Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 157 Records) |
Query Trace: Paddock C [original query] |
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Rickettsia species identified in adult, host-seeking Dermacentor occidentalis (Acari: Ixodidae) from Baja California, Mexico, and Oregon and Washington, United States
Paddock CD . J Med Entomol 2024 The Pacific Coast tick (Dermacentor occidentalis Marx, 1892) is a frequently encountered and commonly reported human-biting tick species that has been recorded from most of California and parts of southwestern Oregon, southcentral Washington, and northwestern Mexico. Although previous investigators have surveyed populations of D. occidentalis for the presence of Rickettsia species across several regions of California, populations of this tick have not been surveyed heretofore for rickettsiae from Baja California, Oregon, or Washington. We evaluated 1,367 host-seeking, D. occidentalis adults collected from 2015 to 2022 by flagging vegetation at multiple sites in Baja California, Mexico, and Oregon and Washington, United States, using genus- and species-specific assays for spotted fever group rickettsiae. DNA of Rickettsia 364D, R. bellii, and R. tillamookensis was not detected in specimens from these regions. DNA of R. rhipicephali was detected in D. occidentalis specimens obtained from Ensenada Municipality in Baja California and southwestern Oregon, but not from Washington. All ompA sequences of R. rhipichephali that were amplified from individual ticks in southwestern Oregon were represented by a single genotype. DNA of the Ixodes pacificus rickettsial endosymbiont was amplified from specimens collected in southwestern Oregon and Klickitat County, Washington; to the best of our knowledge, this Rickettsia species has never been identified in D. occidentalis. Collectively, these data are consistent with a relatively recent introduction of Pacific Coast ticks in the northernmost extension of its recognized range. |
The Brief Case: A traveler's tale-imported scrub typhus in a child returning from Bangladesh
Sultana R , Tiwari M , Gleaton AN , Ramos CJ , Paddock CD , Bianchi-Hayes J , Handel AS . J Clin Microbiol 2023 61 (12) |
Pathology and monkeypox virus localization in tissues from immunocompromised patients with severe or fatal mpox
Ritter JM , Martines RB , Bhatnagar J , Rao AK , Villalba JA , Silva-Flannery L , Lee E , Bullock HA , Hutson CL , Cederroth T , Harris CK , Hord K , Xu Y , Brown CA , Guccione JP , Miller M , Paddock CD , Reagan-Steiner S . J Infect Dis 2024 BACKGROUND: Pathology and monkeypox virus (MPXV) tissue tropism in severe and fatal human mpox is not thoroughly described but can help elucidate the disease pathogenesis and the role of coinfections in immunocompromised patients. METHODS: We analyzed biopsy and autopsy tissues from 22 patients with severe or fatal outcomes to characterize pathology and viral antigen and DNA distribution in tissues by immunohistochemistry and in situ hybridization. Tissue-based testing for coinfections was also performed. RESULTS: Mucocutaneous lesions showed necrotizing and proliferative epithelial changes. Deceased patients with autopsy tissues evaluated had digestive tract lesions, and half had systemic tissue necrosis with thrombotic vasculopathy in lymphoid tissues, lung, or other solid organs. Half also had bronchopneumonia, and one-third had acute lung injury. All cases had MPXV antigen and DNA detected in tissues. Coinfections were identified in 5/16 (31%) biopsy and 4/6 (67%) autopsy cases. DISCUSSION: Severe mpox in immunocompromised patients is characterized by extensive viral infection of tissues and viremic dissemination that can progress despite available therapeutics. Digestive tract and lung involvement are common and associated with prominent histopathological and clinical manifestations. Coinfections may complicate mpox diagnosis and treatment. Significant viral DNA (likely correlating to infectious virus) in tissues necessitates enhanced biosafety measures in healthcare and autopsy settings. |
Rickettsia tillamookensis (Rickettsiales: Rickettsiaceae) in Ixodes scapularis (Acari: Ixodidae) in Oklahoma
Noden BH , Gilliland M , Propst J , Slater K , Karpathy SE , Paddock CD . J Med Entomol 2023 Some of the most prevalent arthropod-borne pathogens impacting humans in the United States are transmitted by Ixodes ticks. However, little is known regarding the Rickettsia species that inhabit Ixodes scapularis in the United States. The aim of this study was to screen adult I. scapularis collected in central Oklahoma over an 8-yr period for the presence of tick-borne rickettsial pathogens or potential pathogens. During 2014-2021, 112 adult specimens of I. scapularis were collected from central Oklahoma. Amplicons for Rickettsia spp. were amplified from 53 (47.3%) of the samples. Of the positive ticks, 42 (79.2%) amplicon-positive Rickettsia samples were 100% identical to Rickettsia buchneri, 10 (18.9%) were 100% identical to R. tillamookensis strain Tillamook 23, and 1 (1.9%) specimen showed high identity for Rickettsia amblyommatis. This study highlights the importance of considering Rickettsia-specific assays when assessing Ixodes species ticks for potential pathogens. |
