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Group A Streptococcus virulence and host factors in two toddlers with rheumatic fever following toxic shock syndrome

Abstract number: P2224

Smeesters P., Drèze P-A., Biarent D., Van Melderen L., Vergison A.

Objective: Rheumatic Fever (RF) 'classically' occurs after Group A Streptococcus (GAS) pharyngitis in children over 5 years in developping countries. GAS Toxic Shock Syndrome (TSS) is uncommon and does not usually lead to RF. Host-pathogen interactions are of utmost importance for the development of RF and TSS since specific combinations of GAS and hosts appear to be necessary for the disease to occur.

The present report describes bacterial and host determinants of non-related Belgian toddlers who developped RF after TSS. A molecular analysis of both the bacterial emm-type and superantigens (exotoxins that are phage-encoded) and HLA host factors was carried out in an attempt to decipher the combination that may lead to such uncommon, but very similar presentations.

Methods: The diagnosis of TSS and RF were based on the consensus definition and modified Jones criteria. emm-typing was performed using the CDC sequencing protocol. The presence of 17 superantigen genes was detected by PCR and sequencing. Phages lysates were obtained by mitomycin C induction and observed by electron microscopy. The HLA molecular typing was performed using PCR and sequence-specific oligo-nucleotide genotyping method.

Results: A 13-month-old boy and a 14-month-old girl presented a GAS TSS with fever, severe hypotension, renal impairment, coagulopathy, thrombocytopenia and meningitis. They were treated with penicillin, clindamycin, intravenous immunoglobulin and intensive care supportive therapy. After 2 and 3 weeks respectively, multiple subcutaneous nodules as well as migratory polyarthritis or monoarthritis developed in both children. RF diagnosis was established since 1 and 2 major plus 3 minor Jones criteria were fulfilled for the 2 children respectively. The molecular analysis of bacterial virulence genes revealed that the 2 GAS isolates belonged to the usual, although distinct, invasive emm-types 1 and 3. Both isolates carried a wide set of prophage-encoded virulence factors, with only the speG and speA superantigen-encoding genes in common. Both patients shared the HLA DQB1*0301 allele which has been associated with susceptibility to GAS necrotising fasciitis.

Morphological diversity bacteriophages in GAS isolates 1 and 2. Transmission electron microscopy after negative staining shows 4 bacteriophages belonging to the siphoviridae family. They present icosahedral heads of variable size and morphology (B and C: 45 nm, A and D: 55 nm) and non-contractile tails of variable length (A: 230 nm, B: 240 nm, C and D: 180 nm) (Magnification ×160,000).

Conclusion: Our study exemplified the complexity and modularity of the host-pathogen interactions in GAS diseases. More documented reports and systematic studies are needed to better understand the underlying molecular and physiologic mechanisms involved in such severe pathologies.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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