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Roger Prichard and Catherine Bourguinat Institute of Parasitology

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:.

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Roger Prichard and Catherine Bourguinat Institute of Parasitology

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  1. 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

  2. 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

  3. The diseases • Lymphatic filariasis • Onchocerciasis • Soil transmitted helminths • Schistosomiasis

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

  5. 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

  6. Soil-transmitted helminths The causal agent of soil-transmitted helminthiasis is any of the following worms: -Ascaris lumbricoidesImpair children’s growth, cognitive development, physical fitness -Trichuris trichiuraRectal 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

  7. 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

  8. 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 – • The drug praziquantel costs 18 cents per dose • >423 million tablets PZQ needed globally/year to treat schistosomiasis S. japonicum S. mansoni S. haematobium

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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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