Redescription of the larval stage of Dermacentor parumapertus Neumann (Acari: Ixodidae), with notes on hosts
Goddard J , Baker GT , Paddock CD , Smith TC , Robbins RG . Syst Appl Acarol 2023 28 (8) 1297-1304 The larva of the ixodid tick Dermacentor parumapertus Neumann, chiefly a parasite of hares and rabbits, is redescribed using scanning electron micrographs of seven specimens derived from two engorged females collected from two black-tailed jackrabbits, Lepus californicus, at the Black Gap Wildlife Management Area, Brewster County, southwestern Texas. The use of chaetotaxy for separating the genera of Ixodidae is discussed, and a morphological key is provided for separating the larvae of D. parumapertus from those of five other Dermacentor species with partly sympatric geographic ranges. © 2023 Systematic and Applied Acarology Society. All rights reserved. |
Anaplasma bovis-Like Infections in humans, United States, 2015-2017
Karpathy SE , Kingry L , Pritt BS , Berry JC , Chilton NB , Dergousoff SJ , Cortinas R , Sheldon SW , Oatman S , Anacker M , Petersen J , Paddock CD . Emerg Infect Dis 2023 29 (9) 1904-1907 We detected the DNA of an Anaplasma bovis-like bacterium in blood specimens from 4 patients from the United States with suspected tickborne illnesses. Initial molecular characterization of this novel agent reveals identity to A. bovis-like bacteria detected in Dermacentor variabilis ticks collected from multiple US states. |
Corrigendum: Characterization of a novel transitional group Rickettsia species (Rickettsia tillamookensis sp. nov.) from the western black-legged tick, Ixodes pacificus
Gauthier DT , Karpathy SE , Grizzard SL , Batra D , Rowe LA , Paddock CD . Int J Syst Evol Microbiol 2023 73 (8) In the published version of this article there was an error with the sequence data. Please see the corrected text below: | | | In the abstract | | Upon reanalysis with corrected 16S rRNA sequence, the closest full-length match to non-genome strains in Genbank at the time of this corrigendum was to ‘Candidatus Rickettsia senegalensis’ strain R184 (Genbank accession number OM311169) at 99.7 % identity. | | | In table 1 | | The 16S rRNA column analysis was performed with the chimeric 16S rRNA sequence and is thus in error. The top non-genome strain match and identity is as described for changes to the Abstract. The best match to a complete genome was to R. felis URRWXCal2 (Genbank CP000053) at 99.8 % identity. | | | In phylogeny | | 16S rRNA comparisons are in error and are corrected as for Abstract and Table 1. | | In summary, we have, through antibiotic clearance of Mycoplasma contamination of R. tillamookensis Tillamook 23T, ascertained that corrections need to be made to the published genome record for 16S and 23S rRNA sequences. Genbank records have been updated accordingly. These changes do not affect the status of R. tillamookensis as a distinct species or its phylogenetic placement among the transitional group of Rickettsia. | | The authors have provided a detailed explanation of this correction in the Supplementary File 1. | | The authors apologise for any inconvenience caused. | |
Feasibility of visualizing cancer incidence data at sub-county level: Findings from 21 National Program of Cancer Registries
Ellington TD , Werner AK , Henley SJ , Paddock LE , Agovino PK . Spat Spatiotemporal Epidemiol 2023 45 100564 Monitoring cancer incidence data by geography is useful for planning public health activities. However, due to anticipated confidentiality and statistical reliability issues, data on cancer incidence and mortality are more often displayed at a national, state, or county level, rather than at more local levels. To address this gap in displaying cancer data at the local level, the CDC's National Environmental Public Health Tracking Program and 21 National Program of Cancer Registries worked together on a pilot project to examine the feasibility of displaying sub-county-level incidence of selected cancer types diagnosed during 2007-2016. The results from this project are important steps for building sub-county cancer displays into data visualizations and using the data in a way that provides meaningful insights. The availability of sub-county cancer data may allow researchers to better examine cancer data at a local level which may help guide public health decisions regarding community-based interventions and screening services. |
Neuroinvasive Onchocerca lupi infection in a ten-year-old girl
Bowers Wu D , Ko B , Lopez Hernandez G , Botros J , Spader H , Sapp S , Qvarnstrom Y , Paddock CD , Cantey PT , Dehority W . Case Rep Infect Dis 2022 2022 9773058 The nematode Onchocerca lupi is an emerging human pathogen. Though its life cycle is not well studied, it likely infects humans after a bite from a black fly vector, which in turn acquires infective microfilariae from an infected canid. These microfilariae mature into an infective larval stage within the fly. Among six reported cases in the United States, five involved children, and all occurred in the southwest. In this report, we present a case of O. lupi infection with cervical spine invasion in a healthy 10-year-old girl. She presented with five months of neurological symptoms from a rural and medically underserved area, highlighting a need for clinical vigilance in such settings for this emerging infectious threat in the American southwest. |
