FINDs programme on diagnostics for NTDs

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1 FINDs programme on diagnostics for NTDs JM Ndung u, A. Picado, I Cruz & S Biéler Presentation at IRD, Montpellier, France, 12March 2018

FIND who we are & what we do A not-for-profit international organization that works

poverty Leverage investments by donors against product affordability and

the price of tests; open access to IP and knowledge) Building capacity in countries

2 FIND who we are & what we do A not-for-profit international organization that works in partnerships to develop diagnostic solutions for diseases associated with poverty Leverage investments by donors against product affordability and royalty-free access (de-linking costs of R&D and manufacturing infrastructure, from the price of tests; open access to IP and knowledge) Building capacity in countries (strengthening laboratory systems and R&D), thus ensuring new technologies are accessible to everyone

3 FIND disease programmes NTDs Tuberculosis Malaria Hepatitis C & HIV -Human African trypanosomiasis -Leishmaniasis -Buruli ulcer -Chagas disease -Schistosomiasis Cross-cutting programmes AMR / Emerging threats Fever Access Connectivity

4 NTDs:15 of 20 WHO-listed, and 7 of the 10 in the London Declaration, lack diagnostic solutions 1 Buruli ulcer Mycetoma, chromoblastomycosis and 11 other deep mycoses 2 Chagas disease 12 Onchocerciasis 3 Dengue and Chikungunya 13 Rabies 4 Dracunculiasis 14 Scabies and other ectoparasites 5 Echinococcosis 15 Schistosomiasis 6 Foodborne trematodiases 16 Soil-transmitted helminthiases 7 Human African trypanosomiasis 17 Snakebite envenoming 8 Leishmaniasis 18 Taeniasis/Cysticercosis 9 Leprosy 19 Trachoma 10 Lymphatic filariasis 20 Yaws NTDs with major unmet needs NTDs with unmet needs Diseases in FIND s NTD portfolio Diseases identified in the London Declaration for eradication, elimination or control by 2020

5 NTDs and priority areas Disease Priority Activities Human African trypanosomiasis Leishmaniasis Chagas Disease Buruli Ulcer Screening test Elimination of gambiense HAT Point of Care Test for VL in eastern Africa Test of cure (TOC) for VL Improving access to VL diagnostics Test for congenital Chagas in newborns Point of care test Confirmatory test at district/microscopy level Schistosomiasis Highly sensitive RDT To be defined Roll out of 1 st & 2 nd gen RDTs & impact assessment Development of HAT/Malaria combo test Integration of screening, diagnosis, treatment and vector control Development of molecular test based on LAMP Use of an ELISA test for urinary antigens Development of RDT for parasite antigens in urine Access to diagnostics and treatment for VL in eastern Africa Development of molecular test based on LAMP (on hold pending funding availability) Development of an RDT for bacterial antigens & mycolactones Development of a molecular test based on LAMP

6 Human African trypanosomiasis (HAT) Humans sleeping sickness 61 million people at risk in 36 countries 2,184 new cases reported in 2016 Usually fatal if not treated Transmission: bite of a tsetse fly Livestock Nagana Losses to agriculture: $4.2b/yr Wildlife: reservoir Parasite: trypanosome Trypanosoma brucei gambiense Trypanosoma brucei rhodesiense

7 Diagnosis of human African trypanosomiasis until 2013 (Trypanosoma brucei gambiense) Screening Confirmation Staging Symptoms Microscopy Lumbar puncture Antibody detection test: CATT CTC maect Suspect Case Choice of treatment

8 HAT: Diagnostics developed through FIND partnerships Fluorescence microscope Primo Star iled (Carl Zeiss, Germany) 1 st generation HAT RDT (native antigens) SD BIOLINE HAT (Standard Diagnostics (SD), South Korea) RDT for HAT and malaria SD BIOLINE HAT/Malaria Duo (Abbott/SD, South Korea) Advantages Isothermal Rapid (40 ) Closed system Visible readout Molecular test LAMP Loop-mediated isothermal amplification of DNA (Eiken Chemical, Japan) 2 nd generation HAT RDT (recombinant antigens) SD BIOLINE HAT 2.0 (Abbott/SD, South Korea)

