# Presentation: 941596

## DoD Global, Laboratory-BasedInfluenza Surveillance Program 

**Sequence Analysis **
**and **
**Vaccine Effectiveness Overview**

**Maj Thomas Gibbons**, PhD, Virologist
**Chris Myers**, PhD, Molecular Biologist
**Angela Owens**, MPH, Epidemiologist
**Jason Garner**, MS, Molecular Biologist
**Anthony Hawksworth**, Epidemiologist

## Background

-   Seasonal Influenza
- Sentinel site surveillance
- - DoD military sites worldwide
- - Countries collaborating with DoD overseas research sites

- Population-based surveillance
- DoD recruit training sites (8)
- Select Navy ships
- Border Infectious Disease Surveillance (BIDS)

## Background

-   **Collection Methods**
- - Patients must have Fever ≥ 100.5oF and cough or sore throat (for less than 72 hrs)
- - Specimen collection kits are provided to collect 6-10 specimens/week
- - Surveillance Questionnaire (vaccination, symptom, and travel history)
**  ****Laboratory Methods**
- 	-  Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
- Universal Influenza A and Influenza B
- -  Viral Culture
- 	Influenza A, Influenza B, Adenovirus, Parainfluenza,
- 	Respiratory Syncytial Virus (RSV), and Enterovirus
- 	- 100% of influenza isolates are subtyped and sequenced

## 2007-2008 Season (as of 19 Feb 08)

**2007-2008 Season **(as of 19 Feb 08)

**Notes:**
We’ve processed about 3,000 specimens to date: 22.6% were lab-confirmed influenza (84% influenza A; 16% influenza B).  

## Vaccine EffectivenessDescriptive Review – Preliminary Data

**Period of Review**
- 30 Sept 2007 –  09 Feb 2008 (non-recruits)
- 01 Aug 2007 – 09 Feb 2008 (recruits)
**Population**
- US military recruits (population-based surveillance)
- US Active Duty members (sentinel site surveillance)
- DoD beneficiaries (sentinel site surveillance)
**Outcome**
- Laboratory-confirmed influenza
- Reverse Transcriptase polymerase chain reaction (RT-PCR)
- Viral culture
**Covered by Vaccination**
- Vaccination date >14 days prior to clinic visit date
- Patients with vaccination date prior to August classified as unvaccinated

## Sentinel Site SurveillancePreliminary Data

- 2,570 specimens; 562 (21.9%) influenza isolates
- 36.1% (203 of 562) identified vaccination status
- 77.3% (157 of 203) identified as “covered by vaccine”
- 68.1% (n=107) LAIV; 30.0% (n=47), Injection, 1.9% (n=3) Not Specified

**Influenza Subtype**
-  A-type pending: 31.8% (n=50)
-  A/H1: 39.5% (n=62)
-  A/H3: 24.2% (n=38)
-  B-type pending: 4.5% (n=7)

## 205 lab-confirmed influenza A cases Aug 07 – Feb 08
59 (29%) A/H1
74 (36%) A/H3
72 (35%) type pending (weeks 4 and 5)

- 205 lab-confirmed influenza A cases Aug 07 – Feb 08
- 59 (29%) A/H1
- 74 (36%) A/H3
- 72 (35%) type pending (weeks 4 and 5)

## Vaccine effectiveness calculation

Only consider periods when all trainees on base are vaccinated
Trainees assumed “covered by vaccination” 14 days after arrival/receiving the vaccine
Proportion “unvaccinated” at each site estimated as those within their first 14 days of arrival
e.g., in 8-week training programs, 2/8 (25%) of the population was assumed to be “unvaccinated” at any given time
Previous estimates of 86-94% VE against lab-confirmed influenza using this method during past 4 seasons

2007-2008 Results from Basic Trainees

102 lab-confirmed cases (40 H1, 61 H3, 1 type pending) in this analyses
34 cases among vaccinated, rate = 2.9/10,000 trainee-weeks
68 cases among unvaccinated, rate = 18.6/10,000 trainee-weeks
VE = 85% (95% CI, 77-90)
Other assumptions (7 days for coverage; 10% less vaccination) resulted in VE estimates of 89% and 75%, respectively
VE by subtype
VE (H1) = 54% Mostly Clade 2b strains
VE (H3) = 92% Brisbane strain variants

- Only consider periods when all trainees on base are vaccinated
- Trainees assumed “covered by vaccination” 14 days after arrival/receiving the vaccine
- Proportion “unvaccinated” at each site estimated as those within their first 14 days of arrival
- e.g., in 8-week training programs, 2/8 (25%) of the population was assumed to be “unvaccinated” at any given time
- Previous estimates of 86-94% VE against lab-confirmed influenza using this method during past 4 seasons
**2007-2008 Results from Basic Trainees**
- 102 lab-confirmed cases (40 H1, 61 H3, 1 type pending) in this analyses
- 34 cases among vaccinated, rate = 2.9/10,000 trainee-weeks
- 68 cases among unvaccinated, rate = 18.6/10,000 trainee-weeks
**VE = 85%** (95% CI, 77-90)
- Other assumptions (7 days for coverage; 10% less vaccination) resulted in VE estimates of 89% and 75%, respectively
- VE by subtype
**VE (H1) = 54% Mostly Clade 2b strains**
- VE (H3) = 92% Brisbane strain variants

## Overall VE remains strong among basic trainees
On the low end of previous four years of VE estimates

Reduced effectiveness against Influenza A/H1 subtype

- On the low end of previous four years of VE estimates
- Reduced effectiveness against Influenza A/H1 subtype

