Neglected tropical diseases - Wikipedia

Neglected tropical diseases - Wikipedia
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Neglected tropical disease
Diverse group of tropical infectious diseases which are common in developing countries
Medical condition
Neglected tropical diseases
Number of people requiring interventions against neglected tropical diseases in 2015
Specialty
Infectious disease
Neglected tropical diseases
NTDs
) are a diverse group of
tropical infections
that 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 parasitic worms (
helminths
) and mites (
acarines
).
These diseases are broadly characterized by neglect within global health policy, 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
neglected tropical diseases as a group is comparable to that of malaria and tuberculosis.
NTD co-infection can also make HIV/AIDS and tuberculosis more deadly.
Some treatments for NTDs are relatively inexpensive. For example,
praziquantel
for
schistosomiasis
costs about 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 $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
efforts (for example,
mass deworming
) have been successful in several countries.
While preventive measures are often more accessible in the
developed world
, they are not universally available in poorer areas.
10
Within developed countries, neglected tropical diseases affect the very poorest in society. In developed countries, 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 well as developing nations. For example, other problems stemming from poverty, such as lack of adequate
housing
, can expose individuals to the vectors of these diseases.
11
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
envenomation were added to the WHO list in 2017.
12
These diseases are
common
in 149 countries, affecting more than 1.4 billion people (including more than 500 million children)
13
and costing developing economies billions of dollars every year.
14
They resulted in 142,000 deaths in 2013, down from 204,000 deaths in 1990.
15
Reasons for neglect
edit
The importance of neglected tropical diseases has been underestimated since many are
asymptomatic
and have long
incubation periods
. The connection between death and a neglected tropical disease that has been latent for a long period is often not realized.
16
Areas of high
endemicity
are often geographically isolated, making treatment and prevention much more difficult.
17
There are three other major reasons that these diseases have been overlooked: they mainly affect the poorest countries of the
developing world
; in recent years public health efforts have focused heavily on decreasing the prevalence of HIV/AIDS, tuberculosis, and malaria
18
(far more resources are given to those three diseases because of their higher mortality rates and higher public awareness of them); and neglected tropical diseases do not currently have a prominent cultural figure to champion their elimination.
17
19
Stigma
edit
Neglected tropical diseases are often associated with
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.
20
Stigma greatly affects disease control by decreasing help-seeking and treatment adherence.
20
Disease control programs since the 1980s have begun to integrate stigma mitigation into their offerings. In
India
, a
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. At the same time, medical resources were optimized to fulfill the promise that the disease could be cured.
20
Economic incentives
edit
Treatment and prevention of neglected tropical diseases are not seen as profitable, so
patents
and profit play a reduced role in stimulating innovation compared to other diseases. Like all non-commercial areas, communities affected by these diseases are reliant on governments and philanthropy.
21
Currently, the pharmaceutical industry views
research and development
as highly risky. For this reason, resources are not often put into the field of NTDs, and new chemical products are often expensive. A review of public and private initiatives found that of the 1,393 new chemical products that were marketed between 1975 and 1999, only 16 were related to tropical diseases or
tuberculosis
. The same review found that there was a 13-fold greater chance of a newly marketed drug being for
central nervous system disorders
or
cancer
than for an NTD.
22
Because of a lack of economic incentives for the pharmaceutical industry, successful NTD treatment programs have often relied on donations. For instance, the Mectizan Donation Program has donated over 1.8 billion tablets of
ivermectin
23
While
developed countries
often rely on government-run and private partnerships to fund such projects,
developing nations
frequently have significantly lower per-person spending on these diseases.
22
A 2006 report found that the
Gates Foundation
funded most extra activities to counter these diseases.
24
25
Neglected diseases in developed nations
edit
Since 2008, the concept of "neglected diseases of poverty" has been developed and explored.
26
This group of diseases, which overlaps with neglected tropical diseases, also pose a threat to human health in developed nations. In the
United States
alone, there are at least 12 million people with neglected parasitic infections.
26
They make up a hidden disease burden among the
poorest people in wealthy societies
10
In developed nations, lack of knowledge in the healthcare industry and lack of conclusive
diagnostic tests
perpetuate the neglect of this group of diseases.
27
In the United States, rates of parasitic infection can be distributed along geographic, racial, and socio-economic lines. Among
African Americans
, there may be up to 2.8 million cases of
toxocariasis
. Toxocariasis,
trichomoniasis
, and some other neglected infections occur in the United States at the same rate as in
Nigeria
10
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.
28
However, in the developed world, diseases that are associated with poverty are often not addressed comprehensively. This may be due to a lack of economic incentives and public policy failings. A lack of awareness prevents effective policy generation and leaves healthcare services unequipped to address the issue. Additionally, little effort is put into creating and maintaining large data sets on neglected diseases 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.
10
In
Europe
, a similar trend is seen. Neglected tropical diseases are concentrated in
eastern
and
southern Europe
, where poverty levels are 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 in this way. In response to a growing awareness of 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.
10
List of diseases
edit
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
18
Fenwick recognizes 12 "core" neglected tropical diseases: the same as above, excluding hookworm.
16
These diseases result from four classes of causative
pathogens
: (i) protozoa (Chagas disease, human African trypanosomiasis, and leishmaniasis); (ii) bacteria (Buruli ulcer, leprosy, trachoma, and
yaws
), (iii) helminths or
metazoan
worms (
cysticercosis
taeniasis
, dracunculiasis,
echinococcosis
foodborne trematodiases
, lymphatic filariasis, onchocerciasis, schistosomiasis, and
soil-transmitted helminthiasis
); and (iv) viruses (
dengue
chikungunya
, and
rabies
).
citation needed
The WHO recognizes the twenty diseases below as neglected tropical diseases.
