Vaccine-induced, but not natural immunity, against the Streptococcal inhibitor of complement protects against invasive disease.

Highly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full-length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole-blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We, therefore, propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full-length SIC permits the development of protective antibodies against all SIC domains.

Bromine, bear-claw scratch fasciotomies, and the Eagle effect: management of group A streptococcal necrotising fasciitis and its association with trauma.

Necrotising fasciitis is a rare, but potentially fatal, soft-tissue infection. Historical depictions of the disease have been described since classical times and were mainly recorded in wartime reports of battle injuries. Although several different species of bacteria can cause necrotising fasciitis, perhaps the most widely known is group A streptococcus (GAS). Infection control, early surgical debridement, and antibiotic therapy are now the central tenets of the clinical management of necrotising fasciitis; these treatment approaches all originate from those used in wars in the past 150 years. We review reports from the 19th century, early 20th century, and mid-20th century onwards to show how the management of necrotising fasciitis has progressed in parallel with prevailing scientific thought and medical practice. Historically, necrotising fasciitis has often, but not exclusively, been associated with penetrating trauma. However, along with a worldwide increase in invasive GAS disease, recent reports have cited cases of necrotising fasciitis following non-combat-related injuries or in the absence of antecedent events. We also investigate the specific association between GAS necrotising fasciitis and trauma. In the 21st century, molecular biology has improved our understanding of GAS pathogenesis, but has not yet affected attributable mortality.

Current views of haemolytic streptococcal pathogenesis.

PURPOSE OF REVIEW: Increasing disease caused by beta-haemolytic streptococci indicates the need for improved understanding of pathogenesis. RECENT FINDINGS: Streptococcus pyogenes, or group A Streptococcus (GAS), causes significant disease worldwide. The closely related Streptococcus dysgalactiae subspecies equisimilis (SDSE) is increasingly recognized as causing a similar disease spectrum. Whole-genome sequencing applied to the study of outbreaks may reveal factors that contribute to pathogenesis and changes in epidemiology. The role of quorum sensing in biofilm formation, and interspecies communication with other streptococci, is discussed. GAS has evolved multiple mechanisms to evade the humoral arm of innate immunity, including complement, which is well known in protecting the host from bacteria, and the coagulation-fibrinolytic system, which is increasingly recognized as an innate immune effector. SUMMARY: Molecular biology has enhanced our understanding of the intricate balance of host-pathogen interactions that result in clearance or establishment of invasive streptococcal infection. Although the skin and oropharynx remain the usual ecological niche of GAS and SDSE, occasionally the bacteria find themselves within deeper tissues and blood. Recent research has armed us with better knowledge of bacterial adaptations to this alternative environment. However, the challenge is to translate this knowledge into clinical practice, through the development of novel therapeutic options and ultimately a vaccine against GAS.

Acute lung injury and other serious complications of Plasmodium vivax malaria.

Plasmodium vivax infection is classified among the so-called benign malarias, but it is increasingly recognised that serious and even life-threatening complications may occur. We present the case of a returning traveller with P vivax infection who developed acute lung injury 3 days into treatment, and discuss the serious complications of this infection. The case highlights the fact that P vivax infection is benign by name but not always by nature.

Hospital-based study of viridans streptococcal bacteraemia in children and adults.

OBJECTIVES: To assess the proportion and clinical significance of bacteraemia caused by viridans streptococci (VS) in immunocompetent adults and children. METHODS: Over a 25-month period, we collected data on all patients with VS bacteraemia at a UK district general hospital. RESULTS: VS caused 50/723 (6.9%) adult and 13/106 (12.3%) paediatric community-acquired bacteraemias. Of the 43 adult and 12 paediatric patient notes reviewed, 26 (47.3%) cultures were of 'definite' or 'probable' clinical significance. No patients were neutropenic and overall penicillin resistance was 11/55 (20.0%). Amongst adults, there were five (11.6%) confirmed or suspected cases of infective endocarditis compared to none in the paediatric cohort. Similar proportions of adults (16.3%) and children (16.7%) had lower respiratory tract infections. Among non-significant cultures, a history of seizures was observed in one (1.3%) adult and four (33.3%) children (p=0.008). Thirty-day mortality was 7.3%. No children and four adults died, one directly attributable to infection. Median adult inpatient stay was 11 days compared to 2 days in the paediatric population (p=0.003). CONCLUSION: Despite cases of infective endocarditis and an incidence of penicillin resistance of 20%, mortality directly attributable to VS infection in immunocompetent adults and children was rare.