| Neglected tropical diseases | |
|---|---|
 | |
| Global overlap of six of the common NTDs. Specifically guinea worm disease, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma in 2011. | |
| Specialty | Infectious disease |
Neglected tropical diseases (NTDs) are a diverse group of tropical infections which are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens such as viruses, bacteria, protozoa and helminths. These diseases are contrasted with the big three infectious diseases (HIV/AIDS, tuberculosis, and malaria), which generally receive greater treatment and research funding. In sub-Saharan Africa, the effect of these diseases as a group is comparable to malaria and tuberculosis. NTD co-infection can also make HIV/AIDS and tuberculosis more deadly.
In some cases, the treatments are relatively inexpensive. For example, the treatment for schistosomiasis is US$0.20 per child per year. Nevertheless, in 2010 it was estimated that control of neglected diseases would require funding of between US$2 billion and US$3 billion over the subsequent five to seven years. Some pharmaceutical companies have committed to donating all the drug therapies required, and mass drug administration (for example mass deworming) has been successfully accomplished in several countries. However, preventive measures are often more accessible in the developed world, but not universally available in poorer areas.
Within developed countries, neglected tropical diseases affect the very poorest in society. In the United States, there are up to 1.46 million families including 2.8 million children living on less than two dollars a day. In countries such as these, the burdens of neglected tropical diseases are often overshadowed by other public health issues. However, many of the same issues put populations at risk in developed as developing nations. For example, other problems can stem from poverty which expose individuals to the vectors of these disease, such as lack of adequate housing.
Twenty neglected tropical diseases are prioritized by the World Health Organization (WHO), though other organizations define NTDs differently. Chromoblastomycosis and other deep mycoses, scabies and other ectoparasites and snakebite envenoming were added to the list in 2017. These diseases are common in 149 countries, affecting more than 1.4 billion people (including more than 500 million children) and costing developing economies billions of dollars every year. They resulted in 142,000 deaths in 2013—down from 204,000 deaths in 1990. Of these 20, two were targeted for eradication (dracunculiasis (guinea-worm disease) by 2015 and yaws by 2020), and four for elimination (blinding trachoma, human African trypanosomiasis, leprosy and lymphatic filariasis by 2020).
List of diseases
There is some debate among the WHO, CDC,
and infectious disease experts over which diseases are classified as
neglected tropical diseases. Feasey, a researcher in neglected tropical
diseases, 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. 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.
These diseases result from four different classes of causative pathogens: (i) protozoa (for Chagas disease, human African trypanosomiasis, leishmaniases); (ii) bacteria (for Buruli ulcer, leprosy, trachoma, yaws), (iii) helminths or metazoan worms (for cysticercosis/taeniasis, dracunculiasis, echinococcosis, foodborne trematodiases, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis); and (iv) viruses (dengue and chikungunya, rabies).
The World Health Organization recognizes the twenty diseases below as neglected tropical diseases.
| WHO/CDC | PLOS Major NTDs |
Others |
|---|---|---|
| Buruli Ulcer Chagas disease Dengue & Chikungunya* Dracunculiasis Echinococcosis Yaws Fascioliasis African trypanosomiasis Leishmaniasis Leprosy Lymphatic filariasis Onchocerciasis Rabies Schistosomiasis Soil-transmitted helminthiasis Cysticercosis Trachoma Scabies and other ectoparasites Snakebite envenoming Mycetoma and deep mycoses |
Protozoan infections:
|
Podoconiosis |
* Only WHO
| ||
Buruli ulcer
Buruli ulcer is caused by the bacterium Mycobacterium ulcerans. It is related to the family of organisms that cause tuberculosis and leprosy, but Mycobacterium ulcerans produces a toxin, mycolactone, that destroys tissue. The prevalence of Buruli ulcer is unknown. The risk of mortality is low, although secondary infections can be lethal.
Morbidity takes the form of deformity, disability, and skin lesions,
which can be prevented through early treatment and treated with
antibiotics and surgery. It is found in Africa, Asia, and Latin America.
Chagas disease
A young boy from Panama with Chagas disease. It has manifested as an acute infection with swelling of one eye (chagoma).
Chagas disease is also known as American trypanosomiasis. There are approximately 15 million people infected with Chagas disease. The chance of morbidity is higher for immuno-compromised individuals, children, and elderly, but very low if treated early. Chagas disease does not kill victims rapidly, instead causing years of debilitating chronic symptoms. It is caused by a vector-borne protozoa 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. 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. The chronic phase occurs in 30 percent of total infections and can take three forms, which are asymptomatic (most prevalent), cardiac, and digestive lesions.
