NEGLECTED TROPICAL DISEASES (NTDs) SLATED FOR ELIMINATION AND ERADICATION (2024)

Dracunculiasis

Dracunculiasis is a painful parasitic infection that people get by drinking contaminated water. The 2- to 3-feet-long (1-meter-long) worms emerge directly through the skin a year later, when they are seeking to deposit hundreds of thousands of larvae back into the water to continue the cycle. People are crippled temporarily for weeks, with severe impact on agricultural productivity and school attendance. There is no cure or vaccine, there is no animal reservoir of the human infection, and recovered patients are not immune to future infection. It can be prevented by teaching people to always filter their drinking water, by not allowing people with emerging worms to enter a water source, by applying ABATE^® Larvicide, or by providing safe water from borehole wells, for example (Ruiz-Tiben and Hopkins, 2008). In addition to the severe constraint of a one-year-long incubation period, Dracunculus medinensis has a serious reproductive potential that can magnify the penalty for a missed case: documented surprise explosions of 58, 85, and 91 cases occurred in three separate incidents one year after a single undetected imported case contaminated a village water supply.

The Carter Center has led this eradication campaign since 1986, in close coordination with the endemic countries, the Centers for Disease Control and Prevention (CDC), the United Nations Children's Fund, and WHO. This program has benefited from many very generous donors, including Dupont Coporation, which donated nylon filter material; American Cyanamid (now BASF), which donates ABATE; the Bill & Melinda Gates Foundation and the Conrad N. Hilton Foundation, the U.S. Agency for International Development, and many other bilateral donors, including the federal government of Nigeria; the U.S. Peace Corps volunteers, and other foreign volunteers from Japan, Canada, and a few other nations; and national service volunteers in Ghana and Nigeria.

Tens of thousands of grassroots village volunteers are the bedrock of the Guinea Worm Eradication Program. They were the first to show the utility of village volunteers in Africa as the basis for a surveillance network that provides reliable monthly village-based reports of a disease. They also help educate their neighbors about how to prevent Guinea worm disease, and they distribute cloth filters. In addition to benefiting from the work of former U.S. President Jimmy Carter, the Guinea Worm Eradication Program has benefited from exceptionally strong participation by a former head of state of Ghana, Flt. Lt. Jerry Rawlings, President Amadou Toumani Toure of Mali, and Nigerian former head of state General (Dr.) Yakubu Gowon.

What are the results? As shown in Figure A6-1, as of 2009 we were down to less than 3,200 cases, from an estimated 3.5 million cases in 1986, with 645 endemic villages compared to more than 23,000 villages, and down to 4 countries, all in Africa, instead of 20 countries on two continents. The program will probably report less than 2,000 cases worldwide in 2010, and 1, 2, or 3 of the 4 remaining endemic countries may interrupt or have already interrupted Guinea worm transmission in 2010 (Hopkins et al., 2010; WHO, 2010b).

The final battleground is Southern Sudan, which reported 86 percent of all cases in 2009 and 97 percent so far this year, and which is also approaching a crucial referendum in January 2011 to determine whether it will remain a part of Sudan or separate to form a new nation. Since the Comprehensive Peace Agreement was signed in January 2005 to end the 22-year-long civil war, the Southern Sudan Guinea Worm Eradication Program has made good progress despite the many challenges of large area, little infrastructure, low literacy, and sporadic insecurity that disrupted program operations 32 times in different places in 2009, for example. It has an excellent national program coordinator. We are now aiming to stop transmission in Southern Sudan by the end of 2012, political and security conditions permitting. WHO has certified 187 countries as free of dracunculiasis (Hopkins et al., 2010; WHO, 2010b).

The global Guinea Worm Eradication Program (GWEP) has progressed over the past 30 years thanks to five key benchmarks: (1) from the outset it had a clear goal; (2) it identified all of the endemic countries; (3) it established effective village-based, active surveillance; (4) it extended interventions throughout the endemic areas; and (5) it monitors and responds to reports of cases and the status of interventions on a monthly basis. When the GWEP succeeds, it will set a precedent as the first parasitic disease of humans to be eradicated, and as the first disease to be eradicated without a vaccine or curative treatment. The GWEP is important evidence of the potential power of health education and community mobilization. Its legacy in endemic areas will include improved health, more productive agriculture, and better school attendance, as well as experienced health workers and village volunteers and changed attitudes.

