School-based deworming and community-wide transmission of soil transmitted helminths Déirdre Hollingsworth University of Warwick Liverpool School of Tropical Medicine

Soil-transmitted helminths Burden of disease (WHO estimates) Up to 1.2 billion people infected with one or more of the soil-transmitted helminths 135,000 deaths per year Disabling effects Anaemia Stunted growth Impaired cognitive development Want to maximise impact of drug donations in London Declaration: 400m albendazole, GlaxoSmithKlein 200m mebendazole, Johnson & Johnson Despommier D et al. Parasitic Diseases. 2001

Key questions for control of soil-transmitted infections by chemotherapy What should be the target of control programmes? Is elimination in a defined area possible by chemotherapy alone? What are the best indicators for assessing the impact of control? What level of infection across a community should trigger mass chemotherapy to minimise morbidity? For a given transmission level, how often should mass or targeted chemotherapy be administered to sustain infection prevalence and intensity below defined levels? Anderson, Hollingsworth et al Lancet (2012)

Key questions for control of soil-transmitted infections by chemotherapy What should be the target of control programmes? Is elimination in a defined area possible by chemotherapy alone? What are the best indicators for assessing the impact of control? What level of infection across a community should trigger mass chemotherapy to minimise morbidity? For a given transmission level, how often should mass or targeted chemotherapy be administered to sustain infection prevalence and intensity below defined levels? Anderson, Hollingsworth et al Lancet (2012)

Key questions for control of soil-transmitted infections by chemotherapy What should be the target of control programmes? Is elimination in a defined area possible by chemotherapy alone? What are the best indicators for assessing the impact of control? What level of infection across a community should trigger mass chemotherapy to minimise morbidity? For a given transmission level, how often should mass or targeted chemotherapy be administered to sustain infection prevalence and intensity below defined levels? Anderson, Hollingsworth et al Lancet (2012)

Key questions for control of soil-transmitted infections by chemotherapy What should be the target of control programmes? Is elimination in a defined area possible by chemotherapy alone? What are the best indicators for assessing the impact of control? What level of infection across a community should trigger mass chemotherapy to minimise morbidity? For a given transmission level, how often should mass or targeted chemotherapy be administered to sustain infection prevalence and intensity below defined levels? Anderson, Hollingsworth et al Lancet (2012)

Key questions for control of soil-transmitted infections by chemotherapy What should be the target of control programmes? Is elimination in a defined area possible by chemotherapy alone? What are the best indicators for assessing the impact of control? What level of infection across a community should trigger mass chemotherapy to minimise morbidity? For a given transmission level, how often should mass or targeted chemotherapy be administered to sustain infection prevalence and intensity below defined levels? Anderson, Hollingsworth et al Lancet (2012)

Key questions for control of soil-transmitted infections by chemotherapy As the prevalence and intensity fall after repeated rounds of treatment, can the interval between treatments increase, and by how much? How is the interval between treatments affected by the species mix in the community? How do the demography of the population and the starting geographical distribution of infection affect the structure of optimum treatment programmes when resources are finite? In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community? How might repeated mass treatment affect the evolution of drug resistance and how can this risk be minimised? Anderson, Hollingsworth et al Lancet (2012)

Key questions for control of soil-transmitted infections by chemotherapy As the prevalence and intensity fall after repeated rounds of treatment, can the interval between treatments increase, and by how much? How is the interval between treatments affected by the species mix in the community? How do the demography of the population and the starting geographical distribution of infection affect the structure of optimum treatment programmes when resources are finite? In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community? How might repeated mass treatment affect the evolution of drug resistance and how can this risk be minimised? Anderson, Hollingsworth et al Lancet (2012)

Key questions for control of soil-transmitted infections by chemotherapy As the prevalence and intensity fall after repeated rounds of treatment, can the interval between treatments increase, and by how much? How is the interval between treatments affected by the species mix in the community? How do the demography of the population and the starting geographical distribution of infection affect the structure of optimum treatment programmes when resources are finite? In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community? How might repeated mass treatment affect the evolution of drug resistance and how can this risk be minimised? Anderson, Hollingsworth et al Lancet (2012)

Key questions for control of soil-transmitted infections by chemotherapy As the prevalence and intensity fall after repeated rounds of treatment, can the interval between treatments increase, and by how much? How is the interval between treatments affected by the species mix in the community? How do the demography of the population and the starting geographical distribution of infection affect the structure of optimum treatment programmes when resources are finite? In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community? How might repeated mass treatment affect the evolution of drug resistance and how can this risk be minimised? Anderson, Hollingsworth et al Lancet (2012)

