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Neglected diseases
Md. Murad Hossain, Maria Elena Sarmiento, Armando Acosta, Mohd Nor Norazmi
Introduction
Neglected diseases often termed as neglected tropical diseases (NTDs) are endemic in 149
countries, affect over one billion of the world’s poorest people, claim an estimated 534000 deaths
each year and cause a disease burden of 57 million disability-adjusted life–years (DALYs) (1-3).
Although billions of peoples are still getting affected with NTDs, much progress has been made in
the efforts of controlling and eliminating the diseases. According to the third World Health
Organization (WHO) report on NTDs published in 2015, over 74 countries worldwide are ready to
implement national NTD master plans, six countries have the elimination of lymphatic filariasis,
incidence of human African trypanosomiasis has been reduced by 90% in African countries, 27
countries achieved the WHO target of 75% treatment coverage of school-age children to prevent
soil-transmitted helminthiases at the end of 2014 (1).
In 2011, WHO Strategic and Technical Advisory Group (STAG) for NTDs adopted a roadmap named
“Accelerating work to overcome the global impact of neglected tropical diseases” for control,
elimination and eradication of NTDs. In this roadmap, WHO has recommended five strategies for
prevention and control of NTDs: preventive chemotherapy intensified case management, control
of disease vectors, provision of clean water and sanitation and veterinary public health measures
(4). Preventive chemotherapy with community based mass drug administration plays central role
in the prevention and control of NTDs in the endemic areas. For many NTDs, low-cost, safe and
effective treatments are available; however, their accessibility often remains limited to the people
living the endemic areas with high risk of getting infected. For some other NTDs, it needs complex
diagnosis and expensive treatment. Therefore, adopting preventive measures such as combined
preventive chemotherapy, increased access to clean water, improved sanitation, reduction of
disease transmission and execution of integrated control measures might play crucial part in the
confinement of the diseases.
The WHO roadmap 2011 has set up numerous targets and milestones for eradication, elimination
and control of NTDs by 2015 and 2020 (4). In 2013, the 66th World Health Assembly adopted
resolution WHA66.12 which calls for intensified, integrated measures and planned investments to
improve the health and social well-being of people affected with NTDs. WHO is working with
Member States to ensure implementation of roadmap of 2011 and resolution of WHA66.12. In
April 2015, the eighth meeting of the STAG for NTDs took place where the meeting agenda
focused on the progress in achieving WHO’s roadmap-2011 targets and increased domestic
investments targets for the control, elimination and eradication of NTDs.
Neglected diseases
Neglected diseases are a group of infectious, chronic, debilitating diseases which are endemic in
the populations of low-income settings of tropical and subtropical countries. These diseases are
caused by bacterial, protozoal, helminth, ectoparasitic, fungal and viral diseases; mostly prevalent
in tropics and subtropics and remain truly neglected, and therefore they are often termed as
NTDs.
NTDs are closely associated with poverty and exert negative effects on the social-ecological
systems. They have emerged as a severe health burdens on the world’s poorest economic regions
of Africa and Asia, which typically affect the poorest people particularly living in areas with poor
sanitation, unsafe drinking water, substandard housing and little or no access to health care. These
diseases cause an estimated death of 0.5 to 1 million per annum which apparently ranked them a
higher global disease burden than that of HIV/AIDS. Moreover, the co-incidence of NTDs with
HIV/AIDS and tuberculosis can cause HIV/AIDS and tuberculosis more lethal. At present, some
NTDs have effective therapeutic drugs which have easy access to the people of the developed
world but, ironically, these drugs are not universally available to the poor people of the developing
or poorer areas, the people who suffer from the NTDs most.
List of neglected diseases and the causative pathogen
There was an argue among theWHO, centers for disease control and prevention (USA),
and infectious disease experts over which diseases would be classified as NTDs. Feasey et al. listed
13 NTDs namely ascariasis, buruli ulcer, Chagas disease, dracunculiasis, hookworm infection,
human African trypanosomiasis, Leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis,
schistosomiasis, trachoma, and trichuriasis (5). Another NTD expert, Fenwick, included 12 of the
above diseases except the hookworm infection in his list of NTDs (6). The WHO recognized 17
diseases as NTDs: African trypanosomiasis, Buruli ulcer, Chagas disease, Cysticercosis and
taeniasis, Dengue fever, Dracunculiasis, Echinococcosis, Leishmaniasis, Leprosy, Lymphatic
filariasis, Onchocerciasis, Rabies, Snakebite, Schistosomiasis, Soil-transmitted helminthiasis,
Trachoma, Yaws (7).
However, with the course of time, the list of NTDs has been largely expanded and currently
comprises over 40 diseases (8). These NTDs result mainly from four different causative pathogens
such as Bacteria, Protoza, Helminths and Viruses. Beside these, a few NTDs are also caused by
Fungal and Ectoparasitic infections. Table 1 presents the causative agent(s) and the endemic areas
of these potential NTDs (3).
. Table 1. List of NTDs, their causative agent(s) and the potential endemic areas of these NTDs
Bacterial infections
NTDs Causative agent(s) Endemic areas
Buruli ulcer Mycobacterium ulcerans Australia, Guyana, Malaysia, Mexico, Peru, Sri Lanka, Papua New Guinea, West and Central Africa
Bartonellosis Bartonella henselae, other Bartonella spp.
