Lee W. Cohnstaedt

A Network-Based Meta-Population Approach to Model Rift Valley Fever Epidemics

Rift Valley fever virus (RVFV) has been expanding its geographical distribution with important implications for both human and animal health. The emergence of Rift Valley fever (RVF) in the Middle East, and its continuing presence in many areas of Africa, has negatively impacted both medical and veterinary infrastructures and human morbidity, mortality, and economic endpoints. Furthermore, worldwide attention should be directed towards the broader infection dynamics of RVFV, because suitable host, vector and environmental conditions for additional epidemics likely exist on other continents; including Asia, Europe and the Americas. We propose a new compartmentalized model of RVF and the related ordinary differential equations to assess disease spread in both time and space; with the latter driven as a function of contact networks. Humans and livestock hosts and two species of vector mosquitoes are included in the model. The model is based on weighted contact networks, where nodes of the networks represent geographical regions and the weights represent the level of contact between regional pairings for each set of species. The inclusion of human, animal, and vector movements among regions is new to RVF modeling. The movement of the infected individuals is not only treated as a possibility, but also an actuality that can be incorporated into the model. We have tested, calibrated, and evaluated the model using data from the recent 2010 RVF outbreak in South Africa as a case study; mapping the epidemic spread within and among three South African provinces. An extensive set of simulation results shows the potential of the proposed approach for accurately modeling the RVF spreading process in additional regions of the world. The benefits of the proposed model are twofold: not only can the model differentiate the maximum number of infected individuals among different provinces, but also it can reproduce the different starting times of the outbreak in multiple locations. Finally, the exact value of the reproduction number is numerically computed and upper and lower bounds for the reproduction number are analytically derived in the case of homogeneous populations.

A hierarchical network approach for modeling Rift Valley fever epidemics with applications in North America

Rift Valley fever is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. In the event Rift Valley fever virus is introduced to the United States or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease vectors and hosts will be vital for developing mitigation strategies. Presented here is a general network-based mathematical model of Rift Valley fever. Given a lack of empirical data on disease vector species and their vector competence, this discrete time epidemic model uses stochastic parameters following several PERT distributions to model the dynamic interactions between hosts and likely North American mosquito vectors in dispersed geographic areas. Spatial effects and climate factors are also addressed in the model. The model is applied to a large directed asymmetric network of 3,621 nodes based on actual farms to examine a hypothetical introduction to some counties of Texas, an important ranching area in the United States of America. The nodes of the networks represent livestock farms, livestock markets, and feedlots, and the links represent cattle movements and mosquito diffusion between different nodes. Cattle and mosquito (Aedes and Culex) populations are treated with different contact networks to assess virus propagation. Rift Valley fever virus spread is assessed under various initial infection conditions (infected mosquito eggs, adults or cattle). A surprising trend is fewer initial infectious organisms result in a longer delay before a larger and more prolonged outbreak. The delay is likely caused by a lack of herd immunity while the infection expands geographically before becoming an epidemic involving many dispersed farms and animals almost simultaneously. Cattle movement between farms is a large driver of virus expansion, thus quarantines can be efficient mitigation strategy to prevent further geographic spread.

Biologically Informed Individual-Based Network Model for Rift Valley Fever in the US and Evaluation of Mitigation Strategies

Rift Valley fever (RVF) is a zoonotic disease endemic in sub-Saharan Africa with periodic outbreaks in human and animal populations. Mosquitoes are the primary disease vectors; however, Rift Valley fever virus (RVFV) can also spread by direct contact with infected tissues. The transmission cycle is complex, involving humans, livestock, and multiple species of mosquitoes. The epidemiology of RVFV in endemic areas is strongly affected by climatic conditions and environmental variables. In this research, we adapt and use a network-based modeling framework to simulate the transmission of RVFV among hypothetical cattle operations in Kansas, US. Our model considers geo-located livestock populations at the individual level while incorporating the role of mosquito populations and the environment at a coarse resolution. Extensive simulations show the flexibility of our modeling framework when applied to specific scenarios to quantitatively evaluate the efficacy of mosquito control and livestock movement regulations in reducing the extent and intensity of RVF outbreaks in the United States.

