Jpn. J. Infect. Dis., 55, 23‑26, 2002

Epidemiological Report

Evaluation of a Sentinel Surveillance System for Influenza,

1995‑2000, Kyoto City, Japan
Hayato Fujiil,3*, Hiroshi Takahashi2, Takaaki Ohyama2, Nobuhiko Okabe2,

Koichi Hashimoto3, wataruDoi4 and Yoshiaki Karouji5
1Field Epidemiology Training Program and2Infectious Disease Surveillance Cente7; National Institute ofInfectious Diseases,
Toyama 1‑23‑1, Shinjuku‑ku,乃b,0 162‑8640,

3communiO, Medicine Section and4Public Health Promotion Section, Health and Welfare Bureau,
Kamihonnoujimae‑cho 488, Teramachi Oike, Nakagyo‑ku, Kyoto 604‑8571 and5Division ofMicrobiology, Kyoto CiO, Institute ofHealth and Environmental Sciences,Higashitakada‑cho 1‑2, Mibu, Nakagyo‑ku, Kyoto 60418845, Japan(Received December 3, 2001. Accepted April 2, 2002)

SUMMARY: We compared a municipal sentinel surveillance system for influenza with the Microbial Isolation
Surveillance System (MISS) in Kyoto City, Japan. Sensitivity, specificity, and predictive value positive (PVP) ofthe Influenza Sentinel Surveillance System (ISSS) Compared to the MISS were calculated by influenza season
and by month. Sensitivity ranged from 80 to 97%, specificityranged from 55 to 77%, and PVP ranged from 29
to 52% by season (P < 0.001). On the other hand, sensitivityranged from 86 to lO0%, specificity ranged from 38
to 66%, and PVP ranged from 3 I to 50% by month (P < 0.001). Specificity was calculated as 93% in November.
The sensitivity of ISSS was found to be sufficient regardless of the magnitude of influenza activity, Specificity
varied by season, indicatlng the difficulty ofclinically diagnoslng Other resplratOry illnesses. The PVP remained

at less than 50% before and after the influenza seasons and it varied year by year. In general, the ISSS is a good
surveillance system for monitorlng influenza activlty.

The Influenza Sentinel Surveillance System (ISSS) is theINTROJ)UCT10N

sole national surveillance system for influenza in Japan; thisInfluenza is one of the most important infectious diseases
requiring suⅣeillance in industrialized countries (1). The

program is administered by the Ministry of Health, Labourand Welfare. In the National EpidemiologlCal Surveillance

reported number of influenza patients from sentinel sites infor Infectious Diseases (NESID) progr竺m, acPuracy of such

Japan was 757,837 (3 10･59/site) during FnApril 1994 throughdata is assured by 〜10% sampling f♭r vlrOloglCal tests at theMarch 1 995 season. A total of4, 1 35 patients died of influenza

municipal and prefectural levels (Fig. 1 ).

during the period from 1995 to 1999. Actual numbers may beo洗en report instead that the patient died of resultant clinical

In Kyoto City, evaluation of the ISSS has not previously
been performed. Influenza activityincreased remarkably during
the 1997/1998 and 1998/1999 seasons due to the A/H3N2states, in particular pneumonia. In order to avoid such under‑(Sydney) strain epidemics (6,7). Befわre and after these seasons,estimation of influenza in view of the disease burden, ai.e., the 1995/1996, 1996/1997, and 1999/2000 season, thehigher, because when a patient dies of influenza, physiciansmeasurement of influenza excess mortalitycan be useful (2,3)･

surveillance system found that influenza activlty remained

Approxlmately 29,000 (22.65 per 1 00,000) cases were reported

nomal or at a low level (8‑10)･ We evaluated the ISSS duringin the 1998/1999 season, which was unprecedentedly highfor the past decade in Japan (4)･ It will become incre.asingly
important to achieve improved inmlenZa SuⅣeillance ln Order

Ministry of

to understand the subsequent disease burden of influenza, asHealth, Labour

well as to assess the effectiveness of influenza vaccinations.

and Welfare

Because the magnitude and epidemic strains of influenza vary&om season to season, serologlCal monitonng will be necessary
in order to test fわr a match between cu汀ent Vaccine strains

RegiOnalInfectiousDiseaseSurveillanceCenterand epidemic strains (5). However, evaluation of innuenza(PrefecturaUMuniclPalDepartmentofHealth)surveillance systems is often not carried out. One reason forthis is that it remains difficult to confirm infection by influenza
among mmerous patients with inf一uenza‑like illness (lLI) thatare contracted in a short period of time.

