Molecular epidemiology of dengue viruses in three provinces of Lao PDR, 2006-2010

Few data on dengue epidemiology are available for Lao PDR. Here, we provide information on the complexity of dengue epidemiology in the country, demonstrating dynamic circulation that varies over space and time, according to serotype. We recruited 1,912 consenting patients presenting with WHO dengue criteria at Mahosot Hospital, Vientiane (central Laos), between 2006 and 2010. Between 2008 and 2010, 1,413 patients with undifferentiated fever were also recruited at Luang Namtha (LNT) Provincial Hospital (northern Laos) and 555 at Salavan (SV) Provincial Hospital (southern Laos). We report significant variations in Dengue virus (DENV) circulation between the three sites. Peaks of DENV infection were observed in the rainy seasons, although 11% of confirmed cases in the provinces and 4.6% in the capital were detected during the dry and cool seasons (between December and February). Four DENV serotypes were detected among the 867 RT-PCR positive patients: 76.9% DENV-1, 9.6% DENV-2, 7.7% DENV-4 and 5.3% DENV-3. DENV-1 was the predominant serotype throughout the study except in LNT in 2008 and 2009 when it was DENV-2. Before July 2009, DENV-2 was not detected in SV and only rarely detected in Vientiane. DENV-3 and DENV-4 were commonly detected in Vientiane, before 2008 for DENV-4 and after 2009 for DENV-3. The phylogenetic analyses of DENV envelope sequences suggest concurrent multiple introductions of new strains as well as active DENV circulation throughout Laos and with neighboring countries. It is therefore of great importance to develop and strengthen a year-round nation-wide surveillance network in order to collect data that would allow anticipation of public health issues caused by the occurrence of large dengue outbreaks.

目前老挝人民民主共和国可获取的登革热流行病学相关数据较为匮乏。本研究针对该国登革热流行病学的复杂性展开调研，揭示了其按血清型划分、随空间与时间动态变化的病毒传播特征。2006年至2010年间，我们在老挝中部万象市的玛霍索医院（Mahosot Hospital）招募了1912名符合世界卫生组织（WHO）登革热诊断标准且签署知情同意书的患者。2008年至2010年间，我们还在老挝北部的琅南塔（LNT）省医院及南部的沙拉湾（SV）省医院分别招募了1413名不明原因发热患者与555名不明原因发热患者。本研究发现，三个采样点的登革病毒（Dengue virus, DENV）传播特征存在显著差异。登革病毒感染高峰多出现于雨季，但仍有11%的省份确诊病例与4.6%的首都确诊病例在干凉季（12月至次年2月）被检出。在867名逆转录聚合酶链反应（RT-PCR）检测呈阳性的患者中，共检出4种登革病毒血清型：其中DENV-1占比76.9%，DENV-2占9.6%，DENV-4占7.7%，DENV-3占5.3%。在整个研究周期内，DENV-1均为优势血清型，仅2008年与2009年的琅南塔采样点例外，彼时优势血清型为DENV-2。2009年7月之前，沙拉湾（SV）采样点未检出DENV-2，万象采样点也仅偶有检出。DENV-3与DENV-4在万象采样点较为常见：DENV-4的检出集中于2008年之前，DENV-3则在2009年之后较为多见。对登革病毒包膜蛋白序列的系统发育分析表明，老挝境内及与周边国家间同时存在多株新毒株的输入事件，且登革病毒传播持续活跃。因此，建立并强化全年运行的全国性监测网络，以收集相关数据从而预判大规模登革热暴发引发的公共卫生问题，具有重要意义。