Tularemia cases increase in the USA from 2011 through 2019.

Tularemia is a rare but potentially serious bacterial zoonosis, which has been reported in the 47 contiguous states of the USA during 2001-2010. This report summarizes the passive surveillance data of tularemia cases reported to the Centers for Disease Control and Prevention from 2011 through 2019. There were 1984 cases reported in the USA during this period. The average national incidence was 0.07 cases per 100,000 person-years (PY), compared to 0.04 cases per 100,000 PY during 2001-2010. The highest statewide reported case 2011-2019 was in Arkansas (374 cases, 20.4% of total), followed by Missouri (13.1%), Oklahoma (11.9%), and Kansas (11.2%). Regarding race, ethnicity, and sex, tularemia cases were reported more frequently among white, non-Hispanic, and male patients. Cases were reported in all age groups; however, individuals 65 years-old and older exhibited the highest incidence. The seasonal distribution of cases generally paralleled the seasonality of tick activity and human outdoor activity, increasing during spring through mid-summer and decreasing through late summer and fall to winter lows. Improved surveillance and education of ticks and tick- and water-borne pathogens should play a key role in efforts to decrease the incidence of tularemia in the USA.

Modeling Effects of Vertebrate Host Exclosures and Host-Targeted Acaricides on Lone Star Tick (Amblyomma americanum, L.) Infestations.

We used a spatially explicit model to simulate the potential effects of exclosures and acaricides targeted at medium-sized mammalian hosts on the local distribution and abundance of lone star ticks (Amblyomma americanum) within forestlands of the southeastern United States. Both exclosures and acaricides were successful in markedly reducing the densities of all off-host tick life stages inside the treatment areas. Densities dropped to almost zero immediately inside the edges of the exclosures, with noticeably depressed densities extending outward 30 to 60 m from the exclosures, and the simulated exclosures maintained their effectiveness as their sizes were decreased from 4.5 to 2.25 to 0.8 ha. Densities exhibited a smooth gradient across the edges of the acaricide-treated areas, with depressed densities extending ≈100 m outward from the edges, but with perceptible densities extending ≈60 m inward from the edges; thus, the simulated acaricide areas lost their effectiveness as size was decreased to slightly less than one-half the diameter of the activity range of the targeted host. Our simulation results indicated that off-host nymph densities responded to reductions of medium-sized host densities. These results suggest that targeting acaricides at medium-sized hosts may be an effective, and currently under-utilized, method for tick suppression.

Increasing Incidence of Spotted Fever Group Rickettsioses in the United States, 2010-2018.

Spotted fever group Rickettsia species are intracellular bacteria transmitted by tick or mite vectors and that cause human diseases referred to as spotted fever group rickettsioses, or spotted fevers. In the United States, the most recognized and commonly reported spotted fevers are Rocky Mountain spotted fever (RMSF) (Rickettsia rickettsii), Rickettsia parkeri rickettsiosis, Pacific Coast tick fever (Rickettsia species 364D), and rickettsialpox (Rickettsia akari). In this study, we summarize and evaluate surveillance data on spotted fever cases reported to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Diseases Surveillance System from 2010 to 2018. During this period, there were 36,632 reported cases of spotted fevers with 95.83% (N = 35,104) reported as meeting the case definition as probable and 4.17% (N = 1528) reported as meeting the case definition as confirmed. The average national incidence of total cases, both probable and confirmed, was 12.77 cases per million persons per year. The highest statewide incidence was in Arkansas, with 256.84 per million per year, whereas the lowest incidence occurred in California, with 0.32 per million per year (note that spotted fevers were not notifiable in Hawaii and Alaska). Cases of spotted fevers were reported more frequently among males by gender, White by race, and non-Hispanic by ethnicity. The incidence of spotted fevers increased significantly from 2010 to 2018, but it is uncertain how many of the reported cases were RMSF and how many developed from more moderate spotted fevers. Improvement of the ability to differentiate between spotted fever group Rickettsia species is needed.

