Transcript Opportunities and challenges for mass

Opportunities and challenges for
mass chemotherapy programs
against parasitic diseases in lowresource settings
Roger Prichard and Catherine Bourguinat
Institute of Parasitology
Centre for Host-Parasite Interactions
McGill University
Sainte Anne-de-Bellevue, Québec
Focus of presentation:
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Diseases caused by helminth parasites
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The burden of disease; diseases of poverty

Mass treatment programs
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New opportunities

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Donations
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CDT
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Integration of programs
Challenges
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Compliance, sustainability, resources, donor fatigue
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Treatment outcomes
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Drug resistance; monitoring efficacy & impact
The diseases
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Lymphatic filariasis
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Onchocerciasis

Soil transmitted helminths
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Schistosomiasis
Burden of high prevalence NTDs
Lancet 2009)
Disease
(modified from Hotez et al.
DALYs
(million)
Deaths /yr
Global
prevalence
Control
Lymphatic
filariasis
5.8
500
120 m
MDA (ABZ
Hookworms
1.8-22.1
3,00065,000
600 m
MDA (ABZ)
Ascariasis
1.2-10.5
3,00060,000
800 m
MDA (ABZ)
Trichuriasis
1.6-6.4
3,00010,000
600 m
MDA (ABZ)
Onchocerciasis
1.5
500
37 m
MDA (IVM)
Schistosom
-iasis
1.7-4.7
15,000280,000
200 m
MDA (PZQ)
+DEC/IVM)
Lymphatic Filariasis
-1.2 billion people in 83 countries at risk
-120 million people infected worldwide
-India, Indonesia, Nigeria and Bangladesh (account for 70 % of global
lymphatic filariasis infections)
-Estimates of annual economic loss in India due to lymphatic filariasis US $1b
-Lymphoedema, hydrocele, elephantiasis, impaired motility, social stigma
Soil-transmitted helminths
The causal agent of soil-transmitted helminthiasis is any of the
following worms:
-Ascaris lumbricoides Impair children’s growth, cognitive development, physical fitness
-Trichuris trichiura Rectal prolapse, impair children’s growth, cognitive development,
physical fitness
- Hookworms (N. americanus, A. duodenale) Anemia in children and pregnant women,
impair children’s growth, cognitive development, physical fitness
STHs affects more than 2,000 million people worldwide
-Globally STHs cause 3 – 24 m DALYs per year
-STH infections predominantly in sub-Saharan Africa, the Americas, east and south Asia
Onchocerciasis- River Blindness
-Onchocerciasis –blindness, visual impairment, severe skin pathology - greatly
reduces income-generating capacity, incurs significant health expenditures,
reduces life expectancy and exerts a very negative socioeconomic impact on
the afflicted populations and land use
-Currently, via APOC/OEPA, more than 40 million people receive regular
ivermectin treatment through a community drug-distribution
Distribution of Onchocerciasis/Current Status of Global Onchocerciasis Control
▀ APOC/OEPA IVM distribution
▀ Former OCP, now National IVM
distribution
▀ IVM + vector control
▀ Epidemiological surveys required
Schistosomiasis
- 200 million people infected; half in Africa (650 million people live in
endemic areas)
- 2nd most socioeconomically devastating parasitic disease, after malaria
- Anemia, malnutrition, impaired cognitive development, damage to liver,
intestines, lungs, bladder (bladder cancer), hepatosplenomegaly
- Found in 74 tropical countries.
-3 main species of Schistosome in humans –
S. japonicum
-The drug praziquantel costs 18 cents per dose
- >423 million tablets PZQ needed globally/year to treat schistosomiasis
S. mansoni
S. haematobium
Lymphatic filariasis: Treatment and control

MDA (national programs + Internat. coord. - GPELF) with ABZ +
DEC or ABZ + IVM to reduce transmission & arrest disease
progression. Drugs not curative
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Coupled with topical sanitation for secondary bacteria & fungi
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ABZ donated by GSK (~180m doses/yr; Σ>1 b doses donated)
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IVM (Mectizan) donated by Merck (>450 m doses donated)
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DEC very inexpensive
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Compliance & ineligible people
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ABZ and IVM have collateral benefits of helping control STH
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Transmission by mosquitoes: impregnated bed nets & insecticide
spraying of houses for malaria control can reduce LF
transmission
BMGF & others supporting LF ‘elimination’ programs
HEALTH IMPACT: ‘BEYOND LF’ BENEFITS
−
Treatment of STH infections through national LF programs
o >170 m treatments for STH (ABZ) given to 56 million children by
GPELF, resulting in:
􀂃 Increased appetite, weight gain and growth
􀂃 Greater eye‐hand coordination, learning ability and concentration
􀂃 Better school attendance, cognitition, fitness scores & spontaneous
play activity
o >140 m treatments for STH (ABZ) given to 44.5 million women of
childbearing age by GPELF, improving nutritional status & iron stores,
leading to:
􀂃 Increased infant birth‐weights by up to 50 grams
􀂃 Decreased infant mortality by up to 40% & decreased maternal
mortality
HEALTH IMPACT: ‘BEYOND LF’ BENEFITS
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Treatment of STH infections through national LF programs
>170 m treatments for STH (ABZ) given to 56 million
children by GPELF, resulting in:
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Increased appetite, weight gain and growth
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Greater eye‐hand coordination, learning ability and concentration


