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A map showing the relative locations of cases of redback spider bites: Osaka, Nara, and Fukuoka Prefectures.
Source publication
Redback spiders (Latrodectus hasselti) (RBSs) are venomous spiders that have recently spread to Asia from Australia. Since the first case report in 1997 (Osaka), RBS bites have been a clinical and administrative issue in Japan; however, the clinical characteristics and effective treatment of RBS bites, particularly outside Australia remains unclear...
Context in source publication
Context 1
... the 5-year study period, 28 patients were identified from 10 hospitals. The areas where RBS bites were re- ported were limited to three prefectures: Osaka, Nara, and Fukuoka (Figure 2). The patient characteristics are summarized in Table 1; 39.3% were male and the median age was 32 years. ...
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Citations
... Currently, the antivenom against R. tigrinus bites is provided for use only in clinical research because it is an unapproved drug in Japan (1,4,8). Our research group is currently working on the supply of antivenom as a serum therapy against R. tigrinus bites (9)(10)(11)(12)(13). ...
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.
... Currently, three types of antitoxin-gas gangrene equine antitoxin (Fig. 1A), diphtheria equine antitoxin (Fig. 1B), and botulism equine antitoxin (Fig. 1C)-are supplied by the government (i.e., they are available under the Kokuyu vaccine supply system), whereas tetanus antitoxin, Gloydius blomhoffii (mamushi) equine antivenom, and Protobothrops flavoviridis (habu) equine antivenom (Fig. 1D) are supplied commercially. 6 Rhabdophis tigrinus (yamakagashi) equine antivenom (Fig. 1E) and Latrodectus hasselti (redback spider) equine antivenom (Fig. 1F) are supplied by research groups in Japan [11][12][13] (Table 1). ...
... Since the first case reported in Osaka in 1997, RBS bites have been a clinical and administrative issue in Japan. 11 The adult female redback is characterized by a spherical black body (approximately 10 mm long) with a prominent red stripe on the upper side of the abdomen and a red streak on the underside (Fig. 3). Alpha-latrotoxin, the main toxin produced by the redback spider, causes synaptic vesicle exocytosis from the presynaptic terminal via a calcium-dependent mechanism, leading to the release of catecholamines and acetylcholine. ...
... Alpha-latrotoxin, the main toxin produced by the redback spider, causes synaptic vesicle exocytosis from the presynaptic terminal via a calcium-dependent mechanism, leading to the release of catecholamines and acetylcholine. 11 Currently, two types of redback spider antivenom exist; these are produced by the Commonwealth Serum Laboratories in Australia and by our research group in Japan. 11,12 Because these antivenoms are used as off-label drugs in Japan, clinicians are required to join a clinical research group to use either of the antivenoms in clinical practice. ...
Blood serum from immunized humans or animals (e.g., horses) contains relevant antibodies and has been used as serum therapy to treat many diseases or envenomation events. The effectiveness of blood serum was initially discovered in 1890 when Kitasato and von Behring observed the effectiveness of this type of therapy against diphtheria and tetanus. Serum therapies played an important role in the advancement of modern medicine prior to the development of penicillin and steroids. At present, several types of serum therapy remain in clinical use. However, some physicians have a limited understanding of the nature and the benefits of serum therapy and the factors that require particular attention. In this review, we set out to clarify the benefits, cautions, and potential applications of serum therapy in the context of conditions such as gas gangrene, diphtheria, botulism, and tetanus and bites from three snake species (mamushi, habu, and yamakagashi) and the redback spider. It is hoped that this review will help clinicians to learn about clinical serum therapies and become familiar with their applications.
... R EDBACK SPIDERS (RBS) were first noticed in metropolitan Tokyo on September 25th, 2014, and they are rapidly becoming a nationwide problem in Japan. 1 However, physicians in Japan are unfamiliar with RBS bites as they rarely occur, resulting in limited clinical experience. 2 These spiders are very common in Australia and have recently spread to Southeast and West Asia. 2 We believe that there is a risk of them spreading to East Asia due to climate change and intensive interaction between people. ...
... R EDBACK SPIDERS (RBS) were first noticed in metropolitan Tokyo on September 25th, 2014, and they are rapidly becoming a nationwide problem in Japan. 1 However, physicians in Japan are unfamiliar with RBS bites as they rarely occur, resulting in limited clinical experience. 2 These spiders are very common in Australia and have recently spread to Southeast and West Asia. 2 We believe that there is a risk of them spreading to East Asia due to climate change and intensive interaction between people. ...
... The symptoms of RBS bites are usually mild and localized, such as localized pain and erythema. 2 However, these bites would often prove fatal until the development of antivenom, which is manufactured by the immunization of horses. 3 Redback spider bites are treated with the specific RBS antivenom produced by the Commonwealth Serum Laboratories in Australia. ...
Aim:
Redback spiders are rapidly becoming a nationwide problem in Japan. The domestic production of antivenom for redback spider bites has been started because of extremely low supply. The purpose of this study was to investigate the ability of emergency physicians to recognize redback spider bites and to examine the demand for antivenom and identify the ideal choice for storage.
Methods:
Questionnaires examining the ability to recognize redback spider bites, the demand for antivenom, and overall level of preparedness were sent to 271 emergency medical service centers in Japan in March 2015.