Interleukin-20 is involved in dry eye disease and is a potential therapeutic target.

BACKGROUND: Dry eye disease (DED) is a common disease in ophthalmology, affecting millions of people worldwide. Recent studies have shown that inflammation is the core mechanism of DED. IL-20 is a proinflammatory cytokine involved in various inflammatory diseases. Therefore, we aimed to explore the role of this cytokine in the pathogenesis of DED and evaluate the therapeutic potential of the anti-IL-20 monoclonal antibody (mAb) 7E for DED treatment. METHODS: Clinical tear samples from patients with DED and non-DED controls were collected and their IL-20 protein levels were determined. We established three DED animal models to explore the role of IL-20 and the efficacy of IL-20 antibody in DED. Benzalkonium chloride (BAC)-induced over-evaporative DED, extra-orbital lacrimal gland excision (LGE)-induced aqueous tear-deficient DED, and desiccating stress (DS)-induced combined over-evaporative and aqueous tear-deficient DED animal models were established to investigate the role of IL-20. The anti-IL-20 antibody 7E was established to neutralize IL-20 activity. The effects of IL-20 or 7E on human corneal epithelial cells and macrophages under hyperosmotic stress were analyzed. 7E was topically applied to eyes to evaluate the therapeutic effects in the DED animal models. RESULTS: IL-20 was significantly upregulated in the tears of patients with DED and in the tears and corneas of DED animal models. Under hyperosmotic stress, IL-20 expression was induced via NFAT5 activation in corneal epithelial cells. 7E suppressed hyperosmotic stress-induced activation of macrophages. IL-20 induced cell death in corneal epithelial cells and 7E protected cells from hyperosmotic stress-induced cell death. Blocking IL-20 signaling with 7E protected mice from BAC-induced, LGE-induced, and DS-induced DED by reducing DED symptoms and inhibiting inflammatory responses, macrophage infiltration, apoptosis, and Th17 populations in the conjunctiva and draining lymph nodes. CONCLUSIONS: Our results demonstrated the functions of IL-20 in DED and presented a potential therapeutic option for this condition.

Landscape Complexity has Mixed Effects on an Invasive Aphid and Its Natural Enemies in Sorghum Agroecosystems.

Landscapes with more complex composition and configuration are generally expected to enhance natural enemy densities and pest suppression. To evaluate this hypothesis for an invasive aphid pest of sorghum, Melanaphis sorghi Theobald (Hemiptera: Aphididae), sampling in sorghum fields for aphids and natural enemies was conducted over two years in a southern U.S. coastal production region. Landscape composition and configuration of crop and noncrop elements were assessed using correlation and multivariate regression modeling to detect relationships with insects at different spatial scales. Significant models found more complex landscape configuration, particularly the amount of habitat edges, was associated with increased aphid and natural enemy abundance. Composition associated with noncrop habitats had the opposite effect. Numerical response of natural enemies was taxa dependent, with parasitism lower as landscape complexity increased, while predator numerical response was not affected by landscape complexity. These results indicate landscape complexity may increase both aphid and natural enemy abundance, but with decreasing parasitism and little association with predator numerical response. These relationships are likely contingent on overall environmental suitability to aphid population increase as results were less evident in the second year when average aphid abundance regularly exceeded the economic threshold. This study supports the importance of configuration, especially habitat borders, as a critical metric for determining pest-natural enemy dynamics within a large-scale cereal agroecosystem.

Evaluation of Areawide Forecasts of Wind-borne Crop Pests: Sugarcane Aphid (Hemiptera: Aphididae) Infestations of Sorghum in the Great Plains of North America.

