Clinical and Microbiological Features of Fulminant Haemolysis Caused by Clostridium perfringens Bacteraemia: Unknown Pathogenesis.

Bacteraemia brought on by Clostridium perfringens has a very low incidence but is severe and fatal in fifty per cent of cases. C. perfringens is a commensal anaerobic bacterium found in the environment and in the intestinal tracts of animals; it is known to produce six major toxins: α-toxin, ß-toxin, ε-toxin, and others. C. perfringens is classified into seven types, A, B, C, D, E, F and G, according to its ability to produce α-toxin, enterotoxin, and necrotising enterotoxin. The bacterial isolates from humans include types A and F, which cause gas gangrene, hepatobiliary infection, and sepsis; massive intravascular haemolysis (MIH) occurs in 7-15% of C. perfringens bacteraemia cases, resulting in a rapid progression to death. We treated six patients with MIH at a single centre in Japan; however, unfortunately, they all passed away. From a clinical perspective, MIH patients tended to be younger and were more frequently male; however, there was no difference in the toxin type or genes of the bacterial isolates. In MIH cases, the level of θ-toxin in the culture supernatant of clinical isolates was proportional to the production of inflammatory cytokines in the peripheral blood, suggesting the occurrence of an intense cytokine storm. Severe and systemic haemolysis is considered an evolutionary maladaptation as it leads to the host's death before the bacterium obtains the benefit of iron utilisation from erythrocytes. The disease's extraordinarily quick progression and dismal prognosis necessitate a straightforward and expedient diagnosis and treatment. However, a reliable standard of diagnosis and treatment has yet to be put forward due to the lack of sufficient case analysis.

Massive intravascular hemolysis is an important factor in Clostridium perfringens-induced bacteremia.

Clostridium perfringens bacteremia is rare but often fatal. In particular, once bacteremia with massive intravascular hemolysis (MIH) occurs, the mortality rate is extremely high. However, because of its rarity, the detailed pathophysiology of this fulminant form of bacteremia is unclear. To elucidate the detailed pathogenesis of MIH, we retrospectively reviewed the data of all patients with C. perfringens bacteremia from two university hospitals from 2000 to 2014. The medical records and laboratory data of 60 patients with bacteremia, including 6 patients with MIH and 54 patients without MIH, were analyzed. Patients with MIH had higher rates of intense pain at onset, impaired consciousness, shock at presentation, hematuria, metabolic acidosis, and gas formation than patients without MIH. The antibiotic susceptibility of the clinical isolates was not significantly different between the two groups. All patients with MIH, although treated with appropriate antimicrobial agents, died within 26 h of admission due to rapidly progressive acute lung injury or acute respiratory distress syndrome, and the median time from arrival at the hospital to death was only 4 h and 20 min. When clinicians observe intravascular hemolysis in blood samples from patients with characteristic symptoms of MIH, they should prepare for a severe disease outcome. The underlying pathophysiology of fulminant cases must be investigated.

Pathogenic Characterization of Clostridium perfringens Strains Isolated From Patients With Massive Intravascular Hemolysis.

Sepsis caused by Clostridium perfringens infection is rare but often fatal. The most serious complication leading to poor prognosis is massive intravascular hemolysis (MIH). However, the molecular mechanism underlying this fulminant form of hemolysis is unclear. In the present study, we employed 11 clinical strains isolated from patients with C. perfringens septicemia and subdivided these isolates into groups H and NH: septicemia with (n = 5) or without (n = 6) MIH, respectively. To elucidate the major pathogenic factors of MIH, biological features were compared between these groups. The isolates of two groups did not differ in growth rate, virulence-related gene expression, or phospholipase C (CPA) production. Erythrocyte hemolysis was predominantly observed in culture supernatants of the strains in group H, and the human erythrocyte hemolysis rate was significantly correlated with perfringolysin O (PFO) production. Correlations were also found among PFO production, human peripheral blood mononuclear cell (PBMC) cytotoxicity, and production of interleukin-6 (IL-6) and interleukin-8 (IL-8) by human PBMCs. Analysis of proinflammatory cytokines showed that PFO induced tumor necrosis factor-α (TNF-α), IL-5, IL-6, and IL-8 production more strongly than did CPA. PFO exerted potent cytotoxic and proinflammatory cytokine induction effects on human blood cells. PFO may be a major virulence factor of sepsis with MIH, and potent proinflammatory cytokine production induced by PFO may influence the rapid progression of this fatal disease caused by C. perfringens.

Case Report: An Outbreak of Food-Borne Typhoid Fever Due to Salmonella enterica Serotype Typhi in Japan Reported for the First Time in 16 Years.

For the first time in 16 years, a food-borne outbreak of typhoid fever due to Salmonella enterica serotype Typhi was reported in Japan. Seven patients consumed food in an Indian buffet at a restaurant in the center of Tokyo, while one was a Nepali chef in the restaurant, an asymptomatic carrier and the implicated source of this outbreak. The multiple-locus variable-number tandem repeat analysis showed 100% consistency in the genomic sequence for five of the eight cases.

