Fatal Case of Heartland Virus Disease Acquired in the Mid-Atlantic Region, United States.

Heartland virus (HRTV) disease is an emerging tickborne illness in the midwestern and southern United States. We describe a reported fatal case of HRTV infection in the Maryland and Virginia region, states not widely recognized to have human HRTV disease cases. The range of HRTV could be expanding in the United States.

Lyme disease, Virginia, USA, 2000-2011.

Lyme disease, caused by the bacterium Borrelia burgdorferi and transmitted in the eastern United States by the black-legged tick (Ixodes scapularis), is increasing in incidence and expanding geographically. Recent environmental modeling based on extensive field collections of host-seeking I. scapularis ticks predicted a coastal distribution of ticks in mid-Atlantic states and an elevational limit of 510 m. However, human Lyme disease cases are increasing most dramatically at higher elevations in Virginia, a state where Lyme disease is rapidly emerging. Our goal was to explore the apparent incongruity, during 2000-2011, between human Lyme disease data and predicted and observed I. scapularis distribution. We found significantly higher densities of infected ticks at our highest elevation site than at lower elevation sites. We also found that I. scapularis ticks in Virginia are more closely related to northern than to southern tick populations. Clinicians and epidemiologists should be vigilant in light of the changing spatial distributions of risk.

Rickettsiosis subcommittee report to the tick-borne disease working group.

Tick-borne rickettsial infections are serious, common, and difficult to diagnose. Among the most important factors leading to failure to diagnose and treat tick-borne rickettsioses effectively is a lack of consideration of the potential diagnosis by primary caregivers and emergency department physicians in patients presenting with undifferentiated acute febrile illness during tick season. This situation exists because of insufficient primary and continuing medical education of medical students, primary care and emergency medicine residents, and practicing physicians regarding tick-borne rickettsioses specific to the region where they practice. Delayed initiation of treatment with an appropriate antibiotic is associated with adverse outcomes including increased rates of hospitalization, admission to an intensive care unit, and mortality. The earliest symptoms are nonspecific, consisting of fever, headache, myalgias, and nausea and/or vomiting. Laboratory abnormalities are typically absent at this time when the therapeutic response to an appropriate antibiotic would be optimal. There is a mistaken idea among a substantial portion of physicians that the best antibiotic available, doxycycline, should not be administered to children 8 years of age or younger or during pregnancy. For all of the above reasons, there is unnecessary morbidity and mortality caused by tick-borne rickettsioses. This report proposes measures to address these critical issues regarding tick-borne rickettsioses.

Tick-borne encephalitis among US travellers, 2010-20.

BACKGROUND: Tick-borne encephalitis (TBE) is an arboviral disease that is focally endemic in parts of Europe and Asia. TBE cases among US travellers are rare, with previous reports of only six cases among civilian travellers through 2009 and nine military-related cases through 2020. A TBE vaccine was licenced in the USA in August 2021. Understanding TBE epidemiology and risks among US travellers can help with the counselling of travellers going to TBE-endemic areas. METHODS: Diagnostic testing for TBE in the USA is typically performed at the Centers for Disease Control and Prevention (CDC) because no commercial testing is available. Diagnostic testing for TBE at CDC since 2010 was reviewed. For individuals with evidence of TBE virus infection, information was gathered on demographics, clinical presentations and risk factors for infection. RESULTS: From 2010-20, six patients with TBE were identified. Cases occurred among both paediatric and adult travellers and all were male. Patients were diagnosed with meningitis (n = 2) or encephalitis (n = 4); none died. Cases had travelled to various countries in Europe or Russia. Three cases reported visiting friends or relatives. Activities reported included hiking, camping, trail running, or working outdoors, and two cases had a recognized tick bite. CONCLUSIONS: TBE cases among US travellers are uncommon, with these six cases being the only known TBE cases among civilian travellers during this 11-year period. Nonetheless, given potential disease severity, pre-travel counselling for travellers to TBE-endemic areas should include information on measures to reduce the risk for TBE and other tick-borne diseases, including possible TBE vaccine use if a traveller's itinerary puts them at higher risk for infection. Clinicians should consider the diagnosis of TBE in a patient with a neurologic or febrile illness recently returned from a TBE-endemic country, particularly if a tick bite or possible tick exposure is reported.