A forty-year review of Rocky Mountain spotted fever cases in California shows clinical and epidemiologic changes
Kjemtrup AM , Padgett K , Paddock CD , Messenger S , Hacker JK , Feiszli T , Melgar M , Metzger ME , Hu R , Kramer VL . PLoS Negl Trop Dis 2022 16 (9) e0010738 Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease documented in North, Central, and South America. In California, RMSF is rare; nonetheless, recent fatal cases highlight ecological cycles of the two genera of ticks, Dermacentor and Rhipicephalus, known to transmit the disease. These ticks occur in completely different habitats (sylvatic and peridomestic, respectively) resulting in different exposure risks for humans. This study summarizes the demographic, exposure, and clinical aspects associated with the last 40 years of reported RMSF cases to the California Department of Public Health (CDPH). Seventy-eight RMSF cases with onsets from 1980 to 2019 were reviewed. The incidence of RMSF has risen in the last 20 years from 0.04 cases per million to 0.07 cases per million (a two-fold increase in reports), though the percentage of cases that were confirmed dropped significantly from 72% to 25% of all reported cases. Notably, Hispanic/Latino populations saw the greatest rise in incidence. Cases of RMSF in California result from autochthonous and out-of-state exposures. During the last 20 years, more cases reported exposure in Southern California or Mexico than in the previous 20 years. The driver of these epidemiologic changes is likely the establishment and expansion of Rhipicephalus sanguineus sensu lato ticks in Southern California and on-going outbreaks of RMSF in northern Mexico. Analysis of available electronically reported clinical data from 2011 to 2019 showed that 57% of reported cases presented with serious illness requiring hospitalization with a 7% mortality. The difficulty in recognizing RMSF is due to a non-specific clinical presentation; however, querying patients on the potential of tick exposure in both sylvatic and peridomestic environments may facilitate appropriate testing and treatment. |
Predicting the northward expansion of tropical lineage Rhipicephalus sanguineus sensu lato ticks in the United States and its implications for medical and veterinary health.
Pascoe EL , Nava S , Labruna MB , Paddock CD , Levin ML , Marcantonio M , Foley JE . PLoS One 2022 17 (8) e0271683 The tropical lineage within the Rhipicephalus sanguineus species complex is cause for growing concern in the U.S. based on its prominent role in creating and perpetuating multiple recently identified outbreaks of Rocky Mountain spotted fever in the southwestern United States and northern Mexico. This lineage is undergoing a northward range expansion in the United States, necessitating the need for enhanced surveillance for Rh. sanguineus. To inform more focused surveillance efforts we use species distribution models (SDMs) to predict current (2015-2019) and future (2021-2040) habitat for the tropical lineage. Models using the MaxEnt algorithm were informed using geolocations of ticks genetically confirmed to be of the tropical lineage, for which data on 23 climatic and ecological variables were extracted. Models predicted that suitability was optimal where temperatures are relatively warm and stable, and there is minimal precipitation. This translated into habitat being predicted along much of the coast of southern states including California, Texas, Louisiana, and Florida. Although the endophilic nature of tropical Rh. sanguineus somewhat violates the assumptions of SDMs, our models correctly predicted known locations of this tick and provide a starting point for increased surveillance efforts. Furthermore, we highlight the importance of using molecular methods to distinguish between ticks in the Rh. sanguineus species complex. |
A 21st century appraisal of Whipple's Disease and Tropheryma whipplei
Paddock CD , Fenollar F , Lagier JC , Raoult D . Clin Microbiol Newsl 2022 44 (14) 123-129 Whipple's disease was formally described more than 100 years ago; nonetheless, only recently have investigators identified, cultivated, and characterized the causative agent, Tropheryma whipplei, and deciphered some of its complex associations with human hosts. The acquisition of knowledge about T. whipplei, a Gram-positive bacterium in the class Actinobacteria, accelerated at an extraordinarily rapid pace during the first two decades of the 21st century, to include the recognition of asymptomatic carriage, localized disease, and acute infections caused by this peculiar bacterium. This review discusses current knowledge of the microbiology and epidemiology of T. whipplei, the expanding clinical spectrum of disease caused by the pathogen, its treatment, and historical and diagnostic assays that facilitate the diagnosis of the various diseases caused by this enigmatic bacterium. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. 2022 Elsevier Inc. |
