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Table 3 Inputs for the DES model of long-term poliovirus excretor prevalence

From: Modeling the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus excretors and the potential benefits of antiviral drugs

Model input Base case value Source Notes
Births, by income level and polio vaccine use as of 2013 [1/month] Varies with time [23, 56] Using number of 0-year old children as of 2013, divided by 12 months; stratification by income level and polio vaccine as of 2013 as in Table 2
Probabilities of attributes determined at birth
PID pre-disposition   [41] Based on reported annual total PID incidence in 0–5 year olds during 2000–2006, attributing 21 % to CVIDs based on total reported fraction of new PID cases, excluding IgA deficiency and transient hypogammaglobulinemia in infancy
 - CVID 1/32,000
 - oPIDs 1/8,500
Potential long-term excretion (if OPV-infected and surviving)   [18, 53] and Table 1 Assumes lower chance of becoming potential chronic than prolonged excretor for CVIDs based on limited observations of both; for oPIDs, no known cases of chronic excretion exist
 - Prolonged, CVID or oPIDs 0.01
 - Chronic, CVID 0.005
 - Chronic, oPID 0
Monthly event probabilities and related relative probabilities
Death, general population, by income level Varies with age [56] Based on 2013 estimates of annualized death rates; does not include fatal VAPP which may occur separately; applies prior to clinical PID onset
Death, PID patients Varies with time since onset/treatment [20, 37, 44]B* Baseline monthly death rates calculated from survival curves (Fig. 2), then multiplied by relative monthly risk of death for R0 and treatment status; does not include fatal VAPP which may occur separately, and effect of treatment lapses, which subject otherwise treated PID patients to the untreated PID death rates for the duration of the lapse
Relative monthly death rate vs. baseline, by treatment status   B Apply death rates as a function of time since treatment start for treated PID patients and since PID onset for untreated patients
 - Treated 1
 - Untreated 5
Relative monthly death rate vs. baseline, by R0   B  
 - 4 or 5 1
 - 6 5
 - 7 10
 - 8 20
 - 9 25
 - 10 35
 - 11 40
 - 12 45
 - 13 50
Treatment lapse   B  
 - Low-income 0.8
 - Lower middle-income 0.75
 - Upper middle-income 0.1
 - High-income 0.001
PID onset   [44, 45] Corresponds to average of onset of approximately 25 (CVID) and 2 (oPIDs) years
 - CVID 1/300
 - oPIDs 1/24
Diagnosis   [4345] Corresponds to average diagnostic delay of approximately 5 (CVID) and 1 (oPID) years
 - CVID 1/60
 - oPIDs 1/12
Primary OPV infection, if OPV-only RI and not diagnosed with PID   B Defined as monthly probability of infection with any serotype due to receipt of OPV; assumes 3 OPV infections during primary vaccination in first year of life, 1 infection from OPV booster dose during ages 1–4 in high-income countries, 1 annual infection from OPV supplemental immunization activity (SIA) doses during ages 1–4 in other countries, and no OPV doses after age 4
 - Any income level, age 0 1/4
 - Not high-income, age 1-4 1/12
 - High-income,age 1-4 1/48
 - Any income level, age > 4 0
Primary OPV infection, if IPV/OPV RI and not diagnosed with PID   B Assumes 2 instead of 3 OPV infections during first year of life, with 1 additional infection during ages 1-4
 - Any income level, age 0 1/6
 - Any income level, age 1-4 1/48
 - Any income level, age > 4 0
Relative probability of primary OPV infection, diagnosed vs. not diagnosed 0.1 B Assume contra-indications typically followed for vaccination
Relative probability of secondary OPV infection, diagnosed vs. not diagnosed 0.5 B Assume siblings will sometimes avoid live vaccines
Relative probability of long-term OPV infection if treated vs. not treated 0.5 B Assumes some effect of IVIG on the ability of an OPV infection to become persistent; excludes treated PID patients experiencing a treatment lapse
Secondary OPV infection, if OPV-only RI   [62, 63] B Defined as probability of infection with any serotype due to secondary OPV exposure; Baseline rates based on approximately 45 % secondarily infected from OPV RI by age 20 months in US [62] and approximately 50 % secondarily infected from SIAs in Oman and Cuba [63, 64], assuming 1 SIA per year on average
 - Not high-income, age 0-4 1/24
 - High-income, age 0-4 0.029
 - Not high-income, age 5-14 0.5 × 1/24
 - High-income, age 0-4 0.5 × 0.029
 - Not high-income, age > 14 0.25 × 1/24
 - High-income, age >14 0.25 × 0.029
Relative probability of secondary OPV infection in any income level if IPV/OPV RI vs. high-income country with OPV-only RI 0.5 B  
Probability of serotype-specific OPV infection given any OPV infection before OPV2 cessation   [18] Based on distribution of isolated serotypes from known long-term poliovirus excretors; see text
 - Serotype 1 0.22
 - Serotype 2 0.62
 - Serotype 3 0.16
Probability of serotype-specific OPV infection given any OPV infection, after OPV2 cessation   B Assumes same relative distribution of serotypes 1 and 3 after OPV2 cessation as before OPV2 cessation; see text
 - Serotype 1 0.58
 - Serotype 2 0
 - Serotype 3 0.42
Recovery from OPV infection, by time since onset of infection   [2, 18, 65] B Implies average duration of approximately 3 months for a “typical” infection (truncated at 6 months), which is somewhat longer than immunocompetent individuals, consistent with observations from Finland;[65] 2 years for a prolonged infection (truncated at 5 years), and 10 years for a chronic infection (not truncated)
 - Typical, months 0-4 1/3
 - Typical, month 5 1
 - Prolonged, month 0-5 0
 - Prolonged, months 6-58 1/18
 - Prolonged, month 59 1
 - Chronic, month 0-59 0
 - Chronic, from month 60 1/120
VAPP   [18, 42, 53] B Based on US VAPP incidence by PID category and calibration to reported paralytic long-term excretors (see text); assumes no chance of VAPP if effectively treated (i.e., with IVIG), excluding during treatment lapse
 - CVID, not treated 0.004
 - oPIDs, not treated 0.008
 - Any PID, treated 0
Fatal VAPP   [53, 66] Based on case-fatality rates among 6 immunodeficient VAPP patients in Iran and 36 immunodeficient VAPP cases in the US; for the latter, we assume that a death within a year of VAPP onset represents death associated with VAPP (even in the case of another cause of death indicated) due to comorbidity
 - Low-income countries 0.5
 - Lower middle-income countries 0.4
 - Upper middle-income countries 0.3
 - High-income countries 0.14
  1. Notes: * B indicates estimate based on judgment