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Emerging & Neglected Parasitic Infections

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Professor Russell Stothard's presentation given to The Royal College of Pathologists on 6th March 2018 during the National Infection Study Day event. Prof Stothard focused on schistosomiasis and urogenital schistosomiasis pathology

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Emerging & Neglected Parasitic Infections

  1. 1. Emerging & Neglected Parasitic Infections A focus on schistosomiasis & genital pathology Russell Stothard Department of Parasitology russell.stothard@lstmed.ac.uk @StothardRuss
  2. 2. Epidemiology & control of malaria infection and disease is typically concurrent with one or more Neglected Tropical Disease
  3. 3. 1. Introduce the global burden of key neglected tropical diseases 2. Highlight issues in control of tropical helminthiases at national levels 3. Draw attention to supportive multi-disciplinary implementation research 4. Focus on schistosomiasis demonstrating its clinical importance in UK & abroad 5. Discuss new methods for diagnosis of schistosomiasis during control 6. Feature the clinical pathology and impact of female genital schistosomiasis 6 learning points for today disease specific – diagnostics & pathology
  4. 4. NTDs can be so grouped IDM Individual disease management PC preventive chemotherapy azithromycin ivermectin/DEC albendazole/mebendazole praziquantel https://www.gatesnotes.com/Health/Neglected-No-More?WT.mc_id=04_18_2017_14_HardtoPronounce_BG-TW_&WT.tsrc=BGTW
  5. 5. And two even more tricky flukes – clonorchiasis & opisthorchiasis Food borne trematodes: infection by consumption of raw fish (i.e. sashimi) A trigger of cholangiocarcinoma (CCA), a ‘late’ health concern for Vietnam veterans https://www.youtube.com/watch?v=KQy5n8G-maM Ongoing national control programme in Thailand
  6. 6. http://www.who.int/neglected_diseases/resources/9789241565448/en/ Some NTDs are travel medicine issues too schistosomiasis (NB Corsica) soil-transmitted helminthiasis
  7. 7. NTDs are strongly associated with poverty-stricken regions within LMIC. Broadly grouped into: PC e.g. helminths IDM e.g. protozoans Control is largely by partnerships typically inspired by the London Declaration in 2012. WHO approved strategies. Highlight of travel medicine aspect in Italy
  8. 8. rTrichuris trichiura COUNTRY Bangladesh Burkina Faso Pakistan Sri Lanka Sénégal Examined Positives % Immigrants 721 31 4,3 positive negative 4.3%
  9. 9. rAncylostoma duodenale Examined Positives % Immigrants 721 25 3,5 COUNTRY Bangladesh Burkina faso Liberia Nigeria Pakistan Sénégal positive negative 3.5%
  10. 10. rAscaris lumbricoides COUNTRY Bangladesh Guinea Nigeria Sénégal Examined Positives % Immigrants 721 8 1,1 positive negative 1.1%
  11. 11. Schistosomiasis is a major water hazard for anyone going to Africa The accumulation of schistosome eggs in the body is BAD – a progressive severity You acquire more worms by repeated water contacts
  12. 12. Schistosomiasis is a major water hazard for anyone going to Africa serological detection is best method for exclusion in travelers in 8163 screened 25% seropositive…a retrospective screen
  13. 13. National control programmes being waged against PC NTDs - some doing better than others, SCH placed RED in 5th NTD score card
  14. 14. COUNTDOWN • Working in Liberia, Ghana, Nigeria & Cameroon • Active research uptake/communications & 5 main research themes
  15. 15. COUNTDOWN PC for SCH & STH is not a complete solution Marginalisation Vulnerability Disability Access & Equity
  16. 16. www.countdownonntds.wordpress.com www.countdownonntds.org @NTDCOUNTDOWN Using twitter to keep informed of on-the-ground activities
  17. 17. 1. Introduce the global burden of key neglected tropical diseases 2. Highlight issues in control of tropical helminthiases at national levels 3. Draw attention to supportive multi-disciplinary implementation research 4. Focus on schistosomiasis demonstrating its clinical importance in UK & abroad 5. Discuss new methods for diagnosis of schistosomiasis during control 6. Feature the clinical pathology and impact of female genital schistosomiasis 6 learning points for today disease specific – diagnostics & pathology
