Opportunities and challenges for by pengxiuhui

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									Opportunities and challenges for
 mass chemotherapy programs
against parasitic diseases in low-
        resource settings

Roger Prichard and Catherine Bourguinat

         Institute of Parasitology
   Centre for Host-Parasite Interactions
             McGill University
     Sainte Anne-de-Bellevue, Québec
                Focus of presentation:
   Diseases caused by helminth parasites
   The burden of disease; diseases of poverty
   Mass treatment programs
   New opportunities
       Donations
       CDT
       Integration of programs

   Challenges
       Compliance, sustainability, resources, donor fatigue
       Treatment outcomes
       Drug resistance; monitoring efficacy & impact
              The diseases

   Lymphatic filariasis

   Onchocerciasis

   Soil transmitted helminths

   Schistosomiasis
Burden of high prevalence NTDs              (modified from Hotez et al.
                           Lancet 2009)

 Disease        DALYs      Deaths /yr       Global         Control
               (million)                  prevalence
Lymphatic        5.8          500           120 m       MDA (ABZ
filariasis                                              +DEC/IVM)
Hookworms      1.8-22.1      3,000-         600 m       MDA (ABZ)
                             65,000
Ascariasis     1.2-10.5      3,000-         800 m       MDA (ABZ)
                             60,000
Trichuriasis   1.6-6.4       3,000-         600 m       MDA (ABZ)
                             10,000
Onchocer-         1.5         500            37 m       MDA (IVM)
ciasis
Schistosom     1.7-4.7      15,000-         200 m       MDA (PZQ)
-iasis                      280,000
                       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
       Coupled with topical sanitation for secondary bacteria & fungi
       ABZ donated by GSK (~180m doses/yr; Σ>1 b doses donated)
       IVM (Mectizan) donated by Merck (>450 m doses donated)
       DEC very inexpensive

   Compliance & ineligible people
   ABZ and IVM have collateral benefits of helping control STH
   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
   Treatment of STH infections through national LF programs
   >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

   >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

   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
       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:
       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.)
   Mainly BZ drugs – ABZ (best) or MBZ
       ABZ being donated by GSK for LF control (not
        specifically for STH)
       MBZ being donated by Johnson & Johnson
   Efficacy ABZ (less for MBZ & other anthelmintics)
       ~ 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
       Need to monitor for drug resistance
    Onchocerciasis: Treatment & control
   MDA by Community Directed Treatment (CDTI)
       Compliance for CDTI variable
   Only IVM (Mectizan) available for MDA
   IVM donated by Merck (>600 m doses donated so far)
       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
       Difficult to monitor efficacy/resistance
   SAE occasionally with heavy Loa loa co-infection
    Schistosomiasis: Treatment & control
   National MDA, particularly of school children
   Praziquantel: must be purchased ~ US $0.18/dose
   Effectively no other drug now available
   PZQ effective against adult parasites, not very
    effective against juvenile stages
   Little immunity – reinfection
   Some PZQ resistance reports – not widespread
   Compliance & lack of resources problems
   Snail vector control sometimes attempted
         General opportunities for NTD
   Can use MDA including CDT

   Drugs donated or cheap to buy

   Donors willing to help

   MDA - major impact on morbidity

   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
   Compliance & ineligible populations (e.g. pregnant women)
   Lack of resources (shadow of big 3 - HIV/Malaria/TB)
   ~ Drugs give ~ poor efficacy
   MDA not curative – how many years MDA - sustainability?
   Donor fatigue (donors want quick & easy fixes)
   SAE with IVM in heavy L. loa infections
   Developing drug resistance in:
       O. volvulus
       N. americanus & T. trichiura
       Potentially in LF & S. mansoni
   V. few drugs no development pipeline
   Limited research funds & trained personnel
                      Conclusions:
   Control of these helminthic NTD - huge returns on
    investment in terms of human health and development,
    reduced suffering & social impacts
   Huge numbers of people affected
   Current tools for control are inadequate
   Compliance/sustainability problems
   Resistance developing to too few drugs
   Control of NTDs appeals to donors; but
   Donor fatigue & lack of realism
   Lack of resources in endemic countries
   Lack of research, drug pipeline, efficacy monitoring &
    trained personnel

								
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