Environmental Correlates of Lyme Disease Emergence in Southwest Virginia, 2005-2014.

Lyme disease is the most common tick-borne disease in North America. Though human infection is mostly transmitted in a limited geography, the range has expanded in recent years. One notable area of recent expansion is in the mountainous region of southwestern Virginia. The ecological factors that facilitate or constrain the range of human Lyme disease in this region remain uncertain. To evaluate this further, we obtained ecological data, including remotely sensed data on forest structure and vegetation, weather data, and elevation. These data were aggregated within the census block groups of a 9,153 km2 area around the cities of Blacksburg and Roanoke, VA, an area with heterogeneous Lyme disease transmission. In this geographic area, 755 individuals were reported to have Lyme disease in the 10 yr from 2006 to 2015, and these cases were aggregated by block group. A zero-inflated negative binomial model was used to evaluate which environmental variables influenced the abundance of Lyme disease cases. Higher elevation and higher vegetation density had the greatest effect size on the abundance of Lyme disease. Measures of forest edge, forest integrity, temperature, and humidity were not associated with Lyme disease cases. Future southward expansion of Lyme disease into the southeastern states may be most likely in ecologically similar mountainous areas.

First glimpse into the origin and spread of the Asian longhorned tick, Haemaphysalis longicornis, in the United States.

Established populations of Asian longhorned ticks (ALT), Haemaphysalis longicornis, were first identified in the United States (US) in 2017 by sequencing the mitochondrial cytochrome c oxidase subunit I (cox1) 'barcoding' locus followed by morphological confirmation. Subsequent investigations detected ALT infestations in 12, mostly eastern, US states. To gain information on the origin and spread of US ALT, we (1) sequenced cox1 from ALT populations across 9 US states and (2) obtained cox1 sequences from potential source populations [China, Japan and Republic of Korea (ROK) as well as Australia, New Zealand and the Kingdom of Tonga (KOT)] both by sequencing and by downloading publicly available sequences in NCBI GenBank. Additionally, we conducted epidemiological investigations of properties near its initial detection locale in Hunterdon County, NJ, as well as a broader risk analysis for importation of ectoparasites into the area. In eastern Asian populations (China/Japan/ROK), we detected 35 cox1 haplotypes that neatly clustered into two clades with known bisexual versus parthenogenetic phenotypes. In Australia/New Zealand/KOT, we detected 10 cox1 haplotypes all falling within the parthenogenetic cluster. In the United States, we detected three differentially distributed cox1 haplotypes from the parthenogenetic cluster, supporting phenotypic evidence that US ALT are parthenogenetic. While none of the source populations examined had all three US cox1 haplotypes, a phylogeographic network analysis supports a northeast Asian source for the US populations. Within the United States, epidemiological investigations indicate ALT can be moved long distances by human transport of animals, such as horses and dogs, with smaller scale movements on wildlife. These results have relevant implications for efforts aimed at minimizing the spread of ALT in the United States and preventing additional exotic tick introductions.

Dementia and cognitive impairment are not associated with earlier mortality after percutaneous endoscopic gastrostomy.

BACKGROUND: Studies have shown varying results with regard to risk factors for mortality after percutaneous endoscopic gastrostomy (PEG). OBJECTIVES: To examine the time to death in patients with dementia or significant cognitive impairment (SCI) due to neurologic injury who had undergone PEG compared with patients without either of these diagnoses, and to examine risk factors for 30-day mortality after PEG. METHODS: Patients who had undergone PEG over a 2-year period were identified. Local medical records and the Social Security Death Index were reviewed to ascertain the patients' age, gender, serum albumin, diagnoses, presence or absence of dementia or SCI, presence or absence of complications related to PEG, and length of survival after PEG. The Charlson Comorbidity Index (CCI) was calculated based on the medical diagnoses at the time of PEG. RESULTS: One hundred ninety patients were identified. Forty-five carried a diagnosis of dementia and/or SCI compared with 145 who did not. Median survival of patients with dementia or SCI was 53 days compared with 78 days in patients without these diagnoses (P=.85). Age (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.04-1.12) and albumin (OR 0.43, 95% CI 0.22-0.84) were associated with 30-day mortality, whereas gender (OR 1.2, 95% CI 0.47-2.90), CCI (OR 1.1, 95% CI 0.86-1.32), and presence of PEG-related complications (OR 1.6, 95% CI 0.36-6.76) were not. CONCLUSIONS: Age and serum albumin are risk factors for 30-day mortality after PEG. Patients with dementia or SCI do not have a significantly shorter survival after PEG than patients with intact cognitive function.

