The Topic of This Month Vol. 29, No. 10 (No. 344)

Respiratory syncytial virus infection, as of September 2008
(IASR 29: 271-273, October 2008)

Respiratory syncytial virus (RSV) is found worldwide and causes an acute respiratory-tract infection.  RSV epidemics occur in winter in the temperate zone.   RSV is classified into genus Pneumovirus in the family Paramyxoviridae .  Besides droplet infection, transmission of RSV occurs via hands or hard surfaces of the environments contaminated with the virus in nasal discharge or sputum.  More than 50% of infants may acquire primary infection during the first year of life and nearly 100% may be infected before their second birthday, although they do not obtain lifelong immunity. Respiratory symptoms tend to become serious in newborns, infants, young children and immunocompromised patients.  It has been reported that 50% of pneumonia and 50-90% of bronchiolitis in infants and young children are caused by RSV infection.  Noticeable complications are apnea, syndrome of inappropriate antidiuretic hormone (SIADH), and acute encephalopathy (see p. 274-275 of this issue).  Usually, reinfection of RSV in older children and adults does not develop serious symptoms, but possibly makes source of infection.  It may sometimes cause lower respiratory tract infection among elderly people, and intra-institutional outbreaks at elderly care facilities or other settings have been reported.  Because other respiratory virus infections bring about similar symptoms, virological tests are essential for differential diagnosis of RSV infection (see p. 277 of this issue).  Since rapid diagnosis of RSV infection becomes important for the control of nosocomial infection at institutions, having admitted high-risk patients.  Health insurance is applicable to RSV antigen-detection for inpatients (moreover, the age of the patients had been limited under 3 years before March 31, 2006).  Symptomatic treatment is fundamental for RSV infection.  RSV vaccine has not been developed.  Palivizumab, a humanized monoclonal antibody to RSV F glycoprotein recently developed in the United States, is administered to prevent serious infection in premature babies and in infants and children with chronic lung disease or congenital heart disease (see p. 274 of this issue).

RSV infection is an important respiratory tract infection like influenza.  In addition, palivizumab appeared on the market in 2002.  Since it became necessary to grasp the epidemic period of RSV infection, the disease was added to the category V infectious disease to be reported by pediatric sentinels under the National Epidemiological Surveillance of Infectious Diseases (NESID) at the time of amendment of the Infectious Diseases Control Law (November 5, 2003) (for reporting guidelines, refer to  Although laboratory diagnosis is required for reporting, some sentinels have difficulties in reporting.  It is not practicable, therefore, to compare the number of cases per sentinel like other diseases reported by pediatric sentinels based on clinical diagnosis.  The epidemic period of the disease is grasped from the deviation of the number of cases.

Case report of RSV infections: In the weekly reports of RSV infection after commencement of NESID (Fig. 1), gradual increase started from around week 36 (early in September).  RSV infection suddenly increased around week 45, in the middle of November, and reached the peak in weeks 50-52 (the middle to late in December).  After the peak, it swiftly decreased, but reporting continued through spring and summer next year.  As compared with influenza prevailing in winter, the epidemic of RSV infection tended to occur earlier every year.  The number of medical institutions having reported at least one RSV infection in 2006 was smaller than that in 2007, but the peak at the end of 2006 was larger than that at the end of 2007.  In 2008, increase started earlier than in the past 4 years, from week 30 (the end of July) (Fig. 1).

Of number of reports by prefecture, top nine prefectures were Hokkaido, Fukushima, Kanagawa, Aichi, Osaka, Hyogo, Hiroshima, Yamaguchi and Fukuoka both in 2006 and 2007.  Especially, the most reports came from Osaka, accounting for >10% of the total.  The prefectures with more reports tended to show earlier start of increase and longer period with comparatively more reports (epidemic period).  It is considered that sufficient reports are necessary to grasp epidemics.

The time of start of epidemics differed from area to area (Fig. 2), and that in Fukuoka was early also in 2008 .  In Hokkaido and Fukushima, many reports came out even in the spring.  In Okinawa, being exceptionally different from other areas, epidemics occurred in the summer (see p. 278 of this issue).

Reported cases during 2004-2007 were 56,422 males (55%) and 45,543 females (45%).  Every year, many cases were seen among those of 0, 1, and 2 years of age in the decreasing order (Fig. 3).  In 2007, cases of <2 year accounted for 74% and <3 years for 87%.  When age distributions of cases during 2006-2007 reported from hospitals were compared with those from clinics, the ratio of 0-5 months-old infants was significantly high at hospitals.

After November 5, 2003, when acute encephalitis (including encephalopathy) was assigned to a category V infectious disease to be reported all cases, 6 cases were ascribed to RSV, one of which was fatal (Table 1).

RSV detection: During 2000/01-2007/08 seasons, influenza viruses accounted for about 90% of reports of respiratory viruses isolated/detected by prefectural and municipal public health institutes (PHIs), and RSV accounted for the largest portion among other viruses (Table 2).  From 2002/03 season, human metapneumovirus was reported and human bocavirus in 2007/08 season (see p. 279-283 of this issue).

Reports of RSV gave a peak between week 46 and week 4 of next year (November-January) (Fig.1).  After the amendment of the Infectious Diseases Control Law in November 2003, reports have increased; 38 PHIs in 30 prefectures reported 1,123 cases during four seasons of 2004/05-2007/08.  RSV-positive specimens were nasopharyngeal swabs 1,083, sputum and tracheal aspirates 39, stools 2, cerebrospinal fluid 1 (including cases from which RSV was isolated/detected from multiple specimens).  Methods of RSV detection were RT-PCR in 764 cases, isolation on cultured cells in 486, and antigen detection in 28 (including cases from which RSV was isolated/detected by multiple methods).  Diagnoses of the RSV-detected cases were lower respiratory infection in 439 cases, upper respiratory infection in 245, RSV infection in 226, influenza/influenza-like illness in 54, common cold in 38, unknown fever in 33, asthma in 11, pharyngoconjunctival fever in 11, infectious gastroenteritis in 9, and acute encephalitis/encephalopathy in 6.  By gender, there were more males, being 643 followed by females in 466, and unknown in 14.  By age, 0 year was 330 cases, 1 year 337 cases, 2 years 163 cases, 3 years 113 cases, 4 years 69 cases, 5-9 years 60 cases, 10-19 years 22 cases, ≥20 years 10 cases, and age unknown 19 cases; 0-1 year children accounted for 60%.

Future problems: Among pediatric sentinels, proportion of sentinels reporting more than one case of RSV infection a year was 42% in 2006 and 52% in 2007.  Of 3,079 pediatric sentinels, hospitals (inpatients and outpatients) counted 709, and clinics (outpatients only) 2,370; there were more clinics than hospitals (as of May 23, 2008).  Actually, the number of clinics which reported RSV infection exceeded that of hospitals and reported cases from clinics were more than those from hospitals, although health insurance is not applicable to rapid diagnostic kits for RSV infection if used for outpatients at clinics.  This indicates that laboratory diagnosis of the disease at a clinic is necessary before getting worse and hospitalization.  It seems necessary to expand application of health insurance to rapid diagnostic kits for outpatients.  Owing to this, it would be possible to grasp epidemic status by local level quickly and more accurately.

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