Detection and isolation of rickettsia tillamookensis (rickettsiales: Rickettsiaceae) from ixodes pacificus (acari: Ixodidae) from multiple regions of California
Paddock CD , Slater K , Swei A , Zambrano ML , Kleinjan JE , Padgett KA , Saunders MEM , Andrews ES , Trent E , Zhong J , Sambado S , Goldsmith CS , Pascoe EL , Foley J , Lane RS , Karpathy SE . J Med Entomol 2022 59 (4) 1404-1412 The western black-legged tick (Ixodes pacificus) is the most frequently identified human-biting tick species in the western United States and the principal vector of at least three recognized bacterial pathogens of humans. A potentially pathogenic Rickettsia species, first described in 1978 and recently characterized as a novel transitional group agent designated as Rickettsia tillamookensis, also exists among populations of I. pacificus, although the distribution and frequency of this agent are poorly known. We evaluated DNA extracts from 348 host-seeking I. pacificus nymphs collected from 9 locations in five California counties, and from 916 I. pacificus adults collected from 24 locations in 13 counties, by using a real-time PCR designed specifically to detect DNA of R. tillamookensis. DNA of R. tillamookensis was detected in 10 (2.9%) nymphs (95% CI: 1.6-5.2%) and 17 (1.9%) adults (95% CI: 1.2-3.0%) from 11 counties of northern California. Although site-specific infection rates varied greatly, frequencies of infection remained consistently low when aggregated by stage, sex, habitat type, or geographical region. Four novel isolates of R. tillamookensis were cultivated in Vero E6 cells from individual adult ticks collected from Alameda, Nevada, and Yolo counties. Four historical isolates, serotyped previously as 'Tillamook-like' strains over 40 yr ago, were revived from long-term storage in liquid nitrogen and confirmed subsequently by molecular methods as isolates of R. tillamookensis. The potential public health impact of R. tillamookensis requires further investigation. |
Autopsy Histopathologic Cardiac Findings in Two Adolescents Following the Second COVID-19 Vaccine Dose.
Paddock CD , Reagan-Steiner S , Su JR , Oster ME , Martines RB , Bhatnagar J , Shimabukuro TT . Arch Pathol Lab Med 2022 146 (8) 921-923 To the Editor.We read with concern the manuscript by Gill et al1 that described autopsy findings for 2 adolescents who died after COVID-19 vaccination. The authors correctly stated that the Centers for Disease Control and Prevention (CDC) performed testing for SARS-CoV-2 and found no evidence of SARS-CoV-2 infection in autopsy tissues from the decedents. However, the authors did not include findings from far more thorough immunohistochemical and molecular testing performed by the CDC for each patient. We believe that all of the CDC's findings should be considered carefully, and that the omission of these data has important implications for the conclusions of this paper. |
Association between growth rate and pathogenicity of spotted fever group Rickettsia
Bourchookarn A , Paddock CD , Macaluso KR , Bourchookarn W . J Pure Appl Microbiol 2022 16 (1) 374-383 Rickettsia parkeri and Rickettsia amblyommatis are spotted fever group Rickettsia (SFGR) associated with Amblyomma ticks. R. parkeri is a recognized human pathogen that causes an eschar-associated febrile illness, while R. amblyommatis has not been confirmed as a causative agent of human disease. We hypothesized that the rate of replication is one of the factors contributing to rickettsial pathogenicity. In this study, growth and infectivity of R. parkeri and R. amblyommatis in mammalian (Vero E6) and tick-derived (ISE6) cell lines were assessed and compared over a 96-hour time course of infection using quantitative real-time polymerase chain reaction and microscopy. The pathogenic R. parkeri displayed a significantly higher level of infection in both Vero E6 and ISE6 cells than R. amblyommatis at 72 hours post-inoculation (hpi). Distinct growth profiles between rickettsial species with known and uncertain pathogenicity were identified. R. parkeri burdens were significantly greater than those of R. amblyommatis from 24 to 96 hpi. The relative fold changes of load were significantly higher in the pathogenic agent than in R. amblyommatis from 48 hpi onward and reached the maximum fold increase of 2002- and 296-fold in Vero E6 cells and 1363- and 161-fold in ISE6 cells, respectively, at 96 hpi. The results from the present study demonstrate that growth rate is associated with the pathogenicity of rickettsiae. Understanding SFGR growth characteristics in mammalian and tick cells will provide insight into rickettsial biology and pathogenesis. The Author(s) 2022. |
Rickettsiosis subcommittee report to the tick-borne disease working group.
Walker DH , Myers CTE , Blanton LS , Bloch KC , Fowler VG Jr , Gaines DN , Paddock CD , Yaglom HD . Ticks Tick Borne Dis 2021 13 (1) 101855 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. |
Complete Genome Sequence of Rickettsia parkeri Strain Black Gap.
