The document discusses neglected tropical diseases (NTDs), including their origin, features, global burden, and approaches to control. Some key points: 1. NTDs refer to a group of chronic, debilitating diseases that primarily affect the world's poorest people in tropical areas. There are currently over 40 NTDs. 2. NTDs disproportionately impact over 1 billion people living on less than $1.25 per day and result in over 500,000 deaths and 25 million disability-adjusted life years lost annually. 3. Control approaches include mass drug administration, vaccination, and public health measures to help reduce transmission and morbidity of NTDs.

1. NEGLECTED TROPICAL DISEASES
(NTD)
Dr Abhijit Chaudhury

2. Outline
1. Origin of the “Brand Name”.
2. Features and significance of NTDs.
3. Spectrum of NTD and Evolving Scope
4. Global Burden
5. Indian Scenario
6. Diagnostic Aspects
7. Approaches to Control and Elimination:
a. Mass Drug Administration
b. Vaccination
c. Public Health Measures
8. Conclusions.

3. 1. Origin of the “Brand Name”.
• The Millennium Development Goals (MDGs) : Eight international
development goals that were established following the Millennium
Summit of the United Nations in 2000.
• All 189 United Nations member states and at least 23 international
organizations committed to help achieve the Millennium Development
Goals by 2015.
The goals were:
1. To eradicate extreme poverty and hunger
2. To achieve universal primary education
3. To promote gender equality and empowering women
4. To reduce child mortality rates
5. To improve maternal health
6. To combat HIV/AIDS, malaria, and other diseases
7. To ensure environmental sustainability
8. To develop a global partnership for development

4. 1. Origin of the “Brand Name”.
The outcome:
 New awareness and action plans for
HIV/AIDS, Malaria, and TB.
 Establishment of Global Fund to fight the
above three diseases (GFATM), US President’s
Emergency Plans for AIDS Relief(PEPFAR),
Funding by Gates Foundation, among others.

5. 1. Origin of the “Brand Name”.
• To combat HIV/AIDS, malaria, and other
diseases---- The Forgotten Entity.
• In response, a group of concerned scientists and
public health experts committed to the study of
parasitic helminth and protozoan infections
began meeting under the auspices of the World
Health Organization (WHO) to discuss how global
efforts to control these conditions could be
scaled and expanded along the lines of PEPFAR
and GFATM ------- THE ORIGIN

6. 1. Origin of the “Brand Name”.
• From these discussions an informal consensus
was created that there are 13 major
conditions, which could be targeted for mass
drug administration or other large-scale
interventions.
• The first published paper with the full term
“neglected tropical diseases” in the title was a
piece put forward by Molyneux, Hotez &
Fenwick, in November 2005 in PLoS Medicine.

7. 1. Origin of the “Brand Name”.
• An interesting case study from India in 2001
discussed the need for establishing local research
and development capacity for neglected
infectious and tropical diseases, emphasising
medicines [Kettler HE, Modi R. Building local research and development
capacity for the prevention and cure of neglected diseases: the case of India.
Bull World Health Organ. 2001;79:742–7].
• From 2005 and 2006, peer-reviewed papers using
the term “neglected tropical diseases” as a
medical subject heading started appearing in
PubMed and other scientific literature databases.

8. 1. Origin of the “Brand Name”.
• In October 2007, the Public Library of Sciences
published the inaugural issue of a new openaccess journal, PLoS Neglected Tropical Diseases.
• In 2003, the creation of the Geneva-based Drugs
for Neglected Diseases initiative (DNDi;
http://www.dndi.org) .
• Establishment of a new Department of Neglected
Tropical Diseases at WHO
(http://www.who.int/neglected_diseases/en/)

9. 2. Features and significance of NTDs.
Neglected tropical diseases refer to a group of
mainly chronic, debilitating and often
stigmatising diseases that primarily affect the
poorest of the poor living in remote rural and
deprived urban settings of tropical and
subtropical countries [ Utzinger J et al; Swiss Med Wkly.
2012:142:w13727]

10. Neglected Tropical Diseases common features
A proxy for poverty and disadvantage
Affect populations with low visibility
and little political voice
Do not travel widely
Cause stigma and discrimination, especially
of girls and women
Have an important impact on
morbidity and mortality
Are relatively neglected by research
Can be controlled, prevented and possibly
eliminated using effective and feasible
solutions

11. Distinguishing Features
1. The 13 NTDs represent the most common
infections of people living in extreme poverty in
sub-Saharan Africa, Asia, and Latin America and
the Caribbean.
2. They disproportionately affect the “bottom
billion,” which refers to the approximately 1.4
billion people who live below the World Bank
poverty figure of US$1.25 per day.
3. Among the bottom billion, the NTDs result in
chronic infections lasting years or even decades.

