A COUNTDOWN on schistosomiasis towards 2030:

From global expectations to local realities

Professor J. Russell Stothard, Liverpool School of Tropical Medicine

…varied portfolio of teaching

major funders include: B&MGF, WT, DFID (Department for International Development, UK)

DirectorProf Janet Hemingwaywww.lstmed.ac.uk

Four research departmentsClinical SciencesInternational Public HealthParasitologyVector Biology

LSTM oldest school of tropical medicine – a research-led institution

Contents

• Control of schistosomiasis: past, present and future

• Scale-up of preventive chemotherapy in sub-Saharan Africa

Research priorities

female genital schistosomiasis

expanded access to treatment

Zoonotic potential

hybrids

chimpanzees

S. haematobium(urogenital)

S. mansoni(intestinal)

What do they know of helminths, who only England know?

A hundred years since the African lifecycle was elucidated

Major discoveries on Guinea worm, loiasis & schistosomiasis

FBTs?

In Egypt (1915), still relevant to the WASH agenda today

Parasitology

Infectious Diseases of Poverty

In Egypt (1915), still relevant to the WASH agenda today

• S. haematobium group

S. haematobium PLUS 7 others

e.g. S. intercalatum

~ 37 Bulinus

• S. mansoni group

S. mansoni PLUS

S. rodhaini

~12 Biomphalaria

Schistosomiasis needs multidisciplinary approaches and thinking

Contents

• Control of schistosomiasis: past, present and future

• Scale-up of preventive chemotherapy in sub-Saharan Africa

Research priorities

female genital schistosomiasis

expanded access to treatment

Zoonotic potential

hybrids

chimpanzees

S. haematobium(urogenital)

S. mansoni(intestinal)

A 2030 agenda: The sustainable development goals (SDGs)

… … … … … …

Goal 3:Ensure healthy lives & promote well-being for all at all ages

A focus on schistosomiasis in Africa

1) Population based chemotherapy

2) WASH adopted to local customs & acceptability

3) Health education particularly in 5-15 year olds

The late Dr Andrew Davis (1988) on the “integrated” approach

https://score.uga.edu/

ZEST - Zanzibar Elimination of Schistosomiasis Transmission

Key ingredients for control of schistosomiasis -> 2020 targets

Preventive chemotherapy 2020 targets – 75% treatment coverage

Preventive chemotherapy becomes the front-line tool

Preventive chemotherapy 2020 targets - Uganda

Difficulties in geographical targeting – Uganda (+ 6M ‘newly’ at-risk)

Preventive chemotherapy becomes the front-line tool

• Setting broader needs for PZQ

- expanded coverage to all DGs

- lower prevalence thresholds

- shorter treatment cycles

Lancet Infectious Diseases

Setting NTDs within the SDGs are vital (i.e. cause and effect)

Contents

• Control of schistosomiasis: past, present and future

• Scale-up of preventive chemotherapy in sub-Saharan Africa

Research priorities

female genital schistosomiasis

expanded access to treatment

Zoonotic potential

hybrids

chimpanzees

S. haematobium(urogenital)

S. mansoni(intestinal)

What we used to know about S. haematobium transmission

Introduction of new molecular epidemiological methods

• Zoonotic transmission

• New questions in West Africa

Complex transmission biology in Senegal…and Corsica!

• Seasonal foci Cavu River

• Tourism

Contents

• Control of schistosomiasis: past, present and future

• Scale-up of preventive chemotherapy in sub-Saharan Africa

Research priorities

female genital schistosomiasis

expanded access to treatment

Zoonotic potential

hybrids

chimpanzees

S. haematobium(urogenital)

S. mansoni(intestinal)

Medical malacology is still relevant and important

• four expeditions undertaken B. choanomphala & sudanica

• attention to the islands and their snail biodiversity

• infected Biomphalaria found on Ngamba in 2008!

• could the chimps be at risk?

Snail collecting around the island perimeter

• chimps make excellent snail collectors…

• still even they are confused by snail taxonomy…

?

Snail collecting around the island perimeter

Variety of diagnostics & DNA barcoding of parasites

Ultrasound morbidity survey for fibrosis (annual health checks)

Contents

• Control of schistosomiasis: past, present and future

• Scale-up of preventive chemotherapy in sub-Saharan Africa

Research priorities

female genital schistosomiasis

expanded access to treatment

Zoonotic potential

hybrids

chimpanzees

S. haematobium(urogenital)

S. mansoni(intestinal)

Connecting HIV/HPV/infertility (www.fgsworkshop.org)

(FGS)

Systematic review: FGS widespread but under-reported

WHO encourage greater surveillance (symptoms to colposcopy)

Female genital schistosomiasis (FGS) in

Ogun State, Nigeria: A pilot

parasitological and epidemiological

survey augmented with clinical

colposcopy.

