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Snakebite is an important problem in Myanmar. Regionally, bites by Eastern Russell's vipers, Daboia siamensis (Viperidae, Viperinae), and monocled cobras, Naja kaouthia are considered medically important, but those categorised as “green snake” bites are not. However, these may include bites by green pit vipers, Trimeresurus spp. (Viperidae, Crotalinae) for which no antivenom is available in Myanmar. Elsewhere in Southeast Asia, these snakes are reported to cause local and systemic envenoming. As part of the Myanmar Snakebite Project, prospective case data were collected over 3 years from five hospitals in the Mandalay region. These included 3803 snakebite cases reported from Mandalay region. Of these, 355 were listed as bites by a witnessed green-coloured snake. In 22 cases, the snakes responsible were retained and preserved, then expertly identified; 21 were medically important white-lipped pit vipers (Trimeresurus albolabris), and one as an Asian vine snake, Ahaetulla prasina (Colubridae, Ahaetuliinae) which is not of medical importance. Among confirmed Trimeresurus albolabris bites, 15/21 developed swelling of the bitten limb, and 3/21 coagulopathy, defined as a positive 20-min whole blood clotting test (20WBCT). None developed necrosis, blistering, thrombocytopenia or acute kidney injury (AKI). Of the remaining 333 patients bitten by green snakes that were not specifically identified, 241 (72%) developed swelling of the bitten limb, and 62 (19%) coagulopathy. AKI occurred in 21/333 patients, but only one required dialysis. At least 10/21 of the cases with AKI in this study were more likely to represent bites from Trimeresurus spp. than D. siamensis because the snake responsible was brought into the hospital, examined and described by the treating physician as “green-coloured”. This study describes a previously unpublished case of AKI from envenoming by T. erythrurus in Yangon, and reviews cases of AKI following bites by this species and T. albolabris in Myanmar. This confirms that, at least on rare occasions, Trimeresurus spp. envenoming can cause AKI. This has important implications for snakebite management in Myanmar as the finding of local swelling, coagulopathy and AKI is generally considered pathognomonic of D. siamensis envenoming. Further collection of confirmed Trimeresurus spp. bites is required in Myanmar in order better to define the syndrome of envenoming and to assess the possible need for antivenom against Trimeresurus spp. in this country.

The first reported snakebite by an African snake-eater, Polemon spp. (Atractaspididae, Aparallactinae); Local envenoming by Reinhardt's snake-eater, Polemon acanthias (Reinhardt, 1860). Toxicon XX, xxx. A 51-yr-old male herpetologist was bitten on the left index finger by a captive male Polemon acanthias while manually removing fragments of incompletely shed skin from the specimen. The snake sustained its bite for approximately 2 mins, advancing its jaws several times. The victim rapidly developed moderate pain, erythema, progressive edema that ultimately extended to the left wrist; a blister later developed in the wound site, as well as joint stiffness in the bitten and adjacent two fingers that limited flexion and extension. These effects regressed during the week following the bite, but recurred thereafter and were similar to the effects that developed immediately post-envenoming. There were no systemic signs or symptoms. The victim sought medical advice and was treated with broad-spectrum antibiotics, antihistamines and wound care; no laboratory investigations were conducted. He improved during the subsequent month with complete resolution in 5 and one-half weeks. This is the first documented bite by a Polemon spp. and the victim's clinical course suggests the development of local effects from venom components. The phylogenetic relationship of Polemon spp. with the burrowing asps (Atractaspis spp.) and the similarity of some of the features of this local envenoming by P. acanthias with mild/moderate envenoming by some Atractaspis spp., suggests that none of these snakes should be handled; they should be considered capable of inflicting potentially serious envenoming.

