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Aims: West Nile Virus (WNV) has remained a persistent source of vector‐borne disease risk in California since first being identified in the state in 2003. The geographic distribution of WNV activity is relatively widespread, but varies considerably across different regions within the state. Spatial variation in human WNV infection depends upon social‐ecological factors that influence mosquito populations and virus transmission dynamics. Measuring changes in spatial patterns over time is necessary for uncovering the underlying regional drivers of disease risk. Methods and Results: In this study, we utilized statewide surveillance data to quantify temporal changes and spatial patterns of WNV activity in California. We obtained annual WNV mosquito surveillance data from 2004 through 2021 from the California Arbovirus Surveillance Program. Geographic coordinates for mosquito pools were analysed using a suite of spatial statistics to identify and classify patterns in WNV activity over time. Conclusions: We detected clear patterns of non‐random WNV risk during the study period, including emerging hot spots in the Central Valley and non‐random periods of oscillating WNV risk in Southern and Northern California subregions. Our findings offer new insights into 18 years of spatio‐temporal variation in WNV activity across California, which may be used for targeted surveillance efforts and public health interventions. [ABSTRACT FROM AUTHOR]

The environments in which we live affect individual and community risk for disease transmission and illness severity. Communities’ and neighborhoods’ waste stream management designs and health care organizations’ spatial and structural architecture also influence individuals’ and communities’ pathogenic vulnerabilities and how well health sector industrial hygiene practices support them. This article describes a One Health approach to planetary environmental health and suggests strategies for implementing a One Health or Planetary Health approach in the context of climate change. [ABSTRACT FROM AUTHOR]

Temperature is a well-known effector of several transmission factors of mosquito-borne viruses, including within mosquito dynamics. These dynamics are often characterized by vector competence and the extrinsic incubation period (EIP). Vector competence is the intrinsic ability of a mosquito population to become infected with and transmit a virus, while EIP is the time it takes for the virus to reach the salivary glands and be expectorated following an infectious bloodmeal. Temperatures outside the optimal range act on life traits, decreasing transmission potential, while increasing temperature within the optimal range correlates to increasing vector competence and a decreased EIP. These relatively well-studied effects of other Aedes borne viruses (dengue and Zika) are used to make predictions about transmission efficiency, including the challenges presented by urban heat islands and climate change. However, the knowledge of temperature and chikungunya (CHIKV) dynamics within its two primary vectors—Ae. aegypti and Ae. albopictus—remains less characterized, even though CHIKV remains a virus of public-health importance. Here, we review the literature and summarize the state of the literature on CHIKV and temperature dependence of vector competence and EIP and use these data to demonstrate how the remaining knowledge gap might confound the ability to adequately predict and, thus, prepare for future outbreaks. [ABSTRACT FROM AUTHOR]

Weather variables has been described as major drivers of vector proliferation and arbovirus transmission. Among them, temperature has consistently been found to be impactful in transmission dynamics, and models that incorporate temperature have been widely used to evaluate and forecast transmission or arboviruses like dengue, zika, or chikungunya virus. Further, there is growing evidence of the importance of micro-environmental temperatures in driving transmission of Aedes aegypti-borne viruses, as these mosquitoes tend to live within domiciles. Yet there is still a considerable gap in our understanding of how accounting for micro-environmental temperatures in models varies from the use of other widely-used, macro-level temperature measures. This effort combines field-collected data of both indoor and outdoor household associated temperatures and weather station temperature data from three Colombian cities to describe the relationship between the measures representing temperature at the micro- and macro-levels. These data indicate that weather station data may not accurately capture the temperature profiles of indoor micro-environments. However, using these data sources, the basic reproductive number for arboviruses was calculated by means of three modeling efforts to investigate whether temperature measure differences translated to differential transmission predictions. Across all three cities, it was determined that the modeling method was more often impactful rather than the temperature data-source, though no consistent pattern was immediately clear. This suggests that temperature data sources and modeling methods are important for precision in arbovirus transmission predictions, and more studies are needed to parse out this complex interaction. [ABSTRACT FROM AUTHOR]