12
WHO
12
/CDC
29
PLOS
Major NTDs
30
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:
Entamoeba histolytica
and
Naegleria fowleri
(both pathogenic amoeba)
Babesiosis
Balantidiasis
Chagas disease
Giardiasis
Human
African Trypanosomiasis
Leishmaniasis
Plasmodium vivax
and other non-
P. falciparum
malarias
Helminth infections:
Dracunculiasis
Echinococcosis
Food-borne Trematodiases
Loiasis
Lymphatic Filariasis
Onchocerciasis
Other food-borne helminthiases (
Trichinosis
Anisakiasis
Gnathostomiasis
Schistosomiasis
Soil-transmitted helminthiases
Ascariasis
Hookworm Diseases
Trichuriasis
Strongyloidiasis
Taeniasis
and
Cysticercosis
Toxocariasis
and
Baylisascaris
(caustive agents of
VLM
).
Viral infections:
Arboviral infections (
Dengue
Chikungunya
Zika
Japanese encephalitis
, Jungle
yellow fever
and others)
Enterovirus 71
and related viruses
HTLV-1
HTLV-2
and other non-
HIV
retrovirus
infections
Rabies
Rift Valley fever
Viral hemorrhagic fevers
Bacterial infections:
Bartonellosis
Atypical mycobacteria
(including
Mycobacterium bovis
and
Buruli ulcer
Cholera
and other enteric bacteria (
Shigella
Salmonella
E. coli
Leprosy
Leptospirosis
Melioidosis
Noma
Relapsing fever
Trachoma
Yaws
Bejel
and
Pinta
Q fever
Fungal infections:
Mycetoma
Paracoccidioidomycosis
Chromoblastomycosis
Other deep tissue
mycoses
Ectoparasites:
Scabies
Myiasis
Non-infectious diseases caused by toxin exposure:
Podoconiosis
Snakebite envenoming
Only WHO
The World Health Organization's 2010 report on neglected tropical diseases offers an expanded list including dengue, rabies, yaws, cysticercosis, echinococcosis, and
foodborne trematode infections
31
Neglected Tropical Diseases Worldwide Burden
32
33
Disease
DALYs (million)
Deaths/Yr
Global Prevalence (million)
Population at Risk (million)
Schistosomiasis
4.5
280,000
207
780
Hookworm
22.1
65,000
576
3200
Ascariasis
10.5
60,000
807
4200
Leishmaniasis
2.1
51,000
12
350
Trypanosomiasis
1.5
48,000
0.3
60
Chagas disease
0.7
14,000
25
Trichuriasis
6.4
10,000
604
3200
Leprosy
0.2
6,000
0.4
Not Determined
Lymphatic filariasis
5.8
120
1300
Trachoma
2.3
84
590
Onchocerciasis
0.5
37
90
Cryptococcosis
12
400,000
Buruli ulcer
edit
Main article:
Buruli ulcer
Buruli ulcer
is caused by the bacterium
Mycobacterium ulcerans
34
It is related to the bacteria that cause tuberculosis and leprosy.
Mycobacterium ulcerans
produces a toxin,
mycolactone
, that destroys tissue.
34
The prevalence of Buruli ulcer is unknown.
18
The risk of mortality is low, although secondary infections can be lethal.
35
Morbidity takes the form of deformity, disability, and skin lesions, which can be prevented through early treatment with antibiotics and surgery.
35
It is found in Africa, Asia, Australia,
36
and Latin America.
37
Chagas disease
edit
Main article:
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.
18
Morbidity rates are higher for
immunocompromised
individuals, children, and the elderly, but can be very low if the disease is treated early.
38
Chagas disease does not kill victims rapidly, instead causing years of debilitating chronic symptoms.
It is caused by the
vector-borne
39
protozoa
Trypanosoma cruzi
38
It is 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 or coming into contact with contaminated bodily fluids.
38
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
lymphadenopathy
, and
fever
, accompanied by a variety of other symptoms depending on the infection site.
38
The chronic phase occurs in 30 percent of all infections
18
and can take three forms: asymptomatic (most prevalent), cardiac, and digestive lesions.
38
Chagas disease can be prevented by avoiding insect bites through insecticide spraying, home improvement, bed nets, hygienic food, medical care, laboratory practices, and testing.
38
It can be diagnosed through a
serological
test, although the test is not very accurate.
18
Treatment is with medication, which may have severe side effects.
38
Dengue and chikungunya
edit
Main article:
Dengue fever
There are 50–100 million
dengue virus
infections annually.
40
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.
40
Dengue fever is caused by a
flavivirus
which is spread mostly by the bite of the
Aedes aegypti
mosquito.
40
No treatment for either dengue or severe dengue exists beyond
palliative care
40
The symptoms are high fever and flu-like symptoms.
40
It is found in Asia, Latin America, and Northern Australia.
40
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.
41
Chikungunya virus is a member of the genus
Alphavirus
and family
Togaviridae
41
The word "chikungunya" is from the
Makonde language
and means "that which bends up", referring to the effect of debilitating joint pain on the patient.
41
Symptoms, generally appearing 5–7 days after exposure, can be confused with dengue and include fever, rash, headache, joint pain, and swelling.
42
The disease mainly occurs in Africa and Asia.
43
Dracunculiasis
edit
Main article:
Dracunculiasis
Dracunculus medinensis
larvae
Dracunculiasis
is also known as Guinea-worm disease. In 2019, 53 cases were reported across four countries,
44
a substantial decrease from 3,500,000 cases in 1986.
45
It is not fatal, but can cause months of inactivity.
46
It is caused by drinking water contaminated by
water fleas
infected with
guinea-worm
larvae.
46
Approximately one year after infection, a painful blister forms and one or more worms emerge. Worms can be up to 1 metre long.
46
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.
46
Dracunculiasis is preventable by water filtration, immediate case identification to prevent spread, health education, and treating ponds with larvicide. An
eradication program
has been able to reduce prevalence.
46
As of 2014
[update]
, the four endemic countries are
Chad
Ethiopia
Mali
, and
South Sudan
46
Echinococcosis
edit
Main article:
Echinococcosis
Lifecycle of
Echinococcus
The rate of
echinococcosis
is higher in rural areas, and there are more than one million people infected currently.