Background\ud Bites by the European adder (Vipera berus) in the UK are uncommon but potentially life threatening, and can be associated with marked limb swelling and disability. Following an interruption in Zagreb Imunološki zavod antivenom supply around 2012, the UK changed its national choice of antivenom for Vipera berus to ViperaTAb, an ovine Fab monospecific antivenom. In the absence of randomised controlled trials, we established an audit to review its use in clinical practice.\ud Methods\ud \ud A prospective audit of ViperaTAb use was conducted from March 2016 until November 2020 by the UK National Poison Information Service (NPIS). Users of the NPIS online toxicology database, TOXBASE, considering the use of antivenom for V. berus envenoming were invited to discuss the case with the on-call clinical toxicology consultant. Information was collected prospectively on indications, administration, adverse reactions and outcome of patients administered ViperaTAb antivenom.\ud Results\ud \ud One hundred and seventy patients were administered ViperaTAb antivenom over five years. One hundred and thirty-two were adults and 38 children (median age and range: 38, 2–87 years). Bites occurred across the UK, but most commonly in coastal regions of Wales and of South-West and East England. Median time to presentation was 2.1 (IQR 1.5–4.0) h and to antivenom administration from presentation was 2.0 (IQR 0.9–3.6) h. A minority of patients presented to hospital more than 12 h after being bitten (n = 19, 11.2%) or received antivenom more than 12 h after presenting to hospital (n = 17, 10.0%). Features of systemic envenoming were present in 64/170 (37.6%) patients, including 23 (13.5%) with anaphylaxis and 26 (15.3%) with hypotension (nine with both). Clinician assessment considered the initial antivenom to have been effective in 122/169 (72.2%) patients. Repeated dosing was common, occurring in 55/169 (32.5%), predominantly due to persisting or worsening local effects (46/51, 90.2%). There were three cases of probable early adverse reaction. No deaths occurred during the study. Complications of envenoming were rare but included four patients that underwent surgery, three patients each with acute kidney injury, mild coagulopathy, or thrombocytopenia (one severe). The median duration of hospital stay was 43.7 (IQR 22.5–66.5) h, longer for children than adults (52.5 vs 41.3 h).\ud Conclusion\ud \ud ViperaTAb antivenom appears to be effective and safe and should be administered as soon as possible for patients meeting clinical criteria. Patients require close observation following antivenom to detect adverse reactions and progression or recurrence of envenoming. Close collaboration with expert NPIS consultant advice can help optimise antivenom timing, ensure repeated dosing is given appropriately, and avoid unnecessary surgical intervention. All hospitals, particularly those located in areas of relatively high incidence, should stock sufficient antivenom available at short notice, 24 h a day.

The twelve Arab countries of the Middle East are inhabited by 117 species of scorpions of varying medical importance within six families. Scorpion stings are a very common occurrence throughout the region. Twenty-two scorpion species are considered to be dangerously venomous, causing potentially life threatening stings. Accessible literature in English and Arabic on scorpions, scorpion stings and available antivenoms was reviewed to document the scorpion fauna and scorpion stings in each country. Saudi Arabia, Iraq and Jordan report the highest numbers of stings and envenomings. Clinically, the most important toxins in Old World scorpion venoms are α-toxins that target voltage-gated sodium (Nav) channels at neurotoxin binding site 3, causing sympathetic excitation and the endogenous release of catecholamines that is responsible for transient, but life-threatening myocardial damage. Most victims of scorpion stings suffer severe local pain, but a few, especially children, develop systemic envenoming which, in the case of most Middle Eastern buthid species, such as Androctonus and Leiurus species, is dominated by the cardiovascular and respiratory consequences of hypercatecholinaemic myocarditis. Other syndromes include paralysis (Parabuthus leiosoma), coagulopathy (Nebo hierichonticus and Hemiscorpius species), and local tissue damage, haemolysis and acute kidney injury (H. lepturus). Early antivenom treatment is recommended but its value remains controversial. However, intensive care, with the ancillary use of vasoactive drugs such as prazosin and dobutamine, has proved effective.

Acute poisoning?, Acute pesticide poisoning?, Organophosphates/carbamates?, Acute poisoning with pharmaceuticals/chemicals?, Mushroom poisoning?, Methanol poisoning?, Fish and shellfish poisoning?, Snake bite?, Scorpion sting?, Spider bite?, Fish stings?, Jelly fish stings?

Differential diagnosis of fevers?, Fever without localizing features?, Sepsis?, Cancer?, General rules of cancer management?, Rheumatoid arthritis?, Osteoarthritis?, Systemic lupus erythematosus?, Typhoid and paratyphoid fevers?, Rickettsioses?, Bartonella?, Ehrlichia?, Coxiella?, Relapsing fevers?, Leptospirosis?, Brucellosis?, Plague?, Melioidosis?, Anthrax?, African trypanosomiasis?, American trypanosomiasis?, Visceral leishmaniasis (kala-azar)?, Infectious mononucleosis?, Measles?, Arboviruses and zoonotic haemorrhagic fever viruses , Ebola and Marburg virus diseases, Crimean-Congo haemorrhagic fever, Rift Valley fever, Lassa fever, Hantavirus infections, Severe fever and thrombocytopenia, Zika virus, Japanese encephalitis , Dengue virus, Yellow fever, West Nile virus , Kyasanur Forest Disease, Chikungunya, Ross River fever, O'nyong nyong