Globally distributed
Bovine tuberculosis
Mycobacterium bovis Globally distributed (highest rates in developing countries)
Cholera Vibrio cholerae Southern and Central Africa, Dominican republic, Haiti, Cambodia, Papua New Guinea, Thailand, Malaysia, Indian subcontinent
ETEC infection Enterotoxigenic Escherichia coli (ETEC)
Globally distributed (highest rates in developing countries)
Salmonellosis Salmonella enteric serovars, S. enteridis, S. typhimurium, S. typhi, S. paratyphi
Globally distributed (highest rates in developing countries)
Shigellosis Shigella dysenteriae, S. boydii, S. flexneri, S. sonnei
Globally distributed (highest rates in developing countries)
Leprosy Mycobacterium leprae Brazil, China, Mozambique, Myanmar, Madagaskar, Indonesia, India, Nepal, Philippines, Vietnam, Sudan and other tropical and subtropical regions
Leptospirosis Leptospira interrogans Globally distributed (highest rates in developing countries)
Trachoma Chlamydia trachomatis Africa, Middle East, part of Asia, Australia, Mexico, South America
Treponematoses Treponema pallidum Globally distributed (highest rates in tropical regions)
Relapsing fever Borrelia recurrentis, B. duttoni, other Borrelia spp.
Africa (highest rates), parts of Americas, Asia, Europe
Viral infections
NTDs Causative agent(s) Endemic areas
Dengue Dengue fever virus (genus: Flavivirus) Indian subcontinent, South-East Asia, Pacific Islands, Central and South America, Parts of Africa and Northern Australia
Rabies Rabies virus (genus: Lyssavirus) Globally distributed
Yellow fever Yellow fever virus (genus: Flavivirus) South America, West and Central Africa, occasionally in East Africa and central America
Japanese encephalitis
Japanese encephalitis virus (genus: Flavivirus) Indian subcontinent, South-East Asia, intermittently in Northern Australia, and the Western Pacific
Rift Valley fever Rift Valley fever virus (genus: Phlebovirus) Africa and Arabian Peninsula
Viral haemorrhagic fevers
Arenaviridae: Lassa virus, Chapare virus, Guanarito virus, Junin virus, Machupo virus, Sabia virus Bunyaviridae: Crimean-Congo haemorrhagic fever virus (HFV), Hanta viruses, Puumala virus, Filoviridae: Ebola virus, Marburg virus Falviviridae: Omsk HFV, Kyasanur forest disease virus
Certain viruses are endemic in certain areas. Lassa virus: Guinea, Liberia, Nigeria, Sierra Leone Crimean-Congo HFV: Africa, Arabian Peninsula, Bulgaria, Central Asia, Turkey, South-West Russia Hanta virus: Globally distributed; Filoviridae: Angola, Congo, Gabon, Kenya, Sudan, Uganda Omsk HFV: West Siberia Kyasanur forest disease virus: India
Helminth infections
NTDs Causative agent(s) Endemic areas
Dracunculiasis Dracunculus medinensis Mali, South Sudan, Ethiopia
Cysticercosis/taeniasis
Taenia solium, T. saginata, Diphyllobothrium latum
Globally distributed
Enterobiasis Enterobius vermicularis Globally distributed (highest rates in developing countries)
Echinococcosis Echinococcus granulosus, E. multilocularis
Globally distributed
Intestinal fluke infection
Echinosoma spp. Fasciolopsis buski, Metagonimus spp.
Bangladesh, India, Malaysia, Indonesia, Taiwan, China, Philippines, Vietnam, Thailand, Cambodia
Fascioliasis Fasciola gigantic, F. hepatica Bolivia, Cuba, Chile, Ecuador, Egypt, Iran, France, Portugal, Peru, Spain
Clonorchiasis Clonorchis sinensis China, South Korea, Taiwan
Paragonimiasis Paragonimus spp. India, Pakistan, Nepal, Sri Lanka, Malaysia, Thailand, Vietnam, Laos, Philippines, Taiwan, China, South Korea, Japan, Cameroon, Nigeria, Liberia, Costa Rica, Ecuador, Guinea, Guatemala, Gabon, Peru, Panama, Mexico
Opisthorchiasis Opisthorchis felineus, O. viverrini Thailand, Vietnam, Laos, Ukraine, Siberia, Kazakhstan, Russia
Lymphatic filariasis
Wuchereria bancrofti, Brugia malayi, B. timori
Africa, Asia, Central and Southern America
Loiasis Loa loa Central and West Africa
Mansonellosis Masonella perstans, M. streptocerca, M. ozzardi
Caribbean, Central and South America, Sub-Saharan Africa
Onchocerciasis Onchocerca volvulus Africa, a small part of Central and Southern America
Schistosomiasis Schistosoma haematobium, S. guineensis, S. intercalatum, S. japonicum, S. mansoni, S. mekongi
Sub-Saharan Africa, Parts of Central and West Africa, some Caribbean islands, China, Indonesia, Philippines, Cambodia, Laos
Ascariasis Ascaris lumbricoides Globally distributed
Hookworm infection
Ancylostoma duodenale, Necator americanus
Globally distributed
Strongyloidiasis Strongyloides stercoralis Globally distributed
Trichuriasis Trichuris trichiura Globally distributed
Toxocariasis Toxocara canis, T. cati Globally distributed
Trichinellosis Trichinella spiralis, other Trichinella spp.
