The suitability of case definition for severe acute respiratory infection in recognising influenza and respiratory syncytial virus (RSV) infection in hospitalised Finnish elderly

1. Results
Of 342 patients with samples available, 38 were excluded because the time
between symptom onset and swabbing was unknown or >7 days (6 influenza
cases, 3 RSV cases). Of the remaining 304 patients, 25 did not fulfil SARI criteria,
mainly because no respiratory symptoms/signs could be recognised; none of
them had influenza or RSV infection.
Of the samples obtained in 2015/16, influenza virus and RSV was detected
from 18% and 13%, respectively, while in 2016/17 the proportions were 23%
and 1%. Proportions of samples with any other virus(es) were similar during
the two seasons. Table 2 shows the occurrence of symptoms/sign according to
the virus detected in 279 respiratory samples.
1Fever, >37C⁰, measured, even anamnestic; feverishness, feeling feverish but temperature measured
under antipyretic medication or not at all. The occurrence of each symptom/sign was compared
between pure influenza cases and all other cases as one group with χ2 statistics. The same comparison
was performed between pure RSV infection cases and all other cases as one group; 2p<0.05, 3p<0.005.
Influenza patients tended to have all the symptoms/signs slightly more often
than all patients without influenza as one group, especially fever/feverishness,
cough and sore throat (Table 2). The only clear difference between influenza
and RSV infection patients was the lower occurrence of malaise in the latter.
Fever/feverishness was the most sensitive sign and sore throat was the most
specific symptom/sign for detecting both influenza and RSV infection (Table 3).
Most symptoms/signs had equal PPV in predicting influenza, but respiratory
symptoms/signs tended to predict RSV infection better than systemic ones. Of
influenza and RSV infections identified in the study, 70% and 25%, respectively,
were recognised in the hospital by samples obtained for clinical purposes.
The suitability of case definition for severe acute
respiratory infection in recognising influenza and
respiratory syncytial virus (RSV) infection in hospitalised
Finnish elderly
Ritva K Syrjänen1, Niina Ikonen2, Anu Haveri2 and Hanna Nohynek3
1Impact Assessment Unit, 2 Expert Microbiology Unit and3 Infectious Disease Control and Vaccinations Unit, National
Institute for Health and Welfare (THL), Finland
ritva.syrjanen@thl.fi
Introduction
Respiratory syncytial virus (RSV) causes severe respiratory infections in
young children. Recently, it has also been recognised as an important
cause of hospitalisation in the elderly(1). RSV vaccines are under
development and evaluation of the disease burden is needed to plan
strategies to prevent severe infections caused by RSV. We evaluated the
occurrence of different symptoms/signs belonging to case definition for
severe acute respiratory infection (SARI) in elderly patients hospitalised
with influenza and RSV infection.
Methods
A test-negative case-control study to measure influenza vaccine
effectiveness against SARI caused by influenza virus among persons aged
>65 years was conducted during seasons 2015/16 and 2016/17 in
Tampere, as part of I-MOVE+ project(2). All patients hospitalised to
participating wards (infectious diseases, pulmonary diseases,
internal/general medicine or geriatric wards) with pre-defined diagnoses
(Table 1) were recognised from the hospital register every working day
and screened. SARI case definition included at least one systemic (fever,
feverishness, malaise, headache, myalgia, deterioration of general
condition) and at least one respiratory (cough, sore throat, shortness of
breath) symptom/sign. In the Finnish study, also patients with suspicion of
influenza, lower respiratory infection or systemic infection with unknown
cause were initially included. Respiratory specimens were obtained <7
days after symptom onset and analysed in THL by multiplex real-time RT-
PCR to detect influenza-, RS-, adeno-, corona- and rhinovirus. The
sensitivity, specificity and positive and negative predictive values (PPV,
NPV) of different symptoms/signs in predicting influenza and RSV infection
were calculated as conditional probabilities from 2 x 2 tables.