Airborne pests pose a major challenge in agriculture. Integrated pest management programs have been considered a viable response to this challenge, and pest forecasting can aid in strategic management decisions. Annually recurrent areawide sugarcane aphid [Melanaphis sacchari (Zehntner) (Hemiptera: Aphididae)] infestations of sorghum [Sorghum bicolor (L.) Moench (Poales: Poaceae)] in the Great Plains of North America is one of such challenges. As part of the response, a spatially-explicit individual-based model was developed that simulates sugarcane aphid infestations over the southern-to-central part of the region. In this work, we evaluated model forecasts using 2015-2018 field data. The ranges of forecasted days of first infestation significantly overlapped with those observed in the field. The average days of first infestation observed in the field were approximated by the model with differences of less than 28 days in Texas and southern Oklahoma (2015-2018), and in northern Oklahoma (2016-2017). In half of these cases the difference was less than 14 days. In general, the modeled average day of first infestation was earlier than the observed one. As conceptual modeling decisions may impact model forecasts and as various socio-environmental factors may impact spatio-temporal patterns of field data collection, agreement between the forecasts and the observed estimates may vary between locations and seasons. Predictive modeling has the potential to occupy a central position within areawide integrated pest management programs. More detailed consideration of local agricultural practices and local environmental conditions could improve forecasting accuracy, as could broader participation of producers in field monitoring efforts.

Natural Enemies, Mediated by Landscape and Weather Conditions, Shape Response of the Sorghum Agroecosystem of North America to the Invasive Aphid Melanaphis sorghi.

The sorghum (Sorghum bicolor [L.]) agroecosystem of North America provided an opportunity to evaluate agroecosystem response to an invading insect herbivore, Melanaphis sorghi (Theobald) (sorghum aphid) (previously published as Melanaphis sacchari Zehntner) (Hemiptera: Aphididae) onto a widely planted crop that experiences a range of agro-landscape and weather conditions. Initial sorghum risk assessments after M. sorghi's invasion in the mid-2010s provided forecasts of range expansion and annual migration, which were based on aphid life history, extent of sorghum cultivation and susceptibility to M. sorghi, and weather (aphid-plant-weather [APW] risk scenario). A more comprehensive risk assessment proposed here brings top-down forces of M. sorghi-natural enemy interactions to the forefront as mediated by agro-landscape and weather conditions (aphid-enemy/landscape-weather mediated [AE/LW] risk scenario). A hypothesis of regional differences in aphids and natural enemies and sensitivity to agro-landscape and weather was tested using empirical data of insect, landscape, and weather data across 5 years and four regions (two in the U.S. Great Plains [South GP and North GP], one farther south (South), and one in the southeast U.S. [South E]). Natural enemies were widespread with two parasitoids and four coccinellid species common across regions, but regional variation in M. sorghi and natural enemy abundance was detected. The AE/LW risk scenario accounted for natural enemy abundance and activity that was highest in the South region, functioned well across agro-landscape and weather conditions, and was accompanied by average low M. sorghi abundance (~23 M. sorghi per leaf). Positive correlations of natural enemy-M. sorghi abundance also occurred in the South GP region where M. sorghi abundance was low (~20 M. sorghi per leaf), and selected natural enemy activity appeared to be mediated by landscape composition. Melanaphis sorghi abundance was highest in the South E region (~136 aphids/leaf) where natural enemy activity was low and influenced by weather. The AE/LW risk scenario appeared suited, and essential in the South region, in assessing risk on a regional scale, and sets the stage for further modeling to generate estimates of the degree of influence of natural enemies under varying agro-landscape and weather conditions considered in the AE/LW risk scenario. Broadly, these findings are relevant in understanding agroecosystem resilience and recommending supportive management inputs in response to insect invasions in context of natural enemy activity and varied environmental conditions.

Environmental determinants of Batrachochytrium dendrobatidis and the likelihood of further dispersion in the face of climate change in Texas, USA.