12. Distinguishing Features
4. The NTDs produce chronic disability that results in
impaired child growth and intellectual and cognitive
development, impaired pregnancy outcomes, and
decreased worker productivity.
5. Through these mechanisms, the NTDs adversely affect
not only health but also childhood education and
ultimately economic productivity; the NTDs represent
an underlying reason why the bottom billion cannot
escape poverty.
6. Many of the NTDs also cause blindness and
disfigurement that are psychologically devastating and
result in social stigma.

13. Distinguishing Features
7. This high level of morbidity, economic
impairment, and stigma does not necessarily
translate into large numbers of deaths; overall,
the NTDs cause high-morbidity but low-mortality
conditions.
8. In contrast to emerging infections such as
HIV/AIDS, SARS, and avian influenza, there is a
“non-emerging” character about the NTDs.
Instead, the NTDs have afflicted humankind for
centuries and there are accurate descriptions of
some of the NTDs in ancient texts.

14. Significance
• DALY = Disability Adjusted Life Years
– Years of healthy life lost as a result of disability
or premature life.
• As most of the NTDs are chronic condition, so
instead of mortality, DALY parameter is used
since it has a direct co-relation with the
morbidity.

16. 3. Spectrum of NTD and Evolving
Scope.
The Original 13 (Hotez et al, 2006,2007):
A. HELMINTH INFECTIONS
1. Ascariasis
2. Trichuriasis
3. Hookworm
4. Schistosomiasis
5. Lymphatic Filariasis
6. Onchocerciasis
7. Dracunculosis

17. 3. Spectrum of NTD and Evolving
Scope.
B. PROTOZOAN INFECTIONS
8. Leishmaniasis
9. Chagas Disease
10. African Trypanosomiasis
C. BACTERIAL INFECTIONS
11. Trachoma
12.Leprosy
13. Buruli Ulcer

18. 3. Spectrum of NTD and Evolving
Scope.
WHO Additions (2010): Total 17
1. Foodborne Trematode Infections
2. Cystic Echinococcosis
3. Cysticercosis
4. Endemic Syphilis
5. Dengue and other Arboviral Infections.
(Ascariasis, Trichuriasis, Hookworm: Grouped
under one heading of Soil Transmitted
Helminths).

19. 3. Spectrum of NTD and Evolving
Scope.
• Meanwhile, the list of neglected tropical
diseases has been further expanded and
currently comprises over 40 diseases, which is
reflected in the escalating scope of PLoS
Neglected Tropical Diseases .

20. 4. Global Burden
• > I billion people suffer from one or more
NTD.
• > 500,000 deaths, and > 25 million DALY/year
• Endemic in 149 countries
- 2-5 NTD in >100 countries.
- 6 or more NTD in about 30 countries.
( Source: WHO 2011)

21. DISEASE
Approximate Global DALY (in Millions)
Prevalence
(Millions)
Hookworm
576
1.0
Ascariasis
807
1.8
Trichuriasis
604
1.0
Lymphatic
Filariasis
120
5.8
Scistosomiasis
207
1.7
Onchocerciasis
37
0.5
Drucunculiasis
0.001
<0.1

22. DISEASE
Approximate Global DALY (in Millions)
Prevalence
(Millions)
Leishmaniasis
12
2.0
African
Trypanosomiasis
>0.03
ND
Chagas Disease
8
0.7
Trachoma
84
2.3
Leprosy
0.4
0.2
Buruli Ulcer
<0.01
ND
Dengue
50
0.6

23. 5.INDIAN AND SOUTH ASIAN
SCENARIO

24. Estimated Number
of DALYs in
South Asia
(Millions)
140M (17%)
287M (29%)
0.4-3.0
147M (24%)
0.5-1.5
71M (12%)
130M (23%)
0.6-5.6
<6M (5%)
ASCARIASIS
Number of Cases
in India and South
Asia(Percentage of
Global Disease
Burden)
73M (12%)
Disease
Number of Cases
in India
(Percentage of
Global Disease
Burden)
<60M (50%)
2.9
TRICHURIASIS
HOOKWORM
FILARIASIS

25. Number of Cases
in India
(Percentage of
Global Disease
Burden)
Number of Cases
in India and South
Asia(Percentage of
Global Disease
Burden)
Estimated Number
of DALYs in
South Asia
(Millions)
Trachoma
1M (1-2%)
2M (2-4%)
<0.1
Visceral
Leishmaniasis
ND
200,000-300,000
(40-60%)
0.4-1.0
Leprosy
87,190 Registered
Cases (41%)
120,456
Registered (57%)
0.1
Dengue
ND
ND
0.4
Disease
Source: Lobo et al. 2011. PLOS Negl Trop Dis 5(10):e1222.doi10.1371.