Onchocerciasis

Onchocerciasis is a potentially blinding parasitic infection spread by repeated bites of black flies, which breed in fast-flowing rivers, rapids, or dams. Increased construction of dams may be increasing suitable habitat for some vector black flies in Africa. Of an estimated 123 million persons at risk in 37 countries, mostly in Africa, some 37 million persons are actually infected. About a half million people are at risk in six countries in the Americas, and a few thousand in Yemen. The infection may also cause severe itching, but it can be treated or prevented by annual doses of Mectizan^® (ivermectin). Because treatment with Mectizan only kills the immature microfilariae and not the adult worms, annual treatments must continue for at least a decade until the adult worms die out. Merck & Company, Inc. set an incredible precedent in 1987, when it announced that it would make its newly discovered Mectizan available to treat populations in poor countries affected by onchocerciasis free of charge, in whatever amounts were needed, for as long as necessary. Three regional programs have waged war on this disease—two in Africa and one in the Americas (Cupp et al., 2010).

In the Americas, the River Blindness Foundation (RBF) launched the Onchocerciasis Elimination Program for the Americas (OEPA) in 1993 in association with CDC, the Pan American Health Organization, and the ministries of health of the six affected countries: Brazil, Colombia, Ecuador, Guatemala, Mexico, and Venezuela. When RBF founder John Moores became a member of the Carter Center's board of trustees, the RBF was absorbed into the Carter Center in 1996 and the Carter Center became OEPA's sponsoring body, providing funding and technical support to assist the national programs. The OEPA strategy is for the national programs to provide mass treatment with Mectizan at least twice per year with a minimum coverage of 85 percent of the eligible population. (Since 2003, some highly endemic communities in Mexico have been treated four times per year.) With one exception, the species of black fly vectors in the Americas are not as efficient transmitters of onchocerciasis as the vectors in Africa, which is part of what makes elimination more feasible in the Americas. The current goal is to stop transmission of onchocerciasis in the Americas by 2012 (WHO, 2010c).

The impact achieved so far in the Americas is summarized in Table A6-1. Two of the six countries (Colombia and Ecuador) and 8 of the 13 endemic foci have interrupted transmission, and two other countries (Guatemala and Mexico) are on the verge of stopping transmission. The main remaining challenge is the small binational focus in the Amazon among the Yanomami population that straddles the border between Brazil and Venezuela. In 2009, the Brazilian side of this focus surpassed the 85 percent coverage goal for the eighth consecutive year, while the Venezuela side achieved the coverage goal for the third consecutive year. So far, Merck's donation accounts for 44 percent of the cumulative expense of this initiative, while the six countries themselves have provided 37 percent, which is a big contrast to the endemic countries in Africa.

The Onchocerciasis Control Program (OCP), which was sponsored by WHO, the World Bank, and others, covered 11 West African countries from 1974 to 2002 and was the first regional African program against onchocerciasis. Using a strategy of vector control that involved aerial spraying of rivers with insecticides to prevent breeding of black flies, to which annual mass drug administration (MDA) of Mectizan was added when that became available in 1987, this program completely eliminated transmission of onchocerciasis in most of the vast area, except for a few areas of Ghana, Côte d'Ivoire, and Sierra Leone. The OCP proved that vector control could eliminate onchocerciasis in much of West Africa, but this approach was expensive, and vector control was not as feasible in forested endemic areas. Fortunately, MDA with Mectizan is feasible in forested endemic areas, and that is what began to happen after Merck's discovery became available (Cupp et al., 2010).