Susceptibility of a North American Culex quinquefasciatus to Japanese Encephalitis Virus

Japanese encephalitis virus (JEV) is a flavivirus that is transmitted by Culex (Cx.) tritaeniorhynchus in tropical and subtropical regions of Asia. The endemic transmission cycle involves domestic pigs and avian species that serve as amplification hosts; humans are incidental hosts that cannot develop a high-titer viremia sufficient for mosquito infection. Although vaccination can be an effective strategy for disease prevention and is used extensively in multiple Asian countries, unvaccinated immunologically naïve human populations can suffer from severe neurological sequelae. The potential introduction of JEV into North America would be a major threat to human and animal health. In this study, field-collected Cx. quinquefasciatus from Valdosta, Georgia, were tested for their susceptibility to JEV and their potential to develop a disseminated infection via per os infection. These results demonstrate that North American Cx. quinquefasciatus are susceptible to JEV infection and subsequent dissemination at 14 days post infection (d.p.i.). Detection of viral RNA in saliva from infected mosquitoes also indicates competent vectors for JEV can be found in North America.

Trapping of Rift Valley Fever (RVF) vectors using Light Emitting Diode (LED) CDC traps in two arboviral disease hot spots in Kenya

BackgroundMosquitoes’ response to artificial lights including color has been exploited in trap designs for improved sampling of mosquito vectors. Earlier studies suggest that mosquitoes are attracted to specific wavelengths of light and thus the need to refine techniques to increase mosquito captures following the development of super-bright light-emitting diodes (LEDs) which emit narrow wavelengths of light or very specific colors. Therefore, we investigated if LEDs can be effective substitutes for incandescent lamps used in CDC light traps for mosquito surveillance, and if so, determine the best color for attraction of important Rift Valley Fever (RFV) vectors.MethodsThe efficiency of selected colored LED CDC light traps (red, green, blue, violet, combination of blue-green-red (BGR)) to sample RVF vectors was evaluated relative to incandescent light (as control) in a CDC light trap in two RVF hotspots (Marigat and Ijara districts) in Kenya. In field experiments, traps were baited with dry ice and captures evaluated for Aedes tricholabis, Ae. mcintoshi, Ae. ochraceus, Mansonia uniformis, Mn. africana and Culex pipiens, following Latin square design with days as replicates. Daily mosquito counts per treatment were analyzed using a generalized linear model with Negative Binomial error structure and log link using R. The incidence rate ratios (IRR) that mosquito species chose other treatments instead of the control, were estimated.ResultsSeasonal preference of Ae.mcintoshi and Ae. ochraceus at Ijara was evident with a bias towards BGR and blue traps respectively in one trapping period but this pattern waned during another period at same site with significantly low numbers recorded in all colored traps except blue relative to the control. Overall results showed that higher captures of all species were recorded in control traps compared to the other LED traps (IRRu2009<u20091) although only significantly different from red and violet.ConclusionBased on our trapping design and color, none of the LEDs outcompeted the standard incandescent light. The data however provides preliminary evidence that a preference might exist for some of these mosquito species based on observed differential attraction to these light colors requiring future studies to compare reflected versus transmitted light and the incorporation of colored light of varying intensities.