Better school attendance, cognitition, fitness scores & spontaneous
play activity
>140 m treatments for STH (ABZ) given to 44.5 million
women of childbearing age by GPELF, improving nutritional
status & iron stores, leading to:


Increased infant birth‐weights by up to 50 grams
Decreased infant mortality by up to 40% & decreased maternal
mortality
HEALTH IMPACT: ‘BEYOND LF’ BENEFITS

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Treatment of onchocerciasis, scabies, and lice with IVM
through the GPELF in Africa
>149 million IVM treatments given by GPELF, coordination
with APOC to >45 million in African communities
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Millions of people living in onchocerciasis‐endemic areas not
previously treated, received IVM through coordination between
GPELF and APOC
IVM’s long‐lasting impact on scabies reduces community
prevalence after 1 cycle and almost eliminates it after >2
treatments:

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Improved sleep patterns and overall well-being
Protection from post‐streptococcal renal disease induced by
group B streptococcus skin infections that often complicate
chronic scabies infection
STH: Treatment & control

MDA programs (Deworm the World – Clinton Initiative;
FRESH – World Bank; etc.)
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Mainly BZ drugs – ABZ (best) or MBZ
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Efficacy ABZ (less for MBZ & other anthelmintics)
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ABZ being donated by GSK for LF control (not
specifically for STH)
MBZ being donated by Johnson & Johnson
~ 98% - Ascaris lumbricoides
~ 50 – 70% Hookworms
~ 30 – 50% Trichuris trichiura
Sometimes efficacy failure against hookworms &
Trichuris. BZ resistance mutations recently found
in N. americanus & T. trichiura
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Need to monitor for drug resistance
Onchocerciasis: Treatment & control
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MDA by Community Directed Treatment (CDTI)
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Only IVM (Mectizan) available for MDA
IVM donated by Merck (>600 m doses donated so far)
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IVM kills microfilaria (mf) and inhibits production of
new mf by adult worms for 3-12 months
IVM reduces morbidity & transmission (mf)
Does not kill adult worms
Oncho as public health problem markedly reduced
20 years of IVM distribution in W. Africa
Transmission reduced but continues
IVM resistance now seen in West Africa
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Compliance for CDTI variable
Difficult to monitor efficacy/resistance
SAE occasionally with heavy Loa loa co-infection
Schistosomiasis: Treatment & control
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National MDA, particularly of school children
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Praziquantel: must be purchased ~ US $0.18/dose
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Effectively no other drug now available
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PZQ effective against adult parasites, not very
effective against juvenile stages
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Little immunity – reinfection
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Some PZQ resistance reports – not widespread
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Compliance & lack of resources problems
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Snail vector control sometimes attempted
General opportunities for NTD
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Can use MDA including CDT
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Drugs donated or cheap to buy
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Donors willing to help
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MDA - major impact on morbidity

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Spectacular benefit/cost ratios (World Bank calculated
intervention against NTD gave greatest returns on
investments in development, compared with all other
investments)
Possible to integrate all of these MDA interventions with
others for Trachoma, malaria, etc.
Challenges
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Compliance & ineligible populations (e.g. pregnant women)
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Lack of resources (shadow of big 3 - HIV/Malaria/TB)
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~ Drugs give ~ poor efficacy
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MDA not curative – how many years MDA - sustainability?
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Donor fatigue (donors want quick & easy fixes)
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SAE with IVM in heavy L. loa infections
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Developing drug resistance in:
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O. volvulus
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N. americanus & T. trichiura
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Potentially in LF & S. mansoni
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V. few drugs no development pipeline
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Limited research funds & trained personnel
Conclusions:
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Control of these helminthic NTD - huge returns on
investment in terms of human health and development,
reduced suffering & social impacts
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Huge numbers of people affected
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Current tools for control are inadequate
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Compliance/sustainability problems
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Resistance developing to too few drugs
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Control of NTDs appeals to donors; but
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Donor fatigue & lack of realism
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Lack of resources in endemic countries
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Lack of research, drug pipeline, efficacy monitoring &
trained personnel