Rwanda is located in the Central East African region where several viral pathogens with global importance were originally described, including human immunodeficiency virus (HIV), Ebola, Zika, Rift Valley Fever (RVF), dengue and a long list of other neglected tropical viral pathogens. Due to many factors, this region has the potential to become a global hotspot for viral emergence. In Rwanda, viral diseases are underreported and the question is whether this is due to the absence of these viruses or a lack of investigation. Like many developing countries, capabilities in Rwanda need improvement despite research efforts throughout the years. This review describes the status of human and animal virus research in Rwanda and identifies relevant research and operational gaps. A comprehensive search was conducted in PubMed for virus research in Rwanda: 233 primary studies on viruses/viral diseases are indexed with connection to Rwanda. From 1958 to 2020, yearly publications generally increased and HIV/acquired immunodeficiency syndrome is the most studied virus. Compared with human viruses, few studies focus on animal and/or zoonotic viruses. The occurrence of the current severe acute respiratory syndrome coronavirus 2 pandemic shows strengthening warning and surveillance systems is critical to efficient preparedness and response. We recommend investment in human capacity, laboratory facilities and research to inform policy for viral surveillance in Rwanda. [ABSTRACT FROM AUTHOR]

In models of mosquito–borne transmission, the mosquito biting rate is an influential parameter, and understanding the heterogeneity of the process of biting is important, as biting is usually assumed to be relatively homogeneous across individuals, with time–between–bites described by an exponentially distributed process. However, these assumptions have not been addressed through laboratory experimentation. We experimentally investigated the daily biting habits of Ae. aegypti at three temperatures (24°C, 28°C, and 32°C) and determined that there was individual heterogeneity in biting habits (number of bites, timing of bites, etc.). We further explored the consequences of biting heterogeneity using an individual–based model designed to examine whether a particular biting profile determines whether a mosquito is more or less likely to 1) become exposed given a single index case of dengue (DENV) and 2) transmit to a susceptible human individual. Our experimental results indicate that there is heterogeneity among individuals and among temperature treatments. We further show that this results in altered probabilities of transmission of DENV to and from individual mosquitoes based on biting profiles. While current model representation of biting may work under some conditions, it might not uniformly be the best fit for this process. Our data also confirm that biting is a non–monotonic process with temperatures around 28°C being optimum. Author summary: Mosquito biting is a necessary and critical part of arbovirus transmission. The mosquito must bite once to acquire a virus and again to transmit, and these two bites must be separated by sufficient time for the virus to reach the salivary glands of the mosquito. Thus, both the number and timing of bites is important. We experimentally investigated how these bite characteristics might be different among individuals and further explored how temperature affected the overall heterogeneity of biting in Aedes aegypti mosquitoes, which carry many arboviruses like dengue virus (DENV). We found that the biting profiles–including number and timing thereof–did vary within temperature groups among individuals and compared outcomes associated with each individual in an individual–based model of household DENV transmission. Our results further confirmed that temperatures around 28°C are optimal for mosquito biting (and transmission), that correlations between biting characteristics and transmission were not uniform across temperature, which represents another layer of heterogeneity, and that–at least at 28°C–the null assumption of an exponential or an exponential–like (geometric) distribution of biting in mathematical models of transmission is not the best and offer an alternative. [ABSTRACT FROM AUTHOR]

Rickettsia felis is an emerging etiological agent of rickettsioses worldwide. The cosmopolitan cat flea (Ctenocephalides felis) is the primary vector of R. felis, but R. felis has also been reported in other species of hematophagous arthropods including ticks and mosquitoes. Canines can serve as a bacteremic host to infect fleas under laboratory conditions, yet isolation of R. felis from the blood of a vertebrate host in nature has not been realized. Cofeeding transmission is an efficient mechanism for transmitting rickettsiae between infected and uninfected fleas; however, the mechanism of transmission among different orders and classes of arthropods is not known. The potential for R. felis transmission between infected fleas and tick (Dermacentor variabilis) and mosquito (Anopheles quadrimaculatus) hosts was examined via cofeeding bioassays. Donor cat fleas infected with R. felis transmitted the agent to naïve D. variabilis nymphs via cofeeding on a rat host. Subsequent transstadial transmission of R. felis from the engorged nymphs to the adult ticks was observed with reduced prevalence in adult ticks. Using an artificial host system, An. quadrimaculatus exposed to a R. felis-infected blood meal acquired rickettsiae and maintained infection over 12 days post-exposure (dpe). Similar to ticks, mosquitoes were able to acquire R. felis while cofeeding with infected cat fleas on rats infection persisting in the mosquito for up to 3 dpe. The results indicate R. felis-infected cat fleas can transmit rickettsiae to both ticks and mosquitoes via cofeeding on a vertebrate host, thus providing a potential avenue for the diversity of R. felis-infected arthropods in nature. Author summary: Primarily associated with the common cat flea, Rickettsia felis is an intracellular bacterial pathogen that can be transmitted from the flea to vertebrate hosts. This flea-borne infection has now been identified worldwide as a human pathogen. In addition to fleas, other blood feeding arthropods including ticks and mosquitoes are being recognized as possible vectors of R. felis. Although the mammalian infectious source for arthropods is still unknown, cofeeding transmission of Rickettsia is known to occur between vectors of the same species. However, potential for flea transmission of R. felis to other orders and classes of arthropods is unknown. Here, we examined the potential for fleas to transmit R. felis to American dog ticks and mosquitoes during feeding events on rat hosts. Our data suggested that ticks and mosquitoes can be infected when simultaneously feeding on a host with R. felis-infected cat fleas. [ABSTRACT FROM AUTHOR]