Novel strategy for intensified screening for

can screen for ghat Symptoms suggestive of HAT

health facility + - Non-case RDT + - Non-case

Parasitology facility Parasitology (GP, AO-FM,

written results slip + - LAMP Dried blood spot

9 Novel strategy for intensified screening for ghat All health facilities in an endemic area can screen for ghat Symptoms suggestive of HAT & persistent fever after malaria treatment RDT health facility + - Non-case RDT + - Non-case (in absence of strong suspicion of HAT) Parasitology facility Parasitology (GP, AO-FM, CTC, maect) Case Results sent back by SMS or written results slip + - LAMP Dried blood spot taken to LAMP centre LAMP facility Strong suspect + - Non-case

FIND-supported HAT diagnostics implementation projects Chad 110 RDT 4 Microscopy 2 LAMP Guinea 95 RDT 2 Microscopy 2 LAMP Côte d Ivoire 17 RDT Connectivity Quality assurance Community mobilization

10 FIND-supported HAT diagnostics implementation projects Chad 110 RDT 4 Microscopy 2 LAMP Guinea 95 RDT 2 Microscopy 2 LAMP Côte d Ivoire 17 RDT Connectivity Quality assurance Community mobilization Nigeria 46 RDT 4 Microscopy 1 LAMP Republic of Congo 51 RDT (14 non functional) 2 Microscopy 1 LAMP Angola 127 RDT 16 Microscopy 4 LAMP South Sudan 138 RDT 5 Microscopy 3 LAMP Uganda 162 RDT 9 Microscopy 3 LAMP Democratic Rep of Congo 574 RDT 18 Microscopy 5 LAMP Malawi 5 Microscopy 1 LAMP Active project Project ended

11 Integrating screening for ghat and control of tsetse fly vectors Working together to eliminate sleeping sickness Chad Côte d Ivoire Guinea Uganda

12 Future plans in HAT diagnostics 1. Combined RDT for diagnosis of malaria and screening for ghat Field evaluation to be conducted in Uganda and in DRC in 2018 Planned to be commercialized by mid Test for post-elimination surveillance Target Product Profile to be developed in Implementation projects in support of WHO elimination goals Continue with current implementation projects Expand to other endemic regions/countries

Leishmaniasis Diagnostic priorities www.who.

different geographies and in HIV+ve patients).

Test of cure/treatment monitoring for VL Strategies to improve access to (early)

13 Leishmaniasis Diagnostic priorities Improved RDT for VL diagnosis (strong performance across different geographies and in HIV+ve patients). Rapid POC test for dermal leishmaniasis (CL, ML, PKDL). Test of cure/treatment monitoring for VL Strategies to improve access to (early) diagnosis and case management. sand fly borne, zoonotic & anthroponotic transmission With the success of the VL elimination programme in the ISC, increasing attention is been given to eastern Africa

RDTs/ELISA (VL, PKDL, Asymptomatic, CL) Strategies to improving access to VL diagnosis Kenya Sudan Bangladesh

14 Leishmaniasis what FIND has been doing COMMUNITY HEALTH WORKER HEALTH POST MICROSCOPY CENTER DISTRICT HOSPITAL REFERENCE CENTRE Molecular diagnosis (VL, PKDL, Asymptomatic, CL, CanL) Ab and Ag detection RDTs/ELISA (VL, PKDL, Asymptomatic, CL) Strategies to improving access to VL diagnosis Kenya Sudan Bangladesh Afghanistan Suriname Spain KEMRI Turkana MOH Wajir MOH DNDi WHO IEND ICDDR,B LSTM NMLCP HealthNetTPO AMC MOH AdKU WHOCCL ISCIII

Leishmaniasis: Progress in development of Dx solutions Loopamp TM

, Japan) Site Disease form Se/Sp (%) Sudan VL 97.6 / 99.

