International Millennium Development Goals and

Control of NTDs in Poverty

Jilong Shen, Ph.D

Dept. of Parasitology
The Key laboratory of Zoonoses, Anhui (AMU)
Provincial Laboratory of Microbiology and Parasitology
（ Referred from Prof. Andreas Ruppel, Germany ） ,
Programs under implementation launched by United Nations

TDR (the Special Programme for Research and Training in Tropical Diseases a
WHO)

NTD (Neglected Tropical Diseases),

2nd WHO report 2013

MDG (Millennium Development Goals)

The MDG Report (UN) 2012

Global Report on Research of Infectious Diseases of Poverty (2012)

Open Access Publications:

PLoS (Public Library of Science), PLoS NTD
 What does it mean to be neglected?

• Budget allocation corresponding to the diseases （ 104 Million

Euro! ）
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 1.Neglected Tropical Disease(NTDs)

• Topical infection particularly endemic in low-

income population in developing regions in
Africa, Asia, and Americas.
• Impact of NTDs in Sub-Sahara of Africa is
comparable with Malaria and TB
• 17 NTDs:

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 (1). Schistosomiasis
• 200 millions case : it causes bladder fibrosis, liver fibrosis,
portal hypertension, and cervical lesions (which increase HIV
susceptibility for women)
• Efficient treatment of preziquantel (0.2US dollars)

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 (2). Lymphatic filariasis
• Called elephantiasis,
• 120 millions individuals infected and 40 millions deformities;
• Mosquito- borne disease
• 1/3 of cases in Southwest Asia and 1/3 in Africa
• Effective antihelminthic treatment with “hetrazan”.

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 (3).Echinococcosis
• Over 1 million people currently infectd in rural areas.
• Cystic ( in the liver )and alveolar (in the lungs) echinococcosis ;
• Infection via ingesting eggs in the animal feces(e.g. dogs in
pasturing areas)
• Surgery treatment CT and
MRI
images of
left side of
liver,
showing
polycystic
lesions

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 (4).Cysticercosis and taeniasis
• Cysticercosis (caused by larvae stage, most comonly in CNS-
epilepsy) is infection by ingesting food contaminated with
eggs of tapeworm; taeniasis (caused by adult) is infection
through eating raw or undercooked pork or beaf.
• Endemic on farms in which pigs are exposed to human
excrement.

Scolex (head) of T. solium

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 (5).Drancunculiasis
• Guinea worm disease, caused through drinking water
containing water-fleas infected with larvae),
• Only 113 cases left in 2013( mostly in South Sudan); 3.5
millions of cases in 1986;
• Eradication program works well
• Prevention includes health education, pond larvacide, and
improving sanitation

Using a matchstick
to remove the worm
from the leg of a
human

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 (6).Onchocerciasis
• known as River blindness, causing general skin lessions
• 37 million people infected;
• Transmitted by blackflies
• 99% of cases in Sub-saharan Africa
• Ivermectin is efefctive

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 (7).Soil-transmitted helminthiasis
• It is named because transmission via exposure to the eggs or
larvae in soil (human open defecation in environment);
• Ascariasis(roundworm); trichuriasis (wipworm); and
strongyloidiasis (while hookworm in China)
• 1.5 billion people currently infected;
• Mainly intestinal manifestations; loss of nutrients and growth
retardation of children
• WHO recommends deworming without prior fecal detection.

