# Presentation: 662823

## Impact working groupInter-meeting work group summary

- June 15-16, 2005
- Atlanta

## Disease impact workgroup goals

- Part I: Describe impact of past pandemics on groups by age and underlying conditions
- Part II: Determine whether data support sub-prioritization of high risk beyond current inter-pandemic tiering

## Participants

- Ted Eickhoff, UCHSC
- Paul Glezen, Baylor Coll. Of Med
- Marika Iwane, NIP, CDC
- Susan Lett, CSTE
- Megan Lindley, ASPH
- Arnold Monto, U. of Mich. School of Public Health
- Kathy Neuzil, ACP
- Ishmael Ortega-Sanchez, NIP, CDC

- David Shay, NCID, CDC
- Rich Schieber, NIP, CDC
- Ben Schwartz, NVPO
- Bill Thompson, NIP, CDC
- Pascale Wortley, NIP, CDC

## Assumptions

- Very limited antiviral supply—some high risk groups may be prioritized for prophylaxis or early therapy
- Vaccine production at rate of approximately 20 million doses per month, necessitating sub-prioritization of high risk

##                  Part I

**a.   Clinical Attack rates**

## Influenza attack rates, 1918 (Frost 1919)*

**Influenza attack rates, 1918 (Frost 1919)***

- *approximations based on figure—household surveys conducted Dec 1918

## Attack rate by community, 1918 (Frost 1920)

**Attack rate by community, 1918 (Frost 1920)**

**Notes:**
Substantial variation across cities

## Clinical attack rates during Fall 1957

|  | Hennessey (1964) | Dunn
(1959) | Jordan*
(1958) | Woodall
(1958) | Chin
(1960) |
| --- | --- | --- | --- | --- | --- |
| Popula
tion | Tecumseh households | 5 schools, 1 factory
Louisiana parish | Cleveland families | General practice, London | Family contacts of Kansas City HS students  |
| 0-4 | 26% | 31% (pre-school) | 43% | 31% | 32% |
| 5-9 | 38% | 39% (elementary) | 58% | 49% | 33% |
| 10-14 | 40% | 48% 
(high school) | 59% |  | 39% |
| 15-19 | 34% |  | 47% | 25% 

(60+ 12%) | 38%  |
| 20-29 | 20% | 20%
(adults) | 19% |  | 27%  |
| 30-39 | 16% |  |  |  |  |
| 40-49 | 14% |  |  |  | 17%  |
| 50+ | 10% |  |  |  |  |

**Clinical attack rates during Fall 1957**

- *lab-confirmed

## Clinical attack rates: Nov 1968-Jan 1969

|  | Monto (1970)* | Davis (1970) |
| --- | --- | --- |
| <1 | 16.5% | 40% |
| 1-4 |  | 40% |
| 5-9 | 11.6% | 43% |
| 10-14 | 9.2% | 40% |
| 15-19 | 8.9% | 38% |
| 20-24 | 12.7% | 35% |
| 25-29 |  | 33% |
| 30-39 | 8.1% | 38% |
| 40-49 | 8.9% | 38% |
| 50-64 |  | 35% |
| 65+ |  | 30% |
| Population | Adrian (comparison to Tecumseh)* | Southwest high school families (Kansas City) |

**Clinical attack rates: Nov 1968-Jan 1969**

- *weekly mean averages

**b. Death rates**

## 1918 P&I death rates (Frost 1919)*

**1918 P&I death rates (Frost 1919)***

- *approximations based on figure

## Age-Specific Influenza Death Rates Among Females in England and Wales, 1918

- Nguyen-Van-Tam, JS, et al. Vaccine, 2003; 21:762-68.

****

**Notes:**
Elderly were less affected by 1918 pandemic—this shows contrast between impact of previous year’s virus (winter 1918) and pandemic virus (fall 1918)

## P&I death rates per 100,000 population, 108 cities,  Aug-Dec 1957 (Dauer 1958)

**P&I death rates per 100,000 population, 108 cities,  Aug-Dec 1957 (Dauer 1958)**

- Age group

## P&I death rates per 100,000 population, 1968-69 (Luk 2001)

**P&I death rates per 100,000 population, 1968-69 (Luk 2001)**

- Age group

**c. Excess death rates**

## 1918 excess death rates (Luk 2001)

**1918 excess death rates (Luk 2001)**

## Fall 1957 excess death rates

**Fall 1957 excess death rates**

- *P&I, compared to previous year
- **All cause, modeling
- ***P&I, modeling

## 1968 excess P&I death rates (Luk 2001)

**1968 excess P&I death rates (Luk 2001)**

## Source: Serfling 1967

## Age-specific excess mortality by pandemic: numbers and rates per 100,000 (Simonson 1998)

|  |          <65 |  |         >65 |  |
| --- | --- | --- | --- | --- |
|  | Rate  | No. | Rate | No. |
| 1918-19
     | 546

    | 538,000
   | 166 | 8,000 |
| 1957-58 | 15 | 24,000 | 273 | 42,000 |
| 1968-69 | 4.3 | 7,800 | 44 | 8,600 |

**Age-specific excess mortality by pandemic: numbers and rates per 100,000 (Simonson 1998)**

##             Part II

**    ****Sub-prioritizing **
**      ****the high risk**

## Specific conditions: pregnancy

- 1918-19 and 1957-58: data are limited but suggest pregnant women were at increased risk of death
- 1968-69: no data on impact on pregnant women
- Interpandemic influenza: pregnant women are “high risk” but not at higher risk than other high risk groups unless they have another underlying HR condition.