Chagas disease can be prevented by avoiding insect bites through
insecticide spraying, home improvement, bed nets, hygienic food, medical
care, laboratory practices, and testing. It can also be treated with medication, although these may have severe side effects. It can be diagnosed through a serological test, although the test is not very accurate.
Dengue and chikungunya fever
There are 50–100 million dengue virus infections annually. 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. Dengue fever is caused by a flavivirus, and is spread mostly by the bite of the Aedes aegypti mosquito. No treatment for either dengue or severe dengue exists beyond palliative care. The symptoms are high fever and flu-like symptoms. It is found in Asia, Latin America, and Northern Australia.
Chikungunya is an arboviral disease transmitted by A. albopictus and A. aegypti mosquitoes. The virus was first isolated from an outbreak in Tanzania in 1952. Chikungunya virus is a member of the genus Alphavirus and family Togaviridae. The word chikungunya is from the Makonde which means "that which bends up," and this refers to the effect of the debilitating joint pain on the patient.
The symptoms can be confused with dengue and include fever, rash, joint
pain, and swelling. The disease mainly occurs in Africa and Asia.
Dracunculiasis
Dracunculiasis is also known as Guinea-worm disease. There were 126 cases of dracunculiasis in 2014, a decrease from 542 cases in 2012, and a substantial decrease from 3,500,000 cases in 1986. It is not fatal, but can cause months of inactivity. It is caused by drinking water contaminated by water fleas infected with guinea-worm larvae.
Approximately one year after infection, a painful blister forms and one
or more worms emerge. Worms can be up to one meter long.
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.
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. As of 2014, the four endemic countries are Chad, Ethiopia, Mali, and South Sudan.
Echinococcosis
The rates of echinococcosis is higher in rural areas, and there are more than one million people infected currently. Untreated alveolar echinococcosis is fatal. It is caused by ingesting parasites in animal feces.
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 liver failure.
Surgery and drugs can both be used to treat echinococcosis.
It can be prevented by deworming dogs, sanitation, proper disposal of
animal feces, health education, and livestock vaccination.
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. It can be diagnosed through imaging techniques and serological tests.
Endemic treponematoses (Yaws)
There are limited data available on the prevalence of yaws, although it primarily affects children. The mortality risk is very low, but the disease causes disfigurement and disability if untreated. The most common symptom is skin lesions. It is a chronic bacterial infection, transmitted by skin contact, and caused by treponemes. It is treated with antibiotics and can be prevented through improved hygiene and sanitation. Yaws is most prevalent in the warm, moist, tropical regions of the Americas, Africa, Asia, and the Pacific.
Foodborne trematodiases
The foodborne trematode infections include clonorchiasis, opisthorchiasis, fascioliasis, and paragonimiasis.
These infections are all zoonotic, primarily affecting domestic or wild
animals, but also transmitted to humans. They are acquired by eating
food, such as raw fish, contaminated with the larval stages of the
parasites. At least 40 million people are thought to be infected.
Human African trypanosomiasis
African trypanosomiasis is also known as African sleeping sickness. There are fewer than 10,000 cases currently. Human African trypanosomiasis is vector-borne, and spread through the bite of the tsetse fly.
The most common symptoms are fever, headache, lymphadenopathy,
nocturnal sleeping pattern, personality changes, cognitive decline, and
coma. The disease is always fatal if untreated.
The current forms of treatment are highly toxic and ineffective
as resistance is spreading. It is diagnosed through an inexpensive serological test.
Leishmaniasis
The three forms of leishmaniasis are visceral (Kala-azar), cutaneous, and mucocutaneous. There are an estimated 12 million people infected. It is fatal if untreated and 20,000 deaths from visceral leishmaniasis occur annually. It is a vector-borne disease that is caused by the bite of sandflies.
At least 90 percent 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 percent of mucocutaneous
leishmaniasis occurs in Bolivia, Brazil, and Peru.
The only method of prevention is a vaccine that is under
development and prevention of sandfly bites. Diagnosis can by made by
identifying clinical signs, serological tests, or parasitological tests. Leishmaniasis can be treated with expensive medications.
Leprosy
There were 189,018 known cases of leprosy in March 2013, and 232,857 new cases were diagnosed in 2012.
It is found in Angola, Brazil, Central African Republic, Democratic
Republic of the Congo, India, Madagascar, Mozambique, Nepal, and
Tanzania. There are one million to two million individuals currently disabled or disfigured due to past or present leprosy. It is caused by bacteria and transmitted through droplets from the mouth and nose of infected individuals. Leprosy causes disfigurement and physical disabilities if untreated. It is curable if treated early.
Treatment requires multidrug therapy. 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.