One of the major drivers of amphibian population declines is Batrachochytrium dendrobatidis (Bd). We sought to identify the major environmental drivers of Bd prevalence in Texas, USA, by drawing results from museum specimens. We sampled one of the largest museum collections in Texas, the Biodiversity Research and Teaching Collections at Texas A&M University. Our sampling focused on the 9 amphibian species with the widest geographical distribution within the state, where we sub-sampled 30% of each species per decade from 1930 to present via skin swabs, totaling 1501 independent sampling events, and used quantitative real-time PCR (qPCR) to detect pathogen presence. We analyzed several geo-referenced variables describing climatic conditions to identify potential factors influencing the likelihood of presence of Bd using boosted regression trees. Our final model suggests the most influential variables are mean temperature of driest quarter, annual mean temperature, temperature annual range, and mean diurnal range. The most likely suitable range for Bd is currently found in the Blackland Prairie and Cross Timbers ecoregions. Results of our future (to the year 2040) projections suggest that Bd could expand its current distribution. Our model could play an important role when developing an integrated conservation plan through (1) focusing future field work on locations with a high likelihood of presence, (2) assisting in the choice of locations for restoration, and (3) developing future research plans including those necessary for projecting reactions to climate change. Our model also could integrate new presence data of Bd when they become available to enhance prediction precision.

Optimizing long-acting acaricide use for integrated tick management of Rhipicephalus australis-infesting cattle in New Caledonia.

The tick Rhipicephalus australis, formerly known as Rhipicephalus microplus, is the most economically important ectoparasite of livestock in New Caledonia, affecting cattle health and production. Decades of control attempts based on the application of chemical acaricides have exerted a strong selective pressure on R. australis populations, some of which have evolved resistance to these treatments. Research to develop integrated tick control programs is now focused on decreasing applications of chemicals. This study reports the implementation of a method of pasture and herd management involving minimal strategic use of long-acting acaricides, here defined as those having substantial efficacy against larvae for several weeks. Diverse parameters concerning the utilization of long-acting acaricides in association with pasture and herd management on 21 New Caledonian farms over a 5-year period were analyzed to optimize their strategic use. Longer larval acaricidal effect was achieved with a commercial pour-on formulation of fluazuron than with a commercial injectable (subcutaneous) formulation containing 3.15% ivermectin. Pasture and herd management allowed an increase in the delay between a long-lasting acaricide application and the subsequent acaricide treatment from 11.0 weeks to 17.7 weeks. However, if ticks were detected and reported by producers on the day of a long-acting acaricide application, the delay to the following treatment was reduced from 18.5 weeks to 11.2 weeks. The impact of a long-acting acaricide treatment on larval populations in pastures was greatest with a stocking rate of 5 animals per hectare grazing during 1 week. These results provide science-based evidence to cattle producers for adaptive integrated tick management in order to delay the development of acaricide resistance.

Integrated control of the cattle tick, Rhipicephalus australis (Acari: Ixodidae), in New Caledonia through the Pasture and Cattle Management method.

Development of the Pasture and Cattle Management (PCM) method is a priority to control the cattle tick, Rhipicephalus australis, in New Caledonia. The PCM method provides the foundation for sustainable integrated tick control because approximately 95% of cattle ticks in infested pastures are off the host in the non-parasitic life stages, and the practice of treating cattle intensely with chemical acaricides is a risk for the emergence of resistance to these active ingredients in commercial acaricidal products available for veterinary use. Here, we report the findings of an assessment survey to document the utility of the PCM method. Analyses of questionnaire data provided by 21 beef cattle producers describing their management of 37 herds informed how to (1) assess the ability of PCM to reduce acaricide use and (2) prioritize best practices and define recommendations to breeders promoting efficient tick control with minimum acaricide use. Boosted regression tree analysis showed a significant (p = 0.002) reduction of ≈33% in the number of acaricide treatments from 7.9 to 5.3 per year by using PCM. Of the 24 factors identified as potentially affecting acaricide use, six factors accounted for ≈86% of the variability in number of acaricide treatments applied annually. The six most influential factors involved farm characteristics as well as pasture and herd management recommendations. These results demonstrated the usefulness of PCM for integrated control of R. australis infestations while reducing acaricide use to improve cattle production in New Caledonia.

Simulated dynamics of southern cattle fever ticks (Rhipicephalus (Boophilus) microplus) in south Texas, USA: investigating potential wildlife-mediated impacts on eradication efforts.

