Snake bites are life-threatening injuries that can require intensive care. The diagnosis and treatment of venomous snake bites is sometimes difficult for clinicians because sufficient information has not been provided in clinical practice. Here we review the literature to present the proper management of bites by mamushi, habu, and yamakagashi snakes, which widely inhabit Japan and other Asian countries. No definite diagnostic markers or kits are available for clinical practice; therefore, definitive diagnosis of snake-venom poisoning requires positive identification of the snake and observation of the clinical manifestations of envenomation. Mamushi (Gloydius blomhoffii) bites cause swelling and pain that spreads gradually from the bite site. The platelet count gradually decreases due to the platelet aggregation activity of the venom and can decrease to <100,000/mm3. If the venom gets directly injected into the blood vessel, the platelet count rapidly decreases to <10,000/mm3 within 1 h after the bite. Habu (Protobothrops flavoviridis) bites result in swelling within 30 min. Severe cases manifest not only local signs but also general symptoms such as vomiting, cyanosis, loss of consciousness, and hypotension. Yamakagashi (Rhabdophis tigrinus) bites induce life-threatening hemorrhagic symptoms and severe disseminated intravascular coagulation with a fibrinolytic phenotype, resulting in hypofibrinogenemia and increased levels of fibrinogen degradation products. Previously recommended first-aid measures such as tourniquets, incision, and suction are strongly discouraged. Once airway, breathing, and circulation have been established, a rapid, detailed history should be obtained. If a snake bite is suspected, hospital admission should be considered for further follow-up. All venomous snake bites can be effectively treated with antivenom. Side effects of antivenom should be prevented by sufficient preparation. Approved antivenoms for mamushi and habu are available. Yamakagashi antivenom is used as an off-label drug in Japan, requiring clinicians to join a clinical research group for its use in clinical practice.

Background: Corynebacterium ulceranscan cause a diphtheria-like illness, especially when the bacterium is lysogenized with atoxgene-carrying bacteriophage that produces diphtheria toxin. Acquisition of toxigenicity upon phage lysogenization is a common feature ofC. ulceransandC. diphtheriae. However, because of a lack ofC. ulceransgenome information, a detailed comparison of prophages has not been possible between these two clinically important and closely related bacterial species.Results: We determined the whole genome sequence of the toxigenicC. ulcerans0102 isolated in Japan. The genomic sequence showed a striking similarity with that ofCorynebacterium pseudotuberculosisand, to a lesser extent, with that ofC. diphtheriae. The 0102 genome contained three distinct prophages. One of these, ΦCULC0102-I, was atox-positive prophage containing genes in the same structural order as fortox-positiveC. diphtheriaeprophages. However, the primary structures of the individual genes involved in the phage machinery showed little homology between the two counterparts.Conclusion: Taken together, these results suggest that thetox-positive prophage in this strain ofC. ulceranshas a distinct origin from that ofC. diphtheriaeNCTC 13129.

Yamakagashi (Rhabdophis tigrinus) is a species of pit viper present throughout Russia and Eastern Asia. Although R. tigrinus venom is known to induce life-threatening hemorrhagic symptoms, the clinical characteristics and effective treatment of R. tigrinus bites remain unknown. The present study aimed to clarify these issues.

Corynebacterium ulcerans is a pathogen causing diphtheria-like illness to humans. In contrast to diphtheria by Corynebacterium diphtheriae circulating mostly among humans, C. ulcerans infection is zoonotic. The present study aimed to clarify how a zoonotic pathogen C. ulcerans circulates among wild birds and animals. By screening 380 birds, a single strain of toxigenic C. ulcerans was isolated from a carnivorous bird, ural owl (Strix uralensis). The bacterium was also isolated from two individuals of Japanese shrew-mole (Urotrichus talpoides), a food preference of the owl. Analysis by ribotyping showed that the owl and mole isolates were classified in a group, suggesting that C. ulcerans can be transmissible among wild birds and their prey animals. Moreover, our isolates were found to belong to a group of previously reported C. ulcerans isolates from dogs and a cat, which are known to serve as sources for human infection. The findings suggest that the shrew-mole may be a potential reservoir of a zoonotic pathogen C. ulcerans.

Rhabdophis tigrinus (Yamakagashi snake) is a rear-fanged colubrid snake present throughout Russia and Asia. Its venom induces life-threatening hemorrhagic symptoms and severe disseminated intravascular coagulation with a fibrinolytic phenotype. R. tigrinus antivenom manufactured by the immunization of horses to neutralize the venom has the risk of adverse events such as anaphylaxis and serum sickness disease. It should be used when benefit is greater than the risk of adverse effects; however, its efficacy has not been well evaluated. Although our previous survey of nine cases demonstrated that seven of all cases treated with antivenom survived, the clinical characteristics and prognosis without antivenom administration remained unclear. We assumed that R. tigrinus antivenom administration overlaps self-recovery with supportive care. We aimed to determine the association between antivenom administration and outcome with further analyzed cases. We retrospectively reviewed the records of the Japan Snake Institute between January 1, 1973 and December 31, 2013. Antivenom and without antivenom groups were compared with regard to baseline demographic features, treatment-related factors, and outcomes. In total, 34 patients were analyzed (97% male, median age 37.5 years). Twenty-five patients were further examined from our previous study. On admission, the median levels of fibrinogen and fibrinogen degradation products were 35 mg/dL and 200 μg/mL, respectively, and platelet counts were 107,000/mm3. The median disseminated intravascular coagulation score (defined by the Japanese Association of Acute Medicine) was 5. Antivenom was administered to 19 patients, with a median interval of 32 h between bite and antivenom administration. The in-hospital mortality rate was 12%. In univariate analysis, baseline characteristics and laboratory data were not significantly different between the antivenom and without antivenom groups. Hospital mortality in the antivenom group was significantly better than that in the without antivenom group (0% vs. 26.7%, P = 0.03). Moreover, the number of patients developing renal failure requiring hemodialysis was significantly lower in the antivenom group (5.3% vs. 40.0%, P = 0.03). In our small retrospective study, antivenom administration was likely to be effective in the management of R. tigrinus bites. Apparently, further research is required to confirm its efficacy.

Many pathogenic bacteria, including Escherichia coli and Vibrio cholerae, can become viable but nonculturable (VBNC) following exposure to specific stress conditions. Corynebacterium diphtheriae, a known human pathogen causing diphtheria, has not previously been shown to enter the VBNC state. Here, we report that C. diphtheriae can become VBNC when exposed to low temperatures. Morphological differences in culturable and VBNC C. diphtheriae were examined using scanning electron microscopy. Culturable cells presented with a typical rod-shape, whereas VBNC cells showed a distorted shape with an expanded center. Cells could be transitioned from VBNC to culturable following treatment with catalase. This was further evaluated via RNA sequence-based transcriptomic analysis and reverse-transcription quantitative PCR of culturable, VBNC, and resuscitated VBNC cells following catalase treatment. As expected, many genes showed different behavior by resuscitation. The expression of both the diphtheria toxin and the repressor of diphtheria toxin genes remained largely unchanged under all four conditions (culturable, VBNC, VBNC after the addition of catalase, and resuscitated cells). This is the first study to demonstrate that C. diphtheriae can enter a VBNC state and that it can be rescued from this state via the addition of catalase. This study helps to expand our general understanding of VBNC, the pathogenicity of VBNC C. diphtheriae, and its environmental survival strategy.