Karpathy SE , Paddock CD , Grizzard SL , Batra D , Rowe LA , Gauthier DT . Microbiol Resour Announc 2021 10 (44) e0062321 A unique genotype of Rickettsia parkeri, designated R. parkeri strain Black Gap, has thus far been associated exclusively with the North American tick, Dermacentor parumapertus. The compete genome consists of a single circular chromosome with 1,329,522 bp and a G+C content of 32.5%. |
Phylogenetic Differentiation of Rickettsia parkeri Reveals Broad Dispersal and Distinct Clustering within North American Strains.
Allerdice MEJ , Paddock CD , Hecht JA , Goddard J , Karpathy SE . Microbiol Spectr 2021 9 (2) e0141721 The tick-borne pathogen Rickettsia parkeri causes a mild rickettsiosis, with cases reported from several countries to its known distribution in the Americas. Molecular analyses have identified a clear distinction between strains of R. parkeri sensu stricto (s. s.) and R. parkeri sensu lato (s. l.) as well as separation between North American and South American R. parkeri s. s. strains. To expand on this previous work, we developed a multilocus sequence typing analysis with two aims: first, to investigate the genetic diversity within strains of North American R. parkeri s. s., and second, to further the understanding of the genetic relationships between R. parkeri s. s. and R. parkeri s. l. Sixty-four R. parkeri isolates and 12 R. parkeri-positive tick lysates were analyzed using a novel typing scheme consisting of four coding regions and two intergenic regions. A concatenated Bayesian phylogeny that identified eight clades was constructed: three represent the R. parkeri s. l. strains, and five represent the R. parkeri s. s. strains. The clades appear to be generally phylogeographically organized and associated with specific tick vectors. However, while one of the four R. parkeri s. s. North American clades appears to be limited to the southwestern United States, the other North American clades exhibit broad dispersal, most notably seen in the largest group, which includes representative samples extending from northern Mexico to Delaware. This work highlights the increasingly recognized geographic range of R. parkeri in the Americas and suggests a potential public health risk for these areas. IMPORTANCE Since 1937, when Rickettsia parkeri was originally identified in Amblyomma maculatum group ticks, the recognized range and associated vectors for this pathogen have expanded significantly. In recent years, R. parkeri has been identified in 12 tick species from seven countries in the Americas. Herein, we provide evidence that the greatest genetic diversity within R. parkeri exists in North America, where one R. parkeri sensu lato and four R. parkeri sensu stricto genotypes are present. While one distinct R. parkeri sensu stricto genotype exists only in the southwestern United States, three genotypes are broadly distributed in the eastern United States, with the largest of these found across the known range of R. parkeri in North America. In contrast, the South American R. parkeri sensu stricto samples represent a single genotype and are completely clonal at the loci analyzed, irrespective of their country of origin. |
Characterization of a novel transitional group Rickettsia species (Rickettsia tillamookensis sp. nov.) from the western black-legged tick, Ixodes pacificus.
Gauthier DT , Karpathy SE , Grizzard SL , Batra D , Rowe LA , Paddock CD . Int J Syst Evol Microbiol 2021 71 (7) A previously unrecognized Rickettsia species was isolated in 1976 from a pool of Ixodes pacificus ticks collected in 1967 from Tillamook County, Oregon, USA. The isolate produced low fever and mild scrotal oedema following intraperitoneal injection into male guinea pigs (Cavia porcellus). Subsequent serotyping characterized this isolate as distinct from recognized typhus and spotted fever group Rickettsia species; nonetheless, the isolate remained unevaluated by molecular techniques and was not identified to species level for the subsequent 30 years. Ixodes pacificus is the most frequently identified human-biting tick in the western United States, and as such, formal identification and characterization of this potentially pathogenic Rickettsia species is warranted. Whole-genome sequencing of the Tillamook isolate revealed a genome 1.43 Mbp in size with 32.4 mol% G+C content. Maximum-likelihood phylogeny of core proteins places it in the transitional group of Rickettsia basal to both Rickettsia felis and Rickettsia asembonensis. It is distinct from existing named species, with maximum average nucleotide identity of 95.1% to R. asembonensis and maximum digital DNA-DNA hybridization score similarity to R. felis at 80.1%. The closest similarity at the 16S rRNA gene (97.9%) and sca4 (97.5%/97.6% respectively) is to Candidatus 'Rickettsia senegalensis' and Rickettsia sp. cf9, both isolated from cat fleas (Ctenocephalides felis). We characterized growth at various temperatures and in multiple cell lines. The Tillamook isolate grows aerobically in Vero E6, RF/6A and DH82 cells, and growth is rapid at 28 °C and 32 °C. Using accepted genomic criteria, we propose the name Rickettsia tillamookensis sp. nov., with the type strain Tillamook 23. Strain Tillamook 23 is available from the Centers for Disease Control and Prevention Rickettsial Isolate Reference Collection (WDCM 1093), Atlanta, GA, USA (CRIRC accession number RTI001(T)) and the Collection de Souches de l'Unité des Rickettsies (WDCM 875), Marseille, France (CSUR accession number R5043). Using accepted genomic criteria, we propose the name Rickettsia tillamookensis sp. nov., with the type strain Tillamook 23 (=CRIRC RTI001=R5043). |
Intersecting Paths of Emerging and Reemerging Infectious Diseases.
