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Ciguatera caused by consumption of humphead wrasse
Toxicon 76 (2013) 255–259
Contents lists available at ScienceDirect
Toxicon journal homepage: www.elsevier.com/locate/toxicon
Review
Ciguatera caused by consumption of humphead wrasse Thomas Y.K. Chan a, b, c, * a Division of Clinical Pharmacology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China b Centre for Food and Drug Safety, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China c Prince of Wales Hospital Poison Treatment Centre, Shatin, New Territories, Hong Kong, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 August 2013 Received in revised form 28 August 2013 Accepted 9 October 2013 Available online 17 October 2013
Humphead wrasse (Cheilinus undulatus) is an apex predator from coral reefs of the IndoPacific region. A food surveillance project using a validated mouse bioassay revealed the presence of ciguatoxins in significantly greater amounts in its flesh than in groupers and other coral reef fishes commonly available in Hong Kong wholesale market. Humphead wrasse has long been known to cause ciguatera, but there was a lack of clinical reports. A 45-year-old woman developed ciguatera after eating humphead wrasse. She required ICU care and infusions of intravenous fluids and dopamine for management of severe hypotension. All 5 published case series are also reviewed to characterise the types, severity and chronicity of ciguatera symptoms after its consumption. In addition to the gastrointestinal, neurological and other features that were typical of ciguatera, some subjects developed sinus bradycardia, hypotension, shock, neuropsychiatric features (e.g. mental exhaustion, depression, insomnia and memory loss), other central nervous system symptoms (e.g. coma, convulsions and ataxia) and myocardial ischaemia. Other subjects still experienced residual symptoms 6 months later; these were mainly neurological or neuropsychiatric complaints and skin pruritus. To prevent ciguatera, the public should avoid eating humphead wrasse and other large coral reef fishes. They should realise that consumption of the high-risk fish may result in more severe and chronic illness, including lifethreatening complications and neuropsychiatric features. Ó 2013 Elsevier Ltd. All rights reserved.
Keywords: Ciguatera Ciguatoxins Humphead wrasse Cheilinus undulatus
1. Introduction Ciguatera fish poisoning is caused by eating ciguatoxins (CTX) contaminated coral reef fish from tropical and subtropical waters (Lewis, 2006; Dickey and Plakas, 2010). These naturally occurring, lipid-soluble, heat-stable CTX originate from dinoflagellates of the genus Gambierdiscus spp. and bioaccumulate up the food chain from smaller fish to large predatory fish. Different CTX from Pacific (P-CTX), * Division of Clinical Pharmacology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China. Tel.: þ852 2632 3907; fax: þ852 2646 8756. E-mail address: [email protected]. 0041-0101/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.toxicon.2013.10.018
Caribbean (C-CTX) and Indian (I-CTX) Oceans have been identified (Dickey and Plakas, 2010). As the concentration of CTX is the highest in the viscera or liver (Vernoux et al., 1985), the large carnivores contain greater amounts and the more polar forms of CTX and P-CTX is more potent than both C-CTX and I-CTX (Lewis, 2006), severe illness is particularly likely after consumption of a large quantity of the most toxic parts and the more toxic fish (FAO, 2004). Typically, a combination of gastrointestinal, neurological, cardiovascular and other signs and symptoms is seen (Lewis, 2006; Friedman et al., 2008). In Hong Kong, ciguatera is reported from time to time, sometimes as large outbreaks, (Choi and Wong, 1994; Wong et al., 2005), mostly involving coral reef fish weighing over 2 kg (Choi and Wong, 1994). Humphead wrasse
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reported skin itchiness over the neck, face, chest wall and vulva, which subsided after 1.5 day. Her other drug treatments included intravenous mannitol (5 g on day 1) and oral hyoscine butylbromide and chlorpheniramine. Apart from leukocytosis (11.4 109/L) on day 1, her blood counts, renal and liver function tests were normal. She stayed in hospital for 4 days. On discharge, she only complained of mild tongue paraesthesia and minimal epigastric discomfort. When seen in the clinic 6 weeks later, she was perfectly well. Fig. 1. Humphead wrasse (Cheilinus undulatus) is a big apex predator from coral reefs of the Indo-Pacific region. (Photo provided by Agriculture, Fisheries and Conservation Department, The Government of the Hong Kong SAR).