Globally distributed
Fungal infections
NTDs Causative agent(s) Endemic areas
Mycetoma (Madura foot)
Various fungi (eumycetoma) and bacteria (actinomycetoma, pseudomycetoma)
Africa, India, Central and South America
Paracoccidiomycosis
Paracoccidioides brasiliensis Argentina, highest rates in Brazil (80%), Colombia, Ecuador, Mexico, parts of central America, Venezuela
Ectoparasitic infections
Myiasis Parasitic fly larvae (Calliphoridae Oestridae, Sarcophagidae and others)
Globally distributed (highest rates in tropical and subtropical regions)
Scabies Sarcoptes scabiei Globally distributed (highest rates in tropical and subtropical regions)
Protozoal infection
NTDs Causative agent(s) Endemic areas
Chagas disease Trypanosoma cruzi Latin America
Human African trypanosomiasis
Trypanosoma brucei gambiense, T. brucei rhodesiense
Africa
Amoebiasis Entamoeba histolytica Globally distributed (highest rates in developing countries)
Balantidiasis Balantidium coli South America, Middle East, Phillipines, Papua New Guinea
Giardiasis Giardia intestinalis Globally distributed (highest rates in developing countries)
Leishmaniasis Visceral leishmaniasis: Leishmania donovani, L. chagasi, L. infantum Muco-cutaneous leishmaniasis: L. major, L. tropica, L. mexicana, L. braziliensis
Indian subcontinent, Asia, Africa, South Africa, Mediterranean basin
Why neglected diseases are called neglected?
Neglected diseases are said to be neglected because they were often overlooked by country’s
public health programs, drug developers, or by government officials involved in drug access and by
the news media. Now why did neglected diseases remain neglected? Reasons for these diseases to
remain neglected are many-fold. Lack in visible danger because they usually do not cause dramatic
outbreaks, and they are not able to kill a large numbers of people at a short course of time.
Instead, they usually toll their due over a longer period of time, leading to crippling deformities,
severe disabilities and/or relatively slow deaths (9). Neglected diseases did not receive high
priorities for their treatment or prevention because they typically affect the poorest of the poor
people in the tropical areas and do not affect people who live in the developed nations. Private
pharmaceutical companies usually focus on their profit and mainly interested to do invest for the
development of treatment tools of the diseases that persist in developed countries from where
they can make profit. In contrary, pharmaceutical companies cannot recover the cost of
developing and producing drugs/treatments for the neglected diseases where the consumers are
mainly the poorest people of the world. Most important reason may be over focusing on the ‘big
three’ diseases ‘Malaria, tuberculosis and HIV/AIDS’ due to their overwhelming role of in major
global health burden, mortality and morbidity rate which are responsible for several million deaths
every year. These ‘big three’ diseases account for millions of disability-adjusted life years (DALYs)
which collectively put a massive negative impact on the social and economic development of the
most severely affected countries, which, in turn, exacerbates poverty (10, 11). For their
devastating role, most of the funding has been allocated for the research and development of new
tools to control, prevent and eventually to eliminate the “big three” diseases.
The other reasons could be the scarcity of data regarding local and global burden estimates,
inadequate political willingness, weak leadership and lack of lobbies for the people who are most
severely affected by these diseases, and insufficient financial support mechanisms for their control
and prevention [12, 13].
Global burden of neglected tropical diseases
The Global Burden of Disease Study 2010 (GBD 2010) and its related articles attempted
comprehensively to quantify the burden of almost 300 diseases, including NTDs (14). The GBD
2010 introduces a metric called “disability-adjusted life year (DALY), in order to assess and
compare the relative impact of a number of diseases locally and globally (15). The DALY values are
the summation of two components: years of life lost due to premature mortality (YLLs) and years
lived with disability (YLDs) (14). So the DALY estimates could represent the metric of estimating
the burden of the chronic effects of NTDs infections. Table 2 presents estimated DALYs caused by
the major NTDs. Recent studies suggest that most of the NTDs are disablers rather than killers.
Therefore the DALYs for many of the NTDs (such as hookworm disease and the food-borne
trematodiases, schistosomiasis, intestinal nematode infections, trachoma, cysticercosis, and
onchocerciasis) result from YLDs (i.e., disability, not deaths).
Table 2. Estimated global burden (in DALYs, YLDs and YLLs) of the NTDs from the Global Burden of Disease Study 2010.
Disease DALYs in millions YLDs in millions
YLLs in millions No. of deaths
Intestinal nematode infections
Hookworm disease 3.23 3.23 0 -
Ascariasis 1.32 1.11 0.20 2700
Trichuriasis 0.64 0.64 0 -
Leishmaniasis 3.32 0.12 3.19 51600
Schistosomiasis 3.31 2.99 0.32 11700
Lymphatic filariasis 2.78 2.77 0 -
Food-borne trematodiases 1.88 1.87 0 -
Rabies 1.46 <0.01 1.46 26400
Dengue 0.83 0.01 0.81 14700
African trypanosomiasis 0.56 0.08 0.55 9100
Chagas disease 0.55 0.30 0.24 10300
Cysticercosis 0.50 0.46 0.05 1200
Onchocerciasis 0.49 0.49 0 -
Trachoma 0.33 0.33 0 -
Echinococcosis 0.14 0.11 0.03 1200
Yellow fever <0.001 <0.01 <0.01 -
Other NTDs 4.72 3.69 1.03 23700
Intestinal nematode infections were the most severe among the NTDs considering the DALY
estimates in the GBD 2010. Among intestinal nematodes, hookworm disease was estimated to
have the largest YLDs which accounts for 62% of the DALYs. The huge contribution of hookworm
disease to the YLDs of nematodes is due to moderate and severe anemia across several different
populations, including children and pregnant women (16, 17).