Epko et al. (submitted)

Parasitology Open

20 women underwent colposcopy

14 (70%) had clinical FGS

Some ‘new’ information in Nigeria

Contents

• Control of schistosomiasis: past, present and future

• Scale-up of preventive chemotherapy in sub-Saharan Africa

Research priorities

female genital schistosomiasis

expanded access to treatment

Zoonotic potential

hybrids

chimpanzees

S. haematobium(urogenital)

S. mansoni(intestinal)

Desirable featuresActive against all schistosome species(and also other worms e.g. cestodes)

Excellent safety record, generic production

Patented by Bayer as broad spectrum anti-fluke medication (in the search for tranquilisers)

Racemate of R- and S-enantiomers

Cmax 1-2 hours, quickly metabolised

Licensed for use at 40 or 60 mg/kg in > 4 yo

LimitationsInactive against immature worms & re-infection

Cumbersome, unpalatable tablets

Global shortage of its availability

Shinn Poong (Merck-KGaA)

Key facts on PZQ and perforamce

ONLY SAC ARE CURENTLY TARGETTED

PZQ treatment gap

neonate infant pre-schooler schooler school-leaver worker

childhood adolescence adulthood

< 1 month < 12 month < 6 years < 16 -18 years

infancy

PZQ treatments........clinical significance?

morbidity prevention

infection........clinical significance......disease

disease evolution

Pre-2003

infection.....clinical significance......disease

disease evolution

Post-2003

When should first treatment start?

• SIMI schistosomiasis in mothers & infants

• 4-year project (Wellcome Trust)

• Uganda (Narcis Kabatereine)

• Epidemiology of infections

• Treatment with PZQ/ALB/ACT

• Environmental factors (snails)

• DNA barcoding parasites

April 2013 – Trends in Parasitology

Expanding access to PZQ

Recommendations

A) Preschool-age children can be at high risk of schistosomiasis and PZQ treatment should be made available to them.

B) PZQ can be administered during children health days/EPI.

C) Crushed or broken tablets can be used until a suitable child-friendly paediatric formulation is developed/available.

WHO acknowledge the problem…

Poor schistosomiasis cure rates in children in Lake Albert, Uganda

40 mg/kg

n=30

60 mg/kg

n=30

Follow up at 24 days for parasitological cure

Pharmacokinetic analysis by LCMS at LSTM

Sousa-Figueiredo et al. (2012). Performance and safety of praziquantel for treatment of intestinal schistosomiasis in infants and preschool children. PLoS Negl Trop Dis 6

Uganda November 2012 - first PK-PD study in children

7 time point blood draws24 hour collection

0.6

0.7

0.8

0.9

1.0

Dose (mg/kg)

Ind

ivid

ua

l C

ure

Ra

te

40 60 80

Young children with S. m. require raised dosing (> 40 mg / kg)

Poor therapeutic zone

acceptable therapeutic zone

Conclusions and outlook

Preventive chemotherapy needs scale-up and expansion (missed targets)

Attention needed to revise morbidity- versus transmission- control objectives

Better integration of disease surveillance in the health system (FGS)

Ensure medical malacology and OneHealth studies are not forgotten

In 2015, I took on a significant new role on a network grant entitled “COUNTDOWN”

occupied about 4-months of writing and co-ordination

So what is COUNTDOWN?

COUNTDOWN

A 5-year (2014-2019) programme of implementation research

Innovative and multidisciplinary methods and approaches

Leading NTD researchers and policy makers in implementation research

Specialists in communications with research uptake and capacity development themes

Focus on preventive chemotherapy for Lymphatic Filariasis, Onchocerciasis, Schistosomiasis, Soil-Transmitted Helminthiasis, Trachoma

Focus on health system strengthening

COUNTDOWN Team

Key Questions

Q1) What are effective, cost-effective, sustainable and acceptable current and complementary strategies for scale-up?

Q2) What generalizable factors influence the acceptance, effectiveness, efficiency, and equity impact of scale-up within the health system?

Q3) What are the most effective strategies to work with communities to extend scale-up of MDA to include hard-to-reach communities?

Q4) How can integrating NTD programmes strengthen health systems and foster cross-sectorworking (e.g. sanitation and agriculture)?

Themes and Cross-Cutting StrategiesMass Scale-Up Theme 1: Evidence SynthesisPaul Garner, Cochrane Group

Mass Scale-Up Theme 2: Applied Social ScienceSally Theobald, Margaret Gyapong

Mass Scale-Up Theme 3: Health EconomicsLouis Niessen

Integrated Control Strategy Theme 1: Macrofilaricides & Vector ControlMark Taylor, Lisa Reimer, Joe Turner, Nana-Kwadwo Biritwum, Mike Osei-Atweneboana, Samuel Wanji

Integrated Control Strategy 2: Schisto/STH & Diagnostics Russ Stothard, Emily Adams, Louis-Albert Tchuem-Tchuenté, Mike Osei-Atweneboana

Capacity StrengtheningImelda Bates

COUNTDOWN Logframe

COUNTDOWN generates research evidence to respond to priority information needs of NTD policy makers and program managers

COUNTDOWN supports incorporation of evidence to improve policies and operational plans and practices for scale-up of NTD control

COUNTDOWN strengthens capacity for evidence-based decision making and planning through learning by doing amongst its staff, associated partners and country based research communities

