a) BACKGROUND
b) ACUTE SYMPTOMS (WITHIN 24 TO 48 HOURS)
c) CHRONIC SYMPTOMS (LASTING MONTHS TO YEARS)
d) FATALITY RATE
e) TIME TO ONSET OF SYMPTOMS
f) DURATION
g) CAUSATIVE ORGANISM
h) TOXIN
i) ROUTE OF EXPOSURE
j) VECTOR
k) DOSE
l) MECHANISM
m) LIKELY GEOGRAPHIC DISTRIBUTION
n) DIFFERENTIAL DIAGNOSIS
o) DIAGNOSIS
p) SUSPECT CASE
q) CONFIRMED CASE
r) ANIMAL SENTINEL DATA
s) ENVIRONMENTAL DATA
t) REFERENCE

1) Harmful algal blooms (HABs) are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. As part of the ongoing efforts by the Centers for Disease Control and Prevention (CDC), the Harmful Algal Bloom-related Illness Surveillance System (HABISS) collects data on the effects to human and animal health due to the potential environmental impact of HABs. The CDC has developed case definitions for HABs toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following information has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdc.gov.

1) In general, Caribbean Ciguatera reportedly presents with gastrointestinal symptoms first followed by neurologic symptoms, while Pacific Ciguatera presents with neurologic symptoms with or without subsequent gastrointestinal symptoms. GI: Diarrhea, nausea, vomiting, abdominal pain. NEURO: Paresthesias of the extremities and circumoral region (i.e. palms of hands, soles of feet, lips, mucous membranes of the mouth). Other sensory effects include metallic taste and dental pain. Other common paresthesias include pruritus and feelings of biting on the skin. Symptoms typically last for several weeks, but may persist for months in severe cases. CV: Hypotension with relative bradycardia (less than 60 beats per minute), generally resolving within 2 to 5 days. RESP: Respiratory depression, dyspnea; respiratory paralysis in severe cases. GU: Painful ejaculation in the male victim and dyspareunia in the unaffected female partner have been reported. Report of sexual transmission from man to woman and vice versa prior to onset of symptoms, but resulting in vaginismus. Both genders report dysuria. MUSCULOSKELETAL: Arthralgias and myalgias. HEENT: Blurred vision, transient vision loss. VITAL SIGNS: Hypotension, bradycardia; respiratory depression may develop in severe cases. SEVERE: Seizures, coma, respiratory depression, respiratory paralysis. More severe symptoms are reported by people who eat the whole fish including the viscera.

1) Paresthesias and extreme fatigue.

1) Less than 1%.

1) Less than 24 hours.

1) Typically weeks to months, although there have been reports of cases with symptoms lasting months to years.

1) Epiphytic/benthic dinoflagellates: Gambierdiscus toxicus, Gambierdiscus spp.

1) Ciguatoxin (CAS 91-21-4)

1) Eating contaminated fish, particularly the viscera.

1) Many species of fish have been implicated, particularly large specimens of predatory fish in and near coral reef areas.

1) Toxic concentrations loosely correlate with the size of the fish. Larger fish tend to be more toxic. Pacific ciguatoxins are about 10 times more potent than Caribbean or tropical Atlantic ciguatoxins.

1) Sodium channel activator

1) The Caribbean, tropical Atlantic and Gulf of Mexico, and the South Pacific and Indian Oceans. However, due to increasing international trade and travel, cases have been reported in areas remote from these oceans associated with either imported seafood or consumption of toxic fish during travel.

1) Other marine toxin poisonings (e.g. neurotoxic, paralytic, diarrheic or azaspiracid shellfish poisoning), scombroid fish poisoning, pesticide poisoning including organophosphate poisoning, cholinesterase inhibitor poisoning, microbial food poisonings and food allergies.

1) Diagnosis of exclusion with history of consumption of potentially toxic fish.

1) Consumption of tropical and subtropical fish AND neurologic signs and symptoms with or without gastrointestinal symptoms.

