The following entry was submitted by Katherine Anderson, a student from the University of New Hampshire majoring in Biomedical Sciences – Medical Laboratory Science.

Written by Katherine Anderson

BMS 720.H. May 2019

Neglected tropical diseases (NTDs) are a group of tropical infections that collectively represent a massive health and socioeconomic problem that is only recently being acknowledged by global health advocates (Hotez 5). As the name implies, these diseases are often overlooked by medical professionals since they only afflict certain parts of the globe, most of them being under-developed nations. Since NTDs flourish mostly in these areas and not in the developed world, research into treatment and prevention is often limited. It is because of this that NTDs are still a major health problem in some areas even though many of them could be eradicated with sufficient resources. The World Health Organization (WHO) has proposed a list of 17 diseases that are considered as NTDs. These include helminth (worm), protozoan, bacterial, and viral infections (Hotez 4). Helminth infections rank as the most prevalent of all of them, with Ascariasis and Hookworm infections topping the chart with estimated global prevalence of 800-900 million and 600-700 million respectfully. The regions of highest prevalence are the same for both of these diseases, affecting predominantly East and South Asia, Africa, and Latin America (Hotez 5). The viral infection Dengue follows these, infecting 50-100 million people predominantly from East and South Asia. The next most prevalent NTD that is of neither helminth nor viral origin is Trachoma, a bacterial infection in 20 million people predominantly residing in Africa, the Middle East, and Asia. Just below this on the list is the first most popular condition caused by a protozoan, Leishmaniasis. This disease is estimated to infect 10 million people globally, most from South Asia, Africa, the Middle East, and Latin America.

The pathogenesis of NTDs is often described as high in morbidity and low in mortality. This is referring to the fact that many NTDs cause serious chronic illness and disability, but do not cause death in the patient as often as other global threats with more attention in the medical community, such as HIV/AIDS. This can make it difficult to assess the full health impact of NTDs since there are no obvious metrics such as death toll to measure the devastation of these diseases. One approach to quantify this would be using disability-adjusted life years, or DALYs. This numerical data considers the number of healthy life years lost from either premature death or disability (Hotez 10). Since NTDs are trademarked by their ability to cause chronic, disfiguring illness, many of them have significantly high DALYs ascribed to them. In fact, when comparted to HIV/AIDS which has an annual total of 84.5 million DALYs, NTDs collectively have an annual 56.6 million. Although this number is still significantly smaller, it still shows how NTDs can be compared to some of the world’s most dangerous conditions. This figure also puts NTDs ahead of other more frequently studied diseases such as malaria (46.5 million DALYs annually) and Tuberculosis (34.7 million DALYs annually) (Hotez 10).

Elephantiasis is the most severe result of lymphatic filariasis (LF), a chronic infection caused primarily by the parasite Wuchereria bancrofti, which is endemic to much of Africa, Asia, and South America (Hotez 61). Although this illness is still a health concern for much of the developing world, there has been significant progress made toward the elimination, or the reduction of prevalence, of the disease. LF is transmitted upon infection of a person with infective larvae from a mosquito bite. Once inside the body, the larvae migrate over a period of several months to their destination, the lymphatics, where they develop into adult worms. These worms can live for years in the lymph vessels and produce microfilariae that continue to inhabit the blood and lymph and can cause blockages in the ducts and inflammation from the immune response leading to the swelling of the lymphatics. Over time the swelling progresses to a point where the limb and the skin covering it look like an elephant’s leg, thus the term elephantiasis. The swelling can result in a loss of mobility, which is a dramatic consequence for working people of the developing world who rely on their health to work in physically demanding jobs such as farming. It was this loss of mobility that also created a massive problem for U.S. troops fighting in the South Pacific during World War II. Approximately 38,300 soldiers were exposed to W. bancrofti during this time, and around one-third of them developed filarial fevers (Hotez 61). This led American scientists to become more interested in controlling LF and resulted in more effective drug treatments for the disease. In the 1950s and 1960s, Frank Hawking helped demonstrate that a compound known as diethylcarbamazine, or DEC, was very effective against the contagious stage of W. bancrofti. It was discovered that even though DEC did not affect the pathological adult stage of the parasite, it did lower the number of microfilariae among mass populations when it was distributed widely. This meant that the transmission step of the disease was interrupted and thus the prevalence of LF in the community decreased. Though this breakthrough was meaningful, it meant little until scientists overcame the challenge of convincing entire communities to take a preventative drug. It was Frank Hawking who thought to fortify dietary salt with DEC and distribute it amongst the population. This idea was adopted by the People’s Republic of China shortly after Hawking proposed it, and the result was blanket coverage of the nation with DEC-fortified salt and eventually the successful elimination of LF. Other countries also began to administer the drug as salt and in tablet form and saw great success. In fact, today 20 countries have eliminated LF through mass drug administration (Hotez 64). The continued success of DEC has encouraged more and more countries around the world to adopt a similar methodology when it comes to controlling LF, a promising ripple effect.

