The impact of the demographic transition on dengue in Thailand: insights from a statistical analysis and mathematical modeling.
The impact of the demographic transition on dengue in Thailand: insights from a statistical analysis and mathematical modeling.
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DOI：
10.1371/journal.pmed.1000139
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发表时间：
2009-09
期刊：
影响因子：
15.8
通讯作者：
Gibbons RV
中科院分区：
文献类型：
--
作者：
Cummings DA;Iamsirithaworn S;Lessler JT;McDermott A;Prasanthong R;Nisalak A;Jarman RG;Burke DS;Gibbons RV
通过分析泰国 72 个省份的数据，Derek Cummings 及其同事发现，出生率和死亡率的下降可以解释登革出血热年龄分布的变化。据报道，泰国登革出血热（DHF）病例的平均年龄有所增加。这种增加的原因尚不清楚。可能的解释包括由于蚊子数量减少、人与蚊子之间的接触减少以及报告的变化而导致传播减少。我们认为，人口出生率和死亡率的转变减少了登革热传播并延长了大规模流行病之间的间隔。我们利用泰国 72 个省份的数据，寻找感染力（一种危险度量，定义为易感个体被感染的人均比率）与人口和气候变量之间的关联。我们根据1985年至2005年病例的年龄分布估算了感染力。我们发现，感染力自1970年代末和1980年代初的高峰以来每年下降2%。与最近的研究结果表明泰国的 DHF 发病率有所增加相反，我们发现自 1985 年以来大多数省份的 DHF 发病率虽小但具有统计显着性下降。感染力和平均感染力变化的最强预测因素是人口的中位年龄。通过对登革热传播的数学模拟，我们发现，在没有其他变化的情况下，出生率的降低和人口年龄结构的变化可以解释病例年龄分布的变化、感染力的降低以及登革热发病率的多年振荡周期性的增加。较低的出生率和死亡率减少了易感个体进入人群的数量，并延长了免疫个体的寿命。免疫人口比例的增加增加了传染性蚊子以免疫个体为食的可能性，从而降低了感染力。虽然感染力下降了一半，但我们发现关键疫苗接种率没有显着变化，从平均85%下降到80%。临床指南应考虑泰国登革热病例年龄持续增加的影响。该地区在人口转型方面落后于泰国的国家可能会随着人口老龄化而经历同样的增长。人口变化对其他疾病感染力的影响已经被假设，但据我们所知，这是对这种现象的首次观察。 请参阅本文后面的编辑摘要 每年，登革热都会感染生活在热带和亚热带地区的 50-1 亿人。引起登革热的四种密切相关的病毒通过雌性埃及伊蚊的叮咬传播给人类，雌性埃及伊蚊通过吸食感染者的血液而获得登革热病毒。尽管一些感染登革热病毒的人没有任何症状，但许多人会出现登革热，这是一种持续几天的严重流感样疾病。其他人（每年超过 50 万人）患上登革出血热，会导致牙龈和鼻子出血和瘀伤，或者会出现登革休克综合症，也会出现循环衰竭。这两种潜在的致命病症都与登革热病毒的连续感染有关——一种类型的登革热病毒的非致命感染可以提供针对该类型的终生免疫力，但只能暂时防止其他类型的登革热病毒的感染。没有疫苗可以预防登革热，也没有针对该疾病的具体治疗方法。然而，标准医疗护理——特别是补充流失的液体——可以预防大多数登革热死亡。从历史上看，登革热主要影响幼儿，但最近，在包括泰国在内的几个东南亚国家，其年龄分布已转向老年人群。此外，登革出血热发病率（流行）大幅增加之间的间隔也已拉长。了解这些变化发生的原因很重要，因为它们可能会影响这些国家处理登革热感染的方式。一种想法是，持续向较低出生率和死亡率的转变（人口转型；这发生在国家从前工业化经济转向工业化经济时）正在通过降低“感染力”（易感个体被感染的速度）来降低登革热传播率。随着出生率和死亡率的下降，免疫个体在人口中所占比例越来越大，因此蚊子更有可能叮咬免疫个体，从而降低了感染力。同样，由于易感个体通过出生而进入人群，出生率的变化会改变流行病之间的间隔。在这项研究中，研究人员测试了人口转变是否可能导致泰国登革热感染模式的变化。研究人员从各种来源检索了泰国1980年至2005年的登革热感染数据、人口数据（人口年龄结构以及出生率和死亡率）、社会经济数据和气候数据。然后，他们将登革热病例的数据拟合到几个数学模型中，以估计每年的感染强度。该分析表明，自20世纪80年代初以来，感染力每年下降2%。接下来，研究人员利用统计方法表明，这种下降的最强预测因素是人口中位年龄（人口平均年龄的衡量标准）的增加。最后，通过对登革热传播的数学模拟，他们表明，出生率的降低和人口年龄结构的变化足以解释最近登革热病例年龄分布的变化、感染力的降低以及登革出血热流行之间的间隔增加。所有建模研究的结果取决于数学模型的构建方式以及输入数据的准确性。然而，这些发现表明，泰国最近出生率和死亡率的变化足以产生观察到的登革热年龄分布和登革热爆发周期的变化。这些发现的一个含义是，随着泰国人口结构转变，东南亚其他国家可能会随着人口年龄结构的变化而经历类似的登革热感染模式变化。这意味着东南亚登革热感染管理的临床指南需要进行调整，以适应登革热病例年龄的增长。最后，尽管研究人员的计算显示，在过去二十年里，感染力已大幅下降，但他们也表明，当登革热疫苗问世时，仍然有必要为大多数人口接种疫苗以阻止登革热传播。请通过此摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.1000139 Cameron Simmons 和 Jeremy Farrar 在 PLoS Medicine Perspective 中进一步讨论了这项研究 美国疾病控制和预防中心提供了有关登革热和登革出血热的详细信息（英语和西班牙语） 世界卫生组织提供了信息 关于世界各地登革热和登革出血热的信息（多种语言）以及东南亚登革热的详细信息 MedlinePlus 提供有关登革热的其他信息的链接（英语和西班牙语） 维基百科有一个关于人口转变的页面（请注意，维基百科是任何人都可以编辑的免费在线百科全书；提供多种语言版本）
Analyzing data from Thailand's 72 provinces, Derek Cummings and colleagues find that decreases in birth and death rates can explain the shift in age distribution of dengue hemorrhagic fever. An increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics. Using data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population's age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes. Lower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon. Please see later in the article for the Editors' Summary Every year, dengue infects 50–100 million people living in tropical and subtropical areas. The four closely related viruses that cause dengue are transmitted to people through the bites of female Aedes aegypti mosquitoes, which acquire dengue virus by feeding on the blood of an infected person. Although some people who become infected with dengue virus have no symptoms, many develop dengue fever, a severe, flu-like illness that lasts for a few days. Other people—more than half a million a year—develop dengue hemorrhagic fever, which causes bleeding from the gums and nose and bruising, or dengue shock syndrome in which circulatory failure also occurs. Both these potentially fatal conditions are associated with sequential infections with dengue virus—nonfatal infection with dengue virus of one type provides lifelong immunity against that type but only temporary protection against infection with dengue viruses of other types. There is no vaccine to prevent dengue and no specific treatment for the disease. However, standard medical care—in particular, replacement of lost fluids—can prevent most deaths from dengue. Historically, dengue has mainly affected