Schistosomiasis is another important NTD that results in chronic pain, inflammation, exercise
intolerance, and malnutrition, among other morbid sequelae. Schistosomiasis, under certain
scenarios, generated higher DALYs compared to that of malaria or other better-known conditions
(18). Recent study showed the link of female urogenital schistosomiasis in the risk of acquiring
HIV/AIDS (19). Trachoma and onchocerciasis are the major NTDs that are linked to blindness.
Trachoma is also evident to affect more than 40 million people in over 50 countries and over 8
million people are at immediate risk of irreversible blindness (4). The food-borne trematodiases,
cysticercosis, and echinococcosis, might be considered as important pathogens of global disability.
Two other key food-borne trematodiases, clonorchiasis or opisthorchiasis, were shown associated
with cholangiocarcinoma in Southeast Asia (20, 21). Cysticercosis is involved in causing epilepsy,
severe chronic headaches and hydrocephalus, depressive disorders, stroke, gliomas, and other
neurological sequelae (22).
NTDs like dengue, rabies, and African trypanosomiasis are considered as killer NTDs and practically
no disability was associated with nonlethal effects from these diseases. However, according to the
roadmap 2011, dengue fever affects millions of people worldwide. In 2010, dengue fever was
reported in all six WHO regions and indigenous outbreaks were reported for the first time in
Europe. Dog-mediated rabies causes the death of nearly 55000 people every year in Africa and
Asia. More than 14 million people worldwide receive post-exposure prophylaxis following bites
from suspected rabid animals (4).
It is argued that the collective global burden of NTDs is higher than that of malaria and
tuberculosis and is close to that of HIV/AIDS. On the basis of technical reports of WHO and the
annex table 3 of the world health report 2004, it was shown that the collective global burden of
the initial set of WHO recognized 13 most important NTDs (56.6 million DALYs) is higher than that
of tuberculosis (34.7 million DALYs) and malaria (46.5 million DALYs) which strongly urges for
adopting measures for the integrated control of NTDs (23). According to GBD 2010, the collective
global burden for NTDs was estimated up to almost 48 million DALYs which is comparable to
tuberculosis (49 million) and is almost half of the global burden of malaria (83 million DALYs) and
HIV/AIDS (82 million DALYs) (24). However, it is worth mentioning that there are substantial
uncertainties and limitations regarding the estimation of global burden, and it particularly proved
challenging for estimating the global burden of NTDs.
Although the global burden of diseases has been measured in terms of DALY, however, DALY itself
has some shortcomings and accounts only the effects on direct health loss by NTDs but do not
consider the economic impact of the NTDs that results from detrimental effects on school
attendance and child development, agriculture (especially from zoonotic NTDs), and overall
economic productivity (12, 25). Even it doesn’t consider the direct costs of treatment, surveillance,
and prevention measures. Besides these, many NTDs also cause a matter of social stigma and the
spillover effects to family and community members (26, 27), loss of tourism (28), and health
system overload (e.g., during dengue outbreaks). Ultimately NTD control and elimination efforts
could produce social and economic benefits not necessarily reflected in the DALY metrics,
especially among the most affected poor communities.
Interventions to prevent NTDs
In the ‘Roadmap 2011’ to overcome the global impact of NTDs approved by strategic and technical
advisory group for NTDs, WHO adopted five strategies for the prevention, control, elimination and
eradication of NTDs (4).
Preventive chemotherapy
Preventive chemotherapy intends to optimize the large-scale use of safe, single-dose medicines
that can effectively reduce the extensive morbidity associated with four helminthiases (lymphatic
filariasis, onchocerciasis, schistosomiasis and soiltransmitted helminthiases). Moreover, the large-
scale administration of azithromycin, a key component of the SAFE (Surgery, Antibiotics, Facial
cleanliness and Environmental improvement) strategy against trachoma, is amenable to close
coordination (and, in future, possibly co-administration) with interventions targeted at
helminthiases. WHO is promoting preventive chemotherapy as a potential intervention to reduce
significantly the morbidity caused by five widely distributed NTDs (lymphatic filariasis,
onchocerciasis, schistosomiasis, soil-transmitted helminthiases and trachoma) since 2001. By the
end of 2009, 705 million people suffering from these five NTDs reached under coverage of the
preventive chemotherapy.
Implementation of preventive chemotherapy with high coverage will reduce morbidity and halt
the recurrence of the above five targeted NTDs which will ensure to reach to WHO’s goals of
elimination of these five NTDs by 2020. Some intermediate milestones for their elimination can be
achieved by 2015. Critical assumptions to reach these objectives are: (1) that solutions be found to
make praziquantel widely available along with the other donated medicines in the preventive
chemotherapy package; and (2) that funding for implementation accompanies the scaling up of
interventions, through sustained commitment of international donors and enhanced in-country
support by the health and education sectors.
Intensified case-detection and case management
Intensified case-detection and management intervention targets the prevention and controlling of
NTDs those have no appropriate medicines available for preventive chemotherapy. This
intervention urges caring for infected people and for those who are at risk of infection. The key
processes are (i) making the diagnosis as early as possible, (ii) providing treatment to reduce
infection and morbidity, and (iii) managing complications. Under the intensified case management
strategy, WHO focuses on the prevention and control of Chagas disease, Buruli ulcer,
leishmaniasis, human African trypanosomiasis, leprosy and yaws. The new focus on better access
to specialized care through improved case-detection and decentralized clinical management aims
to prevent mortality, reduce morbidity and interrupt transmission.
Vector and intermediate host control
Vectors and their intermediate hosts control is an important cross-cuting intervention that aims to
enhance the impact of preventive chemotherapy and intensified disease management. Almost all
NTDs involve transmission by vectors (insects) or intermediate hosts (such as aquatic snails).
