Neglected tropical diseases

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A young boy from Panama with Chagas disease. It has manifested as an acute infection with swelling of one eye (chagoma).

The neglected diseases are a group of tropical infections which are especially endemic in low-income populations in developing regions of Africa, Asia, and the Americas. Different organizations define the set of diseases differently. In sub-Saharan Africa, the impact of these diseases as a group is comparable to malaria and tuberculosis.[1] Some of these diseases have known preventive measures or acute medical treatments which are available in the developed world but which are not universally available in poorer areas. In some cases, the treatments are relatively inexpensive. For example, the treatment for schistosomiasis is USD $0.20 per child per year.[2] Nevertheless, control of neglected diseases is estimated to require funding of between US$2 billion to US$3 billion over the next five to seven years.[3]

These diseases are contrasted with the big three diseases (HIV/AIDS, tuberculosis, and malaria), which generally receive greater treatment and research funding. The neglected diseases can also make HIV/AIDS and tuberculosis more deadly.[4] However, some pharmaceutical companies have committed to donating all the drug therapies required and mass drug administration has been successfully accomplished in several countries.[5]

List of diseases[edit]

There is some debate between the WHO, CDC, and infectious disease experts over which diseases are classified as neglected tropical diseases. Feasey, a neglected tropical disease researcher, notes 13 neglected tropical diseases: ascariasis, Buruli ulcer, Chagas disease, dracunculiasis, hookworm infection, human African trypanosomiasis, Leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma, and trichuriasis.[6] Fenwick recognizes 12 "core" neglected tropical diseases: Ascariasis, Buruli ulcer, Chagas disease, dracunculiasis, human African trypanosomiasis, Leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma, and trichuriasis.[7] The World Health Organization (WHO) recognizes the following as neglected tropical diseases:[8] Cryptococcal meningitis despite its large burden of disease is not considered neglected, as its HIV/AIDS-related.[9]

Buruli ulcer[edit]

It is not known how common Buruli ulcer are.[6] The risk of mortality is low, although secondary infections can be lethal.[10] Morbidity takes the form of deformity, disability, and skin lesions, which can be prevented through early treatment.[10] The disease is caused by bacteria[10] and treated with antibiotics and surgery.[10] It is found in Africa, Asia, and Latin America.[11] The symptoms are skin swellings and lesions.[10]

Chagas disease[edit]

Chagas disease is also known as American trypanosomiasis. There are approximately 15 million people infected with Chagas Disease.[6] The chance of morbidity is higher for immuno-compromised individuals, children, and elderly, but very low if treated early.[12] Chagas disease does not kill victims rapidly, instead causing years of debilitating chronic symptoms. It is caused by a vector-borne[13] protozoa[12] and spread by contact with Trypanosoma cruzi infected feces of the triatomine (assassin) bug. The protozoan can enter the body via the bug's bite, skin breaks, or mucous membranes. Infection can result from eating infected food and coming into contact with contaminated bodily fluids.[12] Chagas disease can be prevented by avoiding insect bites through insecticide spraying, home improvement, bed nets, hygienic food, medical care, laboratory practices, and testing.[12] It can be treated etiologically or with drugs, although the drugs used to treat Chagas disease have severe side effects[12] There are two phases of Chagas disease. The acute phase is usually asymptomatic. The first symptoms are usually skin chancres, unilateral purplish orbital oedema, local lymphoadenopathies, and fever accompanied by a variety of other symptoms depending on infection site.[12] The chronic phase occurs in 30% of total infections[6] and can take three forms, which are asymptomatic (most prevalent), cardiac, and digestive lesions.[12] It can be diagnosed through a serological test, although the test is not very accurate.[6]

Cysticercosis and taeniasis[edit]

Cysticercosis is an adult tapeworm infection. Taeniasis is a tapeworm larvae infection.[14] They are the most common infections of the central nervous system.[15] Taeniasis is not fatal, although cysticercosis can cause epilepsy and neurocystocercosis can be fatal.[15][16] Cysticercosis is usually contracted after eating undercooked contaminated pork. Taeniasis occurs after ingestion of contaminated food, water, or soil.[14] Taeniasis has mild symptoms, including abdominal pain, nausea, diarrhoea or constipation. Cysticercosis involves cysts and lesions that can cause headaches, blindness, seizures, hydrocephalus, meningitis, and dementia.[16] Drugs are used to treat both disease.[16] Infection can be prevented through stricter meat-inspection standards, livestock confinement, improved hygiene and sanitation, health education, safe meat preparation, and identifying and treating human and pig carriers.[17] It is found in Asia, Africa, Latin America, particularly on farms in which pigs are exposed to human excrement.[15]

