Hypervirulent Clone of Group B Streptococcus Serotype III Sequence Type 283, Hong Kong, 1993–2012

We describe a hypervirulent clone of group B Streptococcus serotype III, subtype 4, sequence type 283, that caused invasive disease with a predilection for meningitis in Hong Kong during 1993–2012. The organism is associated with high mortality and increased summer prevalence and is linked to diseased fish from freshwater fish farms.

women, and 692 nonpregnant adults (women and adults were >16 years of age).We used PCR, pulsed-field gel electrophoresis, and multilocus sequence typing for serotyping and subtyping of the isolates, as described (1,6).We reviewed demographic and medical records for the 1,645 patients and performed statistical analysis by using Fisher exact and χ 2 tests.SPSS version 19 (IBM, Armonk, New York, USA) was used for Spearman correlation analysis.We obtained ethical approval from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CRE-2012.054).
Of the 44 nonpregnant adults with GBS III-4/ST283, 41 (93.2%) had isolates from invasive sites.Sex of patients had no effect on whether the GBS disease was invasive: 20 of these patients were women and 21 were men.
To assess contributing factors, we examined possible climatic associations with isolation of serotypes causing the 437 cases of invasive GBS disease in Hong Kong during our study period.We reviewed Hong Kong's average monthly temperature and humidity records for 1997-2012.Serotype III-4 was the only serotype with a prevalence significantly associated with monthly temperature (Spearman correlation r = 0.622; p = 0.031).Isolation of serotype III-4 peaked during the summer months (June-September), when mean temperature was >28°C) (Figure 2, panel A).Humidity was not significantly associated with serotype III-4 prevalence (p>0.05)(Figure 2, panel B).
GBS infects many host species, has become an important pathogen in the aquaculture industry, and has resulted in significant economic loss (8).Serotype Ia/ST7 has been associated with large outbreaks of streptococcosis in cultured tilapia in China (9).The pathogenicity of human ST7 isolates in fish has been well established (10).Although no epidemiologic evidence confirms GBS as a zoonosis in human infections (11), comparative genome analysis revealed that cultured tilapia GBS ST7 was closely related to human ST7 strain A909.These fish and human strains share highly similar clustered regularly interspaced short palindromic repeats, prophages, virulence-associated genes, and extremely short evolutionary relationships in phylogenetic analysis (12).
ST283 and its single-locus variant ST491 have been detected in diseased tilapia with high death rates in Southeast Asia, where fish isolates shared the same mobile genetic elements and surface proteins as the human isolates  described in this article (8,13).This similarity provides molecular evidence for the linkage of ST283 strains in humans and fish.The outbreak in Singapore showed a rise in GBS sepsis and septic arthritis, which were linked to a probable source of raw fish consumption; subsequently, health authorities advised discontinuing sales of the raw fish dish as a precaution (2).A previous study showed that fish consumption caused a 7.3-fold increased risk for acquiring GBS serotype Ia and Ib colonization in humans (14).GBS serotypes Ia, III, and V of clonal complex (CC) 19, CC23, and CC103 from a human and a cow have been shown to infect tilapia experimentally (15); these cross-infections support GBS pathogenicity across different species.Epidemiologic investigations and comparative genomics on a wider scale of animal and human strains may further reveal evolutionary relationships between these GBS lineages.

Conclusions
Our finding of an association of the GBS III-4/ST283 lineage with summer months coincides with the timing of the outbreak in Singapore.Because GBS grows rapidly in warm temperatures, a higher infective dose may occur in warmer months than at other times.Warm temperatures might also cause increased pathogenicity of this organism, a postulation supported by the association of higher temperatures with tilapia deaths caused by GBS III-4 in freshwater fish farms (13).The pathogenicity of this strain in fish has been shown in vivo and further highlights the pathogenic potential of this lineage.
Reports dating from the 1990s indicate that GBS ST283 isolated from humans came exclusively from invasive sites in nonpregnant adults.Our data suggest that these isolates might have undergone adaptive evolution in recent years to colonize and invade neonates with early-and lateonset GBS sepsis.Studies addressing the changing epidemiology of this hypervirulent lineage and its relationship to humans and fish are warranted to reduce potential transmission between the 2 hosts.Etymology is concerned with the origin of words, how they've evolved over time, and changed in form and meaning they were translated from one language to another.Every month, EID publishes a feature highlighting the etymology of a word from medicine or public health.

Figure 2 .
Figure 2. Association of temperature and humidity with distribution of isolates by month of collection from patients infected with invasive Group B Streptococcus (GBS) serotype III, subtype 4 (III-4), Hong Kong, 1993-2012.A) Average annual monthly temperature and distribution of invasive GBS III-4 isolates.B) Average annual monthly humidity and distribution of invasive GBS III-4 isolates.Numbers along data lines indicate monthly values.

Table 1 .
Invasive potential of individual group B Streptococcus serotypes among neonates, nonpregnant adults, and pregnant women, Hong Kong, 1993-2012* Bold indicates statistical significance; p values determined by Fisher exact or χ 2 test.NT, nontypeable. *

Table 2 .
Distribution of GBS serotypes in patients with group B Streptococcus invasive disease, Hong Kong, 1993-2012* *GBS, group B Streptococcus; NA, nonapplicable; NT, nontypeable.Bold indicates statistical significance; p values determined by Fisher exact or χ 2 test.†Meningitis was confirmed by cerebrospinal fluid culture of GBS.‡Nonmeningitis was confirmed by GBS culture from sterile body site or from cerebrospinal fluid.