Eliminating Lymphatic Filariasis
Success
in science, intervention and beyond…..
Eric A. Ottesen, M.D.
30 January 2007
LF Disease
LF Disease
Adult parasites (W. bancrofti) in scrotal lymphatic
Dreyer & Noroes
LF Disease
„ Other clinical manifestations
‘Filarial fevers’
„ Tropical Pulmonary Eosinophilia
„ Chyluria
„ Hematuria/Proteinuria
„ others less well defined
„
LF Infection
Asymptomatic microfilaremia
Adult Worms
L4
L3
Mf
Human
Mosquito
L2
Why do we focus on LF now?
„ Partly, it’s because of LF’s importance
„
LF imposes a health burden
„
affecting 120 million people
ƒ 40 million with overt disease
ƒ 80 million with ‘hidden’ infection and disease
„
„
„
1.1 billion people ‘at risk’ of infection
83 endemic countries throughout the tropics/sub-tropics
leading cause of disability, stigma, economic loss
LF Endemic Countries & Territories – 2006
8|
Fourth GAELF, Fiji-29- 31 Mar 2006
Why do we focus on LF now?
„ Partly, it’s because of LF’s importance
„
LF imposes a health burden
„
affecting 120 million people
ƒ 40 million with overt disease
ƒ 80 million with ‘hidden’ infection and disease
„
„
„
1.1 billion people ‘at risk’ of infection
83 endemic countries throughout the tropics/sub-tropics
leading cause of disability, stigma, economic loss
„ Especially, because we can do something about it!
Why do we focus on LF now?
„
?
It’ a really good ‘science’ story
Research
Understanding
Tools
Strategy
Public Health
Implementation
bedside
“bench”
community
Towards Public Health Implementation
?
Research
Understanding
Tools
Strategy
Public Health
Implementation
1st step: to define a clear goal
Global Program to Eliminate LF (GPELF)
Operational Goals
1)
2)
To interrupt LF transmission
To alleviate and prevent the suffering of those
already affected
Global Program to Eliminate LF (GPELF)
Operational Goals
1)
2)
To interrupt LF transmission
To alleviate and prevent the suffering of those
already affected
New understandings: pathogenesis of
lymphedema/elephantiasis
1)
Recognition that LF is an infection acquired in childhood
%
40
30
26%
Diagnosis by
Antigen
20
10
6%
0
2 years
4 years
age of children in cohort
Antigen
Haiti;
Lammie et al
New understandings: pathogenesis of
lymphedema/elephantiasis
2)
Recognition of ‘sub-clinical’ lymphatic damage
Lymphoscintigraphy
(legs)
normal
Ultrasound
(scrotal lymphatic)
LF (aysmptomatic mf+)
New understandings: pathogenesis of
lymphedema/elephantiasis
3)
Identifying the etiology and importance of ‘filarial fevers’
(acute inflammatory episodes)
ADL
DLA
New understandings: pathogenesis of
lymphedema/elephantiasis
4)
Recognizing that bacterial superinfection was the
principal determinant of disease progression
Entry Lesions
New understandings: management of
lymphedema/elephantiasis
Preventing bacterial infections is
the primary goal of managing
patients with lymphedema
¾
¾
¾
¾
¾
¾
Hygiene
Treatment and prevention
of skin lesions
Exercise
Elevation
Shoes
Bandages
LF genital disease: pathogenesis & management
ƒ Pathogenesis: lymphatic distortion +/- bacterial infection
ƒ Management: for hydrocele, surgery is cure
for genital lymphedema/elephantiasis,
hygiene
Global Program to Eliminate LF (GPELF)
Operational Goals
1)
2)
To interrupt LF transmission
To alleviate and prevent the suffering of those
already affected
For the LF program, the goal is elimination
ƒ What does elimination mean?
ƒThe incidence of infection must become zero
ƒ Transmission must be interrupted
ƒ What does it take to achieve elimination?