Therefore, vector and intermediate host control is crucial to prevent the transmission of NTDs.
Vector control is particularly important for controlling of dengue and Chagas disease, and in
preventing some forms of leishmaniasis. Vector control intervention can play a major role for the
elimination phase of diseases like lymphatic filariasis and schistosomiasis.
WHO is implementing vector control through its integrated vector management (IVM) approach
which is a combination of different intersectoral interventions aimed at improving the efficiency,
ecological soundness and sustainability of disease control measures against vector-borne
neglected tropical diseases, including the sound management of public-health pesticides.
Veterinary public health at the human–animal interface
Veterinary public-health at the human–animal interface implements those actions that are
essential to prevent, control and eliminate suffering and economic loss caused by neglected
zoonotic diseases (NZDs) in both humans and animals. Veterinary public health deals with the
health of peoples as well as animals. An integrated human and animal health program will be
effective in the prevention, control and elimination of a number of NZDs (such as human dog-
mediated rabies, cystic and alveolar echinococcosis, fasciolasis and foodborne trematodiases) and
NTDs with a zoonotic component (including zoonotic trypanosomiasis, and visceral and cutaneous
forms of zoonotic leishmaniasis).
Provision of safe water, sanitation and hygiene
According to the estimation of United Nations, globally 900 million people are in lack of access to
safe drinking-water, and 2500 million live without appropriate sanitation. Without having the
health benefits that can obviously be obtained from safe water, improved sanitation and hygienic
life styles, the targets of Millennium Development Goal 7 would not be achievable, especially in
WHO’s African and South-East Asia regions.
If the current situation of “access to safe water, improved sanitation and hygienic life styles”
doesn’t improve, many of the NTDs and other communicable diseases will not be eliminated, and
certainly not be eradicated.
Eradication, elimination and control of NTDs: Target 2015 and 2020
In the roadmap approved in 2011 for “Accelerating work to overcome the global impact of
neglected tropical diseases”, WHO set up important targets and milestones for the eradication,
elimination and control of NTDs.
Eradication
Among the 17 NTDs, WHO currently aims to global eradication of two NTDs, Dracunculiasis
(guinea-worm disease) by 2015 and Endemic treponematoses (yaws) by 2020.
Dracunculiasis (guinea-worm disease)
Dracunculiasis eradication campaign was started in the early 1980s. Since then, there has been a
significant decline (more than 99%) in the annual incidence of the disease, from 892 055 cases in
1989 to 1058 in 2011. Several initiatives such as active searches of the dracunculiasis infection in
the endemic villages, rapid case-containment, enhanced surveillance and access to improved
drinking-water have helped to drastically reduce the prevalence of dracunculiasis infection.
Dracunculiasis is now on the verge of eradication.
WHO in its roadmap for overcoming the impact of NTDs announced in 2011 has set up a target of
global eradication of dracunculiasis infection by 2015. To achieve WHO’s goal - interruption of
transmission by 2015, a heightened surveillance should be enforced and the momentum should be
maintained - even when a country or a particular area of an endemic region has interrupted the
transmission completely - until global eradication is achieved.
Endemic treponematoses (yaws)
Endemic treponematoses (yaws) infection is the only other NTD that is targeted for global
eradication by 2020. Yaws mainly affects children. According to the estimation by WHO, globally
460000 infectious cases were reported in 1995, and these infections were mostly occurred in west
and central Africa (400000 cases), South-East Asia (50000) and the remainder in other tropical
regions. In 2007, WHO launched a global program for the elimination of yaws and other endemic
treponematoses. Since then, yaws has been eliminated from many endemic countries. In India, no
new case of infection has been reported since 2004. In South-East Asian Region, two endemic
countries - Indonesia and Timor-Leste - who set the goal for Yaws elimination by 2012. Currently
three countries (Papua New Guinea, the Solomon Islands and Vanuatu) in the Western Pacific
Region remain endemic.
WHO’s goal is to eliminate the yaws from the Western Pacific and South-East Asia regions by 2015
and from Africa by 2020, which will lead to eradicate the disease globally.
Elimination
Some of the NTDs are aimed to eliminate their transmission or to reduce their burden regionally or
globally by 2015, while some others are targeted for global elimination by 2020.
Dengue
Millions of people worldwide are being affected by dengue fever. Dengue is mostly prevalent in
poor populations of crowded urban and periurban areas, however, it also affects affluent
neighbourhoods of tropical and sub-tropical countries. In 2010, the incidence of dengue fever has
been recorded in all six WHO regions and indigenous outbreaks were reported for the first time in
Europe. The principal vectors, Aedes aegypti and Aedes albopictus, are gradually spreading their
range of distribution in the European and African continent. Intensive efforts to control the spread
of the vectors and to apply sustainable control measures are required to stop the tide by 2015.
Now the aim is to reduce the rate of morbidity by at least 25% and mortality by 50% through
implementing an integrated vector management approach by 2020.
Human dog-mediated rabies
Domestic dogs are the major sources of human rabies cases. Children are the main victim where
between 30% and 50% of human dog mediated rabies cases (and therefore human rabies deaths)
occur in children aged below 15 years. About 55000 people die from dog-mediated rabies every
year in Africa and Asia. More than 14 million people worldwide receive post-exposure prophylaxis
following bites from suspected rabid animals. Therefore, controlling the disease in dogs is
important for the elimination. WHO is coordinating pilot studies in the Philippines, South Africa
and the United Republic of Tanzania for the immunization of dog in order to prevent dog mediated
rabies in humans.
