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) DiseaseDALYs (million) Deaths /yrGlobal prevalence Control Lymphatic filariasis mMDA (ABZ +DEC/IVM) Hookworms , , m MDA (ABZ) Ascariasis , , m MDA (ABZ) Trichuriasis , , m MDA (ABZ) Onchocer- ciasis m MDA (IVM) Schistosom -iasis , , m MDA (PZQ)

-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 Lymphatic Filariasis

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 –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 Onchocerciasis- River Blindness 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

- 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. mansoniS. haematobium S. japonicum Schistosomiasis

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