Wilson TM , Paddock CD , Reagan-Steiner S , Bhatnagar J , Martines RB , Wiens AL , Madsen M , Komatsu KK , Venkat H , Zaki SR . Emerg Infect Dis 2021 27 (5) 1517-1519 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shares common clinicopathologic features with other severe pulmonary illnesses. Hantavirus pulmonary syndrome was diagnosed in 2 patients in Arizona, USA, suspected of dying from infection with SARS-CoV-2. Differential diagnoses and possible co-infections should be considered for cases of respiratory distress during the SARS-CoV-2 pandemic. |
Rocky Mountain Spotted Fever in a Large Metropolitan Center, Mexico-United States Border, 2009-2019
Zazueta OE , Armstrong PA , Márquez-Elguea A , Hernández Milán NS , Peterson AE , Ovalle-Marroquín DF , Fierro M , Arroyo-Machado R , Rodriguez-Lomeli M , Trejo-Dozal G , Paddock CD . Emerg Infect Dis 2021 27 (6) 1567-76 Epidemic levels of Rocky Mountain spotted fe---ver (RMSF) have persisted in Mexicali, Mexico, since the initial outbreak was first reported in December 2008. We compared clinical and epidemiologic data of cases in Mexicali during 2009-2019 between patients with an IgG titer reactive with Rickettsia rickettsii bacteria by indirect immunofluorescence antibody (IFA) assay and those who demonstrated DNA of R. rickettsii in a whole blood sample when tested by PCR. We identified 4,290 patients with clinical and epidemiologic features compatible with RMSF; of these, 9.74% tested positive by IFA and 8.41% by PCR. Overall, 140 patients died (11-year case-fatality rate 17.97%). Substantial differences in the frequency of commonly recognized clinical characteristics of RMSF were identified between PCR-positive and IFA-positive cases. The Mexicali epidemic is unique in its size and urban centralization. Cases confirmed by PCR most accurately reflect the clinical profile of RMSF. | Longevity, high prevalence, and multifocal distribution of this disease pose unprecedented public health challenges. | eng |
Multi-Locus Sequence Typing of Ehrlichia chaffeensis Reveals Extensive Genotypic Variation across the United States.
Zambrano ML , Paddock CD , Karpathy SE . Am J Trop Med Hyg 2021 104 (4) 1297-304 Ehrlichia chaffeensis causes human monocytic ehrlichiosis, and its principal vector is the Amblyomma americanum tick. The most frequently identified cases of ehrlichiosis come from the southeastern and south central states of the United States. In this study, a molecular typing system was developed that allows for the genetic differentiation of E. chaffeensis isolates. This multi-locus typing system included sequencing and analyzing intergenic regions ECH0033-ECH0035 and ECH0217-ECH0218, plus, variable genes variable length PCR target, 28-kDa, 120-kDa, and hemE. We examined a total of 31 unique isolates from humans and white-tailed deer, and eight DNA samples extracted from infected A. americanum collected from multiple states. This is the largest evaluation of E. chaffeensis isolates and their genotypes. Our findings show that when sequences of all six loci were concatenated and compared, the 39 samples could be separated into 23 genotypes and further grouped into six phylogenetic clades. The data in this study show no clear pattern between the geographic alignment with the genetic differentiation between the strains. As a result, this poses a challenge to understanding the spread of E. chaffeensis in the United States. Interestingly, our findings indicate that multiple strains from distant geographic origins share the same mutations, which suggests that the strains are being moved from one site to another by their hosts or vectors. In addition, we are seeing a northward shift in the lone star tick distribution in the United States. Last, some data also suggest minimal genetic mutations have occurred over time among strains that are within geographical proximity. |
Significant growth by Rickettsia species within human macrophage-like cells is a phenotype correlated with the ability to cause disease in mammals
