Guliz Erdem

Priming the Immune System for Heart Disease: A Perspective on Group A Streptococci

Although immune responses against group A streptococci and the heart have been correlated with antibodies and T cell responses against cardiac myosin, there is no unifying hypothesis about carditis caused globally by many different serotypes. Our study identified disease-specific epitopes of human cardiac myosin in the development of rheumatic carditis in humans. We found that immune responses to cardiac myosin were similar in rheumatic carditis among a small sample of worldwide populations, in which immunoglobulin G targeted human cardiac myosin epitopes in the S2 subfragment hinge region within S2 peptides containing amino acid residues 842-992 and 1164-1272. An analysis of rheumatic carditis in a Pacific Islander family confirmed the presence of potential rheumatogenic epitopes in the S2 region of human cardiac myosin. Our report suggests that cardiac myosin epitopes in rheumatic carditis target the S2 region of cardiac myosin and are similar among populations with rheumatic carditis worldwide, regardless of the infecting group A streptococcal M serotype.

Group A Streptococcal Isolates Temporally Associated with Acute Rheumatic Fever in Hawaii: Differences from the Continental United States

BACKGROUND The annual incidence of acute rheumatic fever (ARF) in Hawaii has remained several times higher than that in the continental United States, particularly among ethnic Polynesians. The emm types of Streptococcus pyogenes that are associated with this nonsuppurative complication have, to our knowledge, not been previously reported in Hawaii. METHODS Patients with ARF were identified through an active surveillance system at Kapiolani Medical Center (Honolulu, HI), the only pediatric tertiary care referral hospital in Hawaii. Specimens were obtained by throat culture from patients who met the Jones criteria for ARF at the time of presentation (63 patients), prior to penicillin treatment, and from consenting family contacts (10 individuals). Eight patients and 2 close family contacts with positive throat culture results were identified from February 2000 through December 2005. Group A streptococci isolates were characterized by emm sequence typing. RESULTS Unusual emm types were temporally associated with the onset of ARF. Emm types 65/69 (from 2 patients), 71, 92, 93, 98, 103, and 122 were isolated from the 8 patients with ARF, and emm types 52 and 101 were isolated from the 2 household contacts. CONCLUSIONS So-called rheumatogenic emm types and/or serotypes, which were previously associated with ARF in the continental United States, were not found in this study. Instead, emm types that are not commonly included among group A streptococci isolates in the continental United States and that are seldom, if ever, temporally associated with ARF were identified. These findings suggest that unusual group A streptococci emm types play a significant role in the epidemiology of ARF in Hawaii.

An insert in the covS gene distinguishes a pharyngeal and a blood isolate of Streptococcus pyogenes found in the same individual

Expression of the extensive arsenal of virulence factors by Streptococcus pyogenes is controlled by many regulators, of which CovRS is one of the best characterized and can influence ∼15 % of the genome. Animal models have established that mutants of covRS arise spontaneously in vivo resulting in highly invasive organisms. We analysed a pharyngeal and a blood isolate of S. pyogenes recovered from the same individual 13 days apart. The two isolates varied in many phenotypic properties including SpeB production, which were reflected in transcriptomic analyses. PFGE, multilocus sequence typing and partial sequencing of some key genes failed to show any differences except for an 11 bp insert in the covS gene in the blood isolate which caused a premature termination of transcription. Complementation of a fully functional covS gene into the blood isolate resulted in high expression of CovS and expression of speB. These results, showing a pharyngeal and a blood isolate from a single individual differing by a simple insertion, provide evidence for the model that regulatory gene mutations allow S. pyogenes to invade different niches in the body.

