School-based deworming and community-wide

transmission of soil transmitted helminths

Déirdre HollingsworthUniversity 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

chemotherapy1. What should be the target of control programmes?2. Is elimination in a defined area possible by

chemotherapy alone?3. What are the best indicators for assessing the impact

of control?4. What level of infection across a community should

trigger mass chemotherapy to minimise morbidity?5. 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

chemotherapy1. What should be the target of control programmes?2. Is elimination in a defined area possible by

chemotherapy alone?3. What are the best indicators for assessing the impact

of control?4. What level of infection across a community should

trigger mass chemotherapy to minimise morbidity?5. 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

chemotherapy1. What should be the target of control programmes?2. Is elimination in a defined area possible by

chemotherapy alone?3. What are the best indicators for assessing the impact

of control?4. What level of infection across a community should

trigger mass chemotherapy to minimise morbidity?5. 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

chemotherapy1. What should be the target of control programmes?2. Is elimination in a defined area possible by

chemotherapy alone?3. What are the best indicators for assessing the impact

of control?4. What level of infection across a community should

trigger mass chemotherapy to minimise morbidity?5. 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

chemotherapy1. What should be the target of control programmes?2. Is elimination in a defined area possible by

chemotherapy alone?3. What are the best indicators for assessing the impact

of control?4. What level of infection across a community should

trigger mass chemotherapy to minimise morbidity?5. 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

chemotherapy6. As the prevalence and intensity fall after repeated

rounds of treatment, can the interval between treatments increase, and by how much?

7. How is the interval between treatments affected by the species mix in the community?

8. 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?

9. In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community?

10.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

chemotherapy6. As the prevalence and intensity fall after repeated

rounds of treatment, can the interval between treatments increase, and by how much?

7. How is the interval between treatments affected by the species mix in the community?

8. 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?

9. In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community?

10.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

chemotherapy6. As the prevalence and intensity fall after repeated

rounds of treatment, can the interval between treatments increase, and by how much?

7. How is the interval between treatments affected by the species mix in the community?

8. 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?

9. In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community?

10.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

chemotherapy6. As the prevalence and intensity fall after repeated

rounds of treatment, can the interval between treatments increase, and by how much?

7. How is the interval between treatments affected by the species mix in the community?

8. 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?

9. In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community?

10.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

chemotherapy6. As the prevalence and intensity fall after repeated

rounds of treatment, can the interval between treatments increase, and by how much?

7. How is the interval between treatments affected by the species mix in the community?

8. 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?

9. In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community?

10.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 studiesReference Main

targetCountry Drug Interv

alRounds

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 levamisole

6 mths

2-4 (1-2yr)

1-191-145-19

Intensity and prevalence

Thein-Hliang et al (1991) Trans RSTMH

Ascaris Myanmar levamisole

3 mths

4 (1 yr)

<152--12

Intensity and prevalence

Bundy et al (1990) Trans RSTMH

TrichurisAscaris

Monserrat

albendazole

4 mths

2, 4 (8, 16 mths)

2-15 Intensity and prevalence

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.

Som

alia

Centr

al ..

.

Djibouti

Benin

Nig

eri

a

Burk

ina..

.

Kenya

Yem

en

Angola

Bangla

...

Uganda

Moza

m..

.

Nepal

Egypt

Unit

ed .

..

Leso

tho

Myanm

ar

Zim

b..

.

Suri

nam

e

Peru

Alg

eri

a

Kaza

kh..

.040

80

Primary urban Primary rural Secondary attendance

Perc

en

tag

e o

f ch

ild

ren

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

Anderson et al PLoS NTDs (2013) in press

18%

Round worm• High worm

burdens in children

49% worms in 5-14yr olds

Anderson et al PLoS NTDs (2013) in press

18%

Hookworm• Lower

burden in children

Anderson et al PLoS NTDs (2013) in press

Hookworm• Lower

burden in children

Anderson et al PLoS NTDs (2013) in press

31%

Hookworm• Lower

burden in children

16% egg output in 5-14yr olds

Anderson et al PLoS NTDs (2013) in press

31%

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

Anderson et al PLoS NTDs (2013) in press

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

Prog

ram

me

impa

ctDrug efficacy

~80-90%

% of parasites treated

Impact on transmission

More studies needed

?

School Enrolment~20-90%

% parasites in school children

~10-50%

Demography X Parasites

A. lumbricoides

Demography

X Parasites

Hookw

orm

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

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 designSampling frameworks

New tools

Research questionsField data

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