P1581 The relative importance of respiratory viruses in - Grace

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The relative importance of respiratory viruses in lower respiratory tract infections in primary care. [P1581]


F. Coenjaerts
1
, C. Lammens
2
, M.
Viveen

1
, L. Tan
1
, K. Loens
2
, H. Goossens
2

, P. Zuithoff
3
, M. Ieven
2
, A. van Loon
1
, and E. Claas
4

on behalf of the GRACE study team


1

Univ. Med. Centre Utrecht


Dept. of Med. Microbiology, The Netherlands;
2

University of Antwerp, Belgium;
3

UMC Utrecht


Julius
Center
;
4

UMC Leiden, the Neth.

Objectives
:

The

microbial

etiology

and

especially

the

role

of

viruses

in

adult

lower

respiratory

tract

infections

(LRTI)

in

the

community

is

not

well

known
.

We

therefore

investigated

the

viral

etiology

in

LRTI

at

the

GP’s

office

in

the

European

GRACE

primary

care

network

(PCN)

using

sensitive

real
-
time

PCR

(RT
-
PCR)
.


Patients
:

From

October

2007

through

May

2010
,

a

total

of

3
,
018

adult

patients

(V
1
)

with

LRTI

in

the

community

were

enrolled

in

a

prospective

study

in

14

PCNs

in

12

European

countries

(Figure

1
)
.

Samples
:

Nasopharyngeal

flocked

swabs

(COPAN)

were

collected

and

analyzed

for

the

presence

of

influenzavirus

(INF)

A/B,

respiratory

syncytial

virus

(RSV),

parainfluenzavirus

(PIV)

1
-
4
,

human

rhinoviruses

(HRV),

human

metapneumovirus

(
hMPV
),

Bocavirus

(Boca),

coronaviruses

(COR)

OC
43
,

NL
63
,

229
E,

adenovirus

(ADE),

as

well

as

the

novel

polyomaviruses

KI

and

WU
.

V
0

samples

(
1185
)

were

taken

from

age
-
,

sex
-
,

and

geographically
-
matched

controls
;

V
2

samples

(
2544
)

were

collected

from

the

same

patients



4

weeks

after

V
1
.

Here,

we

present

primary

etiological

data

and

report

on

the

relative

importance

of

quantitative

measurements

(Ct

values),

as

well

as

the

aetiology

of

double

infections
.


Analysis
:

Specimens

were

transported

to

the

central

lab

in

Antwerp

for

nucleic

acid

extraction

by

the

NucliSens

EasyMAG

(
bioMerieux
)
;

isolates

were

analyzed

by

RT
-
PCR

either

directly

(DNA

viruses)

or

after

cDNA

synthesis

by

using

a

Multiscribe

reverse

transcriptase

kit

together

with

random

hexamers

(Applied

Biosystems
)
.

Viral

loads

were

determined

by

the

number

of

amplification

cycles

needed

for

a

positive

TaqMan

realtime

PCR

test

(cycle

treshold
,

CT)
.

Samples

were

counted

positive

for

CT<
40
.

INTRODUCTION

MATERIALS & METHODS

CONCLUSIONS

Presentation

rates

of

respiratory

pathogens

in

V
1

samples

significantly

exceed

those

found

in

controls

(V
0
)

and

follow

up

(V
2
)

samples
;

this

does

not

hold

true

for

Boca
-
,

WU

and

KI

virus,

which

might

question

them

as

true

respiratory

pathogens
.

The

availability

of

quantitative

viral

load

data

is

unlikely

to

affect

individual

patient

management
.

Double

infections

do

not

affect

patient

presentation

rates
;

even

in

control

patients

follow

up

visits

double

infections

do

occur
.