0 Ongoing studies in Kenya and Bangladesh Strategies to improve access

of health facilities Capacity building (RDT, DAT) Training Reporting

MOH VL ELISA for antigen detection (Kalon Biological Ltd.

15 Leishmaniasis: Progress in development of Dx solutions Loopamp TM Leishmania Detection Kit (Eiken chemical Co., Japan) Site Disease form Se/Sp (%) Sudan VL 97.6 / 99.0 Afghanistan CL 92.2 / 94.1 Spain CL and VL 98.6 / 96.0 Ongoing studies in Kenya and Bangladesh Strategies to improve access to (early) diagnosis and case management of VL in Kenya Characterization of health facilities Capacity building (RDT, DAT) Training Reporting Advocacy Turkana Wajir County MOH Govt. MOH VL ELISA for antigen detection (Kalon Biological Ltd., UK) Studies in Kenya, Sudan, Ethiopia and Bangladesh 86% 95% Se, 100% Sp Sharp decrease in Ag levels during treatment follow up Vallur et al., 2015 BMC Infect Dis; Mukhtar et al., 2018 PLOS NTD

16 Future plans in Leishmaniasis diagnostics Large scale evaluation of rk28 vs. rk39 RDT Ethiopia, Kenya, Sudan, Uganda *In collaboration with DNDi and LEAP Expand strategies to improve access to early diagnosis of VL in Kenya Marsabit, Isiolo Counties *In collaboration with country and county govts., Kenyan leishmaniasis task force, WHO, DNDi Development of antigen detection test(s) for VL and dermal leishmaniasis Development of TPPs and exploring partnerships * Access to an assembly of 48 cell lines producing mabs against different Leishmania species

Buruli ulcer www.who.int/buruli/en/ www.theconversation.

is hampered by the lack of specific signs and available tools.

17 Buruli ulcer Diagnostic challenges Early diagnosis of BU at the Primary health care level is hampered by the lack of specific signs and available tools. Four standard diagnostic methods: PCR, Acid-Fast Bacilli (AFB) microscopy, histopathology and culture. o Only AFB microscopy is available at lower levels of the HS, and has low Se/Sp. The exact mode of transmission of M. ulcerans is unknown The highest burden is in Sub-Saharan Africa, where most patients are children aged under 15 years

Buruli ulcer what FIND is doing 2013: FIND and WHO convened a meeting of BU experts to review unmet diagnostic needs FIND

Prototypes are under evaluation in collaboration with IME (DRC) and other partners A dried reagents based LAMP test for

A prototype DRB LAMP test is ready for prospective evaluation in 2018 Mycolactone detection by f TLC for confirmatory

18 Buruli ulcer what FIND is doing 2013: FIND and WHO convened a meeting of BU experts to review unmet diagnostic needs FIND strategy on BU diagnosis An antigen detection test for diagnosis at the primary healthcare level SwissTPH and Abbott/SD. Prototypes are under evaluation in collaboration with IME (DRC) and other partners A dried reagents based LAMP test for confirmatory diagnosis at the microscopy level DITM/KUM, NMIMR. A prototype DRB LAMP test is ready for prospective evaluation in 2018 Mycolactone detection by f TLC for confirmatory diagnosis and treatment monitoring at the district hospital level The WHO is evaluating f TLC in Benin, DRC and Ghana in collaboration with Harvard University, KNUST, Un of Ghana, CDTUB Allada

