Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 163 Records) |
Query Trace: Kersh E[original query] |
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Comparison of paired immunofluorescent antibody serology and real-time polymerase chain reaction testing for the detection of acute Q fever among febrile patients in Kilimanjaro, Tanzania, 2012-2014
Rolfe RJ , Crump JA , Maro VP , Mmbaga BT , Saganda W , Lwezaula BF , Couturier MR , Hymas WC , Perniciaro JL , Nicholson WL , Kersh GJ , Rubach MP . Am J Trop Med Hyg 2024 Acute Q fever diagnosis via paired serology is problematic because it requires follow-up for convalescent sample collection; as such, it cannot provide a diagnosis to inform a treatment decision at the time of acute presentation. Real-time polymerase chain reaction (PCR) may be a useful approach for the diagnosis of acute Q fever in endemic settings. Among febrile patients enrolled in a sentinel surveillance study for Q fever at two referral hospitals in Moshi, Tanzania, from 2012 to 2014, we analyzed those with paired sera for IgG to Coxiella burnetii (C. burnetii) phase II antigens using immunofluorescent antibody (IFA) testing, and acute serum was tested for C. burnetii with PCR. Acute Q fever was defined as a fourfold or greater rise from the acute to convalescent sample in IFA reciprocal titer or PCR detection that was confirmed through repeat testing. Test characteristics were tabulated. Among 496 participants tested using both paired IFA and PCR testing, 463 (93.3%) tested negative on both IFA and PCR, five (1.0%) tested positive for Q fever on both IFA and PCR, and 28 (5.6%) tested positive for Q fever on IFA alone. The sensitivity of PCR testing using paired IFA testing as an index was 0.15 (5/33), and the specificity was 1 (463/463). C. burnetii PCR testing provides a clinically specific method that may aid in timely diagnosis in settings in which acute Q fever is a common cause of febrile illness. However, we found a low clinical sensitivity of PCR testing on serum when compared with paired IFA serology. |
Neisseria meningitidis serogroup Y sequence type 1466 and urogenital infections
van Hal SJ , Le T , Jenkins F , Kundu RL , Limnios EA , McNamara LA , Sharma S , Kersh EN , Lahra MM . Emerg Infect Dis 2025 31 (1) 86-93 ![]() ![]() Neisseria meningitidis is a common commensal bacterium of the nasopharynx that can cause invasive meningococcal disease (IMD). In comparison, N. gonorrhoeae is always a pathogen usually limited to mucosal sites. However, increased evidence for overlapping clinical syndromes is emerging. We compared N. meningitidis samples from a urogenital outbreak in Australia with sequences from the United States and other countries. We conducted phylogenetic analyses to assess relatedness and examine for genomic changes associated with meningococcal adaptation; we collated a total of 255 serogroup Y (MenY), sequence type (ST) 1466 isolate assemblies. Most urogenital isolates originated from Australia; those isolates formed a distinct clade, most closely related genomically to recent US IMD isolates. No specific genomic changes suggested niche adaptation or associated clinical manifestations. The MenY ST1466 N. meningitidis isolates circulating in Australia and the United States are capable of causing both urethritis and invasive meningococcal disease. |
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. |
Emergence and evolution of mosaic penA-60 and penA-237 alleles in a Neisseria gonorrhoeae core genogroup that was historically susceptible to extended spectrum cephalosporins
Thomas Iv JC , Cartee JC , Hebrank K , St Cyr SB , Schlanger K , Raphael BH , Kersh EN , Joseph SJ . Front Microbiol 2024 15 1401303 ![]() ![]() INTRODUCTION: Neisseria gonorrhoeae (Ng) has successively developed resistance to all previously recommended antimicrobial therapies, with ceftriaxone being the last option for monotherapy of gonorrhea. Global emergence and international spread of the FC428 clone derived mosaic penA-60 allele, associated with highlevel ceftriaxone minimum inhibitory concentrations (MICs) in non FC428 clone Ng lineages, has become an increasing concern. The penA-60 allele carrying Ng was first identified in the U.S. in Las Vegas, Nevada (2019; GCWGS-102723), with a multi-locus sequence type (MLST)-1901 strain, in a non FC428 clone Ng lineage, which is associated with a historically ceftriaxone susceptible core genogroup. Later