Background: In March 2020, an influx of admissions in COVID-19 positive patients threatened to overwhelm healthcare facilities in East Baton Rouge Parish, Louisiana. Exacerbating this problem was an overall shortage of diagnostic testing capability at that time, resulting in a delay in time-to-result return. An improvement in diagnostic testing availability and timeliness was necessary to improve the allocation of resources and ultimate throughput of patients. The management of a COVID-19 positive patient or patient under investigation requires infection control measures that can quickly consume personal protective equipment (PPE) stores and personnel available to treat these patients. Critical shortages of both PPE and personnel also negatively impact care in patients admitted with non-COVID-19 illnesses. Methods: A multisectoral partnership of healthcare providers, facilities and academicians created a molecular diagnostic lab within an academic research facility dedicated to testing inpatients and healthcare personnel for SARS-CoV-2. The purpose of the laboratory was to provide a temporary solution to the East Baton Rouge Parish healthcare community until individual facilities were self-sustaining in testing capabilities. We describe the partnership and the impacts of this endeavor by developing a model derived from a combination of data sources, including electronic health records, hospital operations, and state and local resources. Findings: Our model demonstrates two important principles: the impact of reduced turnaround times (TAT) on potential differences in inpatient population numbers for COVID-19 and savings in PPE attributed to the more rapid TAT. [ABSTRACT FROM AUTHOR]

Abstract Background West Nile virus (WNV) is an arbovirus of public health importance in the genus Flavivirus, a group of positive sense RNA viruses. The NS3 gene has a high level of substitutions and is phylogenetically informative. Likewise, substitutions in the envelope region have been postulated to enable viruses to subvert immune responses. Analysis of these genes among isolates from positive mosquitoes collected in Louisiana illustrates the variation present in the regions and provides improved insight to a phylogenetic model. Employing a GIS eco-regionalization method, we hypothesized that WNV pool positivity was correlated with regional environmental characteristics. Further, we postulated that the phylogenetic delineations would be associated with variations in regional environmental conditions. Results Type of regional land cover was a significant effect (p < 0.0001) in the positive pool prediction, indicating that there is an ecological component driving WNV activity. Additionally, month of collection was significant (p < 0.0001); and thus there is a temporal component that contributes to the probability of getting a positive mosquito pool. All virus isolates are of the WNV 2002 lineage. There appears to be some diversity within both forested and wetland areas; and the possibility of a distinct clade in the wetland samples. Conclusions The phylogenetic analysis shows that there has been no reversion in Louisiana from the 2002 lineage which replaced the originally introduced strain. Our pool positivity model serves as a basis for future testing, and could direct mosquito control and surveillance efforts. Understanding how land cover and regional ecology effects mosquito pool positivity will greatly help focus mosquito abatement efforts. This would especially help in areas where abatement programs are limited due to either funding or man power. Moreover, understanding how regional environments drive phylogenetic variation will lead to a greater understanding of the interactions between ecology and disease prevalence.

