Lathyrism, Ciguatera

...and other diseases caused by biotoxins

Lathyrism
People and livestock consuming grasspea (Lathyrus sativus, also known as chickling pea) as the principal diet for months develop a paralytic disease known as Lathyrism. Livestock that consume grasspea seeds (30-50% of the diet) for 3-6 months develop Neurolathyrism, a disease that leads to microgliosis in the anterior horns and lateral cords and partial degeneration of the motor tracts of the spinal cord and death in extreme cases (Williams et al., 1994; Smartt et al., 1994). Amino acid derivatives from the seeds of other species of the genus Lathyrus and of some species of the genus Vicia produced similar effects on experimental animals (Duke, 1981; Williams et al., 1994).

Beta-N-oxalyl-L-alpha-beta-diamino-propionic acid (ODAP) also referred as Beta-N-oxalylamino-L-alanine (BOAA) occurs in grasspea and is a neurotoxin which causes paralysis (Smartt et al., 1994; Williams et al., 1994). BOAA concentrations vary widely (from 0.2 to greater than 1.01 mg per gramme of seed) among specimens collected from India and Ethiopia, and also the BOAA distribution in embryo was the greatest (400 mg per gramme) followed by cotyledon (126 mg per gramme), seed coat (81 mg per gramme), stem (64 mg per gram), leaf (60 mg per gramme), pod (24 mg per gram) and root (14 mg per gramme) (Campbell et al., 1994). Occasional use is harmless. Seeds, if soaked in water for 24 hours before cooking, are not toxic (Duke, 1981).

More information on Lathyrus sativus may be obtained here.

Mystery Disease of the Chamorros
A rare and obscure disease that includes the features of Parkinson's disease, Alzheimer's disease and Amytrophic Lateral Sclerosis (ALS, better known as Lou Gehrig's disease) has been documented among the indigenous people of Guam, the Chamorros. It is now associated with the consumption of the toxic seed of the falso sago palm, Cycas circinalis. This species of cycad is distributed throughout the Western Pacific region, and it had represented a major source of carbohydates for the Guamanian people before the 1950s. The toxin that is now known to cause the disease is beta-N-methylamino-L-alanine (BMAA) which chemically resembles BOAA, which causes Lathyrism.

More information on Cycas circinalis may be obtained here.

N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
An interesting sidestory concerns Parkinson's disease. In 1982, a group of young heroin addicts near Santa Cruz, California took some "synthetic heroin." Instead of getting the expected high, these substance users found themselves developing all the signs and symptoms of classic Parkinson's disease. The identity of the toxin in the "synthetic heroin" was quickly discovered to be N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a chemical that causes Parkinson's disease in humans and a variety of other animals.

Ciguatera
Ciguatera poisoning was first documented in the early sixteenth century, but has probably been a part of life in the tropics for as long as men have fished the coral reefs. This disease has long been a mystery: fish which are freshly caught, which are to all appearances normal and healthy, and which belong to a species known to be completely harmless suddenly become poisonous. Around two thousand cases are reported every year: a handful in Japan, Australia and the USA, the majority in the islands of the South Pacific. The actual incidence of poisoning is probably much higher.

Marine finfish most commonly implicated in ciguatera fish poisoning include the garoupas (also incorrectly known as groupers), barracudas, snappers, jacks, mackerel, and triggerfish. Many other species of warm-water fish harbour ciguatera toxin. The occurrence of toxic fish is sporadic, and not all fish of a given species or from a given locality will be toxic.

Ciguatera is a form of human poisoning caused by the consumption of tropical and sub-tropical marine coral fish which have accumulated naturally-occurring toxins through their diet. Because ciguatera is associated with coral reef ecosystems, most of the research into its cause and cure is also carried out in the tropical and sub-tropical regions of the world. The toxin is known to originate from the base of the food-chain, being produced by a uni-celIular algae first discovered in 1976 by Dr Raymond Bagnis (Institut Louis Malarde at Papeete) and Dr Takeshi Yasumoto (Tohoku University at Sendai, Japan) in the Gambier Islands and consequently named Gamblerdiscus toxicus. The algae is then consumed by fish, which are apparently immune to the toxin.

It is believed that most reef-dwelling fish carry at least trace quantities of the toxin in their system. In human metabolism, however, the toxin opens voltage-dependent sodium channels in the body's cell membranes, which devastate the nervous and muscular systems. Humans eating the fish can deal with minimal concentrations of the toxin, but above a certain level, its effect varies wildly from inducing mild nausea to, in one or two very rare instances, cardiac arrest and death.

The poison itself, first isolated by workers at the University of Hawaii, is a polyether compound appropriately named ciguatoxin. In April 1989, its molecular structure was jointly elucidated by Anne-Marie Legrand (Institut Louis Malarde), M. Murata, Y. Ishibashi and Professor Emeritus Takeshi Yasumoto (then of Faculty of Agriculture, Tohoku University). The results of the study were published in the Journal of American Chemical Society on June 27, 1989. The discovery of the chemical bonds will now allow the elaboration of a detection method for poisoned fish. Toxicology studies indicate that as little as 0.1 microgramme (= a tenth of a millionth of a gramme) can cause serious illness when consumed at a single meal by an adult human.

Other toxins are also implicated. Workers at the Institut Louis Malarde noted clinical differences in some instances of poisoning, and in collaboration with Japanese research workers, identified two more toxic compounds: scaritoxin, very likely a congener of ciguatoxin, and maitotoxin. All humans are believed to be susceptible to ciguatera toxins. Populations in tropical and subtropical regions are most likely to be affected because of the frequency of exposure to toxic fishes. However, the increasing per capita consumption of fisheries products coupled with an increase in inter-regional transportation of seafood products has expanded the geographic range of human poisonings.

The disease has only recently become known to the general medical community, and there is a concern that incidence is largely under-reported because of the generally non-fatal nature and short duration of the disease. Ciguatera in humans usually involves a combination of gastrointestinal, neurological, and cardiovascular disorders. Symptoms defined within these general categories vary with the geographic origin of the toxic fish. Initial signs of poisoning occur within six hours after consumption of toxic fish and include perioral numbness and tingling (paresthesia), which may spread to the extremities, nausea, vomiting, and diarrhea. Neurological signs include intensified paresthesia, arthralgia, myalgia, headache, temperature sensory reversal and acute sensitivity to temperature extremes, vertigo, and muscular weakness to the point of prostration. Cardiovascular signs include arrhythmia, bradycardia or tachycardia, and reduced blood pressure.

Ciguatera poisoning is usually self-limiting, and signs of poisoning often subside within several days from onset. However, in severe cases the neurological symptoms are known to persist from weeks to months. In a few isolated cases neurological symptoms have persisted for several years, and in other cases recovered patients have experienced recurrence of neurological symptoms months to years after recovery. Such relapses are most often associated with changes in dietary habits or with consumption of alcohol. There is a low incidence of death resulting from respiratory and cardiovascular failure.

For generations, we have called these diseases "degenerative" and of unknown origin. We now know that this "degeneration" is caused by biotoxins contained in particular plants and algae.