The Topic of This Month Vol. 33, No. 8 (No. 390)
Streptococcal infections in Japan, April 2006-2011
(IASR 33: 209-210, August 2012)
Suppurative infection-causing hemolytic streptococci include Streptococcus pyogenes (group A, or Group A streptococci; GAS), S. agalactiae (GBS) (group B) and S. dysgalactiae subsp. equisimilis (SDSE) (group C or G; IASR 25: 257-258, 2004). GAS causes suppurative infections, such as, acute pharyngitis, scarlet fever, erysipelas, cellulitis, and streptococcal toxic shock syndrome (STSS), and post-streptococcal infection sequelae, such as, rheumatic fever and acute glomerulonephritis. GBS causes septicemia or meningitis in neonates and sepsis or pneumonia in adults. SDSE causes septicemia and STSS in adults.
STSS and GAS pharyngitis are Category V notifiable diseases under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (Infectious Diseases Control Law). For the former, physicians are under obligation of notifying all the cases which they diagnosed, and for the latter, pediatric sentinel clinics are under obligation of reporting (for reporting criteria, go to http://www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou11/01-05-06.html and to http://www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou11/01-05-17.html, respectively).
Severe invasive streptococcal infections with toxic shock syndrome (STSS): The previous issue of this topic (IASR 25: 252-253, 2004) indicated that the criteria of STSS notification should be revised. Based on this recommendation, the criteria were modified and implemented in 2006. The reporting criteria of STSS (revised on April 1, 2006) include 1) detection of group A or other β-hemolytic streptococcus as a causative agent, 2) manifestation of toxic shock symptoms, and 3) at least two of the following, i.e., liver failure, renal failure, acute respiratory distress syndrome, disseminated intravascular coagulation, soft tissue inflammation (including necrotic fasciitis), generalized erythrodermatous exanthema, and convulsion, syncope and other central nervous system symptoms.
Under the National Epidemiological Surveillance of Infectious Diseases (NESID), total 698 STSS cases including 248 deaths were reported from April 2006 to the end of 2011. There was a sharp increase in 2011 (Table 1). Half of the fatal cases died within 3 days after clinical onset.
Seasonally, STSS tends to be more frequent from January to June (Fig. 1). All the 47 prefectures reported STSS cases, whose incidence was below 1/100,000 population (Fig. 5) except Toyama (1.29) and Shimane (1.26). The sex ratio of the patients was 1.21 (male 382 and female 316). There was a broad age peak in 60-64 years for males and 75-79 years for females (Fig. 2).
Of the etiological agents, group A has been the most frequent isolate (Fig. 1) occupying 65-80% of the total isolates every year (Table 1).
Since the first report in 1992 of typical STSS cases in Japan, infectious agent surveillance has been conducted at the Streptococcus Reference Center (SRC) of the Associations of Public Health Laboratories for Microbiological Technology (see IASR 18: 25-26, 1997 and p. 211 of this issue) by monitoring of T serotyping, genotyping of the M protein gene (emm), and drug resistance. Of 280 isolates, the most frequent one was T1 (148 isolates; 53%), which has been increasing since 2010 (35% in 2009; 61% in 2010; 71% in 2011) (Fig. 3a) (p. 212 of this issue).
With modified reporting criteria of STSS from April 2006, various β-hemolytic streptococci were found to cause STSS. Among recent isolates sent to SRC, new anginosus groups, such as group C, group F or unclassifiable group, are found (http://www.niid.go.jp/niid/images/lab-manual/reference/13_streptococii.pdf).
Combined administration of penicillin antibiotic at high doses and clindamycin is currently recommended for treating STSS. According to SRC, to ampicillin and penicillin G, all the tested 280 isolates were susceptible, but not necessarily to clindamycin. While 5% of the isolates has been resistant in most recent years, in 2009 as high as 15% of the isolates were found resistant to clindamycin (p. 213 of this issue). To erythromycin, almost all the T1 isolates, which increased in 2011, were resistant (p. 213 of this issue).
Group A streptococcal pharyngitis: Numbers of cases of GAS pharyngitis reported from the sentinel clinics under NESID in 2006-2011 was 202,579-278,990 per year. Every year, the epidemic follows a characteristic seasonal fluctuation with a dip in summer (Fig. 4) and 70% of the patients are under 7 years of age (majority in 4-7 years).
During 2006-2011, annual report of GAS T-serotyping from prefectural and municipal public health institutes to SRC was 1,002-2,188. From 2006 to 2008, T1, T12 and T4 were dominant, but in 2010 T4 decreased. T25 and TB3264 increased in 2009 and 2010, respectively, and in 2011 T1 became more conspicuous as a dominant type (Fig. 3b).
As for antibiotic resistance, the pharyngitis-derived isolates tested by SRC were generally susceptible to ampicillin, but nearly 50% of such isolates were resistant to erythromycin and other macrolide antibiotics (p. 214 & 215 of this issue).
In recent years, pharyngitis outbreaks attributable to GAS-carrier cooks have been reported in Japan and abroad. In July 2005, 298 GAS pharyngitis patients were reported among 461 people who consumed a boxed lunch served in a university in Kanagawa Prefecture (Eur J Clin Microbiol Infect Dis 28: 305-306, 2009), and in June 2010, 21 GAS pharyngitis patients were reported among 78 people who shared the same food in a dormitory in Saitama Prefecture. In Denmark, in June 2006, 200-250 persons who used a staff canteen developed GAS pharyngitis (Epidemiol Infect 136: 1165-1171, 2008). For preventing such incidents, cooks are advised to use a mask and gloves routinely during food handling. In case of pharyngitis outbreak, it is also important to suspect food-borne GAS infection and, where necessary, conduct appropriate food consumption investigation and throat cultures of the cooks and other employees.
Conclusion: The reported number of STSS increased by two-fold from 2006-2009 to 2011 (Table 1). It is important to note, however, that SRC obtained streptococcus isolates from only 40% of the total notified STSS patients. As the trends of circulating pathogen types and their antibiotic resistance in the infectious agents surveillance under NESID are important information for assessing patient’s condition and early commencement of the therapy, the information should be fed back correctly to clinicians and public health servants. In order to know the whole picture of causative agents of STSS and GAS pharyngitis, the current isolate collection system should be further strengthened.
Data obtained for 2012, preliminary report: As of week 28 of 2012, 146 STSS cases have been notified (127 cases as of week 28 of 2011) (Fig.1). At the present pace, total number of STSS in 2012 may exceed 200.
In recent years, invasive infections of humans by Streptococcus suis have been reported in significant numbers from China, Vietnam and Thailand, and in very small numbers from Japan (IASR 26: 241 & 242, 2005 and p. 217 of this issue). Further investigation on this matter is needed.