## Specific conditions: bone marrow transplants

- Limited studies (Nichols 2004, Whimbey 1994) , but both suggest high rates of complications.
- Largest study (Nichols): 18/62 BMT pts with lab confirmed influenza had LRI; 6/62 died (5 of 6 had LRI)
- Likely greater benefit from antiviral drugs than vaccine

## Hospitalizations and Deaths per 1,000 Unvaccinated Persons 65+ 1996-1998

- Source: Hak 2002 CID

- Year 1 range: 36-86
- Year 2 range:  36-56

- *Renal disease, immunodeficiency or receipt of organ transplants, non hematologic cancer

## Hospitalizations and Deaths per 10,000 Persons 15-64 1973-1992

-   Neuzil 1999 JAMA
-   Neuzil 2003 JAIDS

- *NS

- Range 36-76/10,000

- *HIV-HAART data: 1995-1999

## P&I death rates 1968-69 and 72-73, by condition, Oregon HMO, all ages combined (Barker 1982) 

|  | Deaths | Pop | Rate/
10,000 |
| --- | --- | --- | --- |
| CV | 7 | 6,740 | 104 |
| Pulm | 5 | 2,080 | 240 |
| CV+DM | 5 | 1,040 | 481 |
| CV+Pulm | 8 | 920 | 870 |

**P&I death rates 1968-69 and 72-73, by condition, Oregon HMO, all ages combined (Barker 1982)**

## Number of high risk conditions, Oregon HMO, 1968-69 and 1972-73 (Barker 1982)

|  | status | No. P&I deaths | pop | Rate per
10,000 |
| --- | --- | --- | --- | --- |
| 15-44 | No HR | 0 | 134,000 | - |
|  | 1 HR | 0 | 6,260 | - |
|  | >1 HR | 0 | 260 | - |
| 45-64 | No HR | 1 | 43,900 | 2 |
|  | 1 HR | 7 | 6,900 | 10 |
|  | >1 HR | 4 | 1,060 | 377 |
| >64 | No HR | 1 | 11,760 | 9 |
|  | 1 HR | 14 | 6,460 | 217 |
|  | >1 HR | 11 | 1,380 | 797 |

## Previous hospitalization

- Fedson*:
- 	39 to 46% of elderly discharged for influenza-associated respiratory conditions had recent hospitalization
- 	62-67% of those who died had a recent hospitalization
-      6% of 65-74 (12% of 75+) had a hospital discharge during vaccination season **(Sept 1-Nov 30)**

- Annals of Internal Medicine 1992;116:550-5

## Association of clinical characteristics with hospitalization due to pneumonia or influenza and death due to any cause, during the influenza season among persons >64 (Hak 2004)

|  | Adj OR |
| --- | --- |
| Previous P/I hospitalization  | 8.1 (5.7-11.5) |
| Outpatient visits | 1.5 (1.3-1.8) |
| Heart disease | 1.2 (1.0-1.5) |
| Pulm disease | 1.8 (1.4-2.3) |
| Dementia, stroke | 2.1 (1.6-2.7) |
| Renal disease | 1.5 (1.1-2.1) |
| Cancer | 4.9 (3.4-7.0) |
| Diabetes | ns |
| Immunodeficiency* | ns |

**Association of clinical characteristics with hospitalization due to pneumonia or influenza and death due to any cause, during the influenza season among persons **_**>**_**64 (Hak 2004)**

- * Immunodeficiency and organ transplants

## Potential criteria for sub-prioritization of high risk

- Age: high mortality in <1 in pandemics; among adults increasing risk with age (18-49 vs 50-64)
- Number of high risk conditions.
- History of hospitalization for high risk condition or P&I.
- Severe immunosuppression, e.g. BMT.     -data not available for other immuno- compromised subpopulations.

## Inter-pandemic prioritization

| Tier | Group | Est. pop in millions |
| --- | --- | --- |
| 1A
 | >64 with HR |  16.7 (5.2 w/ 2+HR) |
|  | LTC resident |  1.5 |
|  | 2-64 with HR |  42.4  (5.8 w/ 2+HR) |
|  |   50-64
  18-49 
   2-17 |    15.5  (3.6 w/ 2+HR)
   20.0  (1.7 w/ 2+HR)
    6.9   (<0.5 w/ 2+HR) |
| 1B
 | >64 without HR | 18.9 |
|  | 6-23 months |  6 |
|  | Pregnant women |  4 |
| Total | High risk |  88.3 (Some overlap       between categories) |

**Inter-pandemic prioritization**

## Size of specific groups

| Group | Number in millions* | Comment |
| --- | --- | --- |
| Transplants | 0.15 | Includes solid organ transplants |
| Cancer | 1.4 | Annual incidence—assume substantial proportion immunosupp at some point |
| >  2 high risk conditions | 10 | Ages 2-64 and 65+ |
| <12 months | 4 |  |
| Pregnant women  | 4 |  |

- *groups may overlap

**Size of specific groups**

## Potential subprioritization of high risk, con’t

- Pro
- High risk within tiers are not equal, sub-prioritization could help target most vulnerable first as vaccination of some groups will take several months (e.g. >40 million 2-64 with HR)
- Con
- Implementation may be challenging
- Data are limited

## Extra slide

## Pregnancy

**Harris 1919**: case series of pregnant women with influenza; 50% had pneumonia, and 50% case fatality rate w/ pneumonia (7-9th months: 60% vs 1-6 m:45-53%).
**Woolston 1918**: 2154 pts admitted to Cook County Hospital; 50% of pregnant women died compared with 33% of other pts.
**Greenberg 1958**: NYC mortality data fall 1957;47 P&I deaths in women 15-49; 22/47 (47%) were pregnant women.