Kristof MN , Allen PE , Yutzy LD , Thibodaux B , Paddock CD , Martinez JJ . Pathogens 2021 10 (2) Rickettsia are significant sources of tick-borne diseases in humans worldwide. In North America, two species in the spotted fever group of Rickettsia have been conclusively associated with disease of humans: Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, and Rickettsia parkeri, the cause of R. parkeri rickettsiosis. Previous work in our lab demonstrated non-endothelial parasitism by another pathogenic SFG Rickettsia species, Rickettsia conorii, within THP-1-derived macrophages, and we have hypothesized that this growth characteristic may be an underappreciated aspect of rickettsial pathogenesis in mammalian hosts. In this work, we demonstrated that multiple other recognized human pathogenic species of Rickettsia, including R. rickettsii, R. parkeri, Rickettsia africae, and Rickettsiaakari can grow within target endothelial cells as well as within PMA-differentiated THP-1 cells. In contrast, Rickettsia bellii, a Rickettsia species not associated with disease of humans, and R. rickettsii strain Iowa, an avirulent derivative of pathogenic R. rickettsii, could invade both cell types but proliferate only within endothelial cells. Further analysis revealed that similar to previous studies on R. conorii, other recognized pathogenic Rickettsia species could grow within the cytosol of THP-1-derived macrophages and avoided localization with two different markers of lysosomal compartments; LAMP-2 and cathepsin D. R. bellii, on the other hand, demonstrated significant co-localization with lysosomal compartments. Collectively, these findings suggest that the ability of pathogenic rickettsial species to establish a niche within macrophage-like cells could be an important factor in their ability to cause disease in mammals. These findings also suggest that analysis of growth within mammalian phagocytic cells may be useful to predict the pathogenic potential of newly isolated and identified Rickettsia species. |
Rickettsia honei infection in a traveler returning from India
Denison AM , Leitgeb B , Obadiah JM , Schwindt A , Ladd-Wilson SG , Paddock CD , Matkovic E . Open Forum Infect Dis 2021 8 (2) ofaa636 We report a case of Rickettsia honei infection in a US tourist returning from India and the Himalayas. This case highlights a need for awareness of various Rickettsia species endemic to India and the importance for physicians to consider rickettsial diseases in returning travelers with eschar or rash-associated febrile illnesses. |
Evidence of SARS-CoV-2 Replication and Tropism in the Lungs, Airways and Vascular Endothelium of Patients with Fatal COVID-19: An Autopsy Case-Series.
Bhatnagar J , Gary J , Reagan-Steiner S , Estetter LB , Tong S , Tao Y , Denison AM , Lee E , DeLeon-Carnes M , Li Y , Uehara A , Paden CR , Leitgeb B , Uyeki TM , Martines RB , Ritter JM , Paddock CD , Shieh WJ , Zaki SR . J Infect Dis 2021 223 (5) 752-764 BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of SARS-CoV-2 tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case-patients (age range: 1 month to 84 years; COVID-19 confirmed n=21, suspected n=43) by SARS-CoV-2 RT-PCR. For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in-situ hybridization (ISH), subgenomic RNA RT-PCR, and whole genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case-patients (confirmed n=21 and suspected n=11). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case-patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes and macrophages of lungs, epithelial cells of airways, and in endothelial cells and vessels wall of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. D614G variant was detected in 9 RT-PCR-positive case-patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes. |
A new genetic approach to distinguish strains of Anaplasma phagocytophilum that appear not to cause human disease.
Liveris D , Aguero-Rosenfeld ME , Daniels TJ , Karpathy S , Paddock C , Adish S , Keesing F , Ostfeld RS , Wormser GP , Schwartz I . Ticks Tick Borne Dis 2021 12 (3) 101659 Genetic diversity of Anaplasma phagocytophilum was assessed in specimens from 16 infected patients and 16 infected Ixodes scapularis ticks. A region immediately downstream of the 16S rRNA gene, which included the gene encoding SdhC, was sequenced. For the A. phagocytophilum strains from patients no sequence differences were detected in this region. In contrast, significantly fewer ticks had a sequence encoding SdhC that was identical to that of the human strains (11/16 vs. 16/16, p = 0.04). This variation is consistent with the premise that not all A. phagocytophilum strains present in nature are able to cause clinical illness in humans. A strain referred to as A. phagocytophilumVariant-1 that is regarded as non-pathogenic for humans was previously described using a different typing method. Data from the current study suggest that both typing methods are identifying the same non-pathogenic strains. |
Isolate-dependent differences in clinical, pathological, and transcriptional profiles following in vitro and in vivo infections with Rickettsia rickettsii .