The African Program for Onchocerciasis Control (APOC), sponsored by WHO and the World Bank with intimate involvement of several international nongovernmental organizations, embraces 19 endemic countries in Africa. It was officially launched in December 1995 and is scheduled to end in 2015. It aims to help constituent countries develop sustainable systems to administer Mectizan annually to at least 65 percent of the eligible population in areas where onchocerciasis was found to be hyperendemic or mesoendemic. This program pioneered the development of “community-directed treatment with ivermectin” (CDTI) using village volunteers selected by the community to distribute Mectizan at locations and times determined by the community. APOC has an ultimate treatment goal (UTG) of about 90 million persons. In 2008, it treated 57 million people, or 63 percent of the total UTG, in 15 of the 19 countries. The prevalence of onchocerciasis was reduced from 46.5 percent in 1995 to 28.5 percent in 2008 (WHO, 2010d). However, studies conducted by the Carter Center in Cameroon and Nigeria have shown that transmission of the parasite persists after 11 years of annual MDA with Mectizan (Katabarwa et al., 2008), that transmission continues in some untreated hypoendemic areas (Katabarwa et al., 2010), and that the annual MDA with Mectizan is not yet sustainable by several endemic countries without continued external support (Rakers et al., 2009).

In 2002, WHO and the Carter Center co-hosted a Conference on the Eradicability of Onchocerciasis, which concluded that onchocerciasis could not be eliminated in Africa with current tools, but could be eliminated in the Americas. The conference recommended continued research and elimination where possible in certain vulnerable foci in Africa and Yemen, and it underscored the potentially game-changing value of a macrofilaricide to kill the adult worms (Carter Center and WHO, 2002). However, APOC has recently shown that annual or twice per year MDA with Mectizan alone for 15–17 years eliminated onchocerciasis transmission in some hyperendemic foci in Mali and Senegal (Diawara et al., 2009). In 2006, Sudan launched an effort to eliminate onchocerciasis in an isolated focus at Abu Hamad north of Khartoum, and in the next year Uganda launched a nationwide onchocerciasis elimination program, both using twice per year MDA with Mectizan at a desired minimal coverage level of 90 percent, and with technical assistance provided by the Carter Center (Ndyomugyenyi et al., 2007). Uganda's bold decision followed on the heels of its successful elimination of Guinea worm disease, and it had already eliminated onchocerciasis in two foci using focal larviciding and annual MDA with Mectizan. The new offensive by the Government of Uganda takes aim first at 6 more of the 18 endemic foci in the country. Yemen is also conducting MDA twice per year, with the aim of stopping transmission in that relatively minor focus. Unfortunately, Mectizan cannot be used safely in all areas in 10 of the 30 onchocerciasis-endemic African countries where Loa loa infections also occur, because of potentially fatal neurological complications.

So onchocerciasis has been eliminated by using vector control and later MDA with Mectizan in most of the OCP area of West Africa. MDA with Mectizan twice or once per year is eliminating transmission in the Americas, and probably in Yemen and perhaps in some parts of the APOC project area. But some endemic areas of countries included in APOC remain inaccessible because of conflict or co-endemic Loa loa, or because onchocerciasis is only hypo-endemic and thus not eligible for MDA under APOC. So far, annual MDA with Mectizan alone has not yet been shown to stop transmission in many APOC areas that have had MDA with Mectizan for more than a decade (Katabarwa et al., 2008). Sustaining annual MDA with Mectizan in Africa indefinitely is a daunting prospect (Hopkins et al., 2005). We really need a macrofilaricide to speed interruption of onchocerciasis transmission, and we need a strategy for stopping transmission of onchocerciasis in areas where there is Loa loa. Meanwhile, the effort to eliminate lymphatic filariasis is providing some additional help against onchocerciasis.

Lymphatic Filariasis (LF)

Lymphatic filariasis (LF) is a parasitic infection, spread by repeated bites of mosquitoes, that causes extreme swelling of the limbs and genitalia. Of the 1.3 billion people at risk in about 81 countries in Africa, Asia, and the Americas, an estimated 120 million are infected. This disfiguring chronic disease can be prevented by annual MDA with diethylcarbamazine (DEC) and albendazole, or in Africa (where DEC causes unacceptable side effects) with Mectizan and albendazole combined. MDA must continue for at least five to six years until the adult worms that cause LF die. Surgery can reduce disabling hydroceles in men, and palliative care can mitigate secondary infections and swelling of some limbs, thereby also improving people's emotional and social health (Bockarie and Molyneux, 2009).