Lymphatic filariasis
Lymphatic filariasis is also known as elephantiasis. There are approximately 120 million individuals infected and 40 million with deformities. Approximately two-thirds of cases are in Southwest Asia and one-third in Africa. Lymphatic filariasis is rarely fatal.
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 40 percent of
infected individuals have kidney damage. It is a vector-borne disease, caused by nematode worms that are transmitted by mosquitoes.
It can be treated with cost-effective antihelminthic treatments, and washing skin can slow or even reverse damage. It is diagnosed with a finger-prick blood test.
Onchocerciasis
Onchocerciasis is also known as "river blindness". There are 37 million people infected and prevalence is higher in rural areas. Over 99 percent of cases are in Sub-Saharan Africa. It causes blindness, skin rashes, lesions, intense itching, and skin depigmentation. It is a vector-borne disease, caused by filarial worm infected blackflies.
It can be treated with ivermectin. It can be prevented by insecticide spraying or preventative dosing with ivermectin. The symptoms are generally itching and skin lesions.
Rabies
There are two forms of rabies: furious and paralytic. There are 60,000 deaths from rabies annually. It is mostly found in Asia and Africa. There is a higher prevalence in rural areas and it disproportionately affects children. Rabies is usually fatal after symptoms develop. It is caused by a lyssavirus transmitted through wounds or bites from infected animals.
The first symptoms are fever and pain near the infection site which
occur after a one to three 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.
It can be prevented in dogs by vaccination, and cleaning and disinfecting bite wounds (post-exposure prophylaxis). Rabies is undiagnosable before symptoms develop. It can be detected through tissue testing after symptoms develop.
Schistosomiasis
11-year-old boy with ascites and portal hypertension due to schistosomiasis (Agusan del Sur, Philippines)
There are over 200 million cases of schistosomiasis. Approximately 85 percent of cases are in sub-Saharan Africa. The disease can be fatal by causing bladder cancer and hematemesis. Schistosoma
species have a complex life cycle that alternates between humans and
freshwater snails. Infection occurs when skin comes into contact with
contaminated freshwater in which the snail that carry the parasite are
living. Symptoms for schistosomiasis are not caused by the worms but by
the body’s reaction to the eggs. The eggs that do not pass out of the
body can become lodged in the intestine or bladder, causing inflammation
or scarring. Children who are repeatedly infected can develop anemia,
malnutrition and learning difficulties. The symptoms are usually haematuria, bladder obstruction, renal failure, bladder cancer, periportal fibrosis, bladder fibrosis, liver fibrosis, portal hypertension, cervical lesions, ascites, and esophageal varices.
Inexpensive praziquantel
can be used to treat individuals with schistosomiasis, but cannot
prevent reinfection. The cost of prevention is US$0.32 per child per
year. Mass deworming
treatment with praziquantel, better access to safe water, sanitation,
health education can all be used to prevent schistosomiasis. Vaccines are under development. It can be diagnosed through a serological test, but it often produces false negatives.
Soil-transmitted helminthiasis
Adult ascaris worms being removed from the bile duct of a patient in South Africa
The three major worm species responsible for soil-transmitted helminthiasis are Ascaris (roundworms), Trichuris (whipworm), the hookworms Necator americanus and Ancylostoma duodenale, and Strongyloides stercoralis. There are 1.5 billion currently infected. Soil-transmitted heminthiasis occurs in sub-Saharan Africa, the Americas, China, and east Asia. The mortality risk is very low. The most common symptoms are anemia, stunted growth, intestinal problems, lack of energy, and compromised physical and cognitive development. Infected children often fall behind in schooling. The severity of symptoms depends on the number of worms in the body.
Parasitic worms are generally transmitted via exposure to
infected human feces and soil which are spread in the environment, for
example, due to open defecation. The most common treatment is medicine. It can be prevented through hygienically prepared food and clean water, improved sanitation, periodic deworming, and health education. The World Health Organisation recommends mass deworming without prior diagnosis.
Taeniasis/cysticercosis
Cysticercosis is a tapeworm larvae infection, while taeniasis is infection with adult tapeworms . Both are found in Asia, Africa, Latin America, particularly on farms in which pigs are exposed to human excrement.
Cysticercosis is the most common preventable cause of epilepsy in the developing world. Cysticercosis occurs after ingestion of contaminated food, water, or soil. Cysts and lesions can cause headaches, blindness, seizures, hydrocephalus, meningitis, and dementia. Neurocystocercosis, or the parasitic infection of the nervous system, can be fatal. Taeniasis is not fatal.
It is usually contracted after eating undercooked contaminated pork.
Taeniasis has mild symptoms, including abdominal pain, nausea, diarrhea,
or constipation.
Drugs are used to treat both diseases.
