Areas of Expertise (5)
Infection Prevention and Control
Featured Articles (5)
Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodiesJournal of Experimental Medicine
2008 Pneumococcus is one of the most important human pathogens that causes life-threatening invasive diseases, especially at the extremities of age. Capsular polysaccharides (CPSs) are known to induce protective antibodies; however, it is not feasible to develop CPS-based vaccines that cover all of the 90 disease-causing serotypes. We applied a genomic approach and described the antibody repertoire for pneumococcal proteins using display libraries expressing 15–150 amino acid fragments of the pathogen's proteome. Serum antibodies of exposed, but not infected, individuals and convalescing patients identified the ANTIGENome of pneumococcus consisting of ∼140 antigens, many of them surface exposed. Based on several in vitro assays, 18 novel candidates were preselected for animal studies, and 4 of them showed significant protection against lethal sepsis. Two lead vaccine candidates, protein required for cell wall separation of group B streptococcus (PcsB) and serine/threonine protein kinase (StkP), were found to be exceptionally conserved among clinical isolates (>99.5% identity) and cross-protective against four different serotypes in lethal sepsis and pneumonia models, and have important nonredundant functions in bacterial multiplication based on gene deletion studies. We describe for the first time opsonophagocytic killing activity for pneumococcal protein antigens. A vaccine containing PcsB and StkP is intended for the prevention of infections caused by all serotypes of pneumococcus in the elderly and in children.
Streptococcus Pneumoniae: Epidemiology, Risk Factors, and Clinical FeaturesSeminars in Respiratory and Critical Care Medicine
2005 Streptococcus pneumoniae is the most common cause of both pneumonia overall and fatal pneumonia. Antibiotic resistance has developed worldwide and is most frequent in pneumococcal serotypes that are most prevalent in children (types/groups 6, 14, 19, and 23). The incidence of pneumococcal disease is the highest in children < 2 years of age and in adults > 65 years of age. Other important risk factors are chronic heart and lung disease, cigarette smoking, and asplenia. A 23-valent capsular polysaccharide vaccine and a heptavalent proteinpolysaccharide conjugate vaccine are currently available. The latter is specially designed for pediatric use because small children respond poorly to polysaccharide antigens. Both vaccines are efficacious in prevention of invasive pneumococcal disease. The clinical presentation of pneumococcal pneumonia is variable, and neither clinical features nor laboratory or radiographic findings can reliably predict the etiology of pneumonia. Blood culture is the most important tool for establishing a definitive diagnosis, but Gram's stains and sputum culture are also of value in skilled hands. A recently developed urinary antigen test may provide a rapid diagnosis of pneumococcal pneumonia in adults. Penicillin (penicillin G/amoxicillin) remains the drug of choice for strains that are fully sensitive or have a moderately decreased susceptibility to penicillin, whereas cefotaxime and ceftriaxone are the first-line alternatives in cases with higher levels of resistance.
Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in adults aged 65 years or older: a prospective studyThe Lancet
2001 The effectiveness of influenza and pneumococcal vaccination in the prevention of hospital admissions and death has not been assessed prospectively. We have therefore examined the effects of influenza and pneumococcal vaccination in individuals aged 65 years and older in a 3-year prospective study, between Dec 1, 1998 and May 31, 1999.
Pneumococcal disease in Sweden: experiences and current situationThe American Journal of Medicine
1999 During the last decade, the incidence of invasive pneumococcal disease in Sweden has risen, seemingly due chiefly to an increasing incidence of pneumococcal bacteremia among the elderly. On the other hand, mortality due to invasive disease in Sweden is low, approximately 10% for bacteremic pneumococcal pneumonia. Beta-lactam resistance in Streptococcus pneumoniae is still a relatively minor problem in Sweden, with only 3%–4% of strains demonstrating decreased susceptibility to penicillin. However, local outbreaks of pneumococcal disease with up to 10% resistance have occurred among children, especially in southern Sweden.
Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly peopleThe Lancet
1998 We assessed the effectiveness of a 23-valent pneumococcal vaccine in the prevention of pneumococcal pneumonia and of pneumonia overall in non-immunocompromised-middle-aged and elderly people.