Examination of 18 cobras brought to three hospitals in the Mandalay Region by patients bitten or spat at by them distinguished 3 monocled cobras (Naja kaouthia) and 15 Mandalay spitting cobras (N. mandalayensis), based on their morphological characteristics. We confirm and extend the known distributions and habitats of both N. mandalayensis and N. kaouthia in Upper Myanmar. Clinical symptoms of local and systemic envenoming by N. mandalayensis are described for the first time. These included local swelling, blistering and necrosis and life-threatening systemic neurotoxicity. More information is needed about the clinical phenotype and management of bites by N. mandalayensis, the commoner of the two cobras in Upper Myanmar. Since the current cobra antivenom manufactured in Myanmar has lower pre-clinical efficacy against N. mandalayensis than N. kaouthia, there is a need for more specific antivenom therapy.

Latifi's viper (Montivipera latifii), also known as Lar Valley or Damavandi viper, is endemic to Iran. It has rarely been recorded, as it occurs in a highly-protected national park. In this first clinical report of a confirmed bite by this species, a teenage girl was bitten on the chin, causing rapidly-progressive swelling of the face and oropharyngeal mucosa. At a local hospital, a misleading history given by the patient's relatives of a wasp sting and inadequate inspection of the bite wound misled the physicians from making the correct diagnosis, resulting in a considerable delay in the administration of antivenom. This allowed the development of partial obstruction of the upper airway causing respiratory distress. After transfer to a tertiary hospital, attempts at endotracheal intubation failed, necessitating tracheostomy, but this was not implemented early enough to prevent her developing respiratory failure and losing consciousness. After she was stabilized, snakebite envenoming was diagnosed by a clinical toxicologist who observed two fang puncture marks on her chin. This was later confirmed when a snake, identified as M. latifii, was discovered at the room where the bite had occurred. Her facial swelling and ecchymosis, attributable to envenoming, were effectively controlled by high-dose antivenom therapy. However, she did not recover consciousness, remaining in a vegetative state. About three weeks after the bite, she died as an indirect result of hypoxic brain damage complicated by septicemia. Prompt diagnosis, relief of upper airway obstruction and timely antivenom therapy might have prevented this tragic fatal outcome.

The epidemiology features and clinical symptoms associated with 121 cases of snakebite requiring admission to 24 hospitals in Jordan, during 2018-2020, are discussed. Ninety-six of them (79%) brought with them to the hospital the snake that bit them or a photograph of it. Echis coloratus was responsible for 68 of the bites and 6 fatalities. Sex ratio was 3.2 males: 1 female, with an overall average age of 27 ± 14.36 years. The highest incidence of bites was reported in September. Bites were most common on hands and legs. The period of hospitalization ranged from 1 to 36 days. Irbid and Karak governorates had the highest number of snakebites, most cases being reported from agricultural areas and among farmers. Clinical symptoms associated with five species of venomous snakes are described along with illustrative case histories. Symptoms associated with Echis coloratus bites included local swelling and necrosis, coagulopathy and bleeding, microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and chronic renal failure. Daboia palaestinae victims exhibited ecchymoses, local swelling and necrosis, with one case of angioedema. Other symptoms included thrombocytopenia, coagulopathy, microangiopathic hemolysis and local and systemic bleeding, as well as AKI. A single case of envenoming by Macrovipera lebetinus developed the following symptoms; swelling, severe pain, extensive ecchymoses, neutrophil leukocytosis, normochromic normocytic anemia and aggregated platelets with thrombocytopenia. Symptoms associated with two cases of Pseudocerastes fieldi included swelling that spread from bitten hands, and mild abnormalities of platelet count and bleeding time. Four cases of envenoming by Atractaspis engaddensis exhibited severe pain, local swelling, erythema, numbness and tissue necrosis. One of them developed acute systemic symptoms. The only antivenom currently available in Jordan, is VINS "Snake venom antitoxin (Biosnake)", manufactured in India using venoms of three African snakes that do not occur in Jordan. It proved clinically ineffective against envenoming by Jordanian Viperidae, failing to correct coagulopathy and life-threatening hemorrhage, and to prevent AKI.