District laboratory

Jurisdictional(Pre fectural/Mum ic ipal)

Public Health CenterS｡｡｡im｡｡S十lRep｡九十l*Corresponding author: Mailing address: Community MedicineSentinelsites(approx5,000)

Section, Health and Welfare Bureau, KamihonnouJ lmae‑Cho 48 8,ⅠntemalmedicineandPediatrics

Teramachi Oike, Nakagyo‑ku, Kyoto 604‑857 I , Japan. Tel: +8 1 ‑751

222‑342 1 ･ Fax: +8 I ‑75‑222‑34 1 6. E‑mail:fujiih@jmail.plala.or.jp

Fig･ 1 ･ Microbial and sentinel surveillances for innuenza in Japan,

23

these five consecutive influenza seasons in Kyoto City, Japan･

Kyoto City Institute of Health and Environmental Sciences.
Spec.imens were gathered by ISSSfrom patients with ILI (349speclmenS)and other illnesses. Influenza viruses were isolated

METHODSin 161 specimens out of676. Table 1 displays a comparison

We compared the 1995‑2000 data collected by the ISSSof the number of innuenza virus isolates and other pathogens

with those by the Microbial Isolation SuⅣeillance System

recovered from ILI patients by the MISS. Influenza viruses(MISS). We reviewed the clinical infbmation regarding

were identified in 144 of349 specimens; 41 specimens tested

patients with ILI, who submitted throat swab specimens during

positive for influenza A (HINl) virus, 72 for influenza A(H3N2) virus, and 3 1 for influenza B virus. Fifty‑two otherNovember through March of the next year, and we attempted
isolation of the major responsible resplratOry Pathogens,including influenza virus. In addition, patients who werepathogens were identified in 4l specim.ens (2 pathogens
were isolated in ll of the 41); 8 adenovlruS, 3 respiratory

diagnosed with other respiratory illnesses (e･g･, tonsillitis,

symytial (RS) virus, 3 coxsackieviruS, 1 parainfluenFa virus,

upper respiratory infectlOnS, bronchitis, etc.) and viral

9 Staphylococcus aureus, 3 Streptococcus pneumonlae, andgastroenteritises (e.g., viral gastroenteritis of adult, acutevomiting and diarrhea of infancy and childhood), which can

25 Other pathogens were also present, including anunidentified
pathogen. No pathogens were identified in 1 64 0f the speci‑

be included among the influenza su.rveillance data (1 I), weremens. The number of microbiologlCally identified influenza

selected for isolation of influenza vlruSeS and other microbialpathogens. In Kyoto City, throat swab specimens frompatients with ILI were centrifuged with 3 ml of the Eagle's
minimal essential medium (MEM) andfiltrated with millipore

Table 1. Isolation ofpathogens from throat swab specimens

ofpatients diagnosed with lLlfrom November to Marchin 1995/1996 ‑ 1999/2000 in Kyoto Cityfilters (diameter, 0.45 LLm). Then, samples were inoculated on

Madin‑Darby camine kidney (MDCK) cells.When a cytopathic(〟 ‑ 349)

Pathogen Number of specimen (%)

effect was observed, the type of influenza virus was identified
uslng anti‑ferret sera that is provided every preseason by theinfluenza A/H IN 1

41 (ll.7)

National Institute of Infectious Diseases. For other virus
isolations, FL cells (human amniotic membrane), RD‑1 8S
cells (human fetus striated muscle), and Vero cells (African

innuenza A/H3N2

72 (20.6)

influenza B

31( 8.9)

adenovims

8( 2.3)

resplratOry SynCytial vims

3 ( 0.9)of these cell types were inoculated in the ddY strain mousecoxsackievims

3( 0.9)(1‑2 days of age) brain or injected hypocutaneously. Whenparainnuenza virus