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Combined prevalences of
intestinal nematodes (Ascaris,
Trichuris, hookworms)

Hall et al. PLoS NTD, 2009

 (8).Chagas disease
• known as American trypanosomiasis caused by Trypanosoma
cruzi and vector is assassin bug )
• Humans get infection by contact with the bug’s feces on the
wound in bug’s bite
• 15 million people infected
• It causes years of debilitating chronic
symptoms although it does not kill
victims rapidly ( in immunocompromised
population, children and the elderly)
•

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 (9). African trypanosomiasis
• Also known as African sleeping sickness caused by T. brucei
gambiense and T. brucei rhodesiense,
• Only 10,000 cases left currently; fetal if untreated
• Transmitted by tsetse fly
• Manifestations include fever, headache, lymphadenopathy,
personality change, cognitive decline, and coma
• Treatment is highly toxic

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Prevalence and deaths in 2002
 (10).leishmaniasis
• Occurs in 88 tropical and subtropical countries,
• 3 kinds of leishmaniasis: visceral(kala-azar), cutaneous, and
mucocutaneous;
• 12 million people currently infected;
• 20,000 deaths from visceral leishmaniasis
each year;
• Transmitted by sandfly;
• 90% of visceral cases founded in Bangladash, Brazil, Ethiopia,
India, and Sudan

Cutaneous leishmaniasis in North Africa

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Global prevalence of leishmaniasis in 2009

Visceral leishmaniasis cuased by L. donovani

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 (11).Dengue fever
• 50-100 million infections annualy, not fetal usually , but
severe Dengue may be fetal
• Vector-borne by mosquito (A. aegypti)
• Mainly in Asia and latin America
• 35,000 cases have reported in China Guangzhou in 2014

The rash of Dengue fever Mosquito vector on blood meal (A.

in the acute stage of aegypti)
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 (12). leprosy
• 189,018 cases reported Angola, Brazil, Central Africa
Republic, Congo, India, Nepal, Tanzania in 2013
• 1-2 million people disabled or disfigured
• Curable if treated early
• Symptoms are skin, limbs, eye, nerves
• Caused by bacteria and transmitted through droplets from
the mouth or nose of the infected individuals.

World
distribution of
leprosy, 2003

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 (13). Rabies
• 2 forms of rabies: furious and paralytic
• 60,000 deaths from rabies annualy
• A higher prevalence in rural areas, particularly affecting
children
• A high mortality,
• Transmitted through wounds or bites from the infected
animals, mostly family dogs in China,
• Furious rabies may cause death within a few days after onset

A dog with rabies A patient with convulsion Rabies countries

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 (14).Trachoma
• There are 21.4 million people infected with trachoma widely
in Africa, Asia, Central and South America, Middle East , and
Australia;
• Of whom 4.4 million have partial or permanent blindness,
mostly affecting women and children;
• Transmitted by contact with eye discharges or eye-seeking
flies (e.g., fruit fly Amiota okadai)

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 (15). Yaws

• Caused by bacterial (Treponema spp.)infection, mainly in

children, leading to skin lesions, even disability or
disfigurement.
• Data are limited on prevalence;
• Antibiotics are used for treatment;
• Can be prevented by improving hygiene
and sanitation

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 (16). Buruli ulcer
• Caused by bacteria (Mycobacterium lucerne) and treated by
antibiotics;
• Data on prevalence are not available,
• Cases are reported fron Africa, Asia, and Latin America,
• It causes skin lesions, even disfigurement, or disability,

Buruli ulcer on the Buruli ulcer of a

ankle of a person in long-term traveller
Ghana in Senegal

Buruli ulcer reported in 2009

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 (17). Snake bite
• WHO lists it as “other neglected conditions”
category,
• A public health problem in rural areas in Africa,
South Asia and South-east Asia

Severe tissue necrosis caused by

envenomation of snakebite and
amputation is needed above the
knee
(from a 11-yr-old child in Ecuador)
The map of snakebite morbidity Cleopatra suicide
by snakebite to her
left breast (Aegypt
1911)

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 2. Main features of NTDs

Linked to poverty: unsafe water, poor sanitatio

n, poor education
Communicable diseases, not perceived as a thre
at to the rich populations
Mostly disabling and disfiguring, but also killing
Promote poverty, impact education

