Extrinsic Incubation Period of Dengue: Knowledge, Backlog, and Applications of Temperature Dependence

Dengue is generally believed to be one of the most hazardous vector-borne diseases, with over 40% of the world’s population at risk of an infection [1]. While in the past the disease has mainly been observed in the tropical regions, recent studies suggest that, under the pressure of future climate change, new areas as far north as Europe may become endangered. In fact, in 2010 the first European cases of autochthonous dengue since the epidemic outbreak in Greece in the late 1920s [2] were reported from Croatia [3] and France [4]. Recently, Madeira experienced a severe epidemic of dengue fever, with about 2,000 cases within two months [5]. When it comes to determining the risk of dengue occurring in a given region, the extrinsic incubation period (EIP) plays an important role. The EIP is commonly defined as ‘‘the interval between the acquisition of an infectious agent by a vector and the vector’s ability to transmit the agent to other susceptible vertebrate hosts’’ [6]. In the case of dengue, after the virus is ingested by a mosquito through a blood meal, some time is required for the virus to replicate, escape the midgut, and spread through the mosquito’s body until it ultimately reaches the salivary glands (SG), from where it can be passed on to another host during the next blood meal. For dengue, the duration of the pathogen’s EIP is known to be temperaturedependent, but very few mechanistic risk models (usually based on the basic reproductive number R0, i.e., the number of secondary cases produced by one primary case in a completely susceptible population [7]) have taken that into account until now. In fact, most of the models implemented for dengue use fixed values for the duration of the EIP or rather rough estimates of temperature dependence [8]. This may be due to the fact that experimental studies on this topic are rare, and their results may appear to some extent inconsistent or even contradictory. However, the implementation of a realistic, temperaturedependent EIP will greatly improve mechanistic dengue modeling: since EIP appears as an exponent in the equations used for the determination of R0 and vector capacity [7,9,10], even small changes in EIP can have a large impact on the results of mechanistic dengue models that build on the concept of R0. The practical relevance of this issue has been demonstrated for dengue [9] as well as other vector-borne diseases such as malaria [11] and bluetongue [12]. In addition, correlative models based on environmental factors and vector distributions (also referred to as ‘‘climate envelope models’’ or ‘‘environmental niche models’’) have to be revised and enhanced. Currently, these models usually focus on the spatial distribution of vector species. But if temperatures do not support amplification and establishment of the virus even though the vector is present, risk assessment based solely on vector distributions leads to an overestimation of areas at risk. Combining such models with information on temperature requirements for the virus derived from the EIP can reduce uncertainty [13]. Here, we give a short overview of the few experimental studies that are explicitly addressing the temperature dependence of the EIP of dengue. We analyze the implications of these studies and discuss current uncertainties in modeling dengue risk in face of climate change. We identify methodological challenges and formulate suggestions for the design of future studies from a spatio-ecological point of view.