Rhabdophis tigrinus (Yamakagashi) Bites in Japan Over the Last 50 Years: A Retrospective Survey

Introduction:Rhabdophis snakes, which include 27 species, are rear-fanged venomous snakes that are widely distributed from India to East Asia and Russia. Severe envenomation by R. tigrinus (Yamakagashi snake) in Japan and R. subminiatus in Southeast Asia has been reported. The epidemiology of R. tigrinus bites, such as geographical features, the incidence, and changes in the number of bites over time have not been comprehensively examined. Hence, we intended to clarify the epidemiological features of R. tigrinus bites through a careful review of scientific data over the last 50 years in Japan.Methods: Patient records of R. tigrinus bites between 1971 and 2020 at the Japan Snake Institute were examined retrospectively. The following were ascertained: patient characteristics, clinical symptoms, laboratory data, treatment-related factors, and hospital mortality. These variables were compared in the antivenom and the without-antivenom groups.Results: Over the 50-year study period, 43 R. tigrinus bites, including five fatal cases, were encountered. Severe cases of R. tigrinus bites have been treated with antivenom since 1985; however, fatalities occurred in 2006 and 2020. R. tigrinus bite cases have been well-distributed in the western part of Japan since 2000. The mortality rate in the antivenom group was significantly lower in the patient group that was not administered the antivenom (0 vs. 23.8%, p = 0.048).Conclusion: This study clarified the epidemiology of R. tigrinus bites in Japan over a 50-year period. Almost all severe cases of R. tigrinus bites have been treated with the antivenom in the current situation, and fatalities occurred in cases not treated with the antivenom. It is important to diagnose R. tigrinus bites in the early phase of the clinical course. The antivenom, the definitive treatment for R. tigrinus bites, is an unapproved drug. Hence, approval needs to be obtained for the drug.

Attempt to Develop Rat Disseminated Intravascular Coagulation Model Using Yamakagashi (Rhabdophis tigrinus) Venom Injection

Disseminated intravascular coagulation, a severe clinical condition caused by an underlying disease, involves a markedly continuous and widespread activation of coagulation in the circulating blood and the formation of numerous microvascular thrombi. A snakebite, including that of the Yamakagashi (Rhabdophis tigrinus), demonstrates this clinical condition. Thus, an animal model using Yamakagashi venom was constructed. Yamakagashi venom was administered to rats, and its lethality and the changes in blood coagulation factors were detected after venom injection. When 300 μg venom was intramuscularly administered to 12-week-old rats, (1) they exhibited hematuria with plasma hemolysis and died within 48 h; (2) Thrombocytopenia in the blood was observed in the rats; (3) irreversible prolongation of prothrombin time in the plasma to the measurement limit occurred; (4) fibrinogen concentration in the plasma irreversibly decreased below the measurement limit; and (5) A transient increase in the plasma concentration of D-dimer was observed. In this model, a fixed amount of Rhabdophis tigrinus venom injection resulted in the clinical symptom similar to the human pathology with snakebite. The use of the rat model is very effective in validating the therapeutic effect of human disseminated intravascular coagulation condition due to snakebite.