1) Consumption of tropical and subtropical fish and neurologic signs and symptoms with or without gastrointestinal symptoms, AND confirmation of ciguatoxins in implicated fish tissue.

1) Definitely affects prey species that are easier for predators to catch. Implicated in Hawaiian monk seal morbidity and mortality, although no confirmatory data.

1) Reefs affected by storm damage; coral bleaching may be more likely to be populated by Gambierdiscus spp., and thus produce ciguatoxic fish.

1) (HABISS Work-Group et al, Jan 12, 2009)

a) In a study of 12 patients with ciguatera fish poisoning, 4 (33.3%) patients developed tingling/numbness/pain in teeth or gums and 1 patient had a sensation of loose teeth during the first 3 days of illness (Friedman et al, 2007).

a) SUMMARY: Sinus bradycardia (less than 60 bpm) was reported in over 16% of patients following exposure, with some patients becoming symptomatic with heart rates reported in the 40s (Bagnis & Legrand, 1987; Geller et al, 1991; Geller & Benowitz, 1992; Miller et al, 1999).
b) CASE REPORT: Bradycardia (60 beats/minute), along with a blood pressure of 75 mmHg systolic, was reported in a 65-year-old man following ingestion of portions, including the head and liver, of a large reef fish. With supportive care, the bradycardia resolved within three days (Miller et al, 1999).
c) CASE REPORTS: A 54-year-old man was complaining of weakness, and was found prostrate with a pulse of 40 bpm five hours after sharing a fish meal with his family. The patient was hospitalized with ongoing weakness, along with persistent bradycardia (45 to 55 bpm) and hypotension (80 to 90 mmHg systolic), which he tolerated relatively well (no intervention was described). The second patient, a 53-year-old woman (spouse) became bradycardic (less than 60 bpm) and hypotensive 18 hours after ingestion. Her pulse and blood pressure remained low, until on day 9 she received 2 milligrams of atropine (Geller et al, 1991).
d) Persistent bradycardia and hypotension were reported in two patients with ciguatera poisoning from ingesting barracuda fish eggs. Both patients required continuous atropine infusion over a two-day period (total doses up to 40 mg) (Hung et al, 2005).
e) INCIDENCE: According to a 10-year retrospective study, involving 1824 cases of ciguatera poisoning in French Polynesia, bradycardia occurred in 13% of patients (Chateau-Degat et al, 2007).
f) Bradycardia was reported in 75% (n=120) of patients following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008).

a) Hypotension is relatively uncommon following ciguatera fish poisoning (Bagnis et al, 1979), but the effects may be persistent in some individuals (Geller & Benowitz, 1992). Orthostatic hypotension with a relative bradycardia (less than 60 bpm) has been reported for up to 4 to 6 weeks in some cases (Miller et al, 1999; Geller et al, 1991). Fluids and atropine have been used successfully in some symptomatic cases (Miller et al, 1999; Geller & Benowitz, 1992; Geller et al, 1991).
b) INCIDENCE
c) CASE REPORTS

a) Transient T-wave inversion has been described (Miller et al, 1999; Ho et al, 1986) .

a) Extrasystole may occur, possibly due to noradrenergic myocardial stimulation (Swift & Swift, 1993)

a) Cardiomegaly, pulmonary edema and decreased left ventricular function developed in a 54-year-old man approximately 2 weeks after ingesting several large portions of a coral trout (Miller et al, 1999).

a) CASE SERIES: Respiratory paralysis occurs in extremely severe cases and has resulted in death in 6 of 12,890 reported cases (Bagnis & Legrand, 1987).

a) Respiratory depression may occur (Ho et al, 1986).

a) CASE SERIES: Dyspnea was reported in 12.1% of 12,890 cases (Bagnis & Legrand, 1987).
b) CASE REPORT: Acute respiratory distress in conjunction with severe muscle damage was reported in a 35-year-old man several hours after consuming contaminated fish (Kodama et al, 1989). The ingested fish probably contained palytoxin.
c) CASE REPORT: A 54-year-old man experienced progressive dyspnea, dizziness, pulmonary and peripheral edema after ingesting large portions of a coral trout (Miller et al, 1999).

