Presentation to

National Alliance for Radiation ReadinessNovember 16, 2011

Large-Scale Testing for ARS after a Nuclear Detonation

• As a result of a ground burst 10kt nuclear detonation in a major city:– Many thousands of people would be exposed to life-

threatening doses of radiation from fallout – Medical interventions could save many of these people– Resources (medicines, hospital beds, transportation)

would be limited and therefore victims must be triaged

• How can the patients most likely to benefit from medical intervention be rapidly and accurately identified?

THE CHALLENGE

• Modeling estimates ~100,000 people may develop ARS from fallout

• It may not be obvious early on who these people are– early symptoms are non-specific and unreliable– Many other concurrent reasons for symptoms

• “Worried well”, stress reaction, normal illnesses, head injuries, ear drum rupture, etc

– Geographic information may not be sufficient

• Testing many times the 100,000 may be needed to identify all those with impending ARS.

• Reasonable to estimate that in a metro area of 3 million, 1 million people may need to be screened

TESTING ONE MILLION PEOPLE?

• Countermeasures (bone marrow stimulators) are most effective if given early—within 1-2 days.

• Getting patients to care (RITN or other) may take days.

• Many patients with ARS will have a latent period of several days before the onset of severe illness.

SHORT TIME FRAME FOR SCREENING

• Many of the people in the area of the detonation will evacuate (informed or not) and they may be on the move for days given transportation and lodging challenges.

• They may first present for screening in other cities or towns.

• They may not be in the same place if they need follow-up testing.

• They may not be in the same place when they become seriously ill.

A POPULATION ON THE MOVE

• Can 1 million people be screened for ARS over a 24 hour period (starting within 1-2 days of a nuclear detonation) regardless of where they are and have their results be immediately available to any clinician anywhere in the country using only existing technology and systems?

THE THOUGHT EXPERIMENT

• Time to vomiting– Most people exposed to >2 Sv will vomit within 4 hours– However, vomiting is non-specific and unreliable (many

false positives and false negatives)– Severe, repetitive vomiting may be more reliable– Absence of any nausea or vomiting indicates less risk of

significant exposure

POSSIBLE METHODS

• Chromosomal Dicentrics– Gold standard– Not performed in most laboratories– Specially trained personnel– Takes time for results– Current national capacity is 50-100 tests week. May be

able to increase to 1000 week in next few years.

POSSIBLE METHODS FOR SCREENING

• Investigational:– Electroparamagentic spin resonance (EPS) of dental

enamel-Ideally performed on extracted teeth but can be done one nails and teeth in head

– Stress gene and protein signature– Metabolomics (urine)– Ocular albumin– others

• All early stage R&D

POSSIBLE METHODS

• Predictable time-dependent decrease in ALC after radiation exposure– If time of exposure known, approximate whole body

dose can be estimated– For single test, measurement at 48 hour is most useful

• Serial testing adds value• Comparison to neutrophil count adds value

ABSOLUTE LYMPHOCYTE COUNT

• ALC enables prioritizing patients most like to benefit from treatment (hospitalization, G-CSF, blood products, antibiotics): – Too low to benefit from treatment (will die even with

treatment)– Too high to need treatment (will recover without

treatment)– Treatment can make the difference between life and

death

ALC: CATEGORIES OF TRIAGE

• Performed in all clinical laboratories as part of CBC/d

• Automation• No special training of technicians

ALC: ADVANTAGES

• After a nuclear detonation some local hospital labs may be destroyed

• Other hospitals’ labs may be overwhelmed with medical surge (trauma, prompt radiation, evacuated patients, etc)

• Deployable labs have limited capacity—– With people on the move, where to deploy to?

• Physician office and clinic labs: low volume and slow

• Need for ability to track/match results with patients as they move

WHO WOULD PERFORM ALCS?

• 2 major national laboratory chains serve the US– LabCorp (1700 patient care sites, 51 major laboratories)– Quest Diagnostics (2000 patient care sites, 37 major

laboratories)– Both possess transportation fleets including fixed-wing

aircraftTogether they believe that they possess have the capacity to do 1 million ALCs in a 24 hour periodBoth have extensive internet portals that allow patient tracking of results; most physicians and most Americans already are registered with one or both

NATIONAL LABORATORY CHAINS

• Many challenges to implementation– Reagent Supply Chain-JIT inventory principles– Interoperability between IT systems– Need to integrate smaller labs– Logistics of phlebotomy

• Phlebotomy supplies

– Physician order rules• Some states require Rx for labwork

• None seem insurmountable

• Next steps…….?

CHALLENGES