The Samar cobra, Naja samarensis Peters, 1861 is one of the World Health Organization’s category I venomous snakes in the Philippines. Although N. samarensis is known to inhabit Eastern Visayas, unlike N. philippinensis in Luzon, no clinical case reports have yet been published in the international literature. No immuno-diagnostic assays have been developed for venomous snakes in the Philippines, even for research purposes. Therefore, identification of the causative snake in hospitals is challenging. In vivo pre-clinical tests using mice showed that locally-produced antivenom raised against N. philippinensis venom ["Purified Cobra Antivenom (PCAV)"] cross-neutralised N. samarensis venom. Here, we present five snakebite envenomation cases where causative snakes were confirmed in photos as N. samarensis by an expert local herpetologist. Patients’ symptoms and signs varied, from mild to extensive local cytotoxic to systemic neurotoxic envenomation. In one case, venom had been spat into the eye. Out of five patients, two underwent surgical debridement of necrotic tissue at the bite site. One paediatric patient was intubated because of cardiopulmonary arrest. Except for the spitting cobra case, four cases were successfully treated with PCAV and supportive management. These are the first clinical case reports of confirmed N. samarensis envenomation., Toxicon, 223, art. no. 107008; 2022

King Cobra (Ophiophagus hannah) bite is well-known for its potentially fatal neurotoxicity. However, fatalities still occur, despite specific antivenom and respiratory support. Cardiovascular disturbances, which have attracted little attention in published reports of O. hannah envenoming, could contribute to fatality. We present two cases of confirmed O. hannah envenoming in Southern Vietnam in which there were cardiac abnormalities including arrhythmias and electrocardiographic changes, as well as elevated markers of myocardial damage. Cardiac pacing was required. One patient developed critical multi-organ dysfunctions partly explained by extensive necrotizing fasciitis/myositis originating from an Aeromonas sobria wound infection. This resulted in rhabdomyolysis, disseminated intravascular coagulation and acute kidney injury. Specific antivenom reversed neurotoxic effects of envenoming. Additional therapeutic interventions included antibiotics, surgical debridement, continuous renal replacement therapy and therapeutic plasma exchange. Both patients eventually made full recoveries. Apart from the critical problem of rapidly evolving and severe neurotoxicity, our case reports also emphasises the risk of cardiotoxic envenoming, and the complications of an overwhelming secondary bacterial wound infection. We suggest a practical approach to diagnosis and management.

αδ-Bungarotoxins, a novel group of long-chain α-neurotoxins, manifest different affinity to two agonist/competitive antagonist binding sites of muscle-type nicotinic acetylcholine receptors, being more active at the interface of α-δ-subunits. Three isoforms (αδ-BgTx-1-3) were identified in Malayan Krait ( Bungarus candidus ) from Thailand by genomic DNA analysis; two of them (αδ-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to α-bungarotoxin (α-BgTx), a classical blocker of muscle-type and neuronal α7, α8, and α9α10 nicotinic acetylcholine receptors. The toxicity of αδ-BgTx-1 (LD50 0.17-0.28 μg/g mouse, i.p. injection) is essentially as high as that of α-BgTx. In the chick biventer cervicis nerve-muscle preparation, αδ-BgTx-1 completely abolished acetylcholine response, but in contrast to the block by α-BgTx, acetylcholine response was fully reversible by washing. αδ-BgTxs, similar to α-BgTx, bind with high affinity to α7 and muscle-type nicotinic acetylcholine receptors. However, the major difference of αδ-BgTxs from α-BgTx and other naturally-occurring α-neurotoxins is that αδ-BgTxs discriminate the two binding sites in the Torpedo californica and mouse muscle nicotinic acetylcholine receptors showing up to two orders of magnitude higher affinity for the α-δ site as compared to α-e or α-γ binding site interfaces. Molecular modeling and analysis of the literature provided possible explanations for these differences in binding mode; one of the probable reasons being the lower content of positively charged residues in αδ-BgTxs. Thus, αδ-BgTxs are new tools for studies on nicotinic acetylcholine receptors.