a) CASE SERIES: Bronchospasm developed in 19 of 12,890 cases (Bagnis & Legrand, 1987).
b) CASE SERIES: Asthmatic crises have occurred in approximately 0.1% of cases (Swift & Swift, 1993).

a) CASE REPORT: Pulmonary edema, cardiomegaly and bilateral pleural effusions were noted on chest x-ray in a 54-year-old man following the ingestion of coral trout 2 weeks previously. Following supportive therapy, the patient recovered (Miller et al, 1999).

a) Neurologic symptoms occur in most cases, usually present within 12 hours. Neurologic symptoms last up to 18 days for dental pain and 121 days for memory problems (Capra et al, 1991). Neurologic signs and symptoms predominate in Pacific ciguatera fish poisoning, whereas, in Caribbean ciguatera fish poisoning, neurotoxicity, particularly peripheral neuropathies, will generally present following gastrointestinal signs and symptoms (Friedman et al, 2008).
b) CASE REPORT: Four travelers (2 men and 2 women 49 to 53 years of age) in Mauritius developed neurologic symptoms including paresthesias and thermalgesia 1 day after consuming fresh fish (yellow-edged lyretail; Variola louti) contaminated with ciguatoxin. The symptoms resolved within 4 to 7 weeks. However, approximately 11 months after the original ingestion, 2 of the travelers (a 49-year-old woman and a 52-year-old man) suffered a recurrence of symptoms when they consumed giant African threadfin while traveling to southern Senegal. During the recurrence, the 2 travelers reported diffuse paresthesias, cold allodynia, thermalgesia, dysesthesia of the hands and feet described as a feeling of walking on cotton, and restless leg syndrome. Other diners who ate the threadfin did not develop symptoms. The neurologic symptoms resolved within 8 to 11 days (Glaizal et al, 2011).
c) A prospective study of 47 French Polynesian adults with ciguatera disease (CD) with 125 controls, evaluating neurologic abnormalities of CD using a standard neurologic examination, light-touch threshold evaluation, and motor function examinations, showed static and dynamic ataxia, general impairment of the bone tendon reflex (markedly depressed or abolished) in the upper and lower limbs, diminishing sensation to light touch, and errors in hot/cold perception. The light-touch threshold evaluation revealed a significant impairment of tactile perception on the palms of hands compared with controls, as well as paresthesia and cold allodynia, loss of tactile sensation in glove-type distribution, and alteration of gait and postural sway, indicating impairment of the lemniscal sensitivity in sensory neuropathy. On follow-up two months after the onset of the disease, improvement of sway performance was observed which eventually reached control levels. However, light-touch threshold values were still impaired with more than 50% of patients still having high values (Chateau-Degat et al, 2007a).
d) In a longitudinal matched cohort study of 12 patients with ciguatera fish poisoning (CFP) and 12 matched controls, CFP was not associated with short- or long-term objectively measured deficits in cognitive performance in patients untreated with mannitol. However, untreated ciguatera was associated with significant subjective neurologic complaints and anxiety during the first month after poisoning, but these symptoms were transient (Friedman et al, 2007).
e) In a study of 12 patients with ciguatera fish poisoning, the following symptoms were reported in the first 3 days of illness: multitasking problems (n=3; 25%); attention/concentration problems (n=2; 16.7%); language problems (n=2; 16.7%); hallucinations (n=1; 8.3%); memory problems (n=1; 8.3%), coordination problems (n=1; 8.3%); slowed thinking (n=1; 8.3%); and visuospatial difficulties (n=1; 8.3%) (Friedman et al, 2007).
f) LONG-TERM SEQUELAE