in 2022, an allele genetically similar to penA-60, mosaic penA-237, was identified in the UK (H22-722) and France (F92) with high-level ceftriaxone MICs and both belonged to MLST-1901. METHODS: In this study, we assessed phylogenomic relatedness and antimicrobial resistance (AMR) determinant profiles of these three isolates with high-level ceftriaxone MICs among a global collection of 2,104 genomes belonging to the MLST-1901 core genome cluster group 31, which includes strains separated by a locus threshold of 200 or fewer differences (Ng_cgc_200). Recombination events in and around the penA coding region were catalogued and potential sources of inter species recombinant DNA were also inferred. RESULTS: The global population structure of MLST-1901 core genogroup falls into 4 major lineages. Isolates GCWGS-10723, F92, and H22-722 clustered within Lineage 1, which was dominated by non-mosaic penA-5 alleles. These three isolates formed a clade within Lineage 1 that consisted of isolates from North America and southeast Asia. Neisseria subflava and Neisseria sicca were identified as likely progenitors of two independent recombination events that may have led to the generation of mosaic penA-60 and penA-237, within a possible non-mosaic penA-5 background. DISCUSSIONS: Our study suggests that there are multiple evolutionary pathways that could generate concerning mosaic penA alleles via homologous recombination of historically susceptible Ng lineages with Neisseria commensals. Enhanced surveillance of gonococcal strains and Neisseria commensals is crucial for understanding of the evolution of AMR, particularly in less-studied regions (e.g., Asia), where high-level ceftriaxone MICs and multi-drug resistance are more prevalent. |
Whole-genome sequencing resolves biochemical misidentification of Neisseria species from urogenital specimens
Smith AC , Shrivastava A , Cartee JC , Bélanger M , Sharpe S , Lewis J , Budionno S , Gomez R , Khubbar MK , Pham CD , Gernert KM , Schmerer MW , Raphael BH , Learner ER , Kersh EN , Joseph SJ . J Clin Microbiol 2024 e0070424 ![]() ![]() Neisseria meningitidis (Nm) and Neisseria gonorrhoeae (Ng) are human pathogens that sometimes occupy the same anatomical niche. Ng, the causative agent of gonorrhea, infects 87 million individuals annually worldwide and is an urgent threat due to increasing drug resistance. Ng is a pathogen of the urogenital tract and may infect the oropharyngeal or rectal site, often asymptomatically. Conversely, Nm is an opportunistic pathogen. While often a commensal in the oropharyngeal tract, it is also the leading cause of bacterial meningitis with 1.2 million cases globally, causing significant morbidity and mortality. Horizontal gene transfer (HGT) is likely to occur between Ng and Nm due to their shared anatomical niches and genetic similarity, which poses challenges for accurate detection and treatment. Routine surveillance through the Gonococcal Isolate Surveillance Project and Strengthening the U.S. Response to Resistant Gonorrhea detected six concerning urogenital Neisseria isolates with contradicting species identification in Milwaukee (MIL). While all six isolates were positive for Ng using nucleic acid amplification testing (NAAT) and matrix-assisted laser desorption/ionization time of flight identified the isolates as Ng, two biochemical tests, Gonochek-II and API NH, classified them as Nm. To address this discrepancy, we performed whole-genome sequencing (WGS) using Illumina MiSeq on all isolates and employed various bioinformatics tools. Species detection analysis using BMScan, which uses WGS data, identified all isolates as Ng. Furthermore, Kraken revealed over 98% of WGS reads mapped to the Ng genome and <1% to Nm. Recombination analysis identified putative HGT in all MIL isolates within the γ-glutamyl transpeptidase (ggt) gene, a key component in the biochemical tests used to differentiate between Nm and Ng. Further analysis identified Nm as the source of HGT event. Specifically, the active Nm ggt gene replaced the Ng pseudogenes, ggt1 and ggt2. Together, this study demonstrates that closely related Neisseria species sharing a niche underwent HGT, which led to the misidentification of species following biochemical testing. Importantly, NAAT accurately detected Ng. The misidentification highlights the importance of using WGS to continually evaluate diagnostic or bacterial identification tests. |