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.
Trachoma
There are 21.4 million people infected with trachoma,
of whom 2.2 million are partially blind and 1.2 million are blind. It
is found in Africa, Asia, Central and South America, Middle East, and
Australia. The disease disproportionately affects women and children. The mortality risk is very low, although multiple re-infections eventually lead to blindness. The symptoms are internally scarred eyelids, followed by eyelids turning inward. Trachoma is caused by a micro-organism that spreads through eye discharges (on hands, cloth, etc.) and by "eye-seeking flies".
It is treated with antibiotics. The only known prevention method is interpersonal hygiene.
Snakebite envenoming
Snakebite was added to the list in 2017, after years of criticism of the WHO by activists for not making it a priority. The greatest burden of snakebite morbidity
is in India and Southeast Asia. Globally, there are an estimated
421,000 envenomings each year (about 1 in 4 snakebites) and 20,000
deaths, but snakebites often go unreported.
Health effect
Deworming treatment
Deworming treatments in infected children may have some nutritional benefit, as worms are often partially responsible for malnutrition. However, in areas where these infections are common, there is strong evidence that mass deworming campaigns do not have a positive effect on children's average nutritional status, levels of blood haemoglobin, cognitive abilities, performance at school or survival. To achieve health gains in the longer term, improvements in sanitation and hygiene behaviours are also required, together with deworming treatments.
Coinfection
Coinfection is a major concern with neglected tropical diseases, making NTDs more damaging than their mortality
rates might portray. Because the factors that support neglected
tropical diseases (poverty, inadequate healthcare, inadequate sanitation
practices etc.) support all NTDs, they are often found in overlapping
distributions. Helminth infections,
as the most common infection of humans, are often found to be in
multi-infection systems. For example, in Brazil, low socioeconomic
status contributes to overcrowded housing. In these same areas,
connection by Necator americanus and Schistosoma mansoni is common. The effect of each worm weakens the immune system
of those infected, making infection from the other easier and more
severe. For this reason, coinfection carries a higher risk of mortality.
NTDs may also play a role in infection with other diseases, such as malaria, HIV/AIDS, and tuberculosis.
The ability of helminths to manipulate the immune system may create a
physiological environment that could exacerbate the progression of HIV/AIDS. Some evidence from Senegal, Malawi, and Thailand has shown that helminth infections raise the risk of malarial infection.
Integration of treatment
Inclusion of NTDs into initiatives for malaria, HIV/AIDS, and tuberculosis, as well as integration of NTD treatment programs, may have advantages given the strong link between these diseases and NTDs. Some neglected tropical diseases share common vectors (sandflies, black flies, and mosquitos). Both medicinal and vector control efforts may be combined.
A four-drug rapid-impact package has been proposed for widespread
proliferation. Administration may be made more efficient by targeting
multiple diseases at once, rather than separating treatment and adding
work to community workers. This package is estimated to cost US$0.40 per
patient. When compared to stand-alone treatment, the savings are
estimated to be 26–47%. While more research must be done in order to
understand how NTDs and other diseases interact in both the vector and
the human stages, safety assessments have so far produced positive
results.
Many neglected tropical diseases and other prevalent diseases
share common vectors, creating another opportunity for treatment and
control integration. One such example of this is malaria and lymphatic
filariasis. Both diseases are transmitted by the same or related
mosquito vectors. Vector control, through the distribution of
insecticide treated nets, reduces the human contact with a wide variety
of disease vectors. Integrated vector control may also alleviate
pressure on mass drug administration, especially with respect to rapidly
evolving drug resistance. Combining vector control and mass drug
administration deemphasizes both, making each less susceptible to
resistance evolution.
Economic effect
The
low cost of treatment for NTDs can be attributed 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. The economic burden of NTDs is undervalued and therefore the
corresponding economic effect and cost-effectiveness of decreased
prevalence of NTDs is underestimated.
The investment return on measures to control neglected tropical
diseases is estimated to be between 14–30 percent, depending on the
disease and region.
The long-term benefits of deworming include a decrease in school
absenteeism by 25 percent, and an increase in adult earnings by 20
percent.
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 percent, which is a benefit-to-cost
ratio of 100. Each untreated case of Trachoma is estimated to cost
US$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.
Social effect
Social stigma
Several NTDs, such as leprosy,
cause severe deformities that result in social stigma. Stigma is
considered to be the 'hidden burden' of neglected tropical diseases, and
is not accounted for in measures such as DALYs. Other NTDs that carry
heavy social stigma include onchocerciasis, lymphatic filariasis, plague, Buruli ulcer, leishmaniasis, and Chagas disease. Lymphatic filariasis, for example, causes severe deformities that can result in denial of marriage and inability to work.
