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1.
Trop Med Int Health ; 29(5): 365-376, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38480005

RESUMEN

BACKGROUND: In northern Tanzania, Q fever, spotted fever group (SFG) rickettsioses, and typhus group (TG) rickettsioses are common causes of febrile illness. We sought to describe the prevalence and risk factors for these zoonoses in a pastoralist community. METHODS: Febrile patients ≥2 years old presenting to Endulen Hospital in the Ngorongoro Conservation Area were enrolled from August 2016 through October 2017. Acute and convalescent blood samples were collected, and a questionnaire was administered. Sera were tested by immunofluorescent antibody (IFA) IgG assays using Coxiella burnetii (Phase II), Rickettsia africae, and Rickettsia typhi antigens. Serologic evidence of exposure was defined by an IFA titre ≥1:64; probable cases by an acute IFA titre ≥1:128; and confirmed cases by a ≥4-fold rise in titre between samples. Risk factors for exposure and acute case status were evaluated. RESULTS: Of 228 participants, 99 (43.4%) were male and the median (interquartile range) age was 27 (16-41) years. Among these, 117 (51.3%) had C. burnetii exposure, 74 (32.5%) had probable Q fever, 176 (77.2%) had SFG Rickettsia exposure, 134 (58.8%) had probable SFG rickettsioses, 11 (4.8%) had TG Rickettsia exposure, and 4 (1.8%) had probable TG rickettsioses. Of 146 participants with paired sera, 1 (0.5%) had confirmed Q fever, 8 (5.5%) had confirmed SFG rickettsioses, and none had confirmed TG rickettsioses. Livestock slaughter was associated with acute Q fever (adjusted odds ratio [OR] 2.54, 95% confidence interval [CI] 1.38-4.76) and sheep slaughter with SFG rickettsioses case (OR 4.63, 95% CI 1.08-23.50). DISCUSSION: Acute Q fever and SFG rickettsioses were detected in participants with febrile illness. Exposures to C. burnetii and to SFG Rickettsia were highly prevalent, and interactions with livestock were associated with increased odds of illness with both pathogens. Further characterisation of the burden and risks for these diseases is warranted.


Asunto(s)
Fiebre Q , Infecciones por Rickettsia , Rickettsiosis Exantemáticas , Humanos , Tanzanía/epidemiología , Fiebre Q/epidemiología , Masculino , Factores de Riesgo , Femenino , Adulto , Adolescente , Prevalencia , Rickettsiosis Exantemáticas/epidemiología , Rickettsiosis Exantemáticas/microbiología , Adulto Joven , Persona de Mediana Edad , Niño , Infecciones por Rickettsia/epidemiología , Infecciones por Rickettsia/microbiología , Animales , Rickettsia/inmunología , Rickettsia/aislamiento & purificación , Preescolar , Coxiella burnetii/inmunología , Anciano , Zoonosis/microbiología
2.
Ann Allergy Asthma Immunol ; 132(6): 759-764.e2, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38341029

RESUMEN

BACKGROUND: Alpha-gal syndrome (AGS) is an allergy to galactose-α-1,3-galactose (alpha-gal), a carbohydrate found in most mammals. Evidence indicates that AGS develops after a tick bite, and in the United States, AGS is most associated with bites from Amblyomma americanum (lone star tick); however, not all persons bitten by ticks develop clinical AGS. OBJECTIVE: To investigate intrinsic risk factors associated with the development of AGS. METHODS: We performed a case-control study among adults presenting for diagnosis or management of AGS at an allergy clinic in North Carolina during 2019 to 2020 and compared them with controls enrolled from 2 nearby internal medicine clinics. A questionnaire gathered epidemiologic and tick exposure data, and blood was obtained for alpha-gal-specific IgE and other testing. RESULTS: The 82 enrolled case patients and 191 controls did not differ significantly by age or sex. Case patients were more likely than controls to have A or O blood types (non B-antigen), have experienced childhood allergies, and have a family history of AGS and other food allergies. Case patients were also more likely to report experiencing long healing times for insect bites or stings and a family history of allergy to stinging or biting insects. CONCLUSION: This study suggested that intrinsic factors contribute to risk of developing AGS. Some traits are genetic, but common behaviors among households and family units likely also contribute. Identification of these risk factors can inform personal risk, aid health care providers in understanding susceptible populations, and contribute to ongoing understanding of AGS epidemiology.