Dengue fever[edit]

There are 50-100 million dengue fever infections annually.[18] Dengue fever is usually not fatal, but infection with one of four serotypes can increase later susceptibility to other serotypes, resulting in a potentially fatal disease called severe Dengue.[18] Dengue fever is caused by a flavivirus, and is spread mostly by the bite of the A. Aegypti mosquito.[18] No treatment for either Dengue or severe Dengue exists beyond palliative care.[18] The symptoms are high fever and flu-like symptoms.[18] It is found in Asia and Latin America.[18]

Dracunculiasis[edit]

Dracunculiasis is also known as Guinea-worm disease. There were 113 cases of Dracunculiasis in 2013, a decrease from 542 cases in 2012,[19] and a substantial decrease from 3,500,000 cases in 1986.[20] It is not fatal, but can cause months of inactivity.[19] It is caused by drinking water contaminated by water fleas infected with guinea-worm larvae.[19] It is usually treated by World Health Organization volunteers who clean and bandage wounds caused by worms and return daily to pull the worm out a few more inches.[19] Approximately one year after infection, a painful blister forms and one or more worm emerges. Worms can be up to 1 meter long.[19] Dracunculiasis is preventable by water filtration, immediate case identification to prevent spread of disease, health education, and treating ponds with larvicide. An eradication program has been able to reduce prevalence.[19] As of 2012, the four endemic countries are Chad, Ethiopia, Mali, and South Sudan.[19]

Echinococcosis[edit]

The rates of echinococcosis is higher in rural areas, and there are more than one million people infected currently.[21] Untreated alveolar echinococcosis is fatal.[22] It is caused by ingesting parasites in animal feces.[23] Surgery and drugs can both be used to treat echinococcosis.[22] There are two versions of the disease: cystic and alveolar. Both versions involve an asymptomatic incubation period of several years. In the cystic version, liver cysts cause abdominal pain, nausea and vomiting while cysts in the lungs cause chronic cough, chest pain, and shortness of breath. In alveolar echinococcosis, a primary cyst develops, usually in the liver, in addition to weight loss, abdominal pain, general feeling of ill health, and signs of hepatic failure.[22] It can be prevented by deworming dogs, sanitation, proper disposal of animal feces, health education, and livestock vaccination.[24] Cystic echinococcosis is found in the eastern portion of the Mediterranean region, northern Africa, southern and eastern Europe, the southern portion of South America, and Central Asia. Alveolar echinococcosis is found in western and northern China, Russia, Europe, and northern North America.[23] It can be diagnosed through imaging techniques and serological tests.[24]

Human African trypanosomiasis[edit]

Human African trypanosomiasis is also known as African sleeping sickness. There are fewer than 10,000 cases currently.[25] The disease is always fatal if untreated. Human African trypanosomiasis is vector-borne,[13] and spread through the bite of the tsetse fly. The current forms of treatment are highly toxic and ineffective as resistance is spreading. The most common symptoms are fever, headache, lymphadenopathy, nocturnal sleeping pattern, personality change, cognitive decline, and coma. It is diagnosed through an inexpensive serological test.

Leishmaniasis[edit]

The three forms of leishmaniasis are visceral (Kala-azar), cutaneous, and mutocutaneous.[26] There are an estimated 12 million people infected.[6] It is fatal if untreated and 20,000 deaths from visceral leishmaniasis occur annually.[27] It is a vector-borne disease[13] that is caused by the bite of sandflies. The only method of prevention is a vaccine that is under development and preventing sandfly bites. It can be treated with expensive medications.[28] At least 90% of visceral leishmaniasis occurs in Bangladesh, Brazil, Ethiopia, India, South Sudan and Sudan. Cutaneous leishmaniasis occurs in Afghanistan, Algeria, Brazil, Colombia, Iran, Pakistan, Peru, Saudi Arabia and Syria. Around 90% of mutocutaneous leishmaniasis occurs in Bolivia, Brazil, and Peru.[26] Diagnoses can by made by identifying clinical signs, serological tests, or parasitological tests.[29]

Leprosy[edit]