47
It is caused by ingesting
parasites
in animal feces.
48
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,
malaise
, and signs of
liver failure
49
Untreated alveolar echinococcosis is fatal.
49
Surgery and drugs can be used to treat echinococcosis.
49
It can be prevented by deworming dogs, sanitation, proper disposal of animal feces, health education, and livestock vaccination.
50
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.
48
It can be diagnosed through
imaging techniques
and
serological tests
50
Yaws
edit
Main article:
Yaws
A child with yaws
There are limited data available on the prevalence of
yaws
, although it primarily affects children.
51
The mortality risk is very low, but the disease causes disfigurement and disability if untreated.
51
The most common symptom is skin lesions.
51
It is a chronic bacterial infection, transmitted by skin contact, and caused by the
spirochete
bacterium
Treponema pallidum
pertenue
51
It is treated with antibiotics and can be prevented through hygiene and sanitation.
51
Yaws is most prevalent in warm, moist tropical regions of the Americas, Africa, Asia, and the Pacific.
51
Foodborne trematodiases
edit
Foodborne trematode infections include
clonorchiasis
opisthorchiasis
fascioliasis
, and
paragonimiasis
. These infections are all
zoonotic
, primarily affecting domestic or wild animals, but can also be 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.
52
Fasciola hepatica
Human African trypanosomiasis
edit
Main article:
African trypanosomiasis
African trypanosomiasis
(African sleeping sickness) is a somewhat rare protozoal disease, with fewer than 10,000 cases currently.
53
Human African trypanosomiasis is
vector-borne
and spreads through the bite of the
tsetse fly
39
The most common symptoms are fever, headache,
lymphadenopathy
, sleeping disturbances, 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.
medical citation needed
Lifecycle of African Trypanosomiasis
Leishmaniasis
edit
Main article:
Leishmaniasis
Lifecycle of Leishmaniasis
The three forms of
leishmaniasis
, a protozoal disease, are visceral (
Kala-azar
),
cutaneous
, and mucocutaneous.
54
There are an estimated 12 million people infected.
18
It is fatal if untreated, and 20,000 deaths from visceral leishmaniasis occur annually.
55
It is a vector-borne disease caused by the bite of
sandflies
39
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.
54
A vaccine is under development to prevent leishmaniasis. The only other method of prevention is avoidance of sandfly bites. Diagnosis can be made by clinical signs, serological tests, or parasitological tests.
56
Leishmaniasis can be treated with expensive medications.
57
Leprosy
edit
Main article:
Leprosy
According to recent figures from the WHO, 208,619 new cases of
leprosy
were reported in 2018 from 127 countries.
58
It is most prevalent in India (69% of cases), Brazil,
Indonesia
Nigeria
, the
Democratic Republic of the Congo
Madagascar
, and
East Africa
from
Mozambique
to Ethiopia, with the highest relative incidence in India, Brazil, and
Nepal
59
There are one to two million individuals currently disabled or disfigured due to past or present leprosy.
60
It is caused by bacteria and transmitted through droplets from the mouth and nose of infected individuals.
61
Hands deformed by leprosy
Leprosy causes disfigurement and physical disabilities if untreated. It is curable if treated early.
60
Treatment requires multidrug therapy.
59
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.
61
Lymphatic filariasis
edit
Main article:
Lymphatic filariasis
Elephantiasis
Lymphatic filariasis is also known as
elephantiasis
. There are approximately 120 million individuals infected
62
and 40 million with deformities.
16
Approximately two-thirds of cases are in Southwest Asia, and one-third are in Africa.
62
Lymphatic filariasis is rarely fatal
63
but 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.
64
It is a vector-borne disease, caused by
nematode worms
that are transmitted by mosquitoes.
39
64
It can be treated with cost-effective antihelminthic treatments,
65
and washing skin can slow or even reverse damage.
66
It is diagnosed with a finger-prick blood test.
63
Noma
edit
Main article:
Noma (disease)
Noma, an opportunistic bacterial infection causing gangrenous necrosis of the mouth,
67
was added to the World Health Organization's list of neglected tropical diseases in December 2023.
68
Onchocerciasis
edit
Main article:
Onchocerciasis
Onchocerca volvulus
emerging from a blackfly
Onchocerciasis
is also known as river blindness. There are 20.9 million people infected,
69
and prevalence is higher in rural areas.
70
Over 99 percent of cases are in
sub-Saharan Africa
70
It causes blindness, skin rashes, lesions, intense itching, and skin depigmentation.
70
71
It is a vector-borne disease, caused by
blackflies
infected with the
filarial
nematode
Onchocerca volvulus
39
71
It can be treated with
ivermectin
71
and prevented by insecticide spraying or preventative dosing with ivermectin.
70
Rabies
edit
Main article:
Rabies
Rabies virus
There are two forms of
rabies
: furious and paralytic. It is mostly found in Asia and Africa.
72
There is a higher prevalence in rural areas, and it disproportionately affects children.
73
Rabies is fatal after symptoms develop.
74
It is caused by a
lyssavirus
transmitted through wounds or bites from infected animals.
73
The first symptoms are fever and pain near the infection site, which occur after a one- to three-month incubation period. Furious rabies (the more common type) causes hyperactivity, hydrophobia, and aerophobia; death by
cardio-respiratory arrest
occurs within days. Paralytic rabies causes a slow progression from paralysis to coma to death.
73
There are 60,000 deaths from rabies annually.
72
It can be prevented in dogs by vaccination
73
and by cleaning and disinfecting bite wounds and
post-exposure prophylaxis
74
Rabies is undiagnosable before symptoms develop. It can be detected through tissue testing after symptoms develop.
73
Schistosomiasis
edit
Main article:
Schistosomiasis
11-year-old Filipino boy with
ascites
due to schistosomiasis
There are over 200 million cases of
schistosomiasis
16
Approximately 85 percent of cases are in sub-Saharan Africa.
16
The disease can be fatal by causing
bladder cancer
and
hematemesis
16
Schistosoma
species have a complex life cycle that alternates between humans and freshwater snails. Infection occurs when the skin comes into contact with contaminated fresh water in which snails 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.