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.
The social effects of neglected tropical diseases have been shown to
affect men and women in different ways. Men are socially stigmatized in a
way that detrimentally affects their economic prospects. Women are more
likely to be affected in the areas of marriage and family.
Effect on mental health
A
2012 review found that infection with a neglected tropical disease
predisposes individuals to poor mental health. This is partially due to
the social stigma that surround NTDs, but is also likely caused by the
subsequent lack of access to health and social services. Overall, being a
member of the infected community was found to cut individuals off from
multiple aspects of society via civic rights, educational opportunities,
and employment. The authors suggest that more research be directed into
the psychological aspects of neglected tropical diseases in order to
fully untangle their co-effects.
Gender
The effect of NTDs is tied to gender in some situations. NTDs disproportionately affect females. This is especially true in the cases of schistosomiasis, dengue, hookworm, and Chagas disease.
There is also the added risk of hookworm infection during pregnancy and
the potential to transfer diseases such as Chagas during pregnancy. 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 in
Uganda. Additionally, women often bear a heavier social stigma in relation to the pressure to marry.
School attendance
The
effects of mass deworming on school attendance is controversial. It has
been argued that mass deworming has a positive effect on school
attendance.
A systematic review; however, found that there is little or no
difference in attendance in children who receive mass deworming compared
to children who did not.
One study found that boys were enrolled in primary school for more
years than boys who were in schools that did not offer such programs.
Girls in the same study were about a quarter more likely to attend
secondary school if they received treatment. Both groups went on to
participate in more skilled sectors of the labor market. The economic
growth generated from school programs such as this may balance out the
actual expenses of the program.
But the results of this study are disputed (i.a. due to a high risk of
bias in the study) and the positive long-term outcomes of mass deworming
remain unclear.
Reasons for neglect
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. Far more resources are given to the "big three" diseases (HIV/AIDS, malaria, and tuberculosis)
because of their higher mortality and public awareness rates. Neglected
tropical diseases do not have a prominent cultural figure to champion
the cause.
The importance of neglected tropical diseases has been underestimated since many are asymptomatic 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. Areas of high endemicity are often in geographically isolated areas, making treatment and prevention much more difficult.
Stigma
Additionally,
neglected tropical diseases are often associated with some kind of
social stigma, making their treatment more complex. Public health
research has only recently begun to focus on stigma as a component of
the issue. From the 1960s onward, approximately one citation a year
related to social stigma. In 2006, there were 458. Disease control is greatly affected by this stigma, as it decreases help-seeking and treatment adherence.
Disease control programs, starting as early as the 1980s, have begun to
integrate stigma mitigation into their offerings. In India, the leprosy
program prioritized the message that "leprosy is curable, not
hereditary" in order to inspire optimism in highly affected communities.
The goal was to make leprosy a disease "like any other," so as to
reduce stigma. Supplementally, the medical resources available in the
area were optimized in order to fulfill the curable promise made.
Economic incentives
One
reason for neglect for these diseases is that they are not commercial
and consequently patents and profit play no role in stimulating
innovation. Like all non-commercial areas, these diseases are the
responsibility of governments and philanthropy (including industry
philanthropy). Currently, the pharmaceutical industry views research and development
as highly risky. For this reason, resources are not often put into the
field of NTDs (as diseases of the poor) and new chemical products are
often expensive. A review of public and private initiatives found that
of the 1393 new chemical products that were marketed in the period of
1975 and 1999, just 16 related to tropical diseases and tuberculosis.
The same review additionally found that there was a 13-fold greater
chance of a drug entering the marking being for central-nervous-system
disorders and cancer than an NTD.
Due to lack of incentive in the pharmaceutical industry,
successful NTD treatment programs have often relied on the donation
format. The Mectizan Donation Program has donated over 1.8 billion
tablets of ivermectin.
While often developed countries will rely on government-run and private
partnerships to fund such projects, developing nations frequently have
significantly lower per head per annum spending on these diseases.
Developed nations
Since 2008 the concept of neglected diseases of poverty has been developed and explored.
This group overlaps with the neglected tropical diseases, which also
pose a threat to human health in developed nations. In the United States alone, there are at least 12 million people suffering from these neglected parasitic infections. They make up a hidden disease burden among the poorest of wealthy societies.
In developed nations, lack of knowledge in the healthcare industry and
lack of conclusive diagnostic tests perpetuate the neglect of this group
of diseases.
