ADVANCES IN IMMUNOLOGY
CONTENTS GROUP A STREPTOCOCCAL DISEASES AND THEIR GLOBAL BURDEN MOLECULAR MARKERS FOR THE STUDY OF STREPTOCOCCAL EPIDEMIOLOGY EPIDEMIOLOGY AND PATHOGENICITY OF ZOONOTIC STREPTOCOCCI ADHERENCE AND INVASION OF STREPTOCOCCI TO EUKARYOTIC CELLS AND THEIR ROLE IN DISEASE PATHOGENESIS COMMON REGULATORS OF VIRULENCE IN STREPTOCOCCI HOST–PATHOGEN INTERACTIONS IN STREPTOCOCCAL IMMUNE SEQUELAE IMMUNOPATHOGENESIS OF STREPTOCOCCAL DEEP TISSUE INFECTIONS MODULATION OF THE COAGULATION SYSTEM DURING SEVERE STREPTOCOCCAL DISEASE GROUP A STREPTOCOCCAL VACCINE CANDIDATES: POTENTIAL FOR THE DEVELOPMENT OF A HUMAN VACCINE CLINICAL MANAGEMENT OF THE MOST COMMON GROUP A B-HEMOLYTIC STREPTOCOCCAL INFECTIONS GROUP A STREPTOCOCCAL DISEASES AND THEIR GLOBAL BURDEN ABSTRACT GROUP A STREPTOCOCCUS (GAS) OR STREPTOCOCCUS PYOGENES HAS BEEN RECOGNISED AS AN IMPORTANT HUMAN PATHOGEN SINCE EARLY DAYS OF MODERN MICRO- BIOLOGY, AND IT REMAINS AMONG THE TOP TEN CAUSES OF MORTALITY FROM AN INFECTIOUS DISEASE CLINICAL MANIFESTATIONS ATTRIBUTABLE TO THIS ORGANISM ARE PERHAPS THE MOST DIVERSE OF ANY SINGLE HUMAN PATHOGEN THESE ENCOMPASS INVASIVE GAS INFECTIONS, WITH HIGH MORTALITY RATES DESPITE EFFECTIVE ANTIMICROBIALS, TOXIN-MEDIATED DISEASES INCLUDING SCARLET FEVER AND STREPTOCOCCAL TOXIC SHOCK SYNDROME, THE AUTOIMMUNE SEQUELAE OF RHEUMATIC FEVER AND GLOMERULONEPHRITIS WITH POTENTIAL FOR LONG-TERM DISABILITY, AND NUISANCE MANIFESTATIONS OF SUPER?CIAL SKIN AND PHARYNGEAL INFEC- TION, WHICH CONTINUE TO CONSUME A SIZABLE PROPORTION OF HEALTHCARE RESOURCES ALTHOUGH AN HISTORICAL PERSPECTIVE INDICATES MAJOR OVERALL REDUCTIONS IN GAS INFECTION RATES IN THE MODERN ERA, CHIE?Y AS A RESULT OF WIDESPREAD IMPROVEMENTS IN SOCIOECONOMIC CIRCUMSTANCES, THIS PATHOGEN REMAINS AS A LEADING INFECTIOUS CAUSE OF GLOBAL MORBIDITY AND MORTALITY MORE THAN 18 MILLION PEOPLE GLOBALLY ARE ESTIMATED TO SUFFER FROM SERIOUS GAS DISEASE THIS BURDEN DISPROPORTIONALLY AFFECTS LEAST AF?UENT POPULATIONS, AND IS A MAJOR CAUSE OF ILLNESS AND DEATH AMONG CHILDREN AND YOUNG ADULTS, INCLUDING PREGNANT WOMEN, IN LOW-RESOURCE SETTINGS WE REVIEW GAS TRANSMISSION CHARACTERISTICS AND PREVENTION STRATEGIES, HISTORICAL ADVANCES IN IMMUNOLOGY AND GEOGRAPHICAL TRENDS AND REPORT ON THE ESTIMATED GLOBAL BURDEN DISEASE ATTRIBUTABLE TO GAS THE LACK OF SYSTEMATIC REPORTING MAKES ACCURATE ESTIMATION OF RATES DIF?CULT THIS HIGHLIGHTS THE NEED TO SUPPORT IMPROVED SURVEILLANCE AND EPIDEMIOLOGICAL RESEARCH IN LOW-RESOURCE SETTINGS, IN ORDER TO ENABLE BETTER ASSESSMENT OF NATIONAL AND GLOBAL DISEASE BURDENS, TARGET CONTROL STRATEGIES APPROPRIATELY AND ASSESS THE SUCCESS OF CONTROL INTERVENTIONS INTRODUCTION TRANSMISSION AND PREVENTION OF GAS INFECTIONS TRANSMISSION PHARYNGEAL CARRIAGE OF S PYOGENES PREVENTION CONTACT MANAGEMENT TRENDS IN THE BURDEN OF DISEASE DUE TO GAS LONG-TERM TEMPORAL TRENDS EPIDEMICS TRENDS IN GAS DRUG RESISTANCE THE GLOBAL BURDEN OF GAS DISEASE ACUTE RHEUMATIC FEVER RHEUMATIC HEART DISEASE ACUTE POST-STREPTOCOCCAL GLOMERULONEPHRITIS INVASIVE GAS DISEASE SUPERFICIAL GAS DISEASE WITHIN-COUNTRY VARIATION: DISPARITIES BETWEEN DIFFERENT POPULATIONS CONCLUSIONS REFERENCES 1 INTRODUCTION IN THE TWENTY-?RST CENTURY, GROUP A STREPTOCOCCUS (GAS) RETAINS MAJOR IMPORTANCE AS A GLOBAL CAUSE OF MORBIDITY AND MORTALITY THIS GRAM-POSITIVE BACTERIUM WAS INITIALLY RECOGNISED AS THE CAUSATIVE AGENT OF ERYSIPELAS AND PUERPERAL SEPSIS IN THE LATE NINETEENTH CENTURY (BISNO AND STEVENS 2000) LACKING ANY NATURAL HOST APART FROM HUMANS, IT IS WELL ADAPTED TO TRANSMISSION WITHIN POPULATIONS CHARACTERISED BY CROWDING, LIMITED ACCESS TO HYGIENE AND INADEQUATE MEDICAL CARE THUS, IN THE CURRENT AGE, IT IS CHIE?Y A DISEASE OF POVERTY ALTHOUGH THE NAME ‘PYOGENES’ (PUS- FORMING) DESCRIBES THE SUPPURATIVE MANIFESTATIONS OF INFECTION, AN ASTONISHING RANGE OF CLINICAL SYNDROMES IS ATTRIBUTABLE TO GAS (FIG 1) IN ADDITION TO ILLNESS RESULTING FROM DIRECT INFECTION, IMMUNOLOGICALLY AND TOXIN-MEDIATED PATHOLOGY, THE GLOBAL BURDEN OF DISEASE ATTRIBUTABLE TO GAS INCLUDES THE DOWNSTREAM COMPLICATIONS OF THESE CONDITIONS, SUCH AS STROKE AND INFECTIVE ENDOCARDITIS COMPLICATING RHEUMATIC HEART DISEASE (RHD) AND RENAL ADVANCES IN IMMUNOLOGY