Aedes aegypti and Aedes albopictus are both vectors of Zika virus and both are endemic to the New Orleans Metropolitan area. Fortunately, to date there has been no known autochthonous transmission of Zika virus in New Orleans. No studies of the vector competence of local populations of Ae. aegypti and Ae. albopictus for Zika virus transmission have been conducted. To determine if New Orleans Ae. aegypti and Ae. albopictus mosquitoes are competent for Zika virus, mosquitoes were reared to generation F3 from eggs collected in New Orleans during the 2018 mosquito season. Adults were fed an infectious blood meal and kept for 15 days in an environmental chamber. Transmission assays were conducted at 4, 10, and 15 days post exposure and RT-PCR was run on bodies and saliva to detect the presence of Zika virus RNA. We observed remarkably low susceptibility of both Ae. aegypti and Ae. albopictus from New Orleans to a Zika strain from Panama after oral challenge. These results suggest a limited risk of Zika virus transmission should it be introduced to the New Orleans area, and may partially explain why no transmission was detected in Louisiana during the 2016 epidemic in the Americas, despite multiple known travel associated introductions to New Orleans. Despite these results these mosquito populations are known to be competent vectors for some other mosquito-borne viruses and control measures should not be relaxed. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is transmitted by infectious mosquitoes during blood-feeding via saliva containing biologically-active proteins. Here, we examined the effect of varying DENV infection modality in rhesus macaques in order to improve the DENV nonhuman primate (NHP) challenge model. NHPs were exposed to DENV-1 via subcutaneous or intradermal inoculation of virus only, intradermal inoculation of virus and salivary gland extract, or infectious mosquito feeding. The infectious mosquito feeding group exhibited delayed onset of viremia, greater viral loads, and altered clinical and immune responses compared to other groups. After 15 months, NHPs in the subcutaneous and infectious mosquito feeding groups were re-exposed to either DENV-1 or DENV-2. Viral replication and neutralizing antibody following homologous challenge were suggestive of sterilizing immunity, whereas heterologous challenge resulted in productive, yet reduced, DENV-2 replication and boosted neutralizing antibody. These results show that a more transmission-relevant exposure modality resulted in viral replication closer to that observed in humans. Author summary: Dengue virus is transmitted into the skin of humans by mosquitoes as they take a blood meal. In contrast, many animal models are infected in the laboratory using a syringe to inject below the skin. Here, we looked at how different routes and methods of infection altered dengue infection in rhesus macaques. We found that infection via mosquito feeding resulted in a number of changes compared to other routes and methods, including a delay in the time to detection of dengue virus and overall greater quantities of dengue virus in the blood, and changes in the amounts of various components of blood that have been associated with dengue disease in humans. After 15 months, we exposed the macaques again to either the same or a different type of dengue virus. We found that animals exposed to the same type of dengue virus were protected from infection, whereas those animals exposed to a different type were only partially protected. Overall, our results show that dengue virus delivery using the natural transmission vector, mosquitoes, results in infection that is closer to what is observed in humans and may influence the interpretation of future studies of candidate vaccines. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) emerged in Colombia in 2014 into a population presumed fully susceptible. This resulted in a quick and intense spread across Colombia, resulting in an epidemic that affected an estimated 450,000 people. The reported Colombian cases accounted for over 49% of all the cases reported to the PAHO. Eco-environmental factors are known to be associated with the spread of arboviruses such as CHIKV, and likely contribute to the differences in transmission profiles that were observed across several municipalities. To determine the association of eco-environmental factors and CHIKV, the basic reproduction number (R0) in 85 municipalities, which accounted for 65.6% of reported CHIKV cases in Colombia, was estimated. Estimates of R0 ranged from 1 to 9, where over 76% of municipalities had R0 values between 1 and 2. When we looked at the distribution of R0, the cumulative proportions were 20% with R0>2, 14% with R0>3, and 9% with R0>4. Next, we determined that there were different patterns of correlation between environmental and/or ecological variables and R0 when we considered different R0 lower-thresholds. Broadly, we found that temperature-related variables are significantly and positively correlated to R0 regardless of the lower threshold, while other variables like duration of outbreak and size of the urban area are inversely related to R0. Specifically, we conclude that high values of temperature-related variables where R0 > 1 will result in a fast growth of cases in a shorter time period (with faster cessation of outbreak transmission) but will result overall in a fewer total cases compared to outbreak areas (R0 > 1, but classified as lower). Thus, in the absence of vector control, a less explosive outbreak may be more advantageous for the virus in terms of transmission. Author summary: Chikungunya virus emerged in Colombia in 2014 into a presumed fully susceptible population and rapidly spread in the country. Numerous municipalities were differently affected by this virus across the country. The main purpose of this work was understanding why those differences were produced and, in turn, what are the variables addressing such differences. For this purpose, we estimated for 85 municipalities the basic reproduction number (R0), a crucial parameter to understand epidemics that is expressed as the number of secondary cases produced by a primary case. Such parameter was correlated with numerous variables resulting evident a crucial role of temperature in the increase of R0. Interestingly, other variables like size of the urban area and cases showed to be negatively correlated with R0. Results shows that high temperatures produce high R0, but those municipalities that showed high R0 showed an explosive epidemic with faster increase of cases that ceased equally fast, so the duration of epidemic is short producing small amount of cases. In this way, more cases are expected with municipalities with lower values of R0, which is suitably explained by the tortoise-hare model, where the less explosive outbreak results to be more advantageous for the virus. [ABSTRACT FROM AUTHOR]