Dracunculiasis is another chronic infection that is caused by the parasite Dracunculus medinensis, also known as the guinea worm, which is endemic in the poorest areas of Africa, the Middle East, and Asia. Due to the efforts of the Carter Center in cooperation with the CDC, UNICEF, and WHO, the disease is nearly eradicated today. The larvae of D. medinensis survive in freshwater and continue development when they are swallowed by small crustaceans called copepods. Humans become infected when they swallow unfiltered or unboiled water containing copepods which harbor D.medinensis (Hotez 67). The larvae survive the gastric juices of the stomach and penetrate the gut in order to migrate to the connective tissue of the legs where they sexually mature and eventually dig through the skin in a painful blister. In an effort to seek soothing comfort from the burning sensation of the blister, the afflicted person will likely seek a water source to submerge their leg in, and this water is where the blister will rupture and the female adult worm will release thousands of larvae, continuing the life cycle of D. medinensis. The severe pain of the infection often leaves the individual incapacitated and unable to work. In villages where epidemics strike during a harvest or planting season, the agricultural productivity of the entire population would be severely affected (Hotez 68). The grave economic and health impacts of D. medinensis are only part of what made this disease an attractive target for eradication. In the early 1980s the world was ecstatic about the successful eradication of smallpox through widespread vaccination, the last naturally occurring case was recorded in 1977 and by 1981 the world was certified free of smallpox (Hotez 69). Eager to apply this success to other diseases, the CDC suggested dracunculiasis as a new target for eradication because of its relatively low prevalence, and the simple methodology that could be employed to reduce its effect on communities. The most effective strategies were health education and behavioral changes, like filtering water through cloth to remove copepods and avoiding public water supplies during active infection (Hotez 69). Once U.S. President Jimmy Carter began supporting the efforts to eradicate the disease, the world saw great progress in this goal. Resolutions were made to approach the disease by creating deep wells for water which were free of copepods, to filter drinking water, increase the quality of health education on the disease, and case containment and management of people already infected (Hotez 69). Over the last 25 years the Dracunculiasis Eradication Program or DEP has had incredible continued success in the 21^st century, with only about 1,000 cases of guinea worm infection remaining worldwide (Hotez 70).

Despite the strides made to combat infection caused by W. bancrofti and D. medinensis, there are many prevalent NTDs that still devastate much of the world today. Many of these diseases could be eliminated fairly easily with health education and medication, but the world has yet to make substantial progress. This is due to the nature of the organisms that cause NTDs. The organisms are most often obligate parasites that can only survive in a living host. It is in the best interest of the parasite to keep its host alive for many years while it infects and extracts whatever it needs to mature and spread. The biology of these parasites is what leads to the trademark chronic and debilitating symptoms of NTDs. In the case of lymphatic filariasis, for example, the swelling of the limbs is so great over time that mobility can be nearly impossible for the infected individual. It is because of this chronic nature of tropical diseases that we can analyze the neglect the world has for them on an increasing scale from local to international proportions. In areas where NTDs are common there are stigmas associated with debilitating disease that make it difficult for people to seek treatment if they are worried about keeping jobs that involve a great deal of mobility, like those in agriculture or construction. A worker in a developing country who makes barely enough in wages to feed their family is unlikely to acknowledge their disease and seek treatment that may not be readily available to them if they are worried about to making it to work every day. When this person ignores their infection, it can eventually reach a point when the damage is too great and they are either permanently debilitated or now face disabilities that require an extensive treatment to resolve. In the case of a manual worker, the financial consequences to these kinds of diseases are extremely difficult. In the case of a rural village that depends on the export of crops and the people who cultivate them, parasitic outbreaks can drastically affect the economy. Essentially, the outbreaks make poor communities even poorer and therefore limit their resources and funding. The poorest areas of the world are often the most neglected by their nations and subsequently by the rest of the world. Additionally, since NTDs cause damage chronically and are not well quantified by death toll, global health agencies often overlook the seriousness of these conditions. Looking at NTDs in terms of lives taken, the numbers are not as impressive when compared to Tuberculosis or HIV/AIDS. Agencies like the World Health Organization (WHO) have more often spent their time and resources fighting diseases with greater rates of fatalities because those are the more measurably profound threats.