Spatio-temporal analysis of the relationship between WNV dissemination and environmental variables in Indianapolis, USA.

BACKGROUND: This study developed a multi-temporal analysis on the relationship between West Nile Virus (WNV) dissemination and environmental variables by using an integrated approach of remote sensing, GIS, and statistical techniques. WNV mosquito cases in seven months (April-October) of the six years (2002-2007) were collected in Indianapolis, USA. Epidemic curves were plotted to identify the temporal outbreaks of WNV. Spatial-temporal analysis and k-mean cluster analysis were further applied to determine the high-risk areas. Finally, the relationship between environmental variables and WNV outbreaks were examined by using Discriminant Analysis. RESULTS: The results show that the WNV epidemic curve reached its peak in August for all years in the study area except in 2007, where the peak was reached in July. WNV dissemination started from the central longitudinal corridor of the city and spread out to the east and west. Different years and seasons had different high-risk areas, but the southwest and southeast corners show the highest risk for WNV infection due to their high percentages of agriculture and water sources. CONCLUSION: Major environmental factors contributing to the outbreak of WNV in Indianapolis were the percentages of agriculture and water, total length of streams, and total size of wetlands. This study provides important information for urban public health prevention and management. It also contributes to the optimization of mosquito control and arrangement of future sampling efforts.

Plasmodium-infected Anopheles mosquitoes collected in Virginia and Maryland following local transmission of Plasmodium vivax malaria in Loudoun County, Virginia.

Two recent outbreaks of locally acquired, mosquito-transmitted malaria in Virginia in 1998 and 2002 demonstrate the continued risk of endemic mosquito-transmitted malaria in heavily populated areas of the eastern United States. Increasing immigration, growth in global travel, and the presence of competent anopheline vectors throughout the eastern United States contribute to the increasing risk of malaria importation and transmission. On August 23 and 25, 2002, Plasmodium vivax malaria was diagnosed in 2 teenagers in Loudoun County, Virginia. The Centers for Disease Control and Prevention (CDC) deemed these cases to be locally acquired because of the lack of risk factors for malaria, such as international travel, blood transfusion, organ transplantation, or needle sharing. The patients lived approximately 0.5 mi apart; however, 1 patient reported numerous visits to friends who lived directly across the street from the other patient. Two Anopheles quadrimaculatus s.l. female pools collected in Loudoun County, Virginia, and 1 An. punctipennis female pool collected in Fairfax County, Virginia, tested positive for P. vivax 210 with the VecTest panel assay and enzyme-linked immunosorbent assay (ELISA). In addition, 2 An. quadrimaculatus s.l. female pools collected in Montgomery, Maryland, tested positive for P. vivax 210. The CDC confirmed these initial results with the circumsporozoite ELISA. The authors believe that this is the 1st demonstration of Plasmodium-infected mosquitoes collected in association with locally acquired human malaria in the United States since the current national malaria surveillance system began in 1957.

An Examination of the Demographic and Environmental Variables Correlated with Lyme Disease Emergence in Virginia.

Lyme disease is the United States' most significant vector-borne illness. Virginia, on the southern edge of the disease's currently expanding range, has experienced an increase in Lyme disease both spatially and temporally, with steadily increasing rates over the past decade and disease spread from the northern to the southwestern part of the state. This study used a Geographic Information System and a spatial Poisson regression model to examine correlations between demographic and land cover variables, and human Lyme disease from 2006 to 2010 in Virginia. Analysis indicated that herbaceous land cover is positively correlated with Lyme disease incidence rates. Areas with greater interspersion between herbaceous and forested land were also positively correlated with incidence rates. In addition, income and age were positively correlated with incidence rates. Levels of development, interspersion of herbaceous and developed land, and population density were negatively correlated with incidence rates. Abundance of forest fragments less than 2 hectares in area was not significantly correlated. Our results support some findings of previous studies on ecological variables and Lyme disease in endemic areas, but other results have not been found in previous studies, highlighting the potential contribution of new variables as Lyme disease continues to emerge southward.

