Rudolf Geigy Award 2016 A research partnership on neglected

tropical diseases in Côte d’Ivoire

Giovanna Raso Jean Tenan Coulibaly

Basel, 9th December 2016

Overview

• Schistosomes and soil-transmitted helminths (STH)

− Recent epidemiological studies in Côte d’Ivoire

• Tools for the control and elimination of STH and schistosomiasis

− Praziquantel for pre-schoolers

− New diagnostic tools for schistosomiasis

− Health educational and community-led total sanitation

− Integrated interventions

• Conclusion and words of thanks

STHs and schistosomiasis

• Belong to the so-called neglected tropical diseases poverty-promoting, chronic, low- and middle-income countries

• STH most common infections worldwide (1/4 of the world population, 3.3 Mio DALYs); species infecting people are roundworm, whipworm and hookworms

• 240 million people infected by schistosomes (5 species infect humans), 700 Mio people live at-risk, 2.6 Mio DALYs

STHs and schistosomiasis in Côte d’Ivoire

• STHs and schistosomiasis a public health problem

• SNSF project: Effect of the co-distribution of intestinal helminths and Plasmodium on clinical outcomes & quality of life

• Cross-sectional school- and community-based parasitological, clinical and questionnaire surveys

• PhD students: Eveline Hürlimann, Richard Yapi, Clarisse Houngbedji, Prisca N’Dri, Frederique Chammartin

STHs and schistosomiasis in Côte d’Ivoire

• 2011/2012: First national survey on parasitic diseases (intestinal helminths and Plasmodium) among schoolchildren

• Over 5,000 schoolchildren from 93 schools screened

Infection Prevalence (%) Plasmodium 63 Helminths 26.2 Hookworm 17.2 Ascaris lumbricoides 1.9 Trichuris trichiura 1.2 Schistosoma mansoni 3.7 S. haematobium 5.7

Risk mapping and treatment needs for STHs

~1.3 million doses of albendazole or mebendazole needed (Yapi et al. 2016)

Risk mapping and treatment needs for schistosomiasis

~2 million annualized treatments (Chammartin et al 2015)

Control of schistosomiasis and STH

• Preventive chemotherapy cornerstone of control

• Other interventions, i.e. improvement of access to clean water, sanitation and hygiene (WASH) and health education, in addition to mollusciciding in the case of schistosomiasis reduce transmission

Drawing by Megan Petrucci, www. workforce.calu.edu

Sanitation

Mollusciciding

Health education

Treatment

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Schistosomiasis in preschoolers

Key messages

● Schistosomiasis is governed by social–ecological contexts, linked with poverty and lack of essential social services and infrastructure (clean water, improved sanitation, hygiene, and health systems)

● High risk of population living in close proximity to small rivers and standing freshwater bodies on which people depend for their daily occupational and recreational activities

● Infections occurs very early in childhood hence young children need to be treated

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Key messages Ultrasound at baseline: ● PSAC: 43% had urinary tract morbidity, 7% kidney enlargement.

● SAC: 66% presented urinary tract pathology, 4% pseudopolyps on the bladder wall, 6% had pyelo dilatation.

Ultrasound at follow up (6 months post-treatment): ● Significant correlation (p<0.05) was observed between praziquantel treatment and reversal of S. haematobium induced morbidity

● Progression of urinary tract pathology decreased with increasing praziquantel dosages

● A worsening of morbidity was observed among children in the placebo group

Schistosomiasis in preschoolers

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Praziquantel in preschoolers

Key messages ● Crushed praziquantel is efficacious against both schistosome species in preschool-aged children ● Unwanted adverse events in non-infected children following praziquantel administration, call for selective treatment among preschoolers ● New research is needed to accurately determine the frequency and severity of adverse events related to praziquantel in preschoolers ● There is a need to develop a safe and user-friendly formulation of praziquantel for the very young children and evaluate the correct dose

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PZQ for preschoolers: DF studies Key messages ● Diagnostic limitations of Kato-Katz, high CR and ERR in the placebo group

● Significantly lower cure rates with POC CCA

● No difference in mild adverse events seen among treatment arms (Diarrhea, cough, fever mostly observed) ● All adverse events absorbed after 24 hoours ● Our study supports the use of praziquantel at 40 mg/kg for schistosomiasis morbidity control in SAC ● emax modelling suggest that PSAC require a higher dose of praziquantel.

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Need of new diagnostic tools

● Epidemiology: targeting intervention ● Diagnosis: who should be treated? ● Treatment outcome: does intervention work (programme M&E vs clinical research setting)

Need of new diagnostic tools as alternative to the commonly used Kato-Katz technique in a context of schistosomiasis elimination

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Need of new diagnostic tools Kato-Katz technique Advantages ● Specific, quantitative ● Available ● Affordable Disadvantages ● Variable sensitivity ● Multiple samples needed ● Labour-intensive ● Trained technicians ● Fluctuation in egg excretion

VS

CAA/CCA test ● detection of schistosome gut antigen CAA/CCA excretory antigens, living worms ● CAA/CCA are very stable ● present in serum and urine, limited day-to-day variation ● markers of active infection – decrease after treatment ● levels correlate with worm and egg counts

CCA in worm gut CAA excreted by worm in liver vein

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Key messages POC-CCA ● The POC-CCA can become a useful test for S. mansoni diagnosis ● Still need to be evaluated in low S. mansoni-infected communities POC-CCA recommended by WHO for rapid mapping of schistosomiasis UCP-CAA ● seems to be a tool to detect single worm infections => Need assessment in different endemicity settings

Need of new diagnostic tools

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Need of new diagnostic tools