¾ Effective interventions
¾ Effective diagnostics
LF Infection
Asymptomatic microfilaremia
Adult Worms
L4
L3
Mf
Human
Mosquito
L2
Effective tools: for intervention
The anti-filarial drugs
DEC
Adult Worms
Diethylcarbamazine (DEC)
Ivermectin (IVR)
ALB
DEC
L4
Albendazole (ALB)
L3
Mf
Human
Mosquito
L2
IVR
Effectiveness of Single Doses of Antifilarial Drugs
% Pre-treatment (mf/ml)
100
DEC
80
Ivermectin
Albendazole
60
40
20
0
0
1
3
Months Post Treatment
6
12
(Meta-analysis
8-20 studies each)
ALBENDAZOLE, IVERMECTIN & DEC
2-Drug Regimens
Microfilaraemia
(% Pre-Rx)
Blood Microfilaria Levels (W. bancrofti)
Months Post
Treatment
100
90
80
70
60
50
40
30
20
10
0
ALB+IVER
ALB+DEC
0
1
2
3
6
9
11
15
30
Single-Dose Treatment
Ismail et al.’96
What makes a disease ‘eliminatable’?
¾ Effective intervention tools
¾ Effective diagnostic tools
‘New’ diagnostic: antigen-detection test
(W.bancrofti)
•
•
•
•
•
•
•
High sensitivity (>95%)
High specificity (99%)
Uses finger-prick blood
Rapid (1-10 minutes)
Positive night and day
Field-useable
Commercially available (cost:
$2.50/test for public health
programs)
LF does have effective tools
¾
¾
¾
For intervention
For diagnosis
For managing LF disease
The challenge for all our programs
?
Research
Understanding
Tools
Strategy
Public Health
Implementation
Creating a strategy for LF elimination:
Previously
• Diagnose
Individual
• Treat
Individual
Creating a strategy for LF elimination:
major paradigm shift
Previously
Now
• Diagnose
Individual
Population
• Treat
Individual
Population
Creating a strategy to eliminate LF:
Interrupt transmission: 1st major paradigm shift
• Identify all LF-endemic areas
• Treat entire ‘at risk’ populations
• 2-drug, single-dose regimens once-yearly x 4-6 years
• by ‘mass drug administration’ (MDA)
Creating a strategy to eliminate LF:
Interrupt transmission: 1st major paradigm shift
• Identify all LF-endemic areas
• Treat entire ‘at risk’ populations
• 2-drug, single-dose regimens once-yearly x 4-6 years
• by ‘mass drug administration’ (MDA)
Alleviate suffering / Prevent disease
• Introduce new principles of hygiene and patient care
to prevent and manage LF disease
The challenge for all our programs
Phase-1-------------------------------------------------------l
Phase-2
Phase-3------------------l
?
Research
Understanding
Tools
Strategy
Public Health
Implementation
The challenge for all our programs
Phase-1-------------------------------------------------------l
Phase-2
Phase-3------------------l
?
Research
Understanding
Tools
Strategy
Public Health
Implementation
Public Health Implementation
„ Must speak a new ‘language’
?
Research
antigens
primers
receptors
transduction
pharmacokinetics
IL-1, IL-4, IL-13
genomics
proteomics
Understanding
Tools
Strategy
Public Health
Implementation
partnerships
collaborations
alliances
business plans
cost-effectiveness
health systems
equity
MDGs
Public Health Implementation
„ Absolute requirements:
‘Political’ commitment
„ Resources
„ Determination to work together (as partners)
„
LF Elimination:
-‘scientific’ political commitment¾
1993: International Task Force on Disease Eradication
•
•
•
The 2 essential criteria for eradicability were met
Other attributes (biological) favored eradicability
LF elimination has been successful before!
¾ LF: one of 6 diseases eradicable or potentially eradicable
LF Elimination:
-‘governmental’ political commitment„ Ministries of Health
„ individual commitment by MOH to establish national
LF elimination programmes
„ ‘collective commitment’: WHA Resolution ’97
„
„
“Urges Member States......to strengthen activities toward
eliminating lymphatic filariasis as a public health
problem........”
