Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 57 Records) |
Query Trace: Kersh GJ[original query] |
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Conceptual framework for community-based prevention of brown dog tick-associated Rocky Mountain spotted fever
Brophy MK , Weis E , Drexler NA , Paddock CD , Nicholson WL , Kersh GJ , Salzer JS . Emerg Infect Dis 2024 30 (11) 2231-2240 Rocky Mountain spotted fever (RMSF) is a severe tickborne disease that can reach epidemic proportions in communities with certain social and ecologic risk factors. In some areas, the case-fatality rate of brown dog tick-associated RMSF is up to 50%. Because of the spread of brown dog tick-associated RMSF in the southwestern United States and northern Mexico, the disease has the potential to emerge and become endemic in other communities that have large populations of free-roaming dogs, brown dog ticks, limited resources, and low provider awareness of the disease. By using a One Health approach, interdisciplinary teams can identify communities at risk and prevent severe or fatal RMSF in humans before cases occur. We have developed a conceptual framework for RMSF prevention to enable communities to identify their RMSF risk level and implement prevention and control strategies. |
Longitudinal surveillance of Coxiella burnetii following an abortion storm in domestic goats
Miller HK , Priestley RA , Smith CB , Cherry C , Kersh GJ . Front Vet Sci 2024 11 1426573 Q fever is a disease caused by Coxiella burnetii, which can cause serious illness in humans and abortions in goats. A Q fever outbreak among an unvaccinated goat herd led to a 65% loss of the kid crop in spring 2018. To assess the impact of the outbreak on the herd and environment, longitudinal surveillance of the ranch was conducted across three samplings in September 2018, April 2019, and May 2022. Antibodies against C. burnetii were monitored by an indirect immunofluorescence assay. Shedding was monitored through analysis of vaginal/fecal swabs and milk. Environmental swabs and bulk soil were collected from various locations around the ranch. Animal and environmental samples were analyzed for C. burnetii DNA by PCR. Herd-level seroprevalence decreased from 89% in 2018 to 84.3% in 2019, and 64.5% in 2022. Overall herd shedding was 14.4% in 2018, 7.4% in 2019, and 6.7% in 2022. The percentage of C. burnetii-positive environmental samples was 83.7% in 2018, 51.7% in 2019, and 28.6% in 2022. Serological evidence suggests that new infections were occurring in the herd 4 years post-abortion storm. This study demonstrates the presence of C. burnetii shedding and environmental contamination in a goat operation at least four kidding seasons after an outbreak. A better understanding of management practices that can improve outcomes for infected herds, particularly in areas without access to vaccines against C. burnetii, is needed to better protect operators and the public. |
Zoonoses in the workplace: A Seroprevalence study of Coxiella, Brucella, and Leptospira among marine mammal rescue and rehabilitation workers in California
Bjork A , Stoddard RA , Anderson AD , de Perio MA , Niemeier RT , Self JS , Fitzpatrick KA , Gulland FMD , Field CL , Kersh GJ , Gibbins JD . Public Health Chall 2024 3 (2) Background: Q fever, brucellosis, and leptospirosis are zoonoses typically associated with terrestrial animal reservoirs. These bacterial agents are now known to infect marine mammal species, though little is known about potential human health risks from marine mammal reservoir species. We investigated potential risks of these bacteria in humans associated with marine mammal exposure. Methods: The Marine Mammal Center (TMMC) in Sausalito, California, requested a Health Hazard Evaluation by the National Institute for Occupational Safety and Health. In June 2011, an investigation occurred, which included a written questionnaire and serosurvey among workers for Coxiella burnetii, Brucella spp., and Leptospira spp., and an environmental assessment for C. burnetii. Results: Serologic evidence of past exposure was detected in 4% (C. burnetii), 0% (Brucella), and 1% (Leptospira) of 213 participants, respectively. One of 130 environmental samples tested positive for C. burnetii. No significant marine mammal-specific risk factors were identified, but some safety deficiencies were noted that could lead to a higher risk of exposure to zoonotic diseases. Conclusion: Although this study did not identify disease exposure risks associated with marine mammals, additional studies in different settings of other groups with frequent exposure to marine mammals are warranted. Some deficiencies in safety were noted, and based on these, TMMC modified protocols to improve safety. © 2024 The Authors. Public Health Challenges published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. |
Efficacy of rifapentine and other rifamycins against Coxiella burnetii in vitro
Miller HK , Kersh GJ . Microbiol Spectr 2024 e0103424 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. |
Coxiella burnetii in domestic doe goats in the United States, 2019-2020
Miller HK , Branan M , Priestley RA , Álvarez-Alonso R , Cherry C , Smith C , Urie NJ , Wiedenheft A , Bliss C , Marshall K , Kersh GJ . Front Vet Sci 2024 11 1393296 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. |
A mutation associated with resistance to synthetic pyrethroids is widespread in US populations of the tropical lineage of Rhipicephalus sanguineus s.l
Stone NE , Ballard R , Bourgeois RM , Pemberton GL , McDonough RF , Ruby MC , Backus LH , López-Pérez AM , Lemmer D , Koch Z , Brophy M , Paddock CD , Kersh GJ , Nicholson WL , Sahl JW , Busch JD , Salzer JS , Foley JE , Wagner DM . Ticks Tick Borne Dis 2024 15 (4) 102344 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. |
Prevalence and risk factors for Q fever, spotted fever group rickettsioses, and typhus group rickettsioses in a pastoralist community of northern Tanzania, 2016-2017
Moorthy GS , Rubach MP , Maze MJ , Refuerzo RP , Shirima GM , Lukambagire AS , Bodenham RF , Cash-Goldwasser S , Thomas KM , Sakasaka P , Mkenda N , Bowhay TR , Perniciaro JL , Nicholson WL , Kersh GJ , Kazwala RR , Mmbaga BT , Buza JJ , Maro VP , Haydon DT , Crump JA , Halliday JEB . Trop Med Int Health 2024 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. |
Intrinsic risk factors for alpha-gal syndrome in a case-control study, 2019-2020
Taylor ML , Kersh GJ , Salzer JS , Jones ES , Binder AM , Armstrong PA , Choudhary SK , Commins GK , Amelio CL , Biggerstaff BJ , Beard CB , Petersen LR , Commins SP . Ann Allergy Asthma Immunol 2024 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 following 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: This study investigated 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 2019-2020 and compared them to controls enrolled from two nearby internal medicine clinics. A questionnaire gathered epidemiologic and tick exposure data and blood was obtained for alpha-gal specific IgE (sIgE) 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 suggests 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 healthcare providers in understanding susceptible populations, and contribute to ongoing understanding of AGS epidemiology. |
Geographic distribution of suspected alpha-gal syndrome cases - United States, January 2017-December 2022
Thompson JM , Carpenter A , Kersh GJ , Wachs T , Commins SP , Salzer JS . MMWR Morb Mortal Wkly Rep 2023 72 (30) 815-820 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. |
Tick bite as a risk factor for alpha-gal specific IgE antibodies and development of alpha-gal syndrome
Kersh GJ , Salzer J , Jones ES , Binder AM , Armstrong PA , Choudhary SK , Commins GK , Amelio CL , Kato CY , Singleton J , Biggerstaff BJ , Beard CB , Petersen LR , Commins SP . Ann Allergy Asthma Immunol 2023 130 (4) 472-478 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. |
Tropical Q Fever
Kersh GJ . Am J Trop Med Hyg 2022 107 (2) 219-220 Infection with the Gram-negative bacterium Coxiella burnetii can result in a variety of clinical presentations that are collectively referred to as Q fever. These can range from a mild, self-limiting febrile illness to more insidious chronic infections such as Q fever endocarditis. C. burnetii infections have been found in most of the world, with Europe, Australia, and North America seeming to have the majority of cases. In areas where surveillance is conducted for Q fever, it is a disease that most would consider rare. The United States has conducted national surveillance for Q fever since 2000 and reports an annual average incidence of 0.036 cases per 100,000 persons for 2008 through 2017.1 The European Centre for Disease Prevention and Control reported 0.2 Q fever notifications per 100,000 persons for the European Union/European Economic Area in 2019.2 Despite the low numbers of reported cases, many areas report fairly high levels of seroprevalence, suggesting that asymptomatic exposures are common. | | The baseline circumstance of widespread asymptomatic infections with a minority of infections resulting in detected disease makes the occurrence of exceptional outbreaks notable. Perhaps the most notable of such outbreaks occurred in the Netherlands between 2007 and 2010, where more than 4,000 acute Q fever cases were recorded in a limited geographic area.3 During this outbreak, most cases presented with pneumonia. Other, more limited outbreaks have been reported in a variety of locations, including England, Germany, and Bosnia.4–6 |
Clinical and laboratory features of patients diagnosed with Alpha-gal Syndrome - 2010-2019
Binder AM , Cherry-Brown D , Biggerstaff BJ , Jones ES , Amelio CL , Beard CB , Petersen LR , Kersh GJ , Commins SP , Armstrong PA . Allergy 2022 78 (2) 477-487 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 hours after exposure to alpha-gal-containing products. In the United States, lone star tick bites are associated with 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 53years, 56% were female, 95% reported White race, 86% reported a history of tick bite, and 75% met criteria for anaphylaxis based on 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. |
HISTOLOGIC LESIONS IN PLACENTAS OF NORTHERN FUR SEALS (CALLORHINUS URSINUS) FROM A POPULATION WITH HIGH PLACENTAL PREVALENCE OF COXIELLA BURNETII.
Conway R , Duncan C , Foster RA , Kersh GJ , Raverty S , Gelatt T , Frank C . J Wildl Dis 2022 58 (2) 333-340 Coxiella burnetii is an intracellular bacterial pathogen that can be associated with significant reproductive disease or acute mortality in livestock and wildlife. A novel marine mammal-associated strain of C. burnetii has been identified in pinnipeds of the Northwestern Pacific Ocean. Little is known about C. burnetii infection in regard to reproductive success or population status. Our objective was to characterize the severity and extent of histologic lesions in 117 opportunistically collected placentas from presumed-normal northern fur seals (Callorhinus ursinus) in July 2011 on St. Paul Island, Alaska, where a high placental prevalence of C. burnetii had been reported. Sections were examined by histology and immunohistochemistry and impression smears with modified acid-fast stain. The nature and frequency of histologic changes were compared with target COM1 PCR-confirmed C. burnetii positive and negative placentas. Overall, histologic changes were similar to placental lesions described in aborting ruminants; however, changes were variable within and between placentas. Vasculitis and occasional intracellular bacteria were seen only in C. burnetii PCR-positive placentas. Dystrophic mineralization, edema, and inflammation were seen in PCR-positive and negative placentas, although they were statistically more common in PCR-positive placentas. Results suggest that C. burnetti and associated pathologic changes are multifocal and variable in placentas from these presumably live-born pups. Therefore, multiple sections of tissue from different placental areas should be examined microscopically and screened by PCR to ensure accurate diagnosis, as the genomes per gram of placenta may not necessarily represent the severity of placental disease. These limitations should inform field biologists, diagnosticians, and pathologists how best to screen and sample for pathogens and histopathology in marine mammal placental samples. |
Acute and chronic Q fever national surveillance - United States, 2008-2017
Cherry CC , Nichols Heitman K , Bestul NC , Kersh GJ . Zoonoses Public Health 2021 69 (2) 73-82 Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii and can manifest in an acute or chronic form. Many persons with acute Q fever are asymptomatic, but some develop a febrile illness, pneumonia or hepatitis. Chronic infections are rare and occur in less than 5% of persons exposed. Forms of chronic Q fever include endocarditis, infection of vascular grafts or aneurysms, osteomyelitis and osteoarthritis. Acute and chronic Q fever are nationally notifiable diseases, and presented here are the incidence, demographics and distribution of acute and chronic Q fever in the United States during 2008-2017. We summarized passive surveillance data from the Centers for Disease Control and Prevention's (CDC) National Notifiable Diseases Surveillance System (NNDSS) and supplemental case report forms (CRFs). Health departments reported 1,109 cases of acute Q fever and 272 chronic Q fever cases to NNDSS during this period. The 10-year average annual incidence for acute Q fever was 0.36 cases per million persons, and the average annual incidence for chronic Q fever was 0.09. Males accounted for nearly 75% of both acute and chronic Q fever cases. Average annual incidence was highest among persons aged 60-69 years for both acute and chronic Q fever (0.70 cases per million persons and 0.25, respectively). As reported through CRFs, many Q fever cases did not have a known exposure to C. burnetii; 60% (n = 380) of acute Q fever cases did not report exposure to animals in the 2 months before symptom onset. Almost 90% (n = 558) did not report exposure to unpasteurized milk. Only 40% (n = 247) of persons with reported Q fever were employed in high-risk occupations. Even though Q fever is a rare disease in the United States, incidence doubled from 2008 to 2017. |
Comparison of three Coxiella burnetii infectious routes in mice
Miller HK , Priestley RA , Kersh GJ . Virulence 2021 12 (1) 2562-2570 Evidence suggests that Coxiella burnetii, which is shed in the milk, urine, feces, and birth products of infected domestic ruminants, can lead to Q fever disease following consumption of unpasteurized dairy products; however, C. burnetii is not believed to be a major gastrointestinal pathogen. Most infections are associated with inhalation of aerosols generated from the excreta of domestic ruminants. We recently demonstrated that C. burnetii delivered by oral gavage (OG) resulted in dissemination and an immune response; however, it is unclear how infection via the oral route compares to other well-established routes. Therefore, we delivered three strains of C. burnetii (representing three pertinent sequence types in the United States, such as ST16, ST20, and ST8) to immunocompetent mice in four doses via aerosol challenge (AC), intraperitoneal injection (IP), or OG. Low dose (10^5) of ST16 by OG was insufficient to cause infection, yet doses 1,000- or 100-fold lower by IP or AC, respectively, induced a robust immune response and dissemination. Despite being able to induce an immune response in a dose-dependent manner, administration of C. burnetii via OG is the least efficient route tested. Not only were the immune responses and bacterial loads diminished in mice exposed by OG relative to AC or IP, the efficiency of transmission was also inferior. High doses (10^8) were not sufficient to ensure transmission to 100% of the ST20 or ST8 cohorts. These results may provide some basis for why ingestion of C. burnetii as a mode of Q fever transmission is not often reported. |
Coxiella burnetii infections in mice: Immunological responses to contemporary genotypes found in the US.
Priestley RA , Smith CB , Miller HK , Kersh GJ . Virulence 2021 12 (1) 2461-2473 Coxiella burnetii is an obligate intracellular bacterium that causes the human disease Q fever, which can manifest as an acute flu-like illness or a long-term chronic illness, such as endocarditis. Three genotypes (ST8, ST16, and ST20) of Coxiella burnetii are commonly found in the contemporary US and are associated with specific animal hosts. Although all three genotypes have been isolated from humans with Q fever, studies comparing virulence between C. burnetii sequence types have been rare. Here, groups of mice were infected via aerosol inoculation with isolates derived from cow's milk, environmental, animal, and human samples. Mice were monitored for weight loss and blood samples were takenweekly. Animals were euthanized at 2- and 12-weeks post-infection, and bacterial burden was determined for tissues by real-time PCR. The levels of anti-Coxiella antibodies and selected inflammatory cytokines were determined for serum samples. Weight loss and splenomegaly were observed in mice infected with ST20 and ST16 isolates but were absent in the mice infected with ST8 isolates. Bacterial concentrations in the tissues were lower in the ST8 isolates at 2 weeks post-infection relative to all other isolates. ST16 and ST20 isolates induced robust antibody and cytokine responses, while ST8 isolates produced significantly lower anti-C. burnetii titers early in the infection but saw increased titers in some animals several weeks post-infection. The data suggest that the ST8 isolates are less virulent in this mouse model, as they produce less robust antibody responses that are slow to develop, relative to the ST16 and ST20 isolates. |
Q Fever: A Troubling Disease and a Challenging Diagnosis
Miller HK , Priestley RA , Kersh GJ . Clin Microbiol Newsl 2021 43 (13) 109-118 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, highlighting 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. © 2021 Elsevier Inc. |
Diagnostic testing for Galactose-alpha-1,3-galactose (Alpha-gal), United States, 2010-2018
Binder AM , Commins S , Altrich ML , Wachs T , Biggerstaff BJ , Beard CB , Petersen LR , Kersh GJ , Armstrong PA . Ann Allergy Asthma Immunol 2021 126 (4) 411-416 e1 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 is unknown. OBJECTIVE: To characterizes alpha-gal IgE testing patterns and describes trends and distribution during 2010-2018 in the United States. METHODS: This retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee's Summit, MO), 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 one positive test (≥0.1 kU/L) were compared to negatives. Proportions tested and with positive test results were calculated using U.S. Census population estimates. RESULTS: Overall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010-December 31, 2018. Nearly one-third (34,256, 32.4%) had at least one positive result. The number of persons testing positive increased 6-fold from 1,110 in 2011 to 7,798 in 2018. Of those testing positive, mean [SD] age was 46.9 [19.8] years; males were more likely to test positive than females (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 tested positive 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. |
Analysis of recombinant proteins for Q fever diagnostics.
Miller HK , Kersh GJ . Sci Rep 2020 10 (1) 20934 Serology is essential for Q fever diagnostics, a disease caused by the bacterial pathogen Coxiella burnetii. The gold standard test is an immunofluorescence assay utilizing whole cell antigens, which are both dangerous and laborious to produce. Complexities of the antigen coupled with the subjective nature of the assay lead to decreased uniformity of test results and underscore the need for improved methodologies. Thirty-three C. burnetii proteins, previously identified as immunoreactive, were screened for reactivity to naturally infected goat serum. Based on reactivity, 10 proteins were analyzed in a secondary screen against human serum from healthy donors. Assay sensitivity and specificity ranged from 21 to 71% and 90 to 100%, respectively. Three promising antigens were identified based on receiver operating characteristic curve analysis (CBU_1718, CBU_0307, and CBU_1398). Five multiplex assays failed to outperform the individual proteins, with sensitivities and specificities ranging from 29 to 57% and 90 to 100%, respectively. Truncating the top antigen, CBU_1718, had no effect on specificity (90%); yet sensitivity decreased dramatically (71% to 21%). Through this study, we have expanded the subset of C. burnetii immunoreactive proteins validated by enzyme-linked immunosorbent assay and demonstrate the effect of novel antigen combinations and protein truncations on assay performance. |
Association between serological responses to two zoonotic ruminant pathogens and esophageal squamous cell carcinoma
Miller HK , Stoddard RA , Dawsey SM , Nasrollahzadeh D , Abnet CC , Etemadi A , Kamangar F , Murphy G , Sotoudeh M , Kersh GJ , Malekzadeh R , Camargo MC . Vector Borne Zoonotic Dis 2020 21 (2) 125-127 Questionnaire data have linked contact with ruminants to the risk of esophageal squamous cell carcinoma (ESCC) in high-risk Asian populations. To better understand this observed association, we investigated exposure to two major zoonotic ruminant pathogens relative to ESCC risk. Using enzyme-linked immunosorbent assay, immunofluorescence assay, and Brucella microagglutination test assays, we measured immunoglobulin G anti-Coxiella burnetii and anti-Brucella spp. antibodies in patients with ESCC (n = 177) and population-based controls (n = 177) matched by age, gender, and residence area from the Golestan case-control study in Iran. We found a similarly high seroprevalence of C. burnetii in ESCC cases and controls (75% and 80%, respectively), and a similarly low seroprevalence of Brucella spp. (0% and 0.6%, respectively). While documenting a high exposure to one of two zoonotic ruminant infections, this exposure failed to explain the observed association of ruminant contact and ESCC risk in this high-risk population. |
Pediatric Q Fever
Cherry CC , Kersh GJ . Curr Infect Dis Rep 2020 22 (4) Purpose of Review: The non-specific presentation of acute Q fever makes it difficult to diagnose in children, but untreated Q fever can result in chronic infections that have severe complications. Recent Findings: Pediatric Q fever cases continue to be infrequently reported in the literature, and primarily document cases of persistent infections with Coxiella burnetii. Standardized treatment protocols for chronic Q fever in children still do not exist. Doxycycline and hydroxychloroquine are the treatment combination most utilized by healthcare providers to treat Q fever endocarditis or osteomyelitis in children, but a variety of other antibiotic combinations have been reported with varying results. The use of adjunctive therapies, such as such as interferon gamma, has produced mixed outcomes. Summary: The true impact of Coxiella burnetii on the health of children remains unknown; long-term longitudinal follow-up of children with acute or chronic Q fever has not been reported. Both the acute and chronic forms of Q fever are underreported and underdiagnosed. Healthcare providers should consider Q fever in pediatric patients with culture-negative endocarditis or osteomyelitis. |
Transmission of Coxiella burnetii by ingestion in mice
Miller HK , Priestley RA , Kersh GJ . Epidemiol Infect 2020 148 e21 Coxiella burnetii, the causative agent of Q fever, is widely present in dairy products around the world. It has been isolated from unpasteurised milk and cheese and can survive for extended periods of time under typical storage conditions for these products. Although consumption of contaminated dairy products has been suggested as a potential route for transmission, it remains controversial. Given the high prevalence of C. burnetii in dairy products, we sought to examine the feasibility of transmitting the major sequence types (ST16, ST8 and ST20) of C. burnetii circulating in the United States. We delivered three strains of C. burnetii, comprising each sequence type, directly into the stomachs of immunocompetent BALB/c mice via oral gavage (OG) and assessed them for clinical symptoms, serological response and bacterial dissemination. We found that mice receiving C. burnetii by OG had notable splenomegaly only after infection with ST16. A robust immune response and persistence in the stomach and mesenteric lymph nodes were observed in mice receiving ST16 and ST20 by OG, and dissemination of C. burnetii to peripheral tissues was observed in all OG infected mice. These findings support the oral route as a mode of transmission for C. burnetii. |
The effect of pH on antibiotic efficacy against Coxiella burnetii in axenic media
Smith CB , Evavold C , Kersh GJ . Sci Rep 2019 9 (1) 18132 Coxiella burnetii, the etiologic agent of Q fever, replicates in an intracellular phagolysosome with pH between 4 and 5. The impact of this low pH environment on antimicrobial treatment is not well understood. An in vitro system for testing antibiotic susceptibility of C. burnetii in axenic media was set up to evaluate the impact of pH on C. burnetii growth and survival in the presence and absence of antimicrobial agents. The data show that C. burnetii does not grow in axenic media at pH 6.0 or higher, but the organisms remain viable. At pH of 4.75, 5.25, and 5.75 moxifloxacin, doxycycline, and rifampin are effective at preventing growth of C. burnetii in axenic media, with moxifloxacin and doxycycline being bacteriostatic and rifampin having bactericidal activity. The efficacy of doxycycline and moxifloxacin improved at higher pH, whereas rifampin activity was pH independent. Hydroxychloroquine is thought to inhibit growth of C. burnetii in vivo by raising the pH of typically acidic intracellular compartments. It had no direct bactericidal or bacteriostatic activity on C. burnetii in axenic media, suggesting that raising pH of acidic intracellular compartments is its primary mechanism of action in vivo. The data suggest that doxycycline and hydroxychloroquine are primarily independent bacteriostatic agents. |
Prevalence of serum antibodies to Coxiella burnetii in Alaska Native persons from the Pribilof Islands
Kersh GJ , Fitzpatrick K , Pletnikoff K , Brubaker M , Bruce M , Parkinson A . Zoonoses Public Health 2019 67 (1) 89-92 BACKGROUND: Q fever is a febrile illness caused by infection with the bacterium Coxiella burnetii. It is most often transmitted by inhalation of the bacteria after it is shed by infected livestock. Recent studies have found very high C. burnetii infection rates among marine mammals, but it is not known if shedding by marine mammals creates a risk of Q fever among humans. To better understand infection of humans with exposure to marine mammals, the prevalence of antibodies against C. burnetii in serum samples taken from Alaskan Native persons residing on the Pribilof Islands was evaluated. The Pribilof Islands support large populations of northern fur seals infected with C. burnetii that may increase the risk of exposure for island residents. METHODS: Serum testing for IgG antibodies against C. burnetii (phase I and phase II) was performed, and demographic data were analysed utilizing banked serum specimens drawn from island residents from 1980 to 2000. RESULTS: The overall seroprevalence rate was 11.6% (95% CI = 9.3%-14.4%; 72/621). This is higher than the previously reported 3.1% (95% CI = 2.1%-4.3%) seroprevalence for the U.S. POPULATION: CONCLUSIONS: These results suggest that Alaskan Native persons may be at higher risk for exposure to C. burnetii than the general US. population, possibly due to proximity to large populations of infected marine mammals. |
National surveillance data show increase in spotted fever rickettsiosis: United States, 2016-2017
Heitman KN , Drexler NA , Cherry-Brown D , Peterson AE , Armstrong PA , Kersh GJ . Am J Public Health 2019 109 (5) 719-721 From 2016 through 2017, unprecedented increases in all nationally notifiable tickborne diseases were reported to the Centers for Disease Control and Prevention (CDC). The largest percentage increase was seen in reported cases of spotted fever rickettsiosis (SFR): a 46% increase from 4269 cases to a record 6248.1 Increases were reported in both new areas and in known endemic states. Although the New England, East North Central, and Middle Atlantic regions typically report only a handful of cases each year, in 2017, these areas experienced, a 215%, 78%, and 65% increase in reported cases, respectively. Among tickborne diseases, only anaplasmosis, with a 39% increase during this time, approached the rise seen with SFR. Although this increase raises concerns for elevated disease risk, additional factors are likely contributing to the high number of reports. |
Chronic Q fever with vascular involvement: Progressive abdominal pain in a patient with aortic aneurysm repair in the United States
Wiley Z , Reddy S , Jacobs Slifka KM , Brandon DC , Jernigan J , Kersh GJ , Armstrong PA . Case Rep Infect Dis 2019 2019 5369707 Q fever is a zoonotic bacterial infection caused by Coxiella burnetii. Chronic Q fever comprises less than five percent of all Q fever cases and, of those, endocarditis is the most common presentation (up to 78% of cases), followed by vascular involvement. Risk factors for chronic Q fever with vascular involvement include previous vascular surgery, preexisting valvular defects, aneurysms, and vascular prostheses. The most common symptoms of chronic Q fever with vascular involvement are nonspecific, including weight loss, fatigue, and abdominal pain. Criteria for diagnosis of chronic Q fever include clinical evidence of infection and laboratory criteria (antibody detection, detection of Coxiella burnetii DNA, or growth in culture). Treatment of chronic Q fever with vascular involvement includes a prolonged course of doxycycline and hydroxychloroquine (>/=18 months) as well as early surgical intervention, which has been shown to improve survival. Mortality is high in untreated chronic Q fever. We report a case of chronic Q fever with vascular involvement in a 77-year-old man with prior infrarenal aortic aneurysm repair, who lived near a livestock farm in the southeastern United States. |
Human seroprevalence to 11 zoonotic pathogens in the U.S. Arctic, Alaska
Miernyk KM , Bruden D , Parkinson AJ , Hurlburt D , Klejka J , Berner J , Stoddard RA , Handali S , Wilkins PP , Kersh GJ , Fitzpatrick K , Drebot MA , Priest JW , Pappert R , Petersen JM , Teshale E , Hennessy TW , Bruce MG . Vector Borne Zoonotic Dis 2019 19 (8) 563-575 BACKGROUND: Due to their close relationship with the environment, Alaskans are at risk for zoonotic pathogen infection. One way to assess a population's disease burden is to determine the seroprevalence of pathogens of interest. The objective of this study was to determine the seroprevalence of 11 zoonotic pathogens in people living in Alaska. METHODS: In a 2007 avian influenza exposure study, we recruited persons with varying wild bird exposures. Using sera from this study, we tested for antibodies to Cryptosporidium spp., Echinococcus spp., Giardia intestinalis, Toxoplasma gondii, Trichinella spp., Brucella spp., Coxiella burnetii, Francisella tularensis, California serogroup bunyaviruses, and hepatitis E virus (HEV). RESULTS: Eight hundred eighty-seven persons had sera tested, including 454 subsistence bird hunters and family members, 160 sport bird hunters, 77 avian wildlife biologists, and 196 persons with no wild bird exposure. A subset (n = 481) of sera was tested for California serogroup bunyaviruses. We detected antibodies to 10/11 pathogens. Seropositivity to Cryptosporidium spp. (29%), California serotype bunyaviruses (27%), and G. intestinalis (19%) was the most common; 63% (301/481) of sera had antibodies to at least one pathogen. Using a multivariable logistic regression model, Cryptosporidium spp. seropositivity was higher in females (35.7% vs. 25.0%; p = 0.01) and G. intestinalis seropositivity was higher in males (21.8% vs. 15.5%; p = 0.02). Alaska Native persons were more likely than non-Native persons to be seropositive to C. burnetii (11.7% vs. 3.8%; p = 0.005) and less likely to be seropositive to HEV (0.4% vs. 4.1%; p = 0.01). Seropositivity to Cryptosporidium spp., C. burnetii, HEV, and Echinococcus granulosus was associated with increasing age (p </= 0.01 for all) as was seropositivity to >/=1 pathogen (p < 0.0001). CONCLUSION: Seropositivity to zoonotic pathogens is common among Alaskans with the highest to Cryptosporidium spp., California serogroup bunyaviruses, and G. intestinalis. This study provides a baseline for use in assessing seroprevalence changes over time. |
Trends in Q fever serologic testing by immunofluorescence from four large reference laboratories in the United States, 2012-2016
Miller HK , Binder AM , Peterson A , Theel ES , Volpe JM , Couturier MR , Cherry CC , Kersh GJ . Sci Rep 2018 8 (1) 16670 Laboratory testing for Q fever (Coxiella burnetii) is essential for a differential diagnosis, yet little is known about Q fever diagnostic testing practices in the United States. We retrospectively analyzed Q fever immunoglobulin G (IgG) indirect immunofluorescence assay (IFA) testing data between 1/1/2012-10/31/2016 from ARUP, LabCorp, Mayo Medical Laboratories, and Quest Diagnostics. Data included IgG phase I and phase II titers, patient age and sex, and state and date of specimen collection. On average, 12,821 specimens were tested for Q fever annually by the participating laboratories. Of 64,106 total specimens, 84.1% tested negative for C. burnetii-specific antibodies. Positive titers ranged from 16 to 262,144 against both phase I and phase II antigens. Submission of specimens peaked during the summer months, and more specimens were submitted from the West North Central division. Testing occurred more frequently in males (53%) and increased with age. In conclusion, few U.S. Q fever cases are reported, despite large volumes of diagnostic specimens tested. Review of commercial laboratory data revealed a lack of paired serology samples and patterns of serology titers that differ from case reporting diagnostic criteria. |
Vital Signs: Trends in reported vectorborne disease cases - United States and Territories, 2004-2016
Rosenberg R , Lindsey NP , Fischer M , Gregory CJ , Hinckley AF , Mead PS , Paz-Bailey G , Waterman SH , Drexler NA , Kersh GJ , Hooks H , Partridge SK , Visser SN , Beard CB , Petersen LR . MMWR Morb Mortal Wkly Rep 2018 67 (17) 496-501 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. |
Phylogenetic inference of Coxiella burnetii by 16S rRNA gene sequencing.
McLaughlin HP , Cherney B , Hakovirta JR , Priestley RA , Conley A , Carter A , Hodge D , Pillai SP , Weigel LM , Kersh GJ , Sue D . PLoS One 2017 12 (12) e0189910 Coxiella burnetii is a human pathogen that causes the serious zoonotic disease Q fever. It is ubiquitous in the environment and due to its wide host range, long-range dispersal potential and classification as a bioterrorism agent, this microorganism is considered an HHS Select Agent. In the event of an outbreak or intentional release, laboratory strain typing methods can contribute to epidemiological investigations, law enforcement investigation and the public health response by providing critical information about the relatedness between C. burnetii isolates collected from different sources. Laboratory cultivation of C. burnetii is both time-consuming and challenging. Availability of strain collections is often limited and while several strain typing methods have been described over the years, a true gold-standard method is still elusive. Building upon epidemiological knowledge from limited, historical strain collections and typing data is essential to more accurately infer C. burnetii phylogeny. Harmonization of auspicious high-resolution laboratory typing techniques is critical to support epidemiological and law enforcement investigation. The single nucleotide polymorphism (SNP) -based genotyping approach offers simplicity, rapidity and robustness. Herein, we demonstrate SNPs identified within 16S rRNA gene sequences can differentiate C. burnetii strains. Using this method, 55 isolates were assigned to six groups based on six polymorphisms. These 16S rRNA SNP-based genotyping results were largely congruent with those obtained by analyzing restriction-endonuclease (RE)-digested DNA separated by SDS-PAGE and by the high-resolution approach based on SNPs within multispacer sequence typing (MST) loci. The SNPs identified within the 16S rRNA gene can be used as targets for the development of additional SNP-based genotyping assays for C. burnetii. |
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