A mass dog vaccination programme in Latin American countries initiated in 1983 has stopped the
progress of dog-to-dog transmission in most countries. Elimination of human dog-mediated rabies
and dog-to-dog transmission is achievable by 2015 in all endemic areas in Latin America; and in all
affected countries in WHO’s South-East Asia and Western Pacific regions by 2020. Intensified
control and enhanced surveillance should lead to a 50% reduction of the number of human rabies
deaths in these two regions by 2015.
Buruli ulcer
A combined antibiotic treatment with rifampicin and streptomycin, recommended by WHO in
2004, has radically changed the prospects for Buruli ulcer treatment. Almost 36000 people during
2004–2010 became benefited from this combined treatment, 50% of whom were children aged
under 15 years. Combined antibiotic treatment has reduced almost 50% of the need for surgery.
WHO aims to develop oral antibiotic therapy for full incorporation into control and treatment by
2015. WHO also aims to cure 70% of all cases with antibiotics in all endemic countries by 2020.
Cysticercosis
Cysticercosis is a disease which is caused by the development of Taenia solium cysticerci in human
tissues. Cysticercosis may also develop in central nervous system which is called
neurocysticercosis. The infection is prevalent in all six WHO regions. Currently China is the only
country who is running a national surveillance and control programme for cysticercosis.
Elimination of cysticercosis requires improved sanitation, chemotherapy for humans, pig
husbandry and marketing practices, and pig treatment combined with improved vaccination. WHO
aims to launch a sustainable strategy for the control and elimination of T. solium taeniasis/
cysticercosis by 2015 and to scale up the interventions in selected countries in Africa, Asia and
Latin America by 2020.
Chagas Disease
WHO is leading a global awareness campaign to interrupt global transmission of the chagas
disease through blood transfusion and organ transplantation. Sustained vector control over the
years has become successful and significantly reduced the transmission in Latin America. WHO has
set up the target for the elimination of the disease in Latin America through interruption of vector
transmission via intra-domiciliary infestation by 2015 and via peri-domiciliary infestation by 2020.
Interruption of transmission via blood transfusion has also been targeted in Latin America, Europe
and the Western Pacific by 2015. Besides vector control strategy, WHO also largely provided the
first-line treatment with benznidazole and second-line treatment with nifurtimox in the endemic
areas during 2007 - 2010 in order to achieve the goal of global elimination.
Echinococcosis
Echinococcosis is a globally prevalent zoonotic disease which is caused by the larval stages of the
dog tapeworm Echinococcus granulosus. Approximately 200000 new cases of cystic echinococcosis
are diagnosed annually. Elimination of echinococcosis transmission has been achieved in
developed countries by adopting the interventions such as treating dogs regularly, carrying out
strict controls during the slaughter of livestock, destroying infected offal and public education.
However, these interventions may not work in low or middle-income countries and may require
alternative strategy in addition to traditional interventions.
WHO is now willing to validate the efficacy of echinococcosis/hydatidosis control strategies in
selected countries by 2015 to scale up the interventions in selected countries in North Africa,
Central Asia and Latin America for control and elimination of the disease as a public-health
problem by 2020.
Foodborne trematode infections
More than 56 million people worldwide suffer from one or more foodborne trematode infections
(e.g. clonorchiasis, fascioliasis, opisthorchiasis, paragonimiasis and others). WHO is working to
expand preventive chemotherapy to include foodborne trematode infections which can be treated
with praziquantel or triclabendazole.
WHO aims to control morbidity associated with foodborne trematodiases in selected countries by
2015 and in all endemic countries by 2020.
Human African trypanosomiasis in selected countries
Human African trypanosomiasis or sleeping sickness is caused by Trypanosoma brucei gambiense
which is endemic in 24 countries of west and central Africa, and by T. brucei rhodesiense which is
endemic in 13 countries of eastern and southern Africa. Sleeping sickness is highly prevalent in
WHO’s African Region (90% of reported cases) and the remaining 10% in the Eastern
Mediterranean Region. The incidence of new cases has been reduced by 75% during the period of
1999 and 2010.
WHO has been implemented a new strategy for sustaining case detection at the peripheral level in
countries with low endemicity and foci. WHO’s current initiatives aim to enhance wider patient
accessibility in order to eliminate the disease in 80% of foci by 2015 and to achieve 100%
elimination of the foci globally by 2020.
Soil-transmitted helminthiases (intestinal worms)
More than 1 billion people are infected with nematodes that cause soil transmitted helminthiases.
A significant progress has been made in controlling these infections over the past 10 years. In
2010, 31% of all preschool and school-aged children in the world at risk of soil-transmitted
helminthiases were dewormed. However, the target of bringing 75% of school-aged children under
coverage by 2010 was not achieved. WHO now aims to achieve 75% coverage in all endemic
countries by 2020.
Onchocerciasis
Onchocerciasis elimination programme is actively working to interrupt the transmission in the
region of Latin Americas. Elimination of the transmission by 2015 seems feasible in Latin America
(13 foci in 6 endemic countries - Venezuela, Brazil, Colombia, Ecuador, Guatemala and Mexico)
where approximately 0.5 million people are at risk of onchocerciasis infection.
Yemen adopted national plan to eliminate onchocerciasis transmission in the country by 2015
through mass distribution of ivermectin and vector control. Onchocerciasis control in Africa is
being monitored through the African Programme for Onchocerciasis Control (APOC) and the
former Onchocerciasis Control Programme in West Africa (OCP). In African continent, 23 countries
(12 APOC countries and 11 ex-OCP countries) out of a total of 31 endemic countries are expected
to achieve elimination through surveillance activities and mass drug administration with
ivermectin by 2020.
