Study On The Characteristics And Etiology Of The Yunnan Unexplained Sudden Death

ObjectiveThe Yunnan Unexplained Sudden Deaths (YUSD) have occurred in many villages in Yunnan Province since the1970’s. The incidence gradually increased during the1990’s, while the cause remained elusive. To identify the cause of YUSD, the Chinese National Ministry of Science and Technology and Ministry of Health jointly started a project in2005. In2006, some YUSD cases were found to have eaten a certain mushroom before illness onset. This particular mushroom had not been named; local villagers called it the "little white mushroom." After that, many YUSD cases were found to have eaten the mushroom. The results of animal experiments and plant chemistry analysis revealed that the little white mushroom was toxic. In addition to the little white mushroom, there had to be other unknown causes because some YUSD case-patients did not eat the mushroom.The major tasks of this investigation were to further investigate the etiology of this disease, to more thoroughly explore its epidemiologic and ecological characteristics, to compare the characteristics between different clusters of YUSD cases, to evaluate the effectiveness of a health education campaign about YUSD, to study the excess deaths in villages where YUSD occurred, and to conduct a geological survey in the area where YUSD occurred with the assistance of a geologist. The ultimate purpose of the study was to provide more evidence and information for further research of the causes of YUSD and for formulating prevention and control strategies.Methods1. We collected epidemiologic data of YUSD cases during1975-2009and the clinical information of cases during2005-2009, and analyzed the temporal-spatial distribution and clinical characteristics of YUSD. We collected the meteorological and geographical data in China and in Yunnan Province, including temperature, precipitation, and elevation. We constructed a predictive model on the occurrence of YUSD by using spatial analysis techniques.2. We classified YUSD cases by types of clusters, and compared different types of cases with respect to their epidemiologic, clinical, and ecological features and exposure history in relation to the little white mushroom.3. We conducted a field evaluation of a health education campaign in Heqing, Dayao, Tengchong, Xiayun, Fengqing, and Ninglang counties. We performed in-person and questionnaire interviews, and conducted a field investigation to evaluate the health education campaign. In the other counties where YUSD had occurred, we used a questionnaires through e-mail to conduct the interviews.4. We selected four townships with the most number of YUSD cases (i.e., Shiyang, Zhongjiang, Jietou and Midian townships), and collected data about causes of death during2004-2009using retrospective investigation and active surveillance. We compared the characteristics the decedents between villages where YUSD had occurred ("case group", YUSD villages) and villages where YUSD had not occurred ("control group").5. We conducted a geological investigation in places where YUSD occurred during2010, and measured the concentration of various gases in the air, such as carbon dioxide, oxygen, and reviewed similar events from previous YUSD events.6. We summarized the characteristics of YUSD and formed a hypothesis about the causal chain of YUSD.Results1.①In total,414YUSD cases (females:61%) were reported during1975-2009in105villages of25counties in Yunnan Province. The median calendar date of illness onset was July23;95%of the YUSD cases occurred between June18and September2. The peak hours of illness onset were at08:00and18:00hours.②Most of the YUSD villages were located on a belt extending from Tengchong county to Ninglang county in the northwestern part of Yunnan Province; a small number of the YUSD villages were located at the center of Yunnan Province. Villages where YUSD has occurred during one of those years accounted for72%(75/105).③Typically, before a YUSD case occurred, it was rainy and the temperature was relatively high. The annual number of cases positively correlated with the annual average temperature. Also, the higher the altitude was and the lower the annual average temperature was, the earlier was the occurrence of YUSD cases. In addition to Yunnan Province, our model predicted that similar sudden death cases could also occur in southern Sichuan Province and a small area in northwestern Guizhou Province, based on temperature, precipitation, and altitude data.2. Approximately64%of the cases occurred as family clusters (Class Ⅰ),24%as village clusters (Class Ⅱ), and12%as non-clusters (Class Ⅲ). Class Ⅰ and Class Ⅲ(but not Class Ⅱ) cases also showed clustering by the hours of the day. Precipitation typically occurred before Class Ⅰ cases; whereas a high and rising temperature usually preceded Class Ⅱ cases. The median interval from onset to death was25m for Class Ⅰ cases,5m for Class Ⅱ cases, and170m for Class Ⅲ cases.56%of the Class Ⅰ cases had a history of consuming the little white mushroom, whereas none of the Class Ⅱ and Class Ⅲ cases had this history.3. The proportion of village residents who consumed the little white mushroom decreased from16.7%to3.8%. The number of YUSD cases decreased from121during2002-2005to43during2006-2009. In7villages, YUSD occurred during2002-2005and2006-2009; in these7villages, the number of YUSD cases also decreased from28during2002-2005to17during2006-2009.4. The total crude mortality rate was9.05‰(age-adjusted rate:6.84%o) in case group during2004-2009. The crude rate was8.16‰(age-adjusted rate:5.74‰) when YUSD cases were excluded. These rates were both higher than the rate of6.14‰(age-adjusted rate:4.79‰) in the control group. The mortality rate due to YUSD was0.89%o, which ranked fourth of all causes in the case group. The mortality rate in the case group was2.91%o in excess of control group. The excess mortality rate in the case-group was1.05%o for respiratory diseases,0.55%o for injure/poising diseases, and0.32%o for digestive diseases, compared to the control group. Excluding YUSD cases, the excess mortality due to other causes was2.02%o, which was2.3times as that of YUSD.5. The concentrations of carbon dioxide was2490ppm, and oxygen in air was7%. In comparison, in Mile County and Fengqing County, the higher the altitude the later the occurrence of YUSD cases in a calendar year.Conclusions1. YUSD cases had strict seasonality in that they only occurred in the summer. The peak occurrence hours were at breakfast and dinner times. Cases were mainly located in the northwestern and central areas of Yunnan Province and had a clear boundary. However, the exact location for the YUSD cases was unpredictable. In some villages there were multiple occurrences of YUSD, whereas in other villages YUSD only occurred during one of the years during the study period. Temperature, precipitation and altitude were correlated with YUSD. Based on these factors, the predicted regions where YUSD could occur included the northwestern and central Yunnan Province and small regions in southern Sichuan Province and northwestern Guizhou Province.2. Cases exhibiting family clustering and cases exhibiting village clustering had different characteristics. This finding might suggest different causative agents. The epidemiologic data of2006-2009supported the hypothesis that some family-clustering YUSD cases were caused by the little white mushroom.3. Health education campaign about YUSD had achieved significant effects, as shown by the sharp reduction in the rate of the villagers consuming the little white mushrooms and the corresponding decline in the number of YUSD cases in recent years.4. Villages where the YUSD occurred had a higher mortality rate than other villages. This excess mortality cannot be explained by YUSD alone.5. The villages where YUSD occurred had abnormal measurements of geogas which may be causes of some YUSD cases.