a) The most common manifestation of numbing or tingling in the extremities or circumorally occurs in over 75% of patients (Wong et al, 2008; Morris, 1990; Palafox et al, 1988; (MMWR, 1998); Miller et al, 1999).
b) Paresthesias are described as a cold-hot sensation (which is not a true sensory switch, but can be described as the sensation one gets when gripping something very cold (e.g., ice), and the resultant sensation of a "burning" feeling), which is frequently localized to palms of hands, soles of feet, lips, and mucous membranes of the mouth.
c) OTHER SENSORY EFFECTS include a metallic taste, a "carbonated" sensation when food or drink is consumed, and dental pain or dysesthesia ((MMWR, 1998)).
d) DURATION: Symptoms usually last about 3 weeks, but may persist for months in severe cases (Hung et al, 2005; Eastaugh, 1996; Jahns et al, 1995).
e) CASE REPORT: After eating seafood on several occasions during a trip to Mexico and Guatemala, a 32-year-old woman developed sore throat, paresthesia (of the right arm and leg, face, and entire left side), cold sensation, and difficulty falling asleep on the 10th day of her visit. She also experienced pruritus, myalgia, fatigue, and sleepiness which had continued for at least 5 weeks. Symptoms of ciguatera fish poisoning can take weeks or months to resolve (Keynan & Pottesman, 2004).
f) In a study of 12 patients with ciguatera fish poisoning, 7 (58.3%) patients developed perioral tingling/numbness, 8 (66.7%) patients developed tingling/numbness in hands or feet, and 7 (58.3%) developed tingling/burning when touching cold objects in the first 3 days of illness (Friedman et al, 2007).
g) Circumoral paresthesias and paresthesias of the extremities were reported in 31% and 49%, respectively, of patients (n=124) following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008).
h) CASE REPORT: A 45-year-old woman developed dysesthesia, paresthesia, generalized myalgia, retro-orbital pain, and generalized pruritus, as well as gastrointestinal effects (vomiting, abdominal pain, and watery diarrhea) several hours after consuming the internal organs of Sphyraena barracuda. Although a neuropsychological examination of the patient did not indicate callosal syndrome (ie, hemialexia and unilateral agnosia, agraphia, and apraxia), a brain MRI, conducted 4 days post-admission, revealed the presence of a corpus callosum lesion. The patient's signs and symptoms resolved following supportive care; a repeat MRI, conducted 3 months post-discharge, showed resolution of the lesion (Liang et al, 2009).

a) Arthralgias and myalgias are common presenting symptoms (Gatti et al, 2008; Miller et al, 1999; Palafox et al, 1988) . Weakness in the extremities, vertigo, and ataxia are common, and last 12 hours to 10 days.
b) Profound weakness may occur. Patients may be unable to rise or move (Geller et al, 1991).
c) Muscle weakness and pain were reported in 15 of 23 (88%) Norwegian cargo ship crew members two days after eating barracuda. Subsequent immunoassay testing determined that the barracuda was contaminated with ciguatoxins ((MMWR, 1998)).
d) In a study of 12 patients with ciguatera fish poisoning, 11 (91.7%) patients developed muscle weakness in the first 3 days of illness (Friedman et al, 2007).
e) Asthenia was reported in 34% of patients (n=124) following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008).

a) Paralysis of limbs and facial muscles may develop in severe cases (Swift & Swift, 1993). Paresis of the lower extremities or extraocular muscles occurs in about 10% to 15% of cases (Palafox et al, 1988); with paralysis in less than 1% (Bagnis et al, 1979; Bagnis & Legrand, 1987). Facial palsy with drooling, dysphonia and stuporous gaze were present 72 hours post-ingestion in a 27-year-old woman (Jahns et al, 1995). Cranial nerve palsies may be noted.