Bites by the European adder (A prospective audit of ViperaTAb use was conducted from March 2016 until November 2020 by the UK National Poison Information Service (NPIS). Users of the NPIS online toxicology database, TOXBASE, considering the use of antivenom forOne hundred and seventy patients were administered ViperaTAb antivenom over five years. One hundred and thirty-two were adults and 38 children (median age and range: 38, 2-87 years). Bites occurred across the UK, but most commonly in coastal regions of Wales and of South-West and East England. Median time to presentation was 2.1 (IQR 1.5-4.0) h and to antivenom administration from presentation was 2.0 (IQR 0.9-3.6) h. A minority of patients presented to hospital more than 12 h after being bitten (ViperaTAb antivenom appears to be effective and safe and should be administered as soon as possible for patients meeting clinical criteria. Patients require close observation following antivenom to detect adverse reactions and progression or recurrence of envenoming. Close collaboration with expert NPIS consultant advice can help optimise antivenom timing, ensure repeated dosing is given appropriately, and avoid unnecessary surgical intervention. All hospitals, particularly those located in areas of relatively high incidence, should stock sufficient antivenom available at short notice, 24 h a day.

Fifty-two confirmed cases of snakebites in Kuwait were recorded during 2015–2019. The male:female ratio was almost 2:1 and 84.6% of the victims were between 1 and 20 y of age and 14.4% were >30 y. Snakebites peaked in October (23.1%) and July (17.3%), with the lowest number of recorded cases in March.

For most antivenoms there is little information from clinical studies to infer the relationship between dose and efficacy or dose and toxicity. Antivenom dose-finding studies usually recruit too few patients (e.g. fewer than 20) relative to clinically significant event rates (e.g. 5%). Model based adaptive dose-finding studies make efficient use of accrued patient data by using information across dosing levels, and converge rapidly to the contextually defined ‘optimal dose’. Adequate sample sizes for adaptive dose-finding trials can be determined by simulation. We propose a model based, Bayesian phase 2 type, adaptive clinical trial design for the characterisation of optimal initial antivenom doses in contexts where both efficacy and toxicity are measured as binary endpoints. This design is illustrated in the context of dose-finding for Daboia siamensis (Eastern Russell’s viper) envenoming in Myanmar. The design formalises the optimal initial dose of antivenom as the dose closest to that giving a pre-specified desired efficacy, but resulting in less than a pre-specified maximum toxicity. For Daboia siamensis envenoming, efficacy is defined as the restoration of blood coagulability within six hours, and toxicity is defined as anaphylaxis. Comprehensive simulation studies compared the expected behaviour of the model based design to a simpler rule based design (a modified ‘3+3’ design). The model based design can identify an optimal dose after fewer patients relative to the rule based design. Open source code for the simulations is made available in order to determine adequate sample sizes for future adaptive snakebite trials. Antivenom dose-finding trials would benefit from using standard model based adaptive designs. Dose-finding trials where rare events (e.g. 5% occurrence) are of clinical importance necessitate larger sample sizes than current practice. We will apply the model based design to determine a safe and efficacious dose for a novel lyophilised antivenom to treat Daboia siamensis envenoming in Myanmar., Author summary Snakebite envenoming is one of the most neglected tropical diseases considering its burden of mortality and morbidity. Antivenoms are the only known effective treatment for snake-bite envenoming but are frequently responsible for high rates of adverse reactions. Clinical development of antivenoms rarely follows the iterative phases of clinical development applied to other drugs. Dosing is typically based on pre-clinical testing. Here we propose a Bayesian model based adaptive design for phase 2 clinical trials aiming to determine the optimal dose of antivenom needed for treatment of snakebite envenoming. Optimality is defined using safety and efficacy thresholds contextual to the study. This design can be applied to all antivenoms which have binary efficacy and toxicity endpoints. Our design formally specifies a desired efficacy and a maximum tolerated toxicity. We use simulation studies to characterise adequate sample sizes to determine an approximately optimal dose under different scenarios. The simulation studies highlight the advantages of a model based design over simpler rule based alternatives. This design will be used to determine an effective and safe dose of the new lyophilised viper antivenom currently in use to treat Russell’s viper envenoming in Myanmar.