In a landmark partnership, Merck, which produces Mectizan, and GlaxoSmithKline, which produces albendazole, have both agreed to donate their respective drugs for MDA to help eliminate LF in Africa (Gustavsen et al., 2009). As wonderfully positive secondary effects, both drugs also have deworming qualities against certain intestinal helminths such as Ascaris and Trichuris, with consequent positive tertiary effects on children's growth, development, nutrition, and cognition. To date, Merck estimates that it has donated 2.5 billion Mectizan tablets for onchocerciasis and LF treatments, with a value of US$3.75 billion (). GlaxoSmithKline has donated approximately 1.5 billion albendazole treatments to 50 countries, at a value of about $67.5 million. In China, addition of DEC to table salt has been the main tool used to stop LF transmission nationwide.

The International Task Force for Disease Eradication (ITFDE) was the first international body to suggest that LF was potentially eradicable, in a report published in 1993 (CDC, 1993). Soon after WHA adopted the resolution in 1997 calling for LF elimination “as a public health problem,” the Global Alliance to Eliminate Lymphatic Filariasis was established in 2000 to help endemic countries achieve annual MDA with the appropriate drugs, aiming for a minimum coverage of 80 percent. Annual treatments to prevent LF have risen from 10 million in 2000 to 385 million, or 29 percent of the population at risk in 53 of the 71 MDA-eligible countries. Thirteen countries have not yet completed mapping for LF as of 2009 (WHO, 2010e). Elimination of LF is progressing, but it needs to be accelerated in order to reach its goal by 2020.

With Carter Center assistance, two Nigerian states have pioneered integrated health education and MDA for onchcocerciasis, LF, and schistosomiasis since 2000 (Njepuome et al., 2009). I believe APOC and the new war on LF should have joined forces immediately to take advantage of synergies. LF is more widespread than onchocerciasis in Africa and so MDA with Mectizan and albendazole for LF not only covers additional villages where onchocerciasis is hypo-endemic and was not being treated, it also adds a second antihelminthic, albendazole, in all onchocerciasis-endemic areas. It is hoped that combined MDA with Mectizan and albendazole for LF will have an enhanced impact on adult onchocercal parasites. Both drugs are contraindicated for mass drug administration in Loa loa areas, but bednets can be used there instead to block transmission of LF and malaria. Other studies in Nigeria by Blackburn et al. (2006) and other colleagues at CDC and the Carter Center have demonstrated the efficacy of using community-based distributors of Mectizan to also distribute bednets. Thus, scaling up integrated MDA and mass distribution of long-lasting insecticidal nets in Africa by mobilizing CDTI-type volunteers could help control or eliminate malaria, LF, onchocerciasis, and schistosomiasis, with significant collateral impact on soil-transmitted helminths. We have the tools and knowledge to do this now; two states in Nigeria are doing it already.

Before turning to trachoma, I want to highlight another initiative proposed by the ITFDE, which is the elimination of LF and malaria from the island of Hispaniola. This island, comprising the Dominican Republic and Haiti, is the main remaining focus of lymphatic filariasis in the Western Hemisphere and the only Caribbean island that is still endemic for malaria (Figure A6-2). It is a source of exported malaria to neighboring countries, including Jamaica, the Bahamas, and the United States. After a 1.5 year-long collaborative project to combat malaria in two adjacent communities on their shared border, in October 2009 the two countries announced a jointly prepared plan to eliminate malaria from the island by 2020 at an estimated cost of $194 million, while Haiti announced a plan to escalate its existing efforts and also eliminate LF by 2020 at a cost of about $49 million. The Dominican Republic expects to stop transmission of LF in 2010. These are expensive plans, but they are put in perspective by knowledge that a single outbreak of malaria in 2004 cost the Dominican Republic an estimated $200 million in lost tourism revenues alone, apart from loss of life and productivity.