There were 189,018 known cases of leprosy in March 2013, and 232,857 new cases were diagnosed in 2012.[30] There are 1-2 million individuals currently disabled or disfigured due to past or present leprosy.[31] Leprosy causes disfigurement and physical disabilities if untreated. It is curable if treated early.[31] It is caused by bacteria and transmitted through droplets from the mouth and nose of infected individuals.[32] Treatment requires multidrug therapy.[30] The BCG vaccine has some preventative effect against leprosy. Leprosy has a 5-20 year incubation period, and the symptoms are damage to the skin, nerves, eyes, and limbs.[32] It is found in Angola, Brazil, Central African Republic, Democratic Republic of the Congo, India, Madagascar, Mozambique, Nepal, Tanzania.[30]

Lymphatic filariasis[edit]

Lymphatic filariasis is also known as elephantiasis. There are approximately 120 million individuals infected[33] and 40 million with deformities.[7]

It is rarely fatal.[34] Lymphatic filariasis has lifelong implications, such as lymphoedema of the limbs, genital disease, and painful recurrent attacks. Most people are asymptomatic, but have lymphatic damage. Up to of 40% of infected individuals have kidney damage.[35] It is a vector-borne disease,[13] caused by nematode worms that are transmitted by mosquitos.[35] It can be treated with cost-effective antihelminthic treatments,[36] and washing skin can slow or even reverse damage.[37] It is diagnosed with a finger-prick blood test.[34] Approximately two-thirds of cases are in Southwest Asia and one-third in Africa.[33]

Onchocerciasis[edit]

Onchocerciasis is also known as River blindness. There are 37 million people infected[6] and prevalence is higher in rural areas.[38] It causes blindness, skin rashes, lesions, intense itching and skin depigmentation.[39] It is a vector-borne[13] disease, caused by filarial worm infected blackflies.[39] It can be treated through drugs.[39] It can be prevented by insecticide spraying and large scale ivermectin treatment[38] The symptoms are generally itching and skin lesions.[38] Over 99% of cases are in Sub-saharan Africa.[38]

Rabies[edit]

There are two forms of rabies: furious and paralytic. There are 60,000 deaths from rabies annually.[40] There is a higher prevalence in rural areas and it disproportionately affects children.[41] Rabies is usually fatal after symptoms develop.[42] It is caused by a lyssavirus transmitted through wounds or bites from infected animals.[41] It can be prevented through the vaccination of humans and dogs,[41] and cleaning and disinfecting bite wounds (Post-exposure Prophylaxis).[42] The first symptoms are fever and pain near the infection site which occur after a 1-3 month incubation period. Furious (more common type) rabies causes hyperactivity, hydrophobia, aerophobia, and death by cardio-respiratory arrest occurs within days. Paralytic rabies causes a slow progression from paralysis to coma to death.[41] Rabies is undiagnosable before symptoms develop. It can be detected through tissue testing after symptoms develop.[41] It is found in Asia and Africa.[40]

Schistosomiasis[edit]

There are over 200 million cases of schistosomiasis.[7] The disease can be fatal by causing bladder cancer and haematemesis.[7] It causes bladder fibrosis, liver fibrosis, portal hypertension, and cervical lesions (which increase HIV susceptibility for women).[7] It is a vector-borne disease.[13] Schistosoma species have a complex life cycle that alternates between humans and freshwater snails; infection occurs upon contact with contaminated water. This disease is unique in that damage is not caused by the worms themselves, but rather by the large volume of eggs that the worms produce.[43] The symptoms are usually haematuria, bladder obstruction, renal failure, bladder cancer, periportal fibrosis, portal hypertension, ascites, varices[disambiguation needed].[6] Inexpensive praziquantel can be used to treat individuals with schistosomiasis, but cannot prevent reinfection. The cost of prevention is 32 cents per child per year.[7] Mass treatment with praziquantel, better access to safe water, sanitation, health education can all be used to prevent schistosomiasis.[6] Vaccines are under development. It can be diagnosed through a serological test, but it often produces false negatives.[7] Approximately 85% of cases in sub-Saharan Africa.[7]

Soil-transmitted helminthiasis[edit]

The three major species are ascariasis (roundworms), trichuriasis (whipworm), and strongyloidiasis.[44] There are 1.5 billion currently infected.[44] The mortality risk is very low.[6] The severity of symptoms depends on number of worms in body, but can include intestinal problems, lack of energy, and compromised physical and cognitive development.[44] Parasitic worms are generally transmitted via exposure to infected human feces and soil.[44] The most common symptoms are anemia, decreased growth, decreased physical fitness, decreased school performance and attendance.[6] The most common treatment is medicine.[44] It can be prevented through food and water sanitation, periodic de-worming, and health education.[44] The recommends de-worming without prior diagnosis.[44] Soil-transmitted heminthiasis occurs in Sub-Saharan Africa, Americas, China, and east Asia.[44]