Asunto(s)
Hipersensibilidad a los Alimentos , Mordeduras de Garrapatas , Humanos , Estudios de Casos y Controles , Femenino , Masculino , Factores de Riesgo , Persona de Mediana Edad , Adulto , Hipersensibilidad a los Alimentos/epidemiología , Mordeduras de Garrapatas/epidemiología , Mordeduras de Garrapatas/inmunología , Animales , Anciano , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , North Carolina/epidemiología , Amblyomma/inmunología , Adulto Joven , Adolescente
3.
Allergy ; 78(2): 477-487, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36178236

RESUMEN

BACKGROUND: Alpha-gal syndrome (AGS) is an IgE-mediated allergy to galactose-alpha-1,3-galactose. Clinical presentation ranges from hives to anaphylaxis; episodes typically occur 2-6 h after exposure to alpha-gal-containing products. In the United States, lone star tick bites are associated with the development of AGS. To characterize features of AGS, we evaluated a cohort of patients presenting for care at the University of North Carolina, focusing on symptoms, severity, and identifying features unique to specific alpha-gal-containing product exposures. METHODS: We performed a chart review and descriptive analysis of 100 randomly selected patients with AGS during 2010-2019. RESULTS: Median age at onset was 53 years, 56% were female, 95% reported White race, 86% reported a history of tick bite, and 75% met the criteria for anaphylaxis based on the involvement of ≥2 organ systems. Those reporting dairy reactions were significantly less likely to report isolated mucocutaneous symptoms (3% vs. 24%; ratio [95% CI]: 0.1 [0.1, 0.3]) than those who tolerated dairy, and were more likely to report gastrointestinal symptoms (79% vs. 59%; ratio [95% CI]: 1.3 [0.7, 2.6]), although this difference was not statistically significant. Dairy-tolerant patients demonstrated higher alpha-gal sIgE titers (as a percentage of total IgE) than dairy-reactive patients (GM 4.1 [95% CI: 2.7, 6.1] vs. GM 2.5 [95% CI: 1.3, 4.8], respectively; ratio -1.6 [95% CI: -1.0, 3.9]). CONCLUSION: While tick exposure is common in the southern United States, nearly all AGS patients reported a tick bite. Gastrointestinal symptoms were prominent among those reporting reactions to dairy. Anaphylaxis was common, underscoring the severity and need to raise awareness of AGS among patients and providers.


Asunto(s)
Anafilaxia , Hipersensibilidad a los Alimentos , Mordeduras de Garrapatas , Humanos , Femenino , Masculino , Anafilaxia/diagnóstico , Anafilaxia/epidemiología , Anafilaxia/etiología , Mordeduras de Garrapatas/complicaciones , Galactosa , Alérgenos , Inmunoglobulina E , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/complicaciones
4.
MMWR Morb Mortal Wkly Rep ; 72(30): 815-820, 2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37498787

RESUMEN

Alpha-gal syndrome (AGS) is an emerging, tick bite-associated allergic condition characterized by a potentially life-threatening immunoglobulin E (IgE)-mediated hypersensitivity to galactose-alpha-1,3-galactose (alpha-gal), an oligosaccharide found in most nonprimate mammalian meat and products derived from these mammals. Specific symptoms and severity of AGS vary among persons, and no treatment or cure is currently available. During 2010-2018, more than 34,000 suspected cases of AGS were identified in the United States, but current knowledge of where cases occur is limited. This study examined alpha-gal-specific IgE (sIgE) antibody testing results submitted to the commercial laboratory responsible for nearly all testing in the United States before 2022 to assess the geographic distribution and magnitude of this emerging condition. During January 1, 2017-December 31, 2022, a total of 357,119 tests were submitted from residences in the United States, corresponding to 295,400 persons. Overall, 90,018 (30.5%) persons received a positive test result in the study period, and the number of persons with positive test results increased from 13,371 in 2017 to 18,885 in 2021. Among 233,521 persons for whom geographic data were available, suspected cases predominantly occurred in counties within the southern, midwestern, and mid-Atlantic U.S. Census Bureau regions. These data highlight the evolving emergence of AGS and can be used to help state and local health agencies initiate surveillance and target public health outreach and health care provider education to high-risk localities.