(Cheilinus undulatus) (Fig. 1), a large coral reef fish imported from the Indo-Pacific region, is increasingly important as a causative agent (Wong et al., 2005). A food surveillance project using a mouse bioassay revealed the presence of CTX in significantly greater amounts in the flesh of humphead wrasse than in groupers and other coral reef fishes (Wong et al., 2005), suggesting that its consumption may cause severe symptoms. A local case and all published case series are reviewed to characterise the types, severity and chronicity of ciguatera symptoms after consumption of humphead wrasse. 2. Case report Two sisters aged 36 and 45 years became ill after sharing a meal at home. Both were in good health before the dinner, which included 0.6 kg of humphead wrasse cooked by steaming. They presented to hospital the next morning with dizziness, gastrointestinal and neurological symptoms. The latent period was longer (6 h) and the symptoms were less severe in the younger sister, who was discharged after one day of stay in observation ward. The 45-year-old sister developed dizziness, nausea, vomiting, colicky abdominal pain, generalised weakness and paraesthesia of tongue and the extremities 2.5 h after eating the fish. By the time she arrived in hospital (at 11.5 h post-meal), she already vomited once and passed loose stools three times. Her blood pressure was 80/43 mmHg and heart rate 42 beats/minute. She was fully alert with normal muscle power, light touch and pain sensation in the four limbs. ECG showed sinus bradycardia only. After intravenous infusion of 0.9% saline 500 ml at full rate, her blood pressure was 77/37 mmHg and heart rate 52 beats/minute. After infusion of another 1600 ml of 0.9% saline at full rate and dopamine (7.3 mg/kg/minute) for 20 minutes, blood pressure increased to 124/57 mmHg and heart rate to 64 beats/minute. Transient hypertension (blood pressure 166/ 78 mmHg) occurred before her blood pressure was stable at around 126/60 mmHg. She vomited once in the emergency department. During the next 20 h in the ICU, she was given Gelofusine 1750 ml, dopamine infusion (1.0–7.3 mg/kg/ minute) and 5% dextrose/0.45% saline solution 80 ml/h to keep her mean arterial pressure at 65 mmHg. On transfer to the medical ward on day 2 afternoon, she was not on inotropic or intravenous fluid therapy. During the remaining 2.5 days of hospital stay, her blood pressure and heart rate were 100–128/48–73 mmHg and 65–90 beats/minute. She
3. Published case series of ciguatera after consumption of humphead wrasse To identify relevant papers in indexed journals and Chinese medical journals, a search of Medline (1980–2013 June) and China Academic Journals Full-text Database (1994–2013 June) was conducted, using ciguatera, ciguatoxins and humphead wrasse as the search terms. Five case series of 26–39 subjects with ciguatera following consumption of humphead wrasse were identified (Table 1). In outer Melbourne, Australia (Ng and Gregory, 2000), the outbreak in September 1997 involving 30 subjects was traced to a 16.2 kg fish. Information on symptoms was obtained by phone interviews, without details about blood pressure, heart rate and investigations. Three subjects required overnight hospital admission. In Shenzhen, China, 3 hospitals each treated 26-39 subjects during October 2003–October 2004 (Li and Ma, 2005) and October 2004 (Zhang et al., 2005; Wang et al., 2006, 2007). Larger outbreaks affected 12–26 subjects each, involving fish weighing >6 kg–15 kg. All 5 reports were brief, with variable amounts of information about the quantities and fish parts consumed, clinical course of affected subjects, investigations, treatments given and the outcomes. All affected subjects presented with gastrointestinal, neurological and other symptoms (Table 1). New symptoms, such as itch, rash and dysuria, might appear days later. Although gastrointestinal symptoms generally subsided within days, neurological and neuropsychiatric (if any) symptoms could persist for weeks or even months. Variations in the types, severity and chronicity of symptoms were also obvious within and between the case series (Table 1). More severe and prolonged symptoms were generally reported by the hospital-based case series. These subjects presented with a combination of gastrointestinal (e.g. nausea, vomiting, vomiting, abdominal pain and diarrhoea), neurological (e.g. paraesthesia or numbness of lips, tongue or the extremities, myalgia, arthralgia, reversal of hot-cold sensation, formication, general weakness and fatigue), cardiovascular (e.g. sinus bradycardia, hypotension and shock) and other (e.g. dizziness, skin pruritus and metallic taste in mouth) features. Neuropsychiatric symptoms (e.g. insomnia, mental exhaustion, memory loss and depression) and other central nervous system features (e.g. convulsions, coma and ataxia) might be seen. The common occurrence of hypokalaemia (69%), chest discomfort with ECG changes of myocardial ischaemia (18–56%) and dehydration/shock (3–23%) should also be noted. Due to the method of data collection (phone interviews of affected subjects), it was possible that less severe cardiovascular features (e.g. hypotension and sinus
T.Y.K. Chan / Toxicon 76 (2013) 255–259
257
Table 1 Published case series of ciguatera and case number per outbreak after consumption of humphead wrasse. Report
Sex
Age (y)
N
Latent period, clinical features (prevalence or number of subjects affected) and the outcomes
Ng and Gregory (2000),a
–
(13–69)
30c
Li and Ma (2005),b
14M18F
45.2 (12–68)
2–16d
Zhang et al. (2005),b
15M19F
(9–52)
Up to 14e
Wang et al. (2006),b
24M15F
(2–78)
3–12
Wang et al. (2007),b
18M8F
46 (21–62)
26f,g
