Survey for the cause of emerging dengue haemorrhagic fever in Southeast Asia

我们进行了一项研究，以找出登革出血热（DHF）的原因及其在东南亚的出现，通过：（a）在该地区的许多地方分离登革热病毒;（B）分析被病毒感染的患者细胞;（c）进行媒介蚊子调查。然后我们分析了以下三个因素：1）病原体; 2）宿主; 3）媒介。在泰国，发现登革热病毒株和蚊子媒介的敏感性的组合与病毒的传播有关。在菲律宾，观察到2型登革热病毒的基因型在全国范围内发生变化。在越南，发现了一种新的登革热4型病毒基因型暴发。此外，菲律宾和越南的流式细胞术分析表明，外周血单核细胞中存在多群登革病毒感染细胞。1)病毒毒力学说; 2）继发感染学说。通过一系列的研究，我们的结论是，这两个因素都与DHF在东南亚的发展、出现和扩大有关。DHF最明显的生理特征是血浆从外周血管迅速漏出。应阐明是什么病毒蛋白和宿主细胞因子刺激了血浆的快速泄漏。人们还注意到，从不同地方捕获的每一个埃及伊蚊种群对登革热病毒株都表现出独特的易感性。在菲律宾观察到的登革2型病毒的基因型转变可能是由新引入的病毒基因型的更高亲和力促进的。这表明DHF在20世纪60年代的快速扩张可能是由任何增强病毒和媒介蚊子亲和力的病毒突变所促进的。进一步的登革病毒株的遗传分析是必要的，以澄清登革出血热的出现和迅速扩大在东南亚的机制。

We conducted a study to find out the causes of dengue hemorrhagic fever (DHF) and its emergence in Southeast Asia, by : (a)isolating the dengue virus in many parts of the region ; (b)analyzing patient cells infected by the virus ; and (c)conducting a vector mosquito survey. We then analyzed the following three factors of the disease : 1)pathogen ; 2)host ; and 3)vector. In Thailand, a combination of dengue virus strains and the sensitivity of the mosquito vector was found to be associated with the spread of the virus. In the Philippines, a genotype shift of dengue virus type2 across the country was observed. In Vietnam, a new genotype of dengue type4 virus outbreak was witnessed. Also, Flowcytometry analysis in the Philippines and Vietnam demonstrated multipopulation of dengue virus infected cells in peripheral blood monocytes.In the past, two hypothesis on DHF were advocated, i.e., 1)virus virulence theory and 2)secondary infection theory. Our conclusion from these series of research is that both factors were concerned with the development, emergence and expansion of DHF in Southeast Asia. The evident physiological characteristic of DHF is its rapid plasma leakage from peripheral vessels. It should be clarified what viral protein(s) and kind of host cytokines are stimulating such rapid leak of plasma. It has also been noted that each population of Aedes aegypti caught from different localities demonstrated a unique susceptibility to dengue virus strains. The genotype shift of dengue 2 virus observed in the Philippines may have been promoted by a higher affinity of the newly introduced genotype of the virus. This indicates the possibility that rapid expansion of DHF during the 1960s may have been promoted by any virus mutation which enhanced virus and vector mosquito affinity. Further genetic analysis of dengue virus strains are necessary to clarify the mechanism of DHF emergence and rapid expansion in Southeast Asia.