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. |
At-home specimen self-collection as an additional testing strategy for chlamydia and gonorrhoea: a systematic literature review and meta-analysis
Smith AC , Thorpe PG , Learner ER , Galloway ET , Kersh EN . BMJ Glob Health 2024 9 (8) INTRODUCTION: Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng) infections are often asymptomatic; screening increases early detection and prevents disease, sequelae and further spread. To increase Ct and Ng testing, several countries have implemented specimen self-collection outside a clinical setting. While specimen self-collection at home is highly acceptable to patients and as accurate as specimens collected by healthcare providers, this strategy is new or not being used in some countries. To understand how offering at home specimen self-collection will affect testing uptake, test results, diagnosis and linkage to care, when compared with collection in clinical settings, we conducted a systematic literature review and meta-analysis of peer-reviewed studies. METHODS: We searched Medline, Embase, Global Health, Cochrane Library, CINAHL (EBSCOHost), Scopus and Clinical Trials. Studies were included if they directly compared specimens self-collected at home or in other non-clinical settings to specimen collection at a healthcare facility (self or clinician) for Ct and/or Ng testing and evaluated the following outcomes: uptake in testing, linkage to care, and concordance (agreement) between the two settings for the same individuals. Risk of bias (RoB) was assessed using Cochrane Risk of Bias (RoB2) tool for randomised control trials (RCTs). RESULTS: 19 studies, from 1998 to 2024, comprising 15 RCTs with a total of 62 369 participants and four concordance studies with 906 participants were included. Uptake of Ct or Ng testing was 2.61 times higher at home compared with clinical settings. There was a high concordance between specimens collected at home and in clinical settings, and linkage to care was not significantly different between the two settings (prevalence ratio 0.96 (95% CI 0.91-1.01)). CONCLUSION: Our meta-analysis and systematic literature review show that offering self-collection of specimens at home or in other non-clinical settings could be used as an additional strategy to increase sexually transmitted infection testing in countries that have not yet widely adopted this collection method. |
Neisseria gonorrhoeae ST-1901 in Rio de Janeiro from 2006 to 2022: phylogeny and antimicrobial resistance evolution of a well-succeeded pathogen
de Medeiros RC , Barros Dos Santos KT , Costa-Lourenço APR , Skaf LB , Mercadante AM , Rosa MHB , Fracalanzza SEL , Ferreira ALP , Reimche JL , Gernert KM , Kersh EN , Bonelli RR . Int J Antimicrob Agents 2024 107299 ![]() ![]() Neisseria gonorrhoeae is a global threat to public health due to the accumulation of antimicrobial resistance mechanisms. ST-1901 is an internationally important sequence type (ST) because of its high incidence and the usual occurrence of chromosomally determined resistance. In this study, we describe the evolution of the ST-1901 and its single locus variants in Rio de Janeiro from 2006 to 2022. We analyzed 82 N. gonorrhoeae isolates according to antimicrobial susceptibility profile, resistance mechanisms, molecular typing, and phylogenetics. Six different single locus variants were detected. Phylogenetic analysis identified five clades, which share similar characteristics. Resistance rates for penicillin and tetracycline decreased due to the lower occurrence of resistance plasmids, but intermediary resistance to penicillin rose. Resistance to ciprofloxacin remained high throughout all clades and the years of the study. Regarding resistance to azithromycin, alterations in mtrR promoter and gene, and 23S rRNA encoding gene rrl were detected, with a notable rise in the incidence of C2611T mutations in more recent years occurring in 4 out of 5 clades. In contrast, beta-lactam resistance associated penA 34 mosaic was found only in one persisting clade (Clade D), as well as unique G45D and A39T mutations in mtrR gene and its promoter (Nm-Like) were found in only Clade B. Taken together, these data suggest that ST-1901, a persistently circulating lineage of N. gonorrhoeae in Rio de Janeiro, has undergone changes over the years and may evolve to develop resistance to the current recommended dual therapy adopted in Brazil, ceftriaxone and azithromycin. |