75
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
18
16
Inexpensive
praziquantel
can be used to treat individuals with schistosomiasis, but it cannot prevent reinfection. The cost of prevention is US$0.32 per child per year.
16
Mass deworming
treatment with praziquantel, better access to safe water, sanitation, and health education can all be used to prevent schistosomiasis.
18
Vaccines are under development. It can be diagnosed through a serological test, but the test often produces false negatives.
16
Soil-transmitted helminthiasis
edit
Main article:
Soil-transmitted helminthiasis
Adult ascaris worms being removed from the bile duct of a patient in South Africa
Soil-transmitted helminthiasis
is the most prevalent neglected tropical disease.
76
The four major worm species responsible for
soil-transmitted helminthiasis
are
Ascaris
roundworms
),
Trichuris
whipworm
), the hookworms
Necator americanus
and
Ancylostoma duodenale
, and
Strongyloides stercoralis
77
There are 1.5 billion people currently infected.
77
Soil-transmitted helminthiasis occurs in sub-Saharan Africa, the Americas, China, and East Asia.
77
The mortality risk is very low.
18
The most common symptoms are anemia,
stunted growth
, intestinal problems, lack of energy, and compromised physical and cognitive development.
18
77
Infected children often fall behind in schooling.
18
The severity of symptoms depends on the number of worms in the body.
77
Parasitic worms are generally transmitted via exposure to infected human feces and soil that are spread in the environment, for example, due to
open defecation
77
The most common treatment is medicine.
77
It can be prevented through hygienically prepared food and clean water, improved
sanitation
, periodic deworming, and health education.
77
The World Health Organization recommends
mass deworming
without prior diagnosis.
77
Taeniasis/cysticercosis
edit
Main article:
Cysticercosis
Cysticercosis
is a tapeworm larvae infection, while
taeniasis
is infection with adult
tapeworms
78
Both are found in Asia, Africa, and Latin America, particularly on farms in which pigs are exposed to human excrement.
79
Cysticercosis is the most common preventable cause of
epilepsy
in the developing world.
79
Cysticercosis occurs after ingestion of contaminated food, water, or soil.
78
Cysts and lesions can cause
headaches
blindness
seizures
hydrocephalus
meningitis
, and
dementia
80
Neurocysticercosis
, or the parasitic infection of the nervous system, can be fatal. Taeniasis is not fatal.
79
80
It is usually contracted after eating undercooked contaminated pork. Taeniasis has mild symptoms, including abdominal pain, nausea, diarrhea, or constipation.
citation needed
Drugs are used to treat both diseases.
80
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.
81
Trachoma
edit
Main article:
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, the Middle East, and Australia.
82
The disease disproportionately affects women and children.
82
The mortality risk is very low, although multiple re-infections eventually lead to blindness.
18
82
The symptoms are internally scarred eyelids, followed by eyelids turning inward.
82
Trachoma is caused by a micro-organism that spreads through eye discharges (on hands, cloth, etc.) and by "eye-seeking flies".
82
It is treated with antibiotics. The only known prevention method is interpersonal hygiene.
citation needed
Chromoblastomycosis and other deep mycoses
edit
This section is an excerpt from
Chromoblastomycosis
edit
Chromoblastomycosis
is a long-term
fungal infection
of the skin
83
and
subcutaneous tissue
(a
chronic
subcutaneous mycosis
).
84
It can be caused by many different types of
fungi
which become implanted under the
skin
, often by thorns or splinters.
85
Chromoblastomycosis spreads very slowly.
citation needed
It is rarely fatal and usually has a good
prognosis
, but it can be very difficult to cure. Several treatment options exist, including medication and surgery.
86
Other important endemic mycoses with common systemic involvement are histoplasmosis, paracoccidioidomycosis, coccidioidomycosis, blastomycosis and talaromycosis. These infections are also seldomly seen in returning travelers in western countries
87
Scabies
edit
This section is an excerpt from
Scabies
edit
Magnified view of a burrowing trail of the scabies mite. The scaly patch on the left was caused by scratching and marks the mite's entry point into the skin. The mite has burrowed to the top-right, where it can be seen as a dark spot at the end.
Scabies
eɪ
iː
SKAY
-beez
88
also sometimes known as the seven-year itch)
89
is a contagious human skin
infestation
by the tiny (0.2–0.45 mm)
mite
Sarcoptes scabiei
89
90
variety
hominis
. The word is from
Latin
scabere
lit.
to scratch
91
It is a particular public health problem in crowded settings such as care homes, schools, refugee camps, prisons, and hospitals.
92
93
The most common symptoms are severe
itchiness
and a
pimple
-like rash.
94
Occasionally, tiny
burrows
may appear on the skin from eggs that are about to hatch.
94
In a first-ever infection, the infected person usually develops symptoms within two to six weeks.
94
During a second infection, symptoms may begin within 24 hours.
94
These symptoms can be present across most of the body or just in certain areas such as the wrists, between fingers, or along the waistline.
94
The head may be affected, but this is typically only in young children.
94
The itch is often worse at night.
94
Scratching may cause skin breakdown and an additional bacterial infection in the skin.
94
Snakebite envenoming
edit
Main article:
Snakebite
Snakebite was added to the list in 2017, after years of criticism of the WHO by activists for not making it a priority.
95
The
greatest burden of snakebite morbidity
is in India and Southeast Asia. Snakebite envenoming (SBE) affects as many as 2.7 million people every year, most of whom live in some of the world's most remote, poorly developed, and politically marginalised tropical communities. With annual mortality of 81,000 to 138,000 and 400,000 surviving victims suffering permanent physical and psychological disabilities, SBE is a disease in urgent need of attention. but snakebites often go unreported.
96
A policy analysis however found that the placement of snakebite in the global health agenda of WHO is fragile due to reluctance acceptance of the disease in the neglected tropical disease community and the perceived colonial nature of the network driving the agenda.