a) Pruritus occurs in about 50% of cases, often developing more than 30 hours from time of ingestion, and may last for weeks (Chateau-Degat et al, 2007; Achaibar et al, 2007; Keynan & Pottesman, 2004). Itching is generalized and aggravated by alcohol consumption or strenuous activity (Hampton & Hampton, 1989; Jahns et al, 1995; Eastaugh, 1996). Exacerbations may also occur at night (Bagnis & Legrand, 1987).
b) Pruritus may be mild to severe, and may be followed by cellulitis (Geller et al, 1991). It may persist for weeks after an exposure (Hampton & Hampton, 1989).
c) Pruritus of the hands and/or feet occurred in 11 of 23 (65%) crew members, aboard a Norwegian cargo ship, after eating a barracuda that was later determined to be contaminated with ciguatoxins ((MMWR, 1998)). The sensation of itch is experienced during low frequency discharge in C-polymodal nociceptive fibers (cutaneous afferent unmyelinated fibers) which are not normally active during normal temperature of undamaged skin (Cameron & Capra, 1993).
d) CASE REPORT: A 30-year-old woman experienced dysesthesia and pruritus of her legs, hands, and breasts after consuming a fish contaminated with ciguatoxin. The pruritus intensified with exposure to the cold (Perez et al, 2001).
e) CASE REPORT: A 45-year-old man developed neurological symptoms, including temperature reversal (paradoxical dysesthesia), intense pruritus and increased nociception as a result of a small fibre peripheral neuropathy, 24 to 48 hours after ingesting red snapper and group, potentially "ciguatoxic fish". His symptoms improved over the next 12 months. Two years later, he still experienced intermittent dysesthesias in his hands and feet after drinking alcohol or eating fish (Achaibar et al, 2007).
f) In a study of 12 patients with ciguatera fish poisoning, 8 (66.7%) patients developed itching within the first 3 days of illness (Friedman et al, 2007).
g) Pruritus was reported in 64% (n=124) of patients following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008).

a) INCIDENCE: According to a 10-year retrospective study, involving 1824 cases of ciguatera poisoning in French Polynesia, vertigo occurred in 56% of patients (Chateau-Degat et al, 2007).
b) In a study of 12 patients with ciguatera fish poisoning, 3 (25%) patients developed dizziness and vertigo within the first 3 days of illness (Friedman et al, 2007).

a) Seizures and coma have been reported in serious or fatal cases (Emerson et al, 1983; Bagnis et al, 1979; Ho et al, 1986).
b) CASE REPORT: Uncontrollable tonic contractions of all muscle groups was reported in a 35-year-old man within 48 hours of ingestion of contaminated fish (Kodama et al, 1989). The ingested fish probably also contained palytoxin.

a) Drowsiness, dizziness, fatigue, malaise, and tiredness may occur following ingestion of ciguatoxin-contaminated fish and may last for days or weeks (Wong et al, 2008; Gatti et al, 2008; Hung et al, 2005; Keynan & Pottesman, 2004; Ho et al, 1986).

a) Tremor has been reported in about 30% of cases (Gillespie et al, 1986).

a) Severe headache may occur (Hung et al, 2005; Eastaugh, 1996).
b) Headaches were reported in 9% (n=124) of patients following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008). Another review of ciguatera poisoning cases in Hong Kong from January, 2004 to May, 2005, reported the occurrence of headaches in 19% of patients (n=300) (Wong et al, 2008)

a) Patients may experience marked chronic fatigue for months or even years after ingesting contaminated fish (Achaibar et al, 2007).
b) In a study of 12 patients with ciguatera fish poisoning, 10 (83.3%) patients developed fatigue within the first 3 days of illness (Friedman et al, 2007).

a) Suspected Guillain-Barre syndrome (GBS) was reported in a patient with ciguatera-like intoxication. A 32-year-old man who ingested a moray eel that was caught in a ciguatoxic area, subsequently developed symptoms of ciguatera poisoning, including diarrhea, vomiting, pruritus, dysesthesia, and progressing to tetraparesis, diffused amyotrophy, cerebellar syndrome (permanent shaking of the head and upper extremities), and language difficulties over the course of several weeks. The patient gradually recovered (Gatti et al, 2008).