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. |
World Health Organization Enhanced Gonococcal Antimicrobial Surveillance Programme, Cambodia, 2023
Ouk V , Say HL , Virak M , Deng S , Frankson R , McDonald R , Kersh EN , Wi T , Maatouk I , van Hal S , Lahra MM . Emerg Infect Dis 2024 30 (7) 1493-1495 ![]() ![]() To determine antimicrobial susceptibility of Neisseria gonorrhoeae, we analyzed phenotypes and genomes of 72 isolates collected in Cambodia in 2023. Of those, 9/72 (12.5%) were extensively drug resistant, a 3-fold increase from 2022. Genomic analysis confirmed expansion of newly emerging resistant clones and ongoing resistance emergence across new phylogenetic backbones. |
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. |
Summary of the Centers for Disease Control and Prevention/National Institute of Allergy and Infectious Diseases Joint Workshop on Genital Herpes: 3-4 November 2022
Connolly KL , Bachmann L , Hiltke T , Kersh EN , Newman LM , Wilson L , Mena L , Deal C . Open Forum Infect Dis 2024 11 (5) ofae230 Genital herpes is caused by infection with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and currently has no cure. The disease is the second-most common sexually transmitted infection in the United States, with an estimated 18.6 million prevalent genital infections caused by HSV-2 alone. Genital herpes diagnostics and treatments are not optimal, and no vaccine is currently available. The Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases convened a workshop entitled "CDC/NIAID Joint Workshop on Genital Herpes." This report summarizes 8 sessions on the epidemiology of genital herpes, neonatal HSV, HSV diagnostics, vaccines, treatments, cures, prevention, and patient advocacy perspective intended to identify opportunities in herpes research and foster the development of strategies to diagnose, treat, cure, and prevent genital herpes. |
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. |
At-home diagnostics solutions for chlamydia and gonorrhea
Kersh EN , Mena LA . Jama 2024 ![]() ![]() This Viewpoint discusses the US Food and Drug Administration’s authorization of marketing an at-home testing system for chlamydia and gonorrhea as a good first step in boosting access to screening and treatment and in reducing infection rates. | eng |
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. |
Novel strain of multidrug non-susceptible Neisseria gonorrhoeae in the USA
Reimche JL , Pham CD , Joseph SJ , Hutton S , Cartee JC , Ruan Y , Breaux M , Ivanof C , Joshi A , DeMartino M , Kirby JE , Barbee LA , Kersh EN , Roosevelt KA , Hsu KK . Lancet Infect Dis 2024 ![]() ![]() Unsuccessful treatment of gonorrhoea has not yet occurred in the USA, and cases of gonorrhoea that are non-susceptible to cephalosporins have been rare. In 2019, non-susceptibility to ceftriaxone conferred by the mosaic penA 60.001 allele was found in a Neisseria gonorrhoeae multilocus sequence type (MLST) 1901 isolate from Nevada.1 In this Correspondence, we present two additional US cases of the penA 60.001 allele identified in MLST 8123, an emerging international multidrug non-susceptible N gonorrhoeae lineage. Although these cases responded to ceftriaxone treatment, N gonorrhoeae isolates from the first known patient (case 1) demonstrated in-vitro non-susceptibility to ceftriaxone as well as non-susceptibility or resistance to drugs previously recommended for front-line treatment. | | In August, 2022, N gonorrhoeae grown from urine culture from a patient with urethritis in primary care in Massachusetts displayed non-susceptibility to cephalosporins (the minimum inhibitory concentrations were 1·0 μg/mL for ceftriaxone and >1·0 μg/mL for cefixime by agar dilution; the minimum inhibitory concentration for cefixime was 1·5 μg/mL by gradient strip) and azithromycin and resistance to ciprofloxacin, penicillin, and tetracycline (appendix pp 6–7). Antimicrobial susceptibility testing was done with gradient strips at the state public health laboratory Massachusetts and then confirmed via agar dilution at the US Centers for Disease Control and Prevention (CDC). The patient (case 1) had already been successfully diagnosed on nucleic acid amplification test (NAAT) with gonorrhoea and was given 500 mg ceftriaxone intramuscularly and asked to return to primary care where, 9 days after treatment, he was asymptomatic, had normal results during examination, and tested negative by urine culture and pharyngeal and rectal NAAT recommended by the Massachusetts sexually transmitted diseases programme to document N gonorrhoeae clearance from any site of infection. The patient reported that he had not travelled outside USA in the 60 days before onset of symptoms. He disclosed female sex worker contacts, but insufficient information was provided to trace the contacts. |