Trachoma

Trachoma is a blinding bacterial infection that is spread by contaminated hands, cloths, and flies. An estimated 540 million persons were at risk and 84 million infected in about 57 countries in 1998, when WHA established a target to eliminate blinding trachoma (not all infections, and not the bacterium) by 2020 (WHO, 2010a). The “SAFE Strategy” for combatting trachoma consists of (S) surgery to prevent progression to blindness, (A) antibiotic administration to treat active infections and prevent spread, (F) facial cleanliness, and (E) environmental improvement, including access to clean water and building household latrines to suppress breeding of vector flies in human feces deposited on the ground. The minimal coverage target for antibiotic administration is 80 percent. The quantified goals are to reduce scarring trachoma, or trichiasis, to less than 1 case per 1,000 population and reduce active trachoma below 5 percent in 1–9-year-old children. Further recommendations for assessing these targets were considered recently at the third Global Scientific Meeting on Trachoma that was convened by WHO in July 2010. Like the three other elimination and eradication efforts considered here, the trachoma program also has significant ancillary benefits, due to improved personal hygiene, expanded use of household latrines, and advocacy for clean water. An explosion of latrine building is under way in the Amhara Region of Ethiopia (Ngondi et al., 2010) as a result of the trachoma program, totaling almost 1.8 million latrines since 2002. Wider use of latrines also prevents other diseases besides trachoma.

Pfizer has donated Zithromax^® for use in this mass campaign with a cumulative total of 160 million treatments between 1999 and 2009. As of 2009, this program was reaching about 40 million (33 percent) of the 120 million people thought to be at risk, but the full extent of the problem is not clear. At least eight countries, including Morocco and Ghana, have reduced key indices below prevalence thresholds established by WHO. Overall, the number of countries where trachoma is endemic has been reduced from 57 to somewhere between 38 and 49, the estimated population at risk from 540 million to 120 million, and the number of persons with active disease from 84 million to about 41 million between 1998 and 2009 (Mariotti et al., 2009; WHO, 2010a). It is believed that probably only 10 countries contain 75 percent of the problem. Ethiopia, perhaps the most severely affected country, has begun an aggressive campaign in its worst affected region, Amhara, but needs to extend those efforts nationwide.

But much more remains to be done. Figure A6-3 illustrates the principle that it is best to start intervening in the most highly endemic countries first, because they will take longer to be brought under control. The ITFDE, which I chair, reviewed the status of the global effort to eliminate blinding trachoma by 2020 at its meeting in October 2010. It concluded that it is still possible to reach the thresholds defined by WHO by 2020, but doing so will require significant acceleration of interventions, ascertaining the status of the disease in remaining endemic countries quickly, and implementing the full SAFE strategy in all affected areas of the highest endemic countries within the next two or three years.

Table A6-2 summarizes the current status of elimination efforts against these four NTDs. Dracunculiasis is approaching eradication, onchocerciasis will soon be eliminated in the Americas, and LF is scaling up to possibly become the second parasitic disease to be eradicated. We eagerly await results from the current initiatives against onchocerciasis in Africa, and from scaling up the campaign to eliminate blinding trachoma.

These times of exceptional opportunities and inspiring progress are as exciting for us professionals as they are important to improving the human condition. Most NTDs cannot be eradicated or eliminated, but all can and should be much better controlled. The few NTDs that may be vulnerable to elimination or eradication should be pursued ruthlessly.

More than 2,000 years ago, St. Paul reminded his contemporaries that they were surrounded by a cloud of witnesses as they ran the races (of life) before them. And so are we. We should be mindful of what our own witnesses are seeing, and perhaps, of what they will say when we meet them.

Acknowledgments

The author wishes to thank Ms. Shandal Sullivan for assistance in preparing this manuscript. He also acknowledges the work of Drs. Ernesto Ruiz-Tiben, Frank Richards, and Paul Emerson, all from the Carter Center, which contributed to some of the content of this paper.

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