Schistosomiasis
With the current scheme and interventions, elimination of S. haematobium is reasonable in the
countries of Eastern Mediterranean Region such as Egypt, Libya, Saudi Arabia and the Syrian Arab
Republic by 2015. Continuous surveillance is needed to confirm that the transmission of S.
haematobium has stopped in Iran, Jordan and Morocco. By 2015, WHO also aims to eliminate S.
haematobium infections in the Bolivarian Republic of Venezuela, Saint Lucia and Suriname, S.
japonicum infections in Indonesia, S. mansoni infections in the Carribean and S. mekongi infections
in the Mekong River basin. By 2020, S. mansoni infections and S. japonicum infections have been
projected to be eliminated in Brazil and Western Pacific Region respectively. S. mekongi infections
have been targeted to eliminate from parts of Western Pacific region such as two endemic
provinces from each of Cambodia and Lao People’s Democratic Republic by 2020.
However, in sub-Saharan Africa, it is not yet been scheduled for elimination of Schistosomiasis
particularly S. mansoni even by 2020, primarily due to lack of sufficient amounts of medicines.
Necessary steps should be taken immediately for the elimination of the infection in Africa. A large-
scale preventive chemotherapy programme has been enduring for at least 5 years in some
countries in Africa including Uganda, Burkina Faso and Niger. If the necessary medicines (especially
parziquantel treatment) can be made available, then the elimination of schistosomiasis as a public
health problem could be achieved in many countries in Africa by 2020, and globally by 2025 under
the guidance of WHO.
Blinding trachoma
More than 40 million people in over 50 countries are affected by trachoma, and over 8 million are
at immediate risk of irreversible blindness. The prevalence of trachoma has reduced significantly
since 1998 as a result of the implementation of SAFE strategy. Blinding trachoma has been aimed
to be eliminated globally by 2020. Some countries like Ghana, Gambia, Iran, Morocco and Oman
may achieve the target of elimination by 2020, while remaining countries must be needed enough
support from WHO to achieve the targets within the deadline set by resolution WHA51.11. In the
prerequisite of achieving the global elimination goal by 2020, it was expected to attain the
ultimate intervention goal (UIG) in 10% of endemic countries by 2013. By 2016, 40% of endemic
countries are expected to achieve the UIG and to enter the post-endemic surveillance. By 2020,
WHO aims to achieve the UIG in all endemic countries and to be free from blinding trachoma as a
public-health problem.
Leprosy
Leprosy was endemic in 122 countries. Interestingly, the infection has been successfully eliminated
as a public-health problem in 119 out of these 122 countries (elimination is defined as achieving a
prevalence of less than 1 case/10000 population). The incidence of transmission has been reduced
by more than 90% since 1985, primarily because of timely case-finding and multidrug therapy. The
transmission is prevalent in few countries or areas that were previously highly endemic. By 2020,
WHO aims to eliminate the transmission globally through the intervention of prompt case-finding
and treatment.
Visceral leishmaniasis in the Indian subcontinent
Regional leishmaniasis control programmes and the elimination of visceral leishmaniasis in the
Indian subcontinent (mainly in Bangladesh, India and Nepal) over the past five years have
strengthened capacity, improved access to medicines and enhanced surveillance. Leishmaniasis
affects people in more than 90 countries which can be eliminated implanting the intervention of
early case-finding and prompt treatment. WHO has set up the target of detecting at least 70% of
all cutaneous leishmaniasis cases and treating minimum of 90% of all detected cases in the Eastern
Mediterran Region by 2015. With sustained efforts in the Indian subcontinent, 100% case-
detection and treatment of visceral leishmaniasis is feasible by 2020, implying that less than 1 case
per 10 000 population at district and subdistrict levels can be achieved.
Lymphatic filariasis
The Global Programme to Eliminate Lymphatic Filariasis is the key towards the efforts to control
lymphatic filariasis and to interrupt transmission through integrated interventions of regular
treatment with preventive chemotherapy, vector control and morbidity management. Despite
significant successes, achieving the goal of elimination as a public-health problem by interrupting
transmission remains challenging in the many places where clinical cases persist.
If current levels of interventions are maintained, elimination of transmission can be achieved in all
Pacific Islands, excluding Papua New Guinea, by 2015. By 2017, 70% of all 81 endemic countries
will have met the criteria to stop interventions and entered the post-intervention surveillance
phase. By 2020, 100% of all endemic countries will have been verified as free of transmission or
will have entered post-intervention surveillance.
Treatment
Among the five strategies recommended by WHO for the prevention and control of NTDs,
preventive chemotherapy (the intervention of using drugs) is the best affordable measure for the
treatment of those diseases. A large-scale community-based drug intervention has become the
key strategy for the poor settings of the developing world where peoples are mostly affected.
However, as these are neglected diseases and the affected peoples are mostly the poorest of the
poor world, the research and development of drugs for these diseases was limited due to a lack of
market incentives (29). Recently, the public-private partnerships for drug development has been
formed which has accelerated funding for research and drug development (30). Affordable and
effective drugs for many NTDs infections have been developed, however, the access to these
drugs often remain limited for the victims living in NTDs endemic areas (30).
For some NTDs, treatments are easy to administer, do not require health professionals and a non-
medical personnel (e.g., school teachers) can deliver these drugs to large populations (e.g., all
children in a school) as a public health measure (31). The development of albendazole,
mebendazole, ivermectin and praziquantel, which are highly effective against most of the NTDs
including soil-transmitted helminthiases, has become a great blessing for the treatment of NTDs.