VS 11 operating steps with FLOTAC techniques

7 operating steps of mF techniques mini-FLOTAC Devices

Gringoli et al., 2010

mini-FLOTAC (mF) technique: from 11 to 7 operating steps

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Need of new diagnostic tools

Key messages ● Mini-FLOTAC, a useful tool for an accurate diagnosis of major helminth infections and intestinal protozoa ● Can be employed on fixed stool samples, which may reduce logistical and financial barriers to epidemiological surveys ● Comparable accuracy to the more labour-intensive Kato-Katz technique ● Performance of mini-FLOTAC technique on SAF-fixed stool samples with and without a centrifugation step in comparison to the Kato-Katz method needs further scientific inquiry ● Costs and cost-effectiveness studies to assess the usefulness of Mini-FLOTAC on preserved stool samples for public health initiatives and helminthiases control programmes are warranted

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Need of new diagnostic tools

Key messages ● Portable diagnostic devices hold promise for enabling care in remote and resource constrained settings ●The Newton portable microscope demonstrated sufficient diagnostic performance for S. mansoni, S. haematobium and T. trichiura vs standard light microscopy should be studied further in different clinical and epidemiological settings ● The mobile phone (iphone 5S) microscope performed only modestly well at moderate-to-high infection intensities for S. mansoni and T. trichiura ● Newer, low-cost technologies are in the pipeline for global health applications

Life cycle of STH WASH

Health education

Treatment Albendazole and

Mebendazole

Integrated control

• “An integrated approach to control worm infections and diarrhoea”

– Aim 1: Develop new health educational tools and

– Aim II: study the effect of combined interventions (preventive chemotherapy, health education, community-led total sanitation)

• Partners: CSRS, Swiss TPH, UFHB, UNICEF, Fairmed, MoS, MoH. Financial support from UBS Optimus Foundation

• PhD students: Veronique Koffi, Virginie Mahan, Gaoussou Coulibaly

Health education tools

Develop an animated cartoon about

• Safe drinking water

• Use of latrines

• Hand washing

WASH

Bieri et al., 2013

School-based intervention study

Results of the intervention study • Improved knowledge, but no effect on helminthic infections

(Palmeirim M, 2016)

Palmeirim M, 2016

Spontaneous answers to the question: How can we get infected?

Control (# children)

Intervention (# children)

If we do not cover our food (flies will land on it). 5 20

If we do not wash our hands after defecating. 0 11

If we defecate in the bush/river (open defecation). 1 12

Community-led total sanitation (CLTS)

• Participatory approach to achieve and sustain open defecation free (ODF) status of communities (Chambers & Kar, 2008)

• Facilitates the critical analysis by the community of own sanitation-profile, defecation practices and consequences, collective action to become ODF (e.g. construction of latrines)

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CLTS and NTDs (pilot study)

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Infection Group Baseline (%)

Follow-up (%)

Hookworm Control 25.2 7.0

Intervention 36.5 10.6

Int. protozoa Control 73.0 70.4

Intervention 72.0 63.8

PC PC + CLTS PC + HE PC + CLTS + HE

• Cluster randomized trial, 4 intervention arms, 56 communities

• Preliminary results health education improves KAPB and adhesion to latrine construction

• Assessment on parasitological indicators ongoing

Map: Hürlimann E, 2016

29 PARTNERSHIP

NORTH SOUTH

WELL-BEING

Abel Kouamé, Aboulaye Meité, Ahoua Yapi Akré Adja Alan Fenwick Amaya Bustinduy Amelie Dubé, André Barbe, Bassirou Bonfoh, Beatrice Barda Bernadette Akissi Kouadio, Bill & Melinda Gate, Brian Blackburn Carl Campell, Charles H. King Christine Walliser, Cinthia Acka, Clarisse Houngbedji, Clémence Essé, Coulibali Gaoussou, Daniel Colley Dao Daouda, Darin Evans David Addiss David Molyneux Dieter Imhof,

Ed Kuijper Eliézer N’Goran, Emily Dawson Eran Bendavid ERC Eveline Hürlimann, Fabien Zouzou, François Chappuis Frederique Chammartin, Gordana Panic Govert van Dam Guéladio Cissé, Howard Abrams Inza Koné, Isaac Bogoch Ivan Müller Jakob Zinstag, Jan Hattendorf Jana Kovac Jason R. Andrews Jennifer Keiser, Joel A. Yao Jörg Huwyler José Carlos Sousa-Figueiredo Jürg Utzinger,

Justin Chatigre Katarina Stete, Katja Polman Kigbafori Silué, Kouassi Dongo, Lisette van Lieshout Lorenzo Savioli Lutz von Müller Mamadou Ouattara, Marcel Tanner, Margrit Slaoui, Marguerite Guehi, Maria-Gloria Basáñez Marta Palmeirim, Martin Walker Mathias Herrmann Maxim Puchkov Michael J Doenhoff Mirko Nana Diakité Nathan Lo Négnorogo Guindo Nicaise N’Guessan Nicole Probst-Hensch, Pascal Mertens Patrick Yao

Peiling Yap Penelope Vounatsou, Peter Hotez Peter Steinmann Piero L. Olliaro Prisca Bedjou Richard Yapi, Rudolf Geigy, Rufin K. Assaré Russell Stothard Score Sören Becker Stefanie Krauth Steffi Knopp, Swiss National Science Foundation, Thomas Fürst, Thomas Gass, Thomas Schmidlin, UBS Optimus Foundation, Véronique Koffi, Virginie Mahan, Wendelin Moser William Lin Yves-Nathan Tian-Bi AND MANY MORE!!!

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MANY MANY THANKS!!!