97
This section is an excerpt from
Snakebite
edit
cobra
bite on the foot of a girl in
Thailand
snakebite
is an injury caused by the bite of a snake, especially a
venomous snake
98
A common sign of a bite from a venomous snake is the presence of two
puncture wounds
from the animal's
fangs
99
Sometimes
venom injection from the bite
may occur.
100
This may result in redness, swelling, and severe pain at the area, which may take up to an hour to appear.
99
101
Vomiting
, blurred vision, tingling of the limbs, and sweating may result.
99
101
Most bites are on the hands, arms, or legs.
101
102
Fear
following a bite is common with symptoms of a
racing heart
and
feeling faint
101
The
venom
may cause
bleeding
kidney failure
, a
severe allergic reaction
tissue death
around the bite, or breathing problems.
99
100
Bites may result in the
loss of a limb
or other
chronic problems
or even death.
103
100
Effects for patients
edit
Social effects
edit
Social stigma
edit
Several NTDs, such as
leprosy
, cause severe deformities that result in social stigma. Stigma is considered to be the "hidden burden" of NTDs and is not accounted for in measures such as
disability-adjusted life years
(DALYs). Other NTDs that carry heavy social stigma include
onchocerciasis
lymphatic filariasis
plague
Buruli ulcer
leishmaniasis
, and
Chagas disease
20
Lymphatic filariasis, for example, causes severe deformities that can result in denial of marriage and inability to work.
16
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.
20
Mental health
edit
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 surrounds 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.
104
A high prevalence of
post-traumatic stress disorder
(PTSD) and depression was found among people who had survived snakebites.
105
More research needs to be directed to understanding psychological aspects of NTDs to understand their effects more fully
104
and to direct strategies to manage them better in healthcare systems where mental health professionals are scarce.
105
Gender
edit
NTDs disproportionately affect women and children.
106
There is also added risk of hookworm infection during pregnancy and potential to transfer diseases such as Chagas during pregnancy. A study in Uganda found that women were able to obtain treatment more easily than men because they had fewer occupational responsibilities and were more trusting of treatments, but ignorance of the effects of medicines during pregnancy prevented adequate care. The paper concludes that gender should be considered when designing treatment programs in Uganda.
107
Additionally, women often bear a heavier social stigma in relation to the pressure to marry.
16
dubious
discuss
failed verification
Economic effects
edit
The cost of treatment of some of these diseases, such as Buruli ulcer, can be almost the average household income for families in the highest quarter of incomes, while for those in the lowest quarter it can be over twice the yearly income. These enormous financial costs often cause deferral of treatment and financial ruin. These diseases also cost the government in terms of healthcare provision 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 developing countries millions of dollars. Large-scale prevention campaigns are predicted to increase agricultural output and education levels.
108
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 unpaid volunteers who distribute the drugs. The economic burden of NTDs is undervalued and therefore the corresponding economic effect and cost-effectiveness of decreasing prevalence of NTDs is underestimated.
108
The investment return on measures to control NTDs is estimated to be between 14 and 30 percent, depending on the disease and region.
109
Health effects
edit
Coinfection
edit
Coinfection
is a major concern with NTDs, making them more damaging than their
mortality rates
might suggest. Because factors such as poverty, inadequate healthcare and inadequate sanitation practices contribute to 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, coinfection by
Necator americanus
and
Schistosoma mansoni
is common. The effect of each worm weakens the
immune system
, making infection from the other more likely 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.
110
Some evidence from
Senegal
Malawi
, and
Thailand
has shown that helminth infections raise the risk of malarial infection.
111
Prevention, treatment and eradication
edit
Eliminating NTDs in
Côte d'Ivoire
through education and distribution of anti-parasitic drugs
Prevention and eradication are important because "of the appalling stigma, disfigurement, blindness and disabilities caused by NTDs."
16
The principal aim of the
London Declaration on Neglected Tropical Diseases
was the elimination or eradication of
dracunculiasis
leprosy
lymphatic filariasis
onchocerciasis
trachoma
sleeping sickness
visceral leishmaniasis
, and canine
rabies
within ten years of its launch in January 2012.
The declaration 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 the US, UK, United Arab Emirates, Bangladesh, Brazil, Mozambique, and Tanzania.
While there has been a noticeable uptick in biological research into NTDs, prevention may be supplemented by social and development outreach. Spiegel and coauthors advocated for "social offset", which reallocates some funding for biotechnological research to social programs. This attempts to alleviate some of the factors (such as poverty, poor sanitation, overcrowding and poor healthcare) that greatly exacerbate conditions brought on by NTDs. Projects such as these also strengthen the goal of sustained eliminations rather than quickly addressing symptoms.
112
Policy initiatives
edit
There are many prevention and eradication campaigns funded by organizations such as the World Health Organization,
US Agency for International Development
Bill & Melinda Gates Foundation
, and UK
Department for International Development
16
Sustainable Development Goal 3
has the target: "By 2030, [to] end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis,
water-borne diseases
and other
communicable diseases
."
113
WHO Roadmap of 2012
edit
In 2012, WHO published an NTD "roadmap", which contained milestones for 2015 and 2020, and specified targets for eradication, elimination and intensified control of the different NTDs.
114
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
, and lymphatic filariasis
NTDs planned to be eliminated in certain regions: rabies (by 2015 in Latin America, by 2020 in Southeast Asia and the western Pacific),
Chagas disease
(transmission through blood transfusion by 2015, intra-domiciliary transmission by 2020 in the Americas), visceral leishmaniasis (by 2020 in the Indian subcontinent), onchocerciasis (by 2015 in Latin America), and schistosomiasis (by 2015 in the eastern Mediterranean region, the Caribbean, Indonesia, and the Mekong River basin, and by 2020 in the Americas and western Pacific)
NTDs planned to be eliminated in certain countries: human African trypanosomiasis (by 2015 in 80 percent of areas in which it occurs), onchocerciasis (by 2015 in Yemen, by 2020 in selected countries in Africa), and schistosomiasis (by 2020 in selected countries in Africa)
Intensified control with specific targets for 2015 and 2020 are provided for these NTDs: dengue,
Buruli ulcer
cutaneous leishmaniasis
taeniasis
cysticercosis
and
echinococcosis
/hydatidosis, foodborne trematode infections, and soil-transmitted helminthiases.