Because of the increasing threat that Zika virus (ZIKV) poses to more sub-tropical area due to increased global travel, there is a need for better understanding of the effect(s) of temperature on the establishment potential of ZIKV within these subtropical, temperate, and/or seasonal Ae. aegypti populations. The first step to determining risk establishment of ZIKV in these regions is to assess ZIKV's ability to infect mosquitoes at less tropical temperatures, and thus be detected through common surveillance programs. To that end, the effect of two rearing temperatures (RT) and extrinsic incubation temperatures (EIT) on infection and dissemination rates was evaluated, as well as the interactions of such. Total, there were four combinations (RT24-EIT24, RT24-EIT28, RT28-EIT24, RT28-EIT28). Further, a stochastic SEIR framework was adapted to determine whether observed data could lead to differential success of establishment of ZIKV in naive mosquito populations. There was no consistent pattern in significant differences found across treatments for either infection or dissemination rates (p>0.05), where only a significant difference was found in infection rates between RT24-EIT24 (44%) and RT28-EIT24 (82.6%). Across all temperature conditions, the model predicted between a 76.4% and 95.4% chance of successful establishment of ZIKV in naive mosquito populations under model assumptions. We further show that excluding the maximum observed infection and dissemination rates likely overestimates the probability of local establishment of ZIKV. These results indicate that 1) there is no straightforward relationship between RT, EIT, and infection/dissemination rates, 2) in more temperate climates, ZIKV may still have the ability to establish in populations of Aedes aegypti, 3) despite an overall lack of significant differences in infection/dissemination rates, temperature may still alter the kinetics of ZIKV within the mosquito enough to affect the likelihood of infection establishment and detection within the context of mosquito surveillance programs, and 4) both the temporal and magnitude qualities of vector competence are necessary for parameterization of within-mosquito virus kinetics. [ABSTRACT FROM AUTHOR]

Background: The appearance of severe Zika virus (ZIKV) disease in the most recent outbreak has prompted researchers to respond through the development of tools to quickly characterize transmission and pathology. We describe here another such tool, a mouse model of ZIKV infection and pathogenesis using the MR766 strain of virus that adds to the growing body of knowledge regarding ZIKV kinetics in small animal models. Methods: We infected mice with the MR766 strain of ZIKV to determine infection kinetics via serum viremia. We further evaluated infection-induced lesions via histopathology and visualized viral antigen via immunohistochemical labeling. We also investigated the antibody response of recovered animals to both the MR766 and a strain from the current outbreak (PRVABC59). Results: We demonstrate that the IRF3/7 DKO mouse is a susceptible, mostly non-lethal model well suited for the study of infection kinetics, pathological progression, and antibody response. Infected mice presented lesions in tissues that have been associated with ZIKV infection in the human population, such as the eyes, male gonads, and central nervous system. In addition, we demonstrate that infection with the MR766 strain produces cross-neutralizing antibodies to the PRVABC59 strain of the Asian lineage. Conclusions: This model provides an additional tool for future studies into the transmission routes of ZIKV, as well as for the development of antivirals and other therapeutics, and should be included in the growing list of available tools for investigations of ZIKV infection and pathogenesis. [ABSTRACT FROM AUTHOR]