“Requests the Director-General......to mobilize support for
global and national elimination activities.”
Public Health Implementation
„ Absolute requirements:
‘Political’ commitment
„ Resources
„ Determination to work together (as partners)
„
LF Elimination:
-early donations of resourcesTo donate all albendazole required for LF elimination; to
support selected research and program activities
Merck and Co. Inc
Whitehouse Station, NJ, USA
,
UK
To expand Mectizan Donation Program to provide
ivermectin for LF treatment where onchocerciasis co-exists
Long-term support of programme development and
intervention in the countries and globally, through WHO
and the LF support centres
To support activities toward elimination of LF from all
Arab Fund member countries
Arab Fund
To support programme training activities and efforts to
eliminate LF from the Pacific island nations (PacELF)
Japan
The challenge for all our programs
Phase-1-------------------------------------------------------l
Phase-2
Phase-3------------------l
?
Research
Understanding
Tools
Strategy
Public Health
Implementation
What’s the most important thing in real estate?
Location
Location
Location
What’s the most important thing in global health?
Partnership
Partnership
Partnership
Public Health Implementation
„ Absolute requirements:
‘Political’ commitment
„ Resources
„ Determination to work together (as partners)
„
Global Alliance Partnership
Strategic Plan
for the Partners
•Targets
•Milestones
•Roles of partners
Global Alliance
To Eliminate Lymphatic Filariasis
WHO
Japan
Arab Fund for Economic
and Social Development
Liverpool School of
Tropical Medicine
Bill and Melinda Gates Foundation
Unicef
CDC
US Centers for
Disease Control and Prevention
World Bank
Health & Development
International
Success requires partnership
„ Public-sector partners
„ Ministries of Health
„ ‘Overseas Development Agencies’
„ Private-sector partners
„ Pharmaceutical companies
„ Foundations
„ NGOs, technical agencies, academia, others
„ People partners – ‘people-power’
„ in the programmes
„ in the communities
Success requires partnership
Phase-1-------------------------------------------------------l
Phase-2
Phase-3------------------l
?
Research
Understanding
Tools
Strategy
Public Health
Implementation
LF Elimination
The Global Program(me)
(2000-2020)
Global Program to Eliminate LF (GPELF)
Operational Goals
1)
2)
To interrupt LF transmission through MDAs
To alleviate and prevent the suffering of those
already affected
Mass Drug Administration (MDA)
Countries with LF Elimination Programs
(2006)
15 Pacific
Island Countries
Countries with active LF elimination programs
Countries endemic for LF which have only
i
incipient or not yet active elimination
programs
Countries with active LF elimination programs and
specific demonstration projects funded by the Gates Foundation
450
45
400
40
350
35
300
30
250
25
200
20
150
15
100
10
50
5
0
0
2000
2001
2002
2003
Treatments administered (both single and dual drug)
2004
2005
Country programmes
Number of country programmes
Number of treatments (millions)
Global Programme Progress
MDA Reduces Microfilaria Prevalence
Vanuatu
Egypt
K. Bahary
K. Qebly
K. Tahoria
Tahoria
Sola
Mos ina
Port R.
S. River
Sakau
Wanur
Orap
Unm et
Year 2
Year 3
14
35
Prevalence (%)
12
30
Prevalence (%)
10
8
6
4
2
25
20
15
10
5
0
0
Pre-Rx
Year 1
Year 2
Year 3
Pre-RX
Haiti
Mapou
Papua New Guinea
Mas s on
Barrier Jeudi
Site 1
18
90
16
80
14
70
Prevalence (%)
Prevalence (%)
Leogane
Year 1
12
10
8
6
Site 3
Site 4
60
50
40
30
4
20
2
10
0
Site 2
0
Pre-Rx
Year 1
Year 2
Year 3
Pre-RX
Year 1
Year 2
Year 3
Year 4
Impact of MDA on Microfilaria Clearance at
Sentinel Sites After 2 or 3 MDAs
13%
43%
Total clearance
50%-99% clearance
<50% clearance
44%
The Global Programme to
Eliminate Lymphatic Filariasis
on track and doing well…... but are there still
problems/challenges?
