An existing neurotoxicologic test and a cholesterol-lowering drug have promise for diagnosis and treatment of chronic ciguatera, a type of fish poisoning that until recently has been very difficult to diagnose and treat, Dr. Ritchie Shoemaker reported at the annual meeting of the American Society for Tropical Medicine and Hygiene.

Ciguatera is caused by a dinoflagellate toxin carried by several species of reef fish that is not destroyed by cooking. The toxin can produce gastrointestinal, cardiac, and neurologic symptoms. It is acquired only from eating affected fish, not from other types of environmental exposure.

"The explosive onset of an acute ciguatera illness can be readily identified clinically, but there is no consistent mechanism available to confirm the diagnosis in chronic cases," said Dr. Shoemaker, of the Pfiesteria Illness Center, McCready Outpatient Systems, Pocomoke, Maryland. "Symptoms of chronic ciguatera also include extreme fatigue, often incorrectly labeled as chronic fatigue syndrome."

Diagnosing any neurotoxin-mediated illness usually requires identifying a biomarker, but there is no such serologic test for chronic ciguatera. "Early diagnosis must involve a physiologic test as a biomarker because otherwise we have no way of demonstrating the toxin in people."

"We now have the potential for a simple bedside physiologic test, called visual contrast sensitivity (VCS), that measures the ability to visually discriminate among white, black, and gray." It is used by the U.S. Air Force and others as a superior method of vision testing. The test is portable, reproducibly reliable, inexpensive, and suitable for screening, he said.

Most of the illnesses are acquired from eating predator fish, such as grouper, jack, barracuda, and snapper. The disease occurs in tropical areas worldwide. "However, the disease can occur in nonendemic areas, in any place in which affected fish are imported. Cases have occurred in such places as Kiawah Island, South Carolina, and in a fancy restaurant in New Orleans," he said. "The difficulty in such isolated cases is that no definitive diagnosis can be confirmed by epidemiologic studies. The test for ciguatoxin in fish itself is fairly expensive and has a high percentage of false negatives and false positives."

The diagnostic test is based on the ability of the eye to discern contrast among white, gray, and black, which is impaired in the presence of a neurotoxin. A unique deficit in detecting visual contrast was found in 10 patients with possible chronic ciguatera and not found in controls. A similar deficit has been found in individuals affected by the neurotoxin produced by Pfiesteria piscicida and morphologically related dinoflagellates, he noted.

Treatment with cholestyramine in doses approved by the FDA for lowering cholesterol resulted in the correction of the visual contrast sensitivity deficit in these patients and abatement of chronic symptoms, some of which had been present for more than 10 years. The maximum time to recovery was 12 weeks.

The same deficit and successful treatment of symptoms was demonstrated in five patients symptomatic for 3 weeks after they ate grouper while on vacation in the Bahamas, he reported. "All these results suggest that VCS testing has great promise for successful use as a screening tool and as a tool for monitoring response to therapy."

The molecular structure of cholestyramine, an ion exchange resin, matches receptors on the toxin so they fit together as a lock and key, effectively inactivating the toxin. The drug has been used clinically to treat a number of neurotoxin-related syndromes, Dr. Shoemaker said. A clinical trial evaluating its clinical efficacy more extensively is under way.

Initial symptoms of ciguatera lead most people to believe they have food poisoning. Neurologic symptoms develop later. They include a metallic taste in the mouth (a hallmark of the disease), burning sensations in the arms and legs, reversal of hot and cold sensations, and a decrease in mental acuity. "Because these symptoms are rather nonspecific, ciguatera is rarely diagnosed in nonendemic areas," he said. Worldwide, the number of annual cases is estimated between 300,000 and 1 million. Statistics have been skewed for years because of under-reporting, he noted.

The American Society for Tropical Medicine and Hygiene (ASTMH) is the principal organization in the United States representing scientists, clinicians, and others with interests in the prevention and control of tropical diseases through research and education. Additional information on the meeting can be found at http://www.astmh.org/presskit.htm.