Tick paralysis.

The one tick-borne disease that rarely comes under the auspices of the infectious disease specialist is not caused by an infectious agent, but is tick paralysis. This condition is caused by tick bite and typically presents as a flaccid ascending paralysis. This article discusses this entity partly because of completeness, but also because tick paralysis, or tick toxicosis as it is sometimes called, is worth the infectious disease consultant's consideration. The differential diagnosis includes entities that are infectious or caused by toxins of infectious agents, such as epidural abscess, some causes of transverse myelitis, and botulism. Lastly, in an era of antibiotic toxicity, multidrug-resistant bacteria, antigen-switching viruses, and complex antibiotic regimens, the cure for tick paralysis-removing the tick-is as simple as it is gratifying.

Antivenom treatment in arachnidism.

Envenomation by arachnids causes significant medical illness worldwide. Scorpion sting is the most important arachnid envenomation causing adult morbidity and pediatric mortality. Important groups of spiders include the widow spiders (Latrodectus spp.), the recluse spiders (Loxosceles spp.), and two spiders confined to single countries: the Australian funnel web spider (Atrax and Hadronyche spp.) and the armed spider (Phoneutria spp.) from Brazil. There are four widow spider antivenoms available, including the Australian redback spider antivenom and the American black widow antivenom. Despite good in vitro animal work demonstrating effective neutralization with these antivenoms, and cross-reactivity between many species, there continues to be a reluctance to use them in some countries. They are both associated with a relatively low rate of allergic reactions. Redback antivenom is routinely used by the intramuscular route, which may not be as effective as intravenous use based on clinical experience and animal studies. Antivenoms are available for Loxosceles spp., but there is little evidence to support their effectiveness, particularly against local effects. The Australian funnel web spider causes severe neurotoxic envenomation, and antivenom appears to be effective in reported cases. An antivenom exists for the Brazilian armed spider, but is used in only a minority of cases. Many scorpion antivenoms exist worldwide, but there remains significant controversy regarding their efficacy. Animal and human venom level studies demonstrate neutralization of circulating venom in systemic envenomation. Clinical experience in countries where antivenom has been introduced suggests it has reduced pediatric mortality. However, three controlled trials demonstrated that antivenom was not effective, but these included few severe cases. Until controlled trials of antivenom in systemically envenomated patients are undertaken, antivenom use appears justified in severe envenomation. Although envenomation from arthropods is common, no antivenoms exist for these, excepting Lonomia caterpillars in South America, and Ixodes paralysis ticks in Australia.

Tick paralysis: development of a vaccine.

The paralysis tick of Australia, Ixodes holocyclus, causes a severe toxicosis in domestic animals such as dogs and cats, livestock, and in some cases, humans. It is characterised by a rapidly ascending flaccid paralysis. The causative agent of the toxicosis is a neurotoxin(s) produced in the tick salivary glands. The current treatment for tick paralysis is in the form of a polyclonal dog antiserum. This antiserum treatment is expensive and effective only in the early stages of paralysis. The aim of current research is to develop a recombinant veterinary vaccine based on the tick neurotoxin peptide sequence. A successful vaccine would provide cost-effective, long-term protective immunity against tick-induced paralysis.

Identification of an IgE-binding determinant of the major allergen Myr p I from the venom of the Australian jumper ant Myrmecia pilosula.

The structure of the single allergenic determinant of the major ant venom allergen, Myr p I from the Australian jumper ant Myrmecia pilosula has been determined by inhibition studies with synthetic peptides. A 14 amino-acid C-terminal peptide sequence has been shown to constitute this determinant. Half-maximal inhibition of binding of ant venom-specific IgE antibodies to the native venom was obtained with this peptide at a concentration of 5 x 10(-8) M. This allergenic determinant was invariant for all ant venom-allergic subjects tested whose IgE antibodies recognized this allergen.

Activation of human prothrombin by the venom of Lonomia achelous (Cramer) caterpillars.

In this paper, we demonstrated that the procoagulant action of Lonomia achelous (Cramer) is due in part to a component that activates prothrombin. The activation by crude venom and Fractions obtained by gel filtration on Sephadex G-75 is not dependent of phospholipid, Ca++ or Factor V. The activation of prothrombin by Fraction I is greatly stimulated by Factor V in the presence of phospholipid and Ca++; in presence of SBTI, we found that the Fraction I and Factor Xa act in a similar manner. These results suggest that the Fraction I is a Factor Xa - like prothrombin activator.

beta-Bungarotoxin antagonizes the effect of alpha-latrotoxin from black widow spider venom on the neuromuscular junction.