In 2021, WHO updated their NTD roadmap "Together towards 2030", outlining their approach for 2021–2030.
115
116
: v–vi
Others
edit
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 of 2007
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 the 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.
117
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".
118
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.
citation needed
Deworming treatment
edit
Further information:
Mass deworming
Deworming
treatments in infected children may have some nutritional benefit, as worms are often partially responsible for malnutrition.
16
119
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.
119
To achieve health gains in the longer term, improvements in
sanitation
and hygiene behaviours are also required, together with deworming treatments.
citation needed
The effect of mass deworming on school attendance is disputed. It has been argued that mass deworming has a positive effect on school attendance.
16
The long-term benefits of deworming include a decrease in school absenteeism by 25 percent and an increase in adult earnings by 20 percent.
120
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.
121
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.
122
However, the results of this study are disputed (due to a high risk of bias in the study), and the positive long-term outcomes of mass deworming remain unclear.
121
Integration of treatment
edit
School nurse checks student's health in Kenya
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.
111
123
Some neglected tropical diseases share common vectors (sandflies, black flies, and mosquitos).
111
Both medicinal and vector control efforts may be combined.
124
A four-drug rapid-impact package has been proposed that targets multiple diseases together. This package is estimated to cost US$0.40 per patient, with estimated saving of 26–47% compared to treating the diseases separately. 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.
111
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, which are both transmitted by the same or related mosquito vectors. Vector control, through the distribution of insecticide-treated nets, reduces 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.
124
Integration with water, sanitation and hygiene (WASH) programs
edit
Further information:
WASH § Health aspects
Water, sanitation, and hygiene (
WASH
) interventions are essential in preventing many NTDs, such as
soil-transmitted helminthiasis
125
Mass drug administration
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 where more than one NTD is endemic.
125
In August 2015, the World Health Organization unveiled a global strategy and action plan to integrate WASH with other
public health
interventions to accelerate the elimination of NTDs.
126
The plan aimed to intensify control or eliminate certain NTDs in specific regions by 2020, and referred to the NTD "roadmap" milestones from 2012 that included eradication of dracunculiasis by 2015 and of yaws by 2020, elimination of trachoma and lymphatic filariasis as public health problems by 2020, and intensified control of dengue, schistosomiasis, and soil-transmitted helminthiases.
27
116
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.
127
Reasons why WASH plays an important role in NTD prevention and patient care include:
27
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
128
A 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.
129
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.
130
Improved sanitation
and water management can contribute to reduced 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.
131
Feces
and
urine
that 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.
132
Treatment of many NTDs requires clean water and hygienic conditions for healthcare facilities and households. For
Guinea-worm disease
Buruli ulcer
, and
cutaneous leishmaniasis
, wound management is needed to speed up healing and reduce disability.
Lymphatic filariasis
causes chronic disabilities. People who have this disease need to maintain rigorous personal hygiene with water and soap to prevent secondary infections.
133
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 the quality of life of people affected by NTDs.
134
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
135
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.
136
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.
137
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.
138
Pharmaceutical market
edit
Biotechnology
companies in the developing world have targeted neglected tropical diseases due to a need to improve global health.
139
Mass drug administration
is considered a possible method for eradication, especially for lymphatic filariasis, onchocerciasis, and trachoma, although drug resistance is a potential problem.
140
According to Fenwick,
Pfizer
donated 70 million doses of drugs in 2011 to eliminate trachoma through the International Trachoma Initiative.
16
Merck
has helped The African Programme for the Control of Onchocerciasis (APOC) and Oncho Elimination Programme for the Americas to greatly diminish the effect of onchocerciasis by donating
ivermectin
16
Merck KGaA
pledged to give 200 million tablets of
praziquantel
, the only cure for
schistosomiasis
, over 10 years.
141
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.
16
Novartis
has pledged leprosy treatment, and
EISAI
pledged two billion tablets to help treat lymphatic filariasis.
16
NGO initiatives
edit
Non-governmental organizations
that focus exclusively on NTDs include the
Schistosomiasis Control Initiative
Deworm the World
, and the END Fund.
142
Despite under-funding, treatment and prevention of many neglected diseases is cost-effective. 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 the 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.
citation needed
Health Action International
based in Amsterdam worked with the WHO to get snakebite envenoming on the list of neglected tropical diseases.
95
Public-private initiatives
edit
An alternative to the profit-driven
drug development
model emerged in 2000 to address 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 combat neglected diseases.
143
Drugs for Neglected Disease initiative (DNDi) is one of these PDPs that has already developed new treatments for NTDs.
144
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.
145
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.
146
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.
147
148
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, the
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.
149
150
151
Affordability of the resulting drugs and vaccines is one of the key criteria for grant awards.
149
London Declaration on Neglected Tropical Diseases
edit
The London Declaration on Neglected Tropical Diseases, initiated by the Bill and Melinda Gates Foundation launched on 30 January 2012 in London. Inspired by the WHO roadmap to eradicate or prevent transmission for neglected tropical diseases, it aimed to eradicate or reduce NTDs by the year 2020.
152
It was endorsed by governments and organisations around the world, as well as major pharmaceutical companies including
Abbott
AstraZeneca
Bayer HealthCare Pharmaceuticals
Becton Dickinson
Bristol-Myers Squibb
Eisai
Gilead Sciences
GlaxoSmithKline
Johnson & Johnson
Merck KGaA
Merck Sharp & Dohme, MSD
Novartis
Pfizer
, and
Sanofi
153
It was not a complete success, but millions of lives were saved, the burden of the infections was reduced, and 42 countries eliminated at least one disease.