2–27 h; D (67%), AP (47%), N (30%), V (17%), paraesthesia of hands (87%), feet (77%) or circumoral area (57%), reversal of hot-cold sensation (63%), myalgia (77%), weakness (70%), arthralgia (57%), tremors (23%), ataxia (37%), chills (70%), neck stiffness (33%), skin pruritus (27%), dyspnoea (13%), dysuria (10%); 21 sought medical attention – 17 at hospitals with 3 admitted overnight, 4 attended local doctors, 7 treated by intravenous mannitol; at week 3, 22/30 (70%) still symptomatic, some developed late symptoms of itch (13), dysuria (3) and rash (2); by week 10, 9/18 (50%) were still symptomatic 2–10 h; dizziness, fatigue, lips/tongue numbness, N, V, AP, D (100%); knee/calf muscle pain (88%); chest discomfort þ ECG changes of myocardial ischaemia (56%); reversal of hot-cold sensation (50%); throat numbness (38%); sinus bradycardia (34%); formication/skin pruritus (31%); metallic taste in the mouth (19%); dehydration/ shock (3%); discharged from hospital after 1–3 days (n ¼ 14) or 7–14 days (n ¼ 18); reversal of hot-cold sensation could last 14–21 days; all had no complaints 1–2 months later 2–24 h; including V, AP, D, poor appetite, mental exhaustion, generalised weakness, hands/feet numbness, altered sensation, joint/muscle pain (especially knees, thighs and calves); sinus bradycardia and hypotension (n ¼ 3); coma lasting 2–3 h (n ¼ 2); residual symptoms even 6 months later (n ¼ 16) – Y libido, memory loss, scalp numbness, mouth numbness induced by hot/spicy foods (n ¼ 14); right hand numbness after sleep (n ¼ 1), myalgia (n ¼ 1) 2–10 h; dizziness, fatigue, lips paraesthesia, N, V, AP, D (92%); knee/calf muscle pain (74%); hypokalaemia (69%); formication/skin pruritus (54%); reversal of hot-cold sensation (46%); shock and dehydration (23%); ECG changes of myocardial ischaemia (18%); burning sensation (15%) or metallic taste (10%) in mouth; convulsions (13%); sinus bradycardia (10%); insomnia (8%); unsteady gait/ataxia (3%); 5 treated by intravenous mannitol; 1–2 months later, 10 subjects still had fatigue (n ¼ 8) or depression/insomnia (n ¼ 2); 6 months later, skin pruritus in 2 subjects 1–10 h; including N, V, AP, D, numbness of lips, hands and feet, poor appetite, mental exhaustion, general weakness, joint/muscle pain (especially knees and thigh/calf muscles), skin pruritus and reversal of hot-cold sensation; hypokalaemia (n ¼ 3)
Age as mean (range), N ¼ nausea, V ¼ vomiting, AP ¼ abdominal pain, D ¼ diarrhoea. a Information on symptoms obtained by phone interviews might fail to identify hypotension and bradycardia. b Hospital-based studies. c 29 adults and 1 child consumed a 16.2-kg fish (minus a small portion of the flesh and backbones) at a banquet. d Including 16 people who ate a fish weighing >6 kg. e Including 14 people who ate the head of a 15-kg fish. f 26 subjects had eaten a 14.5-kg fish. g All 26 subjects were previously healthy, 25 subjects tested þve for CTX in blood using a US commercial ELISA kit.
bradycardia) among the Melbourne cases were not identified. 4. Discussion Humphead wrasse, also known as Maori wrasse, Napoleon wrasse and Napoleon fish, is found in coral reefs and inshore habitats throughout much of the warm IndoPacific region (Gillett, 2010). It is a much sought-after, high-valued species in the live reef food-fish trade. Overfishing and effects of destructive fishing pose major threats to the sustainability of this fish species (Gillett, 2010). Hong Kong imports humphead wrasse for own consumption and for re-export to mainland China (Sadovy de Mitcheson et al., 2010). Although this large reef fish can reach a record of 250 cm in total length (TL) and 191 kg in weight, the international trade sector was dominated by fish size of <65 cm TL (Sadovy de Mitcheson et al., 2010), equivalent to <4.88 kg in weight, as estimated by the known length– weight relationship (Gillett, 2010). As expected of an apex predator from coral reefs of the Indo-Pacific region (Dickey and Plakas, 2010), humphead
wrasse should contain more CTX than other coral reef fishes. Indeed, in a 2004 food surveillance project using a validated mouse bioassay (Wong et al., 2005), 7 (13%) out of 55 random samples of reef fishes commonly found in Hong Kong market tested positive for CTX; humphead wrasse contained a mice lethal dose (2.5 MU/20 mg ether extract), while leopard coralgrouper, orange-spotted grouper and squaretail coralgrouper only had trace amounts of CTX. Humphead wrasse has long been known to cause ciguatera (FAO, 2004), but there was a lack of clinical reports, especially individual data to characterise the types, severity and chronicity of symptoms associated with its consumption (Au, 2005). As highlighted in previous reviews (Friedman et al., 2008; Dickey and Plakas, 2010), symptomatology was variable (Table 1). In addition to the gastrointestinal, neurological and other features that were typical of ciguatera, some subjects developed sinus bradycardia and hypotension/shock. Their incidences (9–34% and 3–23%) were much higher than previously reported in Hong Kong cases (Choi and Wong, 1994). From 1988 and 1992, 47 outbreaks of ciguatera affecting 397 subjects were reported, including
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one outbreak caused by humphead wrasse. One subject (0.3%) presented with bradycardia and hypotension (Chan and Wang, 1993). Although humphead wrasse is increasingly important as a causative agent (Wong et al., 2005), a higher incidence of such cardiovascular complications has also been observed in ciguatera following consumption of other coral reef fishes commonly available in Hong Kong (Cheng and Chung, 2004; Chan, 2013). Dehydration and hypovolemia caused by vomiting and diarrhoea should first be corrected using intravenous fluid replacement. The low plasma catecholamine levels, reversal of bradycardia by intravenous atropine and marked pressor response to dopamine infusion (as seen in this case report) or noradrenaline infusion suggest that hypotension is the result of both parasympathetic excess and sympathetic failure (Geller