Advantages and limitations of current diagnostic laboratory approaches in syphilis and congenital syphilis
Cao W , Thorpe PG , O'Callaghan K , Kersh EN . Expert Rev Anti Infect Ther 2023 21 (12) 1339-1354 ![]() ![]() INTRODUCTION: The reemergence of syphilis, especially congenital syphilis, presents a significant public health threat. Accurate diagnosis of syphilis depends on recognition of a constellation of symptoms, review of medical and sexual history, and multiple laboratory tests. While reliable, current tests for syphilis can be difficult to interpret, which can lead to delays in treatment. AREA COVERED: This review summarizes the major advantages and limitations of available diagnostic laboratory methods for syphilis, provides an update on recent advances in laboratory tools, and highlights the urgent need for coordinated efforts to create new tools to halt the resurgence of syphilis. EXPERT OPINION: In syphilis, the wide variety of short-lived signs and symptoms followed by periods of latency create diagnostics challenges. Currently available laboratory tests, when positive, require additional information to interpret (prior testing, treatment, and sexual history). Point-of-care tests that can rapidly and accurately detect both treponemal and non-treponemal antibodies would be a huge step toward reducing test turnaround time and time to treatment. Incorporating biological insights and technology innovations to advance the development of direct detection assays is urgently needed. A comprehensive coordinated effort is critical to stem the tide of rising syphilis in the United States and globally. |
Molecular investigation of Treponema pallidum strains associated with ocular syphilis in the United States, 2016-2020
Pillay A , Vilfort K , Debra A , Katz SS , Thurlow CM , Joseph SJ , Lundy S , Ji A , Jaeyoung H , Workowski KA , Barrow RY , Danavall D , Pettus K , Chi KH , Kersh EN , Cao W , Chen CY . Microbiol Spectr 2024 e0058124 ![]() ![]() Ocular syphilis is a serious complication of Treponema pallidum infection that can occur at any stage of syphilis and affect any eye structure. It remains unknown if certain T. pallidum strains are associated with ocular infections; therefore, we performed genotyping and whole genome sequencing (WGS) to characterize strains from patients with ocular syphilis. Seventy-five ocular or non-ocular specimens from 55 ocular syphilis patients in 14 states within the United States were collected between February 2016 and November 2020. Sufficient T. pallidum DNA was available from nine patients for genotyping and three for WGS. Genotyping was done using the augmented Centers for Disease Control and Prevention typing scheme, and WGS was performed on Illumina platforms. Multilocus sequence typing allelic profiles were predicted from whole genome sequence data. T. pallidum DNA was detected in various specimens from 17 (30.9%) of the 55 patients, and typing was done on samples from 9 patients. Four complete strain types (14d10/g, 14b9/g, 14d9/g, and 14e9/f) and five partial types were identified. WGS was successful on samples from three patients and all three strains belonged to the SS14 clade of T. pallidum. Our data reveal that multiple strain types are associated with ocular manifestations of syphilis. While genotyping and WGS were challenging due to low amounts of T. pallidum DNA in specimens, we successfully performed WGS on cerebrospinal fluid, vitreous fluid, and whole blood.IMPORTANCESyphilis is caused by the spirochete Treponema pallidum. Total syphilis rates have increased significantly over the past two decades in the United States, and the disease remains a public health concern. In addition, ocular syphilis cases has also been on the rise, coinciding with the overall increase in syphilis rates. We conducted a molecular investigation utilizing traditional genotyping and whole genome sequencing over a 5-year period to ascertain if specific T. pallidum strains are associated with ocular syphilis. Genotyping and phylogenetic analysis show that multiple T. pallidum strain types are associated with ocular syphilis in the United States. |