Table 1. Screening diagnoses
References
1. Falsey AR, McElhaney JE, Beran J, et al. Respiratory syncytial virus and other respiratory viral infections in older adults with moderate to severe influenza-like illness. J Infect Dis
2014; 209:1873–1881. 2.I-MOVE+ project, http://www.i-moveplus.eu/
Table 2. Symptoms/signs according to the virus finding
Table 3. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for symptoms/signs in detecting influenza and RSV
Influenza
only
(19%)
RSV
only
(8%)
Other
virus only
(10%)
Multiple
viruses
(2%)
No
viruses
(62%)
Fever or
feverishness1
100
(50/50)2
95
(19/20)
100
(26/26)
60
(3/5)
88
(151/172)
Headache
34
(16/47)
16
(3/19)
24
(6/25)
0
(0/5)
26
(41/159)
Myalgia
32
(15/47)
26
(5/19)
24
(6/25)
0
(0/5)
25
(40/160)
Malaise
70
(32/46)
37
(7/19)2
52
(13/25)
40
(2/5)
59
(96/162)
Deterioration of
general condition
96
(49/51)
81
(17/21)
88
(23/26)
60
(3/5)
91
(152/167)
Cough
92
(45/49)3
81
(17/21)
88
(23/26)
100
(5/5)
68
(114/168)
Shortness of breath
90
(46/51)
86
(18/21)
67
(18/27)
60
(3/5)
88
(150/171)
Sore throat
38
(18/47)3
45
9/20)2
20
(5/25)
20
(1/5)
15
(25/162)
Category ICD-10
Diagnoses referring to
influenza like illness
R05, R06,R07.0,R13, R50.9, R51,
M79.1,
R53.1,R53.81,R53.83
Respiratory diagnoses
J43.9, J44.9, J45, R06.0, R06.9, R06.02,
R06.00, R06.09, R06.03, 06.89
Infections
J09-J18, J20-J22, J00-J06, B34.9, A49.9,
J40, J41
Inflammation R65.10, R65.11
Cardiovascular diagnosis I20-23, I24-25, I50, I51
Deterioration of general
condition
R53.1, R53.81, R53.83, R63.0, R63.3,
R63.4, R63.8, R41.0, R42, F05, R40.2
R40.4, R40.0, R40.1, R56.00, R56.01
Influenza (N=56)1 RSV (N=24)1
Sensitivity Specificity PPV NPV Sensitivity Specificity PPV NPV
Fever or feverishness2 98 (96-100) 11 (7-14) 21 (16-23) 96 (93-98) 87 (83-91) 8 (5-12) 8 (5-11) 88 (84-91)
Headache 31 (26-37) 75 (70-81) 24 (19-29) 81 (77-86) 14 (9-18) 73 (68-78) 5 (2-7) 90 (86-94)
Myalgia 29 (24-35) 75 (70-80) 23 (18-28) 81 (76-86) 23 (18-28) 74 (69-79) 8 (4-11) 91 (88-95)
Malaise 66 (60-72) 43 (37-50) 22 (17-27) 84 (80-89) 36 (31-42) 40 (34-46) 5 (3-8) 87 (83-91)
Deterioration of general
condition 93 (90-96) 10 (7-14) 21 (16-26) 85 (80-89) 79 (74-84) 9 (5-12) 8 (5-11) 81 (76-85)
Cough 92 (89-96) 28 (23-34) 24 (19-29) 94 (91-97) 83 (79-88) 25 (20-30) 10 (6-13) 94 (91-97)
Shortness of breath 87 (83-91) 15 (11-19) 20 (16-25) 83 (78-87) 83 (79-88) 14 (10-18) 9 (5-12) 90 (86-94)
Sore throat 35 (29-41) 81 (76-86) 31 (25-37) 84 (79-88) 43 (37-50) 80 (75-85) 17 (13-22) 94 (90-97)
1In two samples, both influenza virus and RSV were detected. 2Fever, >37C⁰, measured, even anamnestic; feverishness, feeling feverish but temperature measured under antipyretic medication or not at all.
The numbers in parentheses, 95% confidence intervals
The I-MOVE+ project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634446
Conclusions
RSV infection is common in hospitalised elderly during extensive RSV seasons, but probably it often remains undetected without extra sampling. It seems
that concurrent surveillance of influenza and RSV infections is feasible. However, using SARI criteria tailored to detect influenza only may not be optimal for
detecting RSV, since the sensitivity and specificity of all symptoms/signs tended to remain inferior for detecting RSV. A study with swabbing all patients with
careful symptom/sign survey would disclose whether adding new criteria, e.g. using an algorithm to the initial case definition of SARI would be needed to
improve the design for detecting both viruses in a single study.