Expansion of mosquito-borne pathogens into more temperate regions of the world necessitates tools such as mathematical models for understanding the factors that contribute to the introduction and emergence of a disease in populations naïve to the disease. Often, these models are not developed and analyzed until after a pathogen is detected in a population. In this study, we develop a spatially explicit stochastic model parameterized with publicly available U.S. Census data for studying the potential for disease spread in Urbanized Areas of the United States. To illustrate the utility of the model, we specifically study the potential for introductions of dengue to lead to autochthonous transmission and outbreaks in a population representative of the Miami Urbanized Area, where introductions of dengue have occurred frequently in recent years. We describe seasonal fluctuations in mosquito populations by fitting a population model to trap data provided by the Miami-Dade Mosquito Control Division. We show that the timing and location of introduced cases could play an important role in determining both the probability that local transmission occurs as well as the total number of cases throughout the entire region following introduction. We show that at low rates of clinical presentation, small outbreaks of dengue could go completely undetected during a season, which may confound mitigation efforts that rely upon detection. We discuss the sensitivity of the model to several critical parameter values that are currently poorly characterized and motivate the collection of additional data to strengthen the predictive power of this and similar models. Finally, we emphasize the utility of the general structure of this model in studying mosquito-borne diseases such as chikungunya and Zika virus in other regions. [ABSTRACT FROM AUTHOR]

Chikungunya virus is an arbovirus spread predominantly by Aedes aegypti and Ae. albopictus mosquitoes, and causes debilitating arthralgia and arthritis. While these are common manifestations during acute infection and it has been suggested they can recur in patients chronically, gaps in knowledge regarding the pathogenesis still exist. Two established mouse models were utilized (adult IRF 3/7 -/- -/- and wild-type C57BL/6J mice) to evaluate disease manifestations in bones and joints at various timepoints. Novel lesions in C57BL/6J mice consisted of periostitis (91%) and foci of cartilage of necrosis (50% of mice at 21 DPI). Additionally, at 21 DPI, 50% and 75% of mice exhibited periosteal bone proliferation affecting the metatarsal bones, apparent via histology and μCT, respectively. μCT analysis did not reveal any alterations in trabecular bone volume measurements in C57BL/6J mice. Novel lesions demonstrated in IRF 3/7 -/- -/- mice at 5 DPI included focal regions of cartilage necrosis (20%), periosteal necrosis (66%), and multifocal ischemic bone marrow necrosis (100%). Contralateral feet in 100% of mice of both strains had similar, though milder lesions. Additionally, comparison of control IRF 3/7 -/- -/- and wild-type C57BL/6J mice demonstrated differences in cortical bone. These experiments demonstrate novel manifestations of disease similar to those occurring in humans, adding insight into disease pathogenesis, and representing new potential targets for therapeutic interventions. Additionally, results demonstrate the utility of μCT in studies of bone and joint pathology and illustrate differences in bone dynamics between mouse strains. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is thought to have emerged from a sylvatic cycle in Africa but has since become adapted to an urban-centric transmission cycle. These urban areas include villages in West Africa where DENV is not often routinely considered for patients presenting with febrile illnesses, as other endemic diseases (malaria, Lassa fever, e.g.) present with similar non-specific symptoms. Thus, dengue is likely under diagnosed in the region. These plaque reduction neutralization test-50 (PRNT50) screening results of patients presenting with fevers of unknown origin (FUO) at a clinic in Kenema, Sierra Leone indicate that all four serotypes of DENV likely circulate in areas surrounding Kenema. Using a more conservative PRNT80 cut-off value, our results still indicate the presence of antibody to all four serotypes in the region. Identifying alternate etiologies of FUOs in this region will assist clinicians in plan-of-care decisions as well as follow-up priorities. This is particularly relevant given the Ebola outbreak in the region, where diagnosis has a range of downstream effects ranging from correct allocation of medical resources, appropriate isolation of patients, and ultimately, a better informed public health sector. [ABSTRACT FROM AUTHOR]

