Although specific antivenom is available in Taiwan, respiratory failure and general pain frequently accompany Bungarus multicinctus envenomation and there have been few reports on the management of B. multicinctus envenomation. We retrospectively analyzed 44 cases of B. multicinctus bite admitted to Taichung Veterans General Hospital (VGH) or to Taipei VGH. Demographic data, treatment, and outcome of patients with and without respiratory failure were compared. In this study, 20.5% patients had bites without noticeable signs or symptoms of significant envenoming, 27.3% developed respiratory failure, and 27.3% experienced general pain. Bivalent specific antivenom for B. multicinctus and N. atra was administered in all envenomed cases. Respiratory failure occurred 1.5–6.5 hours post-bite and general pain occurred 1–12 hours post-bite. Specific antivenom for B. multicinctus and N. atra at the recommended dose (i.e., 2–4 vials) might not effectively prevent respiratory failure and pain. Respiratory failure, general pain, and autonomic effects after B. multicinctus bite were probably caused, at least partly, by β-bungarotoxin. Although general weakness, ptosis, dysarthria, and dilated pupils were significantly associated with respiratory failure, their predictive value could not be accurately determined in such a retrospective study. Due to the rapid onset of respiratory failure, every suspected envenomed case thus should be closely monitored in the first few hours. We recommend the initial administration of four vials of antivenom in all envenomation cases, and a subsequent four vials be considered if the patient's condition is deteriorating. Prospective evaluation of the antivenom dosing regimen is urgently needed to improve B. multicinctus envenomation treatment.

Deinagkistrodon acutus envenomation is associated with severe hematological and wound complications but is rarely described. Herein, we report three cases of victims bitten by D. acutus and indicate that rapid-onset severe coagulopathy and thrombocytopenia are distinct features of D. acutus snakebite, which are not observed in other crotaline snakebites (i.e., Trimeresurus stejnegeri and Protobothrops mucrosquamatus) in Taiwan. The toxic effects could occur as early as 2 to 3 h following D. acutus envenomation and persist if the administration of specific antivenom is delayed or even not commenced. Based on our findings, 2 to 4 vials of specific antivenom as the first dose should be administered to victims and repeated at 6 to 8 h intervals if coagulopathy or thrombocytopenia persists. Fresh frozen plasma or platelet replacement is probably safe as an adjunct therapy for D. acutus bite in the presence of venom-induced consumptive coagulopathy. Severe coagulopathy and thrombocytopenia could occur as early as 2 to 3 h after D. acutus envenomation. The current recommendation for antivenom is 2 to 4 vials as the first dose and repeated every 6– to 8 h if coagulopathy or thrombocytopenia persists. These cases studied may be helpful to first-line medical personnel in the early diagnosis and management of D. acutus envenomation among other crotaline snakebites in Taiwan.

Background: Trimeresurus stejnegeri stejnegeri bite induces tissue swelling, pain, thrombocytopenia, rhabdomyolysis, and acute renal failure. However, the incidence of coagulopathy, factors associated with wound necrosis, and the appropriate management of this condition have not been well characterized yet. Materials: This study included patients bitten by T. s. stejnegeri that were admitted to the study hospitals from 2001 to 2016. Patient characteristics, laboratory data, and management approaches were compared in victims with and without wound necrosis. Results: A total of 185 patients were evaluated: three patients (1.6%) were asymptomatic; whereas tissue swelling and pain, local ecchymosis, wound necrosis, coagulopathy, thrombocytopenia, rhabdomyolysis, and renal impairment were present in 182, 53, 13, 15, 10, 1, and 3 patients, respectively. One patient died from coagulopathy and hemorrhagic shock. Antivenom was administered to all envenomed patients at a median time of 1.8 h after the bite. The median total dose of antivenom was five vials. Chi-square analysis showed that bitten fingers, using cold packs during first aid, presence of bullae or blisters, lymphangitis or lymphadenitis, local numbness and suspected infection to be significantly associated with wound necrosis. After adjustment using a multivariate logistic regression model, only cold packs as first aid, bulla or blister formation, and wound infection remained significant. Conclusions: The main effects of T. s. stejnegeri envenomation are tissue swelling, pain, and local ecchymosis. We do not recommend the use of cold packs during first aid to reduce wound pain, as this may be a risk factor for wound necrosis. In addition, patients with bulla or blister formation should be carefully examined for subsequent wound necrosis. Antiplatelet use may worsen systemic bleeding. No severe rhabdomyolysis or renal failure was observed in this large case series, we therefore considered that they were not prominent effects of T. s. stejnegeri bite.

