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Query: UMLS:C0031350 (pharyngitis)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although most cases of acute pharyngitis are viral in origin, antibiotics are overused in its treatment. Streptococcus pyogenes (group A streptococcus, GAS), the principal bacterial pathogen of acute sore throat, is responsible for merely 5-30% of cases. Moreover, GAS pharyngitis is currently the only commonly occurring form of acute pharyngitis for which antibiotic therapy is definitely indicated. Therefore the differentiation between GAS pharyngitis and that of viral etiology is crucial. Accordingly, scientific societies as well as respected advisory bodies in Europe and North America, issued guidelines for the management of acute pharyngitis with the aim of minimizing unnecessary antibiotic prescriptions in its treatment. The aim of this review work is to confront the state of the art in acute GAS pharyngitis diagnosis and treatment with different approaches to its management represented by current European and North American guidelines. Although based on scientific evidence, international guidelines differ substantially in opinions whether GAS pharyngitis diagnosis should be based on microbiological testing, clinical algorithm or a combination of both. On the other hand, some European guidelines consider GAS pharyngitis to be a mild, self-limiting disease that does not require a specific diagnosis or antimicrobial treatment except in high-risk patients. There is an agreement among guidelines that if antibiotic therapy is indicated, phenoxymethyl penicillin should be the drug of choice to treat GAS pharyngitis.
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PMID:Management of acute streptococcal pharyngitis: still the subject of controversy. 3221 21

Streptococcus pyogenes (group A streptococcus; GAS) causes 600 million cases of pharyngitis annually worldwide. There is no licensed human GAS vaccine despite a century of research. Although the human oropharynx is the primary site of GAS infection, the pathogenic genes and molecular processes used to colonize, cause disease, and persist in the upper respiratory tract are poorly understood. Using dense transposon mutant libraries made with serotype M1 and M28 GAS strains and transposon-directed insertion sequencing, we performed genome-wide screens in the nonhuman primate (NHP) oropharynx. We identified many potentially novel GAS fitness genes, including a common set of 115 genes that contribute to fitness in both genetically distinct GAS strains during experimental NHP pharyngitis. Targeted deletion of 4 identified fitness genes/operons confirmed that our newly identified targets are critical for GAS virulence during experimental pharyngitis. Our screens discovered many surface-exposed or secreted proteins - substrates for vaccine research - that potentially contribute to GAS pharyngitis, including lipoprotein HitA. Pooled human immune globulin reacted with purified HitA, suggesting that humans produce antibodies against this lipoprotein. Our findings provide new information about GAS fitness in the upper respiratory tract that may assist in translational research, including developing novel vaccines.
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PMID:Streptococcus pyogenes genes that promote pharyngitis in primates. 3249 46

Mouse models are invaluable resources for studying the pathogenesis and preclinical evaluation of therapeutics and vaccines against many human pathogens. Infections caused by group A streptococcus (GAS, Streptococcus pyogenes) are heterogeneous ranging from mild pharyngitis to severe invasive necrotizing fasciitis, a subgroup of necrotizing soft-tissue infections (NSTIs). While several strains of mice including BALB/c, C3H/HeN, CBA/J, and C57BL/10 offered significant insights, the human specificity and the interindividual variations on susceptibility or resistance to GAS infections limit their ability to mirror responses as seen in humans. In this chapter, we discuss the advanced recombinant inbred (ARI) BXD mouse model that mimics the genetic diversity as seen in humans and underpins the feasibility to map multiple genes (genetic loci) modulating GAS NSTI. GAS produces a myriad of virulence factors, including superantigens (SAg). Superantigens are potent immune toxins that activate T cells by cross-linking T cell receptors with human leukocyte antigen class-II (HLA-II) molecules expressed on antigen-presenting cells. This leads to a pro-inflammatory cytokine storm and the subsequent multiple organ damage and shock. Inbred mice are innately refractive to SAg-mediated responses. In this chapter, we discuss the versatility of the HLA-II transgenic mouse model that allowed the biological validation of known genetic associations to GAS NSTI. The combined utility of ARI-BXD and HLA-II mice as complementary approaches that offer clinically translatable insights into pathomechanisms driven by complex traits and host genetic context and novel means to evaluate the in vivo efficiency of therapies to improve outcomes of GAS NSTI are also discussed.
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PMID:Systems Genetics Approaches in Mouse Models of Group A Streptococcal Necrotizing Soft-Tissue Infections. 3307 68


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