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Cat fleas ( Ctenocephalides felis) are known as the primary vector and reservoir of Rickettsia felis, the causative agent of flea-borne spotted fever; however, field surveys regularly report molecular detection of this infectious agent from other blood-feeding arthropods. The presence of R. felis in additional arthropods may be the result of chance consumption of an infectious bloodmeal, but isolation of viable rickettsiae circulating in the blood of suspected vertebrate reservoirs has not been demonstrated. Successful transmission of pathogens between actively blood-feeding arthropods in the absence of a disseminated vertebrate infection has been verified, referred to as cofeeding transmission. Therefore, the principal route from systemically infected vertebrates to uninfected arthropods may not be applicable to the R. felis transmission cycle. Here, we show both intra- and interspecific transmission of R. felis between cofeeding arthropods on a vertebrate host. Analyses revealed that infected cat fleas transmitted R. felis to naïve cat fleas and rat fleas ( Xenopsylla cheopis) via fleabite on a nonrickettsemic vertebrate host. Also, cat fleas infected by cofeeding were infectious to newly emerged uninfected cat fleas in an artificial system. Furthermore, we utilized a stochastic model to demonstrate that cofeeding is sufficient to explain the enzootic spread of R. felis amongst populations of the biological vector. Our results implicate cat fleas in the spread of R. felis amongst different vectors, and the demonstration of cofeeding transmission of R. felis through a vertebrate host represents a novel transmission paradigm for insect-borne Rickettsia and furthers our understanding of this emerging rickettsiosis. [ABSTRACT FROM AUTHOR]

Given the recent emergence of chikungunya in the Americas, the accuracy of forecasting and prediction of chikungunya transmission potential in the U.S. requires urgent assessment. The La Reunion-associated sub-lineage of chikungunya (with a valine substitution in the envelope protein) was shown to increase viral fitness in the secondary vector, Ae. albopictus. Subsequently, a majority of experimental and modeling efforts focused on this combination of a sub-lineage of the East-Central-South African genotype (ECSA-V) – Ae. albopictus, despite the Asian genotype being the etiologic agent of recent chikungunya outbreaks world-wide. We explore a collection of data to investigate relative transmission efficiencies of the three major genotypes/sub-lineages of chikungunya and found difference in the extrinsic incubation periods to be largely overstated. However, there is strong evidence supporting the role of Ae. albopictus in the expansion of chikungunya that our R0 calculations cannot attribute to fitness increases in one vector over another. This suggests other ecological factors associated with the Ae. albopictus-ECSA-V cycle may drive transmission intensity differences. With the apparent bias in literature, however, we are less prepared to evaluate transmission where Ae. aegypti plays a significant role. Holistic investigations of CHIKV transmission cycle(s) will allow for more complete assessment of transmission risk in areas affected by either or both competent vectors. [ABSTRACT FROM AUTHOR]

Background Vector-borne disease transmission is dependent on the many nuances of the contact event between infectious and susceptible hosts. Virus acquisition from a viremic human to a susceptible mosquito is often assumed to be nearly perfect and almost always uniform across the infectious period. Dengue transmission models that have previously addressed variability in human to vector transmission dynamics do not account for the variation in infectiousness of a single individual, and subsequent infection of naïve mosquitoes. Understanding the contribution of this variability in human infectiousness is especially important in the context of introduction events where an infected individual carries the virus into a population of competent vectors. Furthermore, it could affect the ability to detect an epidemic (and the timing of detection) following introduction. Methods We constructed a stochastic, compartmental model to describe the heterogeneity of human viremia and calculate the probability of a successful introduction, taking into account the viremia level (and thus acquisition potential) of the index case on, and after, the day of introduction into a susceptible population and varying contact rates between the human and mosquito populations. We then compared the results of this model with those generated by a simpler model that has the same average infectiousness but only a single infectious class. Results We found that the infectivity of the index case as well as the contact rate affected the probability of emergence, but that contact rate had the most significant effect. We also found that the interaction between contact rate and the infectiousness of the index case affected the time to detection relative to the peak of the epidemic curve. Additionally, when compared to our model that accounts for variable infectiousness, a model with a single infectious class underestimates the probability of emergence and transmission intensity. Conclusion Understanding the interplay between individual human heterogeneity of infectiousness and the rate of contact with the vector population will be important when predicting the likelihood, detection, and magnitude of an outbreak. [ABSTRACT FROM AUTHOR]

