or feces every day as a re- Asia, Africa, Ivermectin or diethylcarbamazine Global Program to Eliminate Lymphatic Americas and albendazole Filariasis, Lymphatic Filariasis Support sult. The infl ammation produces pain, malnu- Center, Carter Center trition, growth stunting and anemia. In women, schistosomes deposit eggs in the cervix and va- Mostly in Africa, Ivermectin African Program for gina, causing disabling pain during sexual in- some in Latin America Control, Carter Center, Mectizan Donation Program tercourse and tripling the risk of acquiring HIV/ AIDS [see “Fighting Killer Worms,” by Patrick Skelly; Scientific American, May 2008]. Two other important helminth infections are Africa, Asia, Azithromycin; SAFE strategy: simple International Trachoma Initiative, Americas surgery, antibiotics, face washing, Carter Center, Helen Keller International, lymphatic fi lariasis (LF) and onchocerciasis. The environment (such as ) Sight Savers, Christian Blind Mission worms that cause LF live in the limbs, breasts and genitals of 120 million people in Asia, Afri- worse are hookworms, which are found in 600 ca and Haiti. They lead to elephantiasis, a gross- million people. These half-inch-long worms at- tach to the inside of the small intestine and suck blood, like an internal leech. Over a period of ELEPHANTIASIS (below, in Haiti) months or years they produce severe iron-defi - and blindness (right, in Ethiopia) ciency anemia and protein malnutrition. Chil- are two of the most visible dren with chronic hookworm anemia take on a consequences of neglected sickly and sallow complexion and have trouble tropical diseases.

www.ScientificAmerican.com SCIENTIFIC AMERICAN 93 [PARASITIC INFECTIONS IN THE U.S.] ly disfiguring condition that prevents adults from working and leaves women, in particular, Horrors of the Kissing Bug unable to marry or abandoned by their hus- he U.S., too, suffers high rates of parasitic diseases. These so-called neglected infections bands. Onchocerciasis, or river blindness, causes Tof poverty closely resemble the neglected tropical diseases (NTDs) and are found pre- a horribly itchy and disfi guring skin disease as dominantly in areas of intense poverty. They disproportionately affect African-Americans well as blindness in middle-aged adulthood. Al- and Hispanic-Americans, because a higher percentage of these populations live in poverty most all of its 30 million to 40 million cases oc- and under stressful conditions. cur in Africa, except for a few locations in the In the Mississippi Delta, post-Katrina Louisiana and other areas of the American South, Americas and Yemen. as well as in inner cities, an estimated three million African-Americans are either currently infected or have been infected in the past with a helminth infection known as toxocariasis. The seventh important NTD, trachoma, is The worm eggs are found in soil or sand laced with dog feces and can contaminate food. not caused by a parasitic worm but is a chronic Once the worm eggs hatch in the digestive tract, the released larvae migrate through the bacterial infection caused by the Chlamydia mi- lungs, liver and brain, leading to wheezing, and developmental delays. Another croorganism. Occurring in 60 million to 80 mil- infection is trichomoniasis, a sexually transmitted protozoan parasite that causes infl am- lion people, it is the leading infectious cause of mation and hemorrhages in the cervix. It increases the risk of acquiring additional sexually blindness [see “Can Chlamydia Be Stopped?” by transmitted diseases, possibly including HIV/AIDS. David M. Ojcius, Toni Darville and Patrik M. Among Hispanic-Americans, two important infections of poverty are Chagas disease Bavoil; Scientific American, May 2005]. and cysticercosis. Chagas results from a trypanosome protozoan acquired when people In a series of policy papers, my colleagues are bitten by a kissing bug, a type of assassin bug—a cockroachlike often found in and I studied the repercussions of these seven dilapidated housing where rats nest (photograph above). The parasites can produce a NTDs. Together their damage, as severe dilation of the heart and can prove fatal. An estimated 300,000 people in the U.S. have Chagas disease. Cysticercosis is a parasitic helminth infection that occurs in as many measured by the number of healthy life years as 170,000 people and is the leading cause of seizures in cities near the Mexican border. lost because of disability, is roughly equivalent Most of these infections were not introduced into the U.S. as a result of . to that of HIV/AIDS or malaria. Because of Instead they most likely persist through transmission within U.S. borders. Despite their their devastating toll on child education and de- prevalence, research on these conditions has been fairly limited. Health offi cials do not velopment, pregnancy, and agricultural worker know the precise numbers of people infected or why poverty is a risk factor. Diagnostic productivity, these NTDs are a major cause of methods and treatments are also fairly rudimentary. —P.J.H. poverty. One case study by Hoyt Bleakley, a de- velopment economist, found that chronic hook- worm infection in childhood reduced a person’s lifetime earning power by more than 40 per- cent; K. D. Ramaiah and others in India esti- mated more than $800 million lost annually from reduced worker productivity as a result of LF. Other studies have found similar effects for onchocerciasis and trachoma.