The World Health Organization call to halve global snakebite deaths by 2030 will requires substantial progress in India. We analyzed 2,833 snakebite deaths from 611,483 verbal autopsies in the nationally representative Indian Million Death Study from 2001-14, and conducted a systematic literature review from 2000-19 covering 87,590 snakebites. We estimate that India had 1.2 million snakebite deaths (average 58,000/year) from 2000-19. Nearly half occurred at ages 30-69 years and over a quarter in children

Human pathogens are found in six genera of Reoviridae: Reovirus, Rotavirus, Orthoreovirus, and three arthropod-borne genera: Coltivirus (Colorado tick fever, Salmon River virus, and Eyach viruses); Orbivirus (Kemerovo, Changuinola, Orungo, and Lebombo); and Seadornavirus (Banna virus). Colorado tick fever is common in parts of north-western North America; acquired from tick (ixodid) bites, most often by hikers and campers, presenting 3–6 days later with sudden fever, rigors, generalized aches, myalgia, headache and backache, rashes (12%), and gastrointestinal symptoms (20%). Diagnosis is confirmed by detection of viral antigen in erythrocytes or serum, or by serodiagnosis. Management is symptomatic. Illness usually resolves in 10–14 days, but convalescence may be prolonged. Prevention is by avoiding, repelling, and rapidly removing ticks; no vaccines are available.

Molluscum contagiosum is caused by a Molluscipox DNA virus which infects keratinocytes of the epidermal stratum spinosum, producing distinctive small umbilicated papules on the skin. Its genome encodes a variety of proteins that suppress the host’s immune response. In children it is spread by skin contact, producing few or many lesions, while in sexually active adults it causes anogenital lesions. Molluscum is self-limiting within a few years in the immunocompetent, but those with pre-existing atopic eczema and immunosuppression, notably AIDS, commonly develop persistent diffuse eruptions with larger papules. Lesions can be removed mechanically or chemically. More severe infections can be treated with imiquimod or cidofovir.

This chapter covers poisoning by members of the fungal subkingdom Dikarya that includes most of the ‘higher fungi’. The phylum Ascomycota contains the medically important toxic fungi Claviceps purpurea, the cause of ergotism, Aspergillus flavus, a source of hepatotoxic and carcinogenic aflatoxins, the edible but potentially toxic morel mushrooms (Morchella species), Gyromitra species, and Podostroma cornudamae that has caused multisystem symptoms and signs. The phylum Basidiomycota includes the order Agaricales (gilled mushrooms/toadstools or agarics) to which most of the medically important larger fungi belong. ‘Mushroom’ and ‘toadstool’ may suggest ‘edible’ and ‘poisonous’ respectively, but these terms are not strictly applied. Poisonous species must be distinguished from field (Agaricus campestris) and cultivated (A. bisporus) mushrooms and from the many other mushrooms that are considered to be delicious and are passionately sought after by mycophiles worldwide.

The Rhabdoviridae are a large family of RNA viruses, two genera of which infect animals: the genus Lyssavirus contains rabies and rabies-related viruses that cause at least 55,000 deaths annually in Asia and Africa. The risks and problems posed by rabies and other lyssaviruses vary across the world. Viruses can penetrate broken skin and intact mucosae. Humans are usually infected when virus-laden saliva is inoculated through the skin by the bite of a rabid animal, usually a dog. Although the greatest threat to man is the persistent cycle of infection in stray dogs, several other terrestrial mammal species are reservoirs of infection. In the Americas, bat viruses and also classic type 1 rabies and insectivorous bats have become the principal vectors of infection to humans in the United States of America. Elsewhere in the world, there is increasing evidence of widespread rabies-related lyssavirus infection of bats.

Pentastomida are dioecious, obligate parasites that are currently grouped in subclass Branchiura (fish lice and cycloids) of class Maxillopoda, subphylum Crustacea, phylum Arthropoda. Common names are ‘pentastomes’ (referring to two pairs of hooks above the mouth that give the impression of five stomata) or ‘tongue worms’ (alluding to the tongue-like appearance of some, such as adult Linguatula). Adult pentastomes inhabit the upper respiratory tracts of their end hosts (vertebrates such as reptiles, fish, birds, and mammals) where they feed on blood and other tissues. Their larvae infect internal organs of vertebrate or arthropod intermediate hosts. Pentastomes appear to have coevolved with other maxillopodan/branchiuran parasites and their vertebrate hosts. There are about 100 living species in the orders Cephalobaenida (e.g. genus Raillietiella) and Porocephalida (e.g. genera Linguatula, Armillifer, Porocephalus, Leiperia, and Sebekia).

