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Schistosomiasis towards 2030: From Global Expectations to local realities

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This presentation was given by Prof. Russell Stothard, in his capacity as COUNTDOWN Director to the Global Center for Infectious Diseases (GCID) Symposium in Korea and to the Korean Society for Parasitology in mid-Feb. 2017

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Schistosomiasis towards 2030: From Global Expectations to local realities

  1. 1. A COUNTDOWN on schistosomiasis towards 2030: From global expectations to local realities Professor J. Russell Stothard, Liverpool School of Tropical Medicine
  2. 2. …varied portfolio of teaching major funders include: B&MGF, WT, DFID (Department for International Development, UK) Director Prof Janet Hemingway www.lstmed.ac.uk Four research departments Clinical Sciences International Public Health Parasitology Vector Biology LSTM oldest school of tropical medicine – a research-led institution
  3. 3. 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)
  4. 4. 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?
  5. 5. In Egypt (1915), still relevant to the WASH agenda today Parasitology Infectious Diseases of Poverty
  6. 6. 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
  7. 7. Schistosomiasis needs multidisciplinary approaches and thinking
  8. 8. 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)
  9. 9. 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
  10. 10. 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
  11. 11. Preventive chemotherapy 2020 targets – 75% treatment coverage
  12. 12. Preventive chemotherapy becomes the front-line tool
  13. 13. Preventive chemotherapy 2020 targets - Uganda
  14. 14. Difficulties in geographical targeting – Uganda (+ 6M ‘newly’ at-risk)
  15. 15. 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
  16. 16. Setting NTDs within the SDGs are vital (i.e. cause and effect)
  17. 17. 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)
  18. 18. What we used to know about S. haematobium transmission
  19. 19. Introduction of new molecular epidemiological methods • Zoonotic transmission • New questions in West Africa
  20. 20. Complex transmission biology in Senegal…and Corsica! • Seasonal foci Cavu River • Tourism
  21. 21. 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)
  22. 22. 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?
  23. 23. Snail collecting around the island perimeter
  24. 24. • chimps make excellent snail collectors… • still even they are confused by snail taxonomy… ? Snail collecting around the island perimeter
  25. 25. Variety of diagnostics & DNA barcoding of parasites
  26. 26. Ultrasound morbidity survey for fibrosis (annual health checks)
  27. 27. 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)
  28. 28. Connecting HIV/HPV/infertility (www.fgsworkshop.org) (FGS)
  29. 29. Systematic review: FGS widespread but under-reported
  30. 30. WHO encourage greater surveillance (symptoms to colposcopy)
  31. 31. 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
  32. 32. 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)
  33. 33. Desirable features Active 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 Limitations Inactive 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
  34. 34. 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?
  35. 35. • 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
  36. 36. 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…
  37. 37. 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 draws 24 hour collection
  38. 38. 0.60.70.80.91.0 Dose (mg/kg) IndividualCureRate 40 60 80 Young children with S. m. require raised dosing (> 40 mg / kg) Poor therapeutic zone acceptable therapeutic zone
  39. 39. 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
  40. 40. 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?
  41. 41. 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
  42. 42. COUNTDOWN Team
  43. 43. 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-sector working (e.g. sanitation and agriculture)?
  44. 44. Themes and Cross-Cutting Strategies Mass Scale-Up Theme 1: Evidence Synthesis Paul Garner, Cochrane Group Mass Scale-Up Theme 2: Applied Social Science Sally Theobald, Margaret Gyapong Mass Scale-Up Theme 3: Health Economics Louis Niessen Integrated Control Strategy Theme 1: Macrofilaricides & Vector Control Mark 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 Strengthening Imelda Bates
  45. 45. 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
  46. 46. Communications - Vital for building a strong network www.countdownonntds.wordpress.com www.countdownonntds.org @NTDCOUNTDOWN
  47. 47. Forthcoming Annual Partners’ Meeting Tuesday 28th to Thursday 30th March 2017 Mont Febe Hotel, Yaounde, Cameroon
  48. 48. Themes and Cross-Cutting Strategies Mass Scale-Up Theme 1: Evidence Synthesis Paul Garner, Cochrane Group Mass Scale-Up Theme 2: Applied Social Science Sally Theobald, Margaret Gyapong Mass Scale-Up Theme 3: Health Economics Louis Niessen Integrated Control Strategy Theme 1: Macrofilaricides & Vector Control Mark 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 Strengthening Imelda Bates
  49. 49. ICST2 Ghana and Cameroon: STH and schistosomiasis work in COUNTDOWN Prof Russell Stothard, Dr Emily Adams Dr Suzy Campbell, Lucas Cunningham
  50. 50. 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
  51. 51. 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
  52. 52. 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
  53. 53. 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
  54. 54. 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
  55. 55. 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
  56. 56. Multiplex qPCR assay Trichuris trichiura Jie Liu, et al. 2013 Ascaris lumbricoides Aprilianto E Wiria, et al. 2010 Necator americanus Jaco J. Verweij, et al. 2007 Ancylostoma duodenale Jaco J. Verweij, et al. 2007 Schistosoma spp. B. B. Obeng, et al. 2008 Strongyloides stercoralis Jaco J. Verweij, et al. 2009
  57. 57. 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*
  58. 58. 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)
  59. 59. Final tip on a career in global health simply learn to collaborate, to support others as they support you

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