Recent efforts to combat the growing global threat of dengue disease, including deployment of phase IIb vaccine trials, has continued to be hindered by uncertainty surrounding equitable immune responses of serotypes, relative viral fitness of vaccine vs naturally occurring strains, and the importance of altered immune environments due to natural delivery routes. Human infection models can significantly improve our understanding of the importance of certain phenotypic characteristics of viral strains, and inform strain selection and trial design. With human models, we can further assess the importance of the natural delivery route of DENV and/or the accompanying mosquito salivary milieu. Accordingly, we discuss the use of mosquitoes in such a human infection model with DENV, identify important considerations, and make preliminary recommendations for deployment of such a mosquito improved DENV human infection model (miDHIM). [ABSTRACT FROM AUTHOR]

Background Dengue virus (DENV) is responsible for up to approximately 300 million infections and an increasing number of deaths related to severe manifestations each year in affected countries throughout the tropics. It is critical to understand the drivers of this emergence, including the role of vector-virus interactions. When a DENV-infected Aedes aegypti mosquito bites a vertebrate, the virus is deposited along with a complex mixture of salivary proteins. However, the influence of a DENV infection upon the expectorated salivary proteome of its vector has yet to be determined. Methods Therefore, we conducted a proteomic analysis using 2-D gel electrophoresis coupled with mass spectrometry based protein identification comparing the naturally expectorated saliva of Aedes aegypti infected with DENV-2 relative to that of uninfected Aedes aegypti. Results Several proteins we found differentially expressed in the saliva of DENV-2 infected mosquitoes, in particular proteins with anti-hemostatic and pain inhibitory functions were significantly reduced. Hypothetical consequences of these particular protein reductions include increased biting rates and transmission success, and lead to alteration of transmission potential as calculated in our vectorial capacity model. Conclusions We present our characterizations of these changes with regards to viral transmission and mosquito blood-feeding success. Further, we conclude that our proteomic analysis of Aedes aegypti saliva altered by DENV infection provides a unique opportunity to identify pro-viral impacts key to virus transmission. [ABSTRACT FROM AUTHOR]

The article examines the infectivity and transmission dynamics of Koutango virus in Aedes aegypti Mosquitoes.

Norte de Santander is a region in Colombia with a high incidence of dengue virus (DENV). In this study, we examined the serum concentration of anti-Aedes salivary gland extract (SGE) antibodies as a biomarker of DENV infection and transmission, and assessed the duration of anti-SGE antibody concentration after exposure to the vector ceased. We also determined whether SGE antibody concentration could differentiate between positive and negative DENV infected individuals and whether there are differences in exposure for each DENV serotype. We observed a significant decrease in the concentration of IgG antibodies at least 40 days after returning to an “Ae. aegypti-free” area. In addition, we found significantly higher anti-SGE IgG concentrations in DENV positive patients with some difference in exposure to mosquito bites among DENV serotypes. We conclude that the concentration of IgG antibodies against SGE is an accurate indicator of risk of dengue virus transmission and disease presence. [ABSTRACT FROM AUTHOR]

From November 2008-May 2009 Cairns Queensland Australia was struck by an explosive epidemic of DENV-3 that exceeded the capacity of highly skilled dengue control team to control it. We describe the environmental, virological and entomological factors associated with this outbreak to better understand the circumstances leading to its occurrence. Patient interviews, serological results and viral sequencing strongly suggest that the imported index case was infected in Kalimantan, Indonesia. A delay in notification of 27 days from importation of the index case until Queensland Health was notified of dengue transmission allowed the virus to amplify and spread unchecked through November 2008. Unseasonably warm weather, with daily mean temperatures exceeding 30°C, occurred in late November and would have shortened the extrinsic incubation period of the virus and enhanced transmission. Analysis of case movements early in the outbreak indicated that the total incubation period was as low as 9–11 days. This was supported by laboratory vector competence studies that found transmission by Aedes aegypti occurred within 5 days post exposure at 28°C. Effective vector competence rates calculated from these transmission studies indicate that early transmission contributed to the explosive dengue transmission observed in this outbreak. Collections from BG sentinel traps and double sticky ovitraps showed that large populations of the vector Ae. aegypti occurred in the transmission areas from November – December 2008. Finally, the seasonal movement of people around the Christmas holiday season enhanced the spread of DENV-3. These results suggest that a strain of DENV-3 with an unusually rapid transmission cycle was able to outpace vector control efforts, especially those reliant upon delayed action control such as lethal ovitraps. [ABSTRACT FROM AUTHOR]