154
To commemorate the programme, WHO adopted 30 January as the
World NTD Day
155
Kigali Declaration on Neglected Tropical Diseases
edit
The
Kigali Declaration on Neglected Tropical Diseases
was launched at the Kigali Summit on Malaria and Neglected Tropical Diseases (NTDs) hosted by the Government of Rwanda at its capital city
Kigali
on 23 June 2022.
156
It was signed as a support for the
World Health Organization
's 2021–30 road map for NTDs and the target of Sustainable Development Goal 3 to end NTD epidemics; and as a follow-up project of the London Declaration .
157
Supported by WHO, governments of the
Commonwealth of Nations
pledged the endorsement, along with commitments from
GSK plc
Novartis
, and
Pfizer
158
Others
edit
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 a pioneer in neglected tropical disease research. The Great Neglected Tropical Diseases Network was a consortium of scientists from all over the world, hand-picked by 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 understanding 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
159
Epidemiology
edit
See also:
Neglected tropical diseases in India
Global overlap of six of the common NTDs, specifically guinea worm disease, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma, in 2011
The distribution of neglected tropical disease disproportionally affects about one billion of the world's poorest populations,
160
causing mortality, disability, and morbidity.
161
Lack of funding, resources, and attention can result in treatable and preventable diseases causing death.
162
Factors like political dynamics, poverty, and geographical conditions can make the delivery of NTD control programs difficult.
160
Intersectional collaboration of poverty reduction policies and neglected tropical diseases creates cross-sector approaches to simultaneously address these issues.
160
The six most common NTDs include
soil-transmitted helminths
(STHs)—specifically roundworms (
Ascaris lumbricoides
), whipworm (
Trichuris trichiura
), and hookworms (
Necator americanus
and
Ancylostoma duodenale
)—schistosomiasis, trachoma, and lymphatic filariasis (LF).
125
These diseases affect one-sixth of the world's population, with 90 percent of the disease burden occurring in sub-Saharan Africa.
125
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) widespread inclusion of diseases and injury causes with the estimation of missing data.
163
However, the DALY has been criticized as a "systematic undervaluation" of disease burden. King
164
asserts that 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 have to take the context of poverty more into account. King also emphasizes that DALYs may not capture the non-linear effects of poverty on the cost-utility analysis of disease control. The Socio-Demographic Index (SDI) and Healthy Life Expectancy (HALE) are other summary measures that can be used to take into account other factors.
165
HALE is a metric that weights years lived and health loss before death to provide a summary of population health.
165
SDI is a measurement that includes lag-distributed income per capita, average education, and fertility rate.
161
Socioeconomic factors greatly influence the distribution of neglected tropical diseases, and not addressing these factors in models and measurements can lead to ineffective public health policy.
162
Research and development
edit
The structure of two of the ivermectins, an important class of drug in the control of Onchocerciasis.
NTD interventions include programs to address
environmental
and
social determinants of health
(e.g., vector control, water quality, sanitation) as well as programs offering
mass drug administration
for disease prevention and treatment. Drug treatments exist
166
to confront many of the NTDs and represent some of the world's
essential medicines
167
168
Despite significant health and economic improvements using available medicines,
169
170
171
172
the low number of new compounds being researched and developed for NTDs is an ongoing and significant challenge.
167
173
174
The dearth of candidates in pharmaceutical company
drug pipelines
is primarily attributed to the high costs of drug development and the fact that NTDs are concentrated among the world's poor.
173
175
Other disincentives to investment include weak existing infrastructure for distribution and sales as well as concerns regarding intellectual property protection.
172
However, the major stakeholders in NTD drug development—governments, foundations, pharmaceutical companies, academia, and
NGOs
—are involved in activities to help address the research and development shortfall and meet the many challenges presented by neglected tropical diseases.
176
Initiatives include public-private partnerships, global R&D capacity building, priority vouchers to speed drug approval processes, open source scientific collaborations, and harmonization of global governance structures concerning NTDs.
citation needed
The diseases considered neglected tropical diseases vary. Some researchers no longer consider
malaria
HIV
, and
tuberculosis
to be neglected due to the amount of public attention and increased funding they have received. Outside "The Big Three", the seven most prevalent neglected tropical diseases in order of their global prevalence are
ascariasis
trichuriasis
hookworm infection
schistosomiasis
lymphatic filariasis
, and
trachoma
33
These seven are among a larger list of thirteen major NTDs:
onchocerciasis
leishmaniasis
Chagas disease
leprosy
human African trypanosomiasis
(sleeping sickness),
dracunculiasis
, and
Buruli ulcer
33
Deficient market
edit
In their 2002 review of the U.S.
Food and Drug Administration
(FDA) databases and the
European Agency for the Evaluation of Medicinal Products
, Troullier
et al.
found that 16 out of 1393 new chemical entities were approved for NTDs between 1975 and 1999 (~1%).
167
Cohen
et al.
revisited the data and using the same methodology found 32 new chemical entities during the time period.
168
In a second analysis using an expanded list of NTDs based on the G-FINDER survey,
177
the number was slightly higher, with 46 new drugs and vaccines approved (~3% of the total including HIV drugs).
168
Between 2000 and 2009, there has been some increase with an additional 26 newly approved drugs and vaccines for NTDs.
168
A number of factors are recognized as contributing to the low number. The barrier most reported is the high cost of drug development. Estimates are that pharmaceutical companies' development costs to approval fall between $500 million and $2 billion.
178
DiMasi, Hansen, and Grabowski calculated an average of $802 million in year 2000 dollars.
179
Furthermore, the time that drugs are approved for use averages seven years out of the twenty years on patent, meaning a tendency for the market to focus on diseases of developed nations where high prices can be used to recoup research and development costs, and subsidize failed R&D efforts. In short, NTD research and development is considered a high investment risk, given that NTDs predominantly affect the poor in low- and middle-income countries.
173
175
Additional barriers include drug safety regulatory requirements, intellectual property protection problems, and poor infrastructure for distribution and sales.