a) CASE SERIES: Nausea and vomiting are present within 1 to 6 hours in about 44% and 39% of cases, respectively (Achaibar et al, 2007; Bagnis & Legrand, 1987). In one study nausea and vomiting occurred in 33% of patients (Palafox et al, 1988).
b) Gastrointestinal (GI) symptoms generally abate within 24 hours (Gillespie et al, 1986; Hanno, 1981). In another study the mean duration of nausea was 17 days (Capra et al, 1991).
c) Nausea and vomiting were reported in 13 of 23 (76%) crew members aboard a Norwegian cargo ship who had ingested barracuda. Subsequent immunoassay testing of the barracuda revealed that it was contaminated with ciguatoxins. The nausea and vomiting occurred within 2 to 16 hours after ingestion of the contaminated fish ((MMWR, 1998))
d) INCIDENCE: According to a 10-year retrospective study, involving 1,824 cases of ciguatera poisoning in French Polynesia, vomiting occurred in 32% of patients (Chateau-Degat et al, 2007).
e) In a study or 12 patients with ciguatera fish poisoning, 5 (41.7%) patients developed nausea during the first 3 days of illness (Friedman et al, 2007).
f) Nausea and vomiting were reported in 17% and 55%, respectively, of patients (n=124) following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008). Another review of ciguatera poisoning cases in Hong Kong from January, 2004 to May, 2005, reported the occurrence of nausea and vomiting in 40% and 31% of patients (n=300), respectively (Wong et al, 2008).
g) CASE REPORT: Nausea, vomiting, and diarrhea (up to 10 bowel movements/day) were reported in 2 patients who consumed local fish while on vacation in Costa Rica. The couple also experienced paresthesias, alternating hot and cold sensations of the extremities, fatigue, photophobia, and a perception of flashing lights. Laboratory analysis indicated markers that were similar to samples from other patients with confirmed diagnoses of ciguatera poisoning. The patients' gastrointestinal symptoms resolved after 1 week. Following amitriptyline administration, the neurologic symptoms began to abate over a 3-week period; however, minimal symptoms continued to persist at 3-month followup (Winter, 2009).
h) An outbreak of ciguatera fish poisoning was reported in Northern Germany in November of 2012. Of 11 patients who sent back a questionnaire detailing symptomatology and initial treatment, nausea and vomiting was reported in 6 patients and 5 patients, respectively, 4 to 12 hours after consumption of 80 to 300 g of red snapper (Mattei et al, 2014).

a) Abdominal pain occurred in about 40% (Achaibar et al, 2007; Bagnis & Legrand, 1987). Symptoms were short-lived, often resolving within 12 to 48 hours after ingestion (Withers, 1982).
b) CASE SERIES: The incidence of abdominal pain was 60% of persons involved in an unconfirmed outbreak (Morris, 1990). Onset of symptoms ranged from 2 to 20 hours postingestion and duration was from 1 to 48 hours.
c) Abdominal cramps occurred in 14 of 23 (82%) crew members, aboard a Norwegian cargo ship, within 2 to 16 hours after eating barracuda. Subsequent immunoassay testing of the barracuda confirmed the presence of ciguatoxins ((MMWR, 1998)).
d) In a study or 12 patients with ciguatera fish poisoning, 5 (41.7%) patients developed abdominal pain during the first 3 days of illness (Friedman et al, 2007).
e) Abdominal pain was reported in 40% (n=124) of patients following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008). Another review of ciguatera poisoning cases in Hong Kong from January, 2004 to May, 2005, reported the occurrence of abdominal pain in 59% of patients (n=300) (Wong et al, 2008).