I( 0.3)herpesvims

I( 0.3)echovirus

I( 0.3)

unidenti fledI( 0･3)

Staphylococcus aweus

9( 2.6)

maccaka monkey kidney) were employed. Filtered specimens

the viruses were recovered, they were identified either by aneutralization test, a complement flXation reaction, a hemagglu‑

tination inl1ibition reaction, or afluorescent antibody teclmique.
In those cases that had developed symptoms ofviral gastro‑
enteritis, stool or vom血s specimens were tested f♭r rotavims

and enteric adenoviruS (types 40, 41) antigens by enzyヮeimmunoassay. Cytomegalovirus was recovered from urlne
specimens and identified by gene fragment detection uslng
polymerase chain reaction.

RE StJIXS

Streptococcus pneumoniae

3( 0,9)Streptococcustype A

15( 4･3)

Streptococcus type B

3( 0.9)Streptococcus type G2( 0.6)

Pseudomonas aeruginosa1( 0.3)

Haemophilus injluenzae

1( 0.3)

negativ e

Isolation of pathogens from ILI patients: A total of676

164 (47.0)

The total number of results exceeds 349 because two pathogensthroat swab specimens together with the associated clinicalwere isolated in 1 1 of the 349 specimens.

infbmation were submitted to the Division or Microbiology,%: 349 ‑ denominator′hU 5 4 3 2 1 0000000

7 ∠U 5 4 AJ 2 1 0 0 0 0 0 0 0 0dZuanu こOuO!L]OdoJdsuatupadsJo aqunN

き草野やQ<♂

｡eC♂

㌦でが画画か喜PnEhg:t:in;Z:at hv?rguesn s+ proportion of influenza virus
Fig･ 2･ Results ofmicrobial isolation from patients diagnosedwith lLT frolTI November to March in 1995/1996 ‑ 1999/2000 jnKyoto City (n ‑ 349).

24

Numberof cases
7060
50403020100Nov

De cJa nFOBMarFig. 3, Clinical diagnosis and number of specimens confirmed as innuenza virus by month from November to March in1995/1996 ‑ 1999/2000 in Kyoto City (n ‑ 161).

cases ranged from 0 to 66, and the number of cases fromwith a diagnosis of ILI among those submitted by sentinel

which other pathogens were isolated ranged from 4 to 13.

doctors; among those specimens were ones from which

The number of negative cases ranged from 3 to 57, according

influenza viruses were isolated together withclimical diagnosis.

to the month (Fig. 2). Figure 3 shows the clinical diagnoses

Specificity indicates the percentage of specimens from theamong the cases in which influenza was confirmed. Although

total in which influenzavirus was not isolated; among these

血ere were misdiagnosed cases, e.g., tonsillitis and menlngltlS,specimens were those fわr which any diagnosis other than ILI

89･4% (144/1 61) of the cases were diagnosed correctly. No
specific association was observed betweentypes of pathogen

was tested; these samples were also submitted by sentinel

and the month in which pathogens were recovered.

doctors. PVP indicates the percentage of specimens in which

had been made, and f♭r which isolation of the infhenza vims

Sensitivity, specificity, and predictive value positivein恥enza vimses were isolated; among these latter specimens,(PVP): Regardless of clinical diagnosis, the results of all

also submitted by sentinel doctors, werethose witha diagnosis

throat swab specimens used for isolation of the influenzaof ILII Sensitivlty ranged from 79.I to 96.8%, specificity

vims during the period of obseⅣation were summarized withranged舟om 55 to 76.8%, and PVP ranged丘om 28.9 to 52.1%

the goal ofevaluatlng the accuracy of the physicians'clinicalby season (P < 0･001)･ On the other hand, sensitivity ranged

diagnosis for innuenza; tested values included sensitivlty,

from 85･7 to lO0%, specificity ranged from 38.4 to 92.5%,
and PVP ranged from 31.4 to 50.4% by month (P < 0.001).

specificity, and PVP by season and by month, shownin Table 2.
In this context, sensitivityindicatesthe percentage of specimens