Asunto(s)
Hipersensibilidad a los Alimentos , Mordeduras de Garrapatas , Animales , Humanos , Estados Unidos/epidemiología , Galactosa , Mordeduras de Garrapatas/epidemiología , Inmunoglobulina E , Mamíferos
5.
Ann Allergy Asthma Immunol ; 130(4): 472-478, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36574585

RESUMEN

BACKGROUND: The disaccharide galactose-α-1,3-galactose (alpha-gal) is expressed in mammals other than humans, apes, and old-world monkeys. In humans, elevated immunoglobulin E (IgE) antibodies specific for alpha-gal can result in allergic hypersensitivity known as alpha-gal syndrome (AGS). Case reports and series suggest that tick bites can induce alpha-gal-specific IgE (sIgE) antibodies. OBJECTIVE: To evaluate tick exposure as a risk factor for AGS and elevated alpha-gal sIgE level. METHODS: We conducted a case-control study comparing patients with AGS from a North Carolina allergy clinic with controls who were patients at a nearby internal medicine clinic. Cases and controls were administered a questionnaire to obtain information about demographics, home environment, outdoor activities, and recollection of tick bite. Serum samples taken at the time of enrollment were tested for total IgE, alpha-gal sIgE, and antibodies to other tick-borne pathogens. RESULTS: The patients with AGS were more likely to recall finding a tick on themselves (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.97-25.15), live near wooded forest (OR, 2.27; 95% CI, 0.92-5.55), and spend 17 or more hours per week outdoors in wooded areas (OR, 5.58; 95% CI, 2.56-12.19). The patients with AGS were also more likely to report 4 or more tick bites (OR, 33.05; 95% CI, 9.92-155.12) and reactions at the site of tick bites (OR, 7.93; 95% CI, 3.74-16.80). Furthermore, elevated alpha-gal sIgE level was observed in 33% of the controls and was associated with tick exposure in the controls (OR, 4.25; 95% CI, 2.21-8.18). CONCLUSION: The results define tick bite as a risk factor for AGS and elevated alpha-gal sIgE level.


Asunto(s)
Hipersensibilidad a los Alimentos , Mordeduras de Garrapatas , Garrapatas , Animales , Humanos , Alérgenos , Estudios de Casos y Controles , Galactosa , Inmunoglobulina E , Factores de Riesgo
6.
Ann Allergy Asthma Immunol ; 126(4): 411-416.e1, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33422649

RESUMEN

BACKGROUND: Alpha-gal syndrome (AGS) is an emerging immunoglobulin E (IgE)-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal). The geographic distribution and burden of AGS in the United States are unknown. OBJECTIVE: To characterize alpha-gal IgE testing patterns and describe the trends and distribution from 2010 to 2018 in the United States. METHODS: This retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee's Summit, Missouri), the primary site of testing in the United States. Data included age and sex of person tested, specimen state of origin, collection date, and result value; persons with at least 1 positive test result (≥0.1 kU/L) were compared with negatives. Proportions tested and with positive test results were calculated using the US Census population estimates. RESULTS: Overall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010, to December 31, 2018. Nearly one-third (34,256, 32.4%) had at least 1 positive result. The number of persons receiving positive test results increased 6-fold from 1110 in 2011 to 7798 in 2018. Of those receiving positive test results, mean [SD] age was 46.9 (19.8) years; men were more likely to test positive than women (43.3% vs 26.0%). Arkansas, Virginia, Kentucky, Oklahoma, and Missouri had the highest number of persons who were tested and had a positive result per 100,000 population. CONCLUSION: More than 34,000 persons, most presumably symptomatic, have received positive test results for IgE antibodies to alpha-gal, suggesting AGS is an increasingly recognized public health problem. The geographic distribution of persons who tested positive is consistent with exposure to Amblyomma americanum ticks.