and Benowitz, 1992; Chan, 2013). In two of the hospital-based case series, the incidence of ECG changes of myocardial ischemia was said to be 18–56%, but the actual abnormalities seen and the pathophysiology involved were not described. In previous reports of ciguatera, chest pain as a symptom of ciguatera was rarely mentioned (Cheng and Chung, 2004) and its associated ECG changes were never reported. Compared to the local case and the case series in Melbourne, the hospital-based case series in Shenzhen tended to experience more severe and chronic illness, with the presence of additional features (Table 1). The common occurrence of dehydration and hypokalaemia might indicate the severity of fluid and potassium loss due to vomiting and diarrhoea. Some subjects developed neuropsychiatric features (e.g. mental exhaustion, depression, insomnia and memory loss), other central nervous system symptoms (e.g. coma, convulsions and ataxia) and myocardial ischaemia. Other subjects still had symptoms 6 months later; these were mainly neurological and neuropsychiatric complaints and skin pruritus. Since the fish responsible for larger outbreaks in Shenzhen and the quantities consumed per person were comparatively smaller than the corresponding figures for Melbourne cases (Table 1), factors other than the dose (e.g. types of CTX and individual susceptibility) might determine the types, severity and duration of symptoms (Lewis, 2006). It is also important to recognise the serious and even life-threatening complications of ciguatera, including severe bradycardia, severe hypotension, severe dehydration, convulsions, coma and myocardial ischaemia (Table 1). In those with severe bradycardia and hypotension, prompt treatments with intravenous atropine, intravenous fluid replacement and inotropic therapy are lifesaving (Chan, 2013). Ciguatera can be fatal in severe cases (Friedman et al., 2008) due to severe dehydration, cardiovascular shock or respiratory failure resulting from paralysis of the respiratory musculature. To prevent ciguatera, the public should avoid eating humphead wrasse and other large coral reef fishes, especially the most toxic parts – head, viscera, roe and skin (FAO, 2004; Centre for Food Safety, 2010). They should realise that consumption of the high-risk fish may result in more severe and chronic illness, including life-threatening complications and neuropsychiatric features. Regulatory
measures could also be introduced, including bans on highrisk fish and restrictions on fish from high-risk areas (Lewis, 2006). 5. Summary Humphead wrasse is an apex predator from coral reefs of the Indo-Pacific region. Consumption of humphead wrasse was responsible for several large outbreaks of ciguatera. In addition to the gastrointestinal, neurological and other features that were typical of this condition, some subjects developed sinus bradycardia, hypotension, shock, neuropsychiatric features (e.g. mental exhaustion, memory loss, depression and insomnia), other central nervous system symptoms (e.g. coma, convulsions and ataxia) and myocardial ischaemia. Other subjects still experienced residual symptoms 6 months later. To prevent ciguatera, the public should avoid eating humphead wrasse and other large coral reef fishes. They should realise that consumption of the high-risk fish may result in more severe and chronic illness, including life-threatening complications and neuropsychiatric features. Conflicts of interest statement The author declares no conflicts of interest regarding the preparation of this paper. References Au, A., 2005. Ciguatera fish poisoning on the rise – a review of cases (January 2004–May 2005). Commun. Dis. Watch 13, 49–50. Chan, T.Y.K., 2013. Severe bradycardia and prolonged hypotension in ciguatera. Singap. Med. J. 54, e120–e122. Chan, T.Y.K., Wang, A.Y.M., 1993. Life-threatening bradycardia and hypotension in a patient with ciguatera fish poisoning. Trans. R. Soc. Trop. Med. Hyg. 87, 71. Centre for Food Safety, 2010. Seasonal Food Safety Tips (Hong Kong). PRevention of Ciguatera Fish Poisoning Start with Choosing Coral Reef Fish Carefully. Available at: http://www.cfs.gov.hk/english/whatsnew/ whatsnew_fsf/whatsnew_fsf_poison_fish.html. Cheng, C.C., Chung, C.H., 2004. Ciguatera fish poisoning: a challenge to emergency physicians. Hong Kong J. Emerg. Med. 11, 173–177. Choi, S.M.Y., Wong, M.M.H., 1994. Epidemiology of ciguatera poisoning in Hong Kong. Public Health Epidemiol. Rep. 3, 12–14. Dickey, R.W., Plakas, S.M., 2010. Ciguatera: a public health perspective. Toxicon 56, 123–136. FAO, 2004. Ciguatera fish poisoning. In: Marine Biotoxins, FAO Food and Nutrition Paper 80. Food and Agriculture Organization of the United Nations, Rome, pp. 185–218. Friedman, M.A., Fleming, L.E., Fernandez, M., Bienfang, P., Schrank, K., Dickey, R., Bottein, M.Y., Backer, L., Ayyar, R., Weisman, R., Watkins, S., Granade, R., Reich, A., 2008. Ciguatera fish poisoning: treatment, prevention and management. Mar. Drugs 6, 456–479. Geller, R.J., Benowitz, N.L., 1992. Orthostatic hypotension in ciguatera fish poisoning. Arch. Intern. Med. 152, 2131–2133. Gillett, R., 2010. Monitoring and Management of the Humphead Wrasse, Cheilinus Undulatus. In: FAO Fisheries and Aquaculture Circular No. 1048. Food and Agriculture Organization of the United Nations, Rome. Lewis, R.J., 2006. Ciguatera: Australian perspectives on a global problem. Toxicon 48, 799–809. Li, G.Y., Ma, X.H., 2005. Rescuing and nursing of sumei fish toxicosis patients. [Chin.] J. Mod. Nurs. 11, 781–782. Ng, S., Gregory, J., 2000. An outbreak of ciguatera fish poisoning in Victoria. Commun. Dis. Intell. 24, 344–346. Sadovy de Mitcheson, Y., Liu, M., Suharti, S., 2010. Gonadal development in a giant threatened reef fish, the humphead wrasse Cheilinus undulatus, and its relationship to international trade. J. Fish Biol. 77, 706–718.