Sensitivity and PVP were not calculated f♭r any time period

Table 2･ Sensitivity, specificity, and predictive value positive (PVP) for the physicians'clinical diagnosis
ofinfluenza from November to March in 1995/1996 ‑ 1999/2000 in Kyoto City
Observation

periodSensitivity(%)

Specificity

(%)

PVP

(%)

November to March in 1995/1996 season

18/21 (85.7)

32/49 (65.3)

November to March in 1996/1997 season

9/10 (90.0)

53/69 (76.8)

9/25 (36.0)

November to March in 1997/1998 season

22/24 (91.7)

66/120 (55.0)

22/76 (28.9)

November to March in 1998/1999 season

61/63 (96.8)

76/132 (57.6)

61/117(52.1)

November to March in 1999/2000 season

34/43 (79. 1)

83/145 (57.2)

34/96 (35.4)

18/35 (51.4)

All November in 1995‑1999

0/0 (‑)

86/93 (92.5)

0/7 (‑)All December in 1995‑1999

16/18 (88.9)

63/98 (64.3)

16/51 (31.4)

All January in 1996‑2000

66/77 (85,7)

50/115 (43.5)

66/131 (50.4)

All Febmary ln 1996‑2000

45/49 (91.8)

38/99 (38.4)

45/106 (42.5)

17/17 (100.0)

73/110 (66.4)

17/54 (31.5)

144/161 (89.4)

310/515 (60.2)

144/349 (41.3)

All March jn 199612000
All periods

P<0.001
Sensitivlty: Sentinal doctors submitted this number of specimens with the diagnosis of ILl; among thesewere specimens associated with any clinical diagnosis that had also been tested positive for inf一uenza

VlmSeS.
Specificity: The number of specimens in which the innuenza virus was not isolated; among these specimens

submitted by sentinel doctors were those with any diagnoses other than ILI but which had undergone
testlng for isolation of the innuenza virus.

PVP: The number of specimens jn which innuenzaviruses were isolated; among these specimens submitted bysentinel doctors were thosewith a diagnosis of ILI,

25

Table 3. The number of specimens that tested positive for innuenzavirus and other pathogens, taken from patients diagnosedwithviralgastroenteritis
from November to March in 1 995/1996 I 1999/2000 in Kyoto City
1995‑1996

1 996‑1 997

1997‑1998

1998‑1999

199912000

Nov Dec Jan Feb Mar Nov Dec Jam Feb Mar Nov Dec Jam Feb Mar Nov Dec lan Feb Mar Nov Dec Lan Feb Mar
Number ofTePOrted cases as s/o viral461440 0 00 0 00 0 062 2 010377 5 0

3 1 0

5 4 0

4 つJ 0323121 0

2 00oo001

74qノ へlJ l 1 3 2

gastroenteriti s 辛among above*, with swab specimens**

2 0

4 00000

0 0 00 †1 0tJ 0

2 0

1 00 01 0

4 00 0 00 0 00 0 0

0 0 00 0 00 0

1 0000000

among above**, positive for innuenza virus

Otherpathogens echovims

100<U O ∧U
0 0 00 0 00 0 00 0 0001

0 1 00 0 0O 1 0000000

S. haemolytE'cus typeAadeno vi rus

in November.

lance systems (H1 3‑Shink0‑5).

Of 43 throat swab specimens from patients who wereclinically diagnosed with viral gastroenteritis, one (2.3%) was

REFERENCE S

virologically confirmed as influenza virus (Table 3).

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morbidity and mortality. Vaccine, 17, Suppl. 1, S3‑10.

DISCUSSION

2･ Assad, F., Cockbum, W. C. and Sundaresan, T K. (1973):
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3･ Shindo, N., Taniguchi, K., Okabe, N., Ohi, Y. and Ii, M.

In most industrialized countries, the national infectious
disease surveillance authority usually monitors influenza
activity by routine reportlng from designated sentinel sites.
In order to maintain high efficacy of observation, it is crucial(2000): Excess death associated with influenza. Infect.

to regularly evaluate such sentinel suⅣeillance systems. This

Agents SuⅣeillance Rep., 21 , 265‑267 (in Japanese).