Galletti MFBM , Paddock CD , Hecht JA , Biggerstaff BJ , Ritter JM , Karpathy SE . Infect Immun 2021 89 (4) Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever (RMSF), a life-threatening tick-borne disease that affects humans and various animal species, has been recognized in medicine and science for more than 100 years. Isolate-dependent differences in virulence of R. rickettsii have been documented for many decades; nonetheless, the specific genetic and phenotypic factors responsible for these differences have not been characterized. Using in vivo and in vitro methods, we identified multiple phenotypic differences among six geographically distinct isolates of R. rickettsii, representing isolates from the United States, Costa Rica, and Brazil. Aggregate phenotypic data, derived from growth in Vero E6 cells and from clinical and pathological characteristics following infection of male guinea pigs (Cavia porcellus), allowed separation of these isolates into three categories: non-virulent (Iowa); mildly virulent (Sawtooth and Gila), and highly virulent (Sheila Smith(T), Costa Rica, and Taiaçu). Transcriptional profiles of 11 recognized or putative virulence factors confirmed the isolate-dependent differences between a mildly and a highly virulent isolate. These data corroborate previous qualitative assessments of strain virulence and suggest further that a critical and previously underappreciated balance between bacterial growth and host immune response could leverage strain pathogenicity. Also, this work provide insight into isolate-specific microbiological factors that contribute to the outcome of RMSF and confirms the hypothesis that distinct rickettsial isolates also differ phenotypically, which could influence the severity of disease in vertebrate hosts. |
Established population of the Gulf Coast tick, Amblyomma maculatum (Acari: Ixodidae), infected with Rickettsia parkeri (Rickettsiales: Rickettsiaceae), in Connecticut
Molaei G , Little EAH , Khalil N , Ayres BN , Nicholson WL , Paddock CD . J Med Entomol 2021 58 (3) 1459-1462 We identified an established population of the Gulf Coast tick (Amblyomma maculatum Koch) infected with Rickettsia parkeri in Connecticut, representing the northernmost range limit of this medically relevant tick species. Our finding highlights the importance of tick surveillance and public health challenges posed by geographic expansion of tick vectors and their pathogens. |
Reproductive incompatibility between Amblyomma maculatum (Acari: Ixodidae) group ticks from two disjunct geographical regions within the USA.
Allerdice MEJ , Snellgrove AN , Hecht JA , Hartzer K , Jones ES , Biggerstaff BJ , Ford SL , Karpathy SE , Delgado-de la Mora J , Delgado-de la Mora D , Licona-Enriquez JD , Goddard J , Levin ML , Paddock CD . Exp Appl Acarol 2020 82 (4) 543-557 The Amblyomma maculatum Koch group of ixodid ticks consists of three species: A. maculatum, A. triste, and A. tigrinum. However, since Koch described this group in 1844, the systematics of its members has been the subject of ongoing debate. This is especially true of A. maculatum and A. triste; recent molecular analyses reveal insufficient genetic divergence to separate these as distinct species. Further confounding this issue is the discovery in 2014 of A. maculatum group ticks in southern Arizona (AZ), USA, that share morphological characteristics with both A. triste and A. maculatum. To biologically evaluate the identity of A. maculatum group ticks from southern Arizona, we analyzed the reproductive compatibility between specimens of A. maculatum group ticks collected from Georgia (GA), USA, and southern Arizona. Female ticks from both Arizona and Georgia were mated with males from both the Georgia and Arizona Amblyomma populations, creating two homologous and two heterologous F1 cohorts of ticks: GA ♀/GA ♂, AZ ♀/AZ ♂, GA ♀/AZ ♂, and AZ ♀/GA ♂. Each cohort was maintained separately into the F2 generation with F1 females mating only with F1 males from their same cohort. Survival and fecundity parameters were measured for all developmental stages. The observed survival parameters for heterologous cohorts were comparable to those of the homologous cohorts through the F1 generation. However, the F1 heterologous females produced F2 egg clutches that did not hatch, thus indicating that the Arizona and Georgia populations of A. maculatum group ticks tested here represent different biological species. |
Integrating population genetic structure, microbiome, and pathogens presence data in Dermacentor variabilis .
Lado P , Luan B , Allerdice MEJ , Paddock CD , Karpathy SE , Klompen H . PeerJ 2020 8 e9367 Tick-borne diseases (TBDs) continue to emerge and re-emerge in several regions of the world, highlighting the need for novel and effective control strategies. The development of effective strategies requires a better understanding of TBDs ecology, and given the complexity of these systems, interdisciplinary approaches are required. In recent years, the microbiome of vectors has received much attention, mainly because associations between native microbes and pathogens may provide a new promising path towards the disruption of pathogen transmission. However, we still do not fully understand how host genetics and environmental factors interact to shape the microbiome of organisms, or how pathogenic microorganisms affect the microbiome and vice versa. The integration of different lines of evidence may be the key to improve our understanding of TBDs ecology. In that context, we generated microbiome and pathogen presence data for Dermacentor variabilis, and integrated those data sets with population genetic data, and metadata for the same individual tick specimens. Clustering and multivariate statistical methods were used to combine, analyze, and visualize data sets. Interpretation of the results is challenging, likely due to the low levels of genetic diversity and the high abundance of a few taxa in the microbiome. Francisella was dominant in almost all ticks, regardless of geography or sex. Nevertheless, our results showed that, overall, ticks from different geographic regions differ in their microbiome composition. Additionally, DNA of Rickettsia rhipicephali, R. montanensis, R. bellii, and Anaplasma spp., was detected in D. variabilis specimens. This is the first study that successfully generated microbiome, population genetics, and pathogen presence data from the same individual ticks, and that attempted to combine the different lines of evidence. The approaches and pre-processing steps used can be applied to a variety of taxa, and help better understand ecological processes in biological systems. |
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