26. 6. DIAGNOSTIC ASPECTS
• The lack of rapid, accurate, simple-to-use, pointof-care tests for many of the neglected tropical
diseases is an important feature for their general
neglect and the under-appreciation of their
disease burden.
• Microscopy remains the mainstay of diagnosis
for majority of the NTDs.
• While microscopy of parasites is considered as
highly specific, its sensitivity depends on the
intensity of infection, which is a function of the
number of parasitic elements in a sample

27. 6. DIAGNOSTIC ASPECTS
• Immunodiagnosis is applicable for most of the neglected
tropical diseases, but may lack sensitivity and/or specificity.
• Antibodies produced against one helminth species are
known to cross-react with antigens from other helminths.
• Moreover, antibodies produced against infectious agents do
not give any indication of the severity of infection , and are
often detectable for several months or years after an
infection has cleared, and hence do not allow to distinguish
between current and past infections
• The commercial availability of standardised test kits is still
the exception rather than the norm

28. 6. DIAGNOSTIC ASPECTS
• The development and use of molecular tools such as
polymerase chain reaction (PCR) tests for the diagnosis
of neglected tropical diseases is the focus of multiple
research groups, but the commercial availability of
DNA amplification kits is rare.
• Moreover, the isolation of parasite DNA from stool or
tissue is challenging, cumbersome and quite often not
fruitful at all.
• According to some authors, multi-parasitic screenings
based on molecular assays might one day replace
microscopy and immunodiagnosis.

29. 7. Approaches to Control and
Elimination
• Renewed momentum generated by
unprecedented progress resulted in the World
Health Assembly to adopt resolution WHA 66.12,
in May 2013.
• Of the 17 neglected tropical diseases, two are
targeted for eradication – dracunculiasis (guineaworm disease) by 2015 and yaws by 2020 and
four for elimination (blinding trachoma, human
African trypanosomiasis, leprosy and lymphatic
filariasis) by 2020.

30. 7a. Mass Drug Administration
• Of the 850 new therapeutic products
registered in 2000—11, 37 (4%) were
indicated for neglected diseases, comprising
25 products with a new indication or
formulation and eight vaccines or biological
products. (Pedrique et al. The Lancet Global Health,2013)
• A persistent insufficiency in drug and vaccine
development for neglected diseases

31. 7a. Mass Drug Administration
• Mass interventions comprise of population-based drug
administration (often together with other allied
measures)
• Extremely successful in terms of reaching large
numbers of affected populations, even in the most
remote areas of Africa, Asia, and the Americas, and in
achieving control and elimination targets.
• The medicines used in mass drug administration have
an excellent safety profile and can be administered to
large populations based on community-wide
prevalence assessments.

32. 7a. Mass Drug Administration
• Once a threshold prevalence of a particular
NTDhas been ascertained, WHO has established
algorithms for treating large populations
regardless of whether it has been determined if
any given individual is currently infected.
• The drugs used in mass administration are either
being donated by some of the major
multinational pharmaceutical companies or they
can be purchased as extremely low-cost generics.

33. 7a. Mass Drug Administration
Pharmaceutical Donation Programmes
•
•
•
•
•
•
•
•
Sanofi Aventis
Eflornithine and melarsoprol support for sleeping sickness treatment
Merck & Co Inc
Mectizan for as long as needed for onchocerciasis and filariasis in Africa
GlaxoSmithKline
Albendazole for lymphatic filariasis atleast to 2020
Pfizer
Azithromycin for trachoma 120 million doses
Novartis
MDT and clofazimine for leprosy; triclabendazole for fascioliasis
Johnson & Johnson
Mebendazole for intestinal worms
Bayer
Nifurtimox for Chagas and HAT to 2012
Merck KgaA
Praziquantel for schistosomiasis to 2017.

34. 7a. Mass Drug Administration
• In order to increase coverage for the seven
most common NTDs, it was proposed in 2005
to bundle the drugs in mass drug
administration for these conditions in a “rapid
impact package,” costing as little as US$0.50
per individual.

35. Seven Major NTDs
Targeted by Rapid Impact Major Drugs Used
1. Soil-transmitted
Albendazole or
helminth infections:
mebendazole
ascariasis, trichuriasis,
hookworm
Additional NTDs Targeted
by Rapid Impact
Strongyloidiasis
2. Schistosomiasis
Praziquantel
3. Lymphatic filariasis
Ivermectin or
diethylcarbamazine
citrate + albendazole
Taeniasis
Food-borne
trematodiases
Strongyloidiasis, Scabies
4. Onchocerciasis
Ivermectin
Strongyloidiasis, Scabies
5. Trachoma
Azithromycin
Other bacterial infections
Hotez PJ.2011.