4. Taniguchi, K. (2000): Current situation and impact ofinfluenza in the elderly. Jpn. J. Chest. Dis., 59, 6531661

is the丘rst evaluation of an ISSS in Kyoto City, Japan.

We fわund high sensitivlty throughout the study period,

which supported the efficacy of the present influenza observa‑(in Japチnese)･,tion system. However, the series of procedures required fわr

5. 1mmunlZation Section and ResplratOry Vims Section,isolation testlng lS tedious, thus poslng a major limitation toNational Institute of infectious Diseases (2000) : InnueTza･

the practice of confirming influenza in all patients with ILI.

p･ 1 4‑20･Amual report I 998 0n National EpidemiologlCalSpecificity varied by season, indicatlng the difficulty ofSuⅣeillance ofVaccine‑preventable Diseases (in J叩a‑achievlng a Clinical differential diagnosis of other respiratorynese).

illnesses. However, some patients were shown to have someformof viral gastroenteritis (e.g., Norwalk virus infection),

6. National Institute of Infectious Diseases and Infectious

these cases were excludedfrom the influenza case. High viral( I 998): Influenza, 1 997/98 season, Japan. Infect. Agents
Surveillance Rep., 19, 272'‑273'.
7. National Institute of Infectious Diseases and Infectious

Diseases Control Division, Ministry ofHealth and Welfare

gastroenteritis activitywas observed inthe 1999/2000 season(available on website, http ://idsc.nih. go.jp/kanj a/weeklygraph/

Diseases Control Division, Ministry of Health and Welfare!astro･html) (12), and the MISS demonstrated better results
ln that regard. These findings suggest that a mix of viral(1999): Influenza, 1998/99 season, Japan. Infect. Agents
Surveillance Rep., 20, 289'‑290'.
8. National Institute of Infectious Diseases and Infectious

gastroenteritis and innuenza in an influenza surveillancesystem would not be a serious problem as imagined.

PVP varied by season, and when calculated by month, PVP

Diseases Control Division, Ministry of Health and Welfare

peaked in January. The result may be explained that the(1 996): Innuenza, 1 995/96 season, Japan. Infect. Agents

number of true influenza patients increases rapidly at times

SuⅣeillance Rep., 17, 268'‑269'.

when influenza activity is high (i.e., December‑February).

9. National Institute of Infectious Diseases and Infectious

Improvement of PVP is essential fわr the early detection ofDiseases Control Division, Ministry ofHealth and Welfare

therise and fall of influenza activlty. Since the 2000/2001(2000): Influenza, 1 999/2000 season, Japan. Infect. Agentsseason, rapid innuenza diagnosis kits detecting influenza A

SuⅣeillance Rep., 21, 260'‑261'.

and B viruses have been commercially available, and thereR)re,

1 0. National Institute of Infectious Diseases and TuberculosisPVP should be improved throughout the influenza season.

and Infectious Diseases Control Division, Ministry ofThe well‑evaluated ISSS data are use且ll fわr improvlng

Health, Labour and Welfare (200 1 ): Influenza, 2000/0 1

public health systems･ The ISSS is thus a good suⅣeillanceseason, Japan. Tnfect･ Agents Surveillance Rep･, 22, 309'‑

system, and further monitoring to strengthen the ISSS will310'.

11･ Takahashi, H., Fujii, H･, Shindo, N. and Taniguchi, K.

contribute to an improved understanding of the epidemiologyof influenza in the communlty Of Kyoto City･(200 1): Evaluation orthe Japanese school health suⅣei1‑

1ance system for influenza･ Jpn･ J･ Infect･ Dis･, 54, 27‑30.
12･ InfectiousDisease Surveillance Center (2001 ): Infectious

ACKNOWLEDGMENTS
This study was planned and developed with the Japanese

Ministry of Health, Labour and Welfare scientific research

gastroenteritis･ Weekly reported cases per sentinel incomparison with past 1 0 years･ Infectious Disease Weekly

grant on coordination of the national and prefectural surveil‑

Report Japan.

26