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      Clusters of Sudden Unexplained Death Associated with the Mushroom, Trogia venenata, in Rural Yunnan Province, China

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          Abstract

          Introduction

          Since the late 1970's, time-space clusters of sudden unexplained death (SUD) in northwest Yunnan, China have alarmed the public and health authorities. From 2006–2009, we initiated enhanced surveillance for SUD to identify a cause, and we warned villagers to avoid eating unfamiliar mushrooms.

          Methods

          We established surveillance for SUD, defined as follows: sudden onset of serious, unexplained physical impairment followed by death in <24 hours. A mild case was onset of any illness in a member of the family or close socially related group of a SUD victim within 1 week of a SUD. We interviewed witnesses of SUD and mild case-persons to identify exposures to potentially toxic substances. We tested blood from mild cases, villagers, and for standard biochemical, enzyme, and electrolyte markers of disease.

          Results

          We identified 33 SUD, a 73% decline from 2002–2005, distributed among 21 villages of 11 counties. We found a previously undescribed mushroom, Trogia venenata, was eaten by 5 of 7 families with SUD clusters compared to 0 of 31 other control-families from the same villages. In T. venenata–exposed persons SUD was characterized by sudden loss of consciousness during normal activities. This mushroom grew nearby 75% of 61 villages that had time-space SUD clusters from 1975 to 2009 compared to 17% of 18 villages with only single SUD (p<0.001, Fisher's exact test).

          Discussion

          Epidemiologic data has implicated T. venenata as a probable cause of clusters of SUD in northwestern Yunnan Province. Warnings to villagers about eating this mushroom should continue.

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          Most cited references31

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          Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men.

          Between 1981 and 1988, the Centers for Disease Control and Prevention reported a very high incidence of sudden death among young male Southeast Asians who died unexpectedly during sleep. The pattern of death has long been prevalent in Southeast Asia. We carried out a study to identify the clinical markers for patients at high risk of developing sudden unexplained death syndrome (SUDS) and long-term outcomes. We studied 27 Thai men (mean age, 39.7+/-11 years) referred because they had cardiac arrest due to ventricular fibrillation, usually occurring at night while asleep (n=17), or were suspected to have had symptoms similar to the clinical presentation of SUDS (n=10). We performed cardiac testing, including EPS and cardiac catheterization. The patients were then followed at approximately 3-month intervals; our primary end points were death, ventricular fibrillation, or cardiac arrest. A distinct ECG abnormality divided our patients who had no structural heart disease (except 3 patients with mild left ventricular hypertrophy) into two groups: group 1 (n=16) patients had right bundle-branch block and ST-segment elevation in V1 through V3, and group 2 (n=11) had a normal ECG. Group 1 patients had well-defined electrophysiological abnormalities: group 1 had an abnormally prolonged His-Purkinje conduction time (HV interval, 63+/-11 versus 49+/-6 ms; P=.007). Group 1 had a higher incidence of inducible ventricular fibrillation (93% for group 1 versus 11% for group 2; P=.0002) and a positive signal-averaged ECG (92% for group 1 versus 11% for group 2; P=.002), which was associated with a higher incidence of ventricular fibrillation or death (P=.047). The life-table analysis showed that the group 1 patients had a much greater risk of dying suddenly (P=.05). Right bundle-branch block and precordial injury pattern in V1 through V3 is common in SUDS patients and represents an arrhythmogenic marker that identifies patients who face an inordinate risk of ventricular fibrillation or sudden death.
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            New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives.

            Sudden unexplained death syndrome occurs in previously healthy South-east Asian young adults without any structural cause of death. The common electrocardiographic (ECG) change in sudden unexplained death syndrome survivors is right bundle branch block and ST elevations in leads V(1) to V(3), which are similar to the ECG pattern in the Brugada syndrome (Brugada sign). It is difficult to diagnose the Brugada sign with the 12-lead ECG in sudden unexplained death syndrome survivors and their family members because the ECG could be transiently normalized. We proposed using the higher intercostal space V(1) to V(3) lead ECG, together with procainamide to detect the Brugada sign. Among 20 ventricular fibrillation cardiac arrest patients, 13 sudden unexplained death syndrome survivors and their relatives (n=88) were studied using the single standard 12-lead ECG and the new six higher intercostal space V(1) to V(3) lead ECG (-V(1) to -V(3) and -2V(1) to -2V(3)). Ten sudden unexplained death syndrome survivors and relatives (n=48) who had a normalized ECG were also infused with procainamide (10 mg x kg(-1)i.v.) to unmask the Brugada sign and both ECG methods were recorded. Forty healthy individuals and 13 spouses served as the control group. Prior to the procainamide infusion, the Brugada sign could be detected in nine sudden unexplained death syndrome survivors (69.2%) and three (3.4%) relatives with the standard ECG and in 12 (92.3%) and nine (10.2%) with the new six-lead ECG. After the procainamide infusion, the Brugada sign could be demonstrated in seven sudden unexplained death syndrome survivors (70%) and seven (14.6%) relatives with the standard ECG and in nine (90%) (P=0.26) and 23 (47.9%) (P=0.0004) with the new six-lead ECG, respectively. All the controls were negative for the Brugada sign. Our data suggest that the new higher intercostal space lead ECG, with or without the procainamide test is helpful in detecting the Brugada sign in sudden unexplained death syndrome survivors and their relatives. Copyright 2001 The European Society of Cardiology.
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              Evolving global epidemiology, syndromic classification, general management, and prevention of unknown mushroom poisonings.