36. 7a. Mass Drug Administration
• There are additional NTDs of great public health
importance for which mass drug administration
approaches are not immediately relevant but
which in some cases could still be controlled or
eliminated.
• Drucunculosis, African Trypanosomiasis, Chagas
Disease, Visceral Leishmaniasis.
• Program of early case finding, delivering oral
treatment, and vector control are more relevant
for these diseases.

37. 7b. Vaccination: Hookworm
• Human Hookworm Vaccine Initiative (HHVI) is the group
currently working on vaccines targeting this parasite.
• Sabin Vaccine Institute announced the start of Part II of its
Phase I clinical trial of the Na-GST-1 (Glutathione S
Transferase) vaccine candidate in November, 2012.
• Part II of the trial commenced in Americaninhas, Brazil,
following successful vaccinations in Part I of the study,
which began in Belo Horizonte, Brazil in late 2011.
• Ultimately, Na -GST-1 and Na -APR-1 would be used
together a bivalent vaccine.
• Aim of the vaccine will be to reduce moderate to heavy
infections in the host.

38. 7b. Vaccination: Schistosomes
• Only one schistosome antigen has entered into clinical
trials.
• The Institut Pasteur has taken a recombinant 28 kDa
GST cloned from S. haematobium through both phase
1 and 2 clinical testing in Europe and West Africa
(Senegal and Niger).
• Sh28-GST (Bilhvax) is a recombinant protein formulated
with an aluminum hydroxide adjuvant .
• Bilhvax appears to be immunogenic and well-tolerated
in healthy adults from non-endemic (France) and S.
haematobium endemic areas in Africa.

39. 7b. Vaccination: Schistosomes
• The most important vaccine target of the
schistosome is the tegument.
• The tegument is thought to be involved in several
key physiologic processes: parasite nutrition,
osmoregulation, and the evasion of host
immunity.
• Tetraspanins found in outer tegument play
important role in maintaining the integrity of the
tegument.
• Sm-TSP-2 has been selected by the HHVI for
development as a human vaccine antigen.

40. 7b. Vaccination: Schistosomes
• The Sm -TSP-2 recombinant schistosomiasis
vaccine would be intended primarily for
school-aged children living in the S. mansoni
endemic regions of sub-Saharan Africa and
Brazil.
• The vaccine ideally would prevent the
reacquisition of schistosomes in the blood
stream following initial treatment with
Praziquantel (vaccine-linked chemotherapy).

41. 7b. Vaccination: Leishmania
Second Generation Vaccines: Recombinant protein
vaccines.
 A variety of Leishmania vaccines consist of recombinant
proteins; poly-proteins produced by DNA cloning.
 More recent efforts aim at increasing the immunogenicity
of DNA cloned vaccines, including the use of genetic
adjuvants and plasmid-based expression of viral replicons.
 Some of the important recombinant protein candidate
vaccines include: surface expressed glycoprotein
leishmaniolysin (gp63), Leishmania activated C kinase
(LACK), parasite surface antigen (PSA), Leishmania derived
recombinant polyprotein (Leish-111f) and serine proteases.

42. 7b. Vaccination: Leishmania
• Leish-111f is a single polyprotein composed of three
molecules fused in tandem: the L. major homologue of
eukaryotic thiol-specific antioxidant, TSA; the L. major
stress-inducible protein-1, LmSTI1; and the L.
braziliensis elongation and initiation factor, LeIF.
• The Leish-111f product is the first defined vaccine for
leishmaniasis in human clinical trials and has
completed phase 1 and 2 safety and immunogenicity
testing in normal, healthy human subjects.
• Efficacious against cutaneous or mucosal
leishmaniasis.

43. 7c. Public Health Measures
WHO recommends five public-health strategies for the
prevention and control of neglected tropical diseases:
1.expansion of preventive chemotherapy;
2.intensified case-detection and case management;
3.improved vector control;
4.appropriate veterinary public health measures;
5.provision of safe water, sanitation and hygiene.
Universal health coverage is the single most
powerful concept that public health has to offer.

44. Conclusion
• For almost all of the NTDs, there is a desperate
need for research and development leading new
innovations for control, including improved
diagnostics, medicines, or vaccines.
• Several potential backup anthelminthic drugs
previously developed for veterinary purposes
could potentially be transitioned into human
medicines, and there is a need to establish a
product development public–private partnership
(PD-PPP) for this purpose.

45. Conclusion
• Vaccines , developed for NTDs, have potential
economic impact as well as their effects on
health; hence termed Antipoverty Vaccines.
• For all seven NTDs targeted for rapid impact
packages, there is a pervasive need for new
diagnostics.
•

46. Conclusion
• There is an urgent need for better surveillance
and disease burden assessments for most of
the NTDs.
• Linking of mass drug administration,
vaccinations, integrated vector management,
and improved surveillance together as part of
overall efforts to strengthen health systems in
the region.