BACKGROUND: Cattle fever ticks (CFT), Rhipicephalus (Boophilus) annulatus and R. (B.) microplus, are vectors of microbes causing bovine babesiosis and pose a threat to the economic viability of the US livestock industry. Efforts by the Cattle Fever Tick Eradication Program (CFTEP) along the US-Mexico border in south Texas are complicated by the involvement of alternate hosts, including white-tailed deer (Odocoileus virginianus) and nilgai (Boselaphus tragocamelus). METHODS: In the present study, we use a spatially explicit, individual-based model to explore the potential effects of host species composition and host habitat use patterns on southern cattle fever ticks (SCFT, R. (B.) microplus) infestation dynamics and efficacy of eradication schemes. RESULTS: In simulations without eradication efforts, mean off-host larval densities were much higher when cattle were present than when only white-tailed deer and nilgai were present. Densities in mesquite and meadows were slightly higher, and densities in mixed brush were much lower, than landscape-level densities in each of these scenarios. In eradication simulations, reductions in mean off-host larval densities at the landscape level were much smaller when acaricide was applied to cattle only, or to cattle and white-tailed deer, than when applied to cattle and nilgai. Relative density reductions in mesquite, mixed brush, and meadows depended on host habitat use preferences. Shifting nilgai habitat use preferences increasingly toward mixed brush and away from mesquite did not change mean off-host larval tick densities noticeably at the landscape level. However, mean densities were increased markedly in mesquite and decreased markedly in mixed brush, while no noticeable change in density was observed in meadows. CONCLUSIONS: Our results suggest that continued integration of field data into spatially explicit, individual-based models will facilitate the development of novel eradication strategies and will allow near-real-time infestation forecasts as an aid in anticipating and preventing wildlife-mediated impacts on SCFT eradication efforts.

Using Data Surveillance to Understand the Rising Incidence of Babesiosis in the United States, 2011-2018.

Babesiosis is a tick-borne disease that is caused by intraerythrocytic protozoan parasites of the genus Babesia. Common symptoms of babesiosis are generally characterized as nonspecific flu-like symptoms, such as fever or chills. Human infections are reported to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Diseases Surveillance System (NNDSS). This study summarizes data of Babesia infections reported to the CDC by the NNDSS from 2011 to 2018. In total, there were 14,159 reported cases of babesiosis, and the incidence rate was 5.55 cases per million persons per year, displaying an increasing trend during the study period. The demographic group most affected was middle-aged and elderly white males. Infections were most abundant in the New England and the Mid-Atlantic regions of the United States. Our study provides useful results for a basic understanding of incidence, spatial and temporal distribution, and severity of babesiosis.

Effects of white-tailed deer habitat use preferences on southern cattle fever tick eradication: simulating impact on "pasture vacation" strategies.