Asunto(s)
Alérgenos/inmunología , Hipersensibilidad a los Alimentos/inmunología , Galactosa/inmunología , Adolescente , Adulto , Anciano , Animales , Anticuerpos/inmunología , Niño , Preescolar , Técnicas y Procedimientos Diagnósticos , Femenino , Humanos , Inmunoglobulina E/inmunología , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Mordeduras de Garrapatas/inmunología , Garrapatas/inmunología , Estados Unidos , Adulto Joven
7.
Clin Microbiol Newsl ; 43(13): 109-118, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37701818

RESUMEN

Q fever is a disease caused by the bacterial pathogen Coxiella burnetii. This hardy organism can easily spread long distances in the wind, and only a few infectious aerosolized particles are necessary to cause serious illness. Presentations of Q fever disease can be wide-ranging, allowing it to masquerade as other illnesses and highlight the importance of laboratory testing for diagnosis and treatment. This review summarizes Q fever's epidemiology and clinical presentations and presents classical laboratory diagnostic assays and novel approaches to detecting this troubling disease.

8.
MMWR Morb Mortal Wkly Rep ; 67(17): 496-501, 2018 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-29723166

RESUMEN

INTRODUCTION: Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004-2016. METHODS: Data reported to the National Notifiable Diseases Surveillance System for 16 notifiable vectorborne diseases during 2004-2016 were analyzed; findings were tabulated by disease, vector type, location, and year. RESULTS: A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004-2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Vectorborne diseases are a large and growing public health problem in the United States, characterized by geographic specificity and frequent pathogen emergence and introduction. Differences in distribution and transmission dynamics of tickborne and mosquitoborne diseases are often rooted in biologic differences of the vectors. To effectively reduce transmission and respond to outbreaks will require major national improvement of surveillance, diagnostics, reporting, and vector control, as well as new tools, including vaccines.


Asunto(s)
Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Enfermedad de Lyme/epidemiología , Vigilancia de la Población , Fiebre Maculosa de las Montañas Rocosas/epidemiología , Fiebre del Nilo Occidental/epidemiología , Infección por el Virus Zika/epidemiología , Samoa Americana/epidemiología , Animales , Culicidae , Humanos , Incidencia , Insectos Vectores , Puerto Rico/epidemiología , Garrapatas , Estados Unidos/epidemiología , Islas Virgenes de los Estados Unidos/epidemiología
9.
J Clin Microbiol ; 54(1): 49-58, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26491176

RESUMEN

Acute febrile illness (AFI) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. Convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. We developed a real-time PCR-based TaqMan array card (TAC) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 AFI-associated organisms, including 15 viruses (chikungunya, Crimean-Congo hemorrhagic fever [CCHF] virus, dengue, Ebola virus, Bundibugyo virus, Sudan virus, hantaviruses [Hantaan and Seoul], hepatitis E, Marburg, Nipah virus, o'nyong-nyong virus, Rift Valley fever virus, West Nile virus, and yellow fever virus), 8 bacteria (Bartonella spp., Brucella spp., Coxiella burnetii, Leptospira spp., Rickettsia spp., Salmonella enterica and Salmonella enterica serovar Typhi, and Yersinia pestis), and 3 protozoa (Leishmania spp., Plasmodium spp., and Trypanosoma brucei). Two extrinsic controls (phocine herpesvirus 1 and bacteriophage MS2) were included to ensure extraction and amplification efficiency. Analytical validation was performed on spiked specimens for linearity, intra-assay precision, interassay precision, limit of detection, and specificity. The performance of the card on clinical specimens was evaluated with 1,050 blood samples by comparison to the individual real-time PCR assays, and the TAC exhibited an overall 88% (278/315; 95% confidence interval [CI], 84% to 92%) sensitivity and a 99% (5,261/5,326, 98% to 99%) specificity. This TaqMan array card can be used in field settings as a rapid screen for outbreak investigation or for the surveillance of pathogens, including Ebola virus.


