Biodosimetry in Mass Casualty Events

1. Biodosimetry in Mass Casualty Events Lecture Module 10

2. What is a mass casualty event? Involvement of a large number of people needing to be assessed into: • Exposed and requiring medical treatment • Exposed but below the level needing treatment • Worried well • A multiple casualties event is one that exceeds the response capability of the local responders

3. Planning Important points: • Learn from previous experience • Envisage potential scenarios • Maintain a review of medical / technical resources • Have plans prepared • Exercise

4. Radiation emergencies (1) Accidental Broadly three types: • Reactor emergencies - breach of fuel due to loss of coolant • Criticality - uncontrolled fission • Orphan sources - lost or stolen

5. Radiation emergencies (2) Malicious Again, three broad types: • Radiological exposure devices • Radiological dispersal devices • Improvised nuclear devices

6. Medical triage (1) The immediate sorting of casualties into medical treatment priorities Based on: • Obvious signs (early prodromal effects) • Patient’s account (location, timing etc) • Associated trauma (treating life threatening injury takes precedence over irradiation) • Information on the nature of the event

7. Medical triage (2) The initial sorting of irradiated persons is to establish: • Those requiring no treatment • Those probably needing treatment after further observation • Those needing treatment immediately • Those beyond medical help

8. Medical triage (3) • Treatment is started based on signs and symptoms; not on dose estimates • Dose triaging needs to be only approximate: <1 Gy; 1-2 Gy; 2-4 Gy; 4-6Gy; >6Gy • Based on early clinical responses there will be false positives and false negatives • Biodosimetry can more precisely place persons into dose groups

9. Biodosimetry capacity Definition: A multiple casualties event that exceeds the response capability of the local responders • Biodosimetry labs are rare • Many countries have no lab • Very few countries have more than one lab • Individual biodosimetry labs tend to be small with few specialist trained staff The surge capacity is limited

10. Some examples Some events where mass biodosimetry experience was gained. PlaceYear No. of persons Chernobyl 1986 > 100, 000 Goiania 1997 ~250 Concepcion 2005 ~230 Dakar 2006 ~60 Tokaimura 1999 ~40

11. Biodosimetry: Dealing with a surge Requirement: To speed up the throughput of case investigations Response: Four broad approaches: • Triage dicentric scoring • Change to a different assay endpoint • Automation • Networking

12. Triage scoring Several approaches: • Reduce the number of cells scored per patient for dicentrics • Use the ‘Quickscan’ method of scoring dicentrics • Reduce the number of cells scored for micronuclei

13. Reduced dicentric scoring Strategy: • Ideally score 50 cells (or 30 dicentrics) • Confer with physicians; identify conflicts and prioritize them for resolution • Later - less urgently increase scoring to improve data for: 1. impaired bone marrow management 2. scientific interest - epidemiology

14. Quickscan dicentric scoring Strategy: • Look at metaphases that appear to be complete without doing a count • Spend less time evaluating each metaphase. • Count the dicentrics This approach to scoring reduces microscopy time by a factor of ~6

15. Reduced micronuclei scoring. Strategy: • Culture cells (72h) for the CBMN assay • Stain with acridine orange (fluorescence microscope needed) • Score 200 binucleate cells per patient This approach will detect radiation doses in excess of 1 Gy

16. Automation Various stages can be automated: • The ‘wet work’ – cell culturing, fixing, slide making and staining • Metaphase and binucleate cell detection • Image capture and storage • Dicentric and micronucleus ‘hunting’ software.

17. Operator review at an automated microscope

18. Automatic dicentric hunter

19. Automatic micronucleus hunter

20. The concept of an automated lab Blood handler Incubator Cell harvester Spreader Control computer Satellite scoring station Auto stainer Metaphase finder Slide

21. Networking This can take several forms: • Sharing blood samples among labs for the culturing and scoring • Sharing just the scoring among labs by sending out fixed cell suspensions or slides or by telescoring

22. Existing networks Geographical groupings: • Single countries: Canada, France, Japan, Republic of Korea • Regions: Latin America, European Union • World-wide: RANET

23. Mass casualties - Summary points (1) • We have actual experience from responding to mass accidents • Biodosimetry must work in close collaboration with the medical response • Biodosimetry acts as a secondary triage after initial clinical assessment

24. Mass casualties - Summary points (2) • Labs are small with limited surge capacity • Provision has been made to deal with surges • Other assays than the dicentric are available • Automation is well established in many labs • Biodosimetry can operate in a triage mode • Assistance through networking is set up

25. Mass casualties - Summary points (3) • Biodosimetry community can mount response proportionate to size of most envisaged events • It can comfortably handle tens to hundreds of cases • Possibly a few thousands