Sustained contraction of the chick biventer cervicis nerve-muscle preparations evoked by alpha-latrotoxin was antagonized quickly by beta-bungarotoxin. This effect of beta-bungarotoxin was dependent on its phospholipase A2 activity. In contrast, pancreatic phospholipase A2 was ineffective even at a much higher dose. It is concluded that alpha-latrotoxin needs intact presynaptic membrane to exert its effect.

The chemical nature of the funnel-web spider venom inhibitor found in rat plasma.

Strong evidence has been obtained that the funnel-web spider venom inhibitor, previously found to occur naturally in the blood of rats, is at least partly immunoglobulin in composition. However, the results of chromatographic and immunological studies, including the use of specific antisera, indicate that this inhibitor is not a single chemical entity and apparently resides within more than one immunoglobulin class. In addition, it was observed that challenge of rats with Atrax venom substantially increased the venom-inhibiting powers of their blood and that these powers were located in the same plasma fractions as in unchallenged rats.

Funnel-web spider (Atrax robustus) antivenom. 1. Preparation and laboratory testing.

An antivenom to the Sydney Funnel-web Spider, Atrax robustus, developed in rabbits, passed exhaustive quality control studies and was subsequently tested in monkeys. It was shown to reverse the syndrome that follows envenomation in both a conscious unmonitored monkey and in two anaesthetised, monitored monkeys. This paper reports the results of these experiments. An autonomic crisis appears to be the major cause of mortality and morbidity in human victims and monkeys; this aspect of the syndrome is rapidly attenuated by the antivenom. We observed no ill-effects of antivenom.

Naturally occurring inhibitors of the venom of funnel web spiders (Atrax species).

It has been shown that the blood plasma of rats and many other vertebrate species, but not man, contains a factor that inhibits the toxic actions of the venom of funnel web spiders (Atrax) on isolated toad voluntary muscle and rat lung preparations and also on anaesthetized whole rats. This factor was found to be effective against all obvious symptoms produced by the venom of both sexes of A. infensus and of the females of the other three common species of Atrax, particularly when administration of the factor to the test preparation preceded that of the venom.

Effect of concanavalin A on black widow spider venom activity at the neuromuscular junction: implications for mechanisms of venom action.

Concanavalin A (Con A) inhibits black widow spider venom-induced transmitter release at both tissue-cultured and adult neuromuscular junctions and also inhibits the venom-induced destruction of cultured neurites. This inhibitory action is partially or completely prevented by prior treatment with colchicine. Neither colchicine nor Con A interacts significantly with depolarization-induced transmitter release. These results are analogous to those obtained from experiments on lymphocyte surface receptor capping. They suggest that redistribution of neuronal membrane components may be a crucial step in spider venom action. This membrane redistribution appears to be modulated in neurons, as in other cell types, by microtubule-microfilament array. How such a redistribution causes increased transmitter release cannot as yet be specified. Changes in the ionic permeability of sodium and potassium were examined as likely mechanisms. Increased sodium influx (and seondary release of calcium from intracellular stores) cannot be the basis for spider venom action. Increased potassium efflux remains a possibility, but is not consistent with all of the data. Other possible mechanisms are also suggested.

Suppression by elevated calcium of black widow spider venom activity at frog neuromuscular junctions.

Frog neuromuscular junctions were treated with both concentrated black widow spider venom (BWSV) and elevated extracellular calcium (5-50 mM). This procedure causes a dramatic increase in the frequency of spontaneous miniature endplate potentials (mepps) which persists for only a few minutes. In contrast, BWSV-induced mepp activity, the venom effect (VE), continues for 20 min-1 h at junctions in elevated calcium Ringer solutions treated with doses of dilute venom or at junctions in normal calcium (1.91 mM) Ringer solution treated with concentrated venom. Following the disappearance of the VE in elevated extracellular calcium, only a few normal amplitude mepps and a few giant amplitude mepps are observed. The disappearance of the VE in these preparations is irreversible and occurs whether exposure to elevated extracellular calcium precedes or follows exposure to BWSV. Electron microscopy indicates that the major structural alterations produced by exposure to concentrated BWSV and 20 mM calcium Ringer solution are the swelling of nerve terminal mitochondria and the clumping of synaptic vesicles, large numbers of which remain in the terminals. Exposure to 20 mM calcium Ringer solution alone produces no ultrastructural modifications in these preparations. These observations can best be explained if one of the effects of BWSV is to increase the permeability of the nerve terminal membrane to calcium. Only doses of concentrated venom can sufficiently elevate intracellular calcium to a concentration at which synaptic vesicles clump together, thus interruping the transmitter release process.