BACKGROUND: Rhipicephalus (Boophilus) annulatus and Rhipicephalus (Boophilus) microplus (southern cattle fever tick; SCFT), collectively known as cattle-fever ticks (CFTs), are vectors of protozoal parasites (Babesia bigemina and Babesia bovis) that cause bovine babesiosis (also known as cattle fever). One traditional strategy for CFT eradication involves the implementation of a "pasture vacation," which involves removing cattle (Bos taurus) from an infested pasture for an extended period of time. However, vacated pastures are often inhabited by wildlife hosts, such as white-tailed deer (WTD; Odocoileus virginianus), which can serve as alternate hosts for questing CFTs. We hypothesized that the distribution of host-seeking larvae among habitat types post-pasture vacation would reflect habitat use patterns of WTD, and in turn, affect the subsequent rate of pasture infestation by CFT. METHODS: We adapted a spatially explicit, individual-based model to simulate interactions among SCFT, cattle, and WTD as a tool to investigate the potential effects of WTD habitat use preferences on the efficacy of a pasture vacation. We parameterized the model to represent conditions typical of rangelands in south Texas, USA, simulated a 1-year pasture vacation under different assumptions regarding WTD habitat use preferences, and summarized effects on efficacy through (1) time post-vacation to reach 100% of pre-vacation densities of host-seeking larvae, and (2) the ecological conditions that resulted in the lowest host-seeking larval densities following pasture vacation. RESULTS: Larval densities at the landscape scale varied seasonally in a similar manner over the entire simulation period, regardless of WTD habitat use preferences. Following the removal of cattle, larval densities declined sharply to < 100 larvae/ha. Following the return of cattle, larval densities increased to > 60% of pre-vacation densities ≈ 21 weeks post-vacation, and reached pre-vacation levels in less than a year. Trends in larval densities in different habitat types paralleled those at the landscape scale over the entire simulation period, but differed quantitatively from one another during the pasture vacation. Relative larval densities (highest to lowest) shifted from (1) wood/shrub, (2) grass, (3) mixed-brush during the pre-vacation period to (1) mixed-brush, (2) wood/shrub, (3) grass or (1) wood/shrub, (2) mixed-brush, (3) grass during the post-vacation period, depending on WTD habitat use preferences. CONCLUSIONS: By monitoring WTD-driven shifts in distributions of SCFT host-seeking larvae among habitat types during simulated pasture vacation experiments, we were able to identify potential SCFT refugia from which recrudescence of infestations could originate. Such information could inform timely applications of acaricides to specific refugia habitats immediately prior to the termination of pasture vacations.

Interleukin-24 protects against liver injury in mouse models.

BACKGROUND: Interleukin-24 (IL-24) binds to two kinds of receptor complexes, namely IL-20R1/IL-20R2 and IL-20R2/IL-22R1, which are also bound by IL-20. IL-20 plays a detrimental role in liver fibrosis. Due to the sharing of receptor complexes, we aimed to determine whether IL-24 also participates in liver fibrosis. METHODS: Clinical biopsy specimens from various stages of liver fibrosis were used to analyze IL-24 expression. IL-24 protein was administered to mice with thioacetamide (TAA)-induced liver injury. The direct effects of IL-24 on mouse primary hepatocytes or hepatic stellate cells (HSCs) were analyzed. Wild-type, IL-20R1-, and IL20R2-deficient mice were used to establish a model of acute TAA-induced liver injury. FINDINGS: Among patients with more severe liver fibrosis, there was a reduced IL-24/IL-20 ratio. Administration of IL-24 protein protected mice from TAA-induced liver injury and reduction of liver inflammation by antioxidant effects. IL-24 protected hepatocytes from TAA-induced apoptosis and prevented liver fibrosis through the inhibition of the HSCs activation. The protective role of IL-24 acted on liver cells were mainly IL-20R1-independent. IL-20R2-deficient mice exhibited more severe liver injury upon TAA treatment, thus confirming the protective role of IL-24. INTERPRETATION: IL-24 plays a key protective role in the progression of liver injury and has therapeutic potential for treating liver injuries. FUNDING: This work was supported by the Ministry of Science and Technology of Taiwan (MOST 106-2320-B-006-024) and Taiwan Liver Disease Prevention & Treatment Research Foundation.

Socio-technical scales in socio-environmental modeling: Managing a system-of-systems modeling approach.

System-of-systems approaches for integrated assessments have become prevalent in recent years. Such approaches integrate a variety of models from different disciplines and modeling paradigms to represent a socio-environmental (or social-ecological) system aiming to holistically inform policy and decision-making processes. Central to the system-of-systems approaches is the representation of systems in a multi-tier framework with nested scales. Current modeling paradigms, however, have disciplinary-specific lineage, leading to inconsistencies in the conceptualization and integration of socio-environmental systems. In this paper, a multidisciplinary team of researchers, from engineering, natural and social sciences, have come together to detail socio-technical practices and challenges that arise in the consideration of scale throughout the socio-environmental modeling process. We identify key paths forward, focused on explicit consideration of scale and uncertainty, strengthening interdisciplinary communication, and improvement of the documentation process. We call for a grand vision (and commensurate funding) for holistic system-of-systems research that engages researchers, stakeholders, and policy makers in a multi-tiered process for the co-creation of knowledge and solutions to major socio-environmental problems.