Asunto(s)
Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/epidemiología , Brotes de Enfermedades , Fiebre de Origen Desconocido/diagnóstico , Fiebre de Origen Desconocido/epidemiología , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adulto , Monitoreo Epidemiológico , Humanos , Técnicas de Diagnóstico Molecular/normas , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Estándares de Referencia , Sensibilidad y Especificidad , Factores de Tiempo
10.
Dis Aquat Organ ; 114(1): 83-7, 2015 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-25958809

RESUMEN

Valvular endocarditis has been well described in northern sea otters Enhydra lutris kenyoni of Alaska and in many cases no cause has been identified. It is also one of the most common conditions observed in people with chronic Coxiella burnetii infection. Given the high levels of C. burnetii exposure in marine mammals distributed throughout the same geographic range as the northern sea otter, and the presence of valvular lesions seen in otters, the objective of this study was to determine the level of C. burnetii exposure in otters and investigate any association between exposure, infection and valvular disease in this species. Archived serum from 75 live captured, apparently healthy otters (25 from each of 3 stocks) and 30 dead otters were tested for C. burnetii antibodies by indirect florescent antibody assay (IFA). Archived bone marrow and heart valves were tested for C. burnetii DNA by real-time PCR (qPCR). Overall, the seroprevalence in live otters was 17%, with significantly more exposed animals in the south central (40%) stock relative to the southwest (8%) and southeast (4%). The seroprevalence of animals sampled post mortem was 27%, although none of the bone marrow or heart valve samples were positive by qPCR. Results of this study failed to demonstrate a significant association between C. burnetii infection and valvular endocarditis in sea otters; however, the differing seroprevalence suggests that exposure opportunities vary geographically.


Asunto(s)
Coxiella burnetii , Endocarditis Bacteriana/veterinaria , Nutrias , Fiebre Q/veterinaria , Alaska/epidemiología , Animales , Endocarditis Bacteriana/epidemiología , Endocarditis Bacteriana/microbiología , Femenino , Masculino , Fiebre Q/epidemiología , Estudios Seroepidemiológicos
11.
BMC Microbiol ; 14: 41, 2014 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-24533573

RESUMEN

BACKGROUND: Coxiella burnetii causes Q fever in humans and Coxiellosis in animals; symptoms range from general malaise to fever, pneumonia, endocarditis and death. Livestock are a significant source of human infection as they shed C. burnetii cells in birth tissues, milk, urine and feces. Although prevalence of C. burnetii is high, few Q fever cases are reported in the U.S. and we have a limited understanding of their connectedness due to difficulties in genotyping. Here, we develop canonical SNP genotyping assays to evaluate spatial and temporal relationships among C. burnetii environmental samples and compare them across studies. Given the genotypic diversity of historical collections, we hypothesized that the current enzootic of Coxiellosis is caused by multiple circulating genotypes. We collected A) 23 milk samples from a single bovine herd, B) 134 commercial bovine and caprine milk samples from across the U.S., and C) 400 bovine and caprine samples from six milk processing plants over three years. RESULTS: We detected C. burnetii DNA in 96% of samples with no variance over time. We genotyped 88.5% of positive samples; bovine milk contained only a single genotype (ST20) and caprine milk was dominated by a second type (mostly ST8). CONCLUSIONS: The high prevalence and lack of genotypic diversity is consistent with a model of rapid spread and persistence. The segregation of genotypes between host species is indicative of species-specific adaptations or dissemination barriers and may offer insights into the relative lack of human cases and characterizing genotypes.


Asunto(s)
Coxiella burnetii/clasificación , Coxiella burnetii/genética , Variación Genética , Leche/microbiología , Tipificación Molecular/métodos , Fiebre Q/veterinaria , Animales , Bovinos , Coxiella burnetii/aislamiento & purificación , Genotipo , Cabras , Epidemiología Molecular , Prevalencia , Fiebre Q/microbiología , Estados Unidos/epidemiología
12.
MMWR Recomm Rep ; 62(RR-03): 1-30, 2013 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-23535757

RESUMEN

Q fever, a zoonotic disease caused by the bacterium Coxiella burnetii, can cause acute or chronic illness in humans. Transmission occurs primarily through inhalation of aerosols from contaminated soil or animal waste. No licensed vaccine is available in the United States. Because many human infections result in nonspecific or benign constitutional symptoms, establishing a diagnosis of Q fever often is challenging for clinicians. This report provides the first national recommendations issued by CDC for Q fever recognition, clinical and laboratory diagnosis, treatment, management, and reporting for health-care personnel and public health professionals. The guidelines address treatment of acute and chronic phases of Q fever illness in children, adults, and pregnant women, as well as management of occupational exposures. These recommendations will be reviewed approximately every 5 years and updated to include new published evidence.


