One hypervirulent clone, sequence type 283, accounts for a large proportion of invasive Streptococcus agalactiae isolated from humans and diseased tilapia in Southeast Asia

Abstract

Background In 2015, Singapore had the first and only reported foodborne outbreak of invasive disease caused by the group B Streptococcus (GBS; Streptococcus agalactiae ). Disease, predominantly septic arthritis and meningitis, was associated with sequence type (ST)283, acquired from eating raw farmed freshwater fish. Although GBS sepsis is well-described in neonates and older adults with co-morbidities, this outbreak affected non-pregnant and younger adults with fewer co-morbidities, suggesting greater virulence. Before 2015 ST283 had only been reported from twenty humans in Hong Kong and two in France, and from one fish in Thailand. We hypothesised that ST283 was causing region-wide infection in Southeast Asia. Methodology/Principal findings We performed a literature review, whole genome sequencing on 145 GBS isolates collected from six Southeast Asian countries, and phylogenetic analysis on 7,468 GBS sequences including 227 variants of ST283 from humans and animals. Although almost absent outside Asia, ST283 was found in all invasive Asian collections analysed, from 1995 to 2017. It accounted for 29/38 (76%) human isolates in Lao PDR, 102/139 (73%) in Thailand, 4/13 (31%) in Vietnam, and 167/739 (23%) in Singapore. ST283 and its variants were found in 62/62 (100%) tilapia from 14 outbreak sites in Malaysia and Vietnam, in seven fish species in Singapore markets, and a diseased frog in China. Conclusions GBS ST283 is widespread in Southeast Asia, where it accounts for a large proportion of bacteraemic GBS, and causes disease and economic loss in aquaculture. If human ST283 is fishborne, as in the Singapore outbreak, then GBS sepsis in Thailand and Lao PDR is predominantly a foodborne disease. However, whether transmission is from aquaculture to humans, or vice versa , or involves an unidentified reservoir remains unknown. Creation of cross-border collaborations in human and animal health are needed to complete the epidemiological picture.

Isolation and molecular characterization of streptococcal species recovered from clinical infections in farmed Nile tilapia (Oreochromis niloticus) in the Philippines

“…The data presented showed that S. agalactiae was the more prevalent and geographically widespread aetiological agent, while S. iniae appeared to be confined to a specific area. While we acknowledge the limited sample sizes, these findings are in agreement with reports from neighbouring South‐East Asia (SEA) countries (Anshary, Kurniawan, Sriwulan, Ramil, & Baxa, 2014; Barkham et al., 2019; Jantrakajorn, Maisak, & Wongtavatchai, 2014; Kayansamruaj et al., 2019; Syuhada et al., 2020) and in China (Li et al., 2014; Su et al., 2019) where S. agalactiae is the primary streptococci species associated with fish disease. This observed prevalence of S. agalactiae over S. iniae is similar to reports worldwide, especially in the major tilapia‐producing regions in Asia and Latin America (Liu et al., 2016).…”

Development and Application of a Prophage Integrase Typing Scheme for Group B Streptococcus

“…This may include transfer of prophage content between GBS from different host species, in agreement with the detection of prophage types and integrase types across GBS from different host species in our dataset. We discovered a potential contribution of prophages to the emergence of hypervirulent ST283, which has recently been recognized as a major cause of adult invasive disease in Southeast Asia (Rajendram et al, 2016 ; Kalimuddin et al, 2017 ; Barkham et al, 2019 ). Contradicting the dogma that phage integrase genes are site-specific (Frost et al, 2005 ), the integrase at insertion site GBS7 (5' end of hylB ), was identical to the integrase at GBS1.…”

“…The label GBS Int 7 is not used because the site-specific integrase at insertion site GBS7 was identical to GBS Int 1 at insertion site GBS1 ( Figure 1 , Table 1 ). GBS Int 1 at site GBS7 was only observed in this location when the GBS1 site was occupied by a prophage and it was uniquely observed in ST283, the only known hypervirulent GBS in human adults (Barkham et al, 2019 ).…”

“…In humans, GBS is a leading cause of neonatal invasive disease, and a pathogen of immunocompromised adults and elderly people (Farley and Strasbaugh, 2001 ; High et al, 2005 ; Skoff et al, 2009 ). The epidemiology and clinical manifestations of GBS disease in humans continue to evolve, as exemplified by the recent emergence of hypervirulent GBS in adults without underlying comorbidities (Barkham et al, 2019 ). Phages and other mobile genetic elements (MGE) play an important role in the evolution of GBS, its adaptation to different hosts and niches and its virulence profile (Richards et al, 2019 ).…”

Phenotypic and genotypic characterization of Streptococcus spp. isolated from tilapia (Oreochromis spp.) cultured in river‐based cage and earthen ponds in Northern Thailand

“…The GBS serotype Ⅲ ST283 was detected in three cage farms in the present study, suggesting the possibility of a genetically close relation. GBS serotype Ⅲ ST283 was widespread in South‐East Asia and emergence in Brazil, which has been proven to be associated with severe invasive disease in humans (Barkham et al, ; Leal et al, ). In 2015, GBS serotype Ⅲ ST283 was the causative agent of foodborne outbreaks in Singapore as the consumption of raw fish (Kalimuddin et al, ).…”