Forgotten People Forgotten Diseases: The Neglected Tropical Diseases and Their Impact on Global Health and Development, Second Edition

The neglected tropical diseases (NTDs) are the most common infections of the world’s poorest people, and the soil-transmitted helminth (STH) infections are the most common NTDs. The three most important STH infections of humans, based on their prevalence and global disease burden, are: (i) Ascaris infection (also known as roundworm infection or ascariasis); (ii) hookworm infection (hookworm); and (iii) Trichuris infection (whipworm infection or trichuriasis). Together, these helminth infections afflict more than 1 billion people in developing countries. The intestines of hundreds of millions of children living in Africa, Asia, and the Americas harbor a menagerie of worms. Harold Brown, the late former parasitology professor at Columbia University College of Physicians and Surgeons, frequently referred to Ascaris, Trichuris, and hookworms as “the unholy trinity” to indicate that it was extremely common for a child to be infected with all three parasites simultaneously. In addition to their enormous global prevalence and their intimate link with rural poverty, another important feature of STH infections is their predilection for affecting children more than adults. The unholy trinity adversely affects the neuropsychiatric activities of children, in turn damaging school performance and reducing school attendance. Currently, the most effective approach to the control of STH infections is through deworming of large populations through mass drug administration of anthelmintic drugs belonging to the benzimidazole class (sometimes referred to as benzimidazole anthelmintics or BZAs).

Elephantiasis is the most severe and dramatic complication of lymphatic filariasis (LF), a chronic infection caused primarily by the filarial parasite Wuchereria bancrofti. Dracunculiasis is another chronic infection caused by a filaria-like parasite, Dracunculus medinensis, also known as the guinea worm. Although both LF and dracunculiasis are still important public health problems in the developing world, we are much farther along in our global efforts to control these ancient scourges. For LF, ivermectin, diethylcarbamazine (DEC), and albendazole are donated free of charge. Therefore, LF mass drug administration can be provided for less than US$1 per person. Similarly, the estimated cost of the Dracunculiasis Eradication Program (DEP) between 1987 and 1998 was $87.5 million, or approximately US$5 to $8 per prevented case. In their own ways, LF mass drug administration and the DEP have been wildly successful. Given dramatic rates of guinea worm reduction over the last 25 years and now the stepped-up measures in Sudan through a new Sudan Guinea Worm Eradication Program, there is optimism about achieving these goals. Major reasons for success include the availability of simple interventions together with President Carter’s high-level advocacy and excellent coordination by the Carter Center and its partners. For LF, wherever elimination efforts have been aggressively pursued, the outcome has been extremely favorable.

Mycobacteria are slim bacteria with unusual growth requirements and unique structural and biochemical properties that place them in their own category of microorganisms. Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the best-known mycobacterial infection of humans. Buruli ulcer and leprosy are two highly disfiguring and stigmatizing neglected tropical diseases (NTDs) that occur almost exclusively among the impoverished living in developing countries. Buruli ulcer is a highly disfiguring skin infection caused by M. ulcerans. Buruli typically strikes school-age children and manifests as a large ulcer usually appearing on the limbs. The ulcer of Buruli disease has a number of catastrophic consequences for the patient, including a profound socioeconomic impact and the widespread belief that witchcraft and curses play an important role in transmitting the disease. The most effective treatment of large ulcers requires access not only to antibiotics but also to different surgical modalities, including skin grafting. Leprosy (also known as Hansen’s disease) is caused by M. leprae. Leprosy proceeds along either one of two clinical courses. The majority of patients develop the so-called tuberculoid form. Such patients have the ability to mount strong immunological responses against M. leprae and, as a result, develop only localized disease. Far more severe is the lepromatous form of leprosy. These patients experience widely disseminated disease in the skin and nerves and even the eyes, nose, mouth, and bones. The most widely used multidrug therapy (MDT) drug regimen calls for dapsone to be administered together with the antibacterial drugs rifampin and clofazimine.

The neglected tropical diseases (NTDs) leptospirosis, dengue, and rabies have particular importance as urban health problems in developing countries. Leptospirosis is one of the world’s most common zoonoses, transmitted through contact with bodies of water, such as canals and sewers, contaminated with leptospires. In urban areas, contamination occurs through exposure to the urine of rats and stray dogs, which teems with leptospires. Adequate prevention requires having an intact system of surveillance and case detection as well as environmental control. Dengue fever is one of the most common NTDs of urban areas, and the number of dengue cases is expected to rise as a consequence of increasing urbanization and global warming. Dengue is caused by a single-stranded RNA flavivirus and transmitted by the bite of a female Aedes mosquito. A. aegypti is the most common insect vector species. The most feared complication of dengue is dengue hemorrhagic fever (DHF), which is associated with severe morbidity. No vaccine is yet available for dengue, and public health control relies on labor-intensive practices of environmental vector control. Approximately 50,000 people die from rabies annually. Most of these deaths occur as the result of stray-dog bites in developing countries. There is also an enormous economic toll from rabies. This is because of the need to administer postexposure prophylaxis (PEP) with rabies vaccine to almost anyone bitten by a dog in developing countries. The public health control of rabies in many countries has been achieved through aggressive campaigns to vaccinate dogs in urban centers.

The neglected tropical diseases (NTDs) are among the leading disabling conditions of humankind. According to one estimate the NTDs result in 56.6 million disability-adjusted life years (DALYs ), i.e., the number of healthy life years lost from disability or premature death) lost annually. Mass drug administration (MDA) has been effective against NTDs. The World Health Assembly (WHA) has adopted a number of ambitious resolutions over the years to promote the use of MDA for NTDs. In order to raise awareness about the NTDs and the promise of integrated NTD control, the Global Network for Neglected Tropical Diseases was established by the Sabin Vaccine Institute in 2006 to work with the health ministries in countries where the diseases are endemic. It focuses its activities primarily on advocacy, resource mobilization, bilateral engagement (parliaments and ministries of health), and international development banks in order to achieve the overall goal of increasing access to essential medicines for the estimated 1.4 billion people affected by the major NTDs targeted through preventive chemotherapy. Doing so would improve childhood development, school attendance and performance, pregnancy outcomes, and worker productivity among the world’s poorest populations. Integrated control of the NTDs is under way in at least seven sub-Saharan African countries.

A global assault on the NTDs through both widespread deployment of rapid-impact packages and the simultaneous development and implementation of new control tools could one day become a highly productive application of medical science and public health for repairing the world. The control and elimination of the NTDs may also provide added global benefit in light of the underappreciated link between NTDs and human conflict. The examples of human African trypanosomiasis (HAT), onchocerciasis, lymphatic filariasis (LF), Chagas disease, and leishmaniasis illustrate an intimate link between the NTDs and long-standing conflict. The common features of this relationship include reductions in public health control programs because of violence and a shifting of limited resources in favor of military spending and buildup. A new government-academic- industrial enterprise devoted to NTDs can offer an unprecedented new opportunity for reducing global poverty and repairing the world. We have in hand today an extraordinary toolbox of highly effective preventive chemotherapeutic drugs and the technological capacity to build a new generation of drugs and vaccines. We have a win-win opportunity to control and eliminate humankind’s major NTDs and need to act in a timely manner and with great efficiency.