Geographic Expansion of Lyme Disease in the Southeastern United States, 2000-2014.

Background. The majority of Lyme disease cases in the United States are acquired on the east coast between northern Virginia and New England. In recent years the geographic extent of Lyme disease has been expanding, raising the prospect of Lyme disease becoming endemic in the southeast. Methods. We collected confirmed and probable cases of Lyme disease from 2000 through 2014 from the Virginia Department of Health and North Carolina Department of Public Health and entered them in a geographic information system. We performed spatial and spatiotemporal cluster analyses to characterize Lyme disease expansion. Results. There was a marked increase in Lyme disease cases in Virginia, particularly from 2007 onwards. Northern Virginia experienced intensification and geographic expansion of Lyme disease cases. The most notable area of expansion was to the southwest along the Appalachian Mountains with development of a new disease cluster in the southern Virginia mountain region. Conclusions. The geographic distribution of Lyme disease cases significantly expanded in Virginia between 2000 and 2014, particularly southward in the Virginia mountain ranges. If these trends continue, North Carolina can expect autochthonous Lyme disease transmission in its mountain region in the coming years.

Population genetic structure of the Lyme disease vector Ixodes scapularis at an apparent spatial expansion front.

Modeling and empirical evidence suggests that Lyme disease is undergoing geographic expansion from principal foci in the midwestern and northeastern United States. Virginia is at the southern edge of the current expansion zone and has seen dramatic rise in human Lyme disease cases since 2007, potentially owing to a recent increase in vector abundance. Ixodes scapularis is known throughout the eastern US but behavioral or physiological variation between northern and southern lineages might lead northern-variant ticks to more frequently parasitize humans. We hypothesized that recent spatial and numerical increase in Lyme disease cases is associated with demographic and/or spatial expansion of I. scapularis and that signals of these phenomena would be detectable and discernable in population genetic signals. In summer and fall 2011, we collected nymphal I. scapularis by drag sampling and adult I. scapularis from deer carcasses at hunting check stations at nine sites arranged along an east-west transect through central Virginia. We analyzed 16S mtDNA sequences data from up to 24 I. scapularis individuals collected from each site and detected a total of 24 haplotypes containing 29 segregating sites. We found no evidence for population genetic structure among these sites but we did find strong signals of both demographic and spatial expansion throughout our study system. We found two haplotypes (one individual each) representing a lineage of ticks that is only found in the southeastern United States, with the remaining individuals representing a less genetically diverse clade that is typical of the northern United States, but that has also been detected in the American South. Taken together, these results lead us to conclude that I. scapularis populations in Virginia are expanding and that this expansion may account for recent observed increases in Lyme disease.

Spatial and temporal emergence pattern of Lyme disease in Virginia.

The emergence of infectious diseases over the past several decades has highlighted the need to better understand epidemics and prepare for the spread of diseases into new areas. As these diseases expand their geographic range, cases are recorded at different geographic locations over time, making the analysis and prediction of this expansion complicated. In this study, we analyze spatial patterns of the disease using a statistical smoothing analysis based on areal (census tract level) count data of Lyme disease cases in Virginia from 1998 to 2011. We also use space and space-time scan statistics to reveal the presence of clusters in the spatial and spatiotemporal distribution of Lyme disease. Our results confirm and quantify the continued emergence of Lyme disease to the south and west in states along the eastern coast of the United States. The results also highlight areas where education and surveillance needs are highest.

Ehrlichia and spotted fever group Rickettsiae surveillance in Amblyomma americanum in Virginia through use of a novel six-plex real-time PCR assay.

