# Presentation: 045170

## Live Attenuated Influenza Vaccine (LAIV) Administration in Schoolchildren Coincident with the 2003-2004 Outbreak Provided Herd Immunity Against a Drifted Influenza Variant A/Fujian/411/2002 (H3N2)

- Manjusha Gaglani, Pedro Piedra, Claudia Kozinetz, Gayla Herschler, Charles Fewlass,
**W. Paul Glezen**

- Sponsors: NIAID, NIH and MedImmune Inc. (provided FluMist®)

## Background

- Despite influenza vaccination of over 65% elderly persons in the U. S., influenza-related hospitalizations are increasing and result in 36,000 cardio-respiratory or 50,000 all-cause deaths each year1, 2
- New strategies to control influenza are needed
- Schoolchildren have the highest attack rates of influenza infections and are key to its spread
- Annual influenza immunization of healthy school-age children with LAIV, administered intranasally, is a potential complementary strategy to control epidemic influenza

- 1Thompson, et al. JAMA. 2003;289(2):179-186.
- 2Thompson, et al. JAMA. 2004;292(11):1333-40.

## Control of Epidemic Influenza:Background

- Community-based immunization of 20-25% of children, 18 months to 18 years of age, with the investigational LAIV, significantly reduced medically attended acute respiratory illnesses (MAARI) in adults over 35 years of age by 8-18%3 during 3 consecutive epidemics from 1998 to 2001

- 3Piedra, et al. Vaccine. 2005;23(13):1540-8.

## Control of Epidemic Influenza: Study Design 

- An open-label, non-randomized, community-based trial of annual influenza immunization of school-age children to effect herd immunity

## Control of Epidemic Influenza: Objectives

- The primary objective is to determine the proportion of vaccinated school-age children needed to effect herd immunity (indirect effectiveness) against influenza
- The secondary objectives are to assess the direct effectiveness and safety of LAIV

- For Direct Effectiveness of LAIV in 2003-2004, see Piedra, et al.
- Abstract # 726

## Methods

- Healthy school-age children from the intervention area were offered LAIV and those with high-risk conditions, the trivalent inactivated influenza vaccine (TIV), from October 10th to December 31st, 2003
-  Both vaccines contained A/Panama/2007/99 (H3N2)
- The 2003-2004 variant influenza A/Fujian/411/2002 (H3N2) outbreak occurred unusually early in Texas
- Scott & White Health Plan (SWHP) database was searched for medically attended acute respiratory illnesses (MAARI) by ICD-9-CM codes, and age-specific denominators for the intervention and comparison sites
- Relative risk and 95% confidence intervals for MAARI for _all_ SWHP  members from the intervention and comparison sites were determined

## Demographics

|  | Intervention  | Comparison |
| --- | --- | --- |
| *Total Population | 80,843 | 268,975 |
| SWHP Population | 54,371 | 70,825 |
| *Age 5-19 y  | 18,188 (22.5%) | 65,826 (24.5%) |
| SWHP: 5-18 y | 10,474 (19.3%) | 14,679 (20.7%) |
| 5-18 y: TIV +
LAIV | 1992 +
6569 | 1851 +
Not offered |

- *U.S. Census 2000, intervention and comparison area by cities

## Virus Surveillance and Enrollment

- *October 12 to December 20, 2003 (CDC weeks 42-51)

***Influenza A/Fujian/411/2002 (H3N2)**** ****Epidemic Period**

- Almost 60% of enrollees were vaccinated by end of week 46

## Relative Risk of MAARI by Age Groups

**0.95***

**0.87***

**0.99**

**1.02**

**1.08**

**1.02**

**0.84***

**0.90**

**0.88**

**0.81***

- Of 6,569 children who received LAIV, 66% were 5-11 years old

## LAIV Overall Effectiveness =(1-RR of MAARI) %

| Age Group | LAIV Overall
Effectiveness % | 95% Confidence Interval |
| --- | --- | --- |
| < 5 years | 5% | 1, 8* |
| 5-11 years | 13% | 6, 19* |
| 12-34 years | -5% | -11, 1 |
| ≥ 35 years | 10% | 5, 14* |
| Total | 10% | 7, 12* |

- Number of healthcare encounters prevented – for SWHP was ~800 and that for intervention communities was ~1200
- *statistically significant

## MAARI Rate/1000 for Children <12 y

**MAARI Rate/1000 for Children <12 y**

- Enrollment

- Surveillance

## Conclusion

- Community-based LAIV immunization of school-age children during an influenza outbreak provided herd immunity against a drifted variant influenza A by reducing its spread, possibly from early non-specific and late specific immunity

## Influenza Virus Surveillance in Children 5 to 18 Years of Age in Temple – 2003-2004 Season

| Group | 5-9 years
Positive/ Total (%) | 10-18 years
Positive/ Total (%) | 5-18 years
Positive/ Total (%) | Efficacy
(1-Vac/Never Vac)100 |
| --- | --- | --- | --- | --- |
| Never vaccinated | 39/82 (47.6%) | 88/149 (59.1%) | 127/231*† (55.0%) | reference |
| CAIV-T in 2003 | 8/25 (32.0%) | 11/30 (36.7%) | 19/55* (34.5%) | 37.3% |
| CAIV-T in 1998-02 | 10/30 (33.3%) | 24/49 (49.0%) | 34/79† (43.0%) | 21.8% |
| TIV in 2003 | 3/11 (27.3%) | 11/13 (84.6%) | 14/24 (58.3%) | 0% |