a) Watery, non-bloody diarrhea may occur in 40% to 74% of patients (Wong et al, 2008; Achaibar et al, 2007; Ho et al, 1986; Palafox et al, 1988; Bagnis & Legrand, 1987). In one study, the mean duration of diarrhea was 5 days (Capra et al, 1991).
b) Diarrhea occurred in all 23 norwegian cargo ship crew members 2 to 16 hours after eating ciguatoxin-contaminated barracuda. Treatment consisted of supportive care until resolution of the diarrhea ((MMWR, 1998)).
c) INCIDENCE: According to a 10-year retrospective study, involving 1824 cases of ciguatera poisoning in French Polynesia, diarrhea was very common, occurring in 77% of patients (Chateau-Degat et al, 2007).
d) In a study or 12 patients with ciguatera fish poisoning, 8 (66.7%) patients developed diarrhea during the first 3 days of illness (Friedman et al, 2007).
e) Diarrhea was reported in 80% (n=124) of patients following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008).
f) An outbreak of ciguatera fish poisoning was reported in Northern Germany in November of 2012. Of 11 patients who sent back a questionnaire detailing symptomatology and initial treatment, diarrhea was reported in 10 patients 4 to 12 hours after consumption of 80 to 300 g of red snapper (Mattei et al, 2014).

a) Metallic taste is uncommon (Swift & Swift, 1993).
b) An outbreak of ciguatera fish poisoning was reported in Northern Germany in November of 2012. A persistent metallic taste was reported in 5 patients following consumption of 80 to 300 g of red snapper (Mattei et al, 2014).

a) Hypersalivation is uncommon (Swift & Swift, 1993).

a) Hiccoughs occur in less than 1%, but can be severe and incapacitating (Swift & Swift, 1993).

a) An outbreak of ciguatera fish poisoning was reported in Northern Germany in November of 2012. Of 11 patients who sent back a questionnaire detailing symptomatology and initial treatment, 6 patients experienced a burning sensation of the mouth approximately 45 minutes after consuming 80 to 300 g of red snapper (Mattei et al, 2014).

a) CASE SERIES: Dysuria was reported in 12.6% of 12,890 cases (Bagnis & Legrand, 1987).
b) INCIDENCE: According to a 10-year retrospective study, involving 1824 cases of ciguatera poisoning in French Polynesia, dysuria occurred in 23% of patients (Chateau-Degat et al, 2007).
c) In a study or 12 patients with ciguatera fish poisoning, 1 patient developed pain/difficulty urinating during the first 3 days of illness (Friedman et al, 2007).
d) Dysuria was reported in 1.6% (n=124) of patients following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008).

a) Painful ejaculation, followed by urethritis and meatal tenderness, was described in 2 men with ciguatera fish poisoning.
b) In a related case, a man developed pain at the tip of his penis after intercourse with his wife who had ingested contaminated barracuda. He had eaten none of the fish (Geller et al, 1991).
c) Painful ejaculation following intercourse was reported in 2 men approximately 7 days after eating mackerel suspected to be contaminated with ciguatoxin. The wives of the 2 men also complained of painful intercourse, although they had not consumed the mackerel. Both patients recovered following supportive treatment with IV mannitol and amitriptyline.

a) Bullous or desquamating rashes may occur (Ho et al, 1986).

a) CASE SERIES: Urticaria occurred in 27 of 12,890 cases (Bagnis & Legrand, 1987).

a) Pruritus occurs in about 50% of cases, often developing more than 30 hours from time of ingestion, and may last for weeks (Chateau-Degat et al, 2007; Keynan & Pottesman, 2004). Itching is generalized and aggravated by alcohol consumption or strenuous activity (Hampton & Hampton, 1989; Jahns et al, 1995; Eastaugh, 1996). Exacerbations may also occur at night (Bagnis & Legrand, 1987).
b) Pruritus may be mild to severe, and may be followed by cellulitis (Geller et al, 1991). It may persist for weeks after an exposure (Hampton & Hampton, 1989).
c) Pruritus of the hands and/or feet occurred in 11 of 23 (65%) crew members, aboard a Norwegian cargo ship, after eating a barracuda that was later determined to be contaminated with ciguatoxins ((MMWR, 1998)). The sensation of itch is experienced during low frequency discharge in C-polymodal nociceptive fibers (cutaneous afferent unmyelinated fibers) which are not normally active during normal temperature of undamaged skin (Cameron & Capra, 1993).
d) Pruritus was reported in 64% (n=124) of patients following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008).
e) CASE REPORT: A 30-year-old woman experienced dysesthesia and pruritus of her legs, hands, and breasts after consuming a fish contaminated with ciguatoxin. The pruritus intensified with exposure to the cold (Perez et al, 2001).
f) An outbreak of ciguatera fish poisoning was reported in Northern Germany in November of 2012. Of 11 patients who sent back a questionnaire detailing symptomatology and initial treatment, diffuse pruritus was reported in 7 patients within 24 hours after consumption of 80 to 300 g of red snapper. In some cases, the pruritus persisted for 1 year after intoxication (Mattei et al, 2014).

