Epidemiological shifts in and impact of COVID-19 on streptococcal toxic shock syndrome in Japan: A genotypic analysis of group A Streptococcus isolates.

OBJECTIVES: Streptococcal toxic shock syndrome (STSS) is caused by group A Streptococcus (GAS; Streptococcus pyogenes) strains. In Japan, the number of STSS cases has decreased; however, the underlying reason remains unclear. Moreover, information on distribution and prevalence of specific emm types in STSS cases is scarce. Hence, we investigated the reason for the decreased number of STSS cases in Japan. METHODS: We genotyped emm of 526 GAS isolates obtained from 526 patients with STSS between 2019 and 2022. The distributions of emm types in each year were compared. RESULTS: The emm1 type was predominant, with the highest proportion in 2019, which decreased after 2020 following the onset of the coronavirus disease 2019 (COVID-19) pandemic. Strains isolated during the pandemic correlated with strains associated with skin infection, whereas those isolated during the prepandemic period correlated with strains associated with both throat and skin infections. The decrease in the annual number of STSS cases during the COVID-19 pandemic could be due to a decreased proportion of strains associated with pharyngeal infections. CONCLUSIONS: Potential associations between pandemic and STSS numbers with respect to public health measures, such as wearing masks and changes in healthcare-seeking behavior, may have affected the number of GAS-induced infections.

Molecular characterization and antimicrobial resistance of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2013 to 2018.

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and puerperal sepsis and shows high mortality. Its primary cause is group A streptococcus (GAS, Streptococcus pyogenes). In this study, we genotyped the cell-surface M virulence protein gene (emm) from 621 GAS isolates obtained from patients with STSS in Japan in 2013-2018 and performed antimicrobial susceptibility testing using the broth microdilution method. The predominant emm type was found to be 1, followed by 89, 12, and 3, which were identified in more than 70 % of STSS isolates. The proportions of emm3 and emm89 increased from 2.4 % and 12.0 %, respectively, during 2010-2012 to 5.6 % and 23.3 % during 2013-2018. In contrast, the proportion of emm1 decreased from 60.6 % to 39.3 % during the same two periods. Some emm types showed increasing proportions and were not isolated from patients with STSS in 2010-2012. Among these, an emm76 type increased in prevalence and was not included in the 30-valent M protein-based vaccine. Continual investigation of changes in the epidemiology of GAS which causes STSS can provide useful monitoring information such as future vaccination strategies and the emergence status of antimicrobial-resistant bacteria.

T serotyping of group a streptococcus isolated from patients with pharyngitis or streptococcal toxic shock syndrome in Japan between 2005 and 2017.

Streptococcus pyogenes (group A streptococcus; GAS) is an important gram-positive human pathogen capable of causing diseases ranging from mild superficial skin and pharyngeal infections to more severe invasive diseases, including streptococcal toxic shock syndrome (STSS). GAS produces a T protein, and T serotyping has considerable discriminatory power for epidemiological characterization of GAS. To clarify the relationship between STSS and pharyngitis in Japan, we examined the T serotypes of GAS strains isolated from clinical specimens of streptococcal infections (STSS, 951 isolates; pharyngitis, 16268 isolates) from 2005 to 2017. The most prevalent T serotype from pharyngitis isolates was T12, followed by T1, T4, and TB3264. The most prevalent T serotype from STSS isolates was T1, followed by TB3264. Trend of increase and decrease in the frequency of T1 or TB3264 isolation from pharyngitis was correlated with that of STSS patients. The increase of T1 or TB3264 strain-infection in pharyngitis patients may increase the probability of causing STSS, indicating that careful monitoring of GAS serotypes is essential for the prediction of rapid increase of STSS in time to develop effective management strategies.

Post-marketing surveillance of levofloxacin 0.5% ophthalmic solution for external ocular infections.

BACKGROUND: Levofloxacin 0.5% ophthalmic solution is an antibacterial formulation, which was approved and marketed for the treatment of ocular infections in Japan in 2000. OBJECTIVE: This study was designed to investigate the safety and efficacy of levofloxacin 0.5% ophthalmic solution in patients who received treatment for external ocular bacterial infections in regular clinical practice. METHODS: Patients were recruited from more than 800 medical facilities in Japan, in accordance with Japanese Ministry of Health, Labour and Welfare ordinance guidelines. They were followed during three distinct time periods: April 2000 to December 2001, January 2002 to June 2003, and July 2003 to December 2004. RESULTS: Information from 6760 patients receiving levofloxacin for the treatment of a variety of ocular infections was collected. Levofloxacin was well tolerated: adverse drug reactions (ADRs) were reported in 42 of 6686 patients (0.63%), with no serious ADRs reported. The most commonly reported ADRs were ocular disorders such as blepharitis, eye irritation, and punctate keratitis. The incidence of ADRs did not differ significantly with age, but it was significantly higher in females (0.82%) than in males (0.36%; p = 0.028). A clinical response was observed in 95.5% of patients receiving levofloxacin, with no difference in response between the three time periods. The rate of response to levofloxacin by bacterial disease ranged from 97.4% in keratitis to 88.3% in dacryocystitis. The rate was lower in patients with dacryocystitis, elderly patients, patients with a long duration of illness, and relapsing cases (all p < 0.001). CONCLUSION: This post-marketing surveillance of levofloxacin, conducted over 4 years, confirms the safety and efficacy of levofloxacin in regular clinical use and highlights that levofloxacin is a promising treatment for a variety of external ocular bacterial infections.

Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.

The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.

Effect of vitamin E-bonded dialyzer on eosinophilia in haemodialysis patients.

BACKGROUND: Eosinophilia in haemodialysis patients probably results from allergy to haemodialysis-related materials, including dialyzer membranes. We examined the effects of vitamin E-bonded dialyzers on eosinophil counts in haemodialysis patients. METHODS: We enrolled seven patients who were on regular haemodialysis and had sustained eosinophilia. White blood cell, eosinophil, CD4- and CD8-positive lymphocyte counts, and serum interleukin-5 (IL-5) and IgE levels were determined before, 2 and 4 weeks after switching to vitamin E-bonded dialyzers. RESULTS: Eosinophil and CD4-positive lymphocyte counts and serum IL-5 were significantly (P = 0.003, 0.003 and 0.031, respectively) decreased after switching to vitamin E-bonded dialyzers. CD8-positive lymphocyte counts and serum IgE levels were unaltered. Crossover tests in two cases reproduced the higher eosinophilia within 4 weeks after returning to the original non-vitamin E-bonded dialyzer. CONCLUSION: Vitamin E-bonded dialyzers may ameliorate eosinophilia through a mechanism mediated by a decrease in IL-5 secretion by CD4-positive lymphocytes.

A low-protein diet concomitant with high calorie intake preserves renal function and structure in diabetic OLETF rats.

BACKGROUND: Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a spontaneous type 2 diabetes model, were used to clarify whether and how a low-protein diet prevents progressive diabetic nephropathy, in terms of functional and structural parameters. METHODS: A low-protein diet (LPD) with 11% protein content, was compared to the normal 24% protein diet (NPD) without keeping isocaloric conditions. Daily food intake, body weight, and blood and urine chemistry were serially measured in rats from 10 through 60 weeks of age, and renal clearance studies and histological evaluations were performed at 40 and 60 weeks of age. RESULTS: Daily calorie intake was higher in the OLETF rats fed on the LPD than in those fed on the NPD throughout the experiment. Due to this hyperphagia, fasting blood glucose and hemoglobin (Hb)A1c were dramatically increased in the LPD-fed OLETF rats at 30 weeks and thereafter, whereas urinary protein excretion was decreased by more than half after 26 weeks in the LPD group. Plasma concentrations of total cholesterol and triglyceride were decreased in the LPD-fed OLETF rats at 40 and 60 weeks. Inulin clearance in the LPD group was higher only at 60 weeks of age. The glomerular sclerosis index (GSI) and tubulointerstitial index (TII) were preserved in the LPD group. The LPD induced a decrease in tubulointerstitial macrophage infiltration as compared with the NPD at both 40 and 60 weeks of age, but glomerular macrophage infiltration was not alleviated. CONCLUSIONS: A low-protein diet, despite the worsening hyperglycemia caused by hyperphagia, not only reduced proteinuria but also ameliorated hyperlipidemia in OLETF rats, thereby preserving renal function and structure in diabetic nephropathy, probably via a macrophage-mediated mechanism.

[A case of fulminant acute poststreptococcal glomerulonephritis showing mesangiolysis and crescent formation preceded by erysipelas].

A 66-year-old man with erysipelas was admitted with complaints of oliguria and massive proteinuria/hematuria. He was diagnosed as having acute poststreptococcal glomerulonephritis(APSGN) due to erysipelas infected by group A streptococcus pyogenes. On admission, his white cell count increased to 31,000, and CRP was 27.3 mg/dl. Serum urea nitrogen and creatinine were increased to 90.1 mg/dl and 4.5 mg/dl, respectively. He had diabetes mellitus(HbA1c 7.9%) and liver dysfunction(total bilirubin 3.5 mg/dl, AST 76 IU, ALT 41 IU) caused by alcoholic liver cirrhosis. Hypocomplementemia was found in addition to ASO 216 U/ml and ASK 10,240 x. After antibiotics treatment was initiated, inflammation of the erysipelas began to improve. Disseminated intravascular coagulation syndrome, probably due to sepsis, occurred on the 5th hospital day. He died of gastrointestinal bleeding on the 18th hospital day. Renal autopsy revealed 37% formation of fibrocellular crescents, and marked mesangiolysis was noted by light microscopy. Granular deposition of C3 and IgG was seen along the capillary walls on immunofluorescence study. Intramembranous deposits were scattered on electron microscopy. This case illustrates a fulminant type of APSGN, which was in part attributed to the presence of diabetes and alcoholic liver cirrhosis. Histological findings of crescent formation and marked mesangiolysis may account for the fulminant clinical course.