The “bottom billion” are most at risk

25
Approximately 1 billion people are affected by more than one of NTDs

Ascaris,
Hookworms,
Schistosomiasis,
Echinococcosis

Slide: thanks to Dr. Ruppel, Germany

 Annual deaths due to NTDs
Revised estimates (The Lancet, 2009)
 Schistosomiasis 150,000 – 200,000
 Leishmaniasis 100,000
 Trypanosomiasis 100,000
 Hookworm infections 65,000
 Ascariasis / Trichuriasis 35,000
 Dengue (DHF) 20,000
 Chagas Disease 14,000
 Leprosy 6,000
 LF 0
 Onchocerciasis 0
 Trachoma 0
Many individuals have Infection intensities of
few worms S. japonicum infected rats
(Indonesia)

Few individuals have

many worms
Many individuals have
few parasite species

Few
co-i individu
nfec
tion als hav
s eM
ultip
l e

Kvalsig, Parasit.Tod. 4, 207, 1988

The poor people often have more or heavier infections

Ascaris intensity of infection (Madagascar):

Mean worm Percent

burden not inf
ected
Rice harvest per house hold
<200 kg 21.7 6
> 500 kg 8.9 10

Cattle owned by house hold

none 13.8 5

>5 9.6 14
Reality of poverty:

Infectious dieseases -
the true burden on communities

For the working poor, the economic impact

of infectious diseases can be catastrophic.

Infectious diseases can actually make people

poor.
 Breaking this vicious cycle between infectious diseases and poverty

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Funds for research on poverty-related diseases:
Who gives the money for this research?

Gates Fo
un
Wellcom dation: 456 Mio
e Trust: US$
(togethe 80 Mio U
r 94% o f S$
philantr
opic)

a nd m iddle
w
Public (lo ernments, incl.
ov
income g
China
Who publishes on infectious diseases of poverty?

_____________________
3. The Millennium Development Goals for
2016

Eradicate extreme poverty and hunger

Achieve universal primary education
Promote gender equality and empower women
Reduce child mortality
Improve maternal health
Combat HIV/AIDS, malaria and other diseases
Ensure environmental sustainability
Develop a global partnership for development
 MDG 1 Eradicate extreme poverty and hunger

… confirm that Ascaris is associated with acute poverty.

PLoS NTD 2011

Infections acquired during early childhood (pre-school-age children)
Today approximately 40% of the world's population,
mostly those living in the world's poorest countries,
is at risk of malaria.
• Synergistic effect of concomitant
schistosomiasis, hookworm and Trichuris
infections on children´s anemia burden
(Ezeamama et al. PLoS NTD, 2008 )

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WHO
manual
for program
managers,
2006
Countries requiring preventive chemotherapy (2011)
Free and timely access to high-quality medicines
against soil-transmitted helminths, schistosomiasis, filariasis, onchocerciasis , etc.

Medicine Donator Conditions

Albendazole GlaxoSmithKline Unlimited , for lymphatic filariasis and STD

Eflornithine sanofi-aventis Unlimited until 2020 for human African trypanosomiasis

Ivermectin * Merck & Co Inc. Unlimited, as needed for lymphatic filariasis, onchocerciasis
MDT and Clofazimine Novartis Unlimited, as s needed for Leprosy and its complications

Mebendazole * Johnson & Johnson 200 million tablets/ year until 2020 for STD for children

Melarsoprol sanofi-aventis Unlimited, until 20120 for human African trypanosomiasis

Nifurtimox Bayer 1 mIllion tablets /year 2012 - 2017 for Chagas disease
Pentamidine sanofi-aventis Unlimited, until 2020 for human African trypanosomiasis

Praziquantel Merck KGaA 250 million tablets /year, unlimited for schistosomiasis
Suramine Bayer 10.000 vials / year until 2012 for African trypanosomiasis

Triclabendazole Novartis 600 000 tablets / year for fascioliasis

NTD 2nd World Report 2013

 Proportion of children requiring preventive chemotherapy for soil-transmitted
helminthiasis, by country, 2010

Chin
a 6%
44
NTD Report 2013
Pre-school-age children (pre-SAC) and school-age children
(pre-SAC) in China requiring preventive chemotherapy
(PC) for soil-transmitted helminths annually

PC required for
Year number pre-SAC number SAC

2010 18 millions 33 millions

2011 7.2 millions 18.4 millions

2016 ?
 Projected number of anthelminthics medicines required to
achieve th eglobal targets for treating pre-school children
and school children,2020-2025

NTD Report 2013

 Criminal Fake
Artesunate
Trade in South
East Asia.

