maria rios, ph.d. cber/fda blood products advisory committee may 1st, 2008 2007 wnv epidemiology...
TRANSCRIPT
Maria Rios, Ph.D.CBER/FDA
Blood Products Advisory Committee May 1st, 2008
2007 WNV Epidemiology &
FDA’s Recommendations on the Use of NAT to Reduce the Risk of Transmission of WNV in
Whole Blood and Blood Components for Transfusion and Human Cells, Tissues, and
Cellular and Tissue-Based Products (HCT/Ps)
Outline
Update on the 2007 season Human cases Animal cases including sentinel chickens Mosquito pools Geographical distribution
Draft Guidance on Blood Donor Screening for Infection with WNV Screening test platform
MP-NAT ID-NAT
Additional Testing Donor Counseling
WNV Update for 2007
47 states, DC & PR43 states
USGS and/or State Dept report as WNV positive: 3,628 animal cases8,625 mosquito pools
CDC: 3,623 human cases:1,213 (33%) WNV ND2,347 (65%) WNF (milder) 63 (2%) unspecified
with a total of 124 deaths
2007
Activity in 47 states, DC & PR
Human cases in 43 states
WNV in the U.S. Human cases from 1999 to 2007
64
72
9
284 264
100119 177 124
1,294 1,459 1,2131,1422,8662,942
1959
9,862
2,539 3,000 4,269 3,6234,156
66
2162
9,600
2,8508,850
181,950218,850194,100171,300429,900
441,300
428,189515,027456,782403,126
3,1509,300 9,900
1,038,526 1,011,698
1.0E+00
1.0E+01
1.0E+02
1.0E+03
1.0E+04
1.0E+05
1.0E+06
1.0E+07
1999 2000 2001 2002 2003 2004 2005 2006 2007Fatality (n = 1,086) WNV ND (n = 11,058)
Cases of Disease (27,598) Estimated infections (1:150 ND, n = 1.7M)
Estimated infections (1:353 ND, n = 3.9M)
WNV Activity in the US
April 20084 Human cases TN (1 in Jan), AZ (1 Mar),
MS (2 Mar, Apr)
1 horse (AL)
12 Dead Birds CA (11), SC (1)
10 Mosquito Pools CA (9), FL (1)
4 Sentinel Chickens FL (2), CA (2)
WNV infection is Notifiable to the CDC
Endemic (peak spring/fall)
Since 2002 yearly:
>1,000 WNV ND
≥ 100 fatalities
Since 2005, onset of WNV clinical cases have been reported to the CDC from Jan to Dec
WNV Blood Screening in the U.S.
From 2003 to 2007 resulted in: Interdiction of ~2,600 WNV NAT-reactive units Prevention of ~2,600 to 7,800 potential transmissions
by transfusion
*All seronegative for WNV; + Lack of f/up, sample, recipient loss‡ Negative in MP-NAT and positive on ID-NAT (low viremia)
Transmission by Transfusion Year 2002 2003 2004 2005 2006 2007
NAT-Reactive Units N/A >1,000 224 417 441 511
TT Confirmed* (n=32) 23 6 ‡ 1 ‡ 0 2 ‡ 0
TT Inconclusive+ (n= 26) 19 6 1 0 0 0
Current Testing AlgorithmTest individually each specimen
included in the pool
If suitable:Released for transfusion
MP-NAT
NAT NR
NAT R
Unit (s) discard; Donor deferred for 120 days
Additional tests performed for counseling purposes
ID-NAT NR
ID-NAT R
Repeat NAT using same or alternate NAT assay
of ≥ sensitivity
Ab to WNVNote: Ab cross-reactivity among Flaviviruses
PPV 98% Sensitivity 98%
Algorithm for Additional Testing of Index Donation Specimen Prior to Donor Counseling
ID-NAT Reactive
Repeat NAT using same or alternate NAT assay of
≥ sensitivity
Ab to WNV
Rep ID-NAT R
Positive
Present
PositiveRep ID-NAT NR
Absent
False Positive or TN
2% TP on Follow up
≤ 10% of IRRep NAT NR
TP on Ab
Issues Regarding Testing
2003: 6 cases of TT-WNV after MP-NAT
MP-NAT detects 75% of WNV infected units (25% undetected)
2004: ID-NAT used in high WNV activity regions
ID-NAT implementation criteria: 1 in 1000 donations reactive or 2 MP-NAT positives in a week, whichever comes first
Since selective ID-NAT: Three (3) confirmed cases of WNV transmission by transfusion (1 in 2004 and 2 in 2006)
Issues Regarding Testing
In April 2007, the following considerations were presented to the BPAC
Uniform criteria to initiate ID-NAT is desirable
Fully automated NAT system licensed
Paucity of data to define uniform criteria
AABB voluntary recommendation: Bulletin #07-02
whether blood establishments should define and validate criteria to trigger ID-NAT and to revert back to MP-NAT
2007 ARC studies on suitability of ID-NAT implementation criteria (SL Stramer, 2008)
Results showed that ID-NAT was required to detect:
148/540 (27%) in 2003-2004
44/154 (29%) in 2005
76/212 (36%) in 2006 (in some cases early implementation based on 2 ID-PVD)
65/147 (44%) 2007 ARC evaluated criteria for ID-NAT implementation
ID-NAT Detected 42 Confirmed WNV Positive Donations in Validation Studies (SL Stramer, 2008)
Trigger criteria 1 PVD** 2 PVD 2 PVD & 1:1000
Yield
Incremental Yield
42* 31 5
11 26
37
**12 /42 (29%) were IgG only
20Yield minus IgG (FP?)