T.Y.K. Chan / Toxicon 76 (2013) 255–259 Vernoux, J.P., Lahlou, N., Abbad el Andaloussi, S., Riyeche, N., Magras, L.P., 1985. A study of the distribution of ciguatoxin in individual Caribbean fish. Acta Trop. 42, 225–233. Wang, X., Xie, N., Huo, L.P., 2007. Diagnosis and test method of ciguatoxin poisoning. [Chin.] Shen Zhen J. Integr. Tradit. Chin. West. Med. 17, 105–106, 110.
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Contents lists available at ScienceDirect
Toxicon journal homepage: www.elsevier.com/locate/toxicon
Review
Ciguatera caused by consumption of humphead wrasse Thomas Y.K. Chan a, b, c, * a Division of Clinical Pharmacology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China b Centre for Food and Drug Safety, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China c Prince of Wales Hospital Poison Treatment Centre, Shatin, New Territories, Hong Kong, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 August 2013 Received in revised form 28 August 2013 Accepted 9 October 2013 Available online 17 October 2013
Humphead wrasse (Cheilinus undulatus) is an apex predator from coral reefs of the IndoPacific region. A food surveillance project using a validated mouse bioassay revealed the presence of ciguatoxins in significantly greater amounts in its flesh than in groupers and other coral reef fishes commonly available in Hong Kong wholesale market. Humphead wrasse has long been known to cause ciguatera, but there was a lack of clinical reports. A 45-year-old woman developed ciguatera after eating humphead wrasse. She required ICU care and infusions of intravenous fluids and dopamine for management of severe hypotension. All 5 published case series are also reviewed to characterise the types, severity and chronicity of ciguatera symptoms after its consumption. In addition to the gastrointestinal, neurological and other features that were typical of ciguatera, some subjects developed sinus bradycardia, hypotension, shock, neuropsychiatric features (e.g. mental exhaustion, depression, insomnia and memory loss), other central nervous system symptoms (e.g. coma, convulsions and ataxia) and myocardial ischaemia. Other subjects still experienced residual symptoms 6 months later; these were mainly neurological or neuropsychiatric complaints and skin pruritus. To prevent ciguatera, the public should avoid eating humphead wrasse and other large coral reef fishes. They should realise that consumption of the high-risk fish may result in more severe and chronic illness, including lifethreatening complications and neuropsychiatric features. Ó 2013 Elsevier Ltd. All rights reserved.
Keywords: Ciguatera Ciguatoxins Humphead wrasse Cheilinus undulatus
1. Introduction Ciguatera fish poisoning is caused by eating ciguatoxins (CTX) contaminated coral reef fish from tropical and subtropical waters (Lewis, 2006; Dickey and Plakas, 2010). These naturally occurring, lipid-soluble, heat-stable CTX originate from dinoflagellates of the genus Gambierdiscus spp. and bioaccumulate up the food chain from smaller fish to large predatory fish. Different CTX from Pacific (P-CTX), * Division of Clinical Pharmacology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China. Tel.: þ852 2632 3907; fax: þ852 2646 8756. E-mail address: [email protected]. 0041-0101/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.toxicon.2013.10.018
Caribbean (C-CTX) and Indian (I-CTX) Oceans have been identified (Dickey and Plakas, 2010). As the concentration of CTX is the highest in the viscera or liver (Vernoux et al., 1985), the large carnivores contain greater amounts and the more polar forms of CTX and P-CTX is more potent than both C-CTX and I-CTX (Lewis, 2006), severe illness is particularly likely after consumption of a large quantity of the most toxic parts and the more toxic fish (FAO, 2004). Typically, a combination of gastrointestinal, neurological, cardiovascular and other signs and symptoms is seen (Lewis, 2006; Friedman et al., 2008). In Hong Kong, ciguatera is reported from time to time, sometimes as large outbreaks, (Choi and Wong, 1994; Wong et al., 2005), mostly involving coral reef fish weighing over 2 kg (Choi and Wong, 1994). Humphead wrasse
256
T.Y.K. Chan / Toxicon 76 (2013) 255–259
reported skin itchiness over the neck, face, chest wall and vulva, which subsided after 1.5 day. Her other drug treatments included intravenous mannitol (5 g on day 1) and oral hyoscine butylbromide and chlorpheniramine. Apart from leukocytosis (11.4 109/L) on day 1, her blood counts, renal and liver function tests were normal. She stayed in hospital for 4 days. On discharge, she only complained of mild tongue paraesthesia and minimal epigastric discomfort. When seen in the clinic 6 weeks later, she was perfectly well. Fig. 1. Humphead wrasse (Cheilinus undulatus) is a big apex predator from coral reefs of the Indo-Pacific region. (Photo provided by Agriculture, Fisheries and Conservation Department, The Government of the Hong Kong SAR).