              To assess the evolving global epidemiology of mushroom poisoning and to identify new and emerging mushroom poisonings and their treatments, a descriptive analysis and review of the world's salient scientific literature on mushroom poisoning was conducted. Data sources from observation studies conducted over the period 1959-2002 and describing 28,018 mushroom poisonings since 1951 were collected from case reports, case series, regional descriptive studies, meta-analyses, and laboratory studies of mushroom poisonings and the toxicokinetics of mycotoxins. Studies included in the review were selected by a MEDLINE search, 1966-2004, an Ovid OLDMEDLINE search, 1951-1965, and a medical library search for sources published before 1951. To better guide clinicians in establishing diagnoses and implementing therapies, despite confusing ingestion histories, data were extracted to permit an expanded syndromic classification of mushroom poisoning based on presentation timing and target organ systemic toxicity. The final 14 major syndromes of mushroom poisoning were stratified first by presentation timing and then by target organ systemic toxicity and included early ( or =1 day). There were eight early syndromes (four neurotoxic, two gastrointestinal, two allergic); three late syndromes (hepatotoxic, accelerated nephrotoxic, erythromelalgia); and three delayed syndromes (delayed nephrotoxic, delayed neurotoxic, rhabdomyolysis). Four new mushroom poisoning syndromes were classified including accelerated nephrotoxicity (Amanita proxima, Amanita smithiana), rhabdomyolysis (Tricholoma equestre, Russula subnigricans), erythromelalgia (Clitocybe amoenolens, Clitocybe acromelalgia), and delayed neurotoxicity (Hapalopilus rutilans). In addition, data sources were stratified by three chronological time periods with >1,000 confirmed mushroom ingestions reported and tested for any statistically significant secular trends in case fatalities from mushroom ingestions over the entire study period, 1951-2002. Since the 1950s, reports of severe and fatal mushroom poisonings have increased worldwide. Clinicians must consider mushroom poisoning in the evaluation of all patients who may be intoxicated by natural substances. Since information on natural exposures is often insufficient and incorrect, a new syndromic classification of mushroom poisoning is recommended to guide clinicians in making earlier diagnoses, especially in cases where only advanced critical care, including organ transplantation, may be life saving.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                17 May 2012
                : 7
                : 5
                : e35894
                Affiliations
                [1 ]Chinese Field Epidemiology Training Program, Chinese Center for Disease Control and Prevention, Beijing, China
                [2 ]Yunnan Institute of Endemic Diseases Control and Prevention, Dali, Yunnan Province, China
                [3 ]Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijng, China
                [4 ]Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                [5 ]Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan Province, China
                Jr., The University of Texas at San Antonio, United States of America
                Author notes

                Conceived and designed the experiments: GQS WLH JZ HZ REF GZ. Performed the experiments: GQS WLH JZ HZ TS LY SZ BLL YBW LM ZXL YG. Analyzed the data: GQS TS REF GZ. Wrote the paper: GQS REF GZ. Identified the unknown mushroom from different places as the same: ZLY.

                Article
                PONE-D-11-21093
                10.1371/journal.pone.0035894
                3355161
                22615743
                68f70eeb-f55b-4736-b79c-a3fe4ca7cdec
                Shi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 20 October 2011
                : 23 March 2012
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Plant Science
                Botany
                Mycology
                Fungi
                Medicine
                Epidemiology
                Environmental Epidemiology
                Spatial Epidemiology
                Non-Clinical Medicine
                Evidence-Based Medicine
                Health Informatics
                Public Health
                Environmental Health
                Preventive Medicine
                Toxicology
                Toxic Agents

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