Albendazole and mebendazole are suggested for preventive chemotherapy against hookworm
infection, ascariasis, trichuriasis, strongyloidiasis, toxocariasis and mansonellosis (M. perstans).
Ivermectin is useful against strongyloidiasis, lymphatic filariasis, mansonellosis (M. perstans, M.
streptocerca) and onchocerciasis. Praziquantel is effective killer for schistosomiasis,
paragonimiasis, clonorchiasis, opisthorchiasis and intestinal fluke infections. For human African
trypanosomiasis, pantamidine is commonly used, while nifurtimox or benznidazole is used for the
treatment of Chagas disease (3). The co-administrations of these drugs are often recommended.
For example, ivermectin and albendazole are used in Africa while diethylcarbamazine (DEC) and
albendazole are used in areas outside Africa for the treatment and elimination of lymphatic
filariasis (3, 32). However, the recommended dosages for the treatment of NTDs may vary in the
typical endemic and non-endemic settings.
Recently, a combination of five drugs known as ‘rapid impact package’has shown a lot promise in
the treatment and prevention of five NTDs (e.g. soil-transmitted helminthiasis, schistosomiasis,
lymphatic filariasis, onchocerciasis, trachoma) at once (33). These rapid impact packages are
exceptionally cost-effective which need to be taken only once a year and treatment throughout
one's school years can offer life-long protection. The major advantages of these drugs are the fact
that they do not require refrigeration and are safe to take even if one is not infected which provide
a means of mass prevention of these NTDs. Hence, preventive chemotherapy has been endorsed
by WHO as the key strategy for the control of morbidity and socio-economic damages.
Prevention and control of NTDs
"The global effort to control and eliminate neglected tropical diseases must be led by the countries
themselves,” said by Kesetebirhan Admasu, Minister of Health, Ethiopia in the meeting of “The
Addis Ababa NTD Commitment, 2014”. In the Addis Ababa declaration, Ministers of Health from
the participating countries pledged to take ownership, responsibilities and to increase local
funding in the research and control efforts of national NTD programmes. A good sign in the
elimination and control of NTDs is that recently endemic countries are increasingly taking
ownership and responsibilities of their national NTD programmes, have started providing new
funding and are pursuing innovative approaches to combat these devastating diseases. In doing
so, they are significantly contributing in increasing the overall global coverage rates under the
national NTDs programmes and thereby making a great stride toward elimination of these
diseases. WHO director of the Department of control of NTDs said “sustained political
commitment, innovative domestic financing and greater coordination can bring about game-
changing treatments and care to millions of people and improve the prospects of achieving WHO’s
goal of universal health coverage against NTDs.”
The invention of effective and cheap drugs that are safe and can be administer by non-
professional health personnel spurred the way for preventive chemotherapy (31). And therefore
mass drug administration in the endemic settings has become the best strategy for the prevention
and control of NTDs. However, this strategy has quite a few limitations. As for example, some
interventions are needed to repeat once or twice a year for an unknown period of time. Here,
compliance becomes an issue where quite a good number of people may feel healthy after initial
treatment and, hence, might not appreciate to undergo for the repeated treatments. Preventive
chemotherapy is not available for some diseases in the endemic countries and therefore they need
enhanced patient management. The usage of drugs must be needed to monitor carefully as the
excessive use of may evolve in resistance. Moreover, recurrence of the infection may occur as
preventive chemotherapy does not address the root of behavioral, ecological and socio-economic
causes. Therefore emphasis should be given to adopt preventive measures, such as increased
access to clean drinking water, improved sanitation and hygiene (34-36). It is also important to
step up for the implementation of integrated control measures, with the combination of two or
more interventions together that are suitable to an endemic setting and adapted over time, in
order to prevent and control the infection of NTDs. A profound knowledge regarding the
demographic, health and socio-ecological status could help in tailoring suitable integrated control
measures for a particular area or country (34).
Conclusions
“UK Coalition against NTDs: Annual Report 2014-2015” has been launched on 24th February, 2015
in which a key message was that although a substantial progress has been made on the way to
combat against NTDs, more efforts are needed to reach to WHO’s 2020 targets. Although WHO
recognized 17 NTDs, however, currently the number of NTDs has reached over 40 who are caused
by various bacterial, fungal, helminth, protozoal, viral and ectoparasitic infections. Many of these
infections can effectively be treated with short oral drug regimen (e.g., soil-transmitted
helminthiasis, including strongyloidiasis) while some other NTDs may require extensive and more
costly diagnosis (e.g., leishmaniasis, leprosy). Preventive chemotherapy would play vital role in the
elimination and control of NTDs. In the endemic settings where there is very limited or no access
to preventive chemotherapy, preventive measures including access to safe drinking water,
improved sanitation and hygiene and awareness programmes should be conducted.
In order to achieve WHO’s 2020 goals, individual countries should come up with increased
responsibilities and funding for innovative research that will eventually lead to the development of
new improved tools and strategies that can be applied in the prevention and control of NTDs. In
the meantime, a number of endemic countries including Bangladesh, the Philippines and Honduras
have already taken on primary responsibility for financing their NTD control programmes which
will significantly contribute in achieving elimination goals for individual diseases. In fact, global
coverage (at least with one drug) rates improved to 43% in 2015 compared to around 35% in 2008
(37).
Therefore, increased participation from endemic countries, WHO and other global partners,
biotechnology and pharmaceutical companies in funding for innovative research and support for
the control of NTDs is essentially expected for elimination and gradual eradication of these
devastating diseases for good.
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