Enhanced biosurveillance of high-consequence invasive pests: southern cattle fever ticks, Rhipicephalus (Boophilus) microplus, on livestock and wildlife.

BACKGROUND: Some tick species are invasive and of high consequence to public and veterinary health. Socioeconomic development of rural parts of the USA was enabled partly through the eradication by 1943 of cattle fever ticks (CFT, Rhipicephalus (Boophilus) annulatus and R. (B.) microplus). The southern cattle fever ticks (SCFT, R. (B.) microplus) remain a real and present threat to the USA animal agriculture because they are established in Mexico. Livestock-wildlife interactions in the Permanent Quarantine Zone (PQZ) established by the century-old Cattle Fever Tick Eradication Programme (CFTEP) in south Texas endanger its operations. METHODS: We describe a spatially-explicit, individual-based model that simulates interactions between cattle, white-tailed deer (WTD, Odocoileus virginianus), and nilgai (Boselaphus tragocamelus) to assess the risk for SCFT infestations across the pathogenic landscape in the PQZ and beyond. We also investigate the potential role of nilgai in sustaining SCFT populations by simulating various hypothetical infestation and eradication scenarios. RESULTS: All infestation scenarios resulted in a phase transition from a relatively small proportion of the ranch infested to almost the entire ranch infested coinciding with the typical period of autumn increases in off-host tick larvae. Results of eradication scenarios suggest that elimination of all on-host ticks on cattle, WTD, or nilgai would have virtually no effect on the proportion of the ranch infested or on the proportions of different tick habitat types infested; the entire ranch would remain infested. If all on-host ticks were eliminated on cattle and WTD, WTD and nilgai, or cattle and nilgai, the proportions of the ranch infested occasionally would drop to 0.6, 0.6 and 0.2, respectively. Differences in proportions of the ranch infested from year to year were due to primarily to differences in winter weather conditions, whereas infestation differences among tick habitat types were due primarily to habitat use preferences of hosts. CONCLUSIONS: Infestations in nilgai augment SCFT refugia enabled by WTD and promote pest persistence across the landscape and cattle parasitism. Our study documented the utility of enhanced biosurveillance using simulation tools to mitigate risk and enhance operations of area-wide tick management programmes like the CFTEP through integrated tactics for SCFT suppression.

Increasing Incidence of Anaplasmosis in the United States, 2012 Through 2016.

Anaplasmosis is a tick-borne disease that is primarily caused by the rickettsial bacterium Anaplasma phagocytophilum. Anaplasmosis is a febrile disease with common symptoms, including headaches, fever, and lethargy, but it can cause serious organ failure and even death if left untreated. Human infections are reported annually to the Centers for Disease Control and Prevention (CDC) through the National Notifiable Diseases Surveillance System (NNDSS). This report analyzed the cases of anaplasmosis reported by the NNDSS from 2012 to 2016. In total, there were 15,778 reported A. phagocytophilum infections, and the incidence rate was 7.27 cases per million persons per year, with the number of reported cases increasing each year. The demographic group most affected was middle-aged and elderly white males. Infections were most abundant in the coastal northeast and northern midwest regions. Our study provides useful results for a basic understanding of incidence, distribution, and severity of A. phagocytophilum infections.

Modeling rangelands as spatially-explicit complex adaptive systems.