- Influenza outbreak: Oct 12, 2003 to Dec 20, 2003
- Chi-square test; *p = 0.006; †p = 0.067
- Culture data restricted by date (Oct 12-Dec 20), site (intervention site) and surveillance cultures

## Influenza Culture Positive Medically Attended Acute Respiratory Illness in Children 5-18 Years Old Vaccinated Prior to or During the Influenza Outbreak

|  |  | 
Culture positive/Total |  |  |  |  |
| --- | --- | --- | --- | --- | --- | --- |
| Site | Vaccine | Wk1
(0-6d) | Wk2
(7-13d) | Wk3
(14-20d) | Wk4
(21-27d) | >Wk4
(28+d) |
| Temple | CAIV-T | 5/14 (35.7%) | 5/11 (45.5%) | 2/6 (33.3%) | 2/8 (25%) | 5/16 (31.3%) |
|  | IIV-T | 6/8 (75%) | 1/1 (100%) | 0 | 0 | 7/15 (46.7%) |

- Culture data restricted by date (Oct 12-Dec 20, 2003), site (intervention site) and surveillance cultures

## Table 4. Relative risk of MAARI 0 to 14 and 15 to 42 days after LAIV-T.

|  |  | Pre-vaccination rate (reference) per 10,000 child-days | Relative Risk - post-vaccination/
pre-vaccination period (95%CI) |  |
| --- | --- | --- | --- | --- |
| Vaccine Year | Age groups |  | 0-14 days post-vaccination | 15-42 days post-vaccination |
| 1
1998-99 | 18 mo - 4 yrs | 68.5 | 0.85 (0.61-1.19) | 0.86 (0.62-1.16) |
|  | 5 – 9 yrs | 35.5 | 0.74 (0.50-1.09) | 0.97 (0.71-1.33) |
|  | 10 – 18 yrs | 21.4 | 1.04 (0.64-1.67) | 1.10 (0.72-1.68) |
| 2
1999-00 | 18 mo - 4 yrs | 94.2 | 0.72 (0.54-0.96) | 1.03 (0.80-1.33) |
|  | 5 – 9 yrs | 45.9 | 1.18 (0.89-1.58) | 1.09 (0.81-1.45) |
|  | 10 – 18 yrs | 25.5 | 0.88 (0.59-1.33) | 1.20 (0.84-1.70) |
| 3
2000-01 | 18 mo - 4 yrs | 104.6 | 0.72 (0.53-0.99) | 1.02 (0.72-1.44) |
|  | 5 – 9 yrs | 54.2 | 0.73 (0.52-1.02) | 0.71 (0.49-1.05) |
|  | 10 – 18 yrs | 29.3 | 0.73 (0.47-1.13) | 0.97 (0.59-1.59) |
| 4
2001-02 | 18 mo - 4 yrs | 69.4 | 0.82 (0.55-1.24) | 0.70 (0.45-1.09) |
|  | 5 – 9 yrs | 50.1 | 0.62 (0.40-0.98) | 0.82 (0.53-1.27) |
|  | 10 – 18 yrs | 15.6 | 1.22 (0.67-2.24) | 1.26 (0.67-2.37) |

**Table 4. Relative risk of MAARI 0 to 14 and 15 to 42 days after LAIV-T.**

## Summary

-   In 2003 – 2004, the delivery of influenza vaccine was coincident with occurrence of the epidemic caused by A/ Fujian (H3N2), a new variant significantly different from the vaccine virus.
- Virtually immediate protection provided by LAIV-T resulted in 10% reduction in MAARI at the intervention site; no protection could be attributed to inactivated vaccine.
- The reduction of MAARI at the intervention site was most pronounced in the early stage of the epidemic when large numbers of children received LAIV.
- This and previous safety data showing decreased MAARI 0-14 days after LAIV supports the hypothesis of non-specific (innate) protection against viral infection.

## Acknowledgement*

**Baylor CM****	**Don Wilson	Bob Fader	**Emory U**
- Pedro Piedra	Robin Cameron	Felicia Bagwell	Ira Longini
- W Paul Glezen	Carolyn Connally	Mark Riggs	Betz Halloran
- Claudia Kozinetz	Art Mow	N Zimmerman	**U of Texas**
- Kirti Patel	Matthew Watts	Pat Kirkpatrick	Scott Lilibridge
- Terri Bosshard	Steven Slater	Scott Clark	**MedImmune **
- Sneha Thaker	Chris Morgan	Wendy White	Jeffrey Stoddard
- Sheldon Kaplan	Jeff Wilson	Rinska Flores	Caroleen Becker
**Scott & White****	**Alice Linder	Sonia Holleman	**NIH**
- Gayla Herschler	Olivia Ametane	**TX Dept Health****	**Linda Lambert
- Charles Fewlass	Pat Smith	Peggy Wright	Sonnie Kim
- Hope Gonzales	Debbie Miller	Neil Pascoe
**Tem-Bel Health &Wellness Coalition**

***Communities of Temple-Belton and surrounding area**