A System Dynamic Transmission Model (SYStrans) to Simulate Epidemic Dengue Environment

Dengue is the most significant arthropod-borne virus in terms of human morbidity and mortality. Geographic expansion of dengue and intensity of outbreak has amplified significantly during the last few decades. Thus, the understanding of the dynamic of the large outbreaks has become indispensable for planning of control interventions in future epidemics. In this regard, local entomological, meteorological and epidemiological parameters based dengue models can be an essential tool for better interpretation of dengue-climate relationship at a regional scale. Process based modelling is resourceful in combining the vector and host dynamic along with the response to the meteorological factors for dengue transmission. In previous studies, process based models have not dealt with the integrated impact of vector-host dynamic and dengue transmission epidemiology by incorporating weather dependent transmission mechanism. In this study, a process-based model has been developed and validated for Iquitos of Peru, based on both vector and host population dynamic as well as the whole infection transmission mechanism. The sole objective was to develop a simple model to represent the actual scenario triggering dengue epidemic considering the most important features of vector population dynamics, transmission mechanism and environmental linkages. The model has used remote sensing or satellite based environmental data and also introduced dew point temperature as a new and effective weather parameter to depict the transmission process of dengue. The model has been capable of simulating the peak and moderate scenario in temporal scale, with considerable quantification of the actual number of cases for the 2004 and 2008 epidemics. Eventually, this type of model can be modified to use for different regions to predict the peak scenario based on local weather parameters effecting the infection transmission and vector development process along with population density

Aedes-Chikungunya virus interaction : key role of vector midguts microbiota and its saliva in the host infection

Aedes mosquitoes are important vectors for emerging diseases caused by arboviruses, such as chikungunya (CHIKV). These viruses’ main transmitting species are Aedes aegypti and Ae. albopictus, which are present in tropical and temperate climatic areas all over the globe. Knowledge of vector characteristics is fundamentally important to the understanding of virus transmission. Only female mosquitoes are able to transmit CHIKV to the vertebrate host since they are hematophagous. In addition, mosquito microbiota is fundamentally important to virus infection in the mosquito. Microorganisms are able to modulate viral transmission in the mosquito, such as bacteria of the Wolbachia genus, which are capable of preventing viral infection, or protozoans of the Ascogregarina species, which are capable of facilitating virus transmission between mosquitoes and larvae. The competence of the mosquito is also important in the transmission of the virus to the vertebrate host, since their saliva has several substances with biological effects, such as immunomodulators and anticoagulants, which are able to modulate the host’s response to the virus, interfering in its pathogenicity and virulence. Understanding the Aedes vector-chikungunya interaction is fundamentally important since it can enable the search for new methods of combating the virus’ transmission

Mutagenesis of the dengue virus envelope glycoprotein gene can significantly alter virus infectivity phenotypes in cultured cells and live mosquitoes

2011 Spring.Includes bibliographical references.The dengue virus (DENV) envelope (E) glycoprotein is the primary determinant for initiation of host cell infection. To date, studies investigating the contribution of DENV genetics to mosquito infection are limited. A infectious clone cDNA of DENV type 2 strain 16681 (30P-NBX) provided the ability to introduce site-specific amino acid (AA) mutations into the E protein. The results of the studies herein analyze the effects that AA mutations in the E protein have on infectivity of cultured cells and live mosquitoes. The ability of 30P-NBX to infect Aedes aegypti RexD strain mosquitoes after oral infectious blood-meal was investigated and showed that both 30P-NBX and the parent virus 16681 have low, but equivalent midgut infection rates (MIRs). Mosquito midgut infection with 30P-NBX is not affected by the virus titer in the blood-meal as long as titers are above 6 log 10 pfu/ml or 7 log 10 TCID 50 /ml. Additionally, multiple experimental repetitions with at least 20 mosquitoes per infectious blood-feed were required to obtain an accurate average MIR for 30P-NBX. Serial passage of 30P-NBX in RexD mosquito midguts identified a single AA mutation at position 122 in domain II of the E protein from lysine to glutamic acid that correlated with increased MIRs. Introduction of this AA mutation into the infectious clone (mutant virus K122E) reproduced the results from the serial passage experiment. Compared to 30P-NBX, K122E was not only shown to infect a higher proportion of mosquitoes as early as day 2 post blood-feed, but also to produce a disseminated infection in a higher proportion of mosquitoes by day 6 post blood-feed. Also, K122E consistently produced a midgut infection that spread throughout the entire tissue while 30P-NBX stayed restricted by comparison. Virus attachment to midgut cells was compared and showed that 30P-NBX and K122E could attach with equal efficiencies via our midgut-virus attachment assay. Additionally, incorporation of a single AA mutation into the infectious clone at E protein AA 120 from arginine to threonine significantly enhanced mosquito midgut infection compared to 30P-NBX. This is the first time that mosquito infection determinants have been identified in the DENV E protein. Amino acid mutations were engineered into the E protein on the lateral ridge of domain III, the fusion peptide at the distal end of domain II, and the molecular hinge region between domains I and II. Mutant virus phenotypes were analyzed in cell culture and live mosquitoes. In contrast to previous suggestions, domain III mutant virus phenotypes showed that the FG loop structure (previously suggested as a mosquito-specific infection determinant) and not the specific AA sequence is important for infection of mammalian cells and live mosquitoes, while the structure and sequence of the FG loop is dispensable for infection of cultured C6/36 cells. Additionally, mutations that remove positively charged residues from the A strand in DIII significantly attenuate infection of mosquitoes after oral infectious blood-meal and completely abrogate infection in mammalian cells. The results of this study suggest that there may be multiple structures in the E protein that are contributing to virus-receptor interactions. Viruses with mutations in the fusion peptide and hinge region of the E protein were intrathoracically (IT) inoculated into mosquitoes and showed variable infectivity phenotypes. All of the mutants except for one virus from both the fusion peptide and hinge region viruses attenuated infection of mosquito tissues outside the midgut. Importantly, considering that almost all of these viruses were able to replicate as efficiently as wild type in C6/36 cells, the IT inoculation results provide evidence that C6/36 cells are not a complete surrogate for DENV replication in mosquitoes