The population of the lone star tick Amblyomma americanum has expanded in North America over the last several decades. It is known to be an aggressive and nondiscriminatory biter and is by far the most common human-biting tick encountered in Virginia. Few studies of human pathogen prevalence in ticks have been conducted in our state since the mid-twentieth century. We developed a six-plex real-time PCR assay to detect three Ehrlichia species (E. chaffeensis, E. ewingii, and Panola Mountain Ehrlichia) and three spotted fever group Rickettsiae (SFGR; R. amblyommii, R. parkeri, and R. rickettsii) and used it to test A. americanum from around the state. Our studies revealed a presence of all three Ehrlichia species (0-24.5%) and a high prevalence (50-80%) of R. amblyommii, a presumptively nonpathogenic SFGR, in all regions surveyed. R. parkeri, previously only detected in Virginia's Amblyomma maculatum ticks, was found in A. americanum in several surveyed areas within two regions having established A. maculatum populations. R. rickettsii was not found in any sample tested. Our study provides the first state-wide screening of A. americanum ticks in recent history and indicates that human exposure to R. amblyommii and to Ehrlichiae may be common. The high prevalence of R. amblyommii, serological cross-reactivity of all SFGR members, and the apparent rarity of R. rickettsii in human biting ticks across the eastern United States suggest that clinical cases of tick-borne disease, including ehrlichiosis, may be commonly misdiagnosed as Rocky Mountain spotted fever, and that suspicion of other SFGR as well as Ehrlichia should be increased. These data may be of relevance to other regions where A. americanum is prevalent.

Geographic incidence of human West Nile virus in northern Virginia, USA, in relation to incidence in birds and variations in urban environment.

Previous studies have analyzed the number and location of bird infections with human incidence of West Nile virus (WNV) as well as the effects of environmental and socioeconomic factors on WNV propagation. However, such associations require more quantitative analyses. This study is intended to quantitatively analyze the relationship in eight counties/independent cities in the northern Virginia, based on an integrated analysis of spatially explicit information on precipitation, land cover, infrastructure, and demographic data using Geographical Information Systems, remote sensing, and statistics. Results show that bird infections in years 2002-2003 were closely associated with low to medium level of impervious surface with certain percentage of canopy and precipitation. Environmental and socioeconomic factors such as percentages of impervious surface, canopy, senior population (65 and older), old houses, bird risk areas, and low-income population were important indicators of human WNV risk in 2002. Limited impervious surface with some canopy provides suitable habitats for WNV transmission, where bird-feeding mosquitoes can forage for blood meals from nesting/roosting birds. Certain socioeconomic conditions such as old houses were linked with human infections by providing favorable environmental conditions, i.e., mature trees with abundant canopy and settled storm sewer systems. It should be noted that the current results may be biased toward urban environments, where dead birds were more likely found, and because the sampling efforts for the bird mortality were rather based on local residents' reports than a designed random sampling method. This geospatial study contributes toward better targeting of WNV prevention within the study area. It also provides an example of how geospatial methods and variables may be used in understanding the ecology of human WNV risk for other areas.

Effects of latitude and longitude on the population structure of Culex pipiens s.l., vectors of West Nile virus in North America.

We assessed the structure and latitudinal selection that might result in sensitivities to critical day-lengths that trigger diapause between Culex pipiens populations distributed along North-South and East-West axes in eastern North America. Strong population structure between Cx. p. pipiens and Cx. p. quinquefasciatus existed. Among Cx. p. pipiens, a 100-km increase in the latitudinal change resulted in an increased square root of F(ST) by 0.002. A 100-km increase in the longitudinal change caused an increased square root of F(ST) by 0.035. A lack of latitudinal influence on the structure between Cx. p. pipiens populations suggests a uniform signal using the 12 microsatellite markers, which might increase the risk of West Nile virus (WNV) transmission toward northern areas because of longer breeding season, extend host-seeking period, and larger population size. Northern Cx. p. pipiens may have undergone additional generations before diapause is triggered, magnifying population size when WNV amplification is peaking.

Hepatopulmonary syndrome.

The hepatopulmonary syndrom occurs when pulmonary microvacular dilatation causes hypoxemia in cirrhosis. It is found in between 15-20% of patients with chronic liver diseases and should be considered in the differential diagnosis of dyspnea or abnormal arterial oxygenation in this group. The presence of HPS appears to significantly increase mortality in affected patients with cirrhosis. The mediators of intrapulmonary vasodilatation and HPS are not fully characterized although pulmonary nitric oxide overproduction appears to be a key event in human and experimental models. Contrast echocardiography is the best screening test for pulmonary vasodilatation. Currently there are no effective medical therapies for HPS, although liver transplantation results in reversal of HPS in most cases. However, mortality is higher in patients with HPS undergoing transplantation relative to those without HPS.