Table II

N

Mean

Statistic

Statistic

Std. Error

Adeno_V1

38

35,74

1,05

Adeno_V2

42

37,81

0,59

Adeno_V0

17

37,41

0,28

BOCA_V1

12

35,38

1,77

BOCA_V2

11

38,07

1,08

BOCA_V0

16

37,64

0,87

COR_V1

205

28,09

0,46

COR_V2*

70

31,85

0,80

COR_V0*

20

32,42

1,35

COR229E_V1

42

27,41

0,78

COR229E_V2

15

29,50

1,57

COR229E_V0

5

30,29

2,35

CORNL63_V1

35

26,93

0,86

CORNL63_V2

13

29,51

1,99

CORNL63_V0

4

29,91

1,59

COROC43_V1

88

25,73

,64

COROC43_V2*

22

29,74

1,15

COROC43_V0

4

27,41

3,24

hMPV_V1

124

30,04

0,37

hMPV_V2

7

33,14

1,56

hMPV_V0

3

32,38

1,32

INF_V1

297

29,53

0,35

INF_V2

10

29,55

1,60

INF_V0

4

28,90

3,04

INFA_V1

133

28,99

0,43

INFA_V2

5

28,17

2,90

INFA_V0

3

26,08

1,61

INFB_V1

98

26,86

0,51

INFB_V2

3

31,03

2,70

INFB_V0

0

-

-

KI_V1

27

36,46

0,60

KI_V2

28

35,90

,89

KI_V0

15

35,94

1,41

PIV1_V1*

14

29,98

1,156

PIV1_V2

3

37,48

,66

PIV1_V0

2

32,87

5,87

PIV2_V1

11

28,65

1,61

PIV2_V2

2

32,50

4,50

PIV2_V0

1

36,91

-

PIV3_V1*

23

28,83

1,25

PIV3_V2

7

36,09

1,63

PIV3_V0

2

36,73

2,82

PIV4_V1

22

30,42

0,86

PIV4_V2

0

-

-

PIV4_Vo

1

31,07

-

Rhino_V1

572

30,18

0,21

Rhino_V2*

111

31,46

0,50

Rhino_V0*

54

32,13

0,53

RSV_V1

143

29,130

0,52

RSV_V2

13

30,53

1,57

RSV_V0*

7

35,77

1,69

WU_V1

44

37,81

0,53

WU_V2

54

38,75

0,31

WU_V0

20

38,96

0,35

Table I

V0

% pos.

V1

% pos.

V2

% pos.

RSV

0,5*

3,6

0,4*

INF

0,2*

7,4

0,3*

INFA

0,1*

3,7

0,1*

INFB

0*

2,9

0*

COR

1,5*

5,4

1,4*

229E

0,3*

1,3

0,4*

NL63

0,2*

1,0

0,3*

OC43

0,4*

2,6

0,6*

WU

0,2

0,2

0,1

KI

0,2

0,2

0,2

PIV1

0,1*

0,4

0*

PIV2

0,1*

0,3

0*

PIV3

0,2*

0,6

0,1*

PIV4

0,1*

0,6

0*

HRV

3,6*

15,6

2,7*

hMPV

0,3*

3,7

0,2*

ADE

0,2*

0,4

0,1*

BOCA

0,03

0,1

0,04

Table III

V2

COR

229E

COR

NL63

COR

OC43

WU

KI

HRV

ADE

V1

INFA

0,063

KI

0,017

PIV3

0,03

0,004

PIV4

0,093

HRV

0,07

hMPV

0,09

0,08

ADE

0,009

RESULTS

This

project

is

supported

through

Priority

1

(Life

Sciences,

Genomics

and

Biotechnology

for

Health)

of

European

Union's

FP
6
,

Contract

number
:

LSHM
-
CT
-
2005
-
518226


Correspondence:


f.e.j.coenjaerts@umcutrecht.nl

www.grace
-
lrti.org


TABLE I.

Most
viruses were present at significantly higher
rates in V1 samples when compared to V0 and V2. Boca, WU and KI
presentation rates however, did not differ between V0, V1 and V2. This
finding, added to the extremely low number of samples positive for these
viruses raises doubt to their qualification as respiratory
pathogens
.


TABLE II.

DNA
viruses presented with significantly lower
viral loads (average CT 37) when compared to RNA viruses (average CT
30; CT 27 for INF B and the various COR’s).
Significant differences
between
patients, versus controls
and follow up
samples,
were detected for
RSV, COR (as a group), COR OC43, PIV1, PIV3 and HRV
.


TABLE III.

PIV


in particular PIV3 and PIV4
-

positive
patients were most prone to a positive follow up. For
PIV3,
significant
associations were detected with
Cor

229E (P value = 0.03) and
Cor

OC43
(P = 0.004) as
secundary

pathogens. Also INF A, PIV4, HRV and
hMPV

are frequently followed by
secundary

viral infections. All other
combinations (empty cells in Table III,
as well as
non
-
depicted
combinations) did not shown any association. KI and ADE are significantly
the most
persistent (found in the same patient within a 4
-
week interval)
viruses (P = 0.017 and 0.009, resp.).


Double infections (not shown).

Despite the fact that DNA
viruses are detected substantially in respiratory specimen, their overall
impact is overestimated since these viruses are largely present in
V0
samples,
V1
-
double infections, or
V2 samples.
WU (26.7%) and KI
(21.8%) were most frequently involved in double infections. Of all positive
V1
patients,
6.4% was double
-
infected, in V0 and V2 double infections
reached 7.3 and 6.5%, resp.

* Differing significantly from V1

Positive follow up (V2; columns) after specific V1 pathogens (rows); depicted P values

indicating strong trends (P values <0.10) or significant associations (P values < 0.05).

Figure 1. Primary Care Networks in GRACE.