In the United States, high rates of parasitic infection can be
found to be distributed along geographic, racial, and socio-economic
lines. Within the African-American community, there may be up to
2.8 million cases of toxocariasis. Rates of toxocariasis, trichomoniasis,
and other neglected infections occur in the United States at the same
rate as in Nigeria. Within the Hispanic community, neglected infections
are concentrated near the US–Mexico border. Vector-borne illnesses are
especially high, with some rates approaching those of Latin America. Chagas disease was found in the US as early as the 1970s.
However, in the developed world, diseases that are associated with
poverty are often not addressed comprehensively. This may be due to lack
of economic incentives and public policy failings. Here, a lack of
awareness prevents effective policy generation and leaves health care
services unequipped to address the issue. Additionally, there is little
effort put into taking and maintaining large data sets on neglected
disease in the United States and other developed nations. The first
summit on the issue was held by the Adler Institute on Social Exclusion
in the United States in 2009.
In Europe, a similar trend is seen. Neglected tropical diseases
are concentrated in eastern and southern Europe, where poverty levels
are the highest. The most prevalent diseases in this region are ascariasis, trichuriasis, zoonotic helminth infections, and visceral leishmaniasis.
Migration paths to Europe, most notably to Spain, have brought diseases
to Europe as well. As many as 6,000 cases of Chagas disease have been
introduced via this method. In response to a growing awareness to the
burden on these populations, the European Centre for Disease Prevention and Control
has laid out ten public health guidelines. They cover a variety of
topics, from health education and promotion to community partnerships
and the development of a minority healthcare workforce.
Prevention
Prevention
and eradication are important because "of the appalling stigma,
disfigurement, blindness and disabilities caused by NTDs." The possibility of eliminating or eradicating dracunculiasis, leprosy, lymphatic filariasis, onchocerciasis, trachoma, sleeping sickness, visceral leishmaniasis, and canine rabies within the next ten years was the principal aim of the London Declaration on Neglected Tropical Diseases, which is a collaborative effort involving the WHO, the World Bank,
the Bill & Melinda Gates Foundation, the world's 13 leading
pharmaceutical companies, and government representatives from US, UK,
United Arab Emirate, Bangladesh, Brazil, Mozambique and Tanzania. It was
launched in January 2012.
While the current era has had a noticeable uptick in biological
research into neglected tropical diseases, prevention may be
supplemented by social and development outreach. Spiegal and his
coauthors advocated for this to take the form of "social offset." Social
offset entails the delegation of some of the funding for
biotechnological research to social programs. The attempts to alleviate
some of the surrounding factors (such as poverty, poor sanitation,
overcrowding, poor healthcare etc.) that greatly exacerbate the
conditions brought on by neglected tropical diseases. Projects such as
these also strengthen the goal of sustained eliminations, rather than
quickly addressing symptoms.
Policy initiatives
There are many prevention and eradication campaigns funded for example by the World Health Organization, US Agency for International Development, Bill and Melinda Gates Foundation, UK Department for International Development.
WHO Roadmap of 2012
WHO
published in 2012 the NTD "roadmap" which contains milestones for 2015
and 2020 and which specifies targets for eradication, elimination, and
intensified control of the different NTDs. For example:
- NTDs planned to be eradicated: dracunculiasis (by the year 2015), endemic treponematoses (yaws) (by 2020);
- NTDs planned to be eliminated globally by 2020: blinding trachoma, leprosy, human African trypanosomiasis, lymphatic filariasis;
- NTDs planned to be eliminated in certain regions: rabies (by 2015 in Latin America, by 2020 in Southeast Asia and western Pacific regions), chagas disease (transmission through blood transfusion by 2015, intra-domiciliary transmission by 2020 in the region of the Americas), visceral leishmaniasis (by 2020 in the Indian subcontinent), oncocerciasis (by 2015 in Latin America), schistosomiasis (by 2015 in eastern Mediterranean region, Caribbean, Indonesia and the Mekong River basin, by 2020 in the region of the Americas and western Pacific region);
- NTDs planned to be eliminated in certain countries: human African trypanosomiasis (by 2015 in 80 percent of areas in which it occurs), oncocerciasis (by 2015 in Yemen, by 2020 in selected countries in Africa), schistosomiasis (by 2020 in selected countries in Africa);
- Intensified control with specific targets for the years 2015 and 2020 are provided for these NTDs: dengue, buruli ulcer, cutaneous leishmaniasis, taeniasis/cysticercosis and echinococcosis/hydatidosis, foodborne tremadode infections, soil-transmitted helmintheases.
Others
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.
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." 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.
Integration with WASH programs
Water, sanitation, and hygiene (WASH) interventions are essential in preventing many NTDs, for example soil-transmitted helminthiasis. Mass drug administrations
alone will not protect people from re-infection. A more holistic and
integrated approach to NTDs and WASH efforts will benefit both sectors
along with the communities they are aiming to serve. This is especially
true in areas that are endemic with more than one NTD.