Communications - Vital for building a strong network

www.countdownonntds.wordpress.comwww.countdownonntds.org

@NTDCOUNTDOWN

Forthcoming Annual Partners’ Meeting

Tuesday 28th to Thursday 30th March 2017Mont Febe Hotel, Yaounde, Cameroon

Themes and Cross-Cutting StrategiesMass Scale-Up Theme 1: Evidence SynthesisPaul Garner, Cochrane Group

Mass Scale-Up Theme 2: Applied Social ScienceSally Theobald, Margaret Gyapong

Mass Scale-Up Theme 3: Health EconomicsLouis Niessen

Integrated Control Strategy Theme 1: Macrofilaricides & Vector ControlMark Taylor, Lisa Reimer, Joe Turner, Nana-Kwadwo Biritwum, Mike Osei-Atweneboana, Samuel Wanji

Integrated Control Strategy 2: Schisto/STH & Diagnostics Russ Stothard, Emily Adams, Louis-Albert Tchuem-Tchuenté, Mike Osei-Atweneboana

Capacity StrengtheningImelda Bates

ICST2 Ghana and Cameroon:STH and schistosomiasis work in COUNTDOWN

Prof Russell Stothard, Dr Emily AdamsDr Suzy Campbell, Lucas Cunningham

Alternative mass drug administration (MDA) strategies

WHO goal: Soil-transmitted helminth (STH) & SCH elimination as public health problem [in Africa] by 2020; thinking beyond 2020:

• Interruption of transmission?• Elimination?

Expanding deworming treatments to non-school groups

Increasing frequency of deworming treatments to school-aged children

Schistosomiasis and STH research in Ghana and Cameroon

Field studies in endemic regions

Aims: (i) to better determine disease burden in

non-school cohorts

(ii) to assess the feasibility of increased frequency

and expanded access to deworming drugs against

schistosomiasis and STH

Implementation research: Integrated approach:

combining epidemiology, parasitology, social science and health economics

Integrated approach

Current care: annual school-based MDA (school-aged children)

A. Biannual treatment for school-aged children: second-round MDA provided by teachers in schools

B. Expanded access to treatment for PSAC, out-of-school children, adults incl. pregnant women: annual MDA provided by field staff

Both studies: (i) sites selected according to historical schistosomiasis prevalence; (ii) individuals randomly selected for testing; followed over time

Parasitological surveys, epidemiological questionnaires• Prevalence & intensity at baseline & reductions assessed over time; situational & risk factor analyses (incl. WASH, morbidity, demography)

Social science qualitative interviews• Acceptability and feasibility of changing MDA

Health economics questionnaires• Cost-benefit & cost-effectiveness analyses; factors hindering access and adherence to MDA

Research pivotal in assessing impact, feasibility, & accessibility of alternative MDA in these countries

Manuscripts

Urogenital schistosomiasis and soil-transmitted helminthiasis (STH) in Cameroon:

An epidemiological update at Barombi Mbo and Barombi Kotto crater lakes

assessing prospects for intensified control interventions

Suzy J. Campbell1, J. Russell Stothard1*, Faye O’Halloran1, Deborah Sankey1, Timothy Durant1,

Dieudonné Eloundou Ombede2, Gwladys Djomkam Chuinteu2, Bonnie L. Webster3, Lucas

Cunningham1, James La Course1, Louis-Albert Tchuem-Tchuenté2,4,5

Aims: To assess the suitability of the Global Polio Laboratory Network’s faecal collections to determine prevalence of STH and SCH

Rational: GPLN collect stool from 19 African countries resulting in thousands of samples collected and screened each year.

Success of the polio control programme raises the question of what to do with the legacy of the infrastructure used.

Integrated complementary strategies for surveillance of NTDs in Ghana

Capacity building

Resources

• Well equipped laboratories (GPLN and CSIR)

• Large collection of faecal samples (GPLN)

• Well trained laboratory and field technicians (GPLN and CSIR)

qPCR Workshop was carried out in March 2016:

Theory classes:primer and probe design

Practical classes: qPCR and DNA extraction

Multiplex qPCR assay

Trichuris trichiuraJie Liu, et al. 2013

Ascaris lumbricoidesAprilianto E Wiria, et al. 2010

Necator americanusJaco J. Verweij, et al. 2007

Ancylostoma duodenaleJaco J. Verweij, et al. 2007

Schistosoma spp.B. B. Obeng, et al. 2008

Strongyloides stercoralisJaco J. Verweij, et al. 2009

Work at Noguchi

DNA extractions were carried out on 438 faecal samples

The results for the six helminth types are as follows:

Helminths

Ascaris lumbricoides Necator americanus Ancylostoma duodenale Trichuris trichiura Schistosoma spp Strongyloides stercoralis

Total 36 36 16 0 16 14

% 8 8 4 0 4 3*

Future work

• Prospective screening of new samples at the GPLN

• Implementation of the multiplex qPCR system at CSIR

• Introduction and assessment of novel diagnostics

(CCA, multiplex melt-curve qPCR)

Final tip on a career in global health

simply learn to collaborate, to support others as they support you