Thallium Poisoning: An Epidemic of False Positives -- Georgetown, Guyana

In late 1986, a striking increase in the number of reported cases of presumed thallium intoxication occurred in Georgetown, Guyana. Thallium sulfate had been used in Guyana as a rodenticide until January 1987, and review of hospital records in Georgetown showed that sporadic cases of presumed thallium intoxication had been diagnosed in Guyana since 1983. Most such reported cases had been defined on the basis of a positive blood or urine test for thallium performed at the Government Laboratory in Georgetown.

Because of the increase in the number of reported positive blood thallium tests, a Thallium Treatment Centre was opened at the Government Hospital in Georgetown on February 27, 1987. Approximately 240 persons per day came to the Centre. Those with symptoms thought to be compatible with thallium intoxication had blood drawn for thallium analysis at the Government Laboratory, and those with positive blood tests for thallium were advised to take two 500-mg tablets of Prussian Blue three times a day for 2 weeks. About 1,500 blood specimens and 900 urine specimens were received by the Government Laboratory between February 27 and March 12. In the month of February, the Government Laboratory reported that 263 of the 343 blood specimens tested (77%) were positive for thallium.

Epidemiologic investigation of the striking increase in the number of reported cases of presumed thallium intoxication began on March 1. Clinical case definitions of both acute and chronic thallium intoxication were developed and used to identify persons from whom specimens of blood and urine would be obtained for confirmatory thallium analyses at CDC. Clinical acute thallium intoxication was defined as acute gastrointestinal symptoms (severe abdominal pain or cramps and/or nausea (with or without vomiting)) lasting for 1-4 days, followed within 1 week by development of one or more of the following neurological problems: signs of peripheral neuropathy (paresthesias, hyperesthesias, and/or reflex changes), ataxia, or severe leg and/or foot pains. Clinical chronic thallium intoxication was defined as neurologic signs or symptoms compatible with thallium intoxication and either alopecia or two or more compatible constitutional signs or symptoms. Both case definitions excluded persons with obvious alternative explanations for their signs and symptoms.

All three hospitals in Georgetown and the West Coast Demerara Hospital were visited, and physicians were asked to identify patients who met either of the case definitions. A review of the available information about the distribution of illnesses in the community, including hospital charts and the case records of persons attending the Thallium Treatment Centre, and interviews with physicians and nurses revealed that the majority of persons seeking medical attention had mild, nonspecific complaints. No persons with clinical acute thallium intoxication were identified. There were seven persons with symptoms that met the case definition for chronic thallium intoxication. To determine whether these cases were, in fact, due to thallium intoxication, samples of blood and urine from the seven patients were analyzed for thallium content at the Division of Environmental Health Laboratory Sciences, Center for Environmental Health, CDC. The CDC laboratory also analyzed urine samples from 68 other persons who had symptoms that did not meet either of the case definitions, but, who 1) had positive blood tests for thallium at the Government Laboratory, 2) came to the Thallium Treatment Centre for advice and treatment, or 3) were thought by physicians at local hospitals to have symptoms related to thallium intoxication.

Results of the CDC analyses showed that none of the seven persons with symptoms meeting the case definition for chronic thallium intoxication had elevated thallium levels in blood or urine. Sixty-seven of the 68 other persons had no detectable thallium in the urine; one had 4.9 ng/ml of thallium in the urine. All of these values are considered by CDC to be within normal limits for thallium (0-5 ng/ml). In the CDC laboratory, the detection limit is 1.4 ng/ml for thallium in urine and 2.2 ng/ml for thallium in blood (1).

For the seven persons whose symptoms were compatible with chronic thallium intoxication, the CDC laboratory also analyzed urine samples for arsenic, selenium, and mercury and blood samples for lead. All assays were within normal limits. In addition, serologic tests for syphilis were negative for all seven persons.

The atomic absorption spectrometer for measuring thallium at the Government Laboratory had not been operational for the past year. In place of the instrumental method, a qualitative, colorimetric method (2) was used. This method is known to be subject to interference from many substances (e.g., detergents) that will give false-positive results. Results of blood tests for thallium were available from the Government Laboratory for 25 of the 75 persons whose urine was analyzed at CDC. All had been previously reported as positive. None of them had detectable thallium levels in urine tested at CDC. (For the remaining 50 persons, results of blood tests for thallium from the Government Laboratory were pending.) On the basis of the biological half-life of thallium (about 14 days), persons who had measurable levels of thallium in blood tested by the Government Laboratory should still have had measurable levels of thallium in urine that was retested at the CDC laboratory.

There was no documentation of an epidemic of thallium intoxication in Georgetown and the coastal area. Although numerous suspected cases of thallium intoxication were investigated, none were confirmed by analyses of blood and urine specimens for thallium at CDC. Reported by: N Blackman, MD, E London, MD, Ministry of Health, Georgetown, Guyana. B Zeleke, MD, Pan American Health Organization, Georgetown, Guyana. R St John, MD, Pan American Health Organization, Washington, DC. Caribbean Epidemiology Centre, Pan American Health Organization, Port of Spain, Trinidad. Div of Environmental Hazards and Health Effects, Div of Environmental Health Laboratory Sciences, Center for Environmental Health; National Institute for Occupational Safety and Health; International Health Program Office, CDC.

Editorial Note

Editorial Note: Thallium, an odorless, tasteless powder, is a systemic poison with multisystem toxicities. Toxicity can develop following either acute exposures or chronic, repetitive exposures to low doses. Classically, initial symptoms following acute exposure are predominately gastrointestinal and include nausea; vomiting; and severe, colicky abdominal pain. There may also be fever, changes in sensorium, convulsions, cardiovascular abnormalities, and renal toxicity. Several days to a week after exposure, evidence of peripheral neuropathy may develop. This is characterized by reflex changes, hyperesthesias, and pain in the feet and lower legs. Weakness, gait disturbances, and ataxia may also develop. In cases of chronic exposure, signs of basal ganglia damage may be present with Parkinsonian-like symptoms, such as resting tremor. Typically, alopecia occurs after 1 to 2 weeks have elapsed, and may be accompanied by changes in fingernails and toenails, dry scaly skin with diminished perspiration, and stomatitis.

In 1973, the World Health Organization recommended against the use of thallium sulfate as a rodenticide because of its toxicity (3). However, it is still used for that purpose in many countries. Thallium salts are used in the manufacture of pigments, dyes, luminous paints, artificial gems, window glass, and optical lenses (4).

Given the complex nature of thallium testing, it was difficult for the Government Laboratory in Guyana to accurately measure thallium in human specimens during the crisis. It appears that the great majority (if not all) of the recently reported cases of thallium poisoning in Guyana were diagnosed on the basis of positive laboratory tests for thallium. However, persuasive evidence indicates that these tests were not accurate. Since not even one positive laboratory test could be confirmed, this episode should be characterized as an "epidemic of false positives".

The Pan American Health Organization and CDC have investigated several outbreaks of fatal pesticide poisonings in which the country involved requested help in analyzing toxicologic specimens (5-7). The international environmental health community must focus on providing trained environmental epidemiologists and adequate laboratory resources to accurately detect, evaluate, and prevent acute illness and death from exposure to high levels of environmental toxicants. As this episode demonstrates, this expertise is also required to reliably demonstrate the absence of exposures so that scarce resources are not expended unnecessarily.

References

1. Paschal DC, Bailey GG. Determination of thallium in urine with Zeeman effect graphite furnace atomic absorption. J Anal Toxicol 1986;10:252-4.

2. Sunshine I, ed. Handbook of analytical toxicology. Cleveland, Ohio: CRC Press, 1969.

3. World Health Organization. Safe use of pesticides: 20th report of WHO expert committee on insecticides. WHO Tech Rep Ser 1973;513:40.

4. Saddique A, Peterson CD. Thallium poisoning: a review. Vet Hum

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