Results:
Completed questionnaires were returned by 156 medical institutions (58%). Only 25% of the institutes correctly answered regarding the recognition of redback spider bites. A demand for the new, domestically produced antivenom was reported by 55% of the institutes. Antivenom demand was high and increased with the ability to recognize redback spider bites (0 correct answers, n = 24 [42.9%]; 1-2 answers, n = 32 [55.2%]; three answers, n = 28 [71.8%]; P = 0.02). The storage of antivenom within their prefectures or regions was the best option for initial supply planning. Approximately 90% of the emergency centers showed an ability to use the antivenom safely.
Conclusion:
The recognition of redback spider bites was low; however, the demand for antivenom was high. The storage of antivenom within their own prefectures or regions was considered to be the best option for initial supply planning. Emergency medical service centers are also good candidates for storage and safe use of antivenom.
... We previously reported that symptoms of redback spider (RBS) bites are usually mild and localized, such as local pain and erythema [1]. However, fatal cases had been reported before the development of antivenom, which is manufactured by the immunization of horses [2,3]. ...
... The definitive treatment for RBS envenomation is to use the specific RBS antivenom produced by the Commonwealth Serum Laboratories (CSL) in Australia. However, a serious issue with the current practice is that RBS antivenom is used as an off-label drug in Japan and must be privately imported from Australia [1]. ...
... To compound this issue, RBS antivenom imports from CSL were suspended in autumn 2013. The Ministry of Health, Labour and Welfare (MHLW) launched a research group to evaluate the safety and efficacy of the antivenom and to organize and maintain information on RBS bites from April 2013 [1]. In autumn 2014, with great effort by MHLW, the research group will obtain several vials of antivenom for emergency use. ...
In autumn 2014, with great effort by the Ministry of Health, Labour and Welfare, the research group will obtain several vials of redback spider (RBS) antivenom for emergency use. However, these small amounts of antivenom are insufficient to cover the demands from majority of hospitals in Japan. The research group carefully discussed the domestic RBS antivenom production by themselves for this emergency. We have now entered the second stage for large-scale antivenom production. Although the domestic production of RBS antivenom has started, great caution is required as we move forward with this plan.
Serum prepared from immunized humans or animals (e.g., horses), which contains antibodies, has been used for serum therapy or passive immunization to treat many diseases or envenomation events since its initial discovery in 1890, when Kitasato and von Behring observed the efficacy of this type of therapy against diphtheria and tetanus. At present, several types of serum therapies are used in clinical practice. Currently, three types of antitoxins--the gas gangrene equine antitoxin, diphtheria equine antitoxin, and botulism equine antitoxin are supplied by the government (Kokuyu vaccine), whereas tetanus human immune globulin, Mamushi (Gloydius blomhoffii) equine antivenom, and Habu (Protobothrops flavoviridis) equine antivenom are available commercially. Yamakagashi (Rhabdophis tigrinus) equine antivenom and red back spider equine antivenom are supplied by research groups in Japan. Summaries of clinical serum therapies are unavailable in the literature. As a result, clinicians have little opportunity to learn about and become familiar with these therapies. In this review, we attempt to clarify the benefits, precautions, and potential applications of serum therapies. Through this review, we hope that clinicians will have the opportunity to learn about and become familiar with clinical serum therapies.
In September 1995 it was reported that the redback spider (Latrodectus hasseltii Thorell) had invaded Japan. To date 84 redback spider bite cases have been reported, and of these, seven employed the antivenom. In the past, antivenom have been imported from Australia, but because of restrictions on exportation thereof it was evident that nearly all of the antivenom present in Japan would expire during 2014. In 2014 a plan was proposed to experimentally manufacture and stockpile a horse antiserum for ourselves, employing redback spiders indigenous to Japan. A total of 11,403 female spiders were captured alive: 1,217 from the vicinity of Nishinomiya City, Hyogo prefecture, and 10,186 from Osaka prefecture. Of these, 10,007 females were dissected and the venom was extracted from the venom glands removed from each individual and subjected to crude purification to give 4 lots, of which the majority was α-latrotoxin. Among them, a large amount of single lot with an estimated protein content of 236 mg is subsequently scheduled to be used for immunizing horses. We also determined lethal toxicity of the venom (LD50: 9.17 μg per mouse), and established the assay for the determination of anti-lethal titer of antivenom in mouse.
This is the first report of the large-scale experimentally production of an equine antivenom against redback spider (Latrodectus hasseltii) lived in Japan. We captured 10,000 redback spiders in Japan and prepared the toxoids of crude venom extract, mixed the toxoids with mineral oil adjuvant, and immunized repeatedly it to healthy horses over a period of several weeks. Then, we separated the horse plasma, and purified the γ-globulin fraction and stocked as a purified antivenom concentrate. Consequently, we manufactured approximately 6,500 vials of a single-dose freeze-dried test lot from a portion of the purified γ-globulin fraction, equivalent to the extract derived from 520 spiders. This test lot had an antitoxin titer comparable to that of a similar drug commercially available overseas (liquid preparation), and the other quality met all reference specifications pre-specified based on the Minimum Requirements for Biological Products and other guidelines relevant for existing antivenom drug products in Japan.