Are there still problems/challenges for LF?
„ Very definitely!
?
Research
Understanding
Tools
Strategy
Public Health
Implementation
Are there still problems/challenges for LF?
„ Very definitely!
?
Research
Understanding
Tools
Strategy
Public Health
Implementation
WHO/TDR
Scientific Working Group
May 2005
Gates Foundation
Grant to GAELF
2006-2010
Facing the facts……..
„ Our programmes
in many places, are now starving for funds
„ are extremely well organized and well run
„ are highly popular with communities
„ are successful in achieving their targets
„ are ridiculously inexpensive for the benefit attained
„ could be successfully and fully implemented if
funds were available
„
„ LF has proven to be a major challenge to ‘market’
So what should be done?
¾ It’s time for a 2nd major paradigm shift
What’s the most important thing in global health?
Partnership
Partnership
Partnership
Programme success
2nd major paradigm shift
Strategy to ensure LF elimination:
Previously
Now
Implementation
LF alone
with NTDs
Advocacy/fundraising
LF alone
with NTDs
Package of ‘Neglected Tropical Diseases’
(‘Targets of Opportunity’/‘Rapid impact Diseases’)
„ Lymphatic filariasis (LF)
„ Onchocerciasis
„ Schistosomiasis
„ Soil-transmitted helminthiasis (STH)
„ Trachoma
“The devil is in the detail……..”
„ What could/should be integrated?
„
MDA
„
„
„
„
Medications and their delivery
IEC/Social mobilization
Logistics
Monitoring & Evaluation
Morbidity management
„ Fundraising & Advocacy
„
Promise of the Future – for NTDs
„ Success in implementation: from exploiting the synergies
among public health initiatives sharing similar strategies
„
„
„
„
„
„
Lymphatic Filariasis – GPELF
Onchocerciasis – APOC
Schistosomiasis - SCI
Soil Transmitted Helminths – PPC
Trachoma – ITI
Micronutrient Initiative
„ Success in resource mobilization: from attractiveness of
integrated management of packages of programmes
targeting important but otherwise-neglected diseases
Arguably the ‘best buy’ in global health today!
Comparative Treatment Costs (Range)
HIV/AIDS
Ref: Clinton Foundation, Bertozzi, etal 2004, Bautista 2003
TB
Ref: Global TB Control 2005
Malaria
Ref: Chmia, 2003; Molyneux et al 2005
Ref: Brady et al 2006
NTD Package
0
100
200
300
400
500
600
700
Cost per patient treatment per year (US dollars)
800
900
1000
Global Disease Burden (DALYs)
DALYs (in millions)
Ischemic heart
disease
58.6
Neglected
tropical diseases
56.6
Cerebrovascular
diseases
49.2
Diarrheal
diseases
62.0
Malaria
46.5
Road traffic
accidents
38.7
Unipolar
depression
67.3
HIV / AIDS
84.5
Lower
Respiratory
Infections 91.4
Tuberculosis
34.7
Integrating Neglected Tropical Disease Control
Global Network for Neglected Tropical Diseases
http://www.GNNTDC.org
•
•
•
•
•
•
•
Schistosomiasis Control Initiative
International Trachoma Initiative
Helen Keller International
Liverpool School - GAELF
Human Hookworm Vaccine Initiative
Earth Institute at Columbia Univ.