a) Sweating was reported in 28.7% (Bagnis & Legrand, 1987).
b) CASE REPORT: Profuse sweating occurred in 4 travelers (2 men and 2 women 49 to 53 years of age) while in Mauritius hours after they consumed fresh fish (yellow-edged lyretail; Variola louti) contaminated with ciguatoxin. The sweating, along with gastrointestinal symptoms, resolved within 48 hours (Glaizal et al, 2011).

a) CASE SERIES: Loss of hair and nails was seen in 2 of 12,890 cases (Bagnis & Legrand, 1987).

a) CASE SERIES: Arthralgias and myalgias, primarily of the legs and thighs, were seen in about 85% of cases in a series of 12,890 patients (Bagnis & Legrand, 1987; Leedom & Underman, 1993), and may last for weeks (Keynan & Pottesman, 2004).
b) CASE REPORT: A 37-year-old woman experienced sharp shooting pains in her legs that began several hours after ingesting a fish contaminated with ciguatoxin. The pain decreased following treatment with gabapentin, 400 mg orally three times daily for 3 weeks (Perez et al, 2001).
c) In a study or 12 patients with ciguatera fish poisoning, 8 (66.7%) patients developed muscle pain and 5 (41.7%) had joint pain during the first 3 days of illness (Friedman et al, 2007).
d) Arthralgias and myalgias were reported in 6% and 12%, respectively, of patients (n=124) following ciguatera intoxication, according to a retrospective review of seafood poisoning cases that occurred in French Polynesia between 1999 and 2005 (Gatti et al, 2008).

a) CASE SERIES: Neck stiffness has been reported in 24 to 27% (Bagnis & Legrand, 1987; Gillespie et al, 1986).

a) CASE REPORT: Two patients with a history (6 and 12 years earlier) of ciguatera fish poisoning were diagnosed with polymyositis on biopsy. Both suffered from muscle weakness and discomfort. One improved with prednisone treatment; the other did not.

a) CPK (blood creatine phosphokinase) and lactic dehydrogenase (LDH) may be elevated due to tissue damage caused by muscle spasticity (Swift & Swift, 1993).
b) CASE REPORT: Myopathy, described as muscle destruction with severe muscle spasms leading to tonic contractions of all muscle groups, elevated CPK (41,000 units/L), LDH (673 units/L), SGOT (774 units/L) and dark brown urine, possibly due to myoglobinuria, has been reported. Symptoms developed 48 hours following ingestion of contaminated fish (Kodama et al, 1989). The ingested fish probably also contained palytoxin.

a) The infant, delivered by C-section two days later, exhibited left-sided facial palsy, myotonia of small muscles in the hands, respiratory distress syndrome, and meconium aspiration (Pearn et al, 1982).

a) The mother was among a group of 10 people who developed classical symptoms of ciguatera poisoning after eating a kingfish caught in the Bahamas.
b) The infant was nursed 1 hour and 3 hours after his mother's fish meal and first became "colicky" 10 hours later.
c) As his mother became asymptomatic 3 weeks after the ingestion, the infant normalized within a month. No mention was made of any treatment given to the mother.

a) An ECG may be useful.
b) EMG and nerve conduction studies have been normal in all patients tested (Casanova et al, 1982).

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
b) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):