Varicella-Associated Invasive Group A Streptococcal Disease in Alberta, Canada—2000–2002
- 1Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada
- 2National Center for Streptococcus, Provincial Laboratory for Public Health (Microbiology), Edmonton, Canada
- 3Alberta Health and Wellness, Edmonton, Canada
- Reprints or correspondence: Dr. Gregory J. Tyrrell, 2B3.13 Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Canada T6G 2R7 (g.tyrrell{at}provlab.ab.ca).
Abstract
We determined the incidence of invasive group A streptococcal (GAS) disease among children ⩽14 years of age in Alberta, Canada, with a focus on infections associated with varicella. During 2000–2002, there were 71 cases of invasive GAS disease among patients in this age group. Fourteen cases occurred in children with varicella (19.7%), for an annual incidence of 0.73 varicella-associated cases per 100,000 children. Necrotizing fasciitis was not noted in patients with invasive GAS disease and varicella.
Since the 1980s, invasive group A streptococcal (GAS) disease in North America and other parts of the developed world has received increased attention from the medical community, public health officials, and the public at large [1–3]. Invasive GAS disease has been primarily associated with high-profile diseases, such as necrotizing fasciitis and streptococcal toxic shock syndrome (STSS), and its heightened profile has led to an interest in understanding the epidemiology and rate of invasive GAS disease and the circulating GAS strains associated with GAS infection [3–8]. In children, varicella infection has been shown to have the potential to lead to severe invasive GAS disease. GAS infection associated with varicella was first reported by Hutchinson [9] in the nineteenth century, and in the past 30 years, several investigators have shown that varicella is a risk factor for invasive GAS disease, especially necrotizing fasciitis [10–12]. This study reviewed the incidence and microbiologic data of invasive GAS disease and varicella-associated invasive GAS disease in children ⩽14 years of age (hereafter, “children”) in Alberta, Canada, during 2000–2002.
Methods. Invasive GAS disease, defined as the isolation of GAS from a normally sterile site (e.g., blood, CSF, and pleural fluid), was made reportable in Alberta in August 1999. Clinical microbiology laboratories in the province report isolation of GAS from normally sterile sites to their regional medical officer of health, and isolates are forwarded to the National Center for Streptococcus (Edmonton, Canada). Public health staff obtain clinical information from attending physicians. This report describes data collected for children during the surveillance period from 1 January 2000 through 31 December 2002.
To reduce the likelihood that cases of invasive GAS disease are missed, a representative from the provincial public health department meets with a representative from the National Center for Streptococcus each year to review all cases that were documented by each agency during the current calendar year. If cases were missed by either agency, follow-up is initiated with the laboratory that initially isolated or reported the presence of GAS and/or with the attending physician who treated the case.
Isolates of invasive GAS forwarded to the National Center for Streptococcus were M typed, as described elsewhere [13]. All isolates were assayed for susceptibility to penicillin, vancomycin, chloramphenicol, erythromycin, and clindamycin by means of the disk diffusion method, in accordance with NCCLS guidelines [14].
The mean annual population of children for 2000–2002 was 642,841 [15]. A universal varicella immunization program for infants was begun in Alberta in July 2001, after the study began.
Results. From 1 January 2000 through 31 December 2002, a total of 71 cases of invasive GAS disease were identified in children (mean age, 5.1 years) in the province of Alberta. This translates into an annual incidence of 3.7 cases per 100,000 children, with a nadir incidence of 2.8 cases (in 2002) and a peak incidence of 4.0 cases (in 2001) per 100,000 children. The highest rates were seen among children ⩽1 year of age (figure 1). Of the 71 children with invasive GAS disease, five (7%; age, 6, 9, 10, 11, and 13 years) presented to the hospital or clinic with necrotizing fasciitis, and three (4%; age, 3, 10, and 11 years) presented with STSS, for annual incidences of 0.25 and 0.16 cases per 100,000 children, respectively. Only 1 child presented with both necrotizing fasciitis and STSS (age, 11 years; time of presentation, 2001). Of the 4 children who died, one was a newborn (time of presentation, 2002), one was 10 months old (2000), one was 1 year old (2000), and one was 9 years old (2001); the overall case fatality rate was 5.6%. The patient aged 1 year died from STSS. M1 was found in 23.9% of the cases; M3, 18.3%; M12, 11.3%; M4, 8.5%; and MPT2967, 5.6%. No single serotype predominated in patients who died. Erythromycin resistance was noted in 7 (9.8%) of 71 isolates, and of these, 4 were associated with a single serotype (MPT2967).