Health care provider knowledge regarding alpha-gal syndrome - United States, March-May 2022
Carpenter A , Drexler NA , McCormick DW , Thompson JM , Kersh G , Commins SP , Salzer JS . MMWR Morb Mortal Wkly Rep 2023 72 (30) 809-814 Alpha-gal syndrome (AGS) is an emerging, tick bite-associated immunoglobulin E-mediated allergic condition characterized by a reaction to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), which is found in mammalian meat and products derived from mammals, including milk, other dairy products, and some pharmaceutical products. Symptoms range from mild (e.g., a rash or gastrointestinal upset) to severe (anaphylaxis); onset typically occurs ≥2 hours after exposure to alpha-gal. No treatment or cure is currently available. Despite the potential life-threating reactions associated with AGS, most patients perceive that health care providers (HCPs) have little or no knowledge of AGS. A U.S. web-based survey of 1,500 HCPs revealed limited knowledge of AGS, identified areas for continuing medical education, and described self-reported diagnostic and management practices. Overall, 42% of surveyed HCPs had never heard of AGS, and among those who had, fewer than one third knew how to diagnose the condition. Two thirds of respondents indicated that guidelines for the diagnosis and management of AGS would be useful clinical resources. Limited awareness and knowledge of AGS among HCPs likely contributes to underdiagnosis of this condition and inadequate patient management, and underestimates of the number of AGS patients in the United States, which currently relies on laboratory testing data alone. |
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. |
Global emergence and dissemination of Neisseria gonorrhoeae ST-9363 isolates with reduced susceptibility to azithromycin (preprint)
Joseph SJ , Thomas Iv JC , Schmerer MW , Cartee J , St Cyr S , Schlanger K , Kersh EN , Raphael BH , Gernert KM . bioRxiv 2021 2021.08.05.455198 Neisseria gonorrhoeae multi-locus sequence type (ST) 9363 genogroup isolates have been associated with reduced azithromycin susceptibility (AZMrs) and show evidence of clonal expansion in the U.S. Here we analyze a global collection of ST-9363 genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 genogroup is inferred to have originated from Asia in the mid-19th century; we estimate the three modern lineages emerged from Europe in the late 1970s to early 1980s. The European lineage appears to have emerged and expanded from around 1986 to 1998, spreading into North America and Oceania in the mid-2000s with multiple introductions, along with multiple secondary reintroductions into Europe. Our results suggest two separate acquisition events of mosaic mtrR and mtrR promoter alleles: first during 2009-2011 and again during the 2012-2013 time, facilitating the clonal expansion of this genogroup with AZMrs in the U.S. By tracking phylodynamic evolutionary trajectories of clades that share distinct demography as well as population-based genomic statistics, we demonstrate how recombination and selective pressures in the mtrCDE efflux operon granted a fitness advantage to establish ST-9363 as a successful gonococcal lineage in the U.S. and elsewhere. Although it is difficult to pinpoint the exact timing and emergence of this young genogroup, it remains critically important to continue monitoring it, as it could acquire additional resistance markers.Competing Interest StatementThe authors have declared no competing interest. |
Mechanistic basis for decreased antimicrobial susceptibility in a clinical isolate of Neisseria gonorrhoeae possessing a mosaic-like mtr efflux pump locus (preprint)
Rouquette-Loughlin CE , Reimche JL , Balthazar JT , Dhulipala V , Gernert KM , Kersh EN , Pham CD , Pettus K , Abrams AJ , Trees DL , St Cyr S , Shafer WM . bioRxiv 2018 448712 Recent reports suggest that mosaic-like sequences within the mtr (multiple transferable resistance) efflux pump locus of Neisseria gonorrhoeae likely originating from commensal Neisseria sp. by transformation can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within the mtrR gene encoding the transcriptional repressor (MtrR) of the mtrCDE efflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (Wadsworth et al. 2018. MBio. doi.org/10.1128/mBio.01419-18). We performed detailed genetic and