Transmission of Major Arboviruses in Brazil: The Role of Aedes aegypti and Aedes albopictus Vectors

Arthropod‐borne viruses (arboviruses) are transmitted to a mammalian host by an infected arthropod vector. More than 130 types of arboviruses are known to cause disease in susceptible vertebrate hosts and are responsible for some of the most explosive epidemics of emerging infectious diseases in recent decades. The transmission cycle requires three essential components: virus, vector and vertebrate. Understanding the role of the vector in the arboviruses transmission is critical to improve emerging arbovirus disease control strategies. Since 2015, Brazil is faced with the challenge of three co-circulating arboviruses of major public health importance. Dengue virus (DENV) infection has been a public health for 30 years, which has suffered several epidemics caused by all four serotypes. The emergence of Chikungunya virus (CHIKV) and Zika virus (ZIKV) in Brazil poses new challenges to clinicians and public health authorities. In urban and suburban areas, those arboviruses are transmitted between people by Aedes mosquitoes in the subgenus Stegomyia, especially Ae. aegypti (the main vector) and potentially Ae. albopictus. Factors relating to the environment and the vector‐virus interactions can influence the dynamics of arboviruses transmission. This chapter describes the main biology aspects of the Ae. aegypti and Ae. albopictus that can influence the success of the transmission of main arboviruses in Brazil and provide information to understand the role of those factors in this dynamic relation

Linking Nutrient Stoichiometry to Zika Virus Transmission in a Mosquito

Food quality and quantity serve as the basis for cycling of key chemical elements in trophic interactions; yet the role of nutrient stoichiometry in shaping host–pathogen interactions is under appreciated. Most of the emergent mosquito-borne viruses affecting human health are transmitted by mosquitoes that inhabit container systems during their immature stages, where allochthonous input of detritus serves as the basal nutrients. Quantity and type of detritus (animal and plant) were manipulated in microcosms containing newly hatched Aedes aegypti mosquito larvae. Adult mosquitoes derived from these microcosms were allowed to ingest Zika virus-infected blood and then tested for disseminated infection, transmission, and total nutrients (percent carbon, percent nitrogen, ratio of carbon to nitrogen). Treatments lacking high-quality animal (insect) detritus significantly delayed development. Survivorship to adulthood was closely associated with the amount of insect detritus present. Insect detritus was positively correlated with percent nitrogen, which affected Zika virus infection. Disseminated infection and transmission decreased with increasing insect detritus and percent nitrogen. We provide the first definitive evidence linking nutrient stoichiometry to arbovirus infection and transmission in a mosquito using a model system of invasive Ae. aegypti and emergent Zika virus

The Effects of Infection on Mosquito Rhythmic Behavior

Most organisms live in a rhythmic world, where daily environmental variation has a profound effect on their behavior and physiology. In addition to abiotic influence, interactions with other organisms that have their own particular cycles are also part of circadian rhythm formation. In this chapter, we present aspects of the biology of mosquito vectors, more precisely Aedes aegypti, which is a vector of arboviruses of great epidemiological importance, like dengue, Zika, and chikungunya. The successful transmission of the virus depends on the coordination of several behavioral and physiological traits involved in the virus-vector-host interaction. Thus, understanding the mechanisms of endogenous control of rhythmic traits of the mosquito vector and the impact that both environmental variation and virus infection can have on this regulation is key for a reliable estimate of the vectorial capacity. We discuss the infection-driven changes in traits used to calculate parameters of the vectorial capacity, and finally, we review the current knowledge on the molecular mechanisms underlying vector rhythmic behavior and the potential cellular targets of arbovirus infection

Indoor-Breeding of Aedes albopictus in Northern Peninsular Malaysia and Its Potential Epidemiological Implications

Background: The mosquito Ae. albopictus is usually adapted to the peri-domestic environment and typically breeds outdoors. However, we observed its larvae in most containers within homes in northern peninsular Malaysia. To anticipate the epidemiological implications of this indoor-breeding, we assessed some fitness traits affecting vectorial capacity during colonization process. Specifically, we examined whether Ae. albopictus exhibits increased survival, gonotrophic activity and fecundity due to the potential increase in blood feeding opportunities. Methodology/Principal Findings: In a series of experiments involving outdoors and indoors breeding populations, we found that Ae. albopictus lives longer in the indoor environment. We also observed increased nighttime biting activity and lifetime fecundity in indoor/domestic adapted females, although they were similar to recently colonized females in body size. Conclusion/Significance: Taken together these data suggest that accommodation of Ae. albopictus to indoor/domestic environment may increase its lifespan, blood feeding success, nuisance and thus vectorial capacity (both in terms of increased vector-host contacts and vector population density). These changes in the breeding behavior of Ae. albopictus,