[Contribution of rapid diagnostic test in the treatment of infectious diseases].

According to aging of population and medical progress, the risk and mortality rate of pneumonia have been increased. In the causative organism inspection, smear-culture examination of sputum is the gold standard. When it is difficult to obtain high quality sputum and to culture the causative organism, or when antibiotics are previously administered, we have no choice but to start the treatment with pathogenic bacteria unknown. In these cases, it is necessary to select an appropriate test method for expecting pathogen. If bacteria are detected in laboratory culture, it is difficult to distinguish whether it is a causative or colonizers. Future development is expected in rapid diagnostic methods.

Suppression of osteoblast Toll-like receptor 2 signaling by endothelin-1.

Peripheral endothelin-1 (ET-1) levels are increased in chronic systemic disorders such as congestive cardiac failure, diabetes and chronic renal failure. Bone infections are also associated with poor prognoses in these conditions. In the present study, we examined the alterations in Toll-like receptor 2 (TLR2) signaling induced by ET-1 in an in vitro osteoblast cell model. The TLR2-positive murine osteoblast cell line MC3T3-E1 was treated with heat-killed Listeria monocytogenes (HKLM), a TLR2 ligand, in the presence or absence of ET-1. We examined TLR2 expression, intranuclear NF-κB phosphorylation and interleukin 6 (IL-6) production. ET-1 suppressed cell surface expression of TLR2, NF-κB phosphorylation and IL-6 production. As TLR2 represents an important mechanism by which osteoblasts recognize bacterial pathogens, a continuously elevated ET-1 status may impair pathogenic recognition by osteoblasts and consequently affect bone metabolism during infections.

H1N1/09 influenza A virus infection of immortalized first trimester human trophoblast cell lines.

PROBLEM: Although high maternal mortality was reported in the most recent pandemic of swine-origin influenza A H1N1/09 (H1N1/09), its direct effects on the feto-placental unit are unknown. In the present study, we examined the susceptibility of immortalized human trophoblasts to clinical isolates of pandemic 2009 H1N1 influenza A (H1N1/09) virus. METHOD OF STUDY: The H1N1/09 virus was isolated from a patient with influenza, sequenced and identified as the A/Narita/2009 (H1N1) strain. The trophoblast cell lines Swan71 and HTR8 were challenged with the virus and examined for the expression of H1N1/09 viral RNA and proteins. RESULTS: Viral RNA and proteins were observed 24 hr after inoculation. However, viral release was not detected. CONCLUSION: First trimester human trophoblast cell lines were susceptible to the H1N1/09 influenza A virus. However, viral release and cytopathic effects were minimal. Our data suggest that placental damage by the H1N1/09 virus may be limited.

Disseminated gonococcal infection in Japan: a case report and literature review.

Disseminated gonococcal infection (DGI) is quite a rare condition, especially in the Japanese population; only 10 cases have been reported in case notes and minutes. We describe a man in which Neisseria gonorrhoeae was suspected to have infected the patient through his pharynx. He developed chills, fever, tonsillitis, papules, tenosynovitis and migratory polyarthralgia without genitourinary symptoms. After conducting a literature review, we suggest that being male is a possible risk factor and that blood culture can be used for diagnosing DGI in Japan. DGI should be considered as a diagnosis for patients with fever, dermatitis and joint pain in Japan.

A case of syphilis presenting with initial syphilitic hepatitis and serological recurrence with cerebrospinal abnormality.

We present the case of an immunocompetent 50-year-old Japanese man with a cerebrospinal fluid (CSF) abnormality relevant to syphilis; his original presentation was liver dysfunction, the etiology of which was uncertain until positive serology for syphilis was identified. Liver dysfunction was promptly resolved after oral penicillin therapy; however, serological recurrence developed. CSF abnormality associated with syphilis was confirmed by subsequent lumbar puncture. Syphilis should be included in the differential diagnosis of patients with liver dysfunction of unknown etiology, and possible neurosyphilis should be considered when the treatment becomes refractory, even when there is no evidence of neurological manifestations.

Hepatocellular carcinoma with direct invasion to the stomach causing gastrointestinal hemorrhage.

A 54-year-old man had undergone transcatheter arterial embolization (TAE) three times to treat hepatitis B virus-related hepatocellular carcinoma (HCC), but recurrence was found in June 2005. A large tumor in the left lateral portion of the liver showed extrahepatic growth and was attached to the gastric wall. TAE was performed a forth time. In September 2005, the patient was admitted with worsening anemia. Computed tomography and upper gastrointestinal endoscopy revealed that the HCC had directly invaded the stomach and caused gastrointestinal hemorrhage. Endoscopic hemostasis was effective, but the patient died because of worsening hepatic failure.