(Newton et al.,
PLoS Medicine,
2008 )

Figure 1. Map of the Distribution of Fake Artesunate, … in Relation to Packaging Type

Yang YR, Williams GM, Craig PS, McManus DP (2010)
Impact of Increased Economic Burden Due to Human Echinococcosis
in an Underdeveloped Rural Community of PR China.
PLoS Negl Trop Dis
 The gap between income and hospital payment
accounted for 163% of per capita income if a poor
person sought treatment

Location and per capita income Hospital

Economic level (US $) charges (US $)

Yinchuan 2200 699

Wuzhong 1000 500
Guyan 750 457

Low GDP counties 550 360

Rural Farmer 220 457
 The story of Filariae (lymphatic filariasis)
Wuchereria bancrofti and Brughia malayi

China and the Republic of Korea were declared to have

eliminated lymphatic filariasis as a public health problem in 2007 and 2008
The Global Programme to Eliminate Lymphatic Filariasis:
Health Impact after 8 Years

Cumulative
treatments
SE - ASIA
(% and millions)

rica
A f

PLos Neglected Tropical

Diseases, 8.10.2008
Microfilariae prevalence

Years
Effect of mass drug administration on microfilaremia prevalence
Infectious diseases (incl. parasitic infections)
influence negatively the intelligence Eppig et al. 2010
MDG: Promotes gender equality & empowers women

At the minimum, we strongly advocate for the introduction of low-cost

praziquantel MDA through a Global Network for NTDs. This represents a $0.32
solution that could have enormous benefits for young African women and a huge
potential beneficial impact on Africa’s AIDS epidemic.

Africa's 32 Cents Solution

for HIV/AIDS

Hotez, Fenwick, Kjetland,

PLoSNTDs 2009
 MDG : Reduces child mortality
Ninety per cent of deaths due to malaria occur in Africa south of the Sahara,
mostly among young children.

Malaria kills an African child every 30 seconds. Many children who survive an
episode of severe malaria may suffer from learning impairments or brain damage.

Probability of not having had

a malaria attack in children
presenting S. mansoni infection
or without S. mansoni infection
(Sokhna et al. Malaria Journal 2004 3:43)
without S. mansoni infection
1–100
101–400
401–1000
>1000 eggs/g of stools)
 MDG: Improves maternal health

Common knowledge: Pregnant women and their

unborn children are particularly vulnerable to malaria…

„Evidence indicates that increasing hookworm infection intensity is associated

with lower haemoglobin levels in pregnant women in poor countries …between a
quater and a third of pregnant women in SSA are infected with hookworms...“

PLoS NTD 2008

MDG: Ensures environmental sustainability

The schistosomiasis story

Egypt 1000 BC China 200 BC
Schistosoma japonicum in a Chinese noble, bu
ried on May 13, 167 B.C. in Jiangling
Sudan: an irrigation canal as habitat for aquatic snails
Africa: Humans and bovines harbour different species of Schistosomes: S. mansoni / S.haemato
bium vs S. bovis / S. curassoni
Africa: bovines may be infected with Schistosoma bovis
China
Periodically flooded areas
as habitats for amphibic
snails
China: Humans and bovines harbour the same parasite:
Schistosoma japonicum
Sudan: vegetation in the canal as habitat for water snails
Mali: the newly constructed lake of Sélingué
2008: Population requiring preventive treatment (praziquantel)

i na
h
c .l C
in

Africa
 Lu et al. PLoS NTD 2013. Lessons from One Case of Advanced
Schistosomiasis Japonica
Although the patient was not misdiagnosed from the beginning, she did go through
five medical facilities in pursuing medical treatment, covering a
distance of nearly 1,000 km.
... identification of
advanced cases has
been neglected in
most local stations
since the 1990s.