  18. 18. ICST 2: Schistosomiasis/STH diagnostic surveillance platforms Expanding molecular diagnostics of helminthiasis: Piloting use of the GPLN platform for surveillance of soil transmitted helminthiasis and schistosomiasis in Ghana Cunningham et al. (2018) PLoS NTDs NOTE: real-time DNA diagnostics has several untapped applications e.g. eDNA monitoring (WASH) or interruption of parasite transmission clinical investigations in tissue biopsy for FGS in cervical screening
  19. 19. Selection of faecal samples Bead-beating treatment of sample DNA extraction Real-time PCR analysis Results of qPCR analysis of GPLN faecal samples Expanding molecular diagnostics of helminthiasis: Piloting use of the GPLN platform for surveillance of soil transmitted helminthiasis and schistosomiasis in Ghana Cunningham et al. (2018) PLoS NTDs
  20. 20. ? Available diagnostics and proxy markers Endemic or traveller? Child or adult? Finger-prick blood Antigen: CCA or CAA ++ +/? ++ Antibody: SEAA +++ - +/? Anaemia: Hb ++ - ++ Stool Eggs: Kato-Katz +++ +++/? +++ Formol-ether ++/? ++ ++ FOB tests +++ + +++ Calprotectin RDTs ++ + ++ UrineB Questionnaire: red urine + - +/? Eggs: 10 ml filtration +++ +++/? +++ Centrifugation ++ ++ ++ Antigen: CCA or CAA ++/? ++/? ++/? Reagent stripsC: ++ +/? ++ NB: its all about the cytotoxic eggs:
  21. 21. General diagnostics for schistosomiasis & compromise Al-Shehri et al. in press
  22. 22. Towards integrated control of schistosomiasis - consistent gaps exposure those most vulnerable - poor cross-talk with maternal & child health
  23. 23. Schistosomiasis (like ALL other NTDs) needs multidisciplinary approaches but until 2003 PSAC & FGS were overlooked Stothard et al. (2011) Closing the praziquantel treatment gap: new steps in epidemiological monitoring and control of schistosomiasis in African infants and preschool-aged children. Parasitology (SI entitled Progress in Paediatrics) 2013 Corsica noted in 4 yo child 2008
  24. 24. Points of intervention (~1994) – clues from the lifecycle SAC
  25. 25. Bowel pathology & analogy in experimental animals Advanced morbidity usually takes years to develop …when did this child’s start? …how common this condition?
  26. 26. advanced hepatosplenic disease and EMF • US studies focused on liver/spleen • Further US study described EMF • Vasculature remodelling ‘shunts’ • Are we missing a cryptic EMF burden
  27. 27. Importance of PSAC and disease progression Let’s not create any further medical inequities with our own best intentions
  28. 28. 1. Introduce the global burden of key neglected tropical diseases 2. Highlight issues in control of tropical helminthiases at national levels 3. Draw attention to supportive multi-disciplinary implementation research 4. Focus on schistosomiasis demonstrating its clinical importance in UK & abroad 5. Discuss new methods for diagnosis of schistosomiasis during control 6. Feature the clinical pathology and impact of female genital schistosomiasis 6 learning points for today disease specific – diagnostics & pathology
  29. 29. Revising policy through time – where’s the gap? At-risk groups outside of SAC - adult women (WCBA) / men - pre-school-aged children Access to PZQ insufficient none Awareness/surveillance in health system to genital aspects of S. haematobium - access to colposcopy / questionnaire
  30. 30. Why females and males should be concerned? Background on genital schistosomiasis
  31. 31. Female genital schistosomiasis presentations (acute and chronic manifestations)
  32. 32. Tackling genital schistosomiasis How can we improve this - social context - women’s daily behaviours - capacity for health system change Female genital schistosomiasis - often ignored (everywhere) - not reported in West Africa Need any further convincing?