Progress in development of Dx for Buruli ulcer

Se/Sp compared to qpcr in clinical samples

MUL_3720 surface protein Promising performance

Improving signal amplification Exploring new

19 Progress in development of Dx for Buruli ulcer From an ELISA (Swiss TPH) to an RDT (Abbott/SD) DRB LAMP test targeting M. ulcerans IS2404 (OptiGene chemistry) 100% Se/Sp compared to qpcr in clinical samples from Togo RDT prototypes (Abbott/SD) Targeting MUL_3720 surface protein Promising performance on recombinant protein and cell lysates Improving signal amplification Exploring new sampling and sample preparation methods To improve sensitivity of diagnostic tests

20 Future plans for Buruli ulcer diagnostics Prospective evaluation of DRB BU LAMP Collaborators: DITM/KUM, DAHW, INH Lomé, Togo MUL_3720 & mycolactones as targets for RDT development Collaborators: Swiss TPH and others Strengthening collaboration with WHO *BU experts meeting on diagnostics, March 2018 TPP development, EQA, partnerships for development and evaluation studies

Chagas Disease (American trypanosomiasis) Endemic mainly in of 21

cases of Chagas disease each year Once entirely confined to the

to other continents Infection: Main: contact with feaces of an

Mother-to-baby (congenital) Contaminated blood products Organ

21 Chagas Disease (American trypanosomiasis) Endemic mainly in of 21 Latin American countries Caused by Trypanosoma cruzi new cases of Chagas disease each year Once entirely confined to the Region of the Americas principally Latin America, but has spread to other continents Infection: Main: contact with feaces of an infected triatomine bug (kissing bug), a blood sucking insect Mother-to-baby (congenital) Contaminated blood products Organ transplanted from an infected donor Laboratory accidents Contaminated food or drink (rare)

22 Chagas Disease What FIND has been doing Supporting developed of diagnostic solutions to reduce the burden of Congenital Chagas disease: 15,000 Congenital Chagas disease cases per year in Latin America (WHO, 2012) NEED current diagnostic algorithm is sub-optimal Carried out in stages: -Serological screening of pregnant women -If a woman is positive by serology, the newborn is tested by microscopy -If the newborn is negative, a serological test is performed after 9 months high rates of loss to follow up Molecular tools(e.g. PCR), which have high sensitivity and specificity could be used at birth or at 1 month, but are only applicable at reference laboratories IMPACT OF DIAGNOSIS AT BIRTH Treatment has (almost) 100% success rate Treating infected newborns prevents -progression to chronic disease -Future congenital transmission (in girls)

Chagas Disease: Progress in development of Dx solutions LAMP T.

performed in district hospitals maternities (near the newborn) Result 1: Good

stored clinical samples - Se: 100% (95% CI: 72.5-100%) and Sp : 92.

23 Chagas Disease: Progress in development of Dx solutions LAMP T. cruzi LAMP kit developed with partners Simple and rapid molecular test To be performed in district hospitals maternities (near the newborn) Result 1: Good analytical performance LAMP more sensitive than PCR Result 2: Good Se and Sp in stored clinical samples - Se: 100% (95% CI: %) and Sp : 92.6% (95% CI: 82,4 92.6%) in Argentina - Se: 97,4% (95% CI: 91,2 100%) and Sp: 91,7% (95% CI: 82,8 100%) in Spain Unpublished data

24 Future plans for Chagas Disease diagnostics Test for congenital Chagas disease T. cruzi LAMP is not yet registered RUO test FIND is providing technical support to two clinical trials evaluating T. cruzi LAMP in endemic regions: Argentina: CONICET Bolivia: ISGlobal, CEADES and CONICET Test for early assessment of treatment response Test to improve monitoring of treatment efficacy for chronically infected patients FIND is providing technical support on the development of TPP for this test

25 Funding partners Swiss Development Cooperation German Government DFID Department for International Development In-kind contributions by partners and endemic countries

STRATEGY FOR NEGLECTED TROPICAL DISEASES

STRATEGY FOR NEGLECTED TROPICAL DISEASES 2015-2020 1 ABOUT FIND FIND was established in 2003 to bridge existing development gaps for essential diagnostics by initiating and coordinating research and development