Rangelands cover one third of the earth's land area, provide livelihoods for one billion persons, and most have been degraded by overgrazing of domestic livestock. Recent debate about best management practices often has centered on comparison of continuous grazing and rotational grazing. Resolution to this debate may lie in viewing rangelands as complex adaptive systems. We describe a spatially-structured, individual-based model of rangelands that embodies this perspective, and simulate forage dynamics and cattle production under semi-arid rangeland conditions typical of the southern Great Plains of the USA employing both continuous and rotational grazing. Relative "success" of simulated grazing schemes depended primarily on the evaluation metric used (e.g., rangeland ecological condition, sale weight of cattle, secondary production efficiency) and the particular manage scheme employed, and neither continuous nor rotational grazing schemes were uniformly more successful. Our results demonstrate that solution of the grazing systems debate is unlikely to be found in a single group of grazing schemes, but, rather, in adaptive management of feedbacks among system components. The present work provides an example of how modeling rangelands as complex adaptive systems can aid in the evaluation of management schemes.

Targeting interleukin-20 alleviates paclitaxel-induced peripheral neuropathy.

The role of immune mediators, including proinflammatory cytokines in chemotherapy-induced peripheral neuropathy (CIPN), remains unclear. Here, we studied the contribution of interleukin-20 (IL-20) to the development of paclitaxel-induced peripheral neuropathy. Increased serum levels of IL-20 in cancer patients with chemotherapy were accompanied by increased CIPN risk. In mouse models, proinflammatory IL-20 levels in serum and dorsal root ganglia fluctuated with paclitaxel treatment. Blocking IL-20 with the neutralizing antibody or genetic deletion of its receptors prevented CIPN, alleviated peripheral nerve damage, and dampened inflammatory responses, including macrophage infiltration and cytokine release. Mechanistically, paclitaxel upregulated IL-20 through dysregulated Ca homeostasis, which augmented chemotherapy-induced neurotoxicity. Importantly, IL-20 suppression did not alter paclitaxel efficacy on cancer treatment both in vitro and in vivo. Together, targeting IL-20 ameliorates paclitaxel-induced peripheral neuropathy by suppressing neuroinflammation and restoring Ca homeostasis. Therefore, the anti-IL-20 monoclonal antibody is a promising therapeutic for the prevention and treatment of paclitaxel-induced neuropathy.

Visceral leishmaniasis on the Indian Subcontinent: Efficacy of fipronil-based cattle treatment in controlling sand fly populations is dependent on specific aspects of sand fly ecology.

BACKGROUND: Visceral leishmaniasis (VL) is a deadly disease transmitted by the sand fly Phlebotomus argentipes on the Indian subcontinent, with a promising means of vector control being orally treating cattle with fipronil-based drugs. While prior research investigating the dynamic relationship between timing of fipronil-based control schemes and the seasonality of sand flies provides insights into potential of treatment on a large scale, ecological uncertainties remain. We investigated how uncertainties associated with sand fly ecology might affect our ability to assess efficacy of fipronil-based control schemes. To do this, we used a previously-described, individual-based, stochastic sand fly model to quantify how uncertainties associated with 1) the percentage of female sand flies taking blood meals from cattle, and 2) the percentage of female sand flies ovipositing in organic matter containing feces from treated cattle might impact the efficacy of fipronil-based sand fly control schemes. PRINCIPAL FINDINGS: Assuming no prior knowledge of sand fly blood meal and oviposition sites, the probabilities of achieving effective sand fly population reduction with treatments performed 3, 6 and 12 times per year were ≈5-22%, ≈27-36%, and ≈46-54%, respectively. Assuming ≥50% of sand flies feed on cattle, probabilities of achieving efficacious control increased to ≈8-31%, ≈15-42%, and ≈52-65%. Assuming also that ≥50% of sand flies oviposit in cattle feces, the above probabilities increased further to ≈14-53%, ≈31-81%, and ≈89-97%. CONCLUSIONS: Our assessments of the efficacy of fipronil-based cattle treatments in controlling sand fly populations depend on our assumptions regarding key aspects of sand fly ecology. Assessments are most sensitive to assumptions concerning the percentage of sand flies ovipositing in feces of treated cattle, thus emphasizing the importance of identifying sand fly oviposition sites. Our results place the evaluation of fipronil-based cattle treatment within a broader ecological context, which could aid in the planning and execution of a largescale field trial.