Streptococcal emm Types in Hawaii: A region with high incidence of acute rheumatic fever

Background: The clinical epidemiology of group A streptococcal (GAS) infections in Hawaii seems different from that in the continental United States with frequent skin infections and endemically high rates of acute rheumatic fever (ARF). Methods: GAS emm types in Hawaii were determined to identify any possible association between the emm types and specific clinical manifestations. A convenience sample of 1482 Hawaii GAS isolates collected between February 2000 and December 2005 was used. All isolates were characterized by emm sequence typing. The distribution of emm types in Hawaii was compared with the published continental US data for pharyngeal and invasive GAS strains, the CDC database from similar time periods, as well as with emm types present in a candidate GAS vaccine. Results: Ninety-three distinct emm types were recognized among the 1482 GAS isolates. The most frequently identified emm types in order of decreasing frequency were 12, 1, 28, 4, 22, 77, 81, 58, 65/69, 49, 74, 85, 92, 75, 101 and 2. Of this study sample, 27 of the 50 invasive GAS isolates belonged to uncommon continental US emm types (54% in Hawaii cultures vs. 10% reported from the continental US). Of the 1179 pharyngeal isolates, 509 belonged uncommon continental US emm types (43% in Hawaii cultures vs. 27% reported from the continental US). Conclusions: The prevalent emm types in Hawaii differ from those in the continental US. The prevalence of these unusual emm types might limit the effectiveness of any proposed multivalent type-specific GAS vaccine in Hawaii.

Intracranial hemorrhage in herpes simplex encephalitis: an unusual presentation

We describe a 14-month-old patient with atypical presentation of herpes simplex encephalitis. She initially presented with fever, lethargy, seizures, and large hemorrhages in the right parietal lobe, and clinical findings suggestive of a hypercoagulable state. The etiology of coagulation abnormality was not identified, although it was suggested as a possible causative factor in severe bleeding along with acute neuronal lysis as a result of infection. Although large intracerebral hemorrhages are occasionally described with systemic herpes infection, this presentation is unusual beyond the infant period.

Emergence of Erythromycin- and Clindamycin-Resistant Streptococcus pyogenes emm 90 Strains in Hawaii

ABSTRACT We identified 12 erythromycin- and clindamycin-resistant emm 90 group A streptococcus (GAS) isolates during a retrospective invasive disease survey in Hawaii. A comparison with 20 type-matched isolates showed all resistant isolates to be emm 90.4b with the constitutive or inducible macrolide-lincosamide-streptogramin B resistance phenotype (cMLSB or iMLSB). All isolates had the same pulsed-field gel electrophoresis (PFGE) pattern, suggesting clonal spread.

Erythromycin-Resistant Group A Streptococcal Isolates Collected between 2000 and 2005 in Oahu, Hawaii, and Their emm Types

ABSTRACT We examined erythromycin and clindamycin susceptibilities with Etest methodology among 546 group A streptococcal isolates collected in Hawaii between February 2000 and November 2004. Erythromycin resistance was low (3.1%). No isolate was clindamycin resistant. The prevalence of erythromycin resistance in group A streptococci remains low in Hawaii.

ACUTE RHEUMATIC FEVER IN AMERICAN SAMOA

Acute rheumatic fever is common among Samoans in Hawaii. During 2 visits to evaluate the magnitude of rheumatic fever problem among Samoans in American Samoa, we identified 148 patients with rheumatic fever on penicillin prophylaxis. Retrospective chart reviews were done showing possible delays in diagnosis of acute rheumatic fever.

Molecular Epidemiologic Comparison of 2 Unusual Clusters of Group A Streptococcal Necrotizing Fasciitis in Hawaii

Two clusters of necrotizing fasciitis (NF) due to group A streptococcus (GAS) were identified on the Hawaiian islands of Kauai and Maui during 1997 and 2002, respectively. The emm gene sequence types and the pulsed-field gel electrophoresis patterns were determined for 6 isolates recovered from patients with NF and for 116 isolates recovered from patients with temporally associated community-acquired GAS infection. No predominant emm type was identified, and the emm types of 64 (52.5%) of the isolates were considered to be uncommon in the continental United States. These findings suggest that unusual emm types might be responsible for invasive GAS infections in patients from Hawaii.

Characterization of a community cluster of group a streptococcal invasive disease in Maui, Hawaii.

A community cluster of severe group A streptococcal skin infections occurred in Maui, Hawaii with 3 fatal cases of necrotizing fasciitis in 2002. emm types 1, 12, 58, 74, 85 and 109 were identified from 8 patients. emm types 74 and 109 have not been previously described in the United States according to the Centers for Disease Control and Prevention database. The identification of uncommon emm types suggested that group A streptococcal sero-types in Hawaii are different from those in the continental United States and can result in serious disease.