Trachoma[edit]

There are 21.4 million people infected with trachoma, of whom 2.2 million are partially blind and 1.2 million are blind. The disease disproportionately affects women and children.[45] The mortality risk is very low, although multiple re-infections eventually lead to blindness.[6][45] It is caused by a micro-organism that spreads through eye discharges (on hands, cloth, etc.) and by "eye-seeking flies."[45] It is treated with antibiotics. The only known prevention method is interpersonal hygiene. The symptoms are internally scarred eyelids, followed by eyelids turning inward.[45] It is found in Africa, Asia, Central and South America, Middle East, and Australia.[45]

Yaws[edit]

There is limited data available on the prevalence of yaws, although it primarily affects children.[46] The mortality risk is very low, but the disease causes disfigurement and disability if untreated.[46] It is a chronic bacterial infection, transmitted by skin contact, and caused by treponemes.[46] It is treated with antibiotics.[46] It can be prevented through improved hygiene and sanitation.[46] The most common symptom is skin lesions.[46] It is most prevalent in the warm, moist, tropical regions of the Americas, Africa, Asia, and the Pacific.[46]

Economic impact[edit]

Conteh, Engels, and Molyneux attribute the low cost of treatment for NTDs to the large scale of the programs, free provision of drugs by pharmaceutical companies, delivery modes of drugs, and the un-paid volunteers who distribute the drugs. They also argue that the economic burden of NTDs is undervalued and therefore the corresponding economic impact and cost-effectiveness of decreased prevalence of NTDs is underestimated.[47] The investment return on measures to control neglected tropical diseases is estimated to be between 14-30%, depending on the disease and region.[48] The long term benefits of deworming include a decrease in school absenteeism by 25%, and an increase in adult earnings by 20%.[49]

The cost of treatment of some of these diseases, however, such as Buruli Ulcer, can amount to over twice the yearly income of an average household in the lowest income quartile, while for the highest income quartile, the burden is slightly less than the average household income. These enormous financial costs often cause deferral of treatment and financial ruin, but there is inequality between the wealthy and poor in terms of economic burden. These diseases also cost the government in terms of health care and lost worker productivity through morbidity and shortened life spans.In Kenya, for example, deworming is estimated to increase average adult income by 40%, which is a benefit-to-cost ratio of 100. Each untreated case of Trachoma is estimated to cost $118 in lost productivity. Each case of Schistosomiasis causes a loss of 45.4 days of work per year. Most of the diseases cost the economies of various developing countries millions of dollars. Large scale prevention campaigns are predicted to increase agricultural output and education levels.[47]

Social impact[edit]

Several NTDs, such as leprosy, cause severe deformities that result in social stigma. Lymphatic filariasis, for example, causes severe deformities that can result in denial of marriage and inability to work.[7] Studies in Ghana and Sri Lanka have demonstrated that support groups for patients with lymphatic filariasis can increase participants' self-esteem, quality of life, and social relations through social support and providing practical advice on how to manage their illness.[50]

Deworming treatment is correlated with increased school attendance.[7]

The impact of NTDs is tied to gender in some situations. NTDs disproportionately affect females, especially schistosomiasis, dengue, hookworm infections during pregnancy, and the risk of transferring Chagas Disease during pregnancy.[51] A study in Uganda found that women were more easily able to obtain treatment because they had fewer occupational responsibilities than men and were more trusting of treatment, but ignorance of the effects of medicines on pregnant women prevented adequate care. The paper concludes that gender should be considered when designing treatment programs.[52]

Health impact[edit]

Fenwick claims that the Millennium Development goals, such as education, child mortality, and maternal health are impossible to fulfill with the current high prevalence of NTDs. He also states that many individuals are afflicted by more than one NTD.[7]

Deworming treatments are correlated with healthy weight gain since worms are often partially responsible for malnutrition.[7]

Hotez argues for inclusion of NTDs into initiatives for malaria, HIV/AIDS, and tuberculosis given the strong link between these diseases and NTDs. He also notes the correlation between high rates of NTDs and high rates of non-communicable chronic diseases such as heart disease and cancer. He attributes these to the debilitating effect of NTDs and their long term toll on health.[51]

Reasons for neglect[edit]

Feasey argues that this group of diseases has been overlooked because they mainly affect the poorest countries of the developing world and because of recent emphasis on decreasing the prevalence of HIV/AIDS, tuberculosis, and malaria.[6] Fenwick also argues that far more resources are given to the "big three" diseases, HIV/AIDS, malaria, and tuberculosis, because of their higher mortality and public awareness rates.[7] He states that the importance of neglected tropical diseases has been underestimated since many are asympomatic and have long incubation periods. The connection between a death and a neglected tropical disease that has been latent for a long period of time is not often realized.[7]

Prevention and eradication initiatives[edit]

Fenwick argues that prevention and eradication are important because "of the appalling stigma, disfigurement, blindness and disabilities caused by NTDs."[7] According to a paper by Hotez published in 2013, there is potential for eliminating or eradicating Dracunculiasis, Leprosy, Lymphatic filariasis, Onchocerciasis, Trachoma, Sleeping sickness, Visceral leishmaniasis, and Canine rabies within the next ten years.[51] An open-access journal dedicated to neglected tropical diseases, PLoS Neglected Tropical Diseases, first began publishing in 2007. There is also an international group dedicated to decreasing the prevalence of neglected tropical diseases called the Global Network for Neglected Tropical Diseases Control.[6]

Pharmaceutical market and initiatives[edit]

Biotechnology companies in the developing world have targeted neglected tropical diseases due to need to improve global health.[53]

Mass drug administration is considered a possible method for eradication, especially for lymphatic filariasis, onchocerciasis, and trachoma, although drug resistance is a potential problem.[54] According to Fenwick, Pfizer donated 70 million doses of drugs in 2011 to eliminate trachoma through the International Trachoma Initiative.[7] Merck has helped The African Programme for the Control of Onchocerciasis (APOC) and Oncho Elimination Programme for the Americas to greatly diminished the impact of Onchocerciasis by donating ivermectin.[7] They have also pledged to give 200 million tablets of praziquantel over 10 years.[7] GlaxoSmithKline has donated 2 billion tablets of medicine for lymphatic filariasis and pledged 400 million deworming tablets per year for 5 years in 2010. Johnson & Johnson has pledged 200 million deworming tablets per year.[7] Novartis has pledged leprosy treatment, EISAI pledged 2 billion tablets to help treat lymphatic filariasis.[7]

Policy initiatives[edit]

There are many current prevention and eradication campaigns funded and implemented by the World Health Organization in addition to the US Agency for International Development, the Bill and Melinda Gates Foundation, and the UK Department for International Development.[7]

The U.S. Food and Drug Administration priority review voucher is an incentive for companies to invest in new drugs and vaccines for tropical diseases. A provision of the Food and Drug Administration Amendments Act (HR 3580) awards a transferable “priority review voucher” to any company that obtains approval for a treatment for one of the listed diseases. The voucher can later be used to accelerate review of an unrelated drug. This program is for all tropical diseases and includes medicines for malaria and tuberculosis. The first voucher given was for Coartem, a malaria treatment.[55] It does not use or define the term "neglected" though most of the diseases listed are often included on lists of neglected diseases.

The prize was proposed by Duke University faculty Henry Grabowski, Jeffrey Moe, and David Ridley in their 2006 Health Affairs paper: "Developing Drugs for Developing Countries."[56] In 2007 United States Senators Sam Brownback (R-KS) and Sherrod Brown (D-OH) sponsored an amendment to the Food and Drug Administration Amendments Act of 2007. President George W. Bush signed the bill in September 2007.

NGO initiatives[edit]

There are currently only two donor-funded non-governmental organizations that focus exclusively on NTDs:[57] the Schistosomiasis Control Initiative and Deworm the World. Despite underfunding, many neglected diseases are cost-effective to treat and prevent. The cost of treating a child for infection of soil transmitted helminths and schistosomes (some of the main causes of neglected diseases, as listed above), is less than US $0.50 per year, when administered as part of mass school-based deworming by Deworm the World. This programme is recommended by Giving What We Can and the Copenhagen Consensus Centre as one of the most efficient and cost-effective solutions. The efforts of Schistosomiasis Control Initiative to combat neglected diseases include the use of rapid impact packages; supplying schools with packages including four or five drugs, and training teachers in how to administer them.

See also[edit]

References[edit]

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