In August 2015 the World Health Organization unveiled a global strategy and action plan to integrate WASH with other public health interventions in order to accelerate elimination of NTDs.
The plan aims to intensify control or eliminate certain NTDs in
specific regions by 2020 and refers to the NTD "roadmap" milestones from
2012 that include for example eradication of dracunculiasis by 2015 and
of yaws by 2020, elimination of trachoma and lymphatic filariasis as
public health problems by 2020, intensified control of dengue,
schistosomiasis and soil-transmitted helminthiases.
A closer collaboration between WASH and NTD programmes can lead to synergies.
They can be achieved through collaborative planning, delivery and
evaluation of programmes, strengthening and sharing of evidence, and
using monitoring tools to improve the equity of health services.
Reasons why WASH plays an important role in NTD prevention and patient care include:
- NTDs affect more than one billion people in 149 countries. They occur mainly in regions with a lack of basic sanitation. About 2.4 billion people worldwide do not have adequate sanitation facilities. 663 million do not have access to improved drinking water sources.
- One leading cause of preventable blindness is trachoma. The bacterial infection is transmitted through contact with eye-seeking flies, fingers, and fomites. Prevention components are facial cleanliness which requires water for face washing and environmental improvement which includes safe disposal of excreta to reduce fly populations.
- Improved sanitation prevents soil-transmitted helminthiases. It impedes fecal pathogens such as intestinal worm eggs from contaminating the environment and infecting people through contaminated food, water, dirty hands, and direct skin contact with the soil.
- Improved sanitation and water management can contribute to reduce proliferation of mosquitoes that transmit diseases, such as lymphatic filariasis, dengue and chikungunya. Breeding of the Culex mosquito which transmits filarial parasites is facilitated through poorly constructed latrines. Breeding of the Aedes aegypti and Aedes albopictus mosquitoes which transmit dengue and chikungunya can be prevented through safe storage of water.
- Feces and urine which contain worm eggs can contaminate surface water and lead to transmission of schistosomiasis. This can be prevented through improved sanitation. Not only human but also animal (cow, buffalo) urine or feces can transmit some schistosome species. Therefore, it is important to protect freshwater from animals and animal waste.
- Treatment of many NTDs require clean water and hygienic condition for healthcare facilities and households. For guinea worm, Buruli ulcer, or cutaneous leishmaniasis, wound management is needed to speed up healing and reduce disability. Lymphatic filariasis causes chronic disabilities. People who suffer from this disease need to maintain rigorous personal hygiene with water and soap to prevent secondary infections.
- NTDs that lead to permanent disabilities make tasks such as carrying water long distances or accessing toilets difficult. However, people affected by these diseases often face stigma and can be excluded from accessing water and sanitation facilities. This increases their risk of poverty and severe illness. Clean water and soap are essential for these groups to maintain personal hygiene and dignity. Therefore, additional efforts to reduce stigma and exclusion are needed. In this manner, WASH can improve quality of life of people affected by NTDs.
- In a meta-analysis safe water was associated with significantly reduced odds of Schistosoma infection, and adequate sanitation was associated with significantly lower odds of infection with both S. mansoni and S. haematobium.
- A systematic review and meta-analysis showed that better hygiene in children is associated with lower odds of trachoma. Access to sanitation was associated with 15 percent lower odds of active trachoma and 33 percent lower odds of C. trachomatis infection of the eyes.
- Another systematic review and meta-analysis found a correlation between WASH access and practices and lower odds of soil-transmitted helminthiasis infections by 33 to 77 percent. Persons who washed their hands after defecating were less than half as likely to be infected as those who did not. Traditionally, preventive chemotherapy is used as a measure of control, although this measure does not stop the transmission cycle and cannot prevent reinfection. In contrast, improved sanitation can.
Pharmaceutical market
Biotechnology companies in the developing world have targeted neglected tropical diseases due to need to improve global health.
Mass drug administration
is considered a possible method for eradication, especially for
lymphatic filariasis, onchocerciasis, and trachoma, although drug
resistance is a potential problem. According to Fenwick, Pfizer donated 70 million doses of drugs in 2011 to eliminate trachoma through the International Trachoma Initiative. Merck
has helped The African Programme for the Control of Onchocerciasis
(APOC) and Oncho Elimination Programme for the Americas to greatly
diminished the effect of Onchocerciasis by donating ivermectin. Merck KGaA pledged to give 200 million tablets of praziquantel over 10 years, the only cure for schistosomiasis. GlaxoSmithKline
has donated two billion tablets of medicine for lymphatic filariasis
and pledged 400 million deworming tablets per year for five years in
2010. Johnson & Johnson has pledged 200 million deworming tablets per year. Novartis has pledged leprosy treatment, EISAI pledged two billion tablets to help treat lymphatic filariasis.