Asunto(s)
Antibacterianos/uso terapéutico , Fiebre Q/diagnóstico , Fiebre Q/tratamiento farmacológico , Zoonosis , Enfermedad Aguda , Adulto , Anciano , Animales , Animales Domésticos , Niño , Enfermedad Crónica , Doxiciclina/uso terapéutico , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Embarazo , Riesgo , Estados Unidos/epidemiología
14.
Syst Biol ; 62(5): 752-62, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23736103

RESUMEN

Rooting phylogenies is critical for understanding evolution, yet the importance, intricacies and difficulties of rooting are often overlooked. For rooting, polymorphic characters among the group of interest (ingroup) must be compared to those of a relative (outgroup) that diverged before the last common ancestor (LCA) of the ingroup. Problems arise if an outgroup does not exist, is unknown, or is so distant that few characters are shared, in which case duplicated genes originating before the LCA can be used as proxy outgroups to root diverse phylogenies. Here, we describe a genome-wide expansion of this technique that can be used to solve problems at the other end of the evolutionary scale: where ingroup individuals are all very closely related to each other, but the next closest relative is very distant. We used shared orthologous single nucleotide polymorphisms (SNPs) from 10 whole genome sequences of Coxiella burnetii, the causative agent of Q fever in humans, to create a robust, but unrooted phylogeny. To maximize the number of characters informative about the rooting, we searched entire genomes for polymorphic duplicated regions where orthologs of each paralog could be identified so that the paralogs could be used to root the tree. Recent radiations, such as those of emerging pathogens, often pose rooting challenges due to a lack of ingroup variation and large genomic differences with known outgroups. Using a phylogenomic approach, we created a robust, rooted phylogeny for C. burnetii. [Coxiella burnetii; paralog SNPs; pathogen evolution; phylogeny; recent radiation; root; rooting using duplicated genes.].


Asunto(s)
Clasificación/métodos , Coxiella burnetii/clasificación , Coxiella burnetii/genética , Genómica , Filogenia , Genoma Bacteriano/genética , Genómica/normas
16.
Microbiol Spectr ; 12(7): e0103424, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38864598

RESUMEN

Since 1999, doxycycline and hydroxychloroquine have been the recommended treatment for chronic Q fever, a life-threatening disease caused by the bacterial pathogen, Coxiella burnetii. Despite the duration of its use, the treatment is not ideal due to the lengthy treatment time, high mortality rate, resistant strains, and the potential for contraindicated usage. A literature search was conducted to identify studies that screened large panels of drugs against C. burnetii to identify novel targets with potential efficacy against C. burnetii. Twelve candidate antimicrobials approved for use in humans by the US Food and Drug Administration were selected and minimum inhibitory concentrations (MICs) were determined against the low virulence strain Nine Mile phase II. Rifabutin and rifaximin were the best performing antibiotics tested with MICs of ≤0.01 µg mL-1. Further screening of these top candidates was conducted alongside two drugs from the same class, rifampin, well-characterized, and rifapentine, not previously reported against C. burnetii. These were screened against virulent strains of C. burnetii representing three clinically relevant genotypes. Rifapentine was the most effective in the human monocytic leukemia cell line, THP-1, with a MIC ≤0.01 µg mL-1. In the human kidney epithelial cell line, A-498, efficacy of rifapentine, rifampin, and rifabutin varied across C. burnetii strains with MICs between ≤0.001 and 0.01 µg mL-1. Rifampin, rifabutin, and rifapentine were all bactericidal against C. burnetii; however, rifabutin and rifapentine demonstrated impressive bactericidal activity as low as 0.1 µg mL-1 and should be further explored as alternative Q fever treatments given their efficacy in vitro. IMPORTANCE: This work will help inform investigators and physicians about potential alternative antimicrobial therapies targeting the causative agent of Q fever, Coxiella burnetii. Chronic Q fever is difficult to treat, and alternative antimicrobials are needed. This manuscript explores the efficacy of rifamycin antibiotics against virulent strains of C. burnetii representing three clinically relevant genotypes in vitro. Importantly, this study determines the susceptibility of C. burnetii to rifapentine, which has not been previously reported. Evaluation of the bactericidal activity of the rifamycins reveals that rifabutin and rifapentine are bactericidal at low concentrations, which is unusual for antibiotics against C. burnetii.