molecular studies to define the mechanistic basis for why such strains can exhibit decreased susceptibility to MtrCDE antimicrobial substrates including Azi. We report that a strong cis-acting transcriptional impact of a single nucleotide change within the -35 hexamer of the mtrCDE promoter as well gain-of-function amino acid changes at the C-terminal region of MtrD can mechanistically account for the decreased antimicrobial susceptibility of gonococci with a mosaic-like mtr locus.IMPORTANCE Historically, after introduction of an antibiotic for treatment of gonorrhea, strains of N. gonorrhoeae emerge that display clinical resistance due to spontaneous mutation or acquisition of resistance genes. Genetic exchange between members of the Neisseria genus occurring by transformation can cause significant changes in gonococci that impact the structure of an antibiotic target or expression of genes involved in resistance. The results presented herein provide a framework for understanding how mosaic-like DNA sequences from commensal Neisseria that recombine within the gonococcal mtr efflux pump locus function to decrease bacterial susceptibility to antimicrobials including antibiotics used in therapy of gonorrhea. |
Selective whole genome amplification as a tool to enrich specimens with low Treponema pallidum genomic DNA copies for whole genome sequencing (preprint)
Thurlow CM , Joseph SJ , Ganova-Raeva L , Katz SS , Pereira L , Chen C , Debra A , Vilfort K , Workowski K , Cohen SE , Reno H , Sun Y , Burroughs M , Sheth M , Chi KH , Danavall D , Philip SS , Cao W , Kersh EN , Pillay A . bioRxiv 2021 10 Downstream next generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies pallidum (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T. pallidum genome, and the capture and removal of CpG-methylated host DNA using the NEBNext Microbiome DNA Enrichment Kit followed by MDA with the REPLI-g Single Cell Kit as enrichment methods to improve the yields of T. pallidum DNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93-98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit propagated isolates, containing >14 T. pallidum genomic copies/ul of sample for SWGA and >129 genomic copies/ul for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens, showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole genome sequencing (WGS) of specimens containing very low numbers of T. pallidum, which have been challenging until now. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Considerations for endpoint titer determination in syphilis testing using newly marketed, automated rapid plasma reagin instruments
Shukla M , Pereira L , Sun Y , Fakile YF , Kersh EN , Cao W . Public Health Rep 2023 333549231176007 Syphilis is a sexually transmitted disease (STD) caused by the bacterium Treponema pallidum, subspecies pallidum (T. pallidum).1 The resurgence of syphilis in the last 2 decades is a major public health concern in the United States. In 2020, a total of 133 945 cases of all stages of syphilis were reported in the United States, an increase of more than 70% since 2015. The national rate of congenital syphilis has increased 254% since 2016. In 2020, a total of 2148 cases of congenital syphilis were reported, including 149 congenital syphilis–related stillbirths and infant deaths.2 However, syphilis diagnosis is still challenging, partially because of overlapping and ambiguous clinical presentation, particularly during early infection.3 For laboratory testing, darkfield microscopy examinations and direct molecular detection of T. pallidum from clinical specimens are definitive methods for diagnosing early syphilis, but both methods are currently not widely performed at local, reference, or public health laboratories and have challenges in identifying asymptomatic or early-stage infection without the presence of visible lesions for suitable specimen collection.4 Darkfield microscopy requires special equipment and experienced operators for reliable results.5 US Food and Drug Administration (FDA)–cleared molecular tests for syphilis are still not available, and laboratory-developed molecular tests are limited in availability. Therefore, serological tests that detect treponemal and nontreponemal antibodies remain the mainstay for routine laboratory diagnosis of active syphilis infection.6 |
Evaluation of three automated nontreponemal rapid plasma reagin (RPR) tests for the laboratory diagnosis of syphilis
