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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