Asunto(s)
Antibacterianos , Coxiella burnetii , Pruebas de Sensibilidad Microbiana , Fiebre Q , Rifampin , Rifamicinas , Humanos , Rifampin/farmacología , Rifampin/análogos & derivados , Antibacterianos/farmacología , Coxiella burnetii/efectos de los fármacos , Coxiella burnetii/genética , Rifamicinas/farmacología , Fiebre Q/tratamiento farmacológico , Fiebre Q/microbiología , Rifabutina/farmacología , Rifabutina/análogos & derivados , Línea Celular
17.
Front Vet Sci ; 11: 1393296, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774910

RESUMEN

Coxiella burnetii is a bacterial pathogen capable of causing serious disease in humans and abortions in goats. Infected goats can shed C. burnetii through urine, feces, and parturient byproducts, which can lead to infections in humans when the bacteria are inhaled. Goats are important C. burnetii reservoirs as evidenced by goat-related outbreaks across the world. To better understand the current landscape of C. burnetii infection in the domestic goat population, 4,121 vaginal swabs from 388 operations across the United States were analyzed for the presence of C. burnetii by IS1111 PCR as part of the United States Department of Agriculture, Animal Plant Health Inspection Service, Veterinary Services' National Animal Health Monitoring System Goats 2019 Study. In total, 1.5% (61/4121) of swabs representing 10.3% (40/388) (weighted estimate of 7.8, 95% CI 4.4-13.5) of operations were positive for C. burnetii DNA. The quantity of C. burnetii on positive swabs was low with an average Ct of 37.9. Factors associated with greater odds of testing positive included suspected Q fever in the herd in the previous 3 years, the presence of wild deer or elk on the operation, and the utilization of hormones for estrus synchronization. Factors associated with reduced odds of testing positive include the presence of kittens and treatment of herds with high tannin concentrate plants, diatomaceous earth, and tetrahydropyrimidines. In vitro analysis demonstrated an inhibitory effect of the tetrahydropyrimidine, pyrantel pamoate, on the growth of C. burnetii in axenic media as low as 1 µg per mL. The final multivariable logistic regression modeling identified the presence of wild predators on the operation or adjacent property (OR = 9.0, 95% CI 1.3-61.6, p value = 0.0248) as a risk factor for C. burnetii infection.

18.
Ticks Tick Borne Dis ; 15(4): 102344, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38643721

RESUMEN

The brown dog tick, Rhipicephalus sanguineus sensu lato (s.l.), is an important vector for Rickettsia rickettsii, causative agent of Rocky Mountain spotted fever. Current public health prevention and control efforts to protect people involve preventing tick infestations on domestic animals and in and around houses. Primary prevention tools rely on acaricides, often synthetic pyrethroids (SPs); resistance to this chemical class is widespread in ticks and other arthropods. Rhipicephalus sanguineus s.l. is a complex that likely contains multiple unique species and although the distribution of this complex is global, there are differences in morphology, ecology, and perhaps vector competence among these major lineages. Two major lineages within Rh. sanguineus s.l., commonly referred to as temperate and tropical, have been documented from multiple locations in North America, but are thought to occupy different ecological niches. To evaluate potential acaricide resistance and better define the distributions of the tropical and temperate lineages throughout the US and in northern Mexico, we employed a highly multiplexed amplicon sequencing approach to characterize sequence diversity at: 1) three loci within the voltage-gated sodium channel (VGSC) gene, which contains numerous genetic mutations associated with resistance to SPs; 2) a region of the gamma-aminobutyric acid-gated chloride channel gene (GABA-Cl) containing several mutations associated with dieldrin/fipronil resistance in other species; and 3) three mitochondrial genes (COI, 12S, and 16S). We utilized a geographically diverse set of Rh sanguineus s.l. collected from domestic pets in the US in 2013 and a smaller set of ticks collected from canines in Baja California, Mexico in 2021. We determined that a single nucleotide polymorphism (T2134C) in domain III segment 6 of the VGSC, which has previously been associated with SP resistance in Rh. sanguineus s.l., was widespread and abundant in tropical lineage ticks (>50 %) but absent from the temperate lineage, suggesting that resistance to SPs may be common in the tropical lineage. We found evidence of multiple copies of GABA-Cl in ticks from both lineages, with some copies containing mutations associated with fipronil resistance in other species, but the effects of these patterns on fipronil resistance in Rh. sanguineus s.l. are currently unknown. The tropical lineage was abundant and geographically widespread, accounting for 79 % of analyzed ticks and present at 13/14 collection sites. The temperate and tropical lineages co-occurred in four US states, and as far north as New York. None of the ticks we examined were positive for Rickettsia rickettsii or Rickettsia massiliae.