Figure 1
Annual incidence of invasive group A streptococcal disease (iGAS) among children (age, ⩽14 years) in Alberta, Canada, 2000–2002.
Invasive GBS disease associated with varicella infection was noted in 14 (19.7%) of 71 children, for an annual incidence in Alberta of 0.73 varicella-associated cases of invasive GBS disease per 100,000 children. The median age of the children with varicella was 4.5 years (table 1). None of these 14 children presented with necrotizing fasciitis or STSS. No deaths were associated with varicella. Bacteremia was the most common clinical presentation in children with varicella, accounting for 85.7% of cases of invasive GAS infection (table 1). Arthritis occurred in 3 children (21.4%) with varicella, and osteomyelitis occurred in 2 (14.3%) (table 1). M1 was the predominate M type in children with varicella-associated invasive GAS disease (6 children); M3 was the second most common M type (4 children). Nine (64%) of 14 cases occurred during the winter months (November to March). No GAS isolates recovered from children with varicella were resistant to erythromycin. All 14 isolates were susceptible to clindamycin, penicillin, vancomycin, and chloramphenicol.
Table 1
Characteristics of patients presenting to a hospital or clinic in Alberta, Canada, with invasive group A streptococcal (iGAS) disease subsequent to varicella infection.
Discussion. Varicella infection complicated by invasive GAS disease in children has been documented elsewhere, with rates of 6%-17% reported in both Canada and the United States [3, 12, 16, 17]. The most interesting finding in our study was the lack of necrotizing fasciitis in children with invasive GAS disease associated with varicella. Studies have shown that a significant percentage of children with varicella-associated invasive GAS disease go on to develop necrotizing fasciitis, which was previously thought to be GAS-infected varicella lesions. A Canadian study conducted in Ontario during 1992–1996 found that 5 of 31 children with invasive GAS disease presented with necrotizing fasciitis after chicken pox [12], suggesting a rate that is clinically significant enough to warrant surveillance. It is unlikely that cases of necrotizing fasciitis-associated varicella were missed in our study—5 (7%) of 71 children with invasive GAS disease received a diagnosis of necrotizing fasciitis.
The predominance of M1 and M3 serotypes in cases of invasive GAS disease associated with varicella mirrors the prevalence seen among children without varicella and is similar to that for the general population of Canada [13]. The high rate of erythromycin resistance (19.8%) among GAS isolates recovered from children with invasive disease can be accounted for primarily by the presence of MPT2967. This M type is typically resistant to erythromycin and has been noted in both Canada and the United States [18].
In July 2001, Alberta began a universal varicella immunization program for infants. However, because this program began during the study period, we were unable to determine a measurable effect of varicella vaccination on the incidence of invasive GAS disease. We expect that one of the benefits of a universal varicella immunization program for infants would be a reduced risk of acquiring invasive GAS disease resulting from a decreased incidence of varicella infection.
Acknowledgments
We are grateful to the analysis staff at Alberta Health and Wellness (Edmonton, Alberta, Canada) and to the nurses at the Regional Communicable Diseases offices located in each health region. We are also indebted to the medical officers of health in each study region, staff at participating microbiology laboratories, and physicians, whose time and effort continues to provide important information regarding surveillance of group A streptococci in Alberta.
Financial support. Alberta Health and Wellness, Provincial Microbiology Laboratory for Public Health (Edmonton), and the National Center for Streptococcus (Edmonton).
Potential conflicts of interest. All authors: no conflicts.
- Received June 11, 2004.
- Accepted November 17, 2004.
- © 2005 by the Infectious Diseases Society of America
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