- Population-Based Surveillance, 2007-2008

**Notes:**
H1’s might be lowering the VE

## Influenza B Field IsolatesHA1 HA Phylogenetic Analysis 

- 78.0% (39 0f 50) isolates collected in Nepal, Thailand, & the Philippines
-  66.7% (4 of 6) isolates collected in 2008 within US are of the Yamagata lineage
- 58.0% (29 of 50) isolates belong to B/Victoria lineage: 99.0-99.7 sequence identity

**Victoria Lineage**

**Yamagata Lineage**

- 2006-07 vaccine strain

- Current Reference Strain

**Population**: US Active Duty, DoD beneficiaries, and non-D0D personnel
**Timeframe**:  July 2007  to present
**Location**:  US, Africa, Antarctica, Asia, & South Pacific

## Influenza A (H1N1) Field IsolatesHA1 HA Phylogenetic Analysis 

- Influenza A (H1N1) Field Isolates**HA1 HA Phylogenetic Analysis**** **

- Clade 2

- 2006-07 vaccine strain

- 2007-08 vaccine strain

- Clade 1

**Population**: US Active Duty, DoD beneficiaries, and non-D0D personnel
**Timeframe**:  July 2007  to present
**Location**:  US, Africa, Middle East, Asia, & South Pacific

- 9.8% (5 of 51) isolates characterized as Clade 1 – all collected from Honduras
- Clade 2 isolates collected from US (Alaska, HI, SD, TX), Guam, Saipan, Philippines, South Korea, Nepal, Japan, Thailand, Qatar, Kenya
- Clade 2 subgroup highlighted by change at position 46

- S46N

- T90R

- T90K
- R149K
- E276K

- T90K

- Y101H
- R212K
- K144E
- T269N

- Y256F

## Influenza A (H1N1) Field Isolates continued

**Influenza A (H1N1) Field Isolates** *continued*

**Clade 2 isolates** collected from US (CA, IL, MO, SC, TX)
- Majority of isolates are **Clade 2B**

- 2006-07 vaccine strain

- 2007-08 vaccine strain

**Population**: US military recruits and Border
- Infectious Disease Surveillance (BIDS)
**Timeframe**:  July 2007  to present
**Location**:  US

**Notes:**
The large cluster of IL samples describes one outbreak lasting a few weeks and many are vax breakthrough
All MO isolates are vax breakthrough

## Influenza A (H3N2) Field IsolatesHA1 HA Phylogenetic Analysis

- Influenza A (H3N2) Field Isolates**HA1 HA Phylogenetic Analysis**

-  85.3% (58 of 68) of representative H3N2 isolates possess changes **G50E, D122N, K140I,  I223V**
-  H3N2 isolates collected in 2008 within the US possess additional changes: **L3F, K83N, L157S and K173N**
- 14 overseas and domestic H3N2 isolates collected in 2007 of the 2007-8 season antigenically characterized by CDC as A/Brisbane/10/2007-like via HAI assays

**Population**: US Active Duty, DoD beneficiaries, and non-D0D personnel in allied countries.
**Timeframe**:  July 2007  to present
**Location**:  US, Central America, Asia, Africa, & South Pacific

- G50E
- D122N
- K140
- II223V

- R142G

- L3F
- K83N
- L157S
- K173N

- current vaccine strain

- N144D

**Notes:**
Beginning in July through the earlier part of this year’s influenza season, the dominant subtype identified by AFIOH’s labs was H1 (presumed H1N1). In the early portion of January 2008, there appeared to be a shift in subtype activity as the vast majority of recently-collected isolates subtyped as H3 (presumed H3N2). This was confirmed by sequencing HA1 domain of HA. The majority of recent H3N2 isolates analyzed were collected here in the US, South Korea, and Kuwait. With the exception of ~10% of represented specimens, all H3 HA1 genes sequenced possessed changes at positions 50 (glycine to glutamic acid) and 140 (lysine to isoleucine). Select DoD isolates collected in Kenya, Thailand, and Philippines possessed changes at additional sites within the HA1 domain of HA, and have not been well characterized. Over 150 DoD sentinel isolates received by AFIOH have been passed on to CDC for further antigenic characterization. 

## Influenza A (H3N2) Field Isolates 

-  All sequenced isolates collected in 2008 within the US possess additional changes: **L3F, K83N, L157S and K173N**
-  All BIDS sequenced isolates have either N96K or E280K mutations

**Population**: US military recruits and BIDS
**Timeframe**:  July 07  to present
**Location**: US

- current vaccine strain

**Influenza A (H3N2) Field Isolates **
*continued*

**Notes:**
Phylogenectically Brisbane-like.  Isolates have been submitted to CDC for antigenetic characterization.

## Acknowledgements

**Global Emerging Infections Surveillance and Response System (GEIS)**
**Centers for Health Promotion and Preventive Medicine (CHPPM) / Army Medical Surveillance Activity (AMSA)**
**Air Force Clinical Informatics Branch**
**Centers for Disease Control and Prevention (CDC)**
**Landstuhl Regional Medical Center**
**Sentinel sites in the DoD Global Influenza Surveillance Program**

## Contact Information

**Air Force Institute for Operational Health**
- - Sentinel Site Surveillance
-             _[Influenza@brooks.af.mil](mailto:Influenza@brooks.af.mil)_
**Naval Health Research Center**
- - Population-Based Surveillance
-             _[NHRC-FRI@med.navy.mil](mailto:NHRC-FRI@med.navy.mil)_

## BACKUP SLIDES

## 2007-2008 Season (as of 19 Feb 08)

**Notes:**
We’ve processed about 3,000 specimens to date: 22.6% were lab-confirmed influenza (84% influenza A; 16% influenza B).  Average of 26% of the total specimens received are positive for influenza by culture.