(Cheilinus undulatus) (Fig. 1), a large coral reef fish imported from the Indo-Pacific region, is increasingly important as a causative agent (Wong et al., 2005). A food surveillance project using a mouse bioassay revealed the presence of CTX in significantly greater amounts in the flesh of humphead wrasse than in groupers and other coral reef fishes (Wong et al., 2005), suggesting that its consumption may cause severe symptoms. A local case and all published case series are reviewed to characterise the types, severity and chronicity of ciguatera symptoms after consumption of humphead wrasse. 2. Case report Two sisters aged 36 and 45 years became ill after sharing a meal at home. Both were in good health before the dinner, which included 0.6 kg of humphead wrasse cooked by steaming. They presented to hospital the next morning with dizziness, gastrointestinal and neurological symptoms. The latent period was longer (6 h) and the symptoms were less severe in the younger sister, who was discharged after one day of stay in observation ward. The 45-year-old sister developed dizziness, nausea, vomiting, colicky abdominal pain, generalised weakness and paraesthesia of tongue and the extremities 2.5 h after eating the fish. By the time she arrived in hospital (at 11.5 h post-meal), she already vomited once and passed loose stools three times. Her blood pressure was 80/43 mmHg and heart rate 42 beats/minute. She was fully alert with normal muscle power, light touch and pain sensation in the four limbs. ECG showed sinus bradycardia only. After intravenous infusion of 0.9% saline 500 ml at full rate, her blood pressure was 77/37 mmHg and heart rate 52 beats/minute. After infusion of another 1600 ml of 0.9% saline at full rate and dopamine (7.3 mg/kg/minute) for 20 minutes, blood pressure increased to 124/57 mmHg and heart rate to 64 beats/minute. Transient hypertension (blood pressure 166/ 78 mmHg) occurred before her blood pressure was stable at around 126/60 mmHg. She vomited once in the emergency department. During the next 20 h in the ICU, she was given Gelofusine 1750 ml, dopamine infusion (1.0–7.3 mg/kg/ minute) and 5% dextrose/0.45% saline solution 80 ml/h to keep her mean arterial pressure at 65 mmHg. On transfer to the medical ward on day 2 afternoon, she was not on inotropic or intravenous fluid therapy. During the remaining 2.5 days of hospital stay, her blood pressure and heart rate were 100–128/48–73 mmHg and 65–90 beats/minute. She
3. Published case series of ciguatera after consumption of humphead wrasse To identify relevant papers in indexed journals and Chinese medical journals, a search of Medline (1980–2013 June) and China Academic Journals Full-text Database (1994–2013 June) was conducted, using ciguatera, ciguatoxins and humphead wrasse as the search terms. Five case series of 26–39 subjects with ciguatera following consumption of humphead wrasse were identified (Table 1). In outer Melbourne, Australia (Ng and Gregory, 2000), the outbreak in September 1997 involving 30 subjects was traced to a 16.2 kg fish. Information on symptoms was obtained by phone interviews, without details about blood pressure, heart rate and investigations. Three subjects required overnight hospital admission. In Shenzhen, China, 3 hospitals each treated 26-39 subjects during October 2003–October 2004 (Li and Ma, 2005) and October 2004 (Zhang et al., 2005; Wang et al., 2006, 2007). Larger outbreaks affected 12–26 subjects each, involving fish weighing >6 kg–15 kg. All 5 reports were brief, with variable amounts of information about the quantities and fish parts consumed, clinical course of affected subjects, investigations, treatments given and the outcomes. All affected subjects presented with gastrointestinal, neurological and other symptoms (Table 1). New symptoms, such as itch, rash and dysuria, might appear days later. Although gastrointestinal symptoms generally subsided within days, neurological and neuropsychiatric (if any) symptoms could persist for weeks or even months. Variations in the types, severity and chronicity of symptoms were also obvious within and between the case series (Table 1). More severe and prolonged symptoms were generally reported by the hospital-based case series. These subjects presented with a combination of gastrointestinal (e.g. nausea, vomiting, vomiting, abdominal pain and diarrhoea), neurological (e.g. paraesthesia or numbness of lips, tongue or the extremities, myalgia, arthralgia, reversal of hot-cold sensation, formication, general weakness and fatigue), cardiovascular (e.g. sinus bradycardia, hypotension and shock) and other (e.g. dizziness, skin pruritus and metallic taste in mouth) features. Neuropsychiatric symptoms (e.g. insomnia, mental exhaustion, memory loss and depression) and other central nervous system features (e.g. convulsions, coma and ataxia) might be seen. The common occurrence of hypokalaemia (69%), chest discomfort with ECG changes of myocardial ischaemia (18–56%) and dehydration/shock (3–23%) should also be noted. Due to the method of data collection (phone interviews of affected subjects), it was possible that less severe cardiovascular features (e.g. hypotension and sinus
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257
Table 1 Published case series of ciguatera and case number per outbreak after consumption of humphead wrasse. Report
Sex
Age (y)
N
Latent period, clinical features (prevalence or number of subjects affected) and the outcomes
Ng and Gregory (2000),a
–
(13–69)
30c
Li and Ma (2005),b
14M18F
45.2 (12–68)
2–16d
Zhang et al. (2005),b
15M19F
(9–52)
Up to 14e
Wang et al. (2006),b
24M15F
(2–78)
3–12
Wang et al. (2007),b
18M8F
46 (21–62)
26f,g