This chapter looks at how enteroviruses are responsible for most cases of viral meningitis where a pathogen is identified; many other viruses can also cause meningitis with considerable geographical and seasonal variation. Their typical presentation is with sudden onset of fever, headache, neck stiffness, and photophobia. There is no change in conscious level. Prognosis is generally good, though recent data suggest not always. Viruses invade and damage the central nervous system in two ways: directly, by infecting the leptomeninges, brain, and spinal cord; and, indirectly, by inducing an immunological reaction resulting in para and postinfectious diseases. In both cases, the terms ‘meningitis’, ‘encephalitis’, and ‘myelitis’ are used alone or in combination.

Attacks by wild and domesticated animals are increasing worldwide. They are best prevented by taking local advice about minimizing exposure. Injuries usually occur in places remote from medical care. They may involve extensive trauma, haemorrhagic shock, and a high risk of bacterial contamination. First aid consists of resuscitation, control of bleeding and perforating injuries, intravenous fluid replacement, and rapid evacuation to hospital for emergency surgery and treatment of infection. In hospital, specific antivenom (hyperimmune equine or ovine immunoglobulins) is given if there is evidence of systemic or severe local envenoming. Early anaphylactic or pyrogenic reactions and late serum sickness antivenom reactions are common but not predictable by hypersensitivity tests.

This chapter covers orf and milker’s nodule, which are characteristic nodular skin lesions caused by parapox viruses of sheep and goats, or cattle, respectively. These viruses are epitheliotropic and able to suppress the host’s immune response. The infections are occupational zoonoses of people working with ruminants. A single or small number of somewhat painful pustules develops, usually on the hand, at the site of contact with an animal’s lesions. Fever is unusual, but local lymphadenopathy, erythema multiforme, or secondary infection may occur. Spontaneous resolution within 6 weeks is usual. Multiple, giant lesions may develop in the immunosuppressed. Topical cidofovir is effective in severe cases.

For most antivenoms there is little information from clinical studies to infer the relationship between dose and efficacy or dose and toxicity. Antivenom dose-finding studies usually recruit too few patients (e.g. less than 20) relative to clinically significant event rates (e.g. 5%). Model based adaptive dose-finding studies make efficient use of accrued patient data by using information across dosing levels, and converge rapidly to the contextually defined ‘optimal dose’. Adequate sample sizes for adaptive dose-finding trials can be determined by simulation studies.We propose a model based, Bayesian phase 2 type, adaptive clinical trial design for the characterisation of optimal initial antivenom doses in contexts where both efficacy and toxicity are measured as binary endpoints. This design is illustrated in the context of dose-finding for Daboia siamensis (Eastern Russell’s viper) envenoming in Myanmar. The design formalises the optimal initial dose of antivenom as the dose closest to that giving a pre-specified desired efficacy, but resulting in less than a pre-specified maximum toxicity. For Russell’s viper efficacy is defined as the restoration of blood coagulability within six hours, and toxicity is defined as anaphylaxis. Comprehensive simulation studies compared the expected behaviour of the model based design to a simpler rule based design (a modified ‘3+3’ design). The model based design can identify the optimal dose after fewer patients than the rule based design. Open source code for the simulations can be used to calculate sample sizes under a priori beliefs of efficacy and toxicity.Antivenom dose-finding trials would benefit from using standard model based adaptive designs. Dose-finding trials where rare events (e.g. 5% occurrence) are of clinical importance necessitate larger sample sizes than current practice. We will apply the model based design to determine a safe and efficacious dose for a novel lyophilised antivenom to treat Daboia siamensis envenoming in Myanmar.Author summarySnakebite envenoming is one of the most neglected tropical diseases relative to its mortality and morbidity. Antivenoms are the only known effective treatment for snake-bite envenoming but are frequently responsible for high rates of adverse reactions. Clinical development of antivenoms rarely follows the iterative phases of clinical development applied to other drugs. Dosing is typically based on pre-clinical testing.Here we propose a Bayesian model based adaptive design for clinical trials aiming to determine the optimal dose of antivenom needed. Optimality is defined using safety and efficacy thresholds contextual to the study. This design can be applied to all antivenoms which have binary efficacy and toxicity endpoints. Our design formally specifies a desired efficacy and a maximum tolerated toxicity. We use simulation studies to characterise the sample size necessary to determine the optimal dose in different scenarios. The simulation studies highlight the advantages of a model based design over simpler rule based alternatives. We intend to use this design to determine an effective and safe dose of the new lyophilised viper antivenom currently in use to treat Russell’s viper envenoming in Myanmar.