Chlorfenapyr is a new contact and stomach insecticide derived from natural pyrroles secreted by Streptomyces spp. It is a pro-insecticide and acts after metabolic transformation to its active metabolite tralopyril. Tralopyril is an uncoupler of oxidative phosphorylation in the mitochondria of the target insects and of experiment animals, leading to the disruption of adenosine triphosphate synthesis and death. Several fatal human poisonings had been reported and no blood chlorfenapyr or tralopyril measurements were available. The treatment remains supportive. A 32-year-old healthy man ingested 200 mL of 10% chlorfenapyr as a suicide attempt. Unfortunately, he succumbed at 157 h post-ingestion, shortly after having fever and seizures. His serum level of chlorfenapyr at 4 h post-exposure was 77.4 ng/mL, and was undetectable at 113 and 156 h, respectively. The serum levels of tralopyril were 723.6, 14,179, and 9654.2 ng/mL at 4, 113, and 156 h post-ingestion, respectively. The delay in the rise of serum tralopyril levels was noticeable, which seems to correlate with the patient’s signs and symptoms. The information may have therapeutic implications in the management of this deadly poisoning.

Patients bitten by Naja atra who are treated with bivalent freeze-dried neurotoxic antivenom in Taiwan have an improved survival rate but develop necrotic wound changes. The World Health Organization (WHO) has suggested using the minimum necrotizing dose (MND) of venom as a method of evaluating the neutralization effect of antivenom. The aim of this study was to evaluate the effectiveness of antivenom for the prevention of necrosis based on the MND and clarify which component of the venom of N. atra induces necrosis. The neurotoxins (NTXs) were removed from the crude venom (deNTXs), and different concentrations of deNTXs were injected intradermally into the dorsal skin of mice. After three days, the necrotic lesion diameter was found to be approximately 5 mm, and the MND was calculated. A reduction in the necrotic diameter of 50% was used to identify the MND₅₀. Furthermore, both phospholipase A₂ (PLA₂) and cytotoxins (CTXs) were separately removed from the deNTXs to identify the major necrosis-inducing factor, and the necrotic lesions were scored. All mice injected with deNTXs survived for three days and developed necrotic wounds. The MND of the deNTXs for mice was 0.494 ± 0.029 µg/g, that of the deNTXs-dePLA₂ (major component retained: CTXs) was 0.294 ± 0.05 µg/g, and that of the deNTX-deCTX (major component retained: PLA₂) venom was greater than 1.25 µg/g. These values show that CTX is the major factor inducing necrosis. These results suggest that the use of the deNTXs is necessary to enable the mice to survive long enough to develop venom-induced cytolytic effects. CTXs play a major role in N. atra-related necrosis. However, the MND₅₀ could not be identified in this study, which meant that the antivenom did not neutralize venom-induced necrosis.

Zika virus (ZIKV) is a new and emerging virus that has caused outbreaks worldwide. The virus has been linked to congenital neurological malformations in neonates and Guillain–Barré syndrome in adults. Currently there are no effective vaccines available. As a result, there is a great need for ZIKV treatment. In this study, we developed single chain variable fragment (scFv) antibodies that target the ZIKV envelope protein using phage display technology. We first induced an immune response in white leghorn laying hens against the ZIKV envelope (E) protein. Chickens were immunized and polyclonal immunoglobulin yolk (IgY) antibodies were extracted from egg yolks. A high-level titer of anti-ZIKV_E IgY antibodies was detected using enzyme-linked immunosorbent assay (ELISA) after the third immunization. The titer persisted for at least 9 weeks. We constructed two antibody libraries that contained 5.3 × 10⁶ and 4.5 × 10⁶ transformants. After biopanning, an ELISA phage assay confirmed the enrichment of specific clones. We randomly selected 26 clones that expressed ZIKV scFv antibodies and classified them into two groups, short-linker and long-linker. Of these, four showed specific binding activities toward ZIKV_E proteins. These data suggest that the polyclonal and monoclonal scFv antibodies have the diagnostic or therapeutic potential for ZIKV.