Key questions for control of soil-transmitted infections by chemotherapy As the prevalence and intensity fall after repeated rounds of treatment, can the interval between treatments increase, and by how much? How is the interval between treatments affected by the species mix in the community? How do the demography of the population and the starting geographical distribution of infection affect the structure of optimum treatment programmes when resources are finite? In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community? How might repeated mass treatment affect the evolution of drug resistance and how can this risk be minimised? Anderson, Hollingsworth et al Lancet (2012)

Why school-based deworming? Burden of disease in children Existing infrastructure for delivery Integration with other school health programmes What is the impact on transmission?

Empirical studies Reference Main target Country Drug Interval Rounds Age group targeted (yrs) Impact on untreated Asaolu et al (1991) Parasitology Ascaris, Trichuris, Hookworm Nigeria levamisole 3 mths 4 (1yr) 2-15 Intensity, Ascaris only Thein-Hliang et al (1990) WHO Bulletin Ascaris Myanmar 6 mths 2-4 (1-2yr) 1-19 1-14 5-19 Intensity and prevalence Thein-Hliang et al (1991) Trans RSTMH 4 (1 yr) <15 2--12 Bundy et al (1990) Trans RSTMH Trichuris Monserrat albendazole 4 mths 2, 4 (8, 16 mths) We need a framework for thinking about the impact of treating only 5-14 year olds

How many worms are exposed to treatment? Demography What proportion of population are school-aged? Behaviour What proportion of children attend school? Epidemiology What is the load of worms in children? Anderson, Truscott, Pullan, Brooker, Hollingsworth PLoS NTDs (2013) in press

School attendance Enrolment varies by country, by age and by region Attendance at deworming days may be higher than ordinary school days. Source: UNICEF

How many worms are exposed to treatment? Demography What proportion of population are school-aged? Behaviour What proportion of children attend school? Epidemiology What is the load of worms in children? Anderson, Truscott, Pullan, Brooker, Hollingsworth PLoS NTDs (2013) in press

Round worm High worm burdens in children Anderson et al PLoS NTDs (2013) in press

Round worm High worm burdens in children 18% Anderson et al PLoS NTDs (2013) in press

Round worm High worm burdens in children 18% 49% worms in 5-14yr olds Anderson et al PLoS NTDs (2013) in press

Hookworm Lower burden in children Anderson et al PLoS NTDs (2013) in press

Hookworm Lower burden in children 31% Anderson et al PLoS NTDs (2013) in press

Hookworm Lower burden in children 31% 16% egg output in 5-14yr olds Anderson et al PLoS NTDs (2013) in press

Impact on transmission % of worms or output in school-age children is a crude calculation of likely impact Impact on transmission depends on Extent transmission from children to adults and younger children Vice versa Investigate scenarios using mathematical models

Two separate groups contributing equally to same infected pool Treated group (30%) see much larger effect Untreated group very little impact Anderson et al PLoS NTDs (2013) in press

Children over-contribute to transmission Starting intensity in untreated group is lower Larger impact on this group of treating the children Anderson et al PLoS NTDs (2013) in press

? Programme impact A. lumbricoides Hookworm Drug efficacy ~80-90% Demography X Parasites A. lumbricoides Demography % parasites in school children ~10-50% Hookworm School Enrolment ~20-90% Impact on transmission X Parasites Programme impact % of parasites treated ? More studies needed Anderson et al PLoS NTDs (2013) in press

How to address this question Monitoring impact of school-based treatment on whole communities Whole age-profiles before and after treatment Detailed studies of the dynamics of ‘bounce-back’ in adults and children Robust parameter estimation Trials of different treatment strategies Genetic studies Identifying transmission networks

Responding to programmatic need Research questions Field data Control strategies Mapping, monitoring & evaluation Frequency of & targeting of treatment Programme design Research Mapping, sampling Epidemiology of transmission and control Diagnostic design and evaluation Programme design Sampling frameworks New tools

Acknowledgements Imperial College London Professor Sir Roy Anderson Dr James Truscott Helminth researchers London School of Hygiene and Tropical Medicine Professor Simon Brooker Dr Rachel Pullan Funders Bill and Melinda Gates Foundation Partnership for Child Development Imperial College Junior Research Fellowship