  33. 33. Tackling genital schistosomiasis Molecular diagnostic platforms (HPV detection & typing) using multiplex real-time PCR assays *tissue biopsy / vaginal lavage
  34. 34. Tackling genital schistosomiasis Female genital schistosomiasis - often ignored (everywhere) - not reported in West Africa What about male genital disease? How can we improve this - social context - women's daily behaviours - capacity for health system change
  35. 35. 2017 – LSTM PhD student MGS in Malawi What’s the HIV viral load in semen for men on ARVs?
  36. 36. Tackling genital schistosomiasis Female genital schistosomiasis - often ignored (everywhere) - not reported in West Africa We need a stronger focus on FGS How can we improve this - social context - womens’ daily behaviours - capacity for health system change
  37. 37. Connecting HIV/HPV/sub-fertility (www.fgsworkshop.org) (FGS) COUNTDOWN implementation research
  38. 38. Systematic review: FGS widespread but under-reported COUNTDOWN implementation research
  39. 39. COUNTDOWN implementation research In Nigeria (like elsewhere) a lot of women likely have FGS but sadly don’t know it - a very cryptic health burden - better diagnostics needed (rtPCR) - a PC disease needing an IDM approach - economic forecasting for future resourcing
  40. 40. FGS is a ‘ticking’ public health time-bomb FGS present in a sub-set of those with S. haematobium infection - Infection > disease >…detection NB: annual treatment too late !!! Current MDA approach is an insufficient clinical intervention
  41. 41. Broader challenge of integrated control in a health system Where should FGS actions & intervention(s) be best sited? - prevention & surveillance - individual disease management
  42. 42. COUNTDOWN research uptake more African focused: targeted activities playing into policy action… • Indicators of environmental transmission - WASH factors, e-DNA tracers of NTDs - PZQ MDA + biannual / expanded access • Drivers of national policy change - advocate for increased PZQ supplies - accelerate towards public health goals - widen health system engagement (NB academia) • Special mention to FGS management - access to clinical surveillance & gynaecology
  43. 43. A three point summary Diagnostics - we should do a better job in the UK and abroad Genital schistosomiasis - need to control this aspect for synergy with HIV/HPV Paediatric schistosomiasis in Africa - PZQ needs to be administered to PSAC
  44. 44. Some useful papers 1. Bustinduy et al. (2017). Paediatric and maternal schistosomiasis: shifting the paradigms. British Medical Bulletin, 123, 115-125. 2. Lo et al. (2017). A call to strengthen the global strategy against schistosomiasis and soil- transmitted helminthiasis: the time is now. Lancet Infectious Diseases, 17, E64-E69. 3. Miller-Fellows et al. (2017). Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women. PLoS Neglected Tropical diseases, 11. 4. Stothard et al. (2017a). Towards interruption of schistosomiasis transmission in sub-Saharan Africa: developing an appropriate environmental surveillance framework to guide and to support 'end game' interventions. Infectious Diseases of Poverty, 6. 5. Stothard et al. (2017b). A centenary of Robert T. Leiper's lasting legacy on schistosomiasis and a COUNTDOWN on control of neglected tropical diseases. Parasitology, 144, 1602-1612. 6. Tchuem-Tchuente et al. (2017). Moving from control to elimination of schistosomiasis in sub- Saharan Africa: time to change and adapt strategies. Infectious Diseases of Poverty, 6.
  45. 45. Thank you RCPATH and team today Key COUNTDOWN ICST-2 UK staff Suzanne Campbell (LSTM) Lucas Cunningham Faye O’Halloran Deborah Sankey Tim Durant Grace Macklin Lisa O’Halloran Zikmund Bartoníček James LaCourse Martyn Stewart Emily Adams Supporting the COUNTDOWN consortium NHM David Rollinson Bonnie Webster Univ. of Naples Laura Rinaldi Tilburg Hospital Jaco Verweij Lieden University Medical Centre Lisette van Leishout, Govert van Dam Acknowledgements

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