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）及其在东南亚出现的原因，方法是：(a)在该地区许多地方分离登革病毒；(b)分析受病毒感染的病人细胞；(c)进行病媒蚊子调查。然后我们分析了该疾病的以下三个因素：1)病原体；2)主机;和3)向量。在泰国，发现登革热病毒毒株和蚊子媒介的敏感性与该病毒的传播有关。在菲律宾，观察到全国范围内登革热病毒2型的基因型转移。在越南，发现了一种新的4型登革热病毒基因型暴发。此外，菲律宾和越南的流式细胞术分析显示，外周血单核细胞中存在多群登革热病毒感染细胞。过去，人们对登革出血热提出了两种假说，即1)病毒毒力说和2)继发感染说。通过这一系列的研究，我们得出结论，这两个因素都与登革出血热在东南亚的发展、出现和扩大有关。DHF明显的生理特征是外周血管快速漏浆。应该弄清楚是什么病毒蛋白和哪种宿主细胞因子刺激了血浆的快速泄漏。还注意到，从不同地点捕获的埃及伊蚊种群对登革热病毒株表现出独特的易感性。在菲律宾观察到的2型登革热病毒的基因型转移可能是由于新引入的病毒基因型具有较高的亲和力而促进的。这表明，20世纪60年代登革出血热的迅速扩大可能是由于任何病毒突变促进了病毒和媒介蚊子的亲和力。进一步对登革病毒株进行遗传分析是阐明登革出血热在东南亚出现和迅速蔓延的机制的必要条件。

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.