One of the most serious NTDs that is widely neglected in the public health sector is cysticercosis, a parasitic infection that causes seizures and other long-term neurological symptoms. It is acquired via ingestion of Taenia solium in raw or undercooked pork meat (Hotez 170). Following ingestion of the parasite encysted in the muscle tissue of the infected pig, immature larvae of T. solium will migrate to the intestinal wall where they attach and grow into adult tapeworms. Adult worms are shed in segmented parts filled with eggs in feces, and the infection can be spread from person to person through fecal-oral contamination that enables the ingestion of these eggs. After the eggs are ingested, larvae invade the walls of the digestive tract and enter the circulatory system where they are free to spread to the muscles and the brain, where they form cysts and cause neurocysticercosis (Hotez 170). Cysts in the brain can cause seizures, encephalitis, hydrocephalus, and many other neurological complications. After a diagnosis from radiographic imaging the most effective treatments are anticonvulsants and anti-parasitic drugs like albendazole. Cysticercosis is currently endemic to much of Mexico and Central America, and it is starting to become a health concern in the Southern United States due to a large influx of Hispanic immigrants. Today, an estimated 1,000 to 2,000 new cases of neurocysticercosis are diagnosed annually, making it one of the leading causes of epilepsy in the United States (Hotez 170). This number may even be higher, however, since it has only been within the last few years that states have mandated reporting at all (Hotez 170). There have been many estimates on the prevalence of this condition in the United States, which are based mostly on the number of rural Hispanic immigrants living in the United States. The conclusion is that southwestern U.S. cities with large Hispanic populations tend to have many more reported cases than normal for these areas. For example, neurocysticercosis is now the cause of 10% of all seizures and 10% of neurology neurosurgery admissions to numerous emergency departments in Los Angeles. The large number of possible cases of cysticercosis suggests there is an urgent need for better surveillance and treatment (Hotez 171). I and they ensure that their seal of approval on pork meat indicates safety from organisms like Trichinella spiralis, Escherichia coli, Salmonella, Staphylococcus aureus, Yersinia enterocolitica and Listeria monocytogenes. Currently on the USDA’s watchlist there are no indications or warnings of the dangers of T. solium in pork meat (2). Enhanced efforts on the education and awareness of cysticercosis could make a crucial difference in preventative care. Another control method could be the investment in better diagnosis practices and treatment. Right now, the only such practices for neurocysticercosis are radiographic imaging, which is costly and not practical for America’s poorest populations. This diagnostic strategy is not ideal especially when considering how many imported cases occur in the United States every year. Many people immigrating from Central America could be bringing the infection along with them that was acquired in their country of origin, but without low cost screening for T. solium, the U.S. is left vulnerable to the risk of the infection spreading through this individual. Once the infection spreads and people receive a diagnosis of cysticercosis, the drugs we use to combat the infection are mostly anticonvulsants, which target only the symptoms of the disease and not the causative agent itself. These drugs do not help in the disease progression but rather mask the dangerous effects of it. Research into the formation of T. solium cysts does not provide many answers for a patient who already has them since we currently have no way of removing or reversing them. More widespread education, prevention, and more targeted and informed diagnostic strategies and treatments are methods that have been successful for NTDs in the past and could work for cysticercosis too with enough determination from the health care leaders of the world.

Despite the widespread devastation that neglected tropical diseases bring to the world’s poorest populations, they are largely still fitting of their title. The chronic and debilitating effects that these infections cause is just the beginning of their course, which often leads to financial burden to the individual and in some areas even economic turmoil for the community. Even with the success stories of NTDs like lymphatic filariasis and guinea worm that have largely been eradicated through means of relatively low cost, there remain many parasitic infections that go unnoticed by the world’s leading health agencies. It is these agencies, however, that could make a real difference in the fight against NTDs in the developing world and could help save years of people’s lives.

 

 

Works Cited

 

“Fresh Pork from Farm to Table.” Food Safety and Inspection Service, United States Department

of Agriculture, 6 Aug. 2013, http://www.fsis.usda.gov/wps/portal/fsis/topics/food-safety-education/get-answers/food-safety-fact-sheets/meat-preparation/fresh-pork-from-farm-to-table/ct_index.

 

Hotez, Peter J. Forgotten People Forgotten Diseases: The Neglected Tropical Diseases and

Their Impact on Global Health and Development. 2nd ed., ASM Press, 2013.