2–27 h; D (67%), AP (47%), N (30%), V (17%), paraesthesia of hands (87%), feet (77%) or circumoral area (57%), reversal of hot-cold sensation (63%), myalgia (77%), weakness (70%), arthralgia (57%), tremors (23%), ataxia (37%), chills (70%), neck stiffness (33%), skin pruritus (27%), dyspnoea (13%), dysuria (10%); 21 sought medical attention – 17 at hospitals with 3 admitted overnight, 4 attended local doctors, 7 treated by intravenous mannitol; at week 3, 22/30 (70%) still symptomatic, some developed late symptoms of itch (13), dysuria (3) and rash (2); by week 10, 9/18 (50%) were still symptomatic 2–10 h; dizziness, fatigue, lips/tongue numbness, N, V, AP, D (100%); knee/calf muscle pain (88%); chest discomfort þ ECG changes of myocardial ischaemia (56%); reversal of hot-cold sensation (50%); throat numbness (38%); sinus bradycardia (34%); formication/skin pruritus (31%); metallic taste in the mouth (19%); dehydration/ shock (3%); discharged from hospital after 1–3 days (n ¼ 14) or 7–14 days (n ¼ 18); reversal of hot-cold sensation could last 14–21 days; all had no complaints 1–2 months later 2–24 h; including V, AP, D, poor appetite, mental exhaustion, generalised weakness, hands/feet numbness, altered sensation, joint/muscle pain (especially knees, thighs and calves); sinus bradycardia and hypotension (n ¼ 3); coma lasting 2–3 h (n ¼ 2); residual symptoms even 6 months later (n ¼ 16) – Y libido, memory loss, scalp numbness, mouth numbness induced by hot/spicy foods (n ¼ 14); right hand numbness after sleep (n ¼ 1), myalgia (n ¼ 1) 2–10 h; dizziness, fatigue, lips paraesthesia, N, V, AP, D (92%); knee/calf muscle pain (74%); hypokalaemia (69%); formication/skin pruritus (54%); reversal of hot-cold sensation (46%); shock and dehydration (23%); ECG changes of myocardial ischaemia (18%); burning sensation (15%) or metallic taste (10%) in mouth; convulsions (13%); sinus bradycardia (10%); insomnia (8%); unsteady gait/ataxia (3%); 5 treated by intravenous mannitol; 1–2 months later, 10 subjects still had fatigue (n ¼ 8) or depression/insomnia (n ¼ 2); 6 months later, skin pruritus in 2 subjects 1–10 h; including N, V, AP, D, numbness of lips, hands and feet, poor appetite, mental exhaustion, general weakness, joint/muscle pain (especially knees and thigh/calf muscles), skin pruritus and reversal of hot-cold sensation; hypokalaemia (n ¼ 3)
Age as mean (range), N ¼ nausea, V ¼ vomiting, AP ¼ abdominal pain, D ¼ diarrhoea. a Information on symptoms obtained by phone interviews might fail to identify hypotension and bradycardia. b Hospital-based studies. c 29 adults and 1 child consumed a 16.2-kg fish (minus a small portion of the flesh and backbones) at a banquet. d Including 16 people who ate a fish weighing >6 kg. e Including 14 people who ate the head of a 15-kg fish. f 26 subjects had eaten a 14.5-kg fish. g All 26 subjects were previously healthy, 25 subjects tested þve for CTX in blood using a US commercial ELISA kit.
bradycardia) among the Melbourne cases were not identified. 4. Discussion Humphead wrasse, also known as Maori wrasse, Napoleon wrasse and Napoleon fish, is found in coral reefs and inshore habitats throughout much of the warm IndoPacific region (Gillett, 2010). It is a much sought-after, high-valued species in the live reef food-fish trade. Overfishing and effects of destructive fishing pose major threats to the sustainability of this fish species (Gillett, 2010). Hong Kong imports humphead wrasse for own consumption and for re-export to mainland China (Sadovy de Mitcheson et al., 2010). Although this large reef fish can reach a record of 250 cm in total length (TL) and 191 kg in weight, the international trade sector was dominated by fish size of <65 cm TL (Sadovy de Mitcheson et al., 2010), equivalent to <4.88 kg in weight, as estimated by the known length– weight relationship (Gillett, 2010). As expected of an apex predator from coral reefs of the Indo-Pacific region (Dickey and Plakas, 2010), humphead
wrasse should contain more CTX than other coral reef fishes. Indeed, in a 2004 food surveillance project using a validated mouse bioassay (Wong et al., 2005), 7 (13%) out of 55 random samples of reef fishes commonly found in Hong Kong market tested positive for CTX; humphead wrasse contained a mice lethal dose (2.5 MU/20 mg ether extract), while leopard coralgrouper, orange-spotted grouper and squaretail coralgrouper only had trace amounts of CTX. Humphead wrasse has long been known to cause ciguatera (FAO, 2004), but there was a lack of clinical reports, especially individual data to characterise the types, severity and chronicity of symptoms associated with its consumption (Au, 2005). As highlighted in previous reviews (Friedman et al., 2008; Dickey and Plakas, 2010), symptomatology was variable (Table 1). In addition to the gastrointestinal, neurological and other features that were typical of ciguatera, some subjects developed sinus bradycardia and hypotension/shock. Their incidences (9–34% and 3–23%) were much higher than previously reported in Hong Kong cases (Choi and Wong, 1994). From 1988 and 1992, 47 outbreaks of ciguatera affecting 397 subjects were reported, including
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one outbreak caused by humphead wrasse. One subject (0.3%) presented with bradycardia and hypotension (Chan and Wang, 1993). Although humphead wrasse is increasingly important as a causative agent (Wong et al., 2005), a higher incidence of such cardiovascular complications has also been observed in ciguatera following consumption of other coral reef fishes commonly available in Hong Kong (Cheng and Chung, 2004; Chan, 2013). Dehydration and hypovolemia caused by vomiting and diarrhoea should first be corrected using intravenous fluid replacement. The low plasma catecholamine levels, reversal of bradycardia by intravenous atropine and marked pressor response to dopamine infusion (as seen in this case report) or noradrenaline infusion suggest that hypotension is the result of both parasympathetic excess and sympathetic failure (Geller and Benowitz, 1992; Chan, 