An individual-level network model for a hypothetical outbreak of Japanese encephalitis in the USA

Japanese encephalitis (JE) is a vector-borne disease transmitted by mosquitoes and maintained in birds and pigs. To examine the possible epidemiology of JE in the United States, we use an individual-level network model that explicitly considers the feral pig population and implicitly considers mosquitoes and birds in specific areas of Florida, North Carolina, and South Carolina. To model the virus transmission among feral pigs within a small geographic area (<60xa0sqxa0mi areas), two network topologies are considered: Fully connected and Erdos–Renyi networks. Long-distance connections (interstate) are created with limited probability and based on fall and spring bird migration patterns. Patterns of simulated outbreaks support the use of the Erdos–Renyi network because maximum incidence occurs during the fall migration period which is similar to the peak incidence of the closely related West Nile virus, another virus in the Japanese encephalitis group (Flaviviridae) that is transmitted by both birds and mosquitoes. Simulation analysis suggested two important mitigation strategies: for low mosquito vectorial capacity, insecticidal spraying of infected areas reduces transmission and limits the outbreak to a single geographic area. Alternatively, in high mosquito vectorial capacity areas, birds rather than mosquitoes need to be removed/controlled.

Meta-analyses of the proportion of Japanese encephalitis virus infection in vectors and vertebrate hosts

BackgroundJapanese encephalitis (JE) is a zoonosis in Southeast Asia vectored by mosquitoes infected with the Japanese encephalitis virus (JEV). Japanese encephalitis is considered an emerging exotic infectious disease with potential for introduction in currently JEV-free countries. Pigs and ardeid birds are reservoir hosts and play a major role on the transmission dynamics of the disease. The objective of the study was to quantitatively summarize the proportion of JEV infection in vectors and vertebrate hosts from data pertaining to observational studies obtained in a systematic review of the literature on vector and host competence for JEV, using meta-analyses.MethodsData gathered in this study pertained to three outcomes: proportion of JEV infection in vectors, proportion of JEV infection in vertebrate hosts, and minimum infection rate (MIR) in vectors. Random-effects subgroup meta-analysis models were fitted by species (mosquito or vertebrate host species) to estimate pooled summary measures, as well as to compute the variance between studies. Meta-regression models were fitted to assess the association between different predictors and the outcomes of interest and to identify sources of heterogeneity among studies. Predictors included in all models were mosquito/vertebrate host species, diagnostic methods, mosquito capture methods, season, country/region, age category, and number of mosquitos per pool.ResultsMosquito species, diagnostic method, country, and capture method represented important sources of heterogeneity associated with the proportion of JEV infection; host species and region were considered sources of heterogeneity associated with the proportion of JEV infection in hosts; and diagnostic and mosquito capture methods were deemed important contributors of heterogeneity for the MIR outcome.ConclusionsOur findings provide reference pooled summary estimates of vector competence for JEV for some mosquito species, as well as of sources of variability for these outcomes. Moreover, this work provides useful guidelines when interpreting vector and host infection proportions or prevalence from observational studies, and contributes to further our understanding of vector and vertebrate host competence for JEV, elucidating information on the relative importance of vectors and hosts on JEV introduction and transmission.

Differential Infectivities among Different Japanese Encephalitis Virus Genotypes in Culex quinquefasciatus Mosquitoes

During the last 20 years, the epidemiology of Japanese encephalitis virus (JEV) has changed significantly in its endemic regions due to the gradual displacement of the previously dominant genotype III (GIII) with clade b of GI (GI-b). Whilst there is only limited genetic difference distinguishing the two GI clades (GI-a and GI-b), GI-b has shown a significantly wider and more rapid dispersal pattern in several regions in Asia than the GI-a clade, which remains restricted in its geographic distribution since its emergence. Although previously published molecular epidemiological evidence has shown distinct phylodynamic patterns, characterization of the two GI clades has only been limited to in vitro studies. In this study, Culex quinquefasciatus, a known competent JEV mosquito vector species, was orally challenged with three JEV strains each representing GI-a, GI-b, and GIII, respectively. Infection and dissemination were determined based on the detection of infectious viruses in homogenized mosquitoes. Detection of JEV RNA in mosquito saliva at 14 days post infection indicated that Cx. quinquefasciatus can be a competent vector species for both GI and GIII strains. Significantly higher infection rates in mosquitoes exposed to the GI-b and GIII strains than the GI-a strain suggest infectivity in arthropod vectors may lead to the selective advantage of previously and currently dominant genotypes. It could thus play a role in enzootic transmission cycles for the maintenance of JEV if this virus were ever to be introduced into North America.