172
173
Although drug companies have not invested heavily in NTDs, in several cases, rather than focus on profits, some have decided to donate key drugs to address NTDs. For example, Merck has had a program since the mid-1980s to donate ivermectin (Mectizan) indefinitely to support the global fight against onchocerciasis. GlaxoSmithKline and several other large pharmaceutical companies have donation programs as well. Drug donation, however, does not ameliorate the deficiency of new chemical entities being researched and developed. This is especially of concern with reports of emerging resistance among existing drugs.
180
181
Policy initiatives
edit
Public–private partnerships
edit
Melinda and Bill Gates speak during press conference at the World Economic Forum in Davos, Switzerland, January 30, 2009.
Governments, foundations, the non-profit sector, and the private sector have found new connections to help address market deficiencies by providing funding support and spreading both the costs and risks of NTD research and development. The proliferation of
public–private partnerships
(PPPs) has been recognized as a key innovation in the past decade, helping to unlock existing and new resources.
citation needed
Major PPPs for NTDs include: the
Sabin Vaccine Institute
, Norvartis Vaccines Institute for Global Health, MSD Wellcome Trust
Hilleman Laboratories
, Infectious Diseases Research Institute,
Institut Pasteur
and
INSERM
, WIPO Re:Search, and the
International Vaccine Institute
175
Likewise, a number of new academic drug development centers have been created in recent years drawing in industry partners. Support for these centers is frequently traced to the
Bill & Melinda Gates Foundation
, the
Sandler Foundation
, and the
Wellcome Trust
182
R&D capacity building in middle-income countries
edit
Growing NTD research and development capacity in middle-income countries is an area of policy interest. A 2009 study of biotechnology companies in India, China, Brazil, and South Africa revealed 62 NTD products in development and on the market out of approximately 500 products offered (~14%). When products to fight HIV, malaria, and TB were included in the analysis, the number increased to 123 products, approximately 25% of the total products offered.
citation needed
Researchers have argued that, unlike most multinationals, small and mid-sized "Global South" companies see significant business opportunities in the development of NTD-related diagnostics, biologics, pharmaceuticals, and services.
139
Potential actions to improve and expand this R&D capacity have been recommended, including expansion of human capital, increased private investment, knowledge and patent sharing, infrastructure building for business incubation, and innovation support.
citation needed
Innovation prizes and grants
edit
Competitive innovation prizes have been used to spur development in a range of fields such as aerospace engineering, clean technology, and genomics. The
X-Prize Foundation
is launching a competition for high-speed, point-of-care diagnostics for tuberculosis.
citation needed
A more widely defined annual "Global Health EnterPrize" for neglected tropical diseases has been proposed to reward health innovators, particularly those based in countries where NTDs represent a serious health burden.
citation needed
The
Bill & Melinda Gates Foundation
offers the Grand Challenges Explorations Opportunities on a rolling basis. This grant program allows individuals from any organization or background to apply to address priority global health issues. Each project award is $100,000 and is drawn from a Foundation funding pool of $100 million. Awardees have tended to offer research projects on topics that are highly speculative but offer potentially game-changing breakthroughs in global health.
citation needed
FDA priority review vouchers (PRV)
edit
In 2006, Ridley
et al.
recommended the development of a
priority review voucher
(PRV) in the journal
Health Affairs
. It gained interest from Senator
Sam Brownback
of Kansas, who championed its introduction in the
FDA Amendments Act of 2007
. Under the enacted law, FDA approval of a non-NTD drug can be accelerated through the drug review process if paired with a drug that addresses an NTD. The potential economic benefit to a pharmaceutical company is estimated to be potentially as high as $300 million per drug. Three drugs have earned NTD PRVs to date (December 2014):
Coartem
(by Novartis, for malaria);
bedaquiline
(by Janssen, for TB); and
miltefosine
(by Knight, for leishmaniasis). However, the success of the PRV system is now under much scrutiny, given that Knight benefitted by $125 million from the sale of a PRV earned from a drug (miltefosine) that was largely researched and developed by the WHO.
Médecins Sans Frontières
are now pressuring Knight to guarantee to supply miltefosine at cost price, thus far without success.
citation needed
The PRV isn't limited to the pairing of drugs within a single company as it can be transferred between companies. Companies with NTD drug candidates in their pipelines but without a blockbuster drug are able to sell their vouchers, producing financial returns. In the EU, similar priority review incentives are now under consideration to increase the speed of regulatory pricing and reimbursement decisions.
citation needed
However, PRVs have been criticized as being open to manipulation and possibly encouraging errors through too rapid regulatory decision-making.
183
Open source collaboration initiatives
edit
The Drugs for Neglected Diseases Initiative, a web-focused not-for-profit drug R&D organization dedicated to creating new NTD treatments.
Several companies and scientific organizations are participating in open-source initiatives to share drug data and patent information over the web, and facilitate virtual collaboration on NTD research.
One rich area to explore is the wealth of genomic data resulting from the sequencing of parasite genomes. These data offer opportunities for the exploration of new therapeutic products using computational and
open-source
collaboration methods for drug discovery.
184
185
The Tropical Disease Initiative, for example, has used large amounts of computing power to generate the protein structures for ten parasite genomes. An open-source drug bank was matched algorithmically to determine compounds with protein interaction activity, and two candidates were identified. In general, such methods may hold important opportunities for
off-label use
of existing approved drugs.
History
edit
In 1977,
Kenneth S. Warren
, an American researcher, invented the concept of what is now "neglected tropical diseases".
186
In 2005
Lorenzo Savioli
, a senior United Nations civil servant, was appointed director of the "Department of Control of Neglected Tropical Diseases".
187
The World Health Organization definition of neglected tropical disease has been criticised to be restrictive and described as a form of epistemic injustice.
188
97
See also
edit
Contagious disease
Fecal–oral route
transmission
Neglected Tropical Disease Research and Development
Drugs for Neglected Diseases Initiative
Eradication of infectious diseases
Global Network for Neglected Tropical Diseases
Orphan diseases
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Infectious diseases
Tropical diseases
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Neglected tropical diseases
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