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Expert Consultation on Infectiousness of Organisms Studied in the NEIDL Risk Assessment. Sam A Bozzette, MD, PhD Adi Gundlapali , MD, PhD. May 18, 2010. Overview. Delphi process Informed voting Feedback of group and your own responses Opportunity for discussion
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Expert Consultation on Infectiousness of Organisms Studied in the NEIDL Risk Assessment Sam A Bozzette, MD, PhDAdi Gundlapali, MD, PhD May 18, 2010
Overview • Delphi process • Informed voting • Feedback of group and your own responses • Opportunity for discussion • Re-voting with feedback • Where are we? • Background information distributed • One round of voting complete • Voting analyzed and feedback prepared
Today • Distribute feedback materials • Summary of all votes • Your own vote • By section • Review and discuss the background material • Review feedback • Re-vote on paper forms
Infectious Dose • Inhalation • Percutaneous (sharps) • Mucous membranes • Ingestion • Animal or arthropod Accident event/transmission route 4
Infectious Dose • Inhalation • Percutaneous (sharps) • Mucous membranes • Ingestion • Animal or arthropod Accident event/transmission route Amount, concentration, form of pathogen • The “source term” • Working cultures • Inocula for animal challenges 5
Infectious Dose • Inhalation • Percutaneous (sharps) • Mucous membranes • Ingestion • Animal or arthropod Accident event/transmission route Amount, concentration, form of pathogen • The “source term” • Working cultures • Inocula for animal challenges Amount of infectious inoculum • Atmospheric dilution • Atmospheric stability 6
Infectious Dose • Inhalation • Percutaneous (sharps) • Mucous membranes • Ingestion • Animal or arthropod Accident event/transmission route Amount, concentration, form of pathogen • The “source term” • Working cultures • Inocula for animal challenges Amount of infectious inoculum • Atmospheric dilution • Atmospheric stability Pulmonary infectious dose assumptions: HID50 , HID10 , HID90 Mathematical fit of curves to 3 points; 7
Infectious Dose • Inhalation • Percutaneous (sharps) • Mucous membranes • Ingestion • Animal or arthropod Accident event/transmission route Amount, concentration, form of pathogen • The “source term” • Working cultures • Inocula for animal challenges Amount of infectious inoculum • Atmospheric dilution • Atmospheric stability Pulmonary infectious dose assumptions: HID50 , HID10 , HID90 Mathematical fit of curves to 3 points; Estimated likelihood of initial infection(s) 8
Infectivity ID50 = O.5PFU (95% C.I. 0.3-1.1) via aerosol in rats {Nuzum, 1988 #16358}
R0- Basic Reproduction Number Definition: The expected number of secondary infections caused by a typical primary case in a fully susceptible population, in the absence of interventions to control the infection and its transmission
Estimates of R0in the literature • Direct estimates from early outbreak data • Before intervention / control measures • Indirect estimates from full outbreak data • Formulas derived from mathematical models
How R0 will be used • Branching process modeling • Simulated, infected individuals transmit to R0 other individuals, on average • Applies in early generations of small outbreak (before intervention measures are implemented) • Individual variation will be included • Accounting for chance and atypical individuals • Compartmental modeling • Value used to constrain other parameters
Proposed R0 values for pathogens • Nominal value proposed for each pathogen • Important notes • Value only applies before control measures • Range of values around nominal value will be tested in sensitivity analyses
Infections in the Vulnerable • Problem • Need to account for potential differences in susceptibility to and mortality from infection in specific sub-groups of the population • This is an important concern to the public • Community surrounding the Boston NEIDL site is largely minority and below the poverty line
Vulnerability • Background • Intuitively inferred that certain sub-groups are more susceptible to disease and death from disease • Very young and very old and influenza • Pregnancy and pandemic influenza • Diabetics and pneumonia • HIV/AIDS and tuberculosis • No aggregate estimates available of increased vulnerability to or increased mortality from infections in general
Vulnerability • Request • Estimate increased vulnerability to infection in these sub-groups • Child younger than 5 years of age • Adult older than 65 years of age • A person with diabetes • A person with HIV infection • A pregnant women • Categories: bacteria and viruses • To disease and to mortality • We are requesting a % increase
Vulnerability • How will we use these estimates? • Apply these corrections to estimate increased infection and mortality rate in these scenarios/outputs • Primary exposure to a pathogen • Secondary transmission modeling • Example
Atmospheric Stability • Needed to assess potential for infections as a result of pathogen releases from the building • Atmospheric conditions may inactivate a portion of the particles released • Range of atmospheric conditions must be considered since releases could occur at any time • Rate of Stability is dependent upon • Temperature (less stable at high temperatures) • UV (less stable in high UV) • Humidity (uncertain affect)
Conversion to Half-Lives • Half-life = t½ = t (ln 2) / ln (No/Nt) • Initial abundance (No) • Abundance at time t (Nt) • Time t • Some data reported as D37 • D37 = Ultra violet light fluence (J/m2) which reduces the abundance to 37% of its original level (i.e., Nt / No = 0.37) • The D37 data were converted to half-lives for discussion
Data Requested • Provide the half-life in minutes for each pathogen for • Cold dry night (maximum half-life) • Hot humid sunny day (minimum half-life) • Many values given in Table 3 of the Briefing reflect lowest stability conditions (i.e., mid-day in summer on sunny day)