young children but, recently, its age distribution has shifted towards older age groups in several Southeast Asian countries, including Thailand. In addition, the interval between large increases in incidence (epidemics) of dengue hemorrhagic fever has lengthened. It is important to know why these changes are happening because they could affect how dengue infections are dealt with in these countries. One idea is that an ongoing shift towards lower birth and death rates (the demographic transition; this occurs as countries move from a pre-industrial to an industrial economy) is reducing dengue transmission rates by reducing the “force of infection” (the rate at which susceptible individuals become infected). As birth and death rates decline, immune individuals account for more of the population so mosquitoes are more likely to bite an immune individual, which reduces the force of infection. Similarly, because susceptible individuals enter the population by being born, changing the birth rate alters the interval between epidemics. In this study, the researchers test whether the demographic transition might be responsible for the changing pattern of dengue infection in Thailand. The researchers retrieved data on dengue infection, demographic data (the population's age structure and birth and death rates), socioeconomic data, and climatic data for Thailand from 1980 to 2005 from various sources. They then fitted the data on dengue cases to several mathematical models to estimate the force of infection for each year. This analysis suggested that the force of infection has declined by 2% every year since the early1980s. Next, the researchers used statistical methods to show that the strongest predictor of this decline is the increase in the median age of the population (a measure of the average age of the population). Finally, using mathematical simulations of dengue transmission, they showed that a reduced birth rate and a shift in the population's age structure are sufficient to explain the recent shift in the age distribution of dengue cases, the reduction of the force of infection, and the increased interval between epidemics of dengue hemorrhagic fever. The findings of all modeling studies depend on how the mathematical models are built and the accuracy of the data fed into them. Nevertheless, these findings suggest that recent changes in birth and death rates in Thailand are sufficient to produce the observed changes in the age distribution of dengue and periodicity of dengue outbreaks. One implication of these findings is that other countries in Southeast Asia that follow Thailand in the demographic transition may experience similar shifts in the pattern of dengue infections as the age structure of their populations changes. This means that clinical guidelines for the management of dengue infections in Southeast Asia will need to be adjusted to allow for the increasing age of dengue cases. Finally, although the researchers' calculations show the force of infection has fallen substantially over the past two decades, they also show that when a dengue vaccine becomes available, it will still be necessary to vaccinate most of the population to halt dengue transmission. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000139 This study is further discussed in a PLoS Medicine Perspective by Cameron Simmons and Jeremy Farrar The US Centers for Disease Control and Prevention provides detailed information about dengue fever and dengue hemorrhagic fever (in English and Spanish) The World Health Organization provides information about dengue and dengue hemorrhagic fever around the world (in several languages) and detailed information about dengue in Southeast Asia Links to additional information about dengue are provided by MedlinePlus (in English and Spanish) Wikipedia has a page about the demographic transition (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
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影响因子：
64.8
作者：
Cummings, DAT;Irizarry, RA;Burke, DS
通讯作者：
Burke, DS
DOI：
10.4269/ajtmh.1988.38.172
发表时间：
1988-01-01
影响因子：
3.3
作者：
BURKE, DS;NISALAK, A;SCOTT, RM
通讯作者：
SCOTT, RM
DOI：
10.1073/pnas.0507320102
发表时间：
2005-10-18
影响因子：
11.1
作者：
Cummings, DAT;Schwartz, IB;Burke, DS
通讯作者：
Burke, DS
影响因子：
4.2
作者：
Chareonsook, O;Foy, HM;Silarug, N
通讯作者：
Silarug, N
DOI：
10.1016/s1201-9712(02)90072-x
发表时间：
2002-06-01
影响因子：
8.4
作者：
Guzman, Maria G.;Kouri, Gustavo;Halstead, Scott B.
通讯作者：
Halstead, Scott B.