Curing the Sick with Salt The good news is that these NTDs can be treat- ed, or even prevented, simply and cheaply [see table on preceding two pages]. In many cases , a single pill is enough . The available drugs have an excellent safety record, and each is either ) map provided free of charge by multinational com- panies or available as cheap generics costing less Puerto than 10 cents per tablet. Rico In the early 20th century John D. Rockefell- BLOOD DONORS TESTING POSITIVE FOR CHAGAS DISEASE, BY STATE, 2007–2009 er sponsored mass drug administration to con- LUCY READING-IKKANDALUCY (

1–2 3-4 5–10 11–69 70–375 Data unavailable trol helminth infection in the American South, ); Locations of confirmed cases and similar efforts began in the Caribbean. SOURCE: AABB During the 1950s and 1960s several tropical assassin bug medicine specialists started programs for other CHAGAS DISEASE affl icts an estimated 300,000 people in the U.S. Screening of infections and locations. Among them was donated blood, started in 2007, fi nds that cases are concentrated in areas with Frank Hawking, father of physicist Stephen large numbers of immigrants from Latin America living in substandard housing. Hawking, who in 1967 published the results of

a study in Brazil in which he treated LF by add- PHOTO RESEARCHERS, INC. (

94 SCIENTIFIC AMERICAN January 2010 ing diethylcarbamazine to cooking salt. In 1988 Ultimately, these NTD-control programs Merck & Co. began one of the fi rst public-pri- will need more money. The U.S. and British vate partnerships for the mass treatment of river governments have committed more than $400 blindness. Various such partnerships have since million over the next few years to support in- been established, and today they reach tens of ALYSSA MILANO tegrated NTD control, but estimates suggest millions of people annually. that controlling N T Ds in the 56 endemic coun- Through the delivery of extremely low cost HOW TO HELP tries will require $2 billion to $3 billion for the treatments, these partnerships—in collabora- next fi ve to seven years. To make the case for tion with WHO, health ministries in low-in- The neglected tropical diseases better funding, some of the major public-pri- come countries, and several multinational phar- represent an enormous challenge, vate partnerships came together in 2006 to but because treatment is so inex- maceutical companies—have managed to con- pensive, individuals can make a form the Global Network for NTDs, which trol or eliminate river blindness in 11 African difference. Luminaries ranging works closely with WHO and its regional of- countries, allowing farmers to return to arable from Bill Clinton to actress Alyssa fi ces. Hosted by the Sabin Vaccine Institute, the lands they had abandoned because of high rates Milano have lent their time and network receives support from the Gates foun- of blindness in their communities. Similarly, support to the Global Network. dation and other private donors and works to treatment programs have eliminated LF in more support treatment programs for NTDs around One step is to join the Just 50 Cents than a dozen previously endemic countries and Campaign, the network’s grassroots the world through advocacy, policy and logis- reduced the prevalence of schistosomiasis by up fundraising and awareness cam- tical efforts. to 80 percent in eight African countries. Mea- paign. A donation of just 50 cents The Sabin Vaccine Institute has also estab- sured narrowly in fi nancial terms, the internal can provide a person with treatment lished an international product development rates of return for these programs have ranged for the seven most common NTDs partnership to produce new for hook- for an entire year. Visit: as high as 30 percent. www.globalnetwork.org/just50cents worm infection and schistosomiasis. A hook- worm vaccine is now entering clinical trials, One Pill to Cure Them All which is welcome news because of concerns that Despite these enormous successes, we still one of the drugs now in use for mass treatment have a long way to go to provide complete is showing high failure rates, a sign that the par- drug coverage for the billion or more peo- asite has become resistant. Sabin works with a ple with NTDs. WHO estimates that spectrum of Brazilian research and develop- treatment programs reach fewer than 10 ment institutes and the Brazilian government. percent of people suffering from intestinal Brazil has the largest number of cases of these infections and schistosomiasis. helminth infections in the Americas; these Better organization and technology are part NTDs were originally introduced from the en- of the answer. WHO and other organizations demic areas of West Africa by the slave trade, have studied the simultaneous administration making them living vestiges of slavery. of many NTD drugs, and they are moving If fi ghting NTDs is so obvious and so cheap, quickly to provide these drugs as a single pack- ➥ MORE TO why has it taken so long to act in a systematic age (sometimes referred to as a rapid impact EXPLORE way? That is not an easy question to answer. In package), which can cost as little as 50 cents an- Control of Bancroftian Filariasis the Millennium Development Goals for sustain- nually. A number of African countries have al- by Cooking Salt Medicated with able reduction of poverty, launched in 2000, the ready begun to integrate programs that target Diethylcarbamazine. Frank Hawk- NTDs were lumped in an “other diseases” cat- ing and Ruy João Marques in Bulletin individual NTDs into a single program. Bun- egory, and it is hard to get people excited about ) dling reduces costs and the strain on otherwise of the World Health Organization, “other diseases.” Moreover, the NTDs debili-

Vol. 37, No. 3, pages 405–414; 1967. quarters ( overburdened health systems, as well as provid- Available online at www.ncbi.nlm. tate more than they kill, so that the big donor ing an opportunity to fold in other interven- nih.gov/pmc/articles/PMC2554262 countries have chosen to focus primarily on tions, among them the delivery of antimalaria HIV/AIDS, tuberculosis and malaria, which are bed nets, childhood immunizations and nutri- Forgotten People, Forgotten fatal unless treated. Other development pro- tional supplements such as vitamin A. Diseases: The Neglected Tropical grams, viewing NTDs as a symptom rather than Diseases and Their Impact on Although the integration of NTD-control the disease, have preferred to concentrate on Global Health and Development. ); DON FARRALL Getty Images programs has been largely successful so far, it Peter J. Hotez. ASM Press, 2008. what they see as the underlying problems, such Milano has also encountered some operational chal- as poor sanitation, lack of access to clean water, ( lenges, including an increased workload for Rescuing the Bottom Billion and poverty in general. Those are laudable aims, community drug distributors and the lack of through Control of Neglected but the empirical reality is that NTD drugs are Tropical Diseases. Peter J. Hotez the single most cost-effective way to improve availability of some of the NTD drugs in certain et al. in Lancet, Vol. 373, No. 9674, places. Health workers have had to be vigilant pages 1570–1575; May 2, 2009. Avail- the health, education and well-being of the ■ in looking for signs of drug resistance. able online at tinyurl.com/yh5qbeq world’s poor right now. STEVE GRANITZ Getty Images

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