..necessary for a
schistosomiasis
control station to be
able to conduct the
job.

After elimination expertise is lost

 Vaccination against schistosomes?

Defined proteins including recombinant antigens in the 1990ies:

All of them failed!
Vaccine candidates:
(Bergquist, Al-Sherbiny, Barakat, Olds. 2002 Acta Trop. 82,183-192)
until 2013, NONE of the numerous published
„vaccine candidates“
was developed into a vaccine for humans :

- Purified antigen
- Recombinant antigens
- DNA vaccines
 Possible reasons for inability of “vaccine candidates”
to induce effect immunity

Selective activation of
Tregs

Direct inhibition of
Selective activation of
immune cells by
subpopulations of
Secreted/excreted
macrophages （ M1 ， M
antigens of parasites
2）

Th2-bias induced by parasites

(Th2 polarization) ；
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 Additional molecular evidence:
• The sugar: Schisto-derived lacto-N- neotetraose ） can
induce APC to produceIL-10 ， which inhibits the
degranulation of mast cells;
• LNFP III can obviously inhibit the immune
response(Th1) of host ， showing a therapeutic effect
in psoriasis and T1D ；
• These polysaccharide can improve the proliferation of
Tregs, activate aaMФ(M2 ）， leading to a long survival
of 80% of mice with heart transplantation!

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 Vaccination against Schistosoma japonicum

Measure the effect of the vaccine by

counting the schistosome worms in the buffaloes´ mesenteric veins
Shi, Jiang, Han, Li, Ruppel 1990. Experimental Parasitology 71, 100-106
 • Immunization against schistosomes:

• Nothing works better than

experimental vaccination with
attenuated cercariae (buffaloes and
pigs) …
• …except possibly an existing infection!
Overall conclusion:

To have a light parasitic infection may not be the

worst health condition in an endemic area, where
complete control of the disease is unrealistic.
My debatable opinion:
Biomedical research consumes huge human and financial
ressources, but seems not to lead to commensurate solutions for
the poor sick.

Public health research is financially accessible and may give

significant pro-poor results. It may lead to ethical satisfaction.

My strong recommendation:
Be critical and realistic to evaluate research agendas and
programs.
Kusel& Hagan, 1999
Sudan: irrigation canals
Oman: scooping for aquatic snails: Biomphalaria spec.
Mali: a pond at the end or a canal close to a village
 The agenda of Public Health
• Galileo Galilei:
„… the only justification of science is to
alleviate suffering of mankind…“
• MDGs, health-related:
alleviate poverty
reduce mortality and morbidity
combat diseases
• Improve the health of disadvantaged
populations
• Your personal agenda?
 The dilemma: (a) technological innovation

TDR news : Science, Technology, Innovation and Health

Technological innovation and general advances in science link

automatically to improvements in healthcare.
This is true.
The dilemma:
(b) Improving utilization
 Previous prevalence of schistosomiasis in China
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Buffaloes are the predominant
sources of human infection with
schistosomiasis in Yangzi River
valley

Free range buffaloes

The density of infected

snails was high
 Schistosomiasis will be eliminated by the end of 2025(China
government said)

• Elimination of infectious diseases depends on

elimination of Poverty and reduction of Inequity.

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 Science and discovery in China

Immunisation against smallpox

Moveable type printing

Compass: Circum navigating

the world
Gunpowder: not for the war
All of the above were discovered or
invented in China many years earlier
than in the West. So, there is every
reason to believe the Chinese science
will again become a major influence.
From my experience so far, it is clear
that there is great potential.
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