2013). In two of the hospital-based case series, the incidence of ECG changes of myocardial ischemia was said to be 18–56%, but the actual abnormalities seen and the pathophysiology involved were not described. In previous reports of ciguatera, chest pain as a symptom of ciguatera was rarely mentioned (Cheng and Chung, 2004) and its associated ECG changes were never reported. Compared to the local case and the case series in Melbourne, the hospital-based case series in Shenzhen tended to experience more severe and chronic illness, with the presence of additional features (Table 1). The common occurrence of dehydration and hypokalaemia might indicate the severity of fluid and potassium loss due to vomiting and diarrhoea. Some subjects developed neuropsychiatric features (e.g. mental exhaustion, depression, insomnia and memory loss), other central nervous system symptoms (e.g. coma, convulsions and ataxia) and myocardial ischaemia. Other subjects still had symptoms 6 months later; these were mainly neurological and neuropsychiatric complaints and skin pruritus. Since the fish responsible for larger outbreaks in Shenzhen and the quantities consumed per person were comparatively smaller than the corresponding figures for Melbourne cases (Table 1), factors other than the dose (e.g. types of CTX and individual susceptibility) might determine the types, severity and duration of symptoms (Lewis, 2006). It is also important to recognise the serious and even life-threatening complications of ciguatera, including severe bradycardia, severe hypotension, severe dehydration, convulsions, coma and myocardial ischaemia (Table 1). In those with severe bradycardia and hypotension, prompt treatments with intravenous atropine, intravenous fluid replacement and inotropic therapy are lifesaving (Chan, 2013). Ciguatera can be fatal in severe cases (Friedman et al., 2008) due to severe dehydration, cardiovascular shock or respiratory failure resulting from paralysis of the respiratory musculature. To prevent ciguatera, the public should avoid eating humphead wrasse and other large coral reef fishes, especially the most toxic parts – head, viscera, roe and skin (FAO, 2004; Centre for Food Safety, 2010). They should realise that consumption of the high-risk fish may result in more severe and chronic illness, including life-threatening complications and neuropsychiatric features. Regulatory
measures could also be introduced, including bans on highrisk fish and restrictions on fish from high-risk areas (Lewis, 2006). 5. Summary Humphead wrasse is an apex predator from coral reefs of the Indo-Pacific region. Consumption of humphead wrasse was responsible for several large outbreaks of ciguatera. In addition to the gastrointestinal, neurological and other features that were typical of this condition, some subjects developed sinus bradycardia, hypotension, shock, neuropsychiatric features (e.g. mental exhaustion, memory loss, depression and insomnia), other central nervous system symptoms (e.g. coma, convulsions and ataxia) and myocardial ischaemia. Other subjects still experienced residual symptoms 6 months later. To prevent ciguatera, the public should avoid eating humphead wrasse and other large coral reef fishes. They should realise that consumption of the high-risk fish may result in more severe and chronic illness, including life-threatening complications and neuropsychiatric features. Conflicts of interest statement The author declares no conflicts of interest regarding the preparation of this paper. References Au, A., 2005. Ciguatera fish poisoning on the rise – a review of cases (January 2004–May 2005). Commun. Dis. Watch 13, 49–50. Chan, T.Y.K., 2013. Severe bradycardia and prolonged hypotension in ciguatera. Singap. Med. J. 54, e120–e122. Chan, T.Y.K., Wang, A.Y.M., 1993. Life-threatening bradycardia and hypotension in a patient with ciguatera fish poisoning. Trans. R. Soc. Trop. Med. Hyg. 87, 71. Centre for Food Safety, 2010. Seasonal Food Safety Tips (Hong Kong). PRevention of Ciguatera Fish Poisoning Start with Choosing Coral Reef Fish Carefully. Available at: http://www.cfs.gov.hk/english/whatsnew/ whatsnew_fsf/whatsnew_fsf_poison_fish.html. Cheng, C.C., Chung, C.H., 2004. Ciguatera fish poisoning: a challenge to emergency physicians. Hong Kong J. Emerg. Med. 11, 173–177. Choi, S.M.Y., Wong, M.M.H., 1994. Epidemiology of ciguatera poisoning in Hong Kong. Public Health Epidemiol. Rep. 3, 12–14. Dickey, R.W., Plakas, S.M., 2010. Ciguatera: a public health perspective. Toxicon 56, 123–136. FAO, 2004. Ciguatera fish poisoning. In: Marine Biotoxins, FAO Food and Nutrition Paper 80. Food and Agriculture Organization of the United Nations, Rome, pp. 185–218. Friedman, M.A., Fleming, L.E., Fernandez, M., Bienfang, P., Schrank, K., Dickey, R., Bottein, M.Y., Backer, L., Ayyar, R., Weisman, R., Watkins, S., Granade, R., Reich, A., 2008. Ciguatera fish poisoning: treatment, prevention and management. Mar. Drugs 6, 456–479. Geller, R.J., Benowitz, N.L., 1992. Orthostatic hypotension in ciguatera fish poisoning. Arch. Intern. Med. 152, 2131–2133. Gillett, R., 2010. Monitoring and Management of the Humphead Wrasse, Cheilinus Undulatus. In: FAO Fisheries and Aquaculture Circular No. 1048. Food and Agriculture Organization of the United Nations, Rome. Lewis, R.J., 2006. Ciguatera: Australian perspectives on a global problem. Toxicon 48, 799–809. Li, G.Y., Ma, X.H., 2005. Rescuing and nursing of sumei fish toxicosis patients. [Chin.] J. Mod. Nurs. 11, 781–782. Ng, S., Gregory, J., 2000. An outbreak of ciguatera fish poisoning in Victoria. Commun. Dis. Intell. 24, 344–346. Sadovy de Mitcheson, Y., Liu, M., Suharti, S., 2010. Gonadal development in a giant threatened reef fish, the humphead wrasse Cheilinus undulatus, and its relationship to international trade. J. Fish Biol. 77, 706–718.
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