Asunto(s)
Piretrinas , Rhipicephalus sanguineus , Animales , Rhipicephalus sanguineus/genética , Piretrinas/farmacología , Acaricidas/farmacología , Mutación , Estados Unidos , Resistencia a los Insecticidas/genética , Enfermedades de los Perros/parasitología , Perros , Femenino
19.
Appl Environ Microbiol ; 79(5): 1697-703, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23315737

RESUMEN

Q fever is a zoonotic disease caused by inhalation of the bacterium Coxiella burnetii. Ruminant livestock are common reservoirs for C. burnetii, and bacteria present in aerosols derived from the waste of infected animals can infect humans. The significance of infection from material deposited in the environment versus transmission directly from infected animals is not known. In 2011, an outbreak of Q fever cases on farms in Washington and Montana was associated with infected goats. A study was undertaken to investigate the quantity and spatial distribution of C. burnetii in the environment of these goat farms. Soil, vacuum, and sponge samples collected on seven farms epidemiologically linked to the outbreak were tested for the presence of C. burnetii DNA by quantitative PCR. Overall, 70.1% of the samples were positive for C. burnetii. All farms had positive samples, but the quantity of C. burnetii varied widely between samples and between farms. High quantities of C. burnetii DNA were in goat housing/birthing areas, and only small quantities were found in samples collected more than 50 m from these areas. Follow-up sampling at one of the farms 1 year after the outbreak found small quantities of C. burnetii DNA in air samples and large quantities of C. burnetii persisting in soil and vacuum samples. The results suggest that the highest concentrations of environmental C. burnetii are found in goat birthing areas and that contamination of other areas is mostly associated with human movement.


Asunto(s)
Crianza de Animales Domésticos , Coxiella burnetii/aislamiento & purificación , Brotes de Enfermedades , Microbiología Ambiental , Enfermedades de las Cabras/epidemiología , Fiebre Q/veterinaria , Animales , Carga Bacteriana , ADN Bacteriano/análisis , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Enfermedades de las Cabras/microbiología , Cabras , Montana , Fiebre Q/epidemiología , Fiebre Q/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Washingtón
20.
Transfusion ; 53(7): 1493-6, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23034070

RESUMEN

BACKGROUND: Coxiella burnetii, an obligate intracellular organism, is the causative agent of the zoonotic disease Q fever. The seroprevalence rate for Q fever in the United States is 3.1%, suggesting a high number of infections each year. However, fewer than 200 cases of Q fever are reported to the CDC annually. This discrepancy is likely the result of underutilized diagnostics and a high percentage (>50%) of asymptomatic infections. The detection of C. burnetii in patient blood during the first 2 to 3 weeks of infection raises the possibility that the organism could be present in donated human blood. The purpose of this study was to determine if extracellular C. burnetii would be stable in blood under normal storage conditions. STUDY DESIGN AND METHODS: Donated human blood was separated into whole blood, leukoreduced whole blood, red blood cells, and plasma. Each component was spiked with purified, extracellular C. burnetii strain Nine Mile Phase 1, and the viability and infectivity of the organisms were tested weekly. RESULTS: C. burnetii did not decrease in viability or the ability to infect cells after storage in any of the blood products, even after 6 weeks of storage at 1 to 6 °C. CONCLUSIONS: Extracellular C. burnetii can survive and remain infectious in donated blood products.


Asunto(s)
Bacteriemia/microbiología , Coxiella burnetii/fisiología , Humanos
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