Two Introductions of Lyme Disease into Connecticut: A Geospatial Analysis of Human Cases from 1984 to 2012

Lyme disease has become the most prevalent vector-borne disease in the United States and results in morbidity in humans, especially children. We used historical case distributions to explain vector-borne disease introductions and subsequent geographic expansion in the absence of disease vector data. We used geographic information system analysis of publicly available Connecticut Department of Public Health case data from 1984, 1985, and 1991 to 2012 for the 169 towns in Connecticut to identify the yearly clusters of Lyme disease cases. Our analysis identified the spatial and temporal origins of two separate introductions of Lyme disease into Connecticut and identified the subsequent direction and rate of spread. We defined both epidemic clusters of cases using significant long-term spatial autocorrelation. The incidence-weighted geographic mean analysis indicates a northern trend of geographic expansion for both epidemic clusters. In eastern Connecticut, as the epidemic progressed, the yearly shift in the geographic mean (rate of epidemic expansion) decreased each year until spatial equilibrium was reached in 2007. The equilibrium indicates a transition from epidemic Lyme disease spread to stable endemic transmission, and we associate this with a reduction in incidence. In western Connecticut, the parabolic distribution of the yearly geographic mean indicates that following the establishment of Lyme disease (1988) the epidemic quickly expanded northward and established equilibrium in 2009.

A quantitative risk assessment (QRA) of the risk of introduction of the Japanese encephalitis virus (JEV) in the United States via infected mosquitoes transported in aircraft and cargo ships

Following a qualitative risk assessment, in which we identified and assessed all viable pathways for the introduction of the Japanese encephalitis virus (JEV) into the United States (US), we identified entry through infected vectors via aircraft and cargo ships as the most likely pathway, and thus considered it further in a quantitative risk assessment (QRA) model. The objective of this study was to evaluate the risk of introduction of JEV in the US via infected mosquitoes transported in aircraft and cargo ships arriving from Asia, using a QRA model. We created a stochastic model to quantify the probability of introduction of at least one infected mosquito in the continental US via aircraft and cargo ships, per at-risk period (March to October) or year, respectively. We modeled the following parameters: number of flights (per at-risk period, i.e., March to October) and cargo ships (per year) and per region, number of mosquitoes per flight and ship, number of mosquitoes that were not found and sensitivity of the mosquito collection method in aircraft, mosquito infection rates, and number of mosquitoes coming in aircraft per at-risk period (March to October) and cargo ships per year. Flight and cargo ship data pertained to years 2010-2016. For model building purposes, we only considered port-to-port vessels arriving from Asia to the US, we assumed that mosquitoes survive the trans-Pacific Ocean ship crossing and that the number of mosquitoes in cargo and passenger flights is similar. Our model predicted a very high risk (0.95 median probability; 95% CIu2009=u20090.80-0.99) of at least one infected mosquito being introduced in the US during the at-risk period, i.e., March to October, via aircraft transportation from JEV-affected countries in Asia. We also estimated that a median of three infected mosquitoes can enter the US during the at-risk period, i.e., March to October (95% CIu2009=u20091-7). The highest probability of introduction via aircraft was attributed to the Mediterranean California ecoregion (0.74; 95% CIu2009=u20090.50-0.90). We predicted, however, a negligible risk (0; 95% CIu2009=u20090.00-0.01) of at least one infected mosquito being introduced via cargo ships. Although the risk of introduction of JEV-infected mosquitoes by cargo ships was negligible, the risk via aircraft was estimated to be high. Our findings indicate the need to prioritize JEV prevention and control methods for aircraft-based pathways, such as aircraft disinfection. The quantitative estimates provided in this study are of interest to public health entities and other stakeholders, as they may support future interventions for preventing JEV introduction, as well as other vector-borne diseases, in the US and other countries.