Task Force for Child Survival
– Lymphatic Filariasis Support Center
– Mebendazole Donation Intiative
– Mectizan Donation Program
New NTD Control Projects
The Global Network for Neglected Tropical Disease Control
8 / 56 Countries
Geneva Global
Burundi
Rwanda
Exxon Mobil
Equatorial Guinea
USAID
Burkina Faso
Ghana
Mali
Niger
Uganda
The Buzz on NTDs
“Thelearned
world isthat
nowthis
paying
attention
tolong
these
[neglected]
“We
integration
is
a
process,
but it is
“It
quickly
became
clear
that
this
story
is
not
just
about
the
“Comprehensive,
controlinof
malaria and
NTDs
diseases and Africa-wide
making progress
unprecedented
ways,
worth
doing,
andgoals,
are
learning
bythan
doing
process.”
staggering
numbers
ofwe
the
world’s
citizens
overwhelmed
by
together
would
probably
cost
no more
$3that
billion
agrowing
year,
with ambitious
excellent
interventions,
and
HIV,–evidence
AIDS,
TB,ofand
malaria.
And it’s
not
just
the story
about
Dominique
Kyelem,
Burkina
Ministry
ofbillion
Health,
multiple
benefits
for Faso
health.
The
attention
to
or
just
two
days
of
Pentagon
spending.
If
each
of
the
one Lymphatic
billion
people
who
are
afflicted
with
disabling,
oftentimes
long-neglected
diseases
is athe
positive
sign that
health
Filariasis
Control
Program
people
in theneglected
rich
world
devoted
equivalent
of human
one
$3 is a
stigmatizing,
tropical
diseases,
such
as
responsibility shared by the international community.”
hookworm
infection
elephantiasis…
it’schildren
all about
the
coffee a year
to the and
cause,
several million
every
-Dr.
Margaret
Chan,
Director-General
of
the
World
faces
of dying
children
and
sick and
mothers
whoand
haunt
those
yearHealth
would
be
spared of
death
debility,
world
Organization
who have seen them...What struck me, and what I think
would us
beall…that
spared the
grave
risks when
and despair
struck
these
challenges
aredisease
all interconnected.”
unchecked.
new Global
Network
for Neglected
-run
Clinton
GlobalAInitiative,
Closing
Remarks
Tropical Disease Control is helping make this opportunity a
reality.”
- Jeffrey Sachs, Director of the Earth Institute, Scientific
American January 2007
• World’s first peer-reviewed, open-access journal
devoted to the NTDs
• Launch supported by Bill and Melinda Gates
Foundation
• Papers on pathology, epidemiology, treatment,
control, prevention
• Magazine section devoted to policy and advocacy
• International editorial board—half of the
Associate Editors are from endemic countries
• Accepting submissions in early 2007
“It is expected that the journal will be both catalytic and transformative
in promoting science, policy, and advocacy for these diseases of the poor.”
—Peter Hotez, Editor-in-Chief
Successes, Challenges, Way Forward
„ Must recognize that we have extraordinary opportunities to
make enormous impact on the health and economies of
the developing world, at very low cost
…. “we simply cannot do it …. alone”
„ Success will come from exerting flexibility, changing old
habits, creating new partnerships – new coalitions of
coalitions
„ No longer speak solely of LF and the Global Programme
to eliminate it -- now it’s
LF and Beyond – the NTDs & other Global Health challenges
…maybe this will be the new ‘NTD face’ of
LFelimination, schisto control, ….
Costs for Treating 5 ‘Neglected Diseases’ at
2006 Target Levels in Sub Saharan Africa
Cost per person - treat each disease separately
Total cost - treat each disease separately
Cost per person - treat packaged NTDs
Total cost - treat packaged NTDs
$1.07
$109
million
$0.57
$58
million
Outcomes Projected from Integrated Treatment
of 5 NTDs in SSA (at 2006 Levels)
10.5 million children protected from STH
14.7 million adults protected from STH
5 million cases of skin disease and itching prevented
570,000 pregnant women protected from anemia
100,000 people protected from severe kidney or bladder disease
65,000 cases of hydrocele prevented
28,000 cases of lymphedema prevented
25,000 cases of blindness prevented
5,000 people protected from life-threatening liver disease