Incremental Yield 10 15
25
30
New data show that the previous criteria for ID-NAT implementation are inadequate
6.2-fold increase
8.4-fold increase
4-fold increase
6-fold increase
*Presumed viremic donor defined as ID-NAT with S/CO ≥ 17 or repeat reactive ID-NAT
5
(100%) (74%) (12%)
(88%)
(100%) (18%)
(83%)
(67%)
Draft WNV NAT Guidance for Industry
Draft Guidance published on April 28, 2008 for comment purposes only
90-day comment period closing in July 27, 2008
Recommendations on Testing Screen for WNV should be performed year-round
using a licensed NAT on donor samples of whole blood and blood components intended for transfusion.
Either MP-NAT or ID-NAT may be used for WNV screening.
ID-NAT should replace MP-NAT during high WNV activity in your region (using a previously defined geographic area).
Screening Algorithm for Blood Donations
ID-NAT reactive unit (s)
If suitable, release unit for transfusion
If suitable, release unit(s) for transfusion
Using a licensed MP-NAT for WNV
Using a licensed ID-NAT for WNV
ID-NAT non-
reactive
MP-NAT non-reactive MP-NAT reactive
ID-NAT non-reactive
unit (s)Test each specimen in the pool by ID-NAT
Discard unit (s).Defer donor (s) for 120 days.Retrieve in-date products from prior collections dating back 120 days.
Initiate WNV ID-NAT for that region
Algorithm for ID-NAT Implementation
ONE ID-NAT reactive unit
MP-NAT reactive Test each specimen in the pool by ID-NAT
Discard unit (s); Defer donor (s); Retrieve in-date
products
Initiate ID-NAT for all collections from that
region in 24 hours
If >24 hours of collection: consider performing retrospective ID-NAT testing of retention samples from collections within that time period
If blood establishments wish to revert back to MP-NAT, they may do so when the high WNV activity in the defined geographic area has subsided (e.g., minimum of 7 days has passed without a single WNV ID-NAT reactive donation)
* If NAT for all JE viruses used, we encourage WNV discriminatory prior to counseling ª Cross-reactivity among different Flaviviruses.
ID-NAT reactive unit (s)
Perform additional testing on index donation specimen as follows:1. Repeat ID-NAT using the same assay or an alternate NAT* of ≥ sensitivity
2. Test for WNV-antibodies (WNV-Ab) using a cleared Ab assay
ID-NAT reactive & WNV-Ab either
Pos or Neg
ID-NAT non-reactive &
WNV-Ab Positiveª
ID-NAT non-reactive & WNV-Ab Negative
Notify of deferral & counsel the donor as testing Positive
for WNV infection
Notify of deferral & counsel the donor as inconclusive for WNV infection.Encourage donor return after 30 days for follow-up testing by ID-NAT and WNV-Ab.
Additional Testing Algorithm
Recommendations Regarding Labeling
Container label and instruction circular to reflect results of WNV NAT, consistent with labeling for other infectious disease markers
“A Licensed Nucleic Acid Test (NAT) for West Nile Virus (WNV) RNA has been performed and found to be non-reactive.”
WNV reactive unit not to be shipped or used except as provided in FDA approved programs and/or research or autologous use only, and such units be labeled with appropriate warnings