Genome Sequence of a Lancefield Group C Streptococcus zooepidemicus Strain Causing Epidemic Nephritis: New Information about an Old Disease

Outbreaks of disease attributable to human error or natural causes can provide unique opportunities to gain new information about host-pathogen interactions and new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN), a sequela of infection with pathogenic streptococci, is a common cause of preventable kidney disease worldwide. Although PSGN usually occurs after infection with group A streptococci, organisms of Lancefield group C and G also can be responsible. Despite decades of study, the molecular pathogenesis of PSGN is poorly understood. As a first step toward gaining new information about PSGN pathogenesis, we sequenced the genome of Streptococcus equi subsp. zooepidemicus strain MGCS10565, a group C organism that caused a very large and unusually severe epidemic of nephritis in Brazil. The genome is a circular chromosome of 2,024,171 bp. The genome shares extensive gene content, including many virulence factors, with genetically related group A streptococci, but unexpectedly lacks prophages. The genome contains many apparently foreign genes interspersed around the chromosome, consistent with the presence of a full array of genes required for natural competence. An inordinately large family of genes encodes secreted extracellular collagen-like proteins with multiple integrin-binding motifs. The absence of a gene related to speB rules out the long-held belief that streptococcal pyrogenic exotoxin B or antibodies reacting with it singularly cause PSGN. Many proteins previously implicated in GAS PSGN, such as streptokinase, are either highly divergent in strain MGCS10565 or are not more closely related between these species than to orthologs present in other streptococci that do not commonly cause PSGN. Our analysis provides a comparative genomics framework for renewed appraisal of molecular events underlying APSGN pathogenesis

Co-bedding as a Comfort measure For Twins undergoing painful procedures (CComForT Trial)

<p>Abstract</p> <p>Background</p> <p>Co-bedding, a developmental care strategy, is the practice of caring for diaper clad twins in one incubator (versus separating and caring for each infant in separate incubators), thus creating the opportunity for skin-to-skin contact and touch between the twins. In studies of mothers and their infants, maternal skin-to-skin contact has been shown to decrease procedural pain response according to both behavioral and physiological indicators in very preterm neonates. It is uncertain if this comfort is derived solely from maternal presence or from stabilization of regulatory processes from direct skin contact. The intent of this study is to compare the comfort effect of co-bedding (between twin infants who are co-bedding and those who are not) on infant pain response and physiologic stability during a tissue breaking procedure (heelstick).</p> <p>Methods/Design</p> <p>Medically stable preterm twin infants admitted to the Neonatal Intensive Care Unit will be randomly assigned to a co-bedding group or a standard care group. Pain response will be measured by physiological and videotaped facial reaction using the Premature Infant Pain Profile scale (PIPP). Recovery from the tissue breaking procedure will be determined by the length of time for heart rate and oxygen saturation to return to baseline. Sixty four sets of twins (n = 128) will be recruited into the study. Analysis and inference will be based on the intention-to-treat principle.</p> <p>Discussion</p> <p>If twin contact while co-bedding is determined to have a comforting effect for painful procedures, then changes in current neonatal care practices to include co-bedding may be an inexpensive, non invasive method to help maintain physiologic stability and decrease the long term psychological impact of procedural pain in this high risk population. Knowledge obtained from this study will also add to existing theoretical models with respect to the exact mechanism of comfort through touch.</p> <p>Trial registration</p> <p>NCT00917631</p

M Types of Group A Streptococcal Isolates Submitted to the National Centre for Streptococcus (Canada) from 1993 to 1999

The National Centre for Streptococcus (NCS) (Canada) determined the group A streptococcal (GAS) M types of 4,760 Canadian isolates submitted between 1993 and 1999 by classic serotyping. The 10 most frequently identified M types were M1 (26.4%), M12 (9.8%), M28 (8.9%), M3 (6.8%), M4 (6.2%), M11 (4.8%), M89 (3.1%), M6 (3.0%), M2 (2.6%), and M77 (1.9%). Nontypeable isolates accounted for 15.4% of the collection. The province of Ontario submitted 51.1% of the isolates, followed by Quebec (21.2%) and Alberta (13.9%). Together, these three provinces constituted 71.3% of the Canadian population in 1996. The numbers of M types M1, M12, M28, and M3 occurred most frequently in subjects whose ages were <1 to 15 years and 25 to 45 years, as well as in the elderly (60 to 90 years). Further analysis found that the four most frequently identified M types from blood, brain, and cerebrospinal fluid were M1 (28.2%), M28 (9.2%), M12 (9.1%), and M3 (8.2%), with 13.4% of isolates being nontypeable. The four isolates from throats most frequently identified were M1 (19.5%), M12 (15.3%), M3 (8.6%), and M28 (5%) with 19.4% of isolates being nontypeable. The sic gene of a subset of M1 strains (9.5% of the M1 collection) was sequenced. Of 36 sic types identified, the four most common were sic1.01 (22.8%), sic1.02 (14.9%), sic1.135 (10.5%), and sic1.178 (9.6%). Together these four sic types further characterized nearly 60% of the M1 strains sequenced. In summary, from the years 1993 to 1999, the NCS detected 54 M types, of which 10 different M types constituted 73.5% of the collection. M1 was the most common GAS M type circulating in the Canadian population, responsible for more than a quarter of the isolates typed. The most common throat isolates differed in M-type and proportion from those of invasive isolates. Sequencing the sic gene further characterized the most common M-type serotype 1 in a fashion that may be useful for epidemiologic investigations

Preparing a Community Hospital to Manage Work-related Exposures to Infectious Agents in BioSafety Level 3 and 4 Laboratories

Construction of new BioSafety Level (BSL) 3 and 4 laboratories has raised concerns regarding provision of care to exposed workers because of healthcare worker (HCW) unfamiliarity with precautions required. When the National Institutes of Health began construction of a new BSL-4 laboratory in Hamilton, Montana, USA, in 2005, they contracted with St. Patrick Hospital in Missoula, Montana, for care of those exposed. A care and isolation unit is described. We developed a training program for HCWs that emphasized the optimal use of barrier precautions and used pathogen-specific modules and simulations with mannequins and fluorescent liquids that represented infectious body fluids. The facility and training led to increased willingness among HCWs to care for patients with all types of communicable diseases. This model may be useful for other hospitals, whether they support a BSL-4 facility, are in the proximity of a BSL-3 facility, or are interested in upgrading their facilities to prepare for exotic and novel infectious diseases

Group A Streptococcus Gene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis

The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component regulatory systems) was studied. Several known and previously uncharacterized GAS virulence gene regulators were highly expressed compared to the constitutively expressed control gene proS. To examine in vivo gene transcription in a controlled setting, three cynomolgus macaques were infected with strain MGAS5005, an organism that is genetically representative of most serotype M1 strains recovered from pharyngitis and invasive disease episodes in North America and Western Europe. These three animals developed clinical signs and symptoms of GAS pharyngitis and seroconverted to several GAS extracellular proteins. Real-time RT-PCR analysis of throat swab material collected at intervals throughout a 12-day infection protocol indicated that expression profiles of a subset of GAS genes accurately reflected the profiles observed in the human pediatric patients. The results of our study demonstrate that analysis of in vivo GAS gene expression is feasible in throat swab specimens obtained from infected human and nonhuman primates. In addition, we conclude that the cynomolgus macaque is a useful nonhuman primate model for the study of molecular events contributing to acute pharyngitis caused by GAS