NGO initiatives
There are currently only two donor-funded non-governmental organizations that focus exclusively on NTDs: the Schistosomiasis Control Initiative
and Deworm the World. Despite under-funding, 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), is less than US$0.50 per year,
when administered as part of school-based mass 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.
Public-private initiatives
An
alternative model to the profit-driven drug development emerged in the
years 2000 to provide an answer to the needs of these neglected
patients. Product development partnerships (PDPs) aim at implementing
and accelerating the research and development (R&D) of safe and
effective health tools (diagnostics, vaccines, drugs) to notably combat
diseases that are neglected. Drugs for Neglected Diseases initiative (DNDi) is one of these PDPs that has already developed new treatments for NTDs.
The Sabin Vaccine Institute,
founded in 1993, works to address the issues of vaccine-preventable
diseases as well as NTDs. They run three main programs, Sabin Vaccine
Development, Global Network for Neglected Tropical Diseases, and Vaccine Advocacy and Education. Their product development partnership affiliates them with the Texas Children's Hospital as well as the Baylor College of Medicine. Their major campaign, End7, aims to end seven of the most common NTDs (elephantiasis, river blindness, snail fever, trachoma, roundworm, whipworm and hookworm)
by 2020. Through End7, college campuses undertake fundraising and
educational initiatives for the broader goals of the campaign.
WIPO Re:Search was established in 2011 by the World Intellectual Property Organization
in collaboration with BIO Ventures for Global Health (BVGH) and with
the active participation of leading pharmaceutical companies and other
private and public sector research organizations. It allows
organizations to share their intellectual property, compounds,
expertise, facilities and know-how royalty-free with qualified
researchers worldwide working on new solutions for NTDs, malaria and
tuberculosis.
In 2013, the Government of Japan, five Japanese pharmaceutical
companies, the Bill and Melinda Gates Foundation, and the UNDP
established a new public-private partnership, Global Health Innovative Technology Fund.
They pledged over US$100 million to the fund over five years, to be
awarded as grants to R&D partnerships across sectors in Japan and
elsewhere, working to develop new drugs and vaccines for 17 neglected
diseases, in addition to HIV, malaria and tuberculosis. Affordability of the resulting drugs and vaccines is one of the key criteria for grant awards.
Others
An open-access journal dedicated to neglected tropical diseases called PLoS Neglected Tropical Diseases first began publication in 2007.
One of the first large-scale initiatives to address NTDs came from a collaboration between Kenneth Warren and the Rockefeller Foundation.
Ken Warren is regarded as one of the founding figures in neglected
tropical disease research. The Great Neglected Tropical Diseases Network
was a consortium of scientists from all over the world, hand picked by
Ken Warren, working to expand the research base in neglected diseases.
Many of the scientists that he recruited had not been involved in NTD
research before. The network ran from 1978 to 1988. Warren's vision was
to establish units within biological labs across the world, dedicated to
R&D.
By forming a critical mass of scientists in NTD research, he hoped to
attract new students into the field. The interdisciplinary group met
annually to update the community on research progress. Much of the work
done by this group focused on the understanding of the mechanisms behind
infection. At these informally structured meetings, research
partnerships were formed. Warren himself encouraged these partnerships,
especially if they bridged the divide between developed and developing
nations. Through the Great Neglected Tropical Disease Network, a great
number of scientists were brought into the field of parasitology.
Epidemiology
The six most common NTDs include soil-transmitted helminths (STHs)—specifically roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura) and hookworms (Necator americanus and Ancylostoma duodenale)—schistosomiasis, trachoma, and lymphatic filariasis (LF).
These diseases affect one-sixth of the world's population with 90
percent of the disease burden occurring in sub-Saharan Africa.
Information on the frequency of neglected tropical diseases is of
low quality. It is currently difficult to summarize all of the
information on this family of diseases. One effort to do so is the
Global Burden of Disease framework. It aims to create a standardized
method of measurement. The principle components of the approach involve
1) the measuring of premature mortality as well as disability, 2) the
standardized usage of DALYs (disability-adjusted life years), and 3) wide spread inclusion of diseases and injury causes with the estimation of missing data.
However, the DALY has been criticized as a 'systematic undervaluation'
of disease burden. King asserts that the DALY emphasizes the individual
too much, while ignoring the effects of the ecology of the disease. In
order for the measure to become more valid, it may gave to take the
context of poverty more into account. King also emphasizes that DALYs
may not capture the non-linear effects of poverty on cost-utility
analysis of disease control.