Shukla MR , Pereira L , Gaynor AM , Sun Y , Edwards D , Simmons T , Andrews CW , Park IU , Hong J , Cao W , Kersh EN , Fakile Y . J Clin Microbiol 2023 61 (6) e0016823 Automated nontreponemal rapid plasma reagin (RPR) tests were recently introduced in the United States for syphilis testing and limited performance data are available. In collaboration with the Association of Public Health Laboratories, three public health laboratories (PHL) were chosen through a competitive selection process to evaluate the performance of three FDA-cleared automated RPR test systems: BioPlex 2200 Syphilis Total & RPR assay (Bio-Rad Laboratories), AIX 1000 (Gold Standard Diagnostics), and ASI Evolution (Arlington Scientific). Panels prepared at the CDC included: a qualitative panel comprised of 734 syphilis reactive/nonreactive sera; a quantitative panel of 50 syphilis reactive sera (RPR titer 1:64 to 1:1,024); and a reproducibility panel of 15 nonreactive and reactive sera (RPR titer 1:1 to 1:64). Panels were shipped frozen to the PHL and tested on the automated RPR systems following manufacturers' instructions. Prior test results were blinded to all laboratories. When compared to manual RPR (Arlington Scientific) performed at the CDC as a reference test, the qualitative panel results demonstrated an overall concordance of 95.9% for AIX 1000, 94.6% for ASI Evolution, and 92.6% for Bioplex RPR; quantitative panel showed within range titer of 2-fold for 94% of specimens for AIX 1000, 68% for ASI Evolution, and 64% for BioPlex RPR, and the reproducibility testing panel demonstrated point estimates ranging from 69 to 95%. Automated RPR instruments could reduce turnaround time and minimize interpretation errors. However, additional evaluations with more specimens could assist laboratories with implementing automated RPR tests and understanding their limitations. |
Genomic analysis of 1710 surveillance-based Neisseria gonorrhoeae isolates from the USA in 2019 identifies predominant strain types and chromosomal antimicrobial-resistance determinants
Reimche JL , Clemons AA , Chivukula VL , Joseph SJ , Schmerer MW , Pham CD , Schlanger K , St Cyr SB , Kersh EN , Gernert KM . Microb Genom 2023 9 (5) ![]() This study characterized high-quality whole-genome sequences of a sentinel, surveillance-based collection of 1710 Neisseria gonorrhoeae (GC) isolates from 2019 collected in the USA as part of the Gonococcal Isolate Surveillance Project (GISP). It aims to provide a detailed report of strain diversity, phylogenetic relationships and resistance determinant profiles associated with reduced susceptibilities to antibiotics of concern. The 1710 isolates represented 164 multilocus sequence types and 21 predominant phylogenetic clades. Common genomic determinants defined most strains' phenotypic, reduced susceptibility to current and historic antibiotics (e.g. bla (TEM) plasmid for penicillin, tetM plasmid for tetracycline, gyrA for ciprofloxacin, 23S rRNA and/or mosaic mtr operon for azithromycin, and mosaic penA for cefixime and ceftriaxone). The most predominant phylogenetic clade accounted for 21 % of the isolates, included a majority of the isolates with low-level elevated MICs to azithromycin (2.0 µg ml(-1)), carried a mosaic mtr operon and variants in PorB, and showed expansion with respect to data previously reported from 2018. The second largest clade predominantly carried the GyrA S91F variant, was largely ciprofloxacin resistant (MIC ≥1.0 µg ml(-1)), and showed significant expansion with respect to 2018. Overall, a low proportion of isolates had medium- to high-level elevated MIC to azithromycin ((≥4.0 µg ml(-1)), based on C2611T or A2059G 23S rRNA variants). One isolate carried the penA 60.001 allele resulting in elevated MICs to cefixime and ceftriaxone of 1.0 µg ml(-1). This high-resolution snapshot of genetic profiles of 1710 GC sequences, through a comparison with 2018 data (1479 GC sequences) within the sentinel system, highlights change in proportions and expansion of select GC strains and the associated genetic mechanisms of resistance. The knowledge gained through molecular surveillance may support rapid identification of outbreaks of concern. Continued monitoring may inform public health responses to limit the development and spread of antibiotic-resistant gonorrhoea. |
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 |
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