T he emergence of a recently identified toxic dinoflagellate, Pfiesteria piscicida, creates new human health risks in the laboratory and natural environment.This potential for human illness was first recognized when marine scientists themselves became ill while studying the effects of this microorganism on fish health (Glasgow et al. 1995, Schmechel andKoltai 2000).One investigator's symptoms were so severe that hospitalization was necessary.Similar illnesses in attenuated form were anecdotally reported in persons with extended contact with North Carolina estuary waters where Pfiesteria-associated toxicity was present (Glasgow et al. 1995).When commercial and recreational fishermen in Maryland came in repeated contact with fish kills and estuary waters containing at least 200 to 350 cells per ml of the organism, reports of illness increased and cognitive disturbances were objectively documented (Grattan et al. 1998).Our group at the University of Maryland became interested in these issues when commercial and recreational fisherman in Maryland-after repeated contact with fish kills and estuary water where the organism was known to be present-reported illness, including subjective "memory problems."They reported episodes of confusion, a dramatic increase in distractibility, and forgetfulness, which interfered with their work and other daily activities.Through a series of studies, we found objective evidence for cognitive disturbances in persons with high levels of exposure to the organism.Our findings were consistent with the complaints of the fishermen.This was the first demonstration that disturbances in thinking or cognition could result from environmental contact with P. piscicida (Grattan et al. 1998).Although the fishermen were reassured that there was a potential explanation for their new symptoms, the findings stimulated concern among members of our medical team.Subsequently, the diverse researchers of our medical team embarked on a new series of basic science and clinical studies to unravel the mystery of this newly emerging environmental toxin and its human health effects.However, as one would expect with a newly identified clinical syndrome, knowledge of the human health effects of exposure to a Pfiesteria-related toxin remains in its infancy.Available data suggest that Pfiesteria, when appropriately stimulated by the presence of fish or fish products, releases a toxin into its immediate environment (Burkholder et al. 1992, Glasgow et al. 1995, Noga et al. 1993).The specific triggers from toxin production are not known, nor has the toxin itself been fully characterized or purified.People appear

The convergence of data strongly suggests the presence of an estuary-related toxin (pfiesteria piscicida or similar organism) that produces adverse human health effects. A diversity of methodological approaches is necessary to answer important preliminary questions about the clinical syndrome, its immediate public health risk, prioritize ongoing scientific studies and direct future research. These include intensive case and multiple-case studies; case-control studies; and epidemiological cohort studies that are conducted in parallel with basic science research. Findings to date indicate the estuary-related toxin is neurotoxic to persons with high levels of exposure. The most pronounced effects are neurocognitive and include problems with complex attention, memory, and visual contrast sensitivity. The disturbances are detectable with standard neuropsychological procedures. Although the most debilitating effects are reversible, the possibility of a sensitization phenomenon exists. The Estuary Clinical Syndrome joins other well-documented outbreaks of human illness for which the specific toxin agent remains to be identified. The methodological approaches for identifying and investigating this newly identified syndrome in the absence of a known toxin may provide a model for the early investigation of other emerging toxins and related illnesses.

An outbreak of illness with flulike symptoms among state workers responding to a Pfiesteria bloom that resulted in fish death and distress on the Chicamacomico River on Maryland's Eastern Shore was investigated. Using case-control methodology, seven workers present at the Chicamacomico were compared to seven occupationally matched controls not present. Participants completed questionnaires assessing their exposures to water and their symptom histories and were assessed with a standard neuropsychological test battery. Three months later, the same questionnaires and neuropsychological tests were repeated. Three of the seven exposed workers cited minimal direct contact with water and four cited none. During the event, four developed burning eyes or nares and six developed a headache or sore throat. Six developed crampy abdominal pain, nausea, or diarrhea within 4 h of their exposure. In contrast, the only aforementioned symptom reported by controls was headache in two individuals. Acute and follow-up neuropsychological tests showed no consistent pattern of deficiency among the exposed. In conclusion, a flulike clinical illness was observed following exposure to a Pfiesteria-related fish kill, possibly as a result of inhalation of toxic aerosols.

Preliminary study of the psychologic adjustment of watermen with exposure to Pfiesteria piscicida was conducted on watermen with the most severe exposures and their occupationally matched controls. Participants in the exposed group were seven symptomatic recreational and commercial fishermen who had direct exposure to the Pocomoke River or other estuarial waters on Maryland's Eastern Shore before, during, and/or after periods of documented fish kills and Pfiesteria activity. The control group included eight commercial fishermen who worked on the ocean side of the Eastern Shore and had no reported exposure to estuaries with documented Pfiesteria activity. Both exposed symptomatic and nonexposed watermen completed the Profile of Mood States to assess depression, anxiety, and other relevant mood states as part of their participation in the larger investigation of the human health effects of Pfiesteria piscicida. Preliminary results suggest that both exposed symptomatic and nonexposed watermen are psychologically healthy and exhibit what psychologists refer to as the classic Iceberg Mood Profile. The Iceberg Profile is characterized by endorsement of symptoms suggestive of high energy, enthusiasm and positive mood (e.g., lively, active, energetic, cheerful, vigorous, etc.) and relative minimization of symptoms suggestive of negative or depressed mood (e.g., tense, anxious, restless, grouchy, forgetful). Therefore, the Pfiesteria-related symptom complex documented in the exposed watermen cannot be explained by functional or psychiatric factors and is probably due to exposure.

Over the next year, additional persons in Maryland may be at risk for exposure of toxic Pfiesteria or morphologically related organisms. These persons may present with a variety of memory and other behavioral complaints. This paper examines the kinds of complaints that persons with a documented Pfiesteria-related syndrome have compared to a nonexposed control group. The exposed group was more likely to report difficulties with concentration, forgetfulness, prospective memory, and information overload as well as feelings of confusion, bewilderment, and uncertainty as direct effects of toxin exposure. The exposed group was also more likely to report feeling uneasy, on edge, nervous, and shaky, which is probably a reaction to their newly acquired cognitive deficits and uncertainty about their recovery. In contrast, retrograde memory loss, disturbances of language or social behavior, depression, anger, hostility, or diminished activity levels are not symptoms that exposed persons are likely to report.

Mass hysteria or mass psychogenic illness is the spread of the belief of an illness (symptoms and the origins of the symptoms) through a population. The characteristics of mass psychogenic illness were reviewed and compared to the recent outbreak of human illness in the Pocomoke region in Maryland in the summer of 1997. The findings suggest that the nature of the symptoms complex--the onset and recovery course; the absence of secondary gain or job-related stress for most of the symptomatic persons; the predominance of males in the symptomatic group; and the baseline emotional stability of all persons examined--are inconsistent with the reported features of psychogenic illness in response to unknown environmental or chemical toxins. Although there may be individuals who exhibited hypochondriacal, hysterical, or other functionally based reactions, the recent outbreak of Pfiesteria-related illness probably does not represent an episode of mass psychogenic illness.

In the fall of 1996, fish kills in Maryland rivers were attributed to the dinoflagellate, Pfiesteria piscicida. After a group of researchers established a potential link between exposure to Pfiesteria and an illness causing memory problems, state health authorities closed a portion of the Pocomoke River. To determine the extent of illness, the range of symptoms, potential risk factors for disease, and to provide information to concerned citizens, a toll-free hotline was created. All symptomatic persons who called the toll-free number were administered a standardized questionnaire. Persons who had been exposed to Pfiesteria or Pfiesteria-laden waters were more likely to have respiratory, neurologic, dermatologic, and gastrointestinal problems than those persons without exposure. Among the persons calling the hotline, many had extensive neuropsychologic testing. Of the neuropsychologic test battery, low scores on the Rey Auditory Verbal Learning Test (RAVLT), a standardized measure of learning and memory, best characterized illness related to Pfiesteria exposure. Patients with low RAVLT scores were more likely to have neurologic symptoms and skin lesions than control subjects. Low RAVLT scores were associated with fishing (OR, 9.00, 95% CI, 106, 409.87), catching fish with lesions (OR, 6.17, 95% CI 1.27, 32.10), and handling fish with lesions (OR, 5.34, 95% CI, 1.05, 29.92), but not with consumption of seafood. While preliminary, these results do suggest that some risk factors for Pfiesteria-related illness may be easy to modify and used to prevent unnecessary human exposure.

BackgroundAt the beginning of autumn, 1996, fish with “punched-out” skin lesions and erratic behaviour associated with exposure to toxins produced by Pfiesteria piscicida or Pfiesteria-like dinoflagellate species were seen in the Pocomoke River and adjacent waterways on the eastern shore of the Chesapeake Bay in Maryland, USA. In August, 1997, fish kills associated with Pfiesteria occurred in these same areas. People who had had contact with affected waterways reported symptoms, including memory difficulties, which raises questions about the human-health impact of environmental exposure to Pfiesteria toxins.MethodsWe assessed 24 people who had been exposed. We collected data on exposure history and symptoms, did a complete medical and laboratory assessment (13 people), and carried out a neuropsychological screening battery. Performance on neuropsychological measures was compared with a matched control group.ResultsPeople with high exposure were significantly more likely than occupationally matched controls to complain of neuropsychological symptoms (including new or increased forgetfulness); headache; and skin lesions or a burning sensation of skin on contact with water. No consistent physical or laboratory abnormalities were found. However, exposed people had significantly reduced scores on the Rey Auditory Verbal Learning and Stroop Color-Word tests (indicative of difficulties with learning and higher cognitive function), and the Grooved Pegboard task. There was a dose-response effect with the lowest scores among people with the highest exposure. By 3–6 months after cessation of exposure, all those assessed had test scores that had returned to within normal ranges.InterpretationPeople with environmental exposure to waterways in which Pfiesteria toxins are present are at risk of developing a reversible clinical syndrome characterised by difficulties with learning and higher